Rate Of Severe Adverse Events Research Articles

Efficacy and safety of different cycles of neoadjuvant immunotherapy in resectable non-small cell lung cancer: A systematic review and meta-analysis

BackgroundThere is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. MethodsPubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. ResultsIncorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34–52 %) with two cycles and 33 % (95%CI, 22–45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28–50 %) and 56 % (95%CI, 44–68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21–50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15–35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. ConclusionThere are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

Rare and severe adverse events in children with inflammatory bowel disease: analysis of data from the PIBD-SETQuality Safety Registry

Rare and severe adverse events can occur in children with inflammatory bowel disease (IBD), and the relationship with disease or drug treatment is often uncertain. We aimed to establish a method of reporting adverse events of interest in children with IBD, allowing for estimates of incidence rates with comparison between different regions, and, if possible, to compare with published data on rates of adverse events in children overall. For this analysis, we used data from the Paediatric Inflammatory Bowel Disease Network for Safety, Efficacy and Treatment and Quality improvement of care (PIBD-SETQuality) Safety Registry, which collects data on multiple rare and severe adverse events in children younger than 19 years with IBD. Overall, the registry collected data on ten prespecified rare and severe adverse events in children with IBD, as established by a panel of paediatric IBD experts, via reports from paediatric gastroenterologists at participating hospitals between Nov 1, 2016, and March 31, 2023. Reporting physicians, who could only be paediatric gastroenterologists or IBD nurses reporting on behalf of paediatric gastroenterologists, were recruited through invitations sent to both national and international IBD networks and at conferences. Once per month, participating paediatric gastroenterologists received an email with an anonymous and unique link to an online survey asking them to report whether any of ten rare and severe adverse events had occurred in a patient in their paediatric-IBD population in the previous month. Prevalent or retrospective rare and severe adverse events were excluded, as were events occurring in children with an unconfirmed diagnosis of IBD or for whom inflammatory colitis was part of a monogenic immunodeficiency disorder. Duplicates and events that did not meet the definitions and criteria were excluded. Physicians could also report other, non-categorised adverse events if they considered them rare and severe. In case of no response, up to two reminders were sent for each per-month survey. Annual denominator data surveys were sent to obtain the total number of person-years for the estimation of incidence rates, which were calculated via Poisson regression models. Responses were gathered from 220 paediatric gastroenterologists from 167 centres. 121 centres were in Europe, 23 centres were in North America, 17 centres were in Asia, and six centres were in Oceania. Combined, the total population with paediatric IBD consisted of an estimated 30 193 children with 114 528 person-years of follow-up. 451 adverse events were initially reported. After excluding and reorganising adverse events, 402 were eligible; 261 (65%) were categorised and 141 (35%) were non-categorised. The most frequently reported adverse events were venous-thromboembolic events (n=66), renal failure (n=43), opportunistic infections (n=42), and cancer (n=33). Haemophagocytic lymphohistiocytosis (n=4) and liver failure (n=3) were the least frequently reported adverse events. Incidence rates per 10 000 person-years were 5·50 (95% CI 4·25-6·97) for venous-thromboembolic events, 3·75 (2·74-4·99) for renal failure, 3·67 (2·67-4·89) for opportunistic infection, and 2·88 (2·01-3·98) for cancer. Of 66 venous-thromboembolic events, 31 (47%) involved cerebral venous sinus thrombosis at an incidence rate of 2·71 (95% CI 1·86-3·77). The PIBD-SETQuality Safety Registry enabled us to identify incidence rates of rare and severe adverse events in children with IBD. Our findings can guide physicians and enhance awareness of the incidence of adverse events in children with IBD that are considered to be rare. EU Horizon 2020 Research and Innovation Programme.

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015).

The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24-38%)/GS, 26% (18-33%)], but the Kaplan-Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, -50%/-21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

Integrated Safety Analysis of Abrocitinib in 635 Adolescent Patients With Moderate-To-Severe Atopic Dermatitis With Over 1000 Patient-Years of Exposure

Introduction: Abrocitinib, an oral, once-daily, Janus kinase 1–selective inhibitor, was efficacious and well tolerated in adolescent patients with moderate-to-severe atopic dermatitis (AD) exposed for approximately 1 year of treatment. Here, we describe the updated long-term integrated safety profile of abrocitinib in adolescent patients in the JADE clinical program.Methods: A total of 635 adolescent patients (12 to <18 years; exposure: 1011.4 patient-years [PY]) were pooled for safety analysis from the phase 3 JADE clinical trials MONO-1 (NCT03349060), MONO-2 (NCT03575871), TEEN (NCT03796676), and REGIMEN (NCT03627767) and subsequently enrolled in the ongoing phase 3 extension trial JADE EXTEND (NCT03422822; data cutoff: September 25, 2021). Incidence rates (IRs; number of unique patients with events/100 PY) of severe adverse events (SAEs) and AEs of special interest were assessed.Results: Of the total 635 adolescents, 490 received the same abrocitinib dose throughout exposure (730.6 PY); 289 received abrocitinib 200 mg (424.5 PY) and 201 received abrocitinib 100 mg (306.1 PY). Duration of exposure was ≥96 weeks in 38% and 37%, and ≥144 weeks in 8% and 4% of patients who received abrocitinib 200 mg or 100 mg, respectively. In the 200-mg and 100-mg arms, AEs occurred in 243 (84%) and 153 (76%) patients; 8% (IR [95% CI], 5.87 [3.76-8.74]) and 9% (5.87 [3.48-9.27]) experienced SAEs, and 10% (6.96 [4.69-9.93]) and 8% (5.13 [2.93-8.33]) discontinued the study due to AEs, respectively. IRs of AEs of special interest were 1.84 (95% CI, 0.79-3.62) and 1.28 (0.35-3.27) for serious infection, 2.11 (0.97-4.01) and 1.62 (0.53-3.77) for all herpes zoster (HZ) infections, and 0.69 (0.14-2.03) and 0.32 (0.01-1.77) for opportunistic HZ infections in the 200-mg and 100-mg arms, respectively. One patient (aged 16 years) in the 200-mg arm had a nonfatal venous thromboembolism event (pulmonary embolism; IR, 0.23 [95% CI, 0.01-1.28]); patient had a family history of pulmonary embolism. There were no events of nonmelanoma skin cancer or other malignancies, tuberculosis, or other opportunistic infections (excluding HZ), major adverse cardiovascular events, or deaths.Conclusions: In this integrated safety analysis using the September 2021 data cut from the ongoing JADE EXTEND trial, abrocitinib had an acceptable long-term safety profile in adolescents with moderate-to-severe AD.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol

BackgroundChronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture.Methods/designThis is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period.DiscussionThis study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Batoclimab vs Placebo for Generalized Myasthenia Gravis

Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in the circulation and alleviate symptoms in patients with generalized MG. To examine the efficacy and safety profile of batoclimab, a monoclonal IgG1 antibody, in patients with generalized MG. This was a multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers in China. Adult patients 18 years or older with generalized MG were screened, and those who were antibody positive were enrolled. Eligible patients received batoclimab or matching placebo in addition to standard of care. Each treatment cycle consisted of 6 weekly subcutaneous injections of batoclimab, 680 mg, or matching placebo followed by 4 weeks of observation. A second treatment cycle was conducted in patients who required continuing treatment. The primary outcome was sustained improvement, as defined by a 3-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline for 4 or more consecutive weeks in the first cycle in individuals who were positive for acetylcholine receptor or muscle-specific kinase antibodies. A total of 178 adult patients with generalized MG were screened, 132 were randomly assigned, 131 tested positive for antibodies, and 1 tested negative for antibodies. A total of 132 patients (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) were enrolled. The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). The MG-ADL score diverged between the 2 groups as early as week 2. The mean (SE) maximum difference in MG-ADL score reduction occurred 1 week after the last dose (day 43, 1.7 [0.3] in the placebo group vs 3.6 [0.3] in the batoclimab group; group difference, -1.9; 95% CI, -2.8 to -1.0; nominal P < .001). The rates of treatment-related and severe treatment-emergent adverse events in patients were 36.9% (24 of 65) and 7.7% (5 of 65) in the placebo group vs 70.1% (47 of 67) and 3.0% (2 of 67) in the batoclimab group, respectively. Batoclimab increased the rate of sustained MG-ADL improvement and was well tolerated in adult patients with generalized MG. Clinical effects and the extent of IgG reduction were similar to those previously reported for efgartigimod and rozanolixizumab. Future studies of large sample size are needed to further understand the safety profile of batoclimab. ClinicalTrials.gov Identifier: NCT05039190.

Stent-Graft Placement for Hepatic Arterial Hemorrhage after Pancreaticobiliary Surgery: Long-Term Clinical Outcomes

PurposeTo evaluate the safety and long-term clinical outcomes of stent-graft placement to treat hepatic arterial hemorrhageafter pancreaticobiliary surgery. Materials and MethodsOutcomes were retrospectively evaluated in 61 patients (50 men and 11 women; mean age, 63 years) who underwent stent-graft placement for delayed arterial hemorrhage (after 24 hours) after pancreaticobiliary surgery from 2006 to 2023. Bleeding sites included the gastroduodenal artery stump (n = 54), common or proper hepatic artery (n = 5), and right hepatic artery (n = 2). The stent-grafts used were Viabahn (n = 27), Comvi (n = 11), Jostent (n = 3), Covera (n = 11), and Lifestream (n = 7). Technical and clinical success and adverse events (AE) were evaluated. After stent-graft placement, overall survival (OS), hemorrhage-free survival (HFS), and stent patency were evaluated. ResultsThe technical and clinical success rates of stent-graft placement were 97% and 93%, respectively. The severe AE rate was 12% and was significantly higher in patients who underwent pylorus-sacrificing rather than pylorus-preserving surgery (P = .001). None of the severe AEs were associated with patient mortality. Median OS after stent-graft placement was 854 days, and median HFS was 822 days. The 1-, 3-, 5-, and 10-year stent patency rates were 87%, 84%, 79%, and 72%, respectively. ConclusionsStent-graft placement was safe and provided long-term control of hepatic arterial hemorrhage after pancreaticobiliary surgery.

Role of endoscopic duodenojejunal bypass liner in obesity management and glycemic control.

The treatment of obesity and its comorbidities ranges from clinical management involving lifestyle changes and medications to bariatric and metabolic surgery. Various endoscopic bariatric and metabolic therapies (EBMT) recently emerged to address an important therapeutic gap by offering a less invasive alternative to surgery that is more effective than conservative therapies. This article comprehensively reviews the technical aspects, mechanism of action, outcomes, and future perspectives of one of the most promising EBMT, named duodenojejunal bypass liner (DJBL). The DJBL mimics the mechanism of Roux-en-Y gastric bypass by preventing food contact with the duodenum and proximal jejunum, thereby initiating a series of hormonal changes that lead to delayed gastric emptying and malabsorptive effects. These physiological changes result in significant weight loss and improved metabolic control, leading to better glycemic levels, preventing dyslipidemia and non-alcoholic fatty liver disease, and mitigating cardiovascular risk. However, concern exists regarding the safety profile of this device due to the reported high rates of severe adverse events, particularly liver abscesses. Ongoing technical changes aiming to reduce adverse events are being evaluated in clinical trials and may provide more reliable data to support its routine use in clinical practice.

Intravenous Hemin, a potential heme oxygenase-1 activator, does not protect from post-ERCP acute pancreatitis in humans: Results of a randomized multicentric multinational placebo-controlled trial

ObjectiveHemin, a heme oxygenase 1 activator has shown efficacy in the prevention and treatment of acute pancreatitis in mouse models. We conducted a randomized controlled trial (RCT) to assess the protective effect of Hemin administration to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients at risk. MethodsIn this multicenter, multinational, placebo-controlled, double-blind RCT, we assigned patients at risk for PEP to receive a single intravenous dose of Hemin (4 mg/kg) or placebo immediately after ERCP. Patients were considered to be at risk on the basis of validated patient- and/or procedure-related risk factors. Neither rectal NSAIDs nor pancreatic stent insertion were allowed in randomized patients. The primary outcome was the incidence of PEP. Secondary outcomes included lipase elevation, mortality, safety, and length of stay. ResultsA total of 282 of the 294 randomized patients had complete follow-up. Groups were similar in terms of clinical, laboratory, and technical risk factors for PEP. PEP occurred in 16 of 142 patients (11.3%) in the Hemin group and in 20 of 140 patients (14.3%) in the placebo group (p = 0.48). Incidence of severe PEP reached 0.7% and 4.3% in the Hemin and placebo groups, respectively (p = 0.07). Significant lipase elevation after ERCP did not differ between groups. Length of hospital stay, mortality and severe adverse events rates were similar between groups. ConclusionWe failed to detect large improvements in PEP rate among participants at risk for PEP who received IV hemin immediately after the procedure compared to placebo. Trial registration numberClinicalTrials.gov number, NCT01855841).

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease: A systematic review and meta-analysis.

Background and study aims Gastroesophageal reflux disease (GERD) is a widespread chronic gastrointestinal condition with an increasing worldwide prevalence. This research was a systematic review and meta-analysis evaluating the efficacy, safety, and long-term outcomes of endoscopic full-thickness plication (EFTP) for the treatment of GERD. Methods A comprehensive search of databases was conducted for studies published up to April 2023. We included randomized controlled trials (RCTs) and prospective observational studies that examined the use of EFTP in treating GERD among adult patients. We calculated pooled effect estimates using a random-effects model. Results EFTP significantly improved GERD Health-Related Quality of Life (GERD-HRQL) scores at 3-, 6-, and 12-month follow-up intervals. A considerable proportion of patients discontinued proton pump inhibitors, with cessation rates of 59% (95% confidence interval [CI]: 0.47-0.71), 68% (95% CI: 0.58-0.78), and 67% (95% CI: 0.46-0.89,) at 3, 6, and 12 months, respectively. At 3 and 6 months, 61% (95% CI: 0.54-0.68) and 66% (95% CI: 0.56-0.76) of patients experienced ≥50% improvement in GERD-HRQL scores. EFTP demonstrated a favorable safety profile, with a low rate of severe adverse events. We observed a 6.76% reduction (95% CI: -14.53-1.02) in the percentage of time with esophageal pH <4, a decrease in DeMeester scores, and fewer total reflux episodes. The average procedure time was 22.75 minutes (95% CI: 22.03-23.48). Subgroup analyses suggest that both the GERDx system and the NDO Plicator are effective and safe in treating GERD. Conclusions The findings from our study reveal that EFTP is a safe and effective treatment for GERD patients who have not responded adequately to conventional therapies. Given its minimally invasive nature, effectiveness, and limited adverse effects, EFTP emerges as a compelling alternative to conventional surgical procedures.

P963 The comparative effectiveness and safety of different biologics in young (&amp;lt;60 years) versus elderly (≥60 years) patients with IBD: results from a real-world experience at a Belgian tertiary centre

Abstract Background The therapeutic armamentarium for inflammatory bowel disease (IBD) is rapidly expanding as well as the number of elderly patients with IBD. Given the frailty of this subpopulation, it is of increasing importance to have data on the efficacy and safety of different therapies in this cohort. Aim: To assess the efficacy and severe adverse event (SAE) rate of different biologics in young (&amp;lt;60 years (yr)) versus elderly patients with IBD (≥60 yr) in a real-world tertiary cohort. Methods A retrospective monocentric study was performed at the Ghent University Hospital. Patients starting anti-TNF, ustekinumab (UST) or vedolizumab (VDZ) from 01/2018 to 06/2021 with follow-up until 12/2022 were included. Co-primary endpoints after induction and after 1 yr of therapy were: clinical response (CRp) and remission (CRm), biochemical response (BRp) and remission (BRm) and endoscopic response (ERp) and remission (ERm). The secondary endpoint was treatment survival. Severe adverse events (SAE) were defined as intestinal resection (IR), IBD-inflammation related hospitalization (IBD-hosp), IBD-treatment related hospitalization (e.g. infections) (treat-hosp), malignancy and death. Multivariate logistic regression (MLR) and Cox regression model (CRM) were applied to assess potential risk factors (RF). Results A total of 267 patients were included (33 patients ≥60 yr). Significantly different baseline characteristics are shown in Table 1A. After induction, no differences in CRp, CRm, BRp, ERp or ERm were found between both groups (Table 1B). Only BRm was numerically higher in younger patients, but not statistically significant after MLR (Table 1C). After one year of therapy, no difference was seen for CRp, CRm, BRp, BRm, ERp or ERm (Table 1B). There was no difference regarding treatment survival for both groups (aHR 0.701, [0.346-1.420], P=0.324) (figure 1), as well as for reason to stop biologic (P=0.336). Regarding SAEs, a higher rate was seen for elderly patients (26.9% vs. 45.5%, P=0.028), also after CRM (aHR 1.86, [1.01-3.44], P=0.047), adjusting for type of biologic, use of systemic corticosteroids or immunomodulators, previous IR, disease duration and number of previous biologics used. Regarding different subtypes of SAE, no difference for IR (P=0.503), IBD-hosp (P=0.714), specific IBD related SAE (P=0.480), malignancy (P=0.162) and death (P=1.000) were found. Treat-hosp was higher in elderly patients (5.1% vs. 24.2%, P=0.001), which was confirmed in the CRM (aHR 5.01, [1.92-13.04], P&amp;lt;0.001). Conclusion No difference was seen regarding efficacy of different biologics in younger versus elderly patients with IBD. SAE rate was higher in elderly patients.

Real-world outcomes of nivolumab plus ipilimumab and pembrolizumab with platinum-based chemotherapy in advanced non-small cell lung cancer: a multicenter retrospective comparative study

IntroductionNivolumab plus ipilimumab with chemotherapy (NICT) and pembrolizumab with chemotherapy (PCT) are commonly used in patients with advanced non-small cell lung cancer (NSCLC). Compared with immune checkpoint inhibitor (ICI) monotherapy, ICI combination therapy can increase immune-related toxicity instead of prolonging survival. This study aimed to compare the efficacy and safety of NICT and PCT to decide on the favorable treatment.MethodsWe conducted a multi-center retrospective cohort study on patients who underwent NICT or PCT between December 2018 and May 2022. Propensity score matching (PSM) was performed with the variables age, sex, smoking status, performance status, stage, histology, and programmed cell death ligand-1 (PD-L1). The Kaplan–Meier method was used to compare survival for the matched patients.ResultsSix hundred consecutive patients were included. After PSM, 81 and 162 patients were enrolled in the NICT and PCT groups, respectively. The baseline characteristics were well-balanced. The median progression-free survival was equivalent (11.6 vs. 7.4 months; P = 0.582); however, the median overall survival (OS) was significantly longer in the NICT group than in the PCT group (26.0 vs. 16.8 months; P = 0.005). Furthermore, OS was better in PD-L1-negative patients who underwent NICT than in those who underwent PCT (26.0 vs. 16.8 months; P = 0.045). Safety profiles did not differ significantly in terms of severe adverse event and treatment-related death rates (P = 0.560, and 0.722, respectively).ConclusionsReal-world data suggests that NICT could be a favorable treatment option compared with PCT for patients with advanced NSCLC. Further follow-up is needed to determine the long-term prognostic benefit.

Efficacy and safety of baricitinib in patients with severe COVID-19: A systematic review and meta-analysis.

This study aimed to investigate the efficacy and safety of baricitinib in patients with severe coronavirus disease 2019 (COVID-19). Databases were searched for studies that compared the clinical efficacy and adverse effects of baricitinib with standard therapy for the treatment of severe COVID-19 and clearly reported relevant outcomes published until December 31, 2022. The corresponding data were extracted from these studies. A fixed-effects model was used to calculate the pooled estimates. The study protocol can be accessed at PROSPERO (CRD42023394173). The baricitinib group had a significantly lower mortality rate and proportion of patients who received mechanical ventilation than the control group (OR = 0.61, 0.57; P = .008, 0.02; 95% CI 0.42-0.88; 0.35-0.92; I2 = 71% and 86%, respectively). The length of hospital stay and rates of severe adverse events were not significantly different between the 2 groups. Baricitinib reduces mortality and mechanical ventilation requirements in patients with severe COVID-19. Therefore, we developed a comprehensive understanding of the role of baricitinib in patients with severe COVID-19.

Comparison of perventricular and percutaneous ultrasound-guided device closure of perimembranous ventricular septal defects.

Ultrasound-guided percutaneous device closure of perimembranous ventricular septal defects (PmVSD) is a minimally invasive recent treatment approach. Perventricular PmVSD device closure is an emerging radiation-free intervention, yet it comes with certain limitations. No studies compared both of these treatment approaches. We performed a retrospective institutional data comparison of percutaneous (PCP Group, n = 138) and perventricular (PVP Group, n = 67) ultrasound-guided device closure procedures in 205 patients with PmVSD between March 2017 and December 2022. Patients of the PCP and PVP groups had a median age of 4.9 years (IQR, 3.1-14.0) and 5.3 years (IQR, 3.4-13.1) respectively. The median PmVSD diameter in the PCP Group was 4.0 mm (IQR, 3.3-5.3) and 5.2 mm (IQR, 4.0-7.0) in the PVP Group (p = 0.001). There was no significant difference in success rates between the PCP and PVP Groups (intention-to-treat population, 88.4% vs. 92.5%, p = 0.36; as-treated population, 88.4% vs. 89.3%, p = 0.84). 5/8 failed percutaneous cases that were shifted to the perventricular approach were successful. Compared to the PVP Group, patients of the PCP group experienced a significant decrease in ventilation time, drainage volume, and postoperative hospital stay (p < 0.001). The median follow-up period was 24 months (IQR, 6-42) for the PCP group and 61 months (IQR, 53-65) for the PVP group. The overall severe adverse event rate was 0% in the PCP group and 3.0% in the PVP group. Perventricular and percutaneous ultrasound-guided device closure of PmVSD are both effective and safe treatment options. The percutaneous approach offers less trauma and faster recovery and may be the preferred approach in selected patients.

Timing of SGLT2i initiation after acute myocardial infarction

BackgroundPharmacological post-MI treatment is routinely initiated at intensive/cardiac care units. However, solid evidence for an early start of these therapies is only available for dual platelet therapy and statins, whereas data on beta blockers and RAAS inhibitors are heterogenous and mainly limited to STEMI and heart failure patients. Recently, the EMMY trial provided the first evidence on the beneficial effects of SGLT2 inhibitors (SGLT2i) when initiated early after PCI. In patients with type 2 diabetes mellitus, SGLT2i are considered “sick days drugs” and it, therefore, remains unclear if very early SGLT2i initiation following MI is as safe and effective as delayed initiation.Methods and resultsThe EMMY trial evaluated the effect of empagliflozin on NT-proBNP and functional and structural measurements. Within the Empagliflozin group, 22 (9.5%) received early treatment (< 24 h after PCI), 98 (42.2%) within a 24 to < 48 h window (intermediate), and 111 (48.1%) between 48 and 72 h (late). NT-proBNP levels declined by 63.5% (95%CI: − 69.1; − 48.1) in the early group compared to 61.0% (− 76.0; − 41.4) in the intermediate and 61.9% (− 70.8; − 45.7) in the late group (n.s.) within the Empagliflozin group with no significant treatment groups—initiation time interaction (pint = 0.96). Secondary endpoints of left ventricular function (LV-EF, e/e`) as well as structure (LVESD and LVEDD) were also comparable between the groups. No significant difference in severe adverse event rate between the initiation time groups was detected.ConclusionVery early administration of SGLT2i after acute myocardial infarction does not show disadvantageous signals with respect to safety and appears to be as effective in reducing NT-proBNP as well as improving structural and functional LV markers as initiation after 2–3 days.

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

Association between misoprostol and non-steroidal anti-inflammatory drug-induced kidney injury: a systematic review and meta-analysis.

Misoprostol is a prostaglandin E1 analog that is used to prevent non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal disorders. The aim of this systematic review and meta-analysis was to evaluate whether use of misoprostol also decreases the risk of NSAID-induced kidney injury. Randomized controlled trials that compared misoprostol versus placebo in an adult patient population were selected. The primary outcome was kidney injury and the secondary outcome was severe adverse events. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Twelve studies were eligible for inclusion. Although the rates of kidney injury and severe adverse events did not differ significantly between misoprostol and placebo, a post-hoc sub-group analysis that excluded studies in which different NSAIDs were used in the misoprostol and placebo groups suggested that misoprostol may reduce the risk of NSAID-induced kidney injury (risk difference -0.09, 95% confidence interval -0.15 to -0.03, P<0.01, I2 = 87%; evidence of very low certainty). There is limited evidence that misoprostol reduces the risk of NSAID-induced kidney injury. Misoprostol possibly contributes to reducing the risk of kidney injury associated with chronic NSAID use. The findings of this meta-analysis suggest further high-quality clinical trials are warranted.

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. 4 Laryngoscope, 134:228-235, 2024.

Effectiveness and safety of novel motorized spiral enteroscopy: a systematic review and meta-analysis.

Motorized spiral enteroscopy (MSE) is a novel advance in small bowel examination that is characterized as fast with a deep insertion. The aim of this study was to elucidate the effectiveness and safety of MSE. Relevant articles that were published before November 1, 2022 were identified by searching PubMed, EMBASE, Cochrane, and the Web of Science. The technical success rate (TSR), total (pan)-enteroscopy rate (TER), depth of maximum insertion (DMI), diagnostic yield, and adverse events were extracted and analyzed. Forest plots were graphed based on random effects models. A total of 876 patients from 8 studies were eligible for analysis. The pooled results of the TSR were 95.0% [95% confidence interval (CI) 91.0-98.0%, I2 = 78%, p < 0.01] and the pooled outcome of the TER was 43.1% (95% CI 24.7-62.5%, I2 = 95%, p < 0.01). The pooled results of the diagnostic and therapeutic yields were 77.2% (95% CI 69.0-84.5%, I2 = 84%, p < 0.01) and 49.0% (95% CI 38.0-60.1%, I2 = 89%, p < 0.01), respectively. The pooled estimates of adverse and severe adverse events were 17.2% (95% CI 11.9-23.2%, I2 = 75%, p < 0.01) and 0.7% (95% CI 0.0-2.1%, I2 = 37%, p = 0.13), respectively. MSE is a novel alternative approach for small bowel examination that can achieve high TER and diagnostic and therapeutic yields, and relatively low rates of severe adverse events. Head-to-head studies comparing MSE and other device-assisted enteroscopies are warranted.

Interim results of a phase II trial of first line retifanlimab (R) plus gemcitabine and docetaxel (GD) in patients (pts) with advanced soft tissue sarcoma (STS).

11518 Background: GD is an alternative to doxorubicin in the front line setting in advanced STS. In the Phase I portion of this study, the PD-1 antibody R, plus GD, was generally well tolerated. We hypothesized that R+GD would be more effective than historical controls treated with GD alone. Methods: This is an ongoing open-label single-center study of R+GD in pts with treatment-naïve unresectable or metastatic high-grade STS. G (900 mg/m2) is administered on days 1 and 8 and D (75 mg/m2) on day 8, in 21-day cycles. R (375 mg flat dose) is administered on day 1 starting in cycle 2 and continued as monotherapy ‘maintenance’ after completion of 6 cycles of GD. Up to fifty pts can accrue into five histology-specific cohorts of 10 pts each. The primary endpoint is to estimate the progression-free survival (PFS) rate at 24 weeks. Secondary endpoints included safety, best overall response rate (RR) by RECIST 1.1, disease control rate (DCR), and duration of response (DOR). Subgroup analyses to evaluate all endpoints within each histology-specific cohort are preplanned. An early stopping rule for excessive toxicity will halt accrual if a prespecified severe adverse event rate is surpassed. Results: As of January 11, 2023, 43 pts were enrolled and treated with R+GD. The leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma (MFS), dedifferentiated liposarcoma (DDLPS), and other STS cohorts (n = 10 pts each) were fully accrued. Three of 10 angiosarcoma (AS) pts were enrolled. Median age was 59.5 (range 21 – 81) and 27 (63%) were male. Two DDLPS patients were not yet evaluable for response. Of 41 evaluable pts, the best overall RR was 22% (95% confidence interval [CI]) 11 – 38). Confirmed responses were seen in UPS/MFS (n = 4), LMS (2), AS (2), and follicular dendritic cell sarcoma (1). Three pts (LMS, ossifying fibromyxoid tumor, AS) had an unconfirmed PR, for a best RR of 29% (95% CI 16 – 46). Median PFS was 32.7 weeks (95% CI 26.4 – not estimable [NE]) and median DOR was 24 weeks (95% CI 15 – NE). Safety was evaluated in all 43 pts and the early stopping rule was not triggered. Eighteen (42%) pts had at least one Grade (Gr) 3 or 4 treatment-related adverse event (TRAE). The most common ( &gt; 5%) were anemia (16%), neutropenia (9%), febrile neutropenia (7%), lung infection (7%), and leukopenia (7%). Seven pts (16%) had pneumonitis: one Gr 1, four Gr 2, and two Gr 3. Six pts (14%) stopped treatment due to toxicity, including five with pneumonitis. Conclusions: The median PFS of R+GD appears promising compared to historical controls, although the primary endpoint analysis is pending completion of accrual. There was a higher incidence of pneumonitis with the combination compared to GD alone. Future studies of this combination will need to carefully consider the benefits and risks after the final efficacy and safety analyses are performed. Clinical trial information: NCT04577014 .