Management of Persistent, Post-adenotonsillectomy Obstructive Sleep Apnea in Children: An Official American Thoracic Society Clinical Practice Guideline.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Although adenotonsillectomy is first-line management for pediatric OSA, up to 40% of children may have persistent OSA. This document provides an evidence-based clinical practice guideline on the management of children with persistent OSA. The target audience is clinicians, including physicians, dentists, and allied health professionals, caring for children with OSA. Methods: A multidisciplinary international panel of experts was convened to determine key unanswered questions regarding the management of persistent pediatric OSA. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Results: Recommendations were developed for six management options for persistent OSA. Conclusions: The panel developed recommendations for the management of persistent pediatric OSA based on limited evidence and expert opinion. Important areas for future research were identified for each recommendation.

Review of the clinical outcomes of therapeutic bronchoscopy for central airway obstruction.

Central airway obstruction (CAO) is a debilitating condition with a significant impact on patient's quality of life and risk of hospitalization from respiratory failure. The causes of CAO can be both benign and malignant. Benign CAO may be idiopathic or secondary to other disease processes (infection, intubation, tracheostomy, etc.). Malignant central airway obstruction (MCAO) may occur in patients with primary lung malignancy as well as metastasis from other malignancies including renal cell, colon, and breast. In a cohort review, MCAO was found in up to 13% of patients with newly diagnosed lung cancer. The obstruction may occur either due to endoluminal disease, extrinsic compression, or a combination of both. Several bronchoscopic tools are available to manage such obstruction. Practice patterns and tools used to relieve CAO vary between institutions and may depend on physician preference, patient characteristics, emergency nature of the procedure, and nature of the obstruction. To quantify the effect and added value of such interventions, it is crucial to understand the clinical impact these interventions have on patients. The clinical impact of therapeutic bronchoscopy (TB) must then be weighed against the potential complications to justify its value. Early studies of TB for CAO included patients with both malignant and benign etiologies. The study population's heterogeneity makes it difficult to determine how TB affects clinical outcomes, as clinical outcomes are disease specific. The impact of TB for a MCAO may be different when compared to a benign CAO. Similarly, the clinical outcome of treating an idiopathic benign CAO may be different than that of a post tracheostomy airway obstruction. In this article, we will focus on the clinical outcomes of TB in MCAO. TB has been shown to have a clear impact on weaning from mechanical ventilation, dyspnea, health-related quality of life, survival and quality adjusted survival. The potential impact of TB on these outcomes should be weighed against the potential risk of complications. Understanding the factors associated with improved clinical outcomes will help physicians decide when and if TB is helpful. Future studies should focus on creating a decision analysis tool to further define decision thresholds.

Solitary Lung Nodule: CT-Guided Transthoracic Biopsy vs Transbronchial Biopsy With Endobronchial Ultrasound and Flexible Bronchoscope, a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Transbronchial lung biopsy with radial endobronchial ultrasound (rEBUS-TBB) and Computed tomography (CT) scan-guided transthoracic biopsy (CT-TTB) are commonly used to investigate peripheral lung nodules but high-quality data are still not clear about the diagnostic and safety profile comparison of these two modalities. METHOD: We included all randomized controlled trials (RCT) comparing rEBUS-TBB with a flexible bronchoscope and CT-TTB for solitary lung nodules. Two reviewers extracted data independently on diagnostic performance and complication rates. RESULTS: 170 studies were screened, 4 RCT with a total of 325 patients were included. CT-TTB had a higher diagnostic yield than rEBUS-TBB (83.45% vs 68.82%, risk difference - 0.15, 95% CI, [- 0.24, - 0.05]), especially for lesion size 1-2 cm (83% vs 50%, risk difference - 0.33, 95% CI, [- 0.51, - 0.14]). For malignant diseases, rEBUS-TBB had a diagnostic yield of 75.75% vs 87.7% of CT-TTB. rEBUS-TBB had a significant better safety profile with lower risks of pneumothorax (2.87% vs 21.43%, OR = 0.12, 95% CI [0.05-0.32]) and combined outcomes of hospital admission, hemorrhage, and pneumothorax (8.62% vs 31.81%, OR 0.21, 95% CI, [0.11-0.40]). Factors increasing diagnostic yield of rEBUS were lesion size and localization of the probe but not the distance to the chest wall and hilum. CONCLUSION: CT-TTB had a higher diagnostic yield than rEBUS-TBB in diagnosing peripheral lung nodules, particularly for lesions from 1 to 2 cm. However, rEBUS-TBB was significantly safer with five to eight times less risk of pneumothorax and composite complications of hospital admission, hemorrhage, and pneumothorax. The results of this study only apply to flexible bronchoscopy with radial ebus without navigational technologies. More data are needed for a comparison between CT-TTB with rEBUS-TBB combined with advanced navigational modalities.

Trends in Mortality of Acute Pulmonary Embolism.

Despite substantial advances in the diagnosis and management, pulmonary embolism (PE) continues to be a significant cause of mortality. In this article, we provide a concise overview of the evolution of worldwide mortality trends related to PE. Despite the data being derived mainly from observational studies, there is a clear trend toward decreasing mortality over time from PE. Whether this truly represents a treatment effect or is more related to increased diagnosis of small PEs is not fully clear. Modern approaches to PE management such as the PE response teams have the potential to further reduce the mortality from PE.

Efficacy and Safety of Crizotinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with ROS1 Rearrangement or MET Alteration: A Systematic Review and Meta-Analysis.

BACKGROUND: Crizotinib has been approved for the treatment of non-small-cell lung cancer (NSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion. This drug has also been granted breakthrough designation for NSCLCs with MET exon 14 alterations. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the efficacy and safety of crizotinib in patients with these diseases. METHODS: We searched PubMed and Web of Science for relevant studies. Meta-analysis of proportions was conducted to calculate the pooled rate of complete response, partial response, stable disease, progressive disease, disease control rate (DCR), objective response rate (ORR), and drug adverse effects (AEs) of crizotinib in NSCLCs with ROS1 rearrangement or MET alterations. RESULTS: A total of 20 studies were included for meta-analysis. Among patients with ROS1-positive NSCLC, crizotinib exhibited a pooled DCR of 93.2% (95% confidence interval [CI] 90.8-95.5) and a pooled ORR of 77.4% (95% CI 72.8-82.1). The median progression-free survival (PFS) and overall survival (OS) of patients in this group was 14.5 and 32.6 months, respectively. For NSCLC with MET alterations, crizotinib was associated with a lower efficacy (DCR 78.9% [95% CI 70.3-87.4] and ORR 40.6% [95% CI 28.3-53.0]). The median PFS was 5.2 months, and median OS was 12.7 months. The most common drug AEs were vision impairment (43.7%), edema (42.9%), and fatigue (40.1%). CONCLUSION: Our study highlighted and confirmed the efficacy of crizotinib in patients with NSCLC with ROS1 or MET genetic alterations. Crizotinib had remarkable effects on advanced NSCLC with ROS1 fusion, as previously reported. However, the role of this targeted therapy in MET-altered NSCLC remains investigational.

Clinical spectrum of primary adrenal lymphoma: results of a multicenter cohort study.

Purpose: We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency. Methods: Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017. Results: Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63-613.7, P = 0.008) and 2.69 (95% CI: 0.61-11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004). Conclusion: We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.

Trends and seasonal variation of hospitalization and mortality of interstitial lung disease in the United States from 2006 to 2016.

BACKGROUND: In the recent years, the overall trends in hospital admission and mortality of interstitial lung disease (ILD) are unknown. In addition, there was some evidence that interstitial lung disease death rate highest in the winter but this finding was only available in one study. This study will investigate the trend and seasonal variations in hospital admission and mortality rates of ILD from 2006 to 2016. METHOD: From the Nationwide Inpatient Sample database, we collected all cases with the International Classification of Diseases (ICD)-9 or ICD-10 codes of ILD excluding identifiable external causes (drug, organic or inorganic dusts) from 2006 to 2016. Hospitalization rates of each year were calculated based on U.S Census population data. Monthly hospitalization and in-hospital mortality rates were analyzed by seasonal and trend decomposition. Subgroups of idiopathic interstitial fibrosis (IPF), acute respiratory failure (ARF), pneumonia were analyzed. RESULTS: From 2006 to 2016, all-cause hospital admission rate of patients with interstitial lung disease (ILD) and IPF-only subgroup declined but their overall mortality remained unchanged (except IPF subgroup and acute respiratory failure subgroup). Acute respiratory failure related admission account for 23% of all causes and pneumonia 17.6%. Mortality of ILD in general and subgroup of ILD with ARF was highest in winter, up to 8.13% ± 0.60 and 26.3% ± 10.2% respectively. The seasonal variations of hospital admission and mortality of ILD in general was not changed when infectious pneumonia cases were ruled out. All cause admission rates were highest in months from January to April. Subgroup analysis also showed seasonal variations with highest hospitalization rates for all subgroups (IPF, ARF, pneumonia) in the months from December to April (winter to early Spring). CONCLUSION: From 2006 to 2016, admission rates of ILD of all causes and IPF subgroup declined but in-hospital mortality of ILD of all causes remained unchanged. Mortality of IPF subgroup and acute respiratory failure subgroup trended down. All-cause hospital admissions and mortality of ILD have a strong seasonal variation. Hospitalization rates for all subgroups (IPF, ARF, pneumonia) were highest in the months from December to April.

Is Additional Nebulized Lidocaine Helpful in Flexible Bronchoscopy?: A Meta-Analysis.

BACKGROUND: Conflicting evidence of nebulized lidocaine use in bronchoscopy still exist. This study will identify whether there is any difference in various patient-related, physician-related, or procedure-related outcomes with and without lidocaine nebulization before the procedure. METHOD: The authors performed a search in 4 electronic databases, including Pubmed, Scopus, Virtual Health Library, and Google Scholar from inception to August 2019. Data on patient-reported and physician-reported outcomes, doses of sedation, and lidocaine were extracted and pooled into standardized mean difference (SMD) and mean difference (MD) using the random-effect model. RESULTS: Seven randomized controlled trials with 1366 patients were included. Cough was not different between the nebulized lidocaine group and no nebulized lidocaine group (SMD, -0.12; 95% confidence interval, -0.82 to 0.59; I, 95%; P=0.75), so as operator's satisfaction score, ease of the procedure, patient's discomfort, and unwillingness to repeat the procedure. Additional nebulized lidocaine group required higher lidocaine dose (MD, 81.93; 95% confidence interval, 17.14-146.71). Studies using only local anesthesia favored the "no additional lidocaine" group in improving cough, operator's satisfaction score, and ease of the procedure. Subgroup analysis of studies using moderate sedation showed a decrease in midazolam dose and duration of the procedure in the "additional nebulized lidocaine group." CONCLUSION: Additional administration of nebulized lidocaine increased the total dose of lidocaine used and did not improve cough symptoms, operator-satisfaction score, ease of the procedure, and willingness to repeat the procedure. Subgroup analysis of studies using moderate sedation showed a decrease in midazolam use and in procedure duration but the clinical significance of these findings is uncertain.

Neuromuscular blockade in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Neuromuscular blocking agent (NMBA) has been proposed by medical guidelines for early severe acute respiratory distress syndrome (ARDS) because of its survival benefits. However, new studies have provided evidence contradicting these results. METHOD: A search was performed of the Pubmed, Scopus, Clinicaltrials.gov, and Virtual Health Library databases for randomized controlled trials (RCT) evaluating 28-day mortality in ARDS patients treated with NMBA within 48 h. An English language restriction was applied. Relevant data were extracted and pooled into risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) using random-effect model. Sensitivity and meta-regression analysis were performed. RESULTS: From 2675 studies, we included five RCTs in the analysis, for a total of 1461 patients with a mean PaO2/FIO2 of 104 ± 35 mmHg. The cisatracurium group had the same risk of death at 28 days (RR, 0.90; 95% CI, 0.78-1.03; I 2 = 50%, p = 0.12) and 90 days (RR, 0.81; 95% CI, 0.62-1.06; I 2 = 56%, p = 0.06) as the control group (no cisatracurium). The secondary outcomes of mechanical ventilation duration and ventilator-free days were not different between the two groups. Cisatracurium had a significantly lower risk of barotrauma than the control group with no difference in intensive care unit (ICU)-induced weakness. The PaO2/FIO2 ratio was higher in the cisatracurium group but not until 48 h. Meta-regression analysis of the baseline PaO2/FIO2 ratio, positive end-expiratory pressure (PEEP) revealed no heterogeneity. Subgroup analysis excluding the trial using high PEEP and light sedation strategy yielded an improvement in all mortality outcomes. CONCLUSION: NMBA improves oxygenation only after 48 h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness. However, NMBA does not reduce ventilator-free days, duration of mechanical ventilation or, most importantly, the mortality risk regardless of the severity of ARDS.

Efficacy and toxicity of sorafenib in the treatment of advanced medullary thyroid carcinoma: A systematic review and meta-analysis.

INTRODUCTION: The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs). METHODS: We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib-related AEs were calculated using random-effect model. RESULTS: Eight trials with 101 metastatic MTCs were included for meta-analyses. The overall PR and SD were 21% (95% CI = 9-33) and 58% (95% CI = 41-75), respectively. Hand-foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs. CONCLUSION: Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.

Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer - A systematic review and meta-analysis.

MET exon 14 mutation is an uncommon genomic alteration in non-small cell lung cancer (NSCLC). This meta-analysis aimed at investigating the clinicopathological and prognostic features of NSCLCs with MET exon 14 mutation in comparison with other genetic events. We performed a search in four electronic databases including PubMed, Web of Science, Scopus, and Virtual Health Library from inception to February 2018. Relevant data were extracted and pooled into odds ratio (OR), mean differences (MD), and corresponding 95% confidence intervals (CI) using the random-effect model. From 168 studies, we included 12 studies comprising of 18,464 NSCLCs for final analyses. Overall, the prevalence of MET exon 14 mutation in NSCLC was 3% (95% CI = 2-3), with being most commonly found in pulmonary sarcomatoid carcinoma (13%; 95% CI = 4-21). The mutation was more likely to occur in females (OR = 0.55; 95% CI = 0.33 - 0.90), patients with advanced age (MD = 7.48; 95% CI = 3.99-10.98), non-smoker (OR = 0.48; 95% CI = 0.28 - 0.83), and was associated with a worse prognosis (HR = 1.82; 95% CI = 1.04-3.19). Patients with MET exon 14 mutation had a distinct clinicopathological profile compared to other NSCLC genetic events. To summarize, MET exon 14 is a rare mutation in NSCLC and might be associated with a dismal survival. Patients harboring MET exon 14 skipping are eligible for targeted therapy with c-MET inhibitors, thus emphasizing the need to screen for this mutation in advanced NSCLCs.