Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes.

BACKGROUND: Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. METHODS: In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). RESULTS: Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58-74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7-3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4-3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. CONCLUSIONS: Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea.

PURPOSE: Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnotic zolpidem on the frequency of respiratory-related arousals and central apnea in patients with moderate-to-severe SDB. We hypothesized that zolpidem decreases the severity of SDB by decreasing the frequency of respiratory-related arousals. METHODS: Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5 mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO2 reserve and the respiratory arousal threshold, were also compared. RESULTS: Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO2 reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86 mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmH2O, P = 0.41). CONCLUSION: Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO2 reserve or increase the arousal threshold. TRIAL REGISTRATION: Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).

Cardiovascular outcomes and trends of Transcatheter vs. Surgical aortic valve replacement among octogenarians with heart failure: A Propensity Matched national cohort analysis.

Background: Heart failure (HF) is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood. Limited data is available regarding the in-hospital outcomes of TAVR compared to SAVR in the octogenarian population with HF. Methods: The National Inpatient Sample (NIS) database was used to compare TAVR versus SAVR among octogenarians with HF. The primary outcome was in-hospital mortality. The secondary outcome included acute kidney injury (AKI), cerebrovascular accident (CVA), post-procedural stroke, major bleeding, blood transfusions, sudden cardiac arrest (SCA), cardiogenic shock (CS), and mechanical circulatory support (MCS). Results: A total of 74,995 octogenarian patients with HF (TAVR-HF n = 64,890 (86.5%); SAVR n = 10,105 (13.5%)) were included. The median age of patients in TAVR-HF and SAVR-HF was 86 (83-89) and 82 (81-84) respectively. TAVR-HF had lower percentage in-hospital mortality (1.8% vs. 6.9%;p < 0.001), CVA (2.5% vs. 3.6%; p = 0.009), SCA (9.9% vs. 20.2%; p < 0.001), AKI (17.4% vs. 40.8%); p < 0.001), major transfusion (26.4% vs 67.3%; p < 0.001), CS (1.8% vs 9.8%; p < 0.001), and MCS (0.8% vs 7.3%; p < 0.001) when compared to SAVR-HF. Additionally, post-procedural stroke and major bleeding showed no significant difference. The median unmatched total charges for TAVR-HF and SAVR-HF were 194,561$ and 246,100$ respectively. Conclusion: In this nationwide observational analysis, TAVR is associated with an improved safety profile for octogenarians with heart failure (both preserved and reduced ejection fraction) compared to SAVR.

Anticoagulation management of post-cardiac surgery new-onset atrial fibrillation.

New-onset post-cardiac surgery atrial fibrillation (PCSAF) is a frequent complication with estimated incidence of 17% to 64%, depending on type of surgery. It is associated with higher mortality, morbidity, and predisposition to stroke and systemic embolism postoperatively. Standard care involves rate or rhythm control, in addition to antithrombotic therapy in those with history of stroke, transient ischemic attack, or high risk of systemic thromboembolism. However, risk of bleeding is not negligible, and treating physicians should weigh the risks and benefits before committing to postoperative anticoagulation therapy. More investigations are warranted to explore antithrombotic therapy benefit, particularly postoperative anticoagulation, considering the potentially self-limited nature of the arrhythmia and high risk of postoperative bleeding.

Comparison of left atrial appendage parameters using computed tomography vs. transesophageal echocardiography for watchman device implantation: a systematic review & meta-analysis.

BACKGROUND: Inaccurate sizing of left atrial appendage (LAA) occlusion devices is associated with increased stroke risk. We compared the LAA size to implant the Watchman device assessed by computed tomography (CT) to transesophageal echocardiography (TEE). METHODS: Databases were searched to identify studies comparing LAA anatomical measurements and procedural outcomes across imaging modalities for the Watchman device implantation. RESULTS: Seven studies were included in the analysis (242 patients on TEE, and 232 on CT). The LAA orifice was larger when sized with CT compared to TEE (CT mean vs TEE SMD 0.30 mm, 95%CI 0.09-0.51 mm, P < 0.01; and CT max vs TEE SMD 0.69 mm, 95%CI 0.51-0.87 mm, P < 0.001). Additionally, CT, including CT-based 3-dimensional models, had higher odds of predicting correct device size compared to TEE (OR 1.64; 95%CI 1.05-2.56; P = 0.03). CT resulted in a lower fluoroscopy time vs TEE (SMD -0.78 min, 95% CI -1.39 to -0.18, P = 0.012). No significant differences were found in device clinical outcomes. CONCLUSION: Compared to TEE, CT resulted in larger LAA orifice measurements, improved odds of predicting correct device size, and reduced fluoroscopy time in patients undergoing LAA occlusion with the Watchman device. There were no significant differences in other procedural outcomes.

Safety and efficacy of drug-coated balloon for peripheral artery revascularization-A systematic review and meta-analysis.

BACKGROUND: The relative merits of the drug-coated balloon (DCB) versus uncoated balloon (UCB) angioplasty in endovascular intervention for patients with symptomatic lower extremity peripheral arterial disease (PAD) remains controversial. METHODS: Online databases were queried with various combinations of keywords to identify relevant articles. Net adverse events (NAEs) and its components were compared using a random effect model to calculate unadjusted odds ratios (ORs). RESULTS: A total of 26 studies comprising 26,845 patients (UCB: 17,770 and DCB: 9075) were included. On pooled analysis, DCB was associated with significantly lower odds of NAE (OR: 0.47, 95% confidence interval [CI]: 0.36-0.61), vessel restenosis (OR: 0.46, 95% CI: 0.37-0.57), major amputation (OR: 0.68, 95% CI: 0.47-99), need for repeat target lesion (OR: 0.38, 95% CI: 0.31-0.47) and target vessel revascularization (OR: 0.62, 95% CI: 0.47-0.81) compared with UCB. Similarly, the primary patency rate was significantly higher in patients undergoing DCB angioplasty (OR: 1.44, 95% CI: 1.19-1.75), while the odds for all-cause mortality (OR: 0.96, 95% CI: 0.85-1.09) were not significantly different between the two groups. A subgroup analysis based on follow-up duration (6 months vs. 1 vs. 2 years) followed the findings of the pooled analysis with few exceptions. CONCLUSIONS: The use of DCB in lower extremity PAD intervention is associated with higher primary patency, lower restenosis, lower amputation rate, and decreased need for repeat revascularization with similar all-cause mortality as compared to UCB.

RETRACTED: Cardiovascular outcomes of ethyl eicosapentaenoic acid in diabetes mellitus: A meta-analysis.

Background: We aim to conduct a comprehensive meta-analysis encompassing all studies to assess the efficacy of Vascepa in patients with diabetes mellitus (DM) in preventing or treating existing coronary artery disease (CAD). Methods: Digital databases were queried. Odds ratios (OR) were calculated for the following outcomes: composite outcome, all-cause mortality, and cardiovascular mortality. Results: A total of 4 randomized control trials (33,092 patients; Vascepa n = 16586; Placebo n = 16506) were included in our analysis. The overall mean age was 64.3 years old (Vascepa = 64.3 years; Placebo = 64.3 years). The sample was 61.5% male (Vascepa = 60.8%; Placebo = 62.1%). In patients with DM, Vascepa was found to have no significant effect on the primary composite outcome (OR 0.97, 95%CI 0.91-1.04, p > 0.05), all-cause mortality (OR 0.96, 95%CI 0.90-1.03, p > 0.05), and cardiovascular mortality (OR 0.90, 95%CI 0.74-1.10, p > 0.05). Subgroup analysis by Vascepa type and treatment type was similarly non-significant. Conclusion: Our study concluded that Vascepa did not affect cardiovascular outcomes in patients with DM.

Safety and efficacy of the polymer-free and polymer-coated drug-eluting stents in patients undergoing percutaneous coronary intervention.

INTRODUCTION: The relative safety and efficacy of polymer-free (PF) versus polymer-coated (PC) drug-eluting stents (DES) in patients with angina or acute coronary syndrome (ACS) undergoing percutaneous coronary intervention has received limited study. METHOD: Digital databases were queried to identify relevant studies. Major adverse cardiovascular events (MACE) and secondary outcomes were compared using a random effect model to calculate unadjusted odds ratios (OR). RESULTS: A total of 28 studies consisting of 23,198 patients were included in the final analysis. On pooled analysis, there was no significant difference in the odds of MACE (OR 0.98, 95% CI 0.91-1.08) and major bleeding (OR 0.87, 95% CI 0.61-1.24) between patients undergoing PF-DES versus PC-DES. Similarly, the odds of myocardial infarction, stroke, stent thrombosis, cardiovascular mortality and need for target vessel revascularization was similar between the two groups. PF-DES was favored due to significantly lower odds of non-cardiac death (OR 0.78, 95% CI 0.68-89) and all-cause mortality (OR 0.87, 95% CI 0.80-0.95), but had a higher need for target lesion revascularization (OR 1.2, 95% CI 1.02-1.42). A subgroup analysis based on follow up duration, clinical presentation, presence of diabetes and class of eluting drugs mirrored the net estimates for all outcomes with a few exceptions. A sensitivity and meta-regression analysis showed no influence of single-study and duration of antiplatelet therapy on pooled outcomes. CONCLUSION: In patients presenting with angina or ACS, PF-DES might be favored due to lower all-cause mortality and equal risk of ischemic adverse cardiovascular and major bleeding events compared with PC-DES.

In-hospital outcomes of endovascular versus surgical revascularization for chronic total occlusion in peripheral artery disease.

BACKGROUND: The outcome of endovascular intervention (EVI) compared vs. surgical revascularization in patients with peripheral artery disease (PAD) due to chronic total occlusion (CTO) is unknown. METHODS: Using the National Inpatient Sample database between 2007 and 2014, we identified all PAD patients with CTO who had limb revascularization. Multivariate analysis was performed to estimate the odds of in-hospital mortality and adverse outcomes between both groups. RESULTS: A total of 168,420 patients who had peripheral CTO and underwent limb revascularization were identified. 99,279 underwent EVI, and 69,141 underwent surgical revascularization. The patients who underwent EVI were younger, more likely to be women and African American, and less likely to be white (p < 0.001 for all). EVI was associated with lower in-hospital mortality (1.2% vs 1.7%, adjusted odds ratio [aOR]: 0.54; 95% confidence interval [CI] 0.50-0.59). The EVI group had higher vascular complications, major bleeding, acute kidney injury (AKI), and major amputation compared with surgical revascularization. A subgroup analysis on patients with critical limb ischemia showed lower mortality in the EVI group (1.4% vs. 1.9, aOR 0.56; 95% CI 0.50-0.63). Although there was no difference in the incidence of AKI or major amputation between the two groups, the EVI group had higher vascular complication rates and major bleeding events. CONCLUSION: EVI in PAD with CTO is associated with lower in-hospital mortality, likely due to the procedure's less-invasive nature; however, it is associated with higher postprocedural complications likely due to the CTO's complexity.

Trends and causes of readmission following peripheral vascular intervention in patients with peripheral vascular disease.

OBJECTIVES: To study the risk factors associated with 30-readmission postperipheral vascular intervention (PVI) in peripheral artery disease (PAD). BACKGROUND: There has been a paucity of data regarding the trend and predictors of PVI readmission. METHODS: We performed an observational cohort study of patients admitted with peripheral vascular disease for PVI using the NRD for the years 2010-2014. PVI was defined as angioplasty, atherectomy, and/or stenting of lower limb vessels. RESULTS: A total of 453,278 patients (30-day readmission n = 97,235). The mean age of study population was 68.6 ± 12.2 years and included 43.8% women. The 30-day readmission post-PVI was 21.5% (p = .034). Cardiovascular causes constitute 44% of readmission. Chronic limb ischemia and intermittent claudication were two most common cardiovascular causes constituting 11.7 and 4.9% cases of readmissions. Other cardiac causes of readmissions included heart failure (4.64%), dysrhythmias (1.4%), and acute myocardial infarction (1.7%). The high-risk factors for of all-cause 30-day readmission were hypertension, CLI, diabetes, renal failure, dyslipidemia, smoking, chronic pulmonary disease, and atrial fibrillation (p < .005). Length-of-stay was greater than 5 days for 56.2 and 75.4% paid by Medicare. CONCLUSIONS: Our study shows an average yearly readmission rate of 21.5% post-PVI. Chronic comorbidities and prolonged hospitalization were associated with higher risk of readmission.

Meta-Analysis Comparing the Safety and Efficacy of Single vs Dual Antiplatelet Therapy in Post Transcatheter Aortic Valve Implantation Patients.

The relative safety and efficacy of aspirin versus dual antiplatelet therapy (DAPT; aspirin+clopidogrel) in patients who underwent transcatheter aortic valve implantation (TAVI) and did not have a long-term indication for oral anticoagulation remains controversial. Digital databases were searched to identify relevant articles. The major safety end point was bleeding, while the efficacy end points included after-TAVI ischemic and thrombotic events. Data were analyzed using a random effect model to calculate the pooled unadjusted odds ratio (OR) for dichotomous outcomes. Eleven studies comprising 4805 patients (aspirin 2258, DAPT 2547) were included in the quantitative analysis. Patients receiving aspirin-alone had significantly lower odds of all cause bleeding (OR 0.41, 95% CI 0.29 to .057, p <0.00001), major vascular bleeding (OR 0.51, 95% CI 0.34 to 0.77, p = 0.001), Valve Academic Research Consortium 2 (VARC-2) major bleeding (OR 0.50, 95% CI 0.30 to 0.83 p = 0.008), VARC-2 minor bleeding (OR 0.55, 95% CI 0.31 to 0.97, p = 0.04), transfusion requirement (OR 0.39, 95%CI 0.15 to 0.0.98, p = 0.05) and major vascular complications (OR0.41, 95% CI 0.26 to 0.66, p = 0.0002) compared with after-TAVI patients receiving both aspirin and clopidogrel. These was no significant difference in the odds of VARC-2 life threatening bleeding (OR 0.52, 95% CI 0.25 to 1.07, p = 0.08), prosthetic valve thrombosis (OR 1.17, 95% CI 0.22 to 6.30, p = 0.85), cardiac tamponade (OR 0.77, 95% CI 0.20 to 2.98, p = 0.70), conversion to open procedure (OR 1.99, 95 % CI 0.42 to 9.44, p = 0.39), MI (OR 0.79 95% CI 0.38 to 1.64, p = 0.52), transient ischemic attack (TIA) (OR 0.89, 95% CI 0.12 to 6.44, p = 0.91), major stroke (OR 0.68 95 % CI 0.43 to 1.08, p = 0.10), disabling stroke (0R 1.01, 95% CI 0.41 to 2.48, p = 0.99), cardiovascular mortality (OR 0.81 95% CI 0.38 to 1.74, p = 0.59) and all-cause mortality (OR 0.86, 95% CI 0.63 to 1.16, p = 0.31) between the 2 groups. In conclusion, after-TAVI patients who received aspirin alone had lower bleeding events with no significant differences in mortality and stroke rate compared with those who received DAPT.