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PURPOSE Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer. METHODS This retrospective study included PWH treated with anti–PD-1- or anti–PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC). RESULTS Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti–PD-1/anti–PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load CONCLUSION Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

The tumor-intrinsic NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome–heat shock protein 70 (HSP70) signaling axis is triggered by CD8 + T cell cytotoxicity and contributes to the development of adaptive resistance to anti–programmed cell death protein 1 (PD-1) immunotherapy by recruiting granulocytic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into the tumor microenvironment. Here, we demonstrate that the tumor NLRP3-HSP70 axis also drives the accumulation of PMN-MDSCs into distant lung tissues in a manner that depends on lung epithelial cell Toll-like receptor 4 (TLR4) signaling, establishing a premetastatic niche that supports disease hyperprogression in response to anti–PD-1 immunotherapy. Lung epithelial HSP70-TLR4 signaling induces the downstream Wnt5a-dependent release of granulocyte colony-stimulating factor (G-CSF) and C-X-C motif chemokine ligand 5 (CXCL5), thus promoting myeloid granulopoiesis and recruitment of PMN-MDSCs into pulmonary tissues. Treatment with anti–PD-1 immunotherapy enhanced the activation of this pathway through immunologic pressure and drove disease progression in the setting of Nlrp3 amplification. Genetic and pharmacologic inhibition of NLRP3 and HSP70 blocked PMN-MDSC accumulation in the lung in response to anti–PD-1 therapy and suppressed metastatic progression in preclinical models of melanoma and breast cancer. Elevated baseline concentrations of plasma HSP70 and evidence of NLRP3 signaling activity in tumor tissue specimens correlated with the development of disease hyperprogression and inferior survival in patients with stage IV melanoma undergoing anti–PD-1 immunotherapy. Together, this work describes a pathogenic mechanism underlying the phenomenon of disease hyperprogression in melanoma and offers candidate targets and markers capable of improving the management of patients with melanoma.

Venous thromboembolism (VTE) is a serious complication of orthopedic surgery. Low molecular weight heparin (LMWH) has been the standard of care for thromboprophylaxis in this population. However, direct oral anticoagulants (DOACs) are increasingly being used as alternatives.To assess the efficacy and safety of DOACs versus LMWH for thromboprophylaxis in orthopedic surgery.We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until April 2020, for randomized controlled trials (RCTs) comparing DOACs with LMWH for thromboprophylaxis in orthopedic surgery.Twenty-five RCTs met inclusion criteria, including 40,438 patients, with a mean age of 68 years and 50% were males. Compared to LMWH, DOACs were associated with a significant reduction of major VTE; defined as the composite events of proximal deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE-related mortality (RR 0.33; 95% CI: 0.20-0.53; P0.01), and total DVT (RR: 0.59; 95% CI: 0.48-0.73; P0.01), but not PE (RR 0.81; 95% CI: 0.49-1.34; P=0.42). There was no statistically significant difference between both groups on the incidence of major bleeding (RR 0.99; 95% CI: 0.77-1.27; P=0.92), clinically relevant non-major bleeding (RR 1.04; 95% CI: 0.92-1.17; P=0.52), all-cause mortality (RR 1.06; 95% CI: 0.64-1.76; P=0.83), VTE-related mortality (RR 0.84; 95% CI: 0.40-1.74; P=0.64) and bleeding-related mortality (RR 1.24; 95% CI: 0.30-5.18; P=0.77).For patients undergoing orthopedic surgery, thromboprophylaxis with DOACs is associated with a significant reduction of major VTE and DVT, compared to LMWH. Safety outcomes were not significantly different between both treatment groups.

Background Cancer associated venous thromboembolism (VTE) results in significant morbidity and mortality. Low molecular weight heparin (LMWH) has been standard of care for treatment of cancer-associated VTE, however direct oral anticoagulants (DOACs) are emerging as alternative treatment options. Objective To compare the benefits and harms of DOACs versus LMWH for treatment of VTE in cancer. Data sources MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception to April 2020. Study selection Randomized controlled trials (RCT) comparing DOACs with LMWH for treatment of VTE in cancer patients. Data synthesis Four good-quality RCTs, met inclusion criteria. Compared with LMWH, DOACs were associated with lower rates of VTE recurrence (RR 0.62; 95% CI: 0.44–0.87; P = 0.006), and DVT recurrence (RR 0.61; 95% CI: 0.4–0.94; P = 0.02) but not PE recurrence (RR 0.73; 95% CI: 0.51–1.04; P = 0.08), in cancer patients. However, the risk of clinically relevant non-major bleeding (CRNMB) (RR 1.58; 95% CI: 1.11–2.24; P = 0.01), and major bleeding in gastrointestinal cancer (RR 2.55; 95% CI 1.24–5.27, P = 0.01), were higher with DOACs. The risk of overall major bleeding (RR 1.33; 95% CI: 0.84–2.1; P = 0.22), all-cause mortality (RR 0.99; 95% CI: 0.84–1.17; P = 0.92), VTE-related mortality (RR: 1; 95% CI: 0.29–3.44; P = 1) and bleeding-related mortality (RR: 0.71; 95% CI: 0.17–2.91; P = 0.63), were similar in both treatment groups. Conclusion Among cancer patients with VTE, treatment with DOACs is associated with a significant reduction of VTE and DVT recurrence, compared to LMWH. These benefits were offset by an increased risk of CRNMB, and major bleeding in gastrointestinal cancer.

Critically ill patients (patients treated in a medical or surgical intensive care unit) are at high risk of venous thromboembolism (VTE) development (deep vein thrombosis [DVT] and/or pulmonary embolism). Multiple thromboprophylaxis strategies have been used for the prevention of VTE in this population with various outcomes. Therefore, we aimed to evaluate the efficacy of intermittent pneumatic compression (IPC) prophylaxis in the lower limb compared with no treatment, anticoagulant use, or their combinations in reducing risk. A comprehensive electronic database search was conducted for all randomized clinical trials (RCTs) comparing the clinical outcomes of IPC versus anticoagulants or no treatment or their combinations for the prevention of VTE for critically ill patients. The primary outcome was VTE. The secondary outcome was DVT. We performed a Bayesian network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrIs). We included 5 RCTs with 3133 total patients, represented by a mean age of 49.61 ± 18 years, while 60.28% were male. There was a significant reduction of the primary outcome (incidence of VTE events) when no treatment was compared with IPC (OR = 0.36; 95% CrI = 0.18-0.71), anticoagulation alone (OR = 0.30; 95% CrI = 0.12-0.68), or anticoagulation with IPC (OR = 0.34; 95% CrI = 0.13-0.81). In addition, there was a significant reduction in DVT when no treatment was compared with IPC (OR = 0.45; 95% CrI = 0.21-0.9), anticoagulation alone (OR = 0.16; 95% CrI = 0.03-0.66), or anticoagulation with IPC (OR = 0.18; 95% CrI = 0.03-0.84). However, there were no significant differences between other comparisons (IPC vs anticoagulation alone, anticoagulation alone vs anticoagulation with IPC, or anticoagulation with IPC vs IPC alone) regarding VTE or DVT incidence. Among critically ill patients, IPC alone, anticoagulation alone, and IPC with anticoagulation were associated with a significant reduction of VTE and DVT incidence compared with no treatment. However, there was no significant difference between these modalities when compared together. Therefore, further larger studies comparing those different thromboprophylaxis modalities and their combinations are needed to provide more robust results for future clinical recommendations.

In a hospital setting, nurses and physicians are the two main caregivers for admitted patients. Their communication is an important driver of positive teamwork and ensures proper patient safety and a high level of patient care. In a hospital with a large internal medicine residency program, where the main communication between nurses and residents is by phone calls, the excess number of phone calls received, especially for non-urgent patient-related matters, can be disruptive and cause fatigue and burnout. Alternative means of communication have been reported, namely using the electronic medical records to try and create new means of communication and to decrease the burden of direct communication for non-urgent matters. This manuscript describes the results of a survey administered in an attempt to understand the communication between residents and nurses in the setting of a new communication tool created within the electronic medical records.

BACKGROUND The benefit of extended-duration thromboprophylaxis in patients hospitalised for acute medical illness beyond hospital stay remains controversial. AIMS To perform a meta-analysis of randomised controlled trials (RCT) in order to examine the efficacy and safety of extended-duration anticoagulation for venous-thromboembolism (VTE) prophylaxis in this high-risk population. METHODS An electronic database search was conducted to include all RCT comparing between extended-duration versus short-duration prophylactic anticoagulation in medically ill patients. The primary efficacy outcome was the composite events of asymptomatic deep vein thrombosis (DVT), symptomatic VTE and death from VTE-related causes. RESULTS Five RCT were included totalling 40 124 patients, with a mean age of 71 years and 51% were male. In comparison to standard-duration therapy, extended-duration thromboprophylaxis was associated with a significant reduction in the primary efficacy outcome (risk ratio (RR) 0.75; 95% confidence interval (CI) 0.67-0.85; P < 0.01), symptomatic VTE (RR 0.53; 95% CI 0.33-0.84; P < 0.01) and asymptomatic DVT (RR 0.81; 95% CI 0.71-0.94; P < 0.01). However, there were no significant differences between both groups with regard to VTE-related death (RR 0.81; 95% CI 0.60-1.10; P = 0.18) or all-cause death (RR 0.97; 95% CI 0.88-1.08; P = 0.64). In contrast, extended-duration thromboprophylaxis was associated with an increased risk of major bleeding (RR 2.04; 95% CI 1.42-2.91; P < 0.01) and non-major clinically relevant bleeding (RR 1.81; 95% CI 1.29-2.53; P < 0.01). CONCLUSIONS Among hospitalised medically ill patients, prolonging venous thromboprophylaxis was associated with a decreased risk of composite events of the primary efficacy outcome and increased risk of bleeding with no significant difference in VTE-related death.

The mechanisms underlying tumor immunosurveillance and their association with the immune-related adverse events (irAEs) associated with checkpoint inhibitor immunotherapies remain poorly understood. We describe a metastatic melanoma patient exhibiting multiple episodes of spontaneous disease regression followed by the development of several irAEs during the course of anti-programmed cell death protein 1 antibody immunotherapy. Whole-exome next-generation sequencing studies revealed this patient to harbor a pyrin inflammasome variant previously described to be associated with an atypical presentation of familial Mediterranean fever. This work highlights a potential role for inflammasomes in the regulation of tumor immunosurveillance and the pathogenesis of irAEs.

Simple Summary The tumor-intrinsic NLRP3 inflammasome is a newly recognized player in the regulation of tumor-directed immune responses and promises to provide fresh insight into how tumors respond to immunotherapy. This brief review discusses recent data describing how activation of the tumor-intrinsic NLRP3 inflammasome contributes to immune evasion and what this pathway may provide to the field of immuno-oncology both in terms of pharmacologic targets capable of boosting responses to checkpoint inhibitor therapies and predictive biomarkers indicating which tumors may be most susceptible to these new therapeutic strategies. Abstract The tumor-intrinsic NOD-like receptor family, pyrin-domain-containing-3 (NLRP3) inflammasome, plays an important role in regulating immunosuppressive myeloid cell populations in the tumor microenvironment (TME). While prior studies have described the activation of this inflammasome in driving pro-tumorigenic mechanisms, emerging data is now revealing the tumor NLRP3 inflammasome and the downstream release of heat shock protein-70 (HSP70) to regulate anti-tumor immunity and contribute to the development of adaptive resistance to anti-PD-1 immunotherapy. Genetic alterations that influence the activity of the NLRP3 signaling axis are likely to impact T cell-mediated tumor cell killing and may indicate which tumors rely on this pathway for immune escape. These studies suggest that the NLRP3 inflammasome and its secreted product, HSP70, represent promising pharmacologic targets for manipulating innate immune cell populations in the TME while enhancing responses to anti-PD-1 immunotherapy. Additional studies are needed to better understand tumor-specific regulatory mechanisms of NLRP3 to enable the development of tumor-selective pharmacologic strategies capable of augmenting responses to checkpoint inhibitor immunotherapy while minimizing unwanted off-target effects. The execution of upcoming clinical trials investigating this strategy to overcome anti-PD-1 resistance promises to provide novel insight into the role of this pathway in immuno-oncology.

BACKGROUND: De novo hypoxemic respiratory failure is defined as significant hypoxemia in the absence of chronic lung disease such as COPD, and excluding respiratory failure occurring in the immediate postoperative or postextubation period. We aimed to evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in patients with de novo hypoxemic respiratory failure. METHODS: We performed electronic database searches of PubMed, Cochrane Library, and Embase from inception to December 2018 to include randomized controlled trials that compared various oxygenation strategies in cases of de novo hypoxemic respiratory failure occurring in adult subjects without a preexisting chronic lung disease and excluding respiratory failure in the immediate postoperative or postextubation periods. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrI). RESULTS: 16 studies were included, involving 2,180 subjects with a mean age of 61 ± 17 y (66% were male; 46% of the included subjects were treated with conventional oxygen, 27.8% were treated with NIV, and 25.8% were treated with HFNC). Compared to conventional oxygen, NIV was associated with reduced intubation rates (OR 0.42, 95% CrI 0.26–0.62) but no significant reduction in short-term (OR 0.73, 95% CrI 0.47–1.02) or long-term mortality (OR 0.60, 95% CrI 0.29–1.06). There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes. In a sensitivity analysis, the results remained consistent after exclusion of studies that included subjects with respiratory failure secondary to cardiogenic pulmonary edema. CONCLUSION: Among subjects with hypoxemic respiratory failure, NIV was associated with a significant reduction in intubation rates but not short- or long-term mortality when compared to conventional oxygen therapy. There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes.

Background Despite the high prevalence of ischemic heart disease in older patients, there is a substantial lack of evidence to guide clinical decision-making in this population. Hence, we performed a meta-analysis to determine the safety and efficacy of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare-metal stents (BMS). Methods Electronic databases were searched for randomized trials comparing DES with BMS in patients ≥70 years-old. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included different ischemic and bleeding events. Subgroup analyses for dual-antiplatelet therapy (DAPT) duration were conducted. Results We included 7 trials with a total of 5449 patients. The use of DES compared with BMS was associated with a significant reduction in MACE (odds ratio [OR]:0.76; 95% confidence interval [CI]:0.62–0.93; P = 0.007) with no increased risk of bleeding events (OR: 1.07; 95% CI: 0.89–1.27; P = 0.48). However, longer duration of DAPT (>6 months) for the DES group increased bleeding events (OR: 1.52; 95% CI: 1.05–2.20; P = 0.03). In contrast, shorter DAPT showed persistent efficacy in reducing MACE in DES-treated patients with no increased bleeding events (OR: 0.72; 95% CI: 0.60–0.87; P Conclusions In older patients who had undergone PCI, DES showed superior efficacy in reducing MACE with no increased risk of bleeding compared with BMS. Persistent MACE reduction was evident with shorter DAPT durations in DES-treated patients. Summary This meta-analysis of randomized clinical trials demonstrated that drug-eluting stents were associated with a significant reduction in major adverse cardiovascular events with no increased risk of bleeding compared with bare-metal stents. The risk of bleeding was high with longer dual antiplatelet therapy duration for patients who underwent DES placement. However, short duration of dual antiplatelet therapy substantially reduced major adverse cardiovascular events with no increased bleeding risk.

In the United States, cancer is the second leading cause of mortality, and millions more battle cancer worldwide. As such, primary prevention of cancer is a major interest globally. Aspirin has been studied as a primary prevention method for multiple diseases, mainly cardiovascular disease and various forms of cancer. The role of aspirin as a primary prevention of cancer is still controversial and may be more beneficial in certain cancers over others. With rapidly surfacing large randomized controlled trials (RCTs) studying this subject, we aimed to evaluate the efficacy and safety of aspirin as a primary prophylaxis for cancer. A comprehensive electronic database search was conducted for all RCTs that compared aspirin versus placebo for the prevention of any type of disease, and where cancer incidence or mortality was reported. The primary outcome was cancerrelated mortality. Secondary outcomes were cancer incidence, all-cause mortality, major bleeding, any bleeding and gastrointestinal (GI) bleeding. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up period. We included 16 RCTs with 104,018 total patients, mean age of 60.51 years, mean follow-up of 5.48 years, and a male percentage of 38.72%. We found that aspirin was not associated with a significant reduction of cancer-related mortality compared with placebo (RR 0.99; 95% CI: 0.87–1.12; P = 0.85: I2 = 41%). Compared with placebo, aspirin was not associated with significant reduction of all-cause mortality (RR 0.97; 95% CI: 0.92–1.02; P = 0.19; I2 = 13%) or cancer incidence (RR: 0.98; 95% CI: 0.92–1.04; P = 0.43; I2 = 16%). However, aspirin treatment was associated with significantly increased risks of any bleeding (RR 1.63; 95% CI: 1.31–2.03; P < 0.01), major bleeding (RR 1.41; 95% CI: 1.26–1.57; P < 0.01), and GI bleeding (RR 1.85; 95% CI: 1.38–2.48; P < 0.01) compared with placebo. Our study did not find any significant reductions in cancer-related mortality or cancer incidence when compared aspirin use with placebo or no aspirin. Our study also highlights that the use of aspirin for primary prevention of cancer was found to cause higher rates of bleeding (any bleeding, major bleeding, and GI bleeding) compared to placebo or no aspirin at the longest follow-up period with no significant benefit in cancer primary prevention.

Introduction: Acute hypoxemic respiratory failure (AHRF) is a leading cause of intensive care unit (ICU) admission among immunocompromised patients. Invasive mechanical ventilation is associated with increased morbidity and mortality. Objective: To evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in immunocompromised patients with AHRF. Methods: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to December 2018. We included all randomized controlled trials (RCTs) comparing different modalities of initial oxygenation strategies in immunocompromised patients with AHRF. Our primary outcome was the need for intubation and invasive mechanical ventilation while secondary outcomes were ICU acquired infections and short- and long-term mortality. Data were extracted separately and independently by 2 reviewers. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrIs). Results: Nine RCTs were included (1570 patients, mean age 61.1 ± 13.8 years with 64% male). Noninvasive ventilation was associated with a significantly reduced intubation rate compared with standard oxygen therapy (OR: 0.53; 95% CrI: 0.26-0.91). There were no significant reductions of intubation between NIV versus HFNC (OR: 0.83; 95% CrI: 0.35-2.11) or HFNC versus standard oxygen therapy (OR: 0.65; 95% CrI: 0.26-1.24). There were no significant differences between all groups regarding short-term (28-day or ICU) mortality or long-term (90-day or hospital) mortality or ICU-acquired infections ( P > 0.05). Conclusion: Among immunocompromised patients with AHRF, NIV was associated with a significant reduction of intubation compared with standard oxygen therapy. There were no significant differences among all oxygenation strategies regarding mortality and ICU-acquired infections.

Background: Metastatic clear-cell renal cell carcinoma (RCC) is largely incurable, and its treatment remains challenging. Sunitinib, a tyrosine kinase inhibitor, is one of the current standard-of-care options for treatment-naïve patients with metastatic RCC. Despite the proven efficacy of sunitinib, prolonged treatment with some tyrosine kinase inhibitors (TKIs) has been associated with significant adverse events (AEs). Therefore, we aimed to calculate the exact prevalence of all sunitinib-related AEs in a pooled analysis from all available randomized controlled trials (RCTs). Methods: A comprehensive electronic database search was conducted for all RCTs comparing the clinical outcomes and adverse events of sunitinib versus all other available treatments for treatment-naïve advanced/metastatic clear-cell renal cell carcinoma. We then calculated the pooled prevalence of the most common reported side effects of sunitinib. All statistical analyses were performed using R Statistical Software v3.4.0 (R Foundation, Vienna, Austria). Results: We included 8 RCTs, with a total of 4,106 patients. The mean age was 62, with 66.44% males. Any grade AEs were reported in 72% of patients with the following frequencies: fatigue, 44%; diarrhea, 38%; nausea, 31%; hand-foot syndrome, 30%; hypertension, 27%; dysgeusia, 25%; hypothyroidism, 25%; cconstipation, 20%; stomatitis, 20%; inflammation of the mucosa, 18%; dyspepsia, 16%; vomiting, 14%; rash, 12%; asthenia, 11%; and epistaxis, 10%. Grade 3 (severe) AEs were reported in 52% of patients with the following frequencies: hypertension, 9%; fatigue, 8%; hand-foot syndrome, 5%; asthenia, 5%; diarrhea, 4%; and inflammation of the mucosa, 2%. Laboratory abnormalities were also reported as follows: increased AST, 7%; increased lipase, 6%; neutropenia, 6%; thrombocytopenia, 6%; hypophosphatemia, 5%; lymphocytopenia, 5%; anemia, 4%; and leukopenia, 3%. Conclusion: Despite sunitinib being one of the current standard treatments for patients with metastatic/advanced clear-cell RCC, its safety profile is concerning, with a high prevalence of reported dangerous side effects. These findings underscore the importance of the emergence of newer drugs and treatment plans for patients with metastatic RCC, not only to achieve similar or better clinical outcomes but also to decrease the burden of adverse events.

Human immunodeficiency virus (HIV) characteristically presents as a mononucleosis-like prodrome; rhabdomyolysis as a sole manifestation remains a rare finding from infection to seroconversion. A young male with a vague sexual history presented with myopathy progressing rapidly to rhabdomyolysis and renal failure. Acute HIV rarely presents with classic features, and rhabdomyolysis seems to manifest more in younger patients. Our case also demonstrates the importance of keeping a strong suspicion for HIV in the right setting despite false-negative results in the pre-seroconversion phase. The variability in HIV presentation and stigma of sexual history taking represents a diagnostic challenge. The astute clinician must be privy to these peculiarities to formulate a prompt diagnosis.

Background Venous thromboembolism (VTE) is a well-known complication associated with surgical procedures. The implementation of thromboprophylaxis in this population has become a vital aspect of perioperative care to decrease VTE-associated morbidity and mortality risk. However, data assessing the role of thromboprophylaxis for patients undergoing vascular surgery are sparse. Assessing the role of thromboprophylaxis by low-molecular-weight heparin or unfractionated heparin in vascular surgery. Methods We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until December 2020, for randomized controlled trials assessing the role of thromboprophylaxis in vascular surgery. Results Eight randomized controlled trials met inclusion criteria, including 3130 patients, with a mean age of 55.35 years and 45% were females. Compared with placebo, anticoagulant use was associated with a decrease in deep venous thrombosis (DVT) (risk ratio [RR], 0.34; 95% confidence interval [CI], 0.11-1.05; P = .06; I2 = 68%) and pulmonary embolism (PE) (RR, 0.17; 95% CI, 0.02-1.22; P = .08; I2 = 41%), but this trend did not attain statistical significance. There was no difference for bleeding outcomes between anticoagulants and placebo (RR, 0.90; 95% CI, 0.05-15.01; P = .94; I2 = 76%). There was no significant difference in outcomes when low-molecular-weight heparin was compared directly with unfractionated heparin. In a sensitivity analysis, anticoagulant use was associated with a significant decrease in DVT or PE in patients undergoing venous surgeries, but was not associated with a significant decrease in DVT or PE in patients undergoing arterial surgeries, although this analysis was limited by the small number of studies in each group. Conclusions Among patients undergoing vascular surgery, thromboprophylaxis with anticoagulants showed a trend toward a lesser incidence of VTE when compared with placebo, although this difference was not statistically significant. Bleeding outcomes were comparable between both treatment groups.

Patient: Female, 80-year-old Final Diagnosis: Acute esophageal necrosis • acute pharyngitis • duodenal ulcerations • gastric erosions • gastritis Symptoms: Dysphagia • emesis • globus • hoarseness • sore throat Medication:— Clinical Procedure: Esophagogastroduodenoscopy Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Acute esophageal necrosis (AEN), also known as black esophagus or Gurvits syndrome, is an infrequently seen clinical condition distinguishable by a visually striking endoscopic appearance of necrotic esophageal mucosa that involves the distal esophagus with proximal extensions ending at the gastroesophageal junction. Since its early recognition pathologically in the 1960s and endoscopically in the 1990s, AEN, despite its rarity, is being increasingly recognized as a demonstratable cause of upper gastrointestinal bleeding. Cases of pan-esophageal necrosis are sparsely reported, leaving management guidance to isolated case reports. Case Report: An 80-year-old female smoker with advanced chronic obstructive pulmonary disease presented with signs and symptoms of acute pharyngitis and globus sensation that had been evolving over the preceding weeks. An esophagogastroduodenoscopy revealed circumferential necrotic mucosa encircling the entire lumen of the esophagus. The patient was made nil-per-os and started on high-dose anti-reflux therapy with adequate hemo-dynamic resuscitation. Conclusions: AEN is multifactorial but primarily a combination of decreased tissue perfusion and a massive influx of gastric contents in settings of impaired local defense barriers. Despite its dramatic presentation, the majority of cases resolve with conservative medical management, foregoing surgical interventions.

A 77-year-old African American female was referred to oncology for evaluation of an adrenal fossa mass detected on computed tomography scan of the abdomen and pelvis (CT-scan A/P) that was ordered as a work-up for painless hematuria. Further evaluation by positron emission tomography (PET) scan showed hypermetabolic masses in the left suprarenal and right iliac region. The biopsy of the right iliac mass was consistent with IgG4-related disease (IgG4RD). It was supported by an elevated serum IgG4 level. She was treated with prednisone with a good response.

Acute acquired thrombotic thrombocytopenic purpura (TTP) requires prompt recognition and initiation of plasma exchange (PEX) therapy and immunosuppression. When PEX fails, mortality nears 100%, making finding an effective treatment crucial. Primary refractory TTP occurs when initial therapies fail or if exacerbations occur during PEX therapy, both signifying the need for treatment intensification to achieve clinical remission. Rituximab helps treat most of the refractory TTP cases, except those that are severely refractory. A paucity of studies guiding severely refractory TTP makes management arbitrary and individualised, highlighting the value of isolated reports. We present an extremely rare case of primary refractory TTP with an insufficient platelet response to numerous types of treatments, including emerging therapies such as caplacizumab, on the background of repeated PEX and immunosuppressive therapies.

The pervasive use of counterfeit sexual enhancement supplements is increasing worldwide. There are thousands of vendors on the internet while local gas stations and convenience stores are selling it across the United States (US). We report a case of right coronary artery ST-segment elevation and complete heart block in a nitrate-free patient shortly after consuming three 950 mg pills of a sexual enhancer known as rhino and completing sexual intercourse. Coronary angiography revealed 100% occlusion of the right coronary artery and a drug-eluting stent was inserted with a transvenous pacer that he tolerated well, and recovered without complications. The counterfeit drug has gained traction for its high user satisfaction and low cost among recreational customers. The Food and Drug Administration (FDA), through its MedWatch program, has frequently released citations to consumers warning them against rhino since 2015, while their labs have recognized two prime ingredients: sildenafil and tadalafil. Although adverse cardiac risk with this therapeutic class is low, we aim to parse out its temporal relationship with rhino, an enhancer containing 14-200 times the prescription limits of sildenafil and tadalafil.

2019 has been a landmark year in the world of electronic nicotine delivery systems (ENDS), specifically e-cigarette and vaping. Numerous state health departments across the United States have voiced their concerns in the growing number of lung injury cases from e-cigarettes and vaping. Over the past few decades, many agencies have brought into light the harmful effects of smoking cigarettes, and despite popular belief, a growing movement has started to recognize the harmful effects of ENDS. The Centers for Disease Control and Prevention have released recommendations and provided health practitioners a methodology to identify and diagnose e-cigarette, or vaping, product use-associated lung injury (EVALI). EVALI is a diagnosis of exclusion and comprises a variety of respiratory illnesses, with intubation rates nearing 32%. The most critical risk factor remains product use in the preceding 90 days, although a timeline on the development of symptoms or notable structural changes remains unknown. We present a case of acute lung injury in a traditional cigarette smoker that evolved within hours of switching to e-cigarettes.

Classic or large duct primary sclerosing cholangitis (PSC) is part of the PSC spectrum. It is diagnosed on clinical and biochemical findings of cholestasis supported by biliary tree changes on cholangiography, forgoing the need for an invasive liver biopsy. The spectrum contains various PSC variants with distinct clinical courses and outcomes. We present a case of small duct PSC, a rare variant that manifested insidiously with clinical and objective cholestasis but appeared negative on diagnostic cholangiography. Eventually, a liver biopsy was obtained that revealed chronic bilious disease of the small and microscopic ducts with simultaneous changes consistent with liver cirrhosis. Despite presenting like its classical counterpart, small duct PSC can remain undetectable on cholangiography due to the diminutive size of the bile ducts requiring histological confirmation. In contrast to classic PSC, small duct PSC portends a much better prognosis. However, it eventually progresses to the classic form or end-stage liver disease, requiring patients to receive timely surveillance and transplantation referrals. Due to the limited understanding of this disease process, patients with similar presentations often pose a diagnostic dilemma due to the clinical and cholangiographic mismatch. This case aims to reaffirm that a negative cholangiography does not rule out the PSC spectrum and that small duct disease is a rare but growing entity. The paucity in cases emphasizes the importance of isolated reports in guiding workup and management, especially since surveillance schedules and transplantation guidelines have not been formally established.

Recurrent stroke is common immediately following a transient ischemic attack (TIA) or ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than monotherapy. Electronic databases were searched for randomized clinical trials (RCTs) comparing DAPT with monotherapy in ischemic stroke/TIA. Sixteen RCTs with a total of 29,032 patients were included. Compared with monotherapy, DAPT was associated with significantly lower rates of any stroke (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.72-0.89) and ischemic stroke (RR 0.75; 95% CI 0.66-0.85) during any follow-up period. Although significant increases in intracranial bleeding (RR 1.55; 95% CI 1.20-2.01) and major bleeding (RR 1.90; 95% CI 1.33-2.72) were associated with DAPT, especially with long-term follow-up, the number needed to harm was 258 and 113, respectively. Nevertheless, short-duration DAPT (≤ 1 month) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy. In contrast, long DAPT and DAPT started later after the index event (≥ 1 month) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy. Other clinical outcomes were essentially similar between the two groups and included recurrent TIA (RR 0.88; 95% CI 0.72-1.07), myocardial infarction (RR 1.04; 95% CI 0.84-1.29), vascular death (RR 0.99; 95% CI 0.82-1.19), and any death (RR 1.12; 95% CI 0.88-1.42). Similar findings were observed in patients who presented with minor stroke/TIA. Conclusions: Among patients who presented with ischemic stroke/TIA, short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention.

Anthracycline is a commonly prescribed antineoplastic agent. As a consequence of the growing number of cancer survivors, the incidence of anthracycline-induced cardiotoxicity is increasing. However, the optimal primary preventive strategy is lacking. Therefore, we conducted a meta-analysis of all randomized controlled trials to evaluate the efficacy of carvedilol for the primary prevention of anthracycline-induced cardiotoxicity. A comprehensive search of electronic databases was conducted. The primary and secondary outcomes were the occurrence of low left ventricular ejection fraction, and the absolute change in left ventricular ejection fraction (LVEF), respectively. We calculated the odds ratios for the primary outcome and the weighted mean differences for the secondary outcomes using a random-effects model. We included 8 randomized controlled trials (633 total patients). Our results showed significantly reduced rates of low LVEF favoring the carvedilol group (3.2% vs 5.8%; odds ratios: 0.42; 95% confidence interval: 0.18 to 0.99; p = 0.05). Furthermore, there were significantly smaller reductions in LVEF in carvedilol-treated patients than in placebo-treated patients (mean differences: 2.41%; 95% confidence interval: 0.01 to 4.81; p = 0.05). In conclusion, prophylactic administration of carvedilol in anthracycline-treated cancer patients may reduce the early onset of left ventricular dysfunction compared with placebo.

OBJECTIVES This study aimed to evaluate the efficacy and safety of personalized genotype-guided selection of antiplatelet therapy versus standard of care in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Clopidogrel is the most frequently used P2Y12 receptor antagonist in patients with coronary artery disease. However, genetic variations of clopidogrel are associated with inter-individual response variability which could limit its efficacy. METHODS Electronic databases were searched for all randomized clinical trials (RCTs) evaluating genotype-guided therapy versus standard of care in patients undergoing stent implantation. Aggregated risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS We included 6 RCTs with a total of 2,371 patients. When compared with standard of care, the use of genotype-guided therapy did not significantly reduce major adverse cardiovascular events (MACE) (RR 0.67; 95% CI: 0.35-1.27; P = 0.22). However, MACE was significantly reduced in the subset of trials which enrolled only acute coronary syndromes (ACS) (P < 0.01). In addition, there was a significant reduction in myocardial infarction in the genotype-guided group (RR 0.44; 95% CI: 0.28-0.70; P < 0.01; I2 = 0%). Other clinical outcomes were not significantly different: cardiovascular mortality (RR 0.68; 95% CI: 0.27-1.74; P = 0.42), stroke (RR 0.62; 95% CI: 0.23-1.65; P = 0.34), stent thrombosis (RR 0.37; 95% CI: 0.13-1.06; P = 0.06), and bleeding (RR 0.68; 95% CI: 0.43-1.06; P = 0.09). CONCLUSION In patients undergoing stent implantation, MACE with genotype-guided therapy was not significantly reduced; however, there was a signal towards reduction of MACE in ACS patients, as well as a lower rate of MI, though this will require further confirmation in adequately powered trials.

Atrial fibrillation (AF) and heart failure (HF) often coexist. We conducted this meta-analysis to assess the efficacy and safety of catheter ablation in this population.Electronic databases were searched for all randomized clinical trials (RCTs) that evaluated catheter ablation in patients with left ventricular systolic dysfunction (LVSD). We calculated the weighted mean differences (MDs) and risk ratios (RRs) using a random-effects model.We included 7 RCTs with 851 patients (mean follow-up was 18 months). Catheter ablation in patients with LVSD was associated with significantly lower HF hospitalization rates (RR 0.57; 95% CI: 0.45-0.72; P 0.01), reduced all-cause mortality (RR 0.52; 95% CI: 0.35-0.76; P 0.01), improved left ventricular ejection fraction (MD 7.40; 95% CI: 3.37-11.43; P 0.01), increased 6-minute walk test (MD 26.96; 95% CI: 6.39-47.54; P = 0.01), and improved peak oxygen consumption (VOIn this meta-analysis of RCTs, catheter ablation was associated with significant improvements in the clinical, structural, and functional capacity of patients with AF and coexisting HF compared with medical treatment.

Tenecteplase is a genetically mutated variant of alteplase with superior pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety in acute ischemic strokes are limited. Hence, we conducted a study to evaluate the efficacy and safety of tenecteplase compared with alteplase in acute ischemic stroke. Electronic databases were searched for randomized clinical trials (RCTs) comparing tenecteplase with alteplase in acute ischemic stroke patients eligible for thrombolysis. We evaluated various efficacy and safety outcomes using random-effects models for both pairwise and Bayesian network meta-analyses along with meta-regression analyses. We included 5 RCTs with a total of 1585 patients. Compared with alteplase, tenecteplase treatment was associated with significantly greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval [CI] 1.04-3.87; p = 0.04) and early neurological improvement (OR 1.43; 95% CI 1.01-2.03; p = 0.05). There were no differences between the two thrombolytics in terms of excellent recovery (modified Rankin Scale [mRS] 0-1; OR 1.17; 95% CI 0.95-1.44; p = 0.13), functional independence (mRS 0-2; OR 1.24; 95% CI 0.78-1.98), poor recovery (mRS 4-6; OR 0.78; 95% CI 0.49-1.25; p = 0.31), complete/partial recanalization (OR 1.51; 95% CI 0.70-3.26; p = 0.30), any intracerebral hemorrhage (OR 0.81; 95% CI 0.56-1.17; p = 0.26), symptomatic intracerebral hemorrhage (OR 0.98; 95% CI 0.52-1.83; p = 0.94), or mortality (OR 0.83; 95% CI 0.54-1.26; p = 0.38). In network meta-analysis, there were better efficacy and imaging-based outcomes with tenecteplase 0.25 mg/kg without increased risk of safety outcomes. Our results demonstrate that in acute ischemic stroke, thrombolysis with tenecteplase is at least as effective and safe as alteplase.

Vitamin K antagonist (VKA) is a commonly prescribed anticoagulant with a narrow therapeutic window. Genetic polymorphisms account for high VKA dosage variability. Hence, we performed an updated meta-analysis of all randomized clinical trials (RCTs) comparing genotype-guided VKA versus standard dosing algorithms. We conducted a systematic search of electronic databases from inception to October 2017 for all RCTs. The primary outcome was the percentage of time in therapeutic range (TTR). Secondary outcomes were international normalized ratio >4, major and all bleeding events, thromboembolism, adverse and serious adverse events, and all-cause mortality. We calculated the weighted mean difference for the primary outcome and risk ratio (RR) for secondary outcomes using a random-effect model. We included 20 RCTs and analyzed a total of 5,980 adult patients. Our pooled analysis showed greater improvement in TTR for the genotype-guided group in comparison with the standard group (mean difference 3.41%, 95% confidence interval [CI] 0.71 to 6.10, p = 0.01). In addition, there were significant reductions in major and all bleeding events ((RR 0.35, 95% CI 0.20 to 0.63, p = 0.0004) and (RR 0.79, 95% CI 0.66 to 0.95, p = 0.01), respectively). However, there were no significant differences between the groups for international normalized ratio >4 (RR 0.89, 95% CI 0.80 to 1.00, p = 0.06), thromboembolism (RR 0.81, 95% CI 0.56 to 1.17, p = 0.25), serious adverse events (RR 0.79, 95% CI 0.61 to 1.03, p = 0.08), any adverse events (RR 0.94, 95% CI 0.88 to 1.01, p = 0.07), or all-cause mortality (RR 0.73, 95% CI 0.32 to 1.66, p = 0.46). In conclusion, genotype-guided VKA dosing can improve the TTR and reduce the risk for bleeding episodes, in comparison with standard dosing algorithms.

This is a case of a 62-year-old female, known to have multiple medical problems, who presented to her primary care physician with an intermittent abdominal pain and discomfort for a few months. The initial work-up showed mild leucocytosis and a small mass in the omentum. Given that the most concerning differential diagnosis was malignancy, the patient was referred to oncology, where biopsy of the mass showed omentum extramedullary hematopoiesis. The differential diagnosis was wide; however, a repeat computed tomography (CT) scan of the abdomen and pelvis did show persistence of the omental mass. After ruling out any possible causes, including myelofibrosis, with a normal bone marrow, her extramedullary hematopoiesis was deemed of unknown origin and with no clear explanation. Therefore, the patient was diagnosed with a rare adult idiopathic omental extramedullary hematopoiesis that was stable over time.

Background Patients who undergo knee or hip arthroplasty are at a significant risk of venous thromboembolism (VTE) development (pulmonary embolism and/or deep-vein thrombosis). Many different thromboprophylactic strategies have been used for the prevention of VTE in these patients with different outcomes. Therefore, our aim was to evaluate the efficacy and safety of aspirin prophylaxis when compared with placebo or anticoagulants in this population of patients. Methods A comprehensive electronic database search was conducted for all randomized controlled trials (RCTs) comparing the clinical outcomes of aspirin versus placebo or anticoagulants for the prevention of VTE after knee or hip arthroplasty. The primary outcome was VTE incidence. Secondary outcomes included any bleeding, major bleeding and mortality. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest possible follow-up period. Results We included 13 RCTs with a total of 20,115 patients with a mean age of 67.15 ± 9.54 and 24.39% males. Aspirin was found to be associated with a non-significantly reduced VTE events compared with other thromboprophylactic methods (RR 0.87; 95% CI: 0.61–1.23; P = 0.43). Compared with placebo, aspirin was associated with significant reduction of VTE (RR 0.65; 95% CI: 0.47–0.89; P = 0.008). There were no significant differences in the clinical outcomes between all groups with regard to mortality (RR 0.98; 95% CI: 0.86–1.11; P = 0.72), major bleeding events (RR 0.96; 95% CI: 0.50–1.84; P = 0.91), and any bleeding events (RR: 1.09; 95% CI: 0.82–1.44; P = 0.56). Conclusion Among patients who underwent knee or hip arthroplasty, aspirin prophylaxis was found to be associated with similar efficacy and safety outcomes when compared with anticoagulants. When compared with placebo, aspirin prophylaxis was associated with significantly reduced VTE and a comparable safety profile.

Introduction: Subclinical hypothyroidism is associated with increased carotid intima media thickness (CIMT) and decreased flow-mediated dilation (FMD) – surrogate markers of subclinical atherosclerotic cardiovascular disease (ASCVD). However, treatment with levothyroxine in this population remains controversial. Methods: Electronic database search was conducted for all randomized clinical trials (RCTs) that evaluated the treatment of subclinical hypothyroidism on surrogate markers of subclinical ASCVD. The primary and secondary outcomes were the mean change of CIMT and FMD, respectively. We calculated the weighted mean differences (MDs) and 95% confidence intervals (CIs) using the inverse variance random-effects method for continuous data. Results: Seven RCTs were identified with a total of 541 patients. There were 115 males and the mean age was 54.5 ± 18.7 years with mean baseline thyroid-stimulating hormone of 6.78 ± 2.5. There were no differences between levothyroxine-treated patients and placebo with regard to CIMT differences (MD −0.02; 95% CI −0.08–0.04; P = 0.49; I2 = 59%). However, the levothyroxine-treated group was associated with significantly increased FMD compared with placebo (MD 1.61; 95% CI 1.21–2.01; P

We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of early versus delayed invasive management of non-ST-elevation acute coronary syndrome (NSTE-ACS).Coronary angiography is recommended for patients with NSTE-ACS, however, the optimal timing for this remains controversial.Literature search of Pubmed/MEDLINE, Cochrane Library, and Embase for all RCTs that compared early with delayed invasive approaches in treating NSTE-ACS was conducted by two independent authors. Primary outcome was major adverse cardiovascular events (MACE), while the secondary outcomes included cardiovascular mortality, all-cause mortality, myocardial infarction (MI), and bleeding events. The Mantel-Haenszel random-effects model was used to calculate risk ratios (RRs) and 95% confidence intervals (CIs).We included 14 RCTs (9,637 patients, mean age 65.4, 67% males). The early invasive strategy was associated with a lower incidence of MACE compared with the delayed invasive strategy (RR 0.65, 95%CI 0.49-0.87; p = .003). Subgroup analysis according to GRACE score showed a lower incidence of MACE with early invasive strategies in GRACE140 patients (p for interaction = .002). Furthermore, recurrent ischemia was lower in patients with an early invasive strategy (RR 0.42, 95%CI 0.26-0.69; p.0005). In contrast, there were no significant differences in all-cause mortality, cardiovascular mortality, MI, or bleeding events between groups (all p.05).Among patients with NSTE-ACS, an early invasive strategy was associated with lower incidence of MACE and recurrent ischemia compared with delayed invasive strategy. There were no significant differences in all-cause mortality, cardiovascular mortality, MI, or bleeding events between groups.

Gastrointestinal neuroendocrine neoplasms were recently reclassified into the 2019 World Health Organization schema into well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Among these, gastric MiNENs are exceedingly rare and often metastasize quickly without diagnostic clues. We present a refractory gastric MiNEN with unique presenting features. This case highlights the clinical spectrum of these tumors, the importance of accurate histochemical interpretation, and clinical management in the absence of formalized guidelines. Future therapies looking at novel targets and palliative symptom relief are needed.

523 Background: The Oncotype-DX recurrence score (RS) allows providers to identify hormone receptor positive and HER2-negative breast cancer (BC) patients that may benefit from adjuvant chemotherapy (AC). The TAILORx Trial showed no benefit of AC among patients with RS of 11-25, except for patients younger than 50 years. There are, however, limited studies examining any benefit of AC among those with RS of 26-30. We sought to examine the effect of AC on BC-specific survival among these patients utilizing a national database. Methods: We queried the Surveillance, Epidemiology, and End Results database for newly diagnosed female BC patients between 2010-2015. We included patients with T1-T3, hormone receptor positive, HER2-negative, and lymph node-negative BC with RS of 26-30. Patients with tumors 5 mm or less and with incomplete records were excluded. Cox Proportional-Hazards Model was done to examine the effect of AC on BC-specific survival. A sub-group analysis was performed for patients younger than 50 years to examine the effect of AC on BC-specific survival. Results: We included 2,982 patients, of whom 1,686 (56.5%) received AC. Administration of AC was associated with lower age (56.5 [9.2] vs 61.8 [9.7], p < 0.001), Grade III&IV (39.7% vs 30.2%, p < 0.001), married or patients with partners (66.5% vs 61.5%, p < 0.001), and T stage > 1 (31.3% vs 26.8%, p = 0.03). AC was not associated with insurance status, race, and histology. Overall 5-year BC-specific survival was 97.3% (96.2-98.3%). After adjustment through cox regression, AC was found to not have an effect on survival (HR: 0.54 [0.27-1.10], p = 0.09). There were 579 (19.4%) patients that were younger than 50 years, and AC did not have an effect on survival among these patients (HR: 0.44 [0.08-2.44], p = 0.35). Similarly, among the 2,403 (80.6%) patients aged 50 or older, AC did not have an effect on survival (HR: 0.49 [0.22-1.11], p = 0.09). Conclusions: In this retrospective analysis, administration of AC was associated with lower age, higher grade, marital status, and T stage. AC did not affect BC-specific survival among patients with a RS of 26-30. Subgroup analysis did not show any benefit of AC among patients younger than 50 years or among those 50 or older. Further prospective randomized trials are warranted to identify sub-groups that may potentially benefit from AC.

INTRODUCTION Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. OBJECTIVES To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA). METHODS We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). RESULTS Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P