Post-Operative Outcomes of Pre-Thoracic Surgery Respiratory Muscle Training vs Aerobic Exercise Training: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the postoperative outcomes of preoperative respiratory muscle training (RMT) with a device to preoperative aerobic exercise training (AET) in patients undergoing thoracic surgeries (cardiac and lung). DATA SOURCES: PubMed, EMBASE, Cochrane, and Web of Science were comprehensively searched upon inception to 9/2020. STUDY SELECTION: All randomized control studies, including preoperative RMT and preoperative AET compared with a non-training control group, were included. DATA EXTRACTION: The meta-analysis was performed for outcomes including postoperative pulmonary complications (PPC), pneumonia, postoperative respiratory failure (PRF), hospital length of stay (HLOS), and mortality. We performed a network meta-analysis based on Bayesian random-effects regression models. DATA SYNTHESIS: A total of 25 studies, 2070 patients were included in this meta-analysis. Pooled data for the patients who performed RMT with a device showed a reduction in PPCs, pneumonia, PRF with odds ratio (OR) of 0.35 (P value .006), 0.38 (P value .002), and 0.22 (P value .008), respectively. Pooled data for the patients who performed AET showed reduction in PPC, pneumonia with a OR of 0.33 (P value <.00001) and OR of 0.54 (P value .01), respectively. HLOS was decreased by 1.69 days (P value <.00001) by performing RMT and 1.79 days (P value .0008) by performing AET compared with the usual group. No significant difference in all-cause mortality compared with usual care in both RMT and AET intervention groups. No significant difference in the incidence of PRF compared with usual group in RMT + AET and AET alone intervention groups (OR 0.32; P=.21; OR 0.94; P=.87). Based on rank probability plots analysis, on network meta-analysis, RMT and AET ranked similarly on the primary outcome of PPC and secondary outcomes of pneumonia, PRF and HLOS. CONCLUSIONS: In thoracic surgeries, preoperative RMT is comparable with preoperative AET to prevent PPC, pneumonia, and PRF and reduce HLOS. It can be considered in patients in resource-limited settings.

Epidemiology and Survival of Malignant Central Airway Obstruction in Lung Cancer Identified on Cross-Sectional Imaging.

BACKGROUND: The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020. METHODS: We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years. RESULTS: The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001). CONCLUSION: This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.

Correlation of Bronchoscopy and CT in Characterizing Malignant Central Airway Obstruction.

BACKGROUND: Malignant Central Airway Obstruction (MCAO) presents a significant challenge in lung cancer management, with notable morbidity and mortality implications. While bronchoscopy is the established diagnostic standard for confirming MCAO and assessing obstruction subtype (intrinsic, extrinsic, mixed) and severity, Computed Tomography (CT) serves as an initial screening tool. However, the extent of agreement between CT and bronchoscopy findings for MCAO remains unclear. METHODS: To assess the correlation between bronchoscopy and CT, we conducted a retrospective review of 108 patients at Roswell Park Comprehensive Cancer Center, analyzing CT and bronchoscopy results to document MCAO presence, severity, and subtype. RESULTS: CT correctly identified MCAO in 99% of cases (107/108). Agreement regarding obstruction subtype (80.8%, Cohen's κ = 0.683, p < 0.001), and severity (65%, Quadratic κ = 0.657, p < 0.001) was moderate. CT tended to equally overestimate (7/19) and underestimate (7/19) the degree of obstruction. CT was also poor in identifying mucosal involvement in mixed MCAO. CONCLUSIONS: CT demonstrates reasonable agreement with bronchoscopy in detecting obstruction. Nevertheless, when CT indicates a positive finding for MCAO, it is advisable to conduct bronchoscopy. This is because CT lacks reliability in determining the severity of obstruction and identifying the mucosal component of mixed disease.

Gabapentin to treat acute alcohol withdrawal in hospitalized patients: A systematic review and meta-analysis.

BACKGROUND: Gabapentin is an antiepileptic medication with evidence of benefit in alcohol use disorder patients. The mechanism of action of gabapentin may also benefit patients suffering from acute alcohol withdrawal syndrome (AWS). METHODS: A systematic review and meta-analysis were conducted to examine if gabapentin can effectively replace/reduce the use of benzodiazepines for the treatment of acute alcohol withdrawal symptoms in hospitalized patients. Time to alcohol withdrawal symptom resolution, amount of benzodiazepines administered, rate of resolution of alcohol withdrawal symptoms, serious withdrawal-related complications, and hospital length of stay (LOS) were examined. RESULTS: Eight retrospective studies (n = 2030) were included in this meta-analysis. There were no studies that examined study outcomes for patients who received only gabapentin and no benzodiazepines; in all studies, gabapentin-treated patients may have received benzodiazepines prior to gabapentin. There were no significant differences between gabapentin-treated and benzodiazepine-treated groups in time to symptom resolution, amount benzodiazepines administered, withdrawal-related complications, or LOS. There was a significant difference in the rate of symptom resolution favoring gabapentin-treated patients (p = 0.05); however, this analysis included only one study. Subgroup analyses of severe AWS patients revealed a significant decrease in LOS (p = 0.04) and a decrease in amount of benzodiazepines administered (p = 0.02) in gabapentin-treated patients, but these analyses included only one study. Subgroup analysis of patients receiving only gabapentin without benzodiazepines found a significantly decreased LOS in the gabapentin group compared to the benzodiazepine group (p < 0.001), but this analysis included only two studies. CONCLUSIONS: There is insufficient evidence to support the widespread use of gabapentin to treat inpatients suffering AWS. All studies included in this meta-analysis are retrospective with high risk of confounding. Well-designed, randomized, controlled studies of gabapentin to treat patients with AWS are required.

Poly Adenosine Diphosphate-Ribose Polymerase (PARP) Inhibitors in Pancreatic Cancer.

Pancreatic cancer is the third most common cause of cancer death in the United States and eleventh worldwide. The majority of patients present with advanced disease with five-year overall survival of less than 10%. Traditional chemotherapy has been the mainstay treatment for years, with limited improvement in survival. Relative success has been achieved with agents targeting the DNA damage repair (DDR) mechanisms with poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. The initial benefit was observed in patients with germline breast cancer-associated (BRCA) mutations. Multiple trials are now underway exploring PARP inhibitors in other DDR mutations such as the ataxia-telangiectasia mutated (ATM) gene and the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene (familial atypical multiple mole and melanoma syndrome), mismatch repair genes (Lynch syndrome), and others. PARP inhibitors are being evaluated as a single agent or combination chemotherapy, immunotherapy, and maintenance after chemotherapy. Here, we review current clinical trials targeting various DDR mutations and treatment strategies.

First-In-Human Computer-Optimized Endobronchial Ultrasound-Guided Interstitial Photodynamic Therapy for Patients With Extrabronchial or Endobronchial Obstructing Malignancies.

Objective: Patients with inoperable extrabronchial or endobronchial tumors who are not candidates for curative radiotherapy have dire prognoses with no effective long-term treatment options. To reveal that our computer-optimized interstitial photodynamic therapy (I-PDT) is safe and potentially effective in the treatment of patients with inoperable extra or endobronchial malignancies inducing central airway obstructions. Methods: High-spatial resolution computer simulations were used to personalize the light dose rate and dose for each tumor. Endobronchial ultrasound with a transbronchial needle was used to place the optical fibers within the tumor according to an individualized plan. The primary and secondary end points were safety and overall survival, respectively. An exploratory end point evaluated changes in immune markers. Results: Eight patients received I-PDT with planning, and five of these received additional external beam PDT. Two additional patients received external beam PDT. The treatment was declared safe. Three of 10 patients are alive at 26.3, 12, and 8.3 months, respectively, after I-PDT. The treatments were able to deliver a prescribed light dose rate and dose to 87% to 100% and 18% to 92% of the tumor volumes, respectively. A marked increase in the proportion of monocytic myeloid-derived suppressor cells expressing programmed death-ligand 1 was measured in four of seven patients. Conclusions: Image-guided light dosimetry for I-PDT with linear endobronchial ultrasound transbronchial needle is safe and potentially beneficial in increasing overall survival of patients. I-PDT has a positive effect on the immune response including an increase in the proportion of programmed death-ligand 1-expressing monocytic myeloid-derived suppressor cells.

COVID-19 presenting as pneumatoceles and spontaneous cavitary lesion as a late complication.

We report a case of an adult patient with COVID-19 pneumonia presenting as pneumatoceles as a late complication. These pneumatoceles are steroid-resistant and can predispose to cavitary lesions. These cystic lesions need close follow-up with repeat imaging as these can increase the risk of pneumothorax. It can take up to around 12 weeks for the spontaneous resolution of pneumatoceles.

Clinical Presentation and Outcomes of Myocarditis Post mRNA Vaccination: A Meta-Analysis and Systematic Review.

BACKGROUND: Myocarditis is being increasingly reported as a potential complication of both Pfizer-BioNTech and Moderna vaccines for COVID-19. One thousand five hundred and twenty-two cases were reported as of September 02, 2021, as per CDC's (Centers for Disease Control) vaccine adverse event reporting system. Most of the published data is available in the form of case reports and series. There is a need to compile the demographic data, clinical features, and outcomes in these patients.  Methods: A systematic search was conducted in PubMed, Embase, Web of science, and google scholar for published literature between January 01, 2020, and July 17, 2021. Individual data of 69 patients were pooled from 25 qualifying case reports and case series. RESULTS: The median age of onset was 21 years. 92.7% of the patients were male. 76.8% of patients received the Pfizer-BioNTech vaccine, and 23.2% received the Moderna vaccine. 88.5% developed symptoms after the second dose. Patients were admitted to the hospital a median of three days post-vaccination. All the patients had chest pain and elevated troponin. The myocarditis was confirmed on cardiac MRI in 87% of the patients. Most of the patients had late gadolinium enhancement on MRI. The median length of stay was four days. All the reported patients recovered and were discharged. CONCLUSION: Post-mRNA vaccination myocarditis is seen predominantly in young males within a few days after their second dose of vaccination. The pathophysiology of myocarditis is not well known. The prognosis is good as all the reported patients recovered. The presence of late gadolinium enhancement on cardiac MRI indicated myocardial necrosis/fibrosis and further studies are needed to establish the long-term prognosis of the condition.

Treatment of Acute Exacerbations in Chronic Obstructive Pulmonary Disease.

Management of a chronic obstructive pulmonary disease (COPD) exacerbation begins with an accurate diagnosis. Although more than 80% of exacerbations are managed on an outpatient basis, hospitalization is all too common and associated with considerable health care costs and mortality. Irrespective of the site of treatment, the treatment modalities are the same. Noninvasive ventilation has greatly decreased the mortality in exacerbations that require ventilatory support. Across the range of exacerbation severity, treatment failure and relapses are frequent, and should be carefully evaluated. New therapeutic options to address infection and inflammation in COPD are needed to improve the outcome of exacerbations.

Triple Therapy versus Dual or Monotherapy with Long-Acting Bronchodilators for Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis.

Rationale: There is uncertainty on the use of using triple therapy (inhaled corticosteroids/long-acting ß-agonist/long-acting muscarinic antagonist) inhaler therapy for patients with chronic obstructive pulmonary disease (COPD), who complain of dyspnea and/or exercise intolerance.Objectives: We conducted a systematic review and meta-analyses to estimate the safety and efficacy of using triple therapy compared with long-acting ß-agonist/long-acting muscarinic antagonist dual therapy or monotherapy with a single long-acting bronchodilator in patients with stable COPD who complained of dyspnea and/or exercise intolerance.Methods: A search of MEDLINE, Embase, and the Cochrane Library databases was conducted for randomized controlled trials pertaining to the clinical question. A systematic approach was used to screen, abstract, and critically appraise the studies. The grading of recommendations assessment, development, and evaluation method was applied to rate the certainty/quality of the evidence.Results: Eleven studies were eligible for inclusion (n = 14,145 patients). Pairwise random-effects meta-analysis revealed an increase in risk of pneumonia (relative risk, 1.47; 95% confidence interval [95% CI], 1.20-1.80; P < 0.001) and decreased risk of acute exacerbations of COPD (AECOPDs) (relative risk, 0.75; 95% CI, 0.68-0.82; P < 0.001) with triple therapy compared with treatment with dual and monotherapy long-acting bronchodilator therapy. No significant difference in dyspnea scores (standardized mean difference, 0.09; 95% CI, -0.02 to 0.19; P = 0.09) or risk of hospitalization (rate ratio, 0.78; 95% CI, 0.58-1.06; P = 0.11) was noted. When subgroup analysis based on inhaler class was performed, no significant difference was noted between the groups in any of the critical outcomes studied. For patients with a history of one or more AECOPDs in the past year, triple therapy resulted in 230 fewer AECOPDs and 16 more cases of pneumonia per 1,000 patients.Conclusions: In patients with COPD who complain of dyspnea and/or exercise intolerance, triple therapy is not superior to maintenance long-acting bronchodilator therapy, except in patients with a history of one or more exacerbations in the past year, in whom the benefits of reduction in AECOPD outweigh the increased risk of pneumonia.

Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult.

Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP.

New Treatment Options for Metastatic Thyroid Cancer.

Newer multitargeted kinase inhibitors show prolonged overall and progression-free survival in patients with metastatic differentiated and medullary thyroid cancers.

Sarcomatoid Urothelial Carcinoma: A Single Cancer Center Experience.

BACKGROUND: Sarcomatoid bladder cancer is a rare and aggressive variant of urothelial carcinoma. METHODS: A retrospective review of our experience in managing patients with sarcomatoid bladder cancer (SRBC) between 1997 and 2011 was performed to better define the behavior and outcomes of this disease. RESULTS: The median age of the patients was 63 years. All patients presented with high grade histology. Eighty-five percent of the patients presented with muscle invasive disease and fifty percent presented with stage IV carcinoma. Ten of 14 (71%) of patients underwent a cystectomy. Patients with SRBC was younger (P < 0.01), more commonly presented with higher grade histology (P < 0.01) and advanced stage disease (P < 0.01), in comparison with patients with Urothelial carcinoma (UC). At a median follow-up of 7 months (range 1.3 - 112), five (35.7%) patients have died in last follow-up. Two-year survival was 53.5%. Three patients with long term survival were reported. CONCLUSIONS: Sarcomatoid bladder cancer is associated with poor prognosis. Multimodality therapy may improve these patients outcome.