Event Rates Research Articles

ENDOSCOPIC ULTRASOUND-GUIDED HEPATICOJEJUNOSTOMY IN PATIENTS WITH HISTORY OF TOTAL GASTRECTOMY: A MULTICENTER RETROSPECTIVE FEASIBILITY STUDY

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an effective biliary drainage technique for patients with altered anatomy or duodenal strictures. Endoscopic ultrasound-guided hepaticojejunostomy (EUS-HJS) can be used to create a fistula between the left hepatic duct and the jejunum in patients with a history of total gastrectomy. No specific data on this technique have been published. The aim of this study was to assess the feasibility and safety of EUS-HJS in patients with a history of total gastrectomy. This retrospective multicenter study included all adult patients who underwent EUS-HJS at three tertiary French centers and one tertiary Swiss center between May 2011 and February 2023. The primary outcome was clinical success, which was defined as the disappearance of pruritus, jaundice and/or cholangitis. An improvement in bilirubin greater than 30% within the first week and/or bilirubin normalization within 1 month after the procedure were also considered indicators of clinical success. Secondary outcomes included technical success, the rate of adverse events, the need for endoscopic revision, the possibility of resuming anticancer treatment, median survival, and technical differences compared to EUS-HGS. A total of 21 patients who underwent complete gastrectomy via EUS-HJS were included. Technical success was achieved in 100% of patients (95% CI 85%-100%). Clinical success was achieved in 80% of patients (95% CI 58%-92%). The incidence of recorded adverse events was 33% (95% CI 17%-55%), with cholangitis being the most frequent complication. Seven patients (39%) were able to benefit from anticancer treatment after the procedure. The median survival was 6 months (IQR 1.5-12). EUS-HJS is an effective and feasible procedure for patients whose anatomy has been altered by total gastrectomy.

Early salvage therapy with anti-PD-1 antibody Camrelizumab in patients with advanced cervical cancer: a retrospective study.

To observe the clinical efficacy of Camrelizumab in patients with advanced cervical cancer who presented with resistance to initial therapy. We retrieved data from 25 patients with advanced (stage IIA2-IV) cervical cancer who were administered a combination salvage therapy with Camrelizumab due to the poor response to initial chemotherapy. The primary outcome was objective response rate (ORR) and disease control rate (DCR), the secondary endpoints included progression-free survival (PFS) and the occurrence of adverse events. To evaluate its long-term effect on PFS, we included 64 patients diagnosedwith stage IIA2-IV during the study period, who were responsive to initial radiotherapy or chemotherapy and received conventional therapy as control. Camrelizumab exhibits a high salvage treatment efficacy, with ORR of 80.0% (20/25) and DCR of 88.0% (22/25)in Camrelizumab salvage group (CS group). The PFS in CS group was significantly longer than thatin controlgroup. The median follow-up time were 18.1 and 18.3months in the CS group and the control group, respectively, and neither achieved median PFS. The adverse event (AEs) rates in the CS and control groups were 52.0% (13/25) and 51.6% (33/64), in which the most common adverse events were myelosuppression, cutaneous capillary endothelial proliferation (CCEP), and elevated liver enzymes, and the grade of AEs was less than grade 3 in all patients. Camrelizumab demonstrated promising efficacy and safety as the early salvage treatment for patients with advanced cervical cancer.

Prophylactic pancreatic duct stenting to reduce the risk of post-ampullectomy pancreatitis: a comprehensive review and meta-analysis of 1858 patients.

The effectiveness of prophylactic pancreatic duct stenting (PPDS) in preventing post-ampullectomy pancreatitis (PAP) at the time of endoscopic ampullectomy (EA) has been reported, however, results are conflicting. We conducted a systematic review and meta-analysis looking at the use of PPDS in reducing PAP as well as overall post-ampullectomy complications. Multiple databases were searched through May 2023 for studies reporting on EA. Meta-analysis was performed to determine pooled proportions and relative risk (RR) with 95% confidence intervals (CI) of PAP, with and without PPDS. Pooled rates of adverse events including perforation, delayed bleeding, cholangitis, and procedure related mortality were assessed. Random effects model was used for our meta-analysis and heterogeneity was assessed using the I2 statistics. Thirty-four studies (14 case series, 18 cohort studies and 2 randomized controlled trials) with 1868 patients were included. The overall pooled rate of PAP was 12.3% (CI 10.3-14.5). We found no statistically significant difference in rates of PAP among patients with PPDS, 11.9% (CI 8.9-15.7) and without PPDS, 16.6% (CI 13.4-20.4), RR 0.8 (CI 0.51-1.28), p = 0.4. In terms of severe PAP, we found no difference between the two groups. The overall pooled rates of successful en-bloc and piecemeal resection were 74.8% (CI 67.3-81.1) and 25.1% (CI 19-32.4). Additionally, pooled rates of ampullary stenosis, post procedural bleeding, perforation, cholangitis, and procedure related mortality were 3.6%, 11.1%, 4.2%, 3.5%, and 1.3%, respectively. Our analysis shows that PPDS at the time of EA does not offer a significant protective effect against PAP. While the incidence of PAP was higher among the no PPDS group, it is plausible that this is more likely due to variation among studies in terms of lesion size, length/size of pancreatic stent used and etiology of ampullary lesions. Future well-designed randomized controlled trials are needed to validate our findings.

Changes in the treatment landscape of metastatic hormone-sensitive prostate cancer following approval of upfront androgen receptor signaling inhibitors: A multicenter study.

A multicenter database was utilized to examine the current treatment landscape and clinical outcomes among patients with metastatic hormone-sensitive prostate cancer (mHSPC) following approval of upfront androgen receptor signaling inhibitors (ARSIs). We retrospectively analyzed patients with mHSPC who commenced treatment between February 2018 and June 2023. The Kaplan-Meier method was used to assess oncological outcomes, including time to castration-resistant prostate cancer (CRPC), progression-free survival 2 (PFS2, duration from initial treatment to tumor progression during second-line treatment), cancer-specific survival (CSS), and overall survival (OS). Cox regression analyses were performed to determine the impact of treatment choices on oncological outcomes. In addition, the incidence rate of adverse events was assessed. In total, 829 patients were analyzed; 42.5% received ARSIs with androgen deprivation therapy (ADT), 44.0% received combined androgen blockade (CAB), and 13.5% received ADT alone. Kaplan-Meier curves and multivariate Cox regression analyses indicated higher rates of CRPC and shorter PFS2 in patients treated with CAB versus ARSIs with ADT. By contrast, CSS and OS were not significantly different between the ARSI with ADT group and the CAB group. Grades 3-4 adverse events occurred in 1.9% of patients receiving CAB and 6.0% of those receiving ARSIs with ADT. Initial treatment with ARSIs in combination with ADT resulted in a longer time to CRPC and longer PFS2 compared to CAB. Although CAB and ADT alone were associated with fewer adverse events, ARSIs with ADT should be considered a first-line treatment option given its superior oncological outcomes.

Improving Mechanical Circulatory Support Outcomes in Failing Bidirectional Glenn Physiology.

There remains high morbidity and mortality with mechanical circulatory support (MCS) in failing bidirectional Glenn (BDG) physiology. We performed a retrospective analysis of children with BDG physiology supported with MCS before and after 2018. Fourteen patients met inclusion criteria (median age 1.5years, weight 9kg). Prior to 2018 (n = 7), with variable anticoagulation and strategies including pulsatile VAD, continuous flow VAD, and extracorporeal membrane oxygenation (ECMO), 3 (43%) of patients were transplanted with a total of 536 patient-days of support (median 59days). Major hemocompatability-related adverse event (MHRAE) rate was 63 per 100 patient-months. After 2018 (n = 7), using a staged support strategy (ECMO to pulsatile VAD) and bivalirudin anticoagulation, 5 (71%) patients were transplanted with a total of 1260 patient-days of support (median 188days) and MHRAE rate of 24 per 100 patient-months. Despite challenging physiology, we have observed improved survival and reduced MHRAE despite longer support duration.

Heart Failure Events After Long-term Continuous Screening for Atrial Fibrillation: Results From the Randomized LOOP Study.

Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in elderly individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). In an elderly population with stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Effects of emergent carotid stenting performed before or after mechanical thrombectomy in the endovascular management of patients with tandem lesion: a multicenter retrospective matched analysis.

Mechanical thrombectomy (MT) along with emergent carotid stenting (eCAS) have been suggested to have a greater benefit in patients with tandem lesion (TL), compared to other strategies of treatment. Nonetheless, there is no agreement on whether the intracranial occlusion should be treated before the cervical ICA lesion, or vice versa. In this retrospective multicenter study, we sought to compare clinical and procedural outcomes of the two different treatment approaches in patients with TL. The prospective databases of 17 comprehensive stroke centers were screened for consecutive patients with TL who received MT and eCAS. Patients were divided in two groups based on whether they received MT before eCAS (MT-first approach) or eCAS before MT (eCAS-first approach). Propensity score matching (PSM) was used to estimate the effect of the retrograde versus the anterograde approach on procedure-related and clinical outcome measures. These included the mTICI score 2b-3, other procedure-related parameters and adverse events after the endovascular procedure, and the ordinal distribution of the 90-day mRS scores. A total of 295 consecutive patients were initially enrolled. Among these, 208 (70%) received MT before eCAS. After PSM, 56 pairs of patients were available for analysis. In the matched population, the MT-first approach resulted in a higher rate of successful intracranial recanalization (91% versus 73% in the eCAS-first approach, p=0.025) and shorter groin-to-reperfusion time (72 ± 38 minutes versus 93 ± 50 minutes in the anterograde approach, p=0.017). Despite a higher rate of efficient recanalization in the MT-first group, we did not observe a significant difference concerning the ordinal distribution of the 90-day mRS scores. Rates of procedure-related adverse events and occurrence of both parenchymal hemorrhage type 1 and type 2 were comparable. Our study demonstrates that in patients with TL undergoing endovascular treatment, prioritizing the intracranial occlusion is associated with an increased rate of efficient MT and faster recanalization time. However, this strategy does not bring an advantage in long-term clinical outcome. Future controlled studies are needed to determine the optimal treatment technique. AIS = acute ischemic stroke; eCAS = emergent carotid stenting; ICA = internal carotid artery; GTR = groin-torecanalization; IVT = intravenous thrombolysis; LVO = large vessel occlusion; MCA, middle cerebral artery; MT = mechanical thrombectomy; PSM = propensity score matching; SMD = standardized mean difference; STROBE = STrengthening the Reporting of OBservational studies in Epidemiology; TL = tandem lesion.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry

BackgroundDiabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood.ObjectiveTo investigate the relationship between elevated Lp(a) and DM with CAD outcomes.MethodsRetrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L).ResultsAmong 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% − 0.6%; No-DM and Lp(a) > 90th% − 1.3%; DM and Lp(a) < 90th% − 1.9%; DM and Lp(a) > 90th% − 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55–4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48–2.74], p < 0.001).ConclusionsElevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Multicenter study comparing EUS-guided hepaticogastrostomy and ERCP for malignant biliary obstruction in patients with accessible papillae.

One advantage of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is that it is difficult for reflux cholangitis, caused by duodenal pressure increasing due to duodenal obstruction, to occur. In addition, since stent deployment is performed away from the malignant stricture site, longer stent patency than with endoscopic retrograde cholangiopancreatography (ERCP) may be obtained. However, no study has previously compared EUS-HGS and ERCP for patients without duodenal obstruction or surgically altered anatomy. The aim of the present study was to compare clinical outcomes between EUS-HGS and ERCP in normal anatomy patients without duodenal obstruction. In the ERCP group, patients who initially underwent biliary drainage were included. In the EUS-HGS group, patients who underwent EUS-HGS due to failed biliary cannulation were included. Patients with an inaccessible papilla, such as with surgically altered anatomy or duodenal obstruction, were excluded. A total of 314 patients who underwent ERCP and EUS-HGS were enrolled in this study. Of the 314 patients, 289 underwent biliary stenting under ERCP guidance, and 25 patients underwent biliary stenting under EUS-HGS. After propensity score-matching analysis, the adverse event rate tended to be lower in the EUS-HGS group than in the ERCP group. Although overall survival was not significantly different between the EUS-HGS and ERCP groups (p = .228), stent patency was significantly longer in the EUS-HGS group (median 366.0 days) than in the ERCP group (median 76.5 days). EUS-HGS had a lower adverse event rate, shorter procedure time, and longer stent patency than ERCP in cases of normal anatomy without duodenal obstruction.

Effects of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction: An analysis of DAPA-HF and DELIVER.

The primary aim was to evaluate the effect of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction (LVEF), given that prolongation of QRS duration is associated with less favourable ventricular remodelling with pharmacological therapy and worse outcomes. A pooled analysis of the DAPA-HF and DELIVER trials, excluding patients with a paced rhythm and cardiac resynchronization therapy. Overall, 4008 patients had heart failure (HF) with reduced ejection fraction (HFrEF), and 5816 had HF with mildly reduced/preserved ejection fraction (HFmrEF/HFpEF). QRS duration was <120 ms in 7039 patients (71.7%), 120-149 ms in 1725 (17.6%), and ≥150 ms in 1060 patients (10.8%). The median follow-up time was 23 months. The rate of the primary composite outcome of cardiovascular death or worsening HF was 9.2 (95% confidence interval [CI] 8.7-9.7), 14.3 (13.0-15.7), and 15.9 (14.1-17.9) per 100 patient-years in the <120, 120-149, and ≥150 ms groups, respectively. This gradient in event rates was observed both in HFrEF and HFmrEF/HFpEF. Dapagliflozin, compared with placebo, reduced the risk of the primary outcome consistently across the QRS duration subgroups (hazard ratio [95% CI] 0.75 [0.67-0.85], 0.79 [0.65-0.96], and 0.89 [0.70-1.13] in the <120, 120-149, and ≥150 ms groups, respectively; p for interaction = 0.28). The effect of dapagliflozin on the primary outcome was consistent across the QRS duration regardless of HF phenotype that is, HFrEF or HFmrEF/HFpEF. Prolongation of QRS duration is associated with worse outcomes irrespective of HF phenotype. Dapagliflozin reduced the risk of the primary outcome, regardless of QRS duration, in DAPA-HF and DELIVER.

The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. The LCN consists of a Scientific Data Coordinating Center (SDCC) and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding due to portal gastropathy, and hepatocellular carcinoma were also codified. The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multi-center cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion.

Training and quality indicators in interventional endoscopic ultrasound.

Endoscopic ultrasound (EUS) has transformed the landscape of minimally invasive gastrointestinal procedures, necessitating specialized training for proficiency in interventional EUS (iEUS). This study evaluates the effectiveness of iEUS training, focusing on learning curves, success rates, and the associated risks in various procedures, aiming to recommend practices for standardizing training and ensuring competency. Key metrics such as procedure type, learning curve for proficiency, success rates, and risk of adverse events were analyzed to establish benchmarks for training programs. Proficiency in pancreatic fluid collection drainage was achieved after 20-30 procedures, with a 100% success rate and a complication rate ranging from 1.5 to 80%. Gallbladder drainage required 19 cases to reach an 86% success rate, with adverse events reported in 19% of cases. Choledocoduodenostomy mastery was observed after approximately 100 cases, with postintervention pancreatitis affecting 5.3-6.6% of all cases. Hepaticogastrostomy showed a 93% success rate after 33 cases, with a 24.8% adverse event rate. Hepaticoenterostomy reached 100% success beyond the 40th patient, with a 20% rate of postsurgical strictures. Pancreatic duct drainage achieved 89% technical and 87% clinical success after 27 cases, with 12-15% adverse events. Gastro-enteric anastomosis required 25 cases for proficiency and approximately 40 cases for mastery, with 5.5% immediate and 1% late adverse events. iEUS training outcomes vary significantly across different procedures, highlighting the importance of structured, procedure-specific training programs to achieve proficiency. These findings provide a foundation for developing universal competency benchmarks in iEUS, facilitating consistent and effective training worldwide.

21-Gene Recurrence Score and Survival Outcomes in the Phase III Multicenter TAILORx Clinical Trial.

Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population. We evaluated the association of RS with BCSS and OS plus recurrence-free interval (RFI) and invasive disease-free survival (DFS) using multivariable Cox proportional hazards regression analysis, adjusting for clinicopathologic measures, in 8,916 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer. Likelihood ratio (LR) test was used to assess the relative amount of prognostic information provided by RS to BCSS, OS, RFI, and DFS, comparatively. Event rates for BCSS, OS, RFI, and DFS were 1.7%, 5.2%, 5.6%, and 12.6%, respectively, by up to 11.6 years of follow-up. Compared with low-range RS (0-10), patients with midrange (11-25) and high-range (26-100) RS had inferior BCSS (adjusted hazard ratio [aHR], 5.12 [95% CI, 2.09-16.92] and 8.03 [95% CI, 2.91-28.47], respectively) and RFI (aHR, 1.68 [95% CI, 1.23-2.36] and 3.05 [95% CI, 2.02-4.67], respectively), independent of clinicopathologic factors. High-range score was associated with an increased risk of DFS (aHR, 1.56 [95% CI, 1.20-2.04]) but not significantly associated with OS (aHR, 1.44 [95% CI, 0.95-2.18]). Midrange score was associated with neither DFS (aHR, 1.15 [95% CI, 0.96-1.38]) nor OS (HR 1.14 [95% CI, 0.87-1.52]). LR-χ2 values were 83.0 and 65.1 for RFI and BCSS, respectively, and 17.5 and 33.6 for OS and DFS, respectively (P<.0001). RS is an independent measure for BCSS and recurrence prognoses relative to OS in early-stage breast cancer. It carries more prognostic information for breast cancer-specific outcomes.

Probing Inelastic Signatures of Dark Matter Detection via Polarized Nucleus

Abstract We investigate the inelastic signatures of dark matter-nucleus interactions, explicitly focusing on the ramifications of polarization, dark matter splitting, and the Migdal effect. Direct detection experiments, crucial for testing the existence of dark matter, encounter formidable obstacles such as indomitable neutrino backgrounds and the elusive determination of dark matter spin. To overcome these challenges, we explore the potential of polarized-target dark matter scattering, examining the impact of nonvanishing mass splitting and the role of the Migdal effect in detecting dark matter. &amp;#xD;Our analysis demonstrates the valuable utility of the polarized triple-differential event rate as an effective tool for studying inelastic dark matter. It enables us to investigate both angular and energy dependencies, providing valuable insights into the scattering process.Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. Article funded by SCOAP3 and published under licence by Chinese Physical Society and the Institute of High Energy Physics of the Chinese Academy of Science and the Institute of Modern Physics of the Chinese Academy of Sciences and IOP Publishing Ltd.

Systemic Immunomodulatory Treatments for Atopic Dermatitis

There are multiple approved systemic treatments for atopic dermatitis. Lebrikizumab is a newly licensed biologic medication that has been compared to placebo in clinical trials but not to other systemic treatments. To compare reported measures of efficacy and safety of lebrikizumab to other systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis. The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Latin American and Caribbean Health Science Information database, the Global Resource of Eczema Trials database, and trial registries were searched from inception through November 3, 2023. Randomized clinical trials evaluating 8 or more weeks of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis. Titles, abstracts, and full texts were screened in duplicate. Data were abstracted in duplicate and random-effects bayesian network meta-analyses were performed. Minimal important differences were used to define important differences between medications. Certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). The updated analysis was completed from December 13, 2023, to February 20, 2024. Efficacy outcomes were the Eczema Area and Severity Index (EASI), the Patient Oriented Eczema Measure (POEM) Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS) and were compared using mean difference (MD) with 95% credible intervals (CrI). Safety outcomes were serious adverse events and withdrawal due to adverse events. Other outcomes included the proportion of participants with 50%, 75%, and 90% improvement in EASI (EASI-50, -75, -90) and the proportion with success on the Investigator Global Assessment compared using odds ratios with 95% CrI. The study sample included 98 eligible trials, with a total of 24 707 patients. Lebrikizumab was associated with no important difference in change in EASI (MD, -2.0; 95% CrI, -4.5 to 0.3; moderate certainty), POEM (MD, -1.1; 95% CrI -2.5 to 0.2; moderate certainty), DLQI (MD, -0.2; 95% CrI -2.1 to 1.6; moderate certainty), or PP-NRS (MD, 0.1; 95% CrI -0.4, 0.6; high certainty) compared to dupilumab among adults with atopic dermatitis who were treated for up to 16 weeks. Dupilumab was associated with higher odds of efficacy in binary outcomes compared with lebrikizumab. The relative efficacy of other approved systemic medications was similar to that found by previous updates of this living study, with high-dose upadacitinib and abrocitinib demonstrating numerically highest relative efficacy. For safety outcomes, low event rates limited useful comparisons. In this living systematic review and network meta-analysis, lebrikizumab was similarly effective to dupilumab for the short-term treatment of atopic dermatitis in adults. Clinicians and patients can use these comparative data to inform treatment decisions.

Thoracolumbar fracture and spinal cord injury in blunt trauma: a systematic review, meta-analysis, and meta-regression.

To determine the pooled rate of thoracolumbar fractures and SCI in blunt trauma patients. A systematic review and meta-analysis of observational studies were performed. The search was conducted in the PubMed, Scopus, Web of Science, and Embase databases. The authors screened and selected studies based on predefined inclusion and exclusion criteria. Studies were then evaluated for risk of bias using the JBI checklist. The pooled event rate and 95% confidence intervals (CI) were calculated using random effects models. Subgroup and meta-regression analyses were performed to explore sources of heterogeneity. Twenty-one studies fulfilled the selection criteria. The pooled rate of TL fractures was 8.08% (CI = 6.18-10.50%), with high heterogeneity (I2 = 99.98%, P < 0.001). Thoracic and lumbar fractures accounted for 45.23% and 59.01% of the TL fractures, respectively. Meta-regression revealed that the midpoint of the study period was a significant moderator. The pooled event rate of SCI among TL fracture patients was 15.81% (CI = 11.11 to 22.01%) with high heterogeneity (I2 = 98.31%, P < 0.001). The country of study was identified as a source of heterogeneity through subgroup analysis, and studies from the United States reported higher rates of SCI. Meta-regression revealed that the critical appraisal score was negatively associated with event rate. Our study evaluated the rate of TL fractures in multiple countries at different time points. We observed an increase in the rate of TL fractures over time. SCI results also seemed to vary based on the country of the original study.

Unsedated colonoscopy utilizing virtual reality distraction: a pilot-controlled study.

Sedation increases colonoscopy risks and prolongs recovery time. We examined whether virtual reality (VR) can substitute for sedation. The primary outcome was the overall satisfaction of patients who underwent colonoscopy with VR headset compared with patients who underwent standard sedation. Pain during the procedure, polyp detection rate (PDR), colonoscopy duration, post-colonoscopy adverse events, post-colonoscopy recovery, time-to-return to daily functions, and turnaround time at the endoscopy unit were secondary outcomes. The study was approved by Sheba Medical Center's ethics committee IRB number 21-8177-SMC. Sixty patients were sequentially enrolled in a 1:1 ratio to either standard sedated colonoscopy or VR-unsedated procedure, and all patients signed a written informed consent. 28/30 patients successfully completed the colonoscopy using VR headset. Overall satisfaction score was comparable between the groups. There was no difference between VR and controls in colonoscopy duration, or PDR. VR patients had numerically lower rate of post-colonoscopy adverse events than controls. The proportion of VR patients who reported resuming daily activities on the day of the procedure was significantly higher than in the control group. The VR group patients spent significantly less time in the hospital compared to the control group. VR technology can provide adequate substitution for sedation for most patients undergoing colonoscopy and offers comparable patient satisfaction and faster return to daily activities.

Endoscopic Balloon Dilatation of Ileal Pouch-Anal Anastomosis Strictures in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for medically refractory inflammatory bowel disease (IBD). In this systematic review and meta-analysis, we assess outcomes and safety of endoscopic balloon dilatation (EBD) for IPAA strictures. A systematic search of numerous databases was performed through June 2023 to identify studies reporting on the outcomes of EBD in pouch-related strictures. Outcomes included technical success, clinical success at index dilation and in pouch retention, recurrence of symptoms post-EBD, and adverse events of EBD. Meta-analysis was performed using a random-effects model, and results were expressed in terms of pooled rates along with relevant 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran Q statistical test with I2 statistics. Seven studies with 504 patients were included. The pooled rate of technical success and clinical success of index dilatation was 98.9% (95% CI, 94.8-99.8%; I20%) and 30.2% (95% CI, 7.1-71%; I20%), respectively. The pooled rate of clinical success in pouch retention without the need for additional surgery was 81.4% (95% CI, 69.6-89.3%; I272%). The pooled failure rate of EBD was 18.6% (95% CI, 10.7-30.4%, I272%). The pooled rate of recurrence of symptoms after index dilatation was 58.9% (95% CI, 33.3-80.5%; I213%). The pooled rate of serious adverse events was 1.8% (95% CI, 1-3.5%, I20%). No deaths related to EBD were reported. Endoscopic balloon dilatation is safe and highly effective for management of IPAA strictures. Additional studies are needed to compare its efficacy with surgical interventions.

Preoperative chemotherapy response and survival in patients with colorectal cancer peritoneal metastases.

Treatment guidelines provided by PRODIGE-7 recommend perioperative systemic chemotherapy before cytoreductive surgery (CRS) for colorectal cancer peritoneal metastases (CRPM). Toxicity with multimodal treatment needs to be better defined. Chemotherapy response and impact on survival have not been reported. We assessed CRPM patients who received systemic oxaliplatin/irinotecan before CRS (preoperative) with Mitomycin C (35 mg/m2, 90 min) or Oxaliplatin (368 mg/m2, 30 min) heated intraperitoneal chemotherapy(HIPEC). Secondary analysis was performed from a prospective database. Overall survival (OS) in chemotherapy responders (R) and nonresponders (NR) was compared. Toxicity was assessed by rate of adverse events (AEs). From April 2005 to April 2021, 436 patients underwent CRS + HIPEC; 125 (29%) received preoperative chemotherapy. The 112 (90%) received oxaliplatin (64, 57%) or irinotecan (48, 43%). R, defined as complete (CR) or partial responseon preoperative imaging and/or postoperative histology, was seen in 71, 63% (53.8-72.3); 16, 14% (8.4-22.2) had CR. Median OS in R versusNR was 43.7 months (37.9-49.4) versus 23.9 (16.3-31.4) p = 0.007, HR 0.51 (0.31-0.84). OS multivariable analysis showed HR 0.48 (0.25-0.95), p = 0.03 for chemotherapy response corrected byperitoneal cancer index, completeness of cytoreduction score. CRS led to 21% grade 3-4 AEs versus 4% for preoperative chemotherapy. HIPEC grade 3-4 AEs were 0.5%. Preoperative chemotherapy response is an independent predictor for OS in CRPM.

Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes : A Target Trial Emulation Study.

A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes. To investigate the association between GLP-1 RAs, compared with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D). Two target trial emulation studies comparing propensity score (PS)-matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is. U.S. national Medicare administrative data from January 2017 to December 2020. Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i. The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups. This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, -0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, -0.18 [CI, -0.92 to 0.57] per 1000 person-years). Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes. Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out. American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.