A Systematic Review and Meta-Analysis: Do We Still Need Microscope Surgery in Hepatic Artery Anastomosis to Decrease the Incidence of Complications in Living Donor Liver Transplantation?

Hepatic artery thrombosis (HAT) is the most serious vascular complication after liver transplantation (LT). Moreover, in comparison to deceased donor liver transplantation (DDLT), hepatic artery (HA) anastomosis is more challenging in living donor liver transplantation (LDLT) with a lot of controversial topics about the use of microscopic surgery. We aimed to compare the use of microscopic and loupe surgery in HA anastomosis in adult and pediatric LDLT to decrease the incidence of vascular complications. We searched PubMed, Scopes, Web of Science, and Cochrane Library for eligible studies from inception to April 2023 and a systematic review and a meta-analysis were done. According to our eligibility criteria, 10 studies with a total of 1939 patients were included. In comparison to microscopic surgery, loupe anastomosis has a similar incidence of HAT (thrombosis, risk ratio (RR) = 0.96, 95% CI = 0.26-3.48, P = 0.95). In addition to that, no significant difference was detected between the two types in terms of stenosis, decreased blood flow and hospital stay (decreased blood flow, RR = 0.68, 95% CI = 0.01-86.65, P = 0.88), (stenosis, RR = 1.81, 95% CI = 0.19-17.21, P = 0.60), (hospital stay, mean deviation (MD) = 1.16, 95% CI = -3.79-6.11, P = 0.65). However, the anastomotic time was longer in the case of microscopic surgery (anastomotic time, MD = 24.09, 95% CI = 7.79-40.39, P = 0.004). With an equal incidence of complications and longer anastomotic time, there is no added benefit of the routine use of microscopic surgery in HA anastomosis in LDLT.

Duct-to-Duct Anastomosis Versus Bilioenteric Anastomosis for Pediatrics Living Donor Liver Transplantation: A Systematic Review and Meta-Analysis.

With an incidence exceeding 30%, biliary complications after pediatric liver transplantation remain a great challenge. In addition, the database includes numerous controversial papers about the safety of duct-to-duct anastomosis compared to Reux-en-Y hepaticojejunostomy for pediatric living donor liver transplantation (LDLT). We aim to compare the two techniques in pediatric LDLT by conducting a systematic review and meta-analysis. PUBMED, Web of Science, Scopus, and Cochrane Library were searched for eligible studies from 1989 to October 2022. According to our eligibility criteria, seven articles (561 pediatric LDLT) were included in our study. On one hand, DD anastomosis is associated with a higher rate of biliary stricture in comparison to RYHJ (OR: 2.47, 95% CI = 1.20-5.09, P = 0.01; I2 = 12%). On the other hand, the incidence of cholangitis was higher in RYHJ (OR: 0.10 95% CI = 0.01- 0.84, P = 0.03; I2 = 0%). However, there was no significant difference in the overall incidence of complications, leakage and mortality between the two groups (overall incidence of complication OR: 1.12, 95% CI = 0.34-3.68, P = 0.86; I2 = 62%), (Leakage OR: 2.22, 95% CI = 0.79-6.23, P = 0.13; I2 = 18%) and (Mortality OR: 2.53, 95% CI = 0.61-10.57, P = 0.30; I2 = 0%). In conclusion, with a lower incidence of cholangitis, an equal overall incidence of biliary complication, and the possibility of RY conversion in case of stricture, DD anastomosis offers a feasible, safe, and more physiological alternative to RYHJ for pediatric LDLT.

A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma.

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti-CD38 antibody) in combination with cemiplimab (Cemi, anti-programmed death-1 [PD-1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de-escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti-PD-1/programmed death-ligand 1 [PD-L1] naïve), and objective response rate in Cohorts A2 (cHL anti-PD-1/PD-L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti-PD-1/PD-L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations.

Comparison of Cardiovascular Outcomes Between Dapagliflozin and Empagliflozin in Patients With Type 2 Diabetes: A Meta-Analysis.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are oral diabetes medications that enhance the excretion of glucose by preventing the renal proximal tubules from reabsorbing glucose, which lowers glucose levels in plasma. Currently, studies have shown that SGLT2 inhibitors have beneficial impacts on cardiovascular outcomes, but their effect varies between the individual SGLT2 inhibitors. Thus, the current meta-analysis was conducted to compare the efficacy of dapagliflozin and empagliflozin in preventing cardiovascular events in patients with type 2 diabetes. The current meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A search of studies comparing cardiovascular events between dapagliflozin and empagliflozin in patients with type 2 diabetes published up to 1 July 2022 was done by two reviewers independently on PubMed, Embase and Cumulated Index to Nursing and Allied Health Literature (CINAHIL). The pre-specified primary endpoints were cardiovascular death, stroke, myocardial infarction and heart failure. Overall four studies were included in this meta-analysis. No significant difference was found in the incidence of myocardial infarction (risk ratio (RR)=0.81, 95% confidence interval (CI): 0.60-1.09), heart failure (RR=0.76, 95% CI: 0.56-1.04), cardiovascular mortality (RR=0.46, 95% CI: 0.18-1.20) and stroke (RR=1.07, 95% CI: 0.84-1.38) between dapagliflozin and empagliflozin. Results have shown that the risk of developing stroke, heart failure, myocardial infarction and cardiovascular death were not significantly different in the two groups.

Final results of a phase 1b study of isatuximab short-duration fixed-volume infusion combination therapy for relapsed/refractory multiple myeloma.

Part B of this phase 1b study (ClinicalTrials.gov number, NCT02283775) evaluated safety and efficacy of a fixed-volume infusion of isatuximab, an anti-CD38 monoclonal antibody, in combination with pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma patients. Isatuximab (10 mg/kg weekly for 4 weeks, then every other week) was administered as a fixed-volume infusion of 250 mL (mL/h infusion rate) with standard doses of Pd on 28-day cycles. Patients (N = 47) had a median of three prior treatment lines (range, 1-8). Median duration of exposure was 36.9 weeks and median duration of first, second, and 3+ infusions were 3.7, 1.8, and 1.2 h, respectively. The most common non-hematologic treatment-emergent adverse events were fatigue (63.8%), infusion reactions (IRs), cough, and upper respiratory tract infection (40.4% each). IRs were all grade 2 and occurred only during the first infusion. The overall response rate was 53.2% in all patients (55.5% in response-evaluable population, 60.0% in daratumumab-naïve patients). Efficacy and safety findings were consistent with data from the isatuximab plus Pd infusion schedule in Part A of this study and also from the phase 3 ICARIA-MM study, and these new data confirm the safety, efficacy, and feasibility of fixed-volume infusion of isatuximab.

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.

This phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/d [20 mg/d in patients aged ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cutoff, 13 (11.9%) of 109 and 15 (27.3%) of 55 patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy end point) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859; P = .008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade 3 or higher infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as #NCT01084252.

Preoperative use of enoxaparin increases the risk of postoperative bleeding and re-exploration in cardiac surgery patients.

OBJECTIVE: The purpose of this study was to investigate if the preoperative use of new platelet inhibitors and low-molecular-weight heparins may contribute to bleeding after cardiac surgery. DESIGN: Retrospective data review. SETTING: University teaching hospital. PARTICIPANTS: One hundred eleven patients divided in 5 groups. INTERVENTIONS: Patients were grouped according to preoperative antithrombotic regimen: group 1, control, no agents (n=55); group 2, clopidogrel (n=9); group 3, enoxaparin (n=17); group 4, any GP IIb/IIIa inhibitor (n=14); and group 5, any drug combination (n=15). Data included cumulative mediastinal chest tube drainage, allogeneic blood transfusions, total blood donor exposures, and re-exploration. MEASUREMENTS AND MAIN RESULTS: Use of any drug (groups 2-5) resulted in greater total blood transfusions and donor exposure (p=0.0003) than control, especially red cells (p=0.002) and platelets (p=0.006). A greater percentage of patients on enoxaparin required mediastinal re-exploration for nonsurgical bleeding versus control (3/17 v 0/55, p=0.001). The use of enoxaparin was associated with significantly higher chest tube output after the first 24 hours postoperatively (p=0.048). CONCLUSION: Newer antithrombotic agents were associated with greater transfusion rates and total donor exposures. Enoxaparin use was associated with greater overall blood loss and with higher incidence of mediastinal re-exploration. The relative risk-benefit ratio of reduced periprocedure morbidity versus increased bleeding complications has yet to be determined.