Effectiveness of neuromuscular electrical stimulation in patients with acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This study aimed to investigate the effectiveness and acceptability of neuromuscular electrical stimulation (NMES) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: We conducted a systematic review and meta-analysis to investigate the effectiveness and accessibility of NMES and compared them with usual care in patients with acute exacerbation of COPD by searching databases such as MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials published up to April 2022. Randomized controlled trials (RCTs) involving patients with COPD who were treated within 3 weeks of acute exacerbation onset were included. The risk of bias was assessed using the RoB 2 tools. We pooled limb muscle strength and adverse events and performed a comparison between NMES and usual care. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Five RCTs, including 168 patients, met the eligibility criteria. The meta-analysis showed that limb muscle strength was significantly higher in the NMES group (four studies with 148 patients; standardized mean difference, 0.95; 95% confidence interval, 0.60-1.30; p < 0.001). The quality of evidence was very low due to the risk of bias within the studies, imprecision of the estimates, and small number of studies. Any adverse events served as outcomes in three studies (86 patients), although no adverse events occurred. CONCLUSION: NMES is safe for patients with acute exacerbation of COPD and may maintain and improve limb muscle strength; however, the quality of evidence was very low.

Predictive Factors Associated with Long-Term Response to Combination Immunotherapy in Patients with Untreated Advanced Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

INTRODUCTION: Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. METHODS: This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. RESULTS: The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (p = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, p = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, p = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, p < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. CONCLUSION: The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy.

Rechallenge of afatinib for EGFR-mutated non-small cell lung cancer previously treated with osimertinib: a multicenter phase II trial protocol (REAL study).

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC) and contributed to the development of precision medicine. Osimertinib is a standard first-line (1L) treatment for EGFR-mutated NSCLC and has demonstrated superior survival benefits over previous-generation TKIs. However, resistance to osimertinib is nearly inevitable, and subsequent treatment strategies remain unmet medical needs in this setting. Afatinib, a second-generation EGFR-TKI, exhibits activity against certain uncommon EGFR mutation types in the 1L setting. There are a few case reports on the efficacy of afatinib against EGFR-dependent resistance after osimertinib treatment, although these have not been prospectively investigated. Methods: The present phase II, single-arm multicenter trial aims to verify the efficacy and safety of afatinib rechallenge after 1L osimertinib resistance. Patients (aged ≥20 years) with advanced or recurrent non-squamous NSCLC harboring drug-sensitive EGFR mutations (deletion of exon 19 or L858R) who were previously treated with 1L osimertinib and second-line chemotherapy other than TKIs are considered eligible. Undergoing next-generation sequence-based comprehensive genomic profiling is one of the key inclusion criteria. The primary endpoint is the objective response rate; the secondary endpoints are progression-free survival, overall survival, and tolerability. Thirty patients will be recruited in December 2023. Discussion: The results of this study may promote incorporating afatinib rechallenge into the treatment sequence after 1L osimertinib resistance, a setting in which concrete evidence has not been yet established. Registration: UMIN Clinical Trial Registry: UMIN000049225.

Does physiotherapy after rotator cuff repair require supervision by a physical therapist?: a meta-analysis.

BACKGROUND: A supervised physiotherapy program (SPP) is a standard regimen after surgical rotator cuff repair (RCR); however, the effect of a home-based exercise program (HEP), as an alternative, on postoperative functional recovery remains unclear. Therefore, the purpose of this meta-analysis was to compare the functional effects of SPP and HEP after RCR. METHODS: We searched electronic databases including Central, Medline, and Embase in April 2022. The primary outcomes included the Constant score, American Shoulder and Elbow Surgeons score, University of California Los Angeles shoulder score, and pain score. Secondary outcomes included range of motion, muscle strength, retear rate, and patient satisfaction rate. A meta-analysis using random-effects models was performed on the pooled results to determine the significance. RESULTS: The initial database search yielded 848 records, five of which met our criteria. Variables at 3 months after surgery were successfully analyzed, including the Constant score (mean difference, -8.51 points; 95% confidence interval [CI], -32.72 to 15.69; P=0.49) and pain score (mean difference, 0.02 cm; 95% CI, -2.29 to 2.33; P=0.99). There were no significant differences between the SPP and HEP. Other variables were not analyzed owing to the lack of data. CONCLUSIONS: Our data showed no significant differences between SSP and HEP with regard to the Constant and pain scores at 3 months after RCR. These results suggest that HEP may be an alternative regimen after RCR. Level of evidence: I.

High-intensity interval training versus moderate-intensity continuous training in patients with heart failure: a systematic review and meta-analysis.

The effects of high-intensity interval training (HIIT) in patients with heart failure (HF) remain controversial. This systematic review and meta-analysis aimed to examine the efficacy of HIIT versus moderate-intensity continuous aerobic training (MCT) on exercise tolerance in patients with HF. We searched for studies published up to 4 March 2022 in Embase, MEDLINE, PubMed, and the Cochrane Library with no limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result. We identified 15 randomized controlled trials with 557 patients. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; participants = 557; studies = 15; I2 = 65.7%; very low-quality evidence). The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the difference in peak VO2 between HIIT and MCT was inversely associated with body mass index (r = - 0.508, p = 0.028, 95% confidence interval - 0.95 to - 0.07). Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with HF. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.

Update on the treatment of cancer cachexia.

Cancer cachexia is a complex multifaceted syndrome involving functional impairment and changes in body composition that cannot be reversed by nutritional support. Cancer cachexia is characterized by decreased skeletal muscle mass, increased lipolysis, and decreased food intake. Cancer cachexia decreases chemotherapy tolerance as well as quality of life. However, because no fully effective interventions are available, cancer cachexia remains an unmet need in cancer treatment. In recent years, several discoveries and treatments for cancer cachexia have been studied, and guidelines have been published. We believe that the development of effective strategies for the diagnosis and treatment of cancer cachexia will lead to breakthroughs in cancer treatment.

C-PLAN index as a prognostic factor for patients with previously untreated advanced non-small cell lung cancer who received combination immunotherapy: A multicenter retrospective study.

BACKGROUND: Combination immunotherapy (immune checkpoint inhibitors and cytotoxic anticancer agents) is widely used as first-line treatment for advanced non-small cell lung cancer (NSCLC). However, the therapeutic effect of combination immunotherapy has not been fully investigated. C-reactive protein, performance status, lactate dehydrogenase, albumin, and derived neutrophil-to-lymphocyte ratio (C-PLAN) are useful biomarkers for predicting the prognosis of NSCLC; however, there are no reports examining the C-PLAN index, which combines these five factors in a single prognostic factor. METHODS: We retrospectively collected data from 178 patients with previously untreated advanced NSCLC who received combination immunotherapy at multicenter institutions in Nagano Prefecture between December 2018 and April 2022. We investigated the utility of the C-PLAN index as a prognostic factor using Cox regression analysis and correlated it with survival. RESULTS: The good and poor C-PLAN index groups included 85 and 93 patients, respectively. The good C-PLAN index group had a longer median progression-free survival (PFS) (10.7 vs. 6.0 months; p = 0.022) and overall survival (OS) (25.3 vs. 16.5 months; p = 0.003) than the poor C-PLAN index group. The C-PLAN index was an independent favorable prognostic factor that correlated with PFS and OS in multivariate analysis. The good C-PLAN index group had a higher proportion of never-smokers (16.5 vs. 4.3%; p = 0.007) and stage III disease/postoperative recurrence (32.9 vs. 15.1%; p = 0.005) than the poor C-PLAN index group. CONCLUSION: The C-PLAN index is a useful prognostic factor for patients with previously untreated advanced NSCLC undergoing combination immunotherapy.

Predictive value of post-treatment C-reactive protein-to-albumin ratio in locally advanced non-small cell lung cancer patients receiving durvalumab after chemoradiotherapy.

BACKGROUNDS: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation-related parameters in patients with LA-NSCLC treated with CCRT plus durvalumab. METHODS: We recruited 76 LA-NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre-treatment) and 2 months after (post-treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression-free survival (PFS) after durvalumab therapy. RESULTS: The median follow-up time was 17 (range, 3.3-35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non-infectious pneumonitis being the most common reason. Post-treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not-reached vs. 9.6 months. Log-rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post-treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). CONCLUSIONS: This study suggests that post-treatment CAR has predictive value for LA-NSCLC patients treated with CCRT plus durvalumab consolidation therapy.

Anamorelin for cancer cachexia.

Cancer anorexia-cachexia syndrome is a multifactorial condition characterized by significant weight loss due to muscle loss. It is associated with functional impairment, changes in body composition and nutritional disorders. Ghrelin receptors are involved in the release of growth hormone (GH) in the pituitary gland and increase appetite via the hypothalamus. The secretion of GH from the pituitary gland stimulates the liver to secrete insulin-like growth factor 1 (IGF-1), which promotes muscle protein synthesis. Anamorelin is a ghrelin receptor agonist used to treat cancer cachexia. It promotes GH secretion via ghrelin receptor activation and increases appetite, resulting in increased muscle mass and weight. Clinical trials of anamorelin have demonstrated a significant increase in lean body mass index, improved cachexia and no significant increase in serious adverse events. The present review describes the processes leading to the approval of anamorelin in Japan, focusing on pharmacology, metabolism, efficacy, safety and clinical trials.

Successful Radiotherapy of Primary Malignant Peripheral Nerve Sheath Tumor of the Lung.

A 71-year-old man presented with cough and bloody sputum. Computed tomography showed a mass in the lower lobe of the left lung. Histological findings in biopsy tissue revealed a malignant peripheral nerve sheath tumor (MPNST). The patient was diagnosed with primary lung MPNST based on a systemic examination. Although initial chemotherapy treatment with doxorubicin failed to control the disease, radiotherapy considerably shrank the tumor. Primary lung MPNSTs are rare, and there is no established treatment for inoperable cases. This case suggests that radiotherapy is a treatment option for primary lung MPNST.

Usual Interstitial Pneumonia Pattern Interstitial Lung Disease Developed in a Patient with IgG4-related Chronic Sclerosing Sialadenitis.

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.

Pulmonary Rehabilitation for Patients After COPD Exacerbation.

BACKGROUND: The aim of this study was to clarify the effectiveness of pulmonary rehabilitation in patients after exacerbations of COPD and to explore the initiation timing of pulmonary rehabilitation. METHODS: Systematic review and meta-analysis were performed to assess the effects of pulmonary rehabilitation in subjects with exacerbations of COPD on mortality and readmission compared with usual care. We searched for studies published up to October 2020 in MEDLINE, Embase, Cochrane Library, and other sources. Risk of bias was assessed for the randomization process, deviations from intended interventions, missing outcome data, outcome measurements, and selection of the reported result using the Risk of Bias 2 tool. We pooled mortality and readmission data and performed comparisons between pulmonary rehabilitation and usual care. The subgroup analysis compared pulmonary rehabilitation at different start times (early: ≤ 1 week from admission; and late: > 1 week from admission). RESULTS: We identified 10 randomized trials (1,056 participants). Our meta-analysis showed a clinically relevant reduction in readmission up to 3-6 months after pulmonary rehabilitation in both early group (4 trials, 190 subjects; risk ratio [RR] 0.58, [95% CI 0.34-0.99]) and late group (3 trials, 281 subjects; RR 0.48, [95% CI 0.32-0.71]). However, pulmonary rehabilitation had no significant effect on mortality 1 y later compared with usual care (4 trials, 765 subjects; RR 1.27, [95% CI 0.91-1.79]). CONCLUSIONS: Pulmonary rehabilitation showed short-term effects for subjects with exacerbations of COPD even if initiated within 1 week; however, further study is required to determine its long-term effects.

The effectiveness of supplemental oxygen during exercise training in patients with chronic obstructive pulmonary disease who show severe exercise-induced desaturation: a protocol for a meta-regression analysis and systematic review.

BACKGROUND: Supplemental oxygen during exercise training is used to increase the training effect of an exercise program in patients with chronic obstructive pulmonary disease (COPD) who show exercise-induced desaturation. Exercise-induced desaturation is not clearly defined in the guidelines; however, it is generally defined in clinical studies as a decrease in SpO2 of more than 4% from rest or a decrease to less than 88% during exercise. Although some meta-analyses examined the effectiveness of supplemental oxygen during exercise training, these studies concluded that it does not further improve exercise tolerance compared to exercise training alone. However, supplemental oxygen during exercise training may be effective in improving exercise tolerance in COPD patients with severe exercise-induced desaturation. Therefore, this study will be performed to elucidate the effectiveness of supplemental oxygen during exercise training and the relationship between its effectiveness and severity of exercise-induced desaturation at baseline. METHODS: We will first assess the effectiveness of supplemental oxygen during exercise training in COPD. The main outcome is the change in exercise tolerance before and after the intervention, indicated by the 6-min walking distance, the walking distance, or the walking time in incremental shuttle walking test, and analyzed as the standardized mean difference (SMD). The quality and risk of bias in individual studies will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and risk-of-bias tool (RoB ver.2). If statistical heterogeneity in terms of the effectiveness of exercise tolerance is shown, we will conduct meta-regression analyses to examine the association between the effectiveness of exercise training with supplemental oxygen and severity of exercise-induced desaturation at baseline. DISCUSSION: One strength of this study is that it is a systematic review with meta-regression analysis to elucidate the effectiveness of supplemental oxygen during exercise training in patients with COPD who show severe exercise-induced desaturation. Furthermore, we will assess the severity of exercise-induced desaturation for which exercise training with supplemental oxygen is effective, the influence of acute effects at baseline, and the effect of supplemental oxygen on adverse events. SYSTEMATIC REVIEW REGISTRATION: Registration number, UMIN000039960.

Impact of physical performance on prognosis among patients with heart failure: Systematic review and meta-analysis.

BACKGROUND: This study aimed to clarify the relationship between physical performance and prognosis of patients with heart failure using a meta-analysis given the inconsistencies in published studies regarding the same. METHODS: A total of 22 studies with 10,368 patients were included in this review. Hazard ratios were used for analysis, while meta-analysis was performed using the inverse-variance method. Among all physical performance tests reported in the literature, the six-minute walk distance (6MD) test was most frequently used. However, short physical performance battery (SPPB) and walking speed were more frequently used as outcomes among studies investigating patients with a higher mean age. RESULTS: The results of our meta-analysis showed that 6MD cut-off values were significantly associated with mortality [hazard ratio (HR), 2.04; 95% confidence interval (CI), 1.48-2.83; p<0.001] and cardiovascular disease (HR, 2.18; 95% CI, 1.68-2.83; p<0.001). Although a number of studies have also reported on the relationship between other physical performance tests and prognosis, meta-analysis could not be performed. Our results revealed that physical performance was strongly correlated with prognosis among patients with heart failure. CONCLUSIONS: Our meta-analysis showed a strong relationship between 6MD and prognosis. However, studies investigating more elderly patients have tended to more frequently utilize walking speed and SPPB as outcomes.

Positive airway pressure therapy for the treatment of central sleep apnoea associated with heart failure.

BACKGROUND: Ischaemic heart disease including heart failure is the most common cause of death in the world, and the incidence of the condition is rapidly increasing. Heart failure is characterised by symptoms such as fatigue and breathlessness during light activity, as well as disordered breathing during sleep. In particular, sleep disordered breathing (SDB), including central sleep apnoea (CSA) and obstructive sleep apnoea (OSA), is highly prevalent in people with chronic heart failure. A previous meta-analysis demonstrated that positive airway pressure (PAP) therapy dramatically increased the survival rate of people with heart failure who had CSA, and thus could contribute to improving the prognosis of these individuals. However, recent trials found that adaptive servo-ventilation (ASV) including PAP therapy had a higher risk of all-cause mortality and cardiovascular mortality. A meta-analysis that included recent trials was therefore needed. OBJECTIVES: To assess the effects of positive airway pressure therapy for people with heart failure who experience central sleep apnoea. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, and Web of Science Core Collection on 7 February 2019 with no limitations on date, language, or publication status. We also searched two clinical trials registers in July 2019 and checked the reference lists of primary studies. SELECTION CRITERIA: We excluded cross-over trials and included individually randomised controlled trials, reported as full-texts, those published as abstract only, and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcome data from the included studies. We double-checked that data had been entered correctly by comparing the data presented in the systematic review with study reports. We analysed dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean difference (MD) or standardised mean difference (SMD) with 95% CIs. Furthermore, we performed subgroup analysis in the ASV group or continuous PAP group separately. We used GRADEpro GDT software to assess the quality of evidence as it relates to those studies that contribute data to the meta-analyses for the prespecified outcomes. MAIN RESULTS: We included 16 randomised controlled trials involving a total of 2125 participants. The trials evaluated PAP therapy consisting of ASV or continuous PAP therapy for 1 to 31 months. Many trials included participants with heart failure with reduced ejection fraction. Only one trial included participants with heart failure with preserved ejection fraction. We are uncertain about the effects of PAP therapy on all-cause mortality (RR 0.81, 95% CI 0.54 to 1.21; participants = 1804; studies = 6; I2 = 47%; very low-quality evidence). We found moderate-quality evidence of no difference between PAP therapy and usual care on cardiac-related mortality (RR 0.97, 95% CI 0.77 to 1.24; participants = 1775; studies = 5; I2 = 11%). We found low-quality evidence of no difference between PAP therapy and usual care on all-cause rehospitalisation (RR 0.95, 95% CI 0.70 to 1.30; participants = 1533; studies = 5; I2 = 40%) and cardiac-related rehospitalisation (RR 0.97, 95% CI 0.70 to 1.35; participants = 1533; studies = 5; I2 = 40%). In contrast, PAP therapy showed some indication of an improvement in quality of life scores assessed by all measurements (SMD -0.32, 95% CI -0.67 to 0.04; participants = 1617; studies = 6; I2 = 76%; low-quality evidence) and by the Minnesota Living with Heart Failure Questionnaire (MD -0.51, 95% CI -0.78 to -0.24; participants = 1458; studies = 4; I2 = 0%; low-quality evidence) compared with usual care. Death due to pneumonia (N = 1, 3% of PAP group); cardiac arrest (N = 18, 3% of PAP group); heart transplantation (N = 8, 1% of PAP group); cardiac worsening (N = 3, 9% of PAP group); deep vein thrombosis/pulmonary embolism (N = 1, 3% of PAP group); and foot ulcer (N = 1, 3% of PAP group) occurred in the PAP therapy group, whereas cardiac arrest (N = 16, 2% of usual care group); heart transplantation (N = 12, 2% of usual care group); cardiac worsening (N = 5, 14% of usual care group); and duodenal ulcer (N = 1, 3% of usual care group) occurred in the usual care group across three trials. AUTHORS' CONCLUSIONS: The effect of PAP therapy on all-cause mortality was uncertain. In addition, although we found evidence that PAP therapy did not reduce the risk of cardiac-related mortality and rehospitalisation, there was some indication of an improvement in quality of life for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low- or very low-quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life.

Peripherally acting µ-opioid antagonist for the treatment of opioid-induced constipation: Systematic review and meta-analysis.

BACKGROUND AND AIM: Opioid-induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting µ-opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated. METHODS: We conducted a quantitative meta-analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases. RESULTS: We included 31 RCTs with 7849 patients. A meta-analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18-1.68; n = 5622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55-2.12; n = 4821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, -0.22; 95% CI, -0.28 to -0.17; n = 2884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06-1.15; n = 7715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85-1.28; n = 5890). CONCLUSION: Peripherally acting µ-opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta-analysis. The possibility of publication bias was the limitation of this study.

Bevacizumab-induced tracheoesophageal fistula in a patient suffering from lung cancer with bulky subcarinal lymph node: a case report.

A 66-year-old male with advanced non-small-cell lung cancer (NSCLC) who was previously treated with carboplatin, pemetrexed, and bevacizumab consequently suffered from severe coughing during deglutition. Chest computed tomography (CT) revealed a tracheoesophageal fistula (TEF) between the left main bronchus and esophagus through a subcarinal metastatic lymph node. Given the extreme swelling of the lymph node due to metastatic cancer, it was determined that the walls of the bronchus and esophagus had been injured simultaneously. Delayed and dysfunctional wound healing due to bevacizumab resulted in necrosis of the contact region leading to fistula formation. This case suggests that using bevacizumab for NSCLC in patients with bulky subcarinal lymphadenopathy may increase the risk for TEF.

Anamorelin for advanced non-small-cell lung cancer with cachexia: Systematic review and meta-analysis.

INTRODUCTION: Cancer anorexia-cachexia syndrome (CACS) is characterized by involuntary weight loss. CACS is commonly observed in advanced non-small-cell lung cancer (NSCLC), and it leads to a poor quality of life (QOL). No effective standard treatment exists for this condition. However, anamorelin has reportedly caused improvement in patients with several cancers. MATERIALS AND METHODS: We conducted a quantitative meta-analysis to explore the efficacy of anamorelin for treating CACS in patients with NSCLC. We systematically searched CENTRAL, MEDLINE, EMBASE, CINAHL, and OvidSP. We pooled the data and calculated and compared total body weight (TBW), lean body mass (LBM), overall survival (OS), hand grip strength (HGS), QOL, and adverse events (AEs) between patients treated with anamorelin (anamorelin group) and those not (placebo group). RESULT: Six randomized controlled trials included 1641 patients with NSCLC. Both TBW and LBM were significantly increased in the anamorelin group compared to the placebo group (mean differences [MD] 1.78, 95%CI: 1.28-2.28, p<0.00001; MD 1.10, 95%CI: 0.35-1.85, p=0.004, respectively). The groups showed no difference in OS or HGS (hazard ratio 0.99, 95%CI: 0.85-1.14, p=0.84; MD 0.52, 95% CI: -0.09-1.13, p=0.09, respectively). Anamorelin significantly improved the QOL (standardized MD 0.19, 95%CI: 0.08-0.30, p=0.0006). The frequency of any AEs and grade 3 or 4 AEs were not significantly different between groups (risk ratio[RR] 1.03, 95%CI: 0.95-1.10, p=0.49; RR 0.86, 95%CI: 0.48-1.54, p=0.62). CONCLUSION: This analysis demonstrated that anamorelin represents a promising treatment option for CACS in patients with advanced NSCLC.

Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma.

We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immune-related adverse events.