Steroid therapy in acute exacerbation of fibrotic interstitial lung disease.

BACKGROUND AND OBJECTIVE: Evidence for the benefit of steroid therapy in acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) is limited; however, they remain a cornerstone of management in other fibrotic interstitial lung diseases. This retrospective observational study assesses the effect of steroid treatment on in-hospital mortality in patients with acute exacerbation of fibrotic interstitial lung disease (AE-FILD) including IPF and non-IPF ILDs. METHODS: AE-FILD cases over a 10-year period were filtered using a code-based algorithm followed by individual case evaluation. Binary logistic regression analysis was used to assess the relationship between corticosteroid treatment (defined as ≥0.5 mg/kg/day of prednisolone-equivalent for ≥3 days within the first 72 h of admission) and in-hospital mortality or need for lung transplantation. Secondary outcomes included readmission, overall survival, requirement for domiciliary oxygen and rehabilitation. RESULTS: Across two centres a total of 107 AE-FILD subjects were included, of which 46 patients (43%) received acute steroid treatment. The steroid cohort was of younger age with fewer comorbidities but had higher oxygen requirements. Pre-admission FVC and DLCO, distribution of diagnoses and smoking history were similar. The mean steroid treatment dose was 4.59 mg/kg/day. Steroid use appeared to be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00-16.83; p = 0.049). In the steroid group, there appeared to be a reduced risk of all-cause mortality in non-IPF patients (HR 0.21; 95% CI 0.04-0.96; p = 0.04) compared to their IPF counterparts. Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all-cause mortality (HR 3.25; 95% CI 1.56-6.77; p < 0.01). CONCLUSION: In this two-centre retrospective study of 107 patients, AE-FILD demonstrates a high risk of mortality, at a level similar to that seen for AE-IPF, despite steroid treatment. Clinicians should consider other precipitating factors for exacerbations and use steroids judiciously. Further prospective trials are needed to determine the role of corticosteroids in AE-FILD.

Multidisciplinary meeting review in nonsmall cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure. METHODS: A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase and ClinicalTrials.gov were searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool. RESULTS: 2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30-3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43-4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29-3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21-0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85-3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55-0.72; p<0.00001). DISCUSSION: MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.

Occupational Interstitial Lung Diseases.

Occupational exposures are directly causal or partially contributory to the development of interstitial lung diseases. A detailed occupational history, relevant high-resolution computed tomography findings, and where relevant additional histopathology, are required to make a diagnosis. Treatment options are limited, and further exposure avoidance is likely to reduce disease progression.

How Involved Do Patients Want to Be in the Medical Decision-Making at the Initial Urogynecology Clinic Visit?

OBJECTIVE: The aim of this study was to compare patients' preferred role in medical decision-making before the initial urogynecology visit to their perceived role after the visit. METHODS: This prospective cohort study enrolled women presenting for their initial urogynecology visit. Before and after the visit, patients completed the Control Preference Scale (CPS), which categorizes the role that patients want to have in medical decision-making: active, collaborative, or passive. Patients also completed the Pelvic Floor Distress Inventory, CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, and Short Test of Functional Health Literacy in Adults questionnaires. Univariable and multivariable generalized estimating equations were used. RESULTS: Women (n = 100) with a mean age of 59.1 years (SD = 15.5) participated in the study. Based on CPS before the visit, 50% of the women preferred active involvement, whereas 45% preferred collaborative and 5% preferred passive involvement. After the visit, these rates change to 40%, 48%, and 11%, respectively. On univariable analysis, women were 1.56 times more likely to report a collaborative or passive CPS response after the visit (P = 0.02). This remained true on multivariable analysis (odds ratio, 1.57; P = 0.04). Patients' CPS responses were not associated with their responses on CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, or Short Test of Functional Health Literacy in Adults. Eighty-eight percent of women reported a fully collaborative visit based on CollaboRATE, and 87% reported being "completely satisfied" with the visit. CONCLUSIONS: Despite a change in women's reported involvement in decision-making after their first urogynecology visit compared with their preferences before the visit, most women perceived collaboration during their visit and were completely satisfied.

Hypersensitivity pneumonitis: Current concepts in pathogenesis, diagnosis, and treatment.

Hypersensitivity pneumonitis is an immune-mediated interstitial lung disease caused by an aberrant response to an inhaled exposure, which results in mostly T cell-mediated inflammation, granuloma formation, and fibrosis in some cases. HP is diagnosed by exposure identification, HRCT findings of ground-glass opacities, centrilobular nodules, and mosaic attenuation, with traction bronchiectasis and honeycombing in fibrotic cases. Additional testing including serum IgG testing for the presence of antigen exposure, bronchoalveolar lavage lymphocytosis, and lung biopsy demonstrating granulomas, inflammation, and fibrosis, increases the diagnostic confidence. Treatment for HP includes avoidance of the implicated exposure, immunosuppression, and anti-fibrotic therapy in select cases. This narrative review presents the recent literature in the understanding of the immunopathological mechanisms, diagnosis, and treatment of HP.

Preoperative Music Listening in Pelvic Reconstructive Surgery: A Randomized Trial.

OBJECTIVES: We aimed to investigate the effect of music listening on preoperative anxiety compared with usual care in patients undergoing pelvic reconstructive surgery. METHODS: Patients scheduled for pelvic reconstructive surgery were enrolled on the day of surgery. Participants were randomized to either the usual care (control group) or to music listening on headphones (music group) before their surgery. Participants completed the Spielberg State-Trait Anxiety Inventory form Y1 to measure baseline state anxiety levels before surgery and again after 30 minutes of usual care or music listening. The primary outcome was the change in state anxiety score as measured by the State-Trait Anxiety Inventory form Y1. RESULTS: Sixty-nine women completed the study (35 assigned to the control group and 34 assigned to the music group). Analysis of the primary outcome included 66 participants (34 in the control group and 32 in the music group). Improvement in state anxiety was significantly better for patients assigned to music listening (-6.69; SD, 6.98) than for patients assigned to the control group (-1.32; SD, 8.03; P = 0.01). Six weeks postoperatively, patients in the music group (n = 29) reported higher overall satisfaction when compared with those in the control group (n = 31, P = 0.03). CONCLUSION: Patients undergoing pelvic reconstructive surgery present with moderate anxiety on the day of surgery. Allowing patients to listen to their preferred music is a simple intervention that may lower preoperative anxiety and improve satisfaction in this patient population.

You're How Old? Correlating Perioperative Complication Risk in Octogenarians Undergoing Colpocleisis for Pelvic Organ Prolapse.

OBJECTIVES: Colpocleisis is a surgical treatment of pelvic organ prolapse for elderly women who are no longer sexually active. The risk calculator of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) predicts perioperative complications. We aim to determine if the NSQIP calculated risk correlates with true perioperative complications in women 80 years or older undergoing colpocleisis. METHODS: Octogenarian women who underwent colpocleisis at our institution from 2007 to 2017 were included in this retrospective chart review. Medical comorbidities were entered into ACS NSQIP calculator, and the calculated risk was compared with actual complications. RESULTS: One hundred twenty-six octogenarians were included in the analysis. The true complication rate was higher than predicted by NSQIP (28.6% [36/126] vs 4.3% (SD, ±1.1%), which we attribute to our relatively high detection rate of urinary tract infection (32/36). Four patients (3.2%) had serious complications (pulmonary embolus, deep vein thrombosis, sepsis, and reintubation). In only 57% of cases, NSQIP risk calculation was concordant with true complication, showing significant departure from correct classification (P < 0.0001). The sensitivity and specificity of the NSQIP calculator were 66.7% and 53.3%, respectively. Multivariable analysis showed higher-than-predicted incidence of complications for patients requiring antiplatelet medication (Plavix or aspirin >81 mg vs none; odds ratio, 4.84, 95% confidence interval, 1.72-13.60; P = 0.002) and a diagnosis of hypertension (odds ratio, 4.24; 95% confidence interval, 1.31-13.72; P = 0.016). CONCLUSION: Serious complication rates are low in octogenarians undergoing colpocleisis. The ACS NSQIP risk calculator does not strongly correlate with actual complications. Further refinement and evolvement of the database may improve its predictive value.

Prognosis of idiopathic pulmonary fibrosis without anti-fibrotic therapy: a systematic review.

In addition to facilitating healthcare delivery planning, reliable information about prognosis is essential for treatment decisions in patients with idiopathic pulmonary fibrosis (IPF). This review aimed to evaluate the prognosis of patients with IPF without anti-fibrotic therapy. We included all cohort studies and the placebo arms of randomised controlled trials (RCTs) in IPF and follow-up of ≥12 months. Two reviewers independently evaluated studies for inclusion, assessed risk of bias and extracted data. A total of 154 cohort studies and 16 RCTs were included. The pooled proportions of mortality were 0.12 (95% CI 0.09-0.14) at 1-2 years, 0.38 (95% CI 0.34-0.42) between 2-5 years, and 0.69 (95% CI 0.59-0.78) at ≥5 years. The pooled mean overall survival was 4 years (95% CI 3.7-4.6) for studies with a follow-up duration of 10 years. At <2 years, forced vital capacity and diffusing capacity of the lung for carbon monoxide declined by a mean of 6.76% predicted (95% CI -8.92 -4.61) and 3% predicted (95% CI -5.14 -1.52), respectively. Although heterogeneity was high, subgroup analyses revealed lower pooled proportions of mortality at 1 year in the RCT participants (0.07 (95% CI 0.05-0.09)) versus cohort study participants (0.14 (95% CI 0.12-0.17)). This review provides comprehensive information on the prognosis of IPF, which can inform treatment discussions with patients and comparisons for future studies with new therapies.

Pulmonary adverse events of small molecule JAK inhibitors in autoimmune disease: systematic review and meta-analysis.

OBJECTIVES: Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical. METHODS: We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm. RESULTS: We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism. CONCLUSION: SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low.

The effect of surgical weight loss on obstructive sleep apnoea: A systematic review and meta-analysis.

This review aimed to examine the relationship between surgical weight loss and obstructive sleep apnoea (OSA) severity (i.e., apnoea-hypopnoea index [AHI]), and how this relationship is altered by the various respiratory events scoring (RES) criteria used to derive the AHI. A systematic search of the literature was performed up to December 2017. Before-and-after studies were considered due to a paucity of randomised controlled trials (RCTs) available to be reviewed in isolation. Primary outcomes included pre- and post-surgery AHI and body mass index (BMI). Secondary outcomes included sleep study type and RES criteria. Meta-analysis was undertaken where possible. Overall, surgical weight loss resulted in reduction of BMI and AHI, however, OSA persisted at follow-up in the majority of subjects. There was high between-study heterogeneity which was largely attributable to baseline AHI and duration of follow-up when analysed using meta-regression. There was insufficient data to evaluate the impact of different RES criteria on OSA severity. Therefore, more RCTs are needed to verify these findings given the high degree of heterogeneity and future studies are strongly encouraged to report the RES criteria used to enable fair and uniform comparisons of the impact of any intervention on OSA severity.

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

BACKGROUND: Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. OBJECTIVES: To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. SEARCH METHODS: We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non-cyclophosphamide-containing therapies for at least six months, with follow-up of at least 12 months from the start of treatment. DATA COLLECTION AND ANALYSIS: We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were change in lung function (change in forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted), adverse events, and health-related quality of life measures. Secondary outcomes included all-cause mortality, dyspnoea, cough, and functional exercise testing. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and created 'Summary of findings' tables. MAIN RESULTS: We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results.The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants).Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide treatment. The data demonstrates statistically significant improvement in one-measure of quality of life in one trial favouring cyclophosphamide over placebo and clinically and statistically significant improvement in breathlessness in one trial favouring cyclophosphamide compared with placebo, with no significant impact on mortality.Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months (FVC % MD -0.82, 95% CI -3.95 to 2.31; P = 0.61; two trials, 149 participants; DLCO % MD -1.41, 95% CI -10.40 to 7.58; P = 0.76; two trials, 149 participants).Risk of side effects was increased with cyclophosphamide versus mycophenolate, in particular, leukopenia and thrombocytopenia.The data demonstrates no significant impact on health-related quality of life, all-cause mortality, dyspnoea, or cough severity in the cyclophosphamide group compared with the mycophenolate group. No trials reported outcomes associated with functional exercise tests.We performed subgroup analysis to determine whether severity of lung function, connective tissue disease diagnosis, or radiological pattern had any impact on outcomes. One trial reported that cyclophosphamide protected against decreased FVC in individuals with worse fibrosis scores, and also showed that cyclophosphamide may be more effective in those with worse lung function. No association could be made between connective tissue disease diagnosis and outcomes. AUTHORS' CONCLUSIONS: This review, which is based on studies of varying methodological quality, demonstrates that overall, in this population, small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo, but not of the difference in % DLCO, or when compared with mycophenolate. Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide. Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC. Clinicians should carefully monitor for adverse effects during treatment and in the years thereafter.Further studies are required to examine the use of cyclophosphamide; they should be adequately powered to compare outcomes within different subgroups, specifically, stratified for extent of pulmonary infiltrates on high-resolution computed tomography (HRCT) and skin involvement in SSc. Studies on other forms of connective tissue disease are needed. Researchers may consider comparing cyclophosphamide (a potent immunosuppressant) versus antifibrotic agents, or comparing both versus placebo, in particular, for those with evidence of rapidly progressive fibrotic disease, who may benefit the most.

The Adoption of Single-port Laparoscopy for Full Staging of Endometrial Cancer: Surgical and Oncology Outcomes and Evaluation of the Learning Curve.

STUDY OBJECTIVE: To study the safety, feasibility, learning curve, and surgical outcome for single-port laparoscopic full staging of endometrial cancer. DESIGN: A retrospective study (Canadian Task Force classification II-3). SETTING: A university academic hospital. PATIENTS: Women with endometrial cancer undergoing single-port laparoscopic full surgical staging. INTERVENTIONS: This was a single-center, retrospective consecutive study of patients undergoing single-port laparoscopic full staging of endometrial cancer from March 2012 to December 2015. MEASUREMENTS AND MAIN RESULTS: One hundred ten consecutive cases were included in the study. The mean age was 63 years (standard deviation = 14), and the mean body mass index was 34 kg/m2 (standard deviation = 7). Medical comorbidity was noted in 62% (68/110) of patients, and 55% (61/110) of patients had previous abdominal surgery. Preoperative histology included grade 1 (63%), grade 2 (23%), grade 3 (4%), papillary serous (6%), clear cell (3%), and mixed (1%). Postoperatively, 73% of patients were stage I, 2% were stage II, 21% were stage III, and 4% were stage IV. The conversion rate to multiple ports or to laparotomy was 6.3%. The average total surgical time was 186 minutes. Comparing the last 30 cases of our cohort with the first 20, there was a significant improvement in the reduction of the total operative time (191 vs 152 minutes, p = .036), estimated blood loss (389 vs 121 mL, p = .002), conversion rate (20 % vs 0%, p = .02), and rate of surgical complication (10% vs. 0%, p = .03). The readmission rate was 11% (12/110) with 75% of those patients being readmitted for surgical indications and 25% for medical indications. The rate of ventral hernia was 1.8% (2/110) with an average follow-up of 298 days (31-1085 days). CONCLUSION: Single-port laparoscopic staging of endometrial cancer is a safe and feasible technique to introduce into a gynecologic oncology practice that is compatible with other minimally invasive modalities with similar complication rates, discharge timing, and operative times. Drastic improvement in surgical time can be seen after approximately the first 20 cases.

Surgery for limited-stage small-cell lung cancer.

BACKGROUND: Current treatment guidelines for limited-stage small-cell lung cancer (SCLC) recommend concomitant platinum-based chemo-radiotherapy plus prophylactic cranial irradiation, based on the premise that SCLC disseminates early, and is chemosensitive. However, although there is usually a favourable initial response, relapse is common and the cure rate for limited-stage SCLC remains relatively poor. Some recent clinical practice guidelines have recommended surgery for stage 1 (limited) SCLC followed by adjuvant chemotherapy, but this recommendation is largely based on the findings of observational studies. OBJECTIVES: To determine whether, in patients with limited-stage SCLC, surgical resection of cancer improves overall survival and treatment-related deaths compared with radiotherapy or chemotherapy, or a combination of radiotherapy and chemotherapy, or best supportive care. SEARCH METHODS: We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 11 January 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with adults diagnosed with limited-stage SCLC, confirmed by cytology or histology, and radiological assessment, considered medically suitable for resection and radical radiotherapy, which randomised participants to surgery versus any other intervention. DATA COLLECTION AND ANALYSIS: We imported studies identified by the search into a reference manager database. We retrieved the full-text version of relevant studies, and two review authors independently extracted data. The primary outcome measures were overall survival and treatment-related deaths; and secondary outcome measures included loco-regional progression, quality of life, and adverse events. MAIN RESULTS: We included three trials with 330 participants. We judged the quality of the evidence as very low for all the outcomes. The quality of the data was limited by the lack of complete outcome reporting, unclear risk of bias in the methods in which the studies were conducted, and the age of the studies (> 20 years). The methods of cancer staging and types of surgical procedures, which do not reflect current practice, reduced our confidence in the estimation of the effect.Two studies compared surgery to radiation therapy, and in one study chemotherapy was administered to both arms. One study administered initial chemotherapy, then responders were randomised to surgery versus control; following, both groups underwent chest and whole brain irradiation.Due to the clinical heterogeneity of the trials, we were unable to pool results for meta-analysis.All three studies reported overall survival. One study reported a mean overall survival of 199 days in the surgical arm, compared to 300 days in the radiotherapy arm (P = 0.04). One study reported overall survival as 4% in the surgical arm, compared to 10% in the radiotherapy arm at two years. Conversely, one study reported overall survival at two years as 52% in the surgical arm, compared to 18% in the radiotherapy arm. However this difference was not statistically significant (P = 0.12).One study reported early postoperative mortality as 7% for the surgical arm, compared to 0% mortality in the radiotherapy arm. One study reported the difference in mean degree of dyspnoea as -1.2 comparing surgical intervention to radiotherapy, indicating that participants undergoing radiotherapy are likely to experience more dyspnoea. This was measured using a non-validated scale. AUTHORS' CONCLUSIONS: Evidence from currently available RCTs does not support a role for surgical resection in the management of limited-stage small-cell lung cancer; however our conclusions are limited by the quality of the available evidence and the lack of contemporary data. The results of the trials included in this review may not be generalisable to patients with clinical stage 1 small-cell lung cancer carefully staged using contemporary staging methods. Although some guidelines currently recommend surgical resection in clinical stage 1 small-cell lung cancer, prospective randomised controlled trials are needed to determine if there is any benefit in terms of short- and long-term mortality and quality of life compared with chemo-radiotherapy alone.

Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness.

BACKGROUND: Breathlessness is a common and disabling symptom which affects many people with advanced cardiorespiratory disease and cancer. The most effective treatments are aimed at treating the underlying disease. However, this may not always be possible, and symptomatic treatment is often required in addition to maximal disease-directed therapy. Opioids are increasingly being used to treat breathlessness, although their mechanism of action is still not completely known. A few good sized, high quality trials have been conducted in this area. OBJECTIVES: To determine the effectiveness of opioid drugs in relieving the symptom of breathlessness in people with advanced disease due to malignancy, respiratory or cardiovascular disease, or receiving palliative care for any other disease. SEARCH METHODS: We performed searches on CENTRAL, MEDLINE, EMBASE, CINAHL, and Web of Science up to 19 October 2015. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised double-blind controlled trials that compared the use of any opioid drug against placebo or any other intervention for the relief of breathlessness. The intervention was any opioid, given by any route, in any dose. DATA COLLECTION AND ANALYSIS: We imported studies identified by the search into a reference manager database. We retrieved the full-text version of relevant studies, and two review authors independently extracted data. The primary outcome measure was breathlessness and secondary outcome measures included exercise tolerance, oxygen saturations, adverse events, and mortality. We analysed all studies together and also performed subgroup analyses, by route of administration, type of opioid administered, and cause of breathlessness. Where appropriate, we performed meta-analysis. We assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and created three 'Summary of findings' tables. MAIN RESULTS: We included 26 studies with 526 participants. We assessed the studies as being at high or unclear risk of bias overall. We only included randomised controlled trials (RCTs), although the description of randomisation was incomplete in some included studies. We aimed to include double blind RCTs, but two studies were only single blinded. There was inconsistency in the reporting of outcome measures. We analysed the data using a fixed-effect model, and for some outcomes heterogeneity was high. There was a risk of imprecise results due to the low numbers of participants in the included studies. For these reasons we downgraded the quality of the evidence from high to either low or very low.For the primary outcome of breathlessness, the mean change from baseline dyspnoea score was 0.09 points better in the opioids group compared to the placebo group (ranging from a 0.36 point reduction to a 0.19 point increase) (seven RCTs, 117 participants, very low quality evidence). A lower score indicates an improvement in breathlessness. The mean post-treatment dyspnoea score was 0.28 points better in the opioid group compared to the placebo group (ranging from a 0.5 point reduction to a 0.05 point increase) (11 RCTs, 159 participants, low quality evidence).The evidence for the six-minute walk test (6MWT) was conflicting. The total distance in 6MWT was 28 metres (m) better in the opioids group compared to placebo (ranging from 113 m to 58 m) (one RCT, 11 participants, very low quality evidence). However, the change in baseline was 48 m worse in the opioids group (ranging from 36 m to 60 m) (two RCTs, 26 participants, very low quality evidence).The adverse effects reported included drowsiness, nausea and vomiting, and constipation. In those studies, participants were 4.73 times more likely to experience nausea and vomiting compared to placebo, three times more likely to experience constipation, and 2.86 times more likely to experience drowsiness (nine studies, 162 participants, very low quality evidence).Only four studies assessed quality of life, and none demonstrated any significant change. AUTHORS' CONCLUSIONS: There is some low quality evidence that shows benefit for the use of oral or parenteral opioids to palliate breathlessness, although the number of included participants was small. We found no evidence to support the use of nebulised opioids. Further research with larger numbers of participants, using standardised protocols and with quality of life measures included, is needed.

Infections and neutrophils in the pathogenesis of bronchiolitis obliterans syndrome in children after allogeneic stem cell transplantation.

It is plausible that infections post-hematopoietic SCT play a role in the pathogenesis of BOS. A prospective study for children with history, questionnaire, examination, PFTs, and blood counts at one, three, six, nine, 12, 18, and 24 months post-SCT was conducted. Between September 2009 and September 2011 (n = 39), six developed BOS at 200 days (range 94-282), three patients had probable clinical respiratory infection, and all six had higher neutrophil count compared to non-BOS patients (4.7 vs. 2.4 at three months and 6.3 vs. 2.9 at six months ×10(9) /L, p = 0.03). Contribution of clinical and subclinical infection needs to be considered in the pathogenesis of BOS.

Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation.

Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n = 6) versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3] versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR, 20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month KL-6 levels continued to be higher in BOS group but were not statistically significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum of children receiving allo-SCT may identify patients at high risk for the development of BOS. These patients will benefit from intensive surveillance protocol and early therapy before irreversible lung damage.