Francesca Conway

<h2>ABSTRACT</h2><h3>Study Objective</h3> To correlate the type and degree of adenomyosis, scored through a new system based on the features of transvaginal sonography, to patients' symptoms and fertility. <h3>Design</h3> This is a multicenter, observational, prospective study. <h3>Setting</h3> Two endometriosis tertiary referral centers (University of Rome "Tor Vergata" and University of Siena). <h3>Patients</h3> A total of 108 patients with ultrasonographic signs of adenomyosis. <h3>Interventions</h3> A new ultrasonographic scoring system designed to assess the severity and the extent of uterine adenomyosis was used to stage the disease in correlation with the clinical symptoms. Menstrual uterine bleeding was assessed by a pictorial blood loss analysis chart, painful symptoms were evaluated using a visual analog scale, and infertility factors were considered. <h3>Measurements and Main Results</h3> A total of 108 patients with ultrasonographic signs of adenomyosis (mean age ± standard deviation, 37.7 ± 7.7 years) were classified according to the proposed scoring system. Women with ultrasound diagnosis of diffuse adenomyosis were older (p = .04) and had heavier menstrual bleeding (p = .04) than women with focal disease; however, no statistically significant differences were found regarding the presence and severity of dyspareunia and dysmenorrhea. Higher values of menstrual bleeding were found for severe diffuse adenomyosis, with the highest values being found in those with adenomyomas. In patients trying to conceive, the presence of ultrasound findings of focal disease was associated with a higher percentage of infertility than in those with diffuse disease, and the focal involvement of the junctional zone showed a higher percentage of at least 1 miscarriage than in those with diffuse adenomyosis. <h3>Conclusion</h3> The ultrasonographic evaluation of the type and extension of adenomyosis in the myometrium seems to be important in correlation to the severity of symptoms and infertility.

Severe acute respiratory syndrome coronavirus-2 can affect the cardiovascular system yielding a wide range of complications, including acute myocardial injury. The myocardium can be damaged by direct viral invasion or indirect mechanisms, sustained by systemic inflammation, immune-mediated response, and dysregulation of the renin-angiotensin system. Myocardial injury affects about one-quarter of patients with COVID-19, can manifest even in the absence of previous cardiovascular disease, and is associated to higher mortality rates and long-term sequelae. This review describes the pathophysiological mechanisms of myocardial injury and infarction and discusses the main clinical outcomes and diagnostic challenges associated with myocardial damage during COVID-19.

There is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum. We aimed to determine its incidence among patients hospitalised with COVID-19 in the United Kingdom and describe factors associated with outcome.A structured survey of pneumomediastinum and its incidence was conducted from September 2020 to February 2021. United Kingdom-wide participation was solicited via respiratory research networks. Identified patients had SARS-CoV-2 infection and radiologically proven pneumomediastinum. The primary outcomes were to determine incidence of pneumomediastinum in COVID-19 and to investigate risk factors associated with patient mortality.377 cases of pneumomediastinum in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 pneumomediastinum was 195/377 (51.7%). Pneumomediastinum in COVID-19 was associated with high rates of mechanical ventilation. 172/377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 pneumomediastinum at the time of diagnosis and thereafter (p<0.001) along with increasing age (p<0.01) and diabetes mellitus (p=0.08). Switching patients from continuous positive airways pressure support to oxygen or high flow nasal oxygen after the diagnosis of pneumomediastinum was not associated with difference in mortality.Pneumomediastinum appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom pneumomediastinum was identified had not been mechanically ventilated at the point of diagnosis.

COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733.Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87).Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19.LifeArc and CW+.

Purpose: Women with endometriosis represent a significant proportion of all outpatient gynecological consultations. Endometriosis is a benign chronic condition characterized by the spreading of endometrial-like tissue outside the uterus. A correlation between endometriosis and infertility has been strongly underlined in the literature about the topic: recent data suggest that up to 50% of women with infertility may suffer from this disease. The aim of this brief commentary is to focus the attention on the importance of a multidisciplinary approach for patients with endometriosis, including an accurate psychological and sexological counselling.Materials and Methods: We propose a brief point of view about a multidisciplinary approach in the treatment of endometriosis and associated infertility.Results and conclusions: Endometriosis is associated to a worse quality of life. Women with endometriosis also report higher levels of psychological conditions such as anxiety and depression. For this reason, an integrative approach is strongly advisable in order to improve social functions and mental health of these women and their partners. This may allow a more correct therapeutic management of these patients, reducing the potential negative impact of the disease on the mental wellbeing of the couple.

<h3>Objective</h3> To evaluate the ultrasonographic presence of different forms of endometriosis and the associated clinical symptoms in adolescent women. <h3>Design</h3> Retrospective observational study. <h3>Setting</h3> University hospital. <h3>Patient(s)</h3> Two hundred and seventy women aged 12–20 years referred to the gynecologic ultrasound unit from January 2014 to June 2019. <h3>Intervention(s)</h3> Two-dimensional, three-dimensional, and power Doppler ultrasound (US) pelvic examination (transvaginal or transrectal in pre–sexually active adolescents) were performed in all included adolescents. Medical history was collected for each patient before the scan. <h3>Main Outcome Measure(s)</h3> All possible locations of endometriosis evaluated and recorded using a dedicated ultrasound mapping sheet and severity of painful symptoms evaluated through a visual analogue scale (VAS). <h3>Result(s)</h3> Dysmenorrhea was detected in 147 (54.4%) of 270 patients and heavy menstrual bleeding in 76 (28.1%) of 270. At least one ultrasound feature of endometriosis was identified in 36 (13.3%) of 270 cases. Ovarian endometriomas were found in 22 (11%) patients, adenomyosis in 16 (5.2%), and deep infiltrating endometriosis (DIE) in 10 (3.7%). Ultrasound signs of endometriosis were found in 21% of adolescents who reported dysmenorrhea and 33% with dyspareunia. The presence of DIE at ultrasound was associated with bowel symptoms in 33% of patients and associated with dyspareunia in 25% of patients. <h3>Conclusion(s)</h3> The detection rate of pelvic endometriotic lesions at ultrasound was 13%. The rates of dysmenorrhea, dyspareunia and heavy menstrual bleeding in adolescents with endometriosis ultrasound signs were statistically significantly higher compared with those without. In patients with dysmenorrhea, the detection rate of pelvic endometriosis at ultrasound increased to 20%. Professionals involved with teens should be aware of the clinical presentation of endometriosis to reduce the delay between the onset of symptoms and the diagnosis, referring these young women to dedicated centers.

COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization.TLD was performed in COPD patients (FEV1 30-60% predicted, CAT≥10 or mMRC≥2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed.Eighty-two subjects (FEV1 41.6±7.4% predicted, 50.0% male, age 63.7±6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups.In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD.NCT02058459.

In the present pictorial we show the ultrasonographic appearances of endometriosis in atypical sites. Scar endometriosis may present as a hypoechoic solid nodule with hyperechoic spots while umbilical endometriosis may appear as solid or partially cystic areas with ill-defined margins. In the case of endometriosis of the rectus muscle, ultrasonography usually demonstrates a heterogeneous hypoechogenic formation with indistinct edges. Inguinal endometriosis is quite variable in its ultrasonographic presentation showing a completely solid mass or a mixed solid and cystic mass. The typical ultrasonographic finding associated with perineal endometriosis is the presence of a solid lesion near to the episiotomy scar. Under ultrasonography, appendiceal endometriosis is characterized by a solid lesion in the wall of the small bowel, usually well defined. Superficial hepatic endometriosis is characterized by a small hypoechoic lesion interrupting the hepatic capsula, usually hyperechoic. Ultrasound endometriosis of the pancreas is characterized by a small hypoechoic lesion while endometriosis of the kidney is characterized by a hyperechoic small nodule. Diaphragmatic endometriosis showed typically small hypoechoic lesions. Only peripheral nerves can be investigated using ultrasound, with a typical solid appearance. In conclusion, ultrasonography seems to have a fundamental role in the majority of endometriosis cases in “atypical” sites, in all the cases where “typical” clinical findings are present.

Ulipristal acetate (UPA) is used for medical treatment of uterine fibroids. The aim of this study was to describe the effects on painful symptoms and the sonographic uterine modifications in patients with adenomyosis erroneously treated with UPA. This is an observational study on six women affected by adenomyosis and treated with three months of UPA (5 mg/24h). The baseline ultrasonography (US) was not performed at out center nor was the diagnosis of fibroids. The patients came to our attention after the treatment with UPA, prescribed by an external physician. During our post-treatment scan we found aspects of adenomyosis, while no fibroids were detected. Symptoms, myometrial and endometrial ultrasound features were evaluated. All patients reported an increase in pelvic pain. At US evaluation intramyometrial cystic areas were found in all six cases (100%). All patients showed an enhancement of adenomyosis features.The intra-myometrial cysts appeared enlarged and the vascularization enhanced when compared to the images of the pretreatment scan. In patients with adenomyosis treated with UPA due to an erroneous diagnosis of uterine fibroids we observed a worsening of the US features of adenomyosis and of the painful symptoms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic. People with airways disease are at higher risk of respiratory infection, and viruses can trigger respiratory exacerbations. Patients with airways disease may therefore be more susceptible to SARS-CoV-2 infection, development of covid-19, or be at higher risk of adverse outcomes. Here we review susceptibility, based on current epidemiological studies, and explore biological mechanisms. Evidence from multiple large observational studies has shown chronic obstructive pulmonary disease (COPD) is a significant risk factor for covid-19 related mortality. Whether people with asthma are more susceptible to infection or severe outcomes has been much debated but appears to be related to their asthma phenotype and severity. To what extent these differences are biological or influenced by public health non-pharmacological interventions is difficult to quantify. Biological mechanisms that may influence susceptibility and adverse outcomes in airways disease include the increased expression of protein receptors enabling viral cell entry, dysfunctional epithelial airway immunity, type-2 inflammation and the use of inhaled corticosteroids. A better understanding of the susceptibility and mechanisms is essential for developing preventative and therapeutic strategies. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity.We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection.Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score at 6 months.Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by -10.6 [-15.9 to -5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported.Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

A previous systematic review has shown associations between exposure to high temperatures and negative birth outcomes. To date, a scoping review for heat indices and their use to measure effects of heat on maternal and perinatal health has not been considered. Objectives To provide a scoping review on heat stress and indices for those interested in the epidemiology and working in extreme heat and maternal perinatal health. Methods This study is a scoping review based on a previous review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. It identifies the main ways heat stress through different heat indices impacts maternal and perinatal health in available literature. For documents that met the inclusion criteria, we extracted 23 publications. Results We find four heat indices: heat index, apparent temperature, wet bulb globe temperature and universal thermal climate index. Exposure to elevated levels of heat stress can be associated with preterm birth. In addition, the more intense and prolonged duration of exposure to heat stress, the greater the risk of stillbirth. Negative birth outcomes can occur from change in hormonal levels (ie, cortisol), dehydration and blood flow diversion away from the placenta and fetus when suffering from heat stress. All studies demonstrate that certain socioeconomic factors influence the effect of heat on maternal and perinatal health outcomes. Conclusion We make three suggestions based on the results: (1) heat indices should be standardised across studies and explained. (2) An increased number of perinatal and maternal health outcomes explored. Finally, (3) enhanced collaboration across climate and health to improve understanding.

Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach.

Climate change represents a fundamental threat to human health, with pregnant women and newborns being more susceptible than other populations. In this review, we aimed to describe the current landscape of available epidemiological evidence on key climate risks on maternal and newborn health (MNH).

Abstract Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM. A thorough knowledge of the risk factors and genes involved in the development of GDM, along with an understanding of the underlying pathophysiological mechanisms are crucial to properly identify patients at risk of developing this condition. There is growing evidence showing that myo-inositol, combined with an appropriate therapeutic regimen for GDM, can provide additional benefits to the patient. The aim of this review is to analyze the role of inositol isomers – especially myo-inositol (MYO-INS) – in the treatment of patients with GDM.

<b>Introduction:</b> Metered cryospray (MCS) is a bronchoscopic treatment that uses liquid nitrogen to ablate, and repopulate the bronchial epithelium with a healthier phenotype, in patients with COPD with chronic bronchitis (CB). <b>Aims and Objectives:</b> To investigate the effect of MCS on symptoms of CB in patients with COPD with CB. <b>Methods:</b> St. George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were collected from 17 subjects, in patients receiving open-label crossover MCS treatment. NCT03892694. <b>Results:</b> Change in SGRQ total (-8.5 points n=15 p=<b>0.04</b>) and CAT (-3.5 points n=15 p=<b>0.02</b>) scores, were observed at 6-months post-MCS, relative to baseline. Change at 6-months post-MCS relative to baseline, was observed in SGRQ total (-12.1 points n=15 p=<b>0.02</b>) and CAT (-3.3 points n=15 p=<b>0.03</b>) scores, compared to change at 6-months post-sham procedure relative to baseline. Changes in SGRQ and CAT scores at 6-months post-MCS, relative to baseline. p-value calculated with paired t-test; n=15 <b>Conclusions:</b> The clinically meaningful and statistically significant changes in measures of symptoms of CB, in patients receiving cross-over MCS, reiterates that MCS is efficacious in improving quality of life in patients with COPD with CB.

Objectives To evaluate transvaginal ultrasound (TVUS) findings in patients who underwent segmental rectosigmoid resection for deep infiltrating endometriosis (DIE) and to correlate postsurgical ultrasound findings with symptoms. Methods A retrospective study including 50 premenopausal women with bowel endometriosis who underwent segmental rectosigmoid resection was conducted. Within 12 months after surgery, a TVUS examination was conducted in all patients to evaluate the presence of postsurgical endometriosis locations and symptoms, including dysmenorrhea, dyspareunia, dysuria, dyschezia, and chronic pelvic pain. Pelvic pain was assessed in all women by a visual analog scale. Results At the follow‐up 32 of 50 patients were receiving medical treatment, whereas 18 women declined postsurgical medical therapy and tried to conceive. A high percentage of adhesions (90%) was found. A negative sliding sign (a simple diagnostic sign that can be performed during a TVUS examination, consisting of gentle pressure applied by both the vaginal transducer and the examiner's hand on the abdomen; if the uterus does not glide freely along with the rectum and posterior fornix, the sign is considered negative, and adhesions can be suspected) was found in 29 (58%) women and was associated with bowel symptoms. Recurrence of posterior DIE was found in 9 cases (18%) and endometriomas in 8 cases (16%). Adenomyosis was observed in 80% of women and was present in all symptomatic patients. Conclusions After rectosigmoid segmental resection patients with DIE may continue to be symptomatic, and postoperative TVUS may reveal foci of disease or pelvic adhesions. Moreover, adenomyosis could be linked to symptoms experienced during follow up. Women should be aware that painful symptoms and alterations of pelvic organs could still be present after surgery and be detectable by TVUS.

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. &lt;b&gt;&lt;i&gt;Method:&lt;/i&gt;&lt;/b&gt; The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30–60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, &lt;i&gt;p&lt;/i&gt; = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, &lt;i&gt;p&lt;/i&gt; = 0.227, not statistically significant). Symptom scores and lung function showed stability. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD.

A 79-year-old female was referred to our Gynecologic Department presenting with a pelvic magnetic resonance imaging (MRI), showing an adnexal mass, later confirmed at the pelvic examination. The patient's routine laboratory tests were normal. A sonographic examination was performed with inconclusive results. Although the ultrasonography excluded the presence of vascularization and malignant degeneration, the adnexal localization appeared to be dubious. The laparoscopy and the subsequent histologic examination revealed the presence of a mucocele of the appendix. The following case report focuses the attention on a misdiagnosis of appendiceal mucocele. The misdiagnosis caused no negative impact on the treatment that in this case was adequate and successful.

#### What you need to know A 55 year old man attends surgery with a productive cough for nine months, which he has put down to his smoking. He had “chest infections” the previous winter and takes ramipril for hypertension. His breathing is now preventing him from climbing stairs.

Targeted lung denervation (TLD) is a novel bronchoscopic treatment for COPD GOLD-D patients. The TLD treatment disrupts the peribronchial vagal innervation of the airways by radiofrequency energy, and consequently decreases the release of acetylcholine [[1]Slebos D.-J. Shah P.L. Herth F.J. Pison C. Schumann C. Hübner R.-H. Bonta P.I. Kessler R. Gesierich W. Darwiche K. Lamprecht B. Perez T. Skowasch D. Deslee G. Marceau A. Sciurba F.C. Gosens R. Hartman J.E. Srikanthan K. Duller M. Valipour A. Safety and adverse events after targeted lung denervation for symptomatic moderate to severe COPD (AIRFLOW): a multicenter randomized controlled trial.Am. J. Respir. Crit. Care Med. 2019; 200: 1477-1486https://doi.org/10.1164/rccm.201903-0624ocCrossref PubMed Scopus (0) Google Scholar]. TLD has shown to have a positive effect on the occurrence of COPD exacerbations after treatment [[1]Slebos D.-J. Shah P.L. Herth F.J. Pison C. Schumann C. Hübner R.-H. Bonta P.I. Kessler R. Gesierich W. Darwiche K. Lamprecht B. Perez T. Skowasch D. Deslee G. Marceau A. Sciurba F.C. Gosens R. Hartman J.E. Srikanthan K. Duller M. Valipour A. Safety and adverse events after targeted lung denervation for symptomatic moderate to severe COPD (AIRFLOW): a multicenter randomized controlled trial.Am. J. Respir. Crit. Care Med. 2019; 200: 1477-1486https://doi.org/10.1164/rccm.201903-0624ocCrossref PubMed Scopus (0) Google Scholar]. Recently, it was shown that 3 years after TLD treatment the lung function was stable compared to before treatment [[2]Pison C. Shah P. Slebos D.-J. Ninane V. Janssens W. Perez T. Kessler R. Garner J. Hartman J. Deslee G. Bruno D. Mayr A. Peterson A. Mayse M. Valipour A. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 three-year outcomes.Respir. Res. 2021; 22https://doi.org/10.1186/s12931-021-01664-5Crossref Scopus (2) Google Scholar]. However, it is not known how this relates to the lung function decline before treatment. Therefore, our aim was to investigate the annual decline in FEV1 before and up to 3 years after TLD. We included patients who underwent TLD in the AIRFLOW-1 [[3]Valipour A. Shah P.L. Pison C. Ninane V. Janssens W. Perez T. Kessler R. Deslee G. Garner J. Abele C. Hartman J.E. Slebos D.J. Safety and dose study of targeted lung denervation in moderate/severe COPD patients.Respiration. 2019; 98: 329-339https://doi.org/10.1159/000500463Crossref PubMed Scopus (17) Google Scholar] or AIRFLOW-2 [[1]Slebos D.-J. Shah P.L. Herth F.J. Pison C. Schumann C. Hübner R.-H. Bonta P.I. Kessler R. Gesierich W. Darwiche K. Lamprecht B. Perez T. Skowasch D. Deslee G. Marceau A. Sciurba F.C. Gosens R. Hartman J.E. Srikanthan K. Duller M. Valipour A. Safety and adverse events after targeted lung denervation for symptomatic moderate to severe COPD (AIRFLOW): a multicenter randomized controlled trial.Am. J. Respir. Crit. Care Med. 2019; 200: 1477-1486https://doi.org/10.1164/rccm.201903-0624ocCrossref PubMed Scopus (0) Google Scholar] trials in 5 study sites with the highest patient enrolment and who completed the 3 year follow up (FU) visit. Local teams such as referral hospitals and patients’ primary care teams were contacted to try to obtain as many pre-treatment spirometry results as possible. To be able to calculate a reliable decline in FEV1, we only included patients for which we were able to obtain at least 4 pre-treatment spirometry results within at least the preceding 2 years prior to their TLD procedure. At baseline and annually for up to 3 years after treatment, patients visited the study-sites and performed spirometry measurements according to the study protocol. The studies were approved by the ethics committees of all participating hospitals and all patients provided informed consent. In the selected study sites, 61 patients were treated of whom 23 did not complete the 3 year FU and of 20 patients we were not able to obtain reliable pre-treatment spirometry results. Therefore, 18 patients fulfilled our inclusion criteria for this analysis (50% male, mean age 62 ± 6 years, FEV1: 38 ± 10% of predicted, FVC: 90 ± 16% of predicted). Table 1 shows the FEV1 and FVC over time. FEV1 was not statistically significantly different between the different time points (Repeated measure ANOVA: F = 2.70, p = 0.08), while FVC was only statistically significantly different between the 1 and 2 year FU time point (F = 4.99, p = 0.014). The mean annual decline in FEV1 before treatment was −59 ± 61 mL/year and after treatment −20 ± 51 mL/year, which was statistically significantly different (p = 0.041, paired sample t-test) (see Fig. 1).Table 1Lung function outcomes at baseline and up to 3 year follow up after TLD treatment.Baseline1 year follow up2 year follow up3 year follow upFp-valueFEV1, liter1.05 ± 0.321.09 ± 0.401.05 ± 0.380.99 ± 0.352.700.080FVC, liter3.09 ± 0.783.22 ± 0.74*2.97 ± 0.75*3.00 ± 0.764.990.014Data are presented as mean ± standard deviation. Repeated-measures ANOVA was used to test for differences between the different timepoints.FEV1: Mauchly's test indicated that the assumption of sphericity had been violated (X2(5) = 12.82, p = 0.025), therefore Greenhouse-Geisser corrected tests are reported (ϵ = 0.69). FVC: Mauchly's test indicated that the assumption of sphericity had been violated (X2(5) = 13.33, p = 0.021), therefore Greenhouse-Geisser corrected tests are reported (ϵ = 0.64). FVC was only statistically significantly different between the 1 and 2 year follow up time point. Open table in a new tab Data are presented as mean ± standard deviation. Repeated-measures ANOVA was used to test for differences between the different timepoints. FEV1: Mauchly's test indicated that the assumption of sphericity had been violated (X2(5) = 12.82, p = 0.025), therefore Greenhouse-Geisser corrected tests are reported (ϵ = 0.69). FVC: Mauchly's test indicated that the assumption of sphericity had been violated (X2(5) = 13.33, p = 0.021), therefore Greenhouse-Geisser corrected tests are reported (ϵ = 0.64). FVC was only statistically significantly different between the 1 and 2 year follow up time point. Our results show that the FEV1 did not significantly decrease compared to baseline at 3 years after treatment. It could be that our findings are an overestimation and positively influenced by the fact that we only included patients who visited the study-sites at 3 year FU and had at least 4 pre-treatment FEV1 results over a 2 year period. However, our results are comparable with the recently published paper of Pison et al. who also showed that the lung function did not change at 3 years after TLD treatment in 74% of the AIRFLOW-1 study patients who completed 3-year study FU [[2]Pison C. Shah P. Slebos D.-J. Ninane V. Janssens W. Perez T. Kessler R. Garner J. Hartman J. Deslee G. Bruno D. Mayr A. Peterson A. Mayse M. Valipour A. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 three-year outcomes.Respir. Res. 2021; 22https://doi.org/10.1186/s12931-021-01664-5Crossref Scopus (2) Google Scholar]. Furthermore, a control group is lacking with information on the actual decline in lung function over time in this specific patient group. Currently a large clinical trial with 5 year follow up is underway (Airflow-3, NCT03639051) [[4]Slebos D.J. Degano B. Valipour A. Shah P.L. Deslée G. Sciurba F.C. Design for a multicenter, randomized, sham-controlled study to evaluate safety and efficacy after treatment with the Nuvaira® lung denervation system in subjects with chronic obstructive pulmonary disease (AIRFLOW-3).BMC Pulm. Med. 2020; 20https://doi.org/10.1186/s12890-020-1058-5Crossref PubMed Scopus (8) Google Scholar] which has the potential to confirm our results. The decline in FEV1 before treatment in our patients (59 mL/year) was in line with a review that reported an average FEV1 decline in GOLD stage III patients of 56–59 mL/year [[5]Tantucci C. Modina D. Lung function decline in COPD.Int. J. COPD. 2012; : 95-99https://doi.org/10.2147/COPD.S27480Crossref Scopus (179) Google Scholar]. Of course, as COPD progresses and the FEV1 decreases the decline in FEV1 will also flatten. However, the FEV1 decline after treatment in our population (20 mL/year) was 66% lower compared to before treatment, and also lower than the 23 and 34 mL/year found earlier in GOLD stage IV patients [[5]Tantucci C. Modina D. Lung function decline in COPD.Int. J. COPD. 2012; : 95-99https://doi.org/10.2147/COPD.S27480Crossref Scopus (179) Google Scholar]. There is previous documentation that frequent COPD exacerbations were associated with a more rapid lung function decline [[6]Donaldson G.C. Seemungal T.A.R. Bhowmik A. Wedzicha J.A. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.Thorax. 2002; 57: 847-852https://doi.org/10.1136/thorax.57.10.847Crossref PubMed Scopus (1711) Google Scholar]. Therefore, the amelioration of the decline in FEV1 may be explained by the previously reported decrease in COPD exacerbations after TLD treatment [[1]Slebos D.-J. Shah P.L. Herth F.J. Pison C. Schumann C. Hübner R.-H. Bonta P.I. Kessler R. Gesierich W. Darwiche K. Lamprecht B. Perez T. Skowasch D. Deslee G. Marceau A. Sciurba F.C. Gosens R. Hartman J.E. Srikanthan K. Duller M. Valipour A. Safety and adverse events after targeted lung denervation for symptomatic moderate to severe COPD (AIRFLOW): a multicenter randomized controlled trial.Am. J. Respir. Crit. Care Med. 2019; 200: 1477-1486https://doi.org/10.1164/rccm.201903-0624ocCrossref PubMed Scopus (0) Google Scholar]. In contrast, no difference in FEV1 decline was found in a study that investigated tiotropium versus placebo, while there was a significant reduction in exacerbation frequency in the tiotropium-group compared to the placebo-group [[7]Tashkin D. Celli B. Senn S. Burkhart D. Kesten S. Menjoge S. Decramer M. A 4-year trial of tiotropium in chronic obstructive pulmonary disease.N. Engl. J. Med. 2008; 359: 1543-1554Crossref PubMed Scopus (1859) Google Scholar]. However, this study did not have information on pre-treatment spirometry results. It would have been interesting to have been able to investigate whether the difference between pre-treatment and post-treatment exacerbation rate was associated with the lung function decline following treatment. Unfortunately, the exacerbation rate before treatment was not captured in this study and our sample size is too small for such analysis. Other potential reasons for the amelioration in lung function decline after TLD could be a positive effect of the treatment on bronchial hyperreactivity and/or airway inflammation [[8]Rijcken B. Schouten J.P. Xu X. Rosner B. Weiss S.T. Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1.Am. J. Respir. Crit. Care Med. 1995; 154: S246-S249Crossref Google Scholar,[9]Kistemaker L.E. Slebos D.J. Meurs H. Kerstjens H.A. Gosens R. Anti-inflammatory effects of targeted lung denervation in patients with COPD.Eur. Respir. J. 2015; 46: 1489-1492https://doi.org/10.1183/13993003.00413-2015Crossref PubMed Scopus (22) Google Scholar]. Recently, a systematic review also showed that pharmacotherapy ameliorated the rate of lung function decline with a 5 mL/yr reduction in favor of active treatment arms [[10]Celli B. Julie A. Cowans N. Crim C. Hartley F. Martinez Benjamin Morris A. Quasny H. Yates J. Vestbo J. Calverley P. Pharmacotherapy and lung function decline in patients with chronic obstructive pulmonary disease. A Systematic Review.AJRCCM. 2021; 203: 689-698Google Scholar]. Nonetheless, the evidence of the effect of TLD on both outcomes needs to be investigated further. A further explanation could be due to the patient's having frequent respiratory specialist care as part of the clinical trial for the 3 years following their TLD. However, we perceive this to likely only have a small role, due to the patients selected having already been undergoing lung function monitoring, and thus likely already to be under care of a physician for their COPD. To conclude, our results show that the lung function remained stable up to 3 years after TLD treatment and that the annual rate of decline in FEV1 decreased after treatment. The currently executed AIRFLOW-3 trial is currently recruiting and will hopefully confirm our results and explore whether a reduction in COPD exacerbation is the explanation for our findings. JEH and DJS designed the analysis, wrote the first draft of the manuscript, and made revisions after feedback from co-authors. All the authors meet the definition of an author as stated by the International Committee of Medical Journal Editors, and all have seen and approved the final manuscript. The AIRFLOW-1 and AIRFLOW-2 trials were funded by Nuvaira Inc, Minneapolis, MN, USA . The funding source had no involvement in this analysis or in the writing of this manuscript.

Approximately 1.2 million people in the UK suffer from chronic obstructive pulmonary disease (COPD), leading to 115,000 unplanned hospital admissions per year. Smoking remains the leading cause (over 70% of cases) of COPD in high-income countries, but globally, especially in low-middle income countries only 30–40% of cases are attributed to smoking. COPD should be suspected among individuals with typical symptoms (dyspnoea, cough, wheeze, recurrent chest infections) but diagnosis requires confirmatory obstructive spirometry. Clinicians should aim to exclude alternative diagnoses, grade disease severity, personalize treatment and identify co-morbidities. The mainstays of COPD management are smoking cessation, vaccination, inhaled therapies and pulmonary rehabilitation. Therapy should particularly target symptom burden and exacerbation frequency. Recently developed interventional techniques and emerging evidence for the use of monoclonal antibody therapies appear promising. That said, the current frontier for improving outcomes might lie in a better understanding of disease trajectories, prompt diagnosis and earlier intervention to limit progressive lung function decline.

SESSION TITLE: Valves, Sprays, and Air Leaks: Things We Do for Lung SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/10/2023 12:55 pm - 01:40 pm PURPOSE: Introduction: COPD is a progressive respiratory condition associated with declining health metrics.1 Chronic bronchitis (CB) is a biomarker of COPD, indicative of accelerated lung function loss, worse health-related quality of life, and increased mortality.2 Metered cryospray (MCS) is a bronchoscopic treatment that uses liquid nitrogen to ablate the bronchial epithelium, permitting repopulation with a healthier phenotype, in patients with COPD and CB.3 Aims and objectives: To investigate the long-term effects of MCS on patient-reported outcome measures (PROM) in patients with COPD and CB. METHODS: Methods: St Georges respiratory questionnaire (SGRQ), COPD assessment test (CAT), and the Leicester Cough Questionnaire (LCQ) were collected from 34 patients with COPD with CB to 36-months post-MCS treatment in an open labelled trial. P-values <0.05 calculated using a paired t-test were considered significant. Data to 12 months post-MCS have been described in this cohort (NCT02483637)3. RESULTS: Results: A clinically meaningful and statistically significant change in SGRQ impact (-6.8 ± 13.9 points; n=25; p=0.022), CAT (-2.2 ± 5.0 points; n=25; p=0.038), and LCQ (15.3 ± 23.4 points; n=15; p=0.024) scores were observed at 24-months post-MCS, relative to baseline. Clinically meaningful change in SGRQ total score (-5.2 ± 12.7 points; n=25; p=0.053) was observed to 24 months post-MCS, relative to baseline. A clinically meaningful change in LCQ score (12.1 ± 32.9 points; n=11; p=0.250) was observed at 36-months post-MCS, relative to baseline. No clinically meaningful or statistically significant changes in SGRQ (total -1.7 ± 14.7 points; n=20; p=0.605, symptoms -3.7 ± 24.0 points; p=0.497, impacts -5.8 ± 18.5 points; n=20; p=0.175, activity 6.4 ± 16.7 points; n=20; p=0.101), CAT (-1.3 ± 6.2 points; n=19; p=0.376) scores were observed at 36-months post-MCS, relative to baseline. CONCLUSIONS: Conclusions: Enduring clinically meaningful and statistically significant changes in SGRQ, CAT and LCQ scores are demonstrated at 24-months post-MCS treatment. Despite attrition, the trend towards improvement persists across health metrics at 36 months, justifying the need for randomised controlled studies investigating MCS treatment, to better understand treatment effects, and the consideration of retreatment. References Burge PS et al. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000 May 13;320(7245):1297-303 2. Vestbo J et al. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. AJRCC. 1996 May;153(5):1530-5 3. Garner JL et al. A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD. ERJ. 2020 Dec 1;56(6) CLINICAL IMPLICATIONS: Long-term enhancement in patient-reported-outcome measures is demonstrated post-MCS in patients with COPD and CB. Randomised controlled trials are needed to better understand treatment effects, and the impact of repeat treatment in patients with COPD and CB DISCLOSURES: No relevant relationships by Francesca Conway No relevant relationships by Justin Garner No relevant relationships by Jorine Hartman No relevant relationships by Karin Klooster No relevant relationships by Christopher Orton No relevant relationships by Pallav Shah No disclosure on file for Tawimas Shaipanich No relevant relationships by Don Sin Scientific Medical Advisor relationship with PulmonX Corp, USA Please note: 2014-2023 Added 04/10/2023 by DJ Slebos, value=Consulting fee Investigator relationship with CSA Medical, USA Please note: 2016-2020 Added 04/10/2023 by DJ Slebos, source=Web Response, value=payment to institution Principal investigator relationship with Nuvaira, USA Please note: 2018-2023 Added 04/10/2023 by DJ Slebos, source=Web Response, value=consulting fees, study payment Removed 04/10/2023 by DJ Slebos, source=Web Response Principal Investigator relationship with Nuvaira USA Please note: 2018-2023 Added 04/10/2023 by DJ Slebos, source=Web Response, value=payments to insititution No relevant relationships by John Thornton No relevant relationships by James Tonkin

<b>Background:</b> EBVs are an effective treatment for hyperinflation in COPD. Microbial colonisation can occur in COPD, and may affect clinician and multidisciplinary team decision whether to offer patients EBVs. However, little is known about the prevalence or significance of bacterial, fungal or mycobacterial presence in patients undergoing EBV treatment. <b>Aim:</b> To assess the prevalence of bacteria, fungi and mycobacteria in patients undergoing EBV treatment for COPD. <b>Methods:</b> We performed a single-centre retrospective analysis of almost 4 years reviewing bronchoalveolar lavage (BAL) fluid culture results for bacteria, fungi and mycobacteria in patients undergoing EBV treatment for COPD between January 2017 – October 2020 at the Royal Brompton Hospital. Patients who had a baseline BAL (immediately prior to EBV insertion or at chartis bronchoscopy) were included. <b>Results:</b> 32 patients meeting the inclusion criteria were identified. 12 patients (37.5%) had positive BAL cultures for at least 1 organism. 9 patients (28%) had positive cultures for bacteria, 4 patients (12.5%) for fungi, and 2 (6%) for mycobacteria. <b>Conclusion:</b> There is a high prevalence of positive BAL cultures in patients with COPD undergoing EBV treatment. This warrants evaluation of its significance and whether positive cultures correlate with worse clinical outcomes post EBV treatment. Table 1

Accurate diagnosis and staging are essential for optimal management of patients with lung cancer. In this concise review, we take a look at the challenges faced by the respiratory community and patients, and the developments in interventional pulmonology and surgery aimed at overcoming these hurdles. We welcome the advances made in pleural disease, and consider the impact these will have on patient care. In particular, we focus on the diagnosis of peripheral lung lesions and the role of navigational bronchoscopy to obtain histological specimens through guided needle aspiration. We recognize the importance of nodal staging in lung cancer to dictate treatment and prognosis, and provide an update on the important role of endobronchial ultrasound (EBUS). Malignant airway obstruction remains a debilitating and distressing sequela of advanced malignancy. We consider treatment options for malignant airway obstruction, and the effects of a combination approach with endobronchial stents and external beam radiation to alleviate symptoms. We review the current position on the feasibility and safety of endobronchial drug delivery as an option for localized chemotherapy. Updates in thoracic surgery for lung cancer are presented, alongside recommendations for post-operative follow-up assessments. The role of the multidisciplinary team (MDT) remains pivotal to decision-making in lung cancer, and we analyse work suggesting a collection of minimum required data points recommended to improve the efficacy and accountability of the MDT. In addition, we review interesting updates in pleural disease over the last year, encompassing pleural effusions, pleural infection and pneumothoraces. We discuss the optimal management of malignant pleural effusions (MPE), by providing an update on the latest evidence for pleurodesis and indwelling pleural catheters (IPC). We also consider the safety of talc pleurodesis (TP), presenting work which quantifies the important complication of acute respiratory distress syndrome (ARDS). We recognize the challenges presented by trapped lung and review therapeutic approaches. Mechanisms of pleural infection and cell signalling pathways are key to advancing treatment of parapneumonic effusions (PPE), and these are highlighted. A clear knowledge of management of pneumothorax is essential for any respiratory physician. In this review, we pay particular attention to work on pneumothoraces in idiopathic pulmonary fibrosis (IPF), and their presentation as part of the hereditary Birt–Hogg–Dubé (BHD) syndrome. Francesca Conway, Christopher Orton, Samuel Kemp, Pallav Shah Standard initial staging of lung cancer is made on the basis of radiological findings, frequently following positron emission tomography/computed tomography imaging (PET/CT). However, there is increasing evidence that PET-CT alone is insufficient for appropriate nodal staging of lung cancer.1 With advances in therapy for lung cancer and in particular novel ablative techniques, accurate staging of nodal involvement is more crucial than ever. In the absence of evidence of metastatic disease, it is generally accepted that patients with PET-avid hilar or mediastinal nodes should proceed to minimally invasive sampling of mediastinal and/or hilar lymph nodes, commonly performed through EBUS-transbronchial needle aspiration (EBUS-TBNA). In patients with PET negative nodes, the role of EBUS is controversial, and previous work has demonstrated a discrepancy between results from PET-CT and EBUS.2 The most recent American College of Chest Physicians (ACCP) guidelines suggest, that if the tumour is central or hilar N1 nodes are present, to proceed to minimally invasive sampling of the nodes.3 If the tumour is peripheral, and there is no radiological suspicion of mediastinal or hilar nodes, these guidelines advise that there is no role for EBUS. Vial et al. bring into question the appropriateness of this recommendation in their prospective cohort study published in Respirology.4 They consecutively recruited patients with non-small cell lung cancer (NSCLC) between April 2009 and February 2014. A total of 120 participants were enrolled, of whom 75 patients' samples were included. EBUS-TBNA was performed under general anaesthetic in a specialist centre with the availability of rapid on-site evaluation (ROSE). The work demonstrated that the sensitivity of EBUS-TBNA in this cohort was 40% in the identification of N2 disease and 20% of patients with N0 or N1 disease by radiographic criteria were found to have N2 disease. In addition, N2 disease was also present in 5 of 61 (8%) patients with radiologically staged N0 disease and peripheral tumours, which is a group of patients which the ACCP guidelines do not recommend sampling. False negative results arose from lymph nodes which did not meet sampling criteria, for example, due to their small size. The study demonstrates the difficulty in proving N1 disease, which in some cases was due to the inability to sample intraparenchymal lymph nodes inaccessible to EBUS. This highlights potential limitations of current patient and node sampling selection, and whether we should be systematically sampling more nodes from each station, or routinely sample stations 4 and 7 regardless of size. The safety of EBUS has been reviewed in a review published in Respirology in 2017 by Vaidya et al., confirming very low rates of significant complications, with only six pneumothoraces reported out of 10 000 patients undergoing EBUS-TBNA only procedures.5 The review also states that there were five deaths attributed to EBUS to date at the time of the review. This suggests that where there is diagnostic doubt regarding nodal involvement, the risk–benefit will often fall in favour of performing minimally invasive sampling of the nodes to achieve accurate staging, as this alters prognosis and treatment options for the patient. Of course, this will be on an individual basis considering other patient-specific factors. Diagnosis of small peripheral pulmonary lesions can be challenging. Techniques such as radial EBUS, virtual navigational bronchoscopy (VNB) and electromagnetic navigation bronchoscopy (ENB) have been developed to try to improve the diagnostic yield of sampling such lesions. However, results presented in 2016 from the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) Registry suggested that conventional bronchoscopy performed better than guided bronchoscopy, even after adjustment for baseline factors.6 Diagnostic yield was 63.7% when no radial EBUS and no ENB were used, 57.0% with radial EBUS alone, 38.5% with ENB alone and 47.1% when the techniques were combined. This involved longitudinal data collection from 15 centres into a database; however, as the authors state, this was not a randomized control trial (RCT) directly comparing the techniques. These figures are in contrast to the results of the systematic review and meta-analysis published here in 2017 by Ali et al., showing a 70.6% diagnostic rate of radial EBUS at diagnosing peripheral lung lesions.7 The role of navigation techniques in the diagnosis of peripheral lesions remains uncertain, with several techniques and systems available to assist the bronchoscopist in obtaining diagnostic samples. Studies comparing different approaches are therefore very important in defining the role of these methods in the diagnostic work-up of patients. In 2018, Respirology published the first prospective RCT evaluating the use of virtual bronchoscopic navigation to assist CT-guided transbronchial biopsy in the diagnosis of peripheral pulmonary lesions.8 Kato et al. showed that virtual bronchoscopic navigation improves diagnostic yield of CT-guided transbronchial biopsy.8 Patients were recruited with small peripheral pulmonary nodules <20 mm in size and were randomized to CT-guided transbronchial biopsy (n = 50) or virtual bronchoscopic navigation transbronchial biopsy (n = 50). They demonstrated that the diagnostic yield was significantly higher in the VBN group versus the standard CT-guided biopsy group (84% vs 58%, respectively (P = 0.013)). The accompanying editorial by Asano reviews this along with other studies and discusses pros and cons of different imaging modalities in virtual bronchoscopic navigation.9 Malignant airway obstruction may arise from a primary bronchogenic carcinoma, secondary metastatic deposits or from extrathoracic compression or local invasion from nearby tumours such as oesophageal or thyroid tumours. Symptoms can be distressing and debilitating and it can represent a poor prognosis in terms of quality and quantity of life. Presentation may be rapid, requiring immediate treatment, or slower, allowing for a considered approach thus giving rise to a variety of treatment modalities. Management is usually performed with palliative intent, and intervention performed in the absence of significant symptom burden is often ill-advised. It is however necessary to offer active intervention to patients with significant distress to relieve their symptoms, even (and often) in the presence of advanced disease. With this in mind, it is unsurprising that therapeutic bronchoscopy is not without complication. A large prospective review of complications following therapeutic bronchoscopy for malignant central airways obstruction as part of the AQuIRE registry found that complications occurred in 3.9% of patients, with death occurring in 0.5%.10 Phillips’ editorial11 recognizes that the type (extraluminal or intraluminal), site and extent of obstruction are crucial in determining the appropriate treatment, and discusses potential therapeutic options. Options may include bronchoscopic debulking of the tumour (by laser therapy, cryotherapy, electrocautery or mechanical debridement), endobronchial stent placement and external beam radiotherapy (EBRT). These treatment modalities may be used alone or in combination. Bronchoscopic intervention is the mainstay of treatment for acute central airway obstruction, as benefit can be immediate, with successful recanalization being achieved in around 90% when performed by experienced clinicians.10 Complete or severe obstruction is likely to require immediate intervention, and hence is unlikely to be suited to EBRT alone, and conversely small cell tumours which may be highly radio- and chemo-sensitive, may be more suitable for sole treatment with EBRT.11 Respirology has published work by Mallow et al. comparing treatment outcomes in malignant airway obstruction.12 They performed a retrospective single-centre analysis of 237 patients with malignant airway obstruction, and compared EBRT, endobronchial stents and a combination of the two. It showed better survival in the combination group than in either single treatment group; however, the retrospective nature of the study introduces several biases. Also, as acknowledged by the authors, the retrospective design of the study meant it was not possible to assess the impact of treatment on quality of life or symptoms. Further prospective studies are needed to do so, as quality of life is crucial for such patients in their terminal phase of life, and prolonging life at the expense of quality of life is unlikely to be in patients’ best interests. However, previous trials set up to address these questions prospectively have had difficulty recruiting. Nonetheless, there is previous work showing that intervention improves symptoms,13 and it is possible that the same may be found in the combined treatment approach mentioned above. A previous prospective observational study of consecutive patients undergoing therapeutic bronchoscopy for central airway obstruction analysed health-related quality of life (HRQOL) and quality-adjusted survival in 102 patients.13 Improved HRQOL after therapeutic bronchoscopy was demonstrated as compared with baseline, resulting in approximately a 5.8% improvement in HRQOL per day of life.13 With the development of targeted therapies against specific genetic mutations in lung cancer, treatment outcomes have improved. Nonetheless, conventional chemotherapy remains at the core of many treatment regimens. The non-specific nature of these cytotoxic drugs leads to significant adverse effects limiting their utility. Direct administration of chemotherapy to the tumour in theory should allow targeted treatment of that tumour, with reduced systemic side effects. Tsukada et al. demonstrate safety and feasibility of paclitaxel delivery into porcine bronchial tissue.14 Paclitaxel is administered into bronchial tissue via a bronchoscopic catheter involving a balloon and a needle. Following instillation of the drug, sustained tissue concentrations were subsequently recorded up to 28 days following injection, and importantly the drug remained localized to the lung tissue. As no animal models of tumours exist, they were administered into healthy bronchial tissue rather than into a tumour. The group will continue their work looking at paclitaxel in human patients with malignant airway obstruction in an upcoming trial (NCT02066103). Steinfort's accompanying editorial discusses the potential uses of endobronchial intratumoral chemotherapy (EITC) with the possibility of a role in neoadjuvant therapy in NSCLC as well as in malignant airway obstruction.15 The use of intratumoral chemotherapy in severe malignant airway obstruction has been described previously, with work dating back more than 20 years, where a combination of chemotherapeutic agents were administered via flexible bronchoscopy, and relieved the obstruction in 81 of 93 patients.16 Lobectomy and lymph node dissection is the established surgical management of early stage thoracic cancer, whilst the suitability of limited resection remains controversial.17 At present, the only available RCT data comparing the two approaches was published by the Lung Cancer Study Group (LCSG) in 1995 and demonstrated that patients undergoing limited resection suffered increased recurrence rates versus lobectomy.18 The evaluation of segmentectomy in this study was complicated by the inclusion of patients undergoing wedge resection in the same ‘limited resection’ arm, and the 23-year interval has seen the advent of widespread CT and PET/CT availability. With this in mind, Nguyen's editorial in our July edition discusses the importance of these findings in the context of modern practice, and summarizes conflicting results from recent studies.19 One such study published in this journal, a retrospective observational review of the Surveillance, Epidemiology, and End Results (SEER) cancer registry, found no significant difference in the 5-year overall survival rates of 15 358 patients with primary NSCLC ≤ 20 mm, N0, treated with either lobectomy or anatomical segmentectomy (76% vs 74.4%, P = NS).20 Elderly patients were more likely to have undergone segmentectomy, with a subgroup analysis of those >75 years old, demonstrating comparable overall and lung cancer specific survival rates compared with lobectomy. These important findings add considerable weight to the need to reconsider the role of anatomical segmentectomy, which preserves pulmonary function and allows for mediastinal lymph node dissection.20 Several large RCTs (Japanese Clinical Oncology Group trial in Japan (JCOG0802); Alliance trial (CALGB140503) in North America) investigating the role of anatomical segmentectomy are ongoing, which will help establish whether segmentectomy will become the new surgical standard for early stage lung cancer.19, 21 Post-operative pneumonia is a significant cause of morbidity and mortality following lung cancer resection surgery, with laryngeal pathology through injury to the left recurrent laryngeal nerve or double-lumen tube-related vocal cord trauma often implicated.22-24 A prospective study published in Respirology by Fourdrain et al.,22 and considered in an accompanying editorial,23 demonstrated that endoscopic laryngeal assessment performed post-operatively is effective in diagnosing laryngeal pathology, with vocal cord paralysis found in 13 of 250 patients (5.2%). Furthermore, such findings were associated with a higher rate of post-operative pneumonia (P = 0.03), reintubation (P = 0.007) and a trend towards an increased 90-day mortality rate (P = 0.09). Dysphonia was found to be associated in all patients with vocal cord paralysis. The authors propose that post-operative laryngeal endoscopic assessment should be routinely performed in all patients undergoing surgical resection for lung cancer, as the early identification of vocal cord injury can lead to the instigation of measures to reduce the risk of aspiration such as vocal cord medialization, careful swallowing management and speech therapy. MDT meetings play a crucial role in determining the most appropriate, individualized management for patients with suspected and confirmed lung cancer. Stone et al. recently published an article in Respirology describing how they sought expert consensus opinion to formulate a minimum required data set for the lung cancer MDT.25 Their aim was to improve the management decision-making of the MDT, but also to have a systematic way of being able to evaluate the performance of the MDT and to allow benchmarking between different centres. They included lung MDT healthcare professionals in different states of Australia, and their work involved two survey rounds followed by a case conference to create a data set. Criteria suggested inclusion of patient details, risk factors including smoking and asbestos exposure, details on biopsy data and staging from various modalities (including CT, PET, EBUS and surgical pathology). They also include what the authors refer to as ‘timeliness data’, covering date of confirmed diagnosis and date of first treatments, and treatment details. The authors recognize that experts in certain fields were under-represented, including radiologists, pathologists and palliative care clinicians, and they postulate that future work could also involve patient participants. Nonetheless, the suggested data set gives a frame work through which the MDT can operate, and will be implemented in St Vincent's Hospital (Sydney) Lung Cancer MDT. Work such as this is important in constructing national and international guidelines around minimum standards for MDT discussion, and others are encouraged to share their experiences. Justin Garner, Karthi Srikanthan, Samuel Kemp, Pallav Shah Secondary spontaneous pneumothorax (SSP) is the occurrence of pneumothorax in patients with underlying lung disease. Pulmonary fibrosis can cause SSP, with rupture of subpleural blebs as the putative pathophysiological mechanism. One case series reports pulmonary fibrosis as the second highest contributor (8% of cases) behind emphysema (73%).26 Currently, there is very little information about SSP in IPF in the existing literature. One review reported an incidence of 30%.27 Nishimoto et al. strived to address this knowledge gap with a retrospective review of 84 IPF patients, focusing on investigating cumulative incidence and risk factors.28 Seventeen (20%) patients developed SSP with 8.5%, 12.5% and 17.7% at 1, 2 and 3 years, respectively. Multivariate analysis revealed two significant associations with SSP in IPF: lower body mass index (BMI) (hazard ratio (HR): 0.77; 95% CI: 0.64–0.91; p = 0.003) and extensive reticular abnormalities on CT (HR: 4.35; 95% CI: 1.24–15.3; P = 0.022). SSP was also shown to be an independent predictor of poor outcome (HR: 2.85; P = 0.006), with a median survival time from first onset of pneumothorax of 13.3 months. In many patients, SSP was not an isolated episode, with 12 of 17 (70.6%) patients suffering recurrent SSP and 7 of 17 (41%) requiring life-long chest drainage. The refractory nature of SSP in IPF is very likely to be due to the non-compliant parenchyma's inability to re-expand. SSP is an important complication in IPF. It can predict mortality and prove to be difficult to manage, thus requiring more randomized controlled trials to further our knowledge in this area. A less common but equally interesting cause of pneumothorax is BHD syndrome. BHD is an autosomal dominant condition accounting for 10–15% of familial pneumothorax.29 It is caused by inactivating mutations in the FLCN gene encoding the protein, folliculin.30-32 Patients can develop pulmonary cysts, facial fibrofolliculomas and renal tumours.29 Recurrent spontaneous pneumothoraces are a common presentation thought to result from rupture of irregularly shaped cysts abutting the pleura. Diagnosis of this condition is challenging and one that has important implications for both surgical approach in managing recurrent pneumothorax and implementing surveillance for renal malignancy for patients and their families. Ebana et al. have developed a novel composite scoring system with high sensitivity and specificity that distinguishes patients with suspicion of BHD from those with primary spontaneous pneumothorax utilizing five easily acquired clinical variables: (i) family history of pneumothorax, (ii) history of bilateral pneumothorax, (iii) age at first episode of pneumothorax, (iv) female gender and (v) BMI.33 Patients with BHD syndrome frequently have a family history of pneumothoraces, a personal history of bilateral and simultaneous pneumothorax, a later age of presentation (≥25 years old), no gender predominance and a higher BMI (≥18.5). The results of this retrospective single centre study are encouraging and validation in other centres is awaited with interest. TP is a commonly used and effective treatment for refractory pleural effusions and pneumothoraces. However, specific concerns have been raised about its safety, most prominently with regards to the risk of ARDS after TP. The frequency of post-pleurodesis ARDS varies from series to series, ranging from 0% to 9%.34-36 The study by Shinno et al.37 sought to determine risk factors that may predispose to this complication. They retrospectively reviewed patients who underwent pleurodesis with 4g or less of large particle size talc. Of the 27 patients, 4 (15%) developed ARDS, with older age (median age 80 vs 66; P = 0.02) and interstitial abnormalities (2/4 vs 1/23; P < 0.005) significantly higher in the ARDS group. A review of 35 patients who underwent pleurodesis with another agent, OK-432, was carried out in concurrence. Of note was that no patients in this group (with no significant difference in baseline characteristics to the talc group) developed ARDS. The authors suggested that it may be safer to use an alternative pleurodesis agent, such as OK-432, in older patients or those with interstitial abnormalities. However, the results should be interpreted with caution, given the very low number of patients who developed ARDS, and require confirmation with larger studies. The last factor was also found to be associated with TP failure on multivariate analysis (OR: 0.07; 95% CI: 0.02–0.22; P < 0.0001). A subset of patients underwent M-mode thoracic ultrasound prior to TP to assess potential expandability of the underlying atelectatic lung. A top-to-trough distance of the undulating pleural line of <2 mm was the cut-off for decreased lung expandability. This proved to be a successful predictor of incomplete lung re-expansion, with a sensitivity of 91% and a specificity of 88%. Top-to-trough distance in M-mode correlated well with TP success (r = 0.69; 95% CI: 0.44–0.84; P < 0.0001). Thoracic ultrasound has been shown to be adept at detecting pleural adhesions as well as malignant pleural disease.40, 41 This, alongside the marker of lung expandability described above, builds a very convincing argument for the use of thoracic ultrasound in the treatment decisions regarding MPE, particularly as the therapeutic options for MPE are increasing. In this era of personalized medicine and limited resources, thoracic ultrasound could prove a very useful, inexpensive and non-invasive tool to improve patient selection in the management of MPE. The IPC is an established treatment for MPE and is known to induce spontaneous pleurodesis, although studies vary in their incidence reporting. Pilot studies have suggested that administration of talc slurry via an IPC may be efficacious in inducing pleurodesis. IPC-Plus was a randomized, controlled, single-blinded, multicentre trial to investigate outpatient administration of talc slurry via IPC in patients with MPE.42 Subjects were excluded if there were signs of lung entrapment at 10 days after IPC placement. A total of 154 patients were randomized, with 69 randomized to talc slurry and 70 to intrapleural placebo via IPC. In the talc group, 30 of 69 (43%) achieved the primary endpoint of successful pleurodesis at 35 days. This compares with only 16 of 70 (23%) in the placebo group (HR: 2.20; 95% CI: 1.23–3.92; P = 0.008). The effect extended to full follow-up at 70 days (talc 51% vs placebo 27% (HR: 2.24; 95% CI: 1.31–3.85; P = 0.003)). Talc was also superior in improving patient-reported quality of life (mean EQ-5D-5L (EuroQoL-5 Dimension-5 Levels) difference 0.07 points (95% CI: 0.00–0.14; P = 0.04)) and breathlessness (mean visual analogue scale (VAS) difference: −7.9 points; 95% CI: −15.5 to −0.3; P = 0.04). There was no significant difference between adverse events between the two groups (OR: 0.90; 95% CI: 0.47–1.71; P = 0.74). Outpatient talc administration via IPC has thus been shown to be a more effective method of inducing pleurodesis than IPC alone, with a similar safety profile. There are robust data in favour of using IPC in MPE, with similar efficacy in controlling symptoms and maintaining quality of life to conventional talc slurry pleurodesis,43 and some evidence for reduction in hospitalization days in patients’ remaining life span.44 The AMPLE-2 trial was conducted to address the question of the optimal drainage regimen.45 Eighty-seven patients with MPE were randomized to either IPC with aggressive (daily) drainage (n = 43) or IPC with symptom-guided drainage (n = 44). There was no significant difference in the primary outcome which was a VAS for breathlessness (ratio of geometric means: 1.32; 95% CI: 0.88–1.97; P = 0.18). The aggressive regimen was more effective at inducing spontaneous pleurodesis (HR: 3.429; 95% CI: 1.413–8.320; P = 0.0064) and maintaining quality of life (difference in mean EQ-5D-5L scores: 0.112; 95% CI: 0.0198–0.204; P = 0.0174). There were no significant differences between the two arms in pain, hospital days, serious adverse events and mortality. An aggressive drainage programme could help to induce pleurodesis in patients where this is deemed important. Whilst in those whom palliation is prioritized, drainage guided by breathlessness could be just as effective at symptom control without the inconvenience of daily drainages. Despite our advances in knowledge of therapeutic drainage techniques, unexpandable lung can present a problem, and Huggins et al. provide a comprehensive and practical review of approaching this common complication of pleural disease.46 Unexpandable lung results in failure of apposition of the visceral and parietal pleura following therapeutic drainage. Establishing the presence or absence of an active inflammatory or malignant pleural process (‘entrapped’ vs ‘trapped’ lung, respectively) is essential to management. A combination of pleural fluid analysis, manometry and imaging can be used to evaluate the unexpandable lung. Malignant entrapped lung is most appropriately treated using an IPC provided there is relief of dyspnoea after initial drainage. In inflammatory lung entrapment, treatment is directed at the underlying cause and may progress to surgical decortication. Treatment of trapped lung depends on the clinical status of the patient—surgical decortication is reserved for symptomatic patients with extensive disease, while asymptomatic patients can be reassured. Further research is needed to clarify if the development of a trapped lung can be prevented. In patients with active malignancy who develop a pleural effusion with negative fluid cytology, the histological finding of non-specific pleuritis at pleuroscopy presents a diagnostic dilemma. Vakil et al. retrospectively report on long-term outcomes of 199 patients with suspected malignancy and an undiagnosed exudative pleural effusion of 1–1.5 L who underwent pleuroscopy between 2005 and 2015 at a single institution.47 A median of 10 biopsies were performed per patient and mean follow-up was 24.2 ± 10.0 months. Ninety patients (52%) were diagnosed with non-specific pleuritis. The negative predictive value for malignancy at 2-year follow-up was 97%: only three patients subsequently developed malignancy at follow-up. Over half of the cases of non-specific pleuritis were attributable to the effects of chemotherapy and radiotherapy. This pivotal study not only serves to corroborate the early teachings of Boutin et al.48 emphasizing the importance of histopathology, but also the finding of non-specific pleuritis can be relied on as robust evidence to commence aggressive therapy. As highlighted in Fielding's editorial, the use of pleural ultrasound to target smaller effusions, surface imaging such as tissue autofluorescence to better interrogate the pleural surface for abnormalities, and improved biopsy techniques to optimize diagnostic yield, will all serve towards establishing a confident diagnosis of benign disease at pleuroscopy.49 Bacterial PPE is a condition with high morbidity and mortality.50 The pathogenesis reflects a complex interplay of host, bacterial and cellular factors that trigger a cascade of inflammatory pathways that may culminate in empyema and pleural loculation, a therapeutic challenge, but increasingly regarded as a protective mechanism to wall off infection. Popowicz et al. provide an excellent overview of the intricate processes involved in their January 2018 editorial in Respirology.51 The clinical phenotype of affected patients is heterogeneous in presentation and in disease severity, and host susceptibility may be influenced by underlying co-morbidity and timing of therapy. Bacterial virulence is in part determined by a variety of products expressed by the causative organism. Lipoteichoic acid (LTA) is such an example of a major soluble cell wall component of Gram-positive bacteria (GPB) that binds to target cells inducing inflammation and coagulation.52, 53 Pleural mesothelial cells (PMC) are the first line of defence against invading pathogens and their armamentarium.54 In response to infection, they produce plasminogen activator inhibitor-1 (PAI-1) which impedes fibrinolysis and results in loculation.55, 56 PAI-1 is significantly elevated in complicated PPE (i.e. PPE which requires intervention) compared to uncomplicated PPE and is associated with residual pleural thickening.57, 58 However, no studies have implicated LTA in PAI-1 production. Lee et al. studied thirty consecutive patients with PPE of whom 12 had GPB (Staphylococcus aureus in 9 and Streptococcus pneumoniae in 3), 7 had Gram-negative bacteria (Klebsiella pneumoniae in 3, Pseudomonas aeruginosa in 3 and Escherichia coli in 1) and 11 had no growth in their pleural fluid culture.59 Their study showed that culture-positive PPE, especially that caused by GPB, was associated with significantly higher levels of PAI-1 compared to uncomplicated culture-negative PPE. Furthermore, in vitro, LTA upregulates PAI-1 expression through activation of Toll-like receptor 2 (TLR2)/c-Jun N-terminal kinase (JNK)/activator protein 1 (AP-1) signalling in human PMC. It is tempting to speculate that modulation of this pathway might prevent pleural organization. Conversely, advances in this field may help to develop novel pleurodesing agents for those patients with recurrent effusion or pneumothorax utilizing similar principles (e.g. LTA and staphylococcal superantigen). PLS and SK have been investigators in trials of endobronchial valves, coils, thermal ablation and the airway bypass procedure. PLS has consulted for Broncus, CSA Medical, Medtronic, Holaira, Olympus, PneumRx/BTG and Pulmonx.

<b>Introduction:</b> Metered cryospray (MCS) is a bronchoscopic treatment that delivers titrated applications of liquid nitrogen to the airways, to enact the controlled ablation and repopulation with a healthier bronchial epithelium, in patients with COPD with chronic bronchitis. <b>Aims and objectives:</b> To investigate the effect of MCS on quality of life, in patients with COPD, with chronic bronchitis. <b>Methods:</b> Patient-reported outcome measures (PROM) were collected from 31 subjects at baseline and at 6-months post-procedure, in a sham-controlled, blinded, 1:1 randomised trial. <b>Results:</b> A clinically meaningful and statistically significant change in St George9s respiratory questionnaire (SGRQ) total score was observed between arms, at 6-months post-MCS treatment (-9.6 points; p=0.02), compared to baseline. Change in PROM scores at 6-months post-procedure, compared to baseline. ^*Paired t-test for change in the MCS arm, relative to baseline. ^†Two samples t-test for the between arms difference, in change relative to baseline.&nbsp;SGRQ: St George’s respiratory questionnaire; CAT: COPD assessment test <b>Conclusions:</b> The change in patient-reported outcome measures at 6-months post-MCS, relative to baseline, confirms that MCS is efficacious in improving quality of life in patients with COPD, with chronic bronchitis.

To evaluate the effects of medical treatment with norethisterone acetate (NETA) on ultrasound signs of adenomyosis, pain symptoms and abnormal uterine bleeding (AUB). 40 women in fertile age with an ultrasound diagnosis of adenomyosis were enrolled. The ultrasonographic sings of adenomyosis were recorded by 2 and 3-dimensional transvaginal ultrasound. The severity was defined with an ultrasonographic score system which divides the disease in focal or diffuse adenomyosis of the external myometrium and of junctional zone (JZ) and adenomyoma. For each type of lesion a score number from 1 to 4 was assigned according to the myometrial involvement and JZ alterations. The total scores obtained were classified in: mild (1-7), moderate (8-13) and severe (14-20). The presence and the severity of pain symptoms and AUB were investigated. The follow-up evaluation was done 6 months after the beginning of therapy. A subgroup (n = 10) of women underwent an additional visit 3 months after the discontinuation of therapy. Patients were classified according to the ultrasonographic score system for adenomyosis. Before medical therapy, the distribution was: mild adenomyosis in 25% (n = 10), moderate in 40% (n = 16) and severe in 35% (n = 14) of women. After 6 months of administration of NETA 5 mg daily, a significant decrease of the severe ultrasonographic score was shown, when the entire group of women was considered. Concerning each ultrasound features of adenomyosis, the treatment significantly reduced uterine volume, size of focal adenomyosis foci and intramiometrial cysts, while linear striations remained unchanged. After 6-months of treatment, pain symptoms and AUB showed a significant improvement. 3 months after the discontinuation, ultrasonographic severity of disease and clinical symptoms showed a slight worsening without statistically significant differences. Medical treatment with NETA shows a significant change of ultrasonographic features of adenomyosis improving the severity of disease and clinical symptoms.

In their responses to our article,1 Brusasco and colleagues and Quanjer and colleagues suggest that current NICE guidelines on the management of chronic obstructive pulmonary disease (COPD) may lead to overdiagnosis in older people and underdiagnosis in younger people because of age related changes in lung function.2 3 Although this is possible, …

<h3>Introduction and Objectives</h3> The systemic inflammatory response syndrome (SIRS) criteria were developed in part as entry criteria for clinical trials of generalised inflammation from various causes. Despite being commonly used to assess inflammation in cardiac surgery, no one has evaluated whether the clinical defining criteria for inflammation equate to biochemical inflammation in this patient population. Our aim was to investigate whether the SIRS criteria equate to established biochemical indices of inflammation following cardiac surgery. <h3>Methods</h3> Retrospective analysis of prospectively collected data from an adult intensive care unit of a specialist cardiothoracic centre in the UK. 93 adult patients undergoing cardiac surgery admitted over a 34-month period between March 2004 and January 2007 were included. Patients were scored on the SIRS criteria from before to 72 h post-surgery. ELISAs were performed on archived plasma samples taken before surgery and at 4, 24, 48 and 72 h post-operatively to determine concentrations of IL-1ß, IL-1RA, IL-6, IL-8, IL-10, myeloperoxidase (MPO) and C reactive protein (CRP). <h3>Results</h3> Significantly elevated levels of all inflammatory indices were detected post-operatively with the exception of IL-1ß. Patients meeting SIRS criteria demonstrated higher levels of IL-6, IL-1RA and CRP compared to those who did not meet the criteria. An absence or only weak correlation was found between SIRS and mass of biomarker. <h3>Conclusions</h3> The clinical defining criteria for inflammation (SIRS criteria) do not equate to established biochemical indices of inflammation in cardiac surgery patients; hence the criteria alone should not be used to assess inflammation in this patient population.

To describe sonographic findings in patients with adenomyosis erroneously treated with ulipristal acetate (UPA). This an observational ultrasound (US) study on premenopausal patients who were treated with UPA for menorrhagia and uterine fibroids. Patients undergoing UPA treatment (5mg/24h of oral UPA for 3 months) usually had a pre treatment scan to diagnose and evaluate uterine fibroid's volume and endometrial status. The US exam is usually repeated at the end of the 3months treatment in order to assess effects on UPA on fibroids and endometrium. Ideally both these ultrasound scans should be performed in the same unit however not always this occurs. On 42 patients treated with UPA and observed in our ultrasound unit, 18 were scheduled only at the end of the treatment. Of these 6 patients did not show typical fibroids at US but an enlarged uterus with typical US features of adenomyosis. All patients receiving UPA showed after treatment amenorrhea and improvement of symptoms related to their previous anemia. 36 out of 42 patients with US detected fibroids showed also an improvement of their pain due to their uterine pathology whereas in the 6 patients with adenomyosis pelvic pain was increased and 2 of this patients stopped the UPA treatment within the first 2 months. In 21% (10/42) patients we observed typical endometrial thickening induced by UPA therapy of these 3 had adenomyosis. The adenomyosis features and especially intramyometrial cystic areas seem to be enlarged compared to pre-treatment scan not performed in our unit. Our observations on patients with adenomyosis who underwent UPA treatment for an erroneously diagnosis of uterine fibroid showed a worsened of the US adenomyotic features and of their pelvic pain, with an improvement of the bleeding. After these observations we should be aware to prescribe UPA therapy in patients with adenomyosis and a correct US diagnose of fibroids in mandatory to start the UPA treatment.

To correlate the ultrasound appearance of highly vascularised uterine myomas to the histopathological diagnosis. This retrospective study included patients presenting with an ultrasound diagnosis of uterine myoma characterised by a circumferential and intralesional vascular pattern with a colour score assessment of 3 or 4, according to the Morphological Uterus Sonographic Assessment (MUSA). All the patients underwent myomectomy or hysterectomy after the ultrasound examination. The ultrasound appearance of the myomas was analysed and described using the terms and definitions of the MUSA paper. The echogenicity of each myoma, the presence of cystic areas and the total myoma volume were recorded. The ultrasound characteristics were compared with the histological diagnosis. 52 patients were included in this study. Mean patient age was 42.5 years, 45 (86%) were in premenopause, 26 (50%) showed symptoms (pelvic pain, menorrhagia). At histological examination 25 (48%) myomas were compatible with a diagnosis of atypical leiomyoma (76% (19) hypercellular leiomyoma, 16% (4) myxoid leiomyoma, 8% (2) apoplectic leiomyoma). 25 (48%) were typical leiomyomas and 2 (4%) were adenomyomas. Cystic areas within the lesion were found in 32% (8/25) of atypical leiomyomas and in 16% (4/25) of typical leiomyomas. Ultrasound features such as circumferential and intralesional vascularity with a colour score of 3 or 4 and the presence of cystic areas may be predictive of atypical leiomyomas. Such features may be used to differentiate typical uterine myomas from the atypical variants in a pre-operative setting and to identify patients that may benefit from a conservative medical treatment rather than a radiological treatment.

Study Objective: To correlate the ultrasonographic appearance of highly vascularized uterine myomas with the hystopathological diagnosis.

In the last decade, pregnancy was considered as a therapeutic period for patients affected by endometriosis and painful symptoms. However, several studies have taken into consideration how endometriosis affects pregnancy achievement and pregnancy development, including obstetric complications. The adverse effects of endometriosis on the development of pregnancy include miscarriage, hypertensive disorders and pre-eclampsia, placenta previa, obstetric hemorrhages, preterm birth, small for gestational age, and adverse neonatal outcomes. The aim of this review is to analyze the current literature regarding the relationship between different forms of endometriosis (endometrioma, peritoneal endometriosis, deep endometriosis) and infertility, and the impact of endometriosis on pregnancy outcomes.

<h3>Background</h3> Singing for Lung Health (SLH) is an arts-based non-pharmacological intervention for people with long-term respiratory conditions that aims to improve symptoms and quality of life (QOL). Current research suggests face-to-face SLH can improve aspects of QOL and physical performance. There is interest in online, remotely delivered SLH, however no previous studies have assessed its impact. <h3>Methods</h3> A single blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH to usual care (UC) on health related quality of life (HRQoL) (RAND SF-36 Mental (MHC) and Physical (PHC) health composite scores). Secondary outcome measures were breathlessness (MRC dyspnoea scale and Dyspnoea-12), physical activity (daily step-count and PROactive cPACC), balance confidence (ABC score), anxiety (GAD-7), depression (PHQ-19) and COPD symptoms (CAT score). <h3>Results</h3> 115 participants with stable COPD were recruited and allocated into well-matched study arms. Median (IQR) age of 69 (62–74); 56.5% female; 87.8% White British ethnicity; 80% previously participated in pulmonary rehabilitation; MRC dyspnoea scale median (IQR) 4 (3–4); FEV1% predicted 49 (35 to 63); 13.0% current smokers, mean (SD) packyears 33.5 (20.3), BMI 25.7 (6.3); 10.4% were using supplementary oxygen therapy. 50 participants in each arm completed the study. Compared with UC, SLH participation was associated with preferable changes to the RAND SF-36 PHC (regression coefficient 1.77 [95%CI 0.11 - 3.44]; p=0.037)) but not MHC. No statistically significant between groups differences were observed in secondary outcome measures in the prespecified intention to treat analyses. In a prespecified responder analysis based on achieving a 10% improvement from baseline, the response rate for PHC was 32% of the SLH arm and 12.7% of UC (p=0.024). A statistically significant between group difference was not found in relation to a 10% improvement from baseline for the SF-36 MHC. More adverse events were reported in the UC(n=22) than SLH(n=16) arm. <h3>Discussion &amp; Conclusion</h3> Our findings suggest that a 12-week online SLH intervention can improve the physical component of HRQoL for people with COPD. Online SLH may be a useful addition to COPD management for selected individuals. <h3>Trial Registration</h3> ClinicalTrials.gov NCT04034212

<b>Background:</b> Oral anti-viral therapies are licensed worldwide in COVID-19 but indications and efficacy rates vary. <b>Aims and Objectives:</b> To evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19. <b>Methods:</b> We conducted a multi-centre, open-label, randomised controlled trial of oral favipiravir in patients newly hospitalised with COVID-19, in five centres worldwide. 500 participants were randomised 1:1 to receive oral favipiravir (1800 mg twice daily (BD) for one-day; 800 mg BD for nine-days) plus standard care (SC), or SC alone. NCT: 04373733. <b>Results:</b> Recruitment was performed between May 2020 and May 2021, with 251 patients randomised to favipiravir and 249 to SC. There was no difference in time to recovery in all patients (HR 1·06; 95% CI 0·89-1·27; n=499; p=0.52). A faster rate of recovery was observed in patients receiving favipiravir under the age of 60 years (HR 1·35; 95% CI 1·06-1·72; n=247, p=0·01). A 66 % improvement in mechanical ventilation free survival was evident in patients under 60-years of age (HR 0·34; 95% CI 0·13-0·85; n=247, p=0·02). A non-significant 26 % reduction in mortality was observed in patients receiving favipiravir (favipiravir: 26; SC: 34; p=0·24). No significant differences were observed in serious adverse events (SAE) between arms (favipiravir: 36 in 27 patients; SC: 33 in 27 patients). <b>Conclusions:</b> Orally administered favipiravir has a beneficial effect on recovery, and mechanical ventilation free-survival in patients under 60-years of age, hospitalised with COVID-19. Wider evaluation of anti-viral medications and their potential treatment combinations is warranted in patients with COVID-19.

<b><i>Background:</i></b> Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. <b><i>Objectives:</i></b> This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. <b><i>Method:</i></b> The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30–60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. <b><i>Results:</i></b> Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, <i>p</i> = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, <i>p</i> = 0.227, not statistically significant). Symptom scores and lung function showed stability. <b><i>Conclusions:</i></b> AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD.

British Journal of Hospital MedicineVol. 79, No. 1 Images in MedicineCoils to aid recoil: a bronchoscopic approach to lung reduction surgery in emphysemaFrancesca Conway, Simon DubreyFrancesca ConwaySearch for more papers by this author, Simon DubreySearch for more papers by this authorFrancesca Conway; Simon DubreyPublished Online:9 Jan 2018https://doi.org/10.12968/hmed.2018.79.1.51AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Shah PL, Zoumot Z, Singh S et al. (2013) Endobronchial coils for the treatment of severe emphysema with hyperinflation (RESET): a randomised controlled trial. Lancet Respir Med 1(3): 233–240. https://doi.org/https://doi.org/10.1016/S2213-2600(13)70047-X Crossref, Medline, Google ScholarSlebos DJ, Klooster K, Ernst A, Herth FJ, Kerstjens HA (2012) Bronchoscopic lung volume reduction coil treatment of patients with severe heterogeneous emphysema. Chest 142(3): 574–582. https://doi.org/https://doi.org/10.1378/chest.11-0730 Crossref, Medline, Google Scholar FiguresReferencesRelatedDetails 2 January 2018Volume 79Issue 1ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 9 January 2018 Published in print 2 January 2018 Information© MA Healthcare LimitedPDF download

The objective of this study is to evaluate the feasibility of MRI-TVUS fusion imaging in patients with deep infiltrating endometriosis (DIE). This prospective study included 20 patients with deep endometriosis referred to our Gynecology Unit. TVUS was performed in all patients, followed by pelvic MRI and MRI-TVUS fusion imaging. An accurate description of all sites of endometriosis, adenomyosis and DIE was reported for each examination. The mapping obtained through fusion imaging was compared to the results of TVUS and MRI separately. Fusion exams were interpreted by two experts in gynecologic ultrasound and pelvic MRI. Mean patient age was 34.4±6.9 years (range 21.0-48.0). The most frequent symptoms were dysmenorrhea (45%), dyspareunia (35%), infertility (25%). DIE of the rectovaginal septum was identified in 5/5 (100.0%) patients at TVUS, in 1/5 (20.0%) at MRI and in 5/5 (100.0%) at MRI-TVUS fusion imaging; DIE of the parametrium was found in 100.0% (3/3) of patients at MRI, in 0.0 % (0/3) at TVUS and in 100.0% of patients at fusion imaging; Uterosacral ligament involvement was reported in 12/17 (70.5%) at TVUS, in 14/17 (82.3%) at MRI and in 17/17 (100%) through fusion imaging; DIE of torus uterinus was detected in 6/11 (54.5%) at TVUS, in 10/11 (90.9%) at MRI and through fusion imaging in 11/11 (100.0%). Both MRI and fusion detected 8/8 (100.0%) cases of DIE of the round ligaments while only 1/8 cases were seen at TVUS (12.5%). Finally TVUS spotted DIE of ureters in 2/2 (100.0%), while no cases were reported through MRI (0/2 (0.0%)) and only 1 case was found through fusion (1/2(50.0%)). Fusion imaging is a new technology combining both TVUS and MRI. Although its role in daily practice has yet to be established, according to our initial results this technique may overcome the pitfalls of TVUS and MRI, offering a precise and advanced tool in the diagnosis of endometriosis, adenomyosis and DIE. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

To compare the different classifications in use for mullerian anomalies (ASRM, Salim, ESHRE/ESGE, CUME) in the diagnosis of normal/ arcuate/ septate uterus and to correlate the diagnosis with reproductive outcomes. Retrospective observational study conducted on 664 patients with 3D ultrasound diagnosis of arcuate/subseptate uterus (3-30 mm indentation). For each patient the uterine morphology was evaluated offline on the coronal plane and the following measurements were recorded: - uterine cavity width (W); septal length (L); uterine wall thickness (M); fundal indentation angle (α). Each uterus was subsequently subclassified according to the following classifications: ASRM (1988), Salim (2003), ESHRE/ESGE (2013), CUME (2018). The reproductive history of each patient was correlated to the cavitary measurements and the type of malformation according to the four classifications. 38% of patients were infertile, 62% had at least one pregnancy with 75% of abortion, 23% of secondary infertility and 13% of preterm labour. Primary infertility was greater in patients with narrow cavities (W), less uterine wall thickness (M) and greater indentation angle (α). Preterm birth was associated with longer septa (L), recurrent abortion with small and narrow septa (L, W). The current classifications are not homogeneous in the definition of subseptate uterus and are not correlated with reproductive outcomes. This correlation becomes significant by imposing an indentation cutoff ≥ 5mm to the ESHRE classification. According to our results the presence of a partial septum carries a negative effect on reproductive impacts. We identified certain uterine morphological features that seem to have a greater association with negative outcomes. Current classifications don't seem to correlate with reproductive outcomes. In our opinion, the determination of a minimum indentation cut-off could standardise the existing classifications by clearly defining the criteria for corrective surgery.

To correlate type and degree of adenomyosis, scored through a new system based on transvaginal sonographic (TVS) features, to patient's symptoms and fertility. This is a multicentre, prospective study performed in two Endometriosis tertiary referral centre (Canadian Task Force II-2) including 108 patients with ultrasound diagnosis of adenomyosis and 40 controls without any sonographic signs of myometrial pathologies. A new ultrasonographic scoring system designed to assess the severity and the extension of uterine adenomyosis was used to stage the disease in correlation with clinical symptoms. Menstrual uterine bleeding was assessed by a pictorial blood loss analysis chart (PBAC), painful symptoms were evaluated using a visual analogue scale (VAS) and infertility factors were considered. 108 patients with adenomyosis (mean age 37.7±7.7 yrs) were classified according to the proposed scoring system. The 22 patients with a score of focal-mild adenomyosis were younger compared to the patients with severe disease and showed a higher percentage (75.86%) of severe dysmenorrhea (VAS>5) and infertility (24.13%). The 20 patients with severe-diffuse adenomyosis, according to the score, showed in 95.24% of cases heavy menstrual bleeding (PBAC>100) and in 80.95% severe dysmenorrhea. All the 21 patients with adenomyomas had a PBAC>100. The evaluation of the extension of adenomyosis in the myometrium and in the JZ seems important in correlation to the severity of symptoms and infertility, as well as for an emerging request of surgical treatment. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

To assess the prevalence and ultrasound features of pelvic endometriosis in adolescents. This retrospective observational study included 238 adolescents (mean age 17.7 ±1.9 yrs.) referred to our Gynecological Clinic from January 2010 to December 2018. A 2D, 3D and power Doppler ultrasound examination (trans-vaginal or trans-rectal in adolescents with an intact hymen) was conducted in all patients. All possible locations of endometriosis were evaluated and recorded using a dedicated mapping sheet. Levels of pelvic pain were assessed in all adolescents by visual analogue scale (VAS). The most frequent symptoms were dysmenorrhea 57.1 % (136/238) and heavy menstrual bleeding 27% (64/238). Endometriosis was identified in 54 adolescents (22.7%). In particular, endometriomas were found in 17 adolescents (7.1%), deep infiltrating endometriosis (DIE) in 9 (3.8%), adhesions in 18 (7.6%) and ultrasound signs of adenomyosis in 16 (6.7%). In the group that complained dysmenorrhea (136 adolescents) the percentage of endometriosis was 18.5 %; in particular, endometriomas were present in 7.3 %, DIE in 2.9%, adenomyosis in 5.9% and adhesions in 10.3%. The rates of dysmenorrhea and heavy menstrual bleeding in adolescents are high. In teenagers with painful menses ultrasound features of endometriosis are significantly higher compared to those without. Considering the lacking knowledge of the disease among adolescents, those involved with teens, within the health profession or in schools, should be educated about endometriosis and its symptoms, to reduce the significant delay between the onset of symptoms and the diagnosis by referring to appropriate tertiary care centres. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

<b>Introduction:</b> Insertion of chest drains and pleural aspiration are expected competencies for general internal medicine (GIM) registrars, who need to confidently do so unsupervised. Training opportunities for non-respiratory trainees to learn these techniques (including thoracic ultrasound) are limited. <b>Aim:</b> Assess experience and confidence of non-respiratory GIM registrars in performing chest drains and pleural aspiration. <b>Methods:</b> GIM registrars in a Central London teaching hospital were invited to submit the number of pleural procedures performed over the past 6 months, and rate their confidence with pleural procedures (n=15). Respiratory registrars were excluded due to different training. <b>Results:</b> 10 medical registrars participated. In the past 6 months, 0 respondents had independently inserted a chest drain. Under supervision, 50% of respondents had inserted one drain, and the remainder 0 drains. None had inserted more than 1 drain. Most registrars had performed 0 pleural aspirations (60% for unsupervised, and 90% for supervised). Only 1 respondent felt confident inserting a drain unsupervised. 50% medical registrars would only insert a drain for pneumothorax under supervision, or not at all. 100% of respondents considered a pleural procedures simulation training day would be useful, and this was arranged. 100% of attendees rated their confidence as improved following the session. <b>Conclusion:</b> Confidence and experience of medical registrars with pleural procedures is limited in this single-centre study. This has important implications for patient safety, registrar training, and work force management. Current work involves expanding the study to other centres to assess if the results are generalisable.

Recently different classifications have recently been proposed to define a septate uterus mostly based on septal length, however great discrepancy has been observed between them especially for small septa. With regards to small indentations of the fundus the question is still open on the real reproductive impact of these small defects and the need for surgical treatment. The aim of this study was to propose other parameters based on 3D ultrasound (US) measurements to better classify small cavity indentation less 1cm. Retrospective study on patients with 3D US diagnosis of a uterine internal fundal indentation, reproductive history of each patient was correlated to the type of uterine anomaly according to different classifications. Indentation length and other 3D US parameters were correlated to reproductive outcome. 664 patients with 3D US diagnosis of a uterine internal fundal indentation of ≥ 3mm were classify as septate or arcuate/normal according to the following classifications: Salim (2003), ESHRE/ESGE (2013), ASRM (2016), CUME (2018). We divided the study population in 3 group: patients with uteri with a fundal indentation ≤ 5mm, >5<10mm and ≥ 10mm. The reproductive history of each patient was correlated to the type of uterine anomaly according to the four different classifications in the total population and in the 3 sub groups. High discrepancy between classifications were observed for septal lengths >5<10mm whereas patients with uterine indentation ≤ 5mm and ≥ 10mm showed similarity in type and reproductive outcomes. Small uterine septa of >5<10mm were evaluated with other parameters of cavity indentation the like cavity width, fundal myometrial thickness and indentation angle. These other parameters were correlated to reproductive outcome thus in order to determine which one correlate to fertility problems. We observed a large discrepancy between the 4 different classifications in diagnosing septate uterus especially in patients with indentation >5<10mm. Of the 664 patients 215 showed a fundal indentation length >5<10mm, of these 136 tried to conceive before our scan: 69(51%) were infertile, 65(48%) had at least one miscarriage, 38(28%) had recurrent abortion(≥2 miscarriages) and 5(4%) at least one delivery. The U Mann Whitney test showed among patients who try to conceive a significant correlation with recurrent abortion and an indentation angle > 128° Infertility was significantly correlated to a cavity width <32mm and a septal length/ fundal myometrial thickness ratio >75%. Current classifications don't seem to correlate to each other and with reproductive outcomes. These wide discrepancies between different classifications is more evident in small cavity indentation >5<10mm. For these small uterine septa additional parameters like indentation angle > 128° showed more risk for recurrent miscarriage and cavity width < 32mm and septal length/fundal myometrial thickness ratio > 75% is more correlated to infertility. Further prospective study should verify if these parameters could guide the management of patients with small uterine septa.

Journal of Ultrasound in MedicineVolume 40, Issue 10 p. 2259-2259 Response to Letter to the Editor Reply Francesco G. Martire MD, Corresponding Author Francesco G. Martire MD [email protected] orcid.org/0000-0002-0756-535X Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, Italy Address correspondence to E-mail: [email protected]Search for more papers by this authorErrico Zupi MD, Errico Zupi MD Department of Molecular and Developmental Medicine, University of Siena, Siena, ItalySearch for more papers by this authorLucia Lazzeri PhD, Lucia Lazzeri PhD Department of Molecular and Developmental Medicine, University of Siena, Siena, ItalySearch for more papers by this authorGiulia Morosetti MD, Giulia Morosetti MD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorFrancesca Conway MD, Francesca Conway MD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorGabriele Centini PhD, Gabriele Centini PhD Department of Molecular and Developmental Medicine, University of Siena, Siena, ItalySearch for more papers by this authorEugenio Solima PhD, Eugenio Solima PhD Azienda Socio-Sanitaria Territoriale Fatebenefratelli, Hospital Sacco, Milan, ItalySearch for more papers by this authorAdalgisa Pietropolli PhD, Adalgisa Pietropolli PhD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorEmilio Piccione PhD, Emilio Piccione PhD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorCaterina Exacoustos PhD, Caterina Exacoustos PhD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this author Francesco G. Martire MD, Corresponding Author Francesco G. Martire MD [email protected] orcid.org/0000-0002-0756-535X Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, Italy Address correspondence to E-mail: [email protected]Search for more papers by this authorErrico Zupi MD, Errico Zupi MD Department of Molecular and Developmental Medicine, University of Siena, Siena, ItalySearch for more papers by this authorLucia Lazzeri PhD, Lucia Lazzeri PhD Department of Molecular and Developmental Medicine, University of Siena, Siena, ItalySearch for more papers by this authorGiulia Morosetti MD, Giulia Morosetti MD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorFrancesca Conway MD, Francesca Conway MD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorGabriele Centini PhD, Gabriele Centini PhD Department of Molecular and Developmental Medicine, University of Siena, Siena, ItalySearch for more papers by this authorEugenio Solima PhD, Eugenio Solima PhD Azienda Socio-Sanitaria Territoriale Fatebenefratelli, Hospital Sacco, Milan, ItalySearch for more papers by this authorAdalgisa Pietropolli PhD, Adalgisa Pietropolli PhD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorEmilio Piccione PhD, Emilio Piccione PhD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this authorCaterina Exacoustos PhD, Caterina Exacoustos PhD Department of Surgical Sciences, Gynecologic Unit, University of Rome Tor Vergata, Rome, ItalySearch for more papers by this author First published: 12 December 2020 https://doi.org/10.1002/jum.15594Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume40, Issue10October 2021Pages 2259-2259 RelatedInformation

The aim of this study was to evaluate the use of ultrasound (US) soft markers as a first-line imaging tool to raise suspicion of forniceal involvement in women suspected of having deep endometriosis. We included in this prospective observational study all patients with clinical suspicion of deep endometriosis who underwent diagnostic transvaginal US evaluation from January 2016 to February 2017 in two academic department as a part of SANABA (Sardinia-Navarra-Barcelona) collaborative study. Several US soft markers were evaluated for prediction of uterosacral involvement: presence of US signs of uterine adenomyosis, presence of an endometrioma, adhesion of the ovary to the uterus (reduced ovarian mobility), presence of ‘kissing ovaries’ and absence of the ‘sliding sign’, using as the gold standard surgical evaluation for the presence of forniceal endometriosis. We included 194 patients with clinical suspicion of deep endometriosis. Of these, 28 had an surgical diagnosis of forniceal endometriosis. Only the absence of sliding sign showed a significant difference between patients with or without forniceal involvement (71% vs. 37% respectively, P = <0.001). The only significant variable found in the prediction model were absence of the sliding sign, odds ratio (OR), 4.27 95% CI 1.68-11.92. Thus, when the sliding sign was absent, transvaginal US showed a specificity of 63% and a sensitivity of 71%. US findings of absence of the sliding sign in patients with clinical suspicion of endometriosis multiply by 4 the probability of presence of forniceal endometriosis and indicate referral for expert US examination. This study was partly supported by Fondazione di Sardegna grant F74I19001010007.

Rationale:Targeted Lung Denervation (TLD) is a novel therapy being investigated for Chronic Obstructive Pulmonary Disease (COPD).Radiofrequency energy is delivered bronchoscopically to the main bronchi to disrupt the pulmonary parasympathetic nerves and reduce bronchoconstriction and mucus hypersecretion.The objective of this work was to determine the effect of TLD on acute exacerbations of COPD (AECOPD) in crossover subjects in the AIRFLOW-2 trial.Methods: The AIRFLOW-2 trial is a multicentre, randomised, double-blind, sham-controlled cross-over trial of TLD in patients with COPD.On enrolment to AIRFLOW-2, patients with COPD (modified Medical Research Council dyspnoea scale (mMRC) ≥ 2, COPD Assessment Test (CAT) score ≥ 10) on optimal medical therapy with an FEV 1 30-60% predicted were randomised to TLD or sham bronchoscopy in a 1:1 ratio.After 12 months, subjects in the sham arm were invited to cross over to the TLD treatment arm.The primary end point was the rate of respiratory adverse events.Secondary end points included all adverse events, changes in lung function and health related quality of life and symptom scores.Results: Approximately half of the subjects in the sham arm (20 of 41) were eligible and opted to cross over into the TLD arm and were subsequently followed up for 12 months (50% female, mean age 64.9 ± 6.9 years).Comparing the follow up periods after sham bronchoscopy and after crossover for these subjects, there was a trend towards a reduction in time to first AECOPD with a hazard ratio of 0.65, although this was not statistically significant (p = 0.28).There was also a non-statistically significant reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227).St George's Respiratory Questionnaire for COPD score, CAT score and lung function all showed stability over the 12-month period.Safety data was reassuring with no gastrointestinal severe adverse events.Conclusions:The current study was not powered for a significant effect on AECOPDs, but paired data from the 20 subjects in the crossover cohort of the AIRFLOW-2 trial show a trend for reduction in AECOPDs which supports the 12-month data from the randomisation phase.Furthermore, this crossover data provides additional safety information consistent with the 12-month randomisation data.The AIRFLOW-3 trial is a phase III clinical trial currently underway to further investigate the efficacy of TLD in reducing COPD exacerbations.