Almader‐Douglas, Diana

e18574 Background: ND has historically been recommended to reduce infectious complications in cancer patients (pts). While the adoption of ND has declined over the last decade, recent studies - particularly in pts undergoing hematopoietic stem cell transplantation (HSCT) - have raised uncertainty regarding the safety of LD. Herein, we performed a meta-analysis of studies directly comparing ND with LD in pts with cancer. Methods: We conducted a systematic search of MEDLINE, Embase, and Cochrane databases from inception through January 2026. Comparative retrospective and prospective studies were included if they were comparing ND with LD in adults or children with cancer. Primary outcomes were major infections and bacteremia/fungemia. Secondary outcomes were pneumonia, diarrhea, and all-cause mortality. Random-effects meta-analyses were performed to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). The review followed PRISMA 2020 guidelines. Results: Fifteen studies enrolling 4,320 patients were included in the primary analysis. Six studies enrolled only adult patients, three were restricted to pediatric populations, and six included mixed adult and pediatric cohorts. Across these studies, ND was not associated with a significant reduction in major infections (RR 1.02, 95% CI 0.88–1.18; p=0.795), bacteremia/fungemia (RR 0.97, 95% CI 0.78–1.22; p=0.805), pneumonia (RR 0.98, 95% CI 0.59–1.63; p=0.933), diarrhea (RR 1.12, 95% CI 0.96–1.31; p=0.159), or all-cause mortality (RR 0.94, 95% CI 0.77–1.15; p=0.632). Sensitivity analyses restricted to RCTs showed consistent results. Subgroup analysis of hematological/HSCT studies (9 studies; 1,769 pts) also showed no differences across outcome. Analysis restricted to RCTs in hematologic/HSCT pts (6 studies; 855 pts) showed no differences in major infections, pneumonia, diarrhea, or mortality; however, ND was associated with a lower risk of bacteremia/fungemia (RR 0.67, 95% CI 0.47–0.95; p=0.023). Heterogeneity across studies was low to moderate. Conclusions: ND was not associated with reductions in major infections, pneumonia, diarrhea, or mortality compared with LD. A reduction in bacteremia/fungemia was observed in RCTs of hematologic malignancy and HSCT pts. Overall, these findings suggest that routine ND implementation is unnecessary for most cancer pts, although cautious dietary practices may remain reasonable in selected high-risk hematologic malignancy/HSCT populations.

OBJECTIVE Patients with autosomal dominant polycystic kidney disease (ADPKD) have been identified to have a significantly increased risk of developing intracranial aneurysms (IAs). These patients are diagnosed at younger ages and are also at increased risk for IA rupture. The objective of this systematic review and meta-analysis was to identify risk factors associated with IA detection during screening of asymptomatic ADPKD patients. METHODS The authors searched for studies reporting the prevalence of IA among patients with ADPKD screened using MRA, CTA, or DSA on PubMed, Embase, Google Scholar, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov prior to August 2023 by using individualized standardized search strategies. Eligibility of all retrieved studies was assessed according to the PRISMA guidelines. Risk of bias of the included observational studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random-effects model. RESULTS Twenty-four observational studies involving 5907 patients with ADPKD were identified for quantitative analysis. The authors observed an overall prevalence of IA of 12.6%. They identified several risk factors for IA with statistically significantly increased odds for unruptured IA (UIA) detection, including female sex (18 studies, OR 1.63, 95% CI 1.37–1.94, I 2 = 0%), family history of either IA or subarachnoid hemorrhage (SAH) (12 studies, OR 2.17, 95% CI 1.68–2.81, I 2 = 0%), family history of SAH (3 studies, OR 2.67, 95% CI 1.25–5.71, I 2 = 66.0%), stage 3 or greater chronic kidney disease (CKD) (4 studies, OR 2.55, 95% CI 1.84–3.54, I 2 = 0%), and hypertension (13 studies, OR 1.41, 95% CI 1.04–1.91, I 2 = 34%). Age > 45 years, family history of ADPKD, smoking status, and presence of liver cysts did not reach statistical significance as risk factors during this meta-analysis. CONCLUSIONS The results of the authors’ meta-analysis suggest increased risk of UIA detection in screening of ADPKD patients who are female, have a family history of IA or SAH, have hypertension, or have moderate or more severe CKD. Given the increased prevalence of IA in ADPKD patients with these risk factors, these patients may stand to benefit from screening for IA early in treatment or at time of diagnosis, even if neurologically asymptomatic.

ImportanceMeasurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development.ObjectiveTo assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment.Data SourcesClinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023.Study SelectionProspective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded.Data Extraction and SynthesisStudy sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted.Main Outcomes and MeasuresAnalyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model.ResultsA total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40).Conclusions and RelevanceThe findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

e19008 Background: Bispecific antibodies (BsAb) have emerged as a new treatment modality for relapsed/refractory non-Hodgkin lymphomas (R/R NHL). They exert their effect by binding to CD3 on T-cells and CD19 or CD20 on lymphoma cells, activating the T-cell to exert cytotoxic effects against the tumor and normal B-cells. Treatment related adverse events (TRAE) include infections, cytokine release syndrome (CRS), neurotoxicity (ICANS). This meta-analysis was conducted to assess prevalence of TRAEs from prospective clinical trials that evaluated BsAb in R/R NHL. Methods: A systematic review was conducted through PubMed, Embase, Scopus, Web of Science, and Cochrane to identify BsAb clinical trials in NHL through October 2023. Eligible studies included phase I-III trials evaluating BsAb in any type of NHL, either as monotherapy or combination therapy irrespective of prior lines of treatment. Primary outcomes of interest include infection, neutropenia, CRS, and ICANS. All studies were weighted equally. Pooled prevalence estimates of TRAE were calculated using common and random effects models. Heterogeneity tests were performed using Cochran’s Q test. Subgroup analysis examined infection rates in monotherapy versus combination therapy cohorts. Results: After screening 1039 studies, 36 clinical trials with 2162 patients were included. The lymphoma subtypes were diffuse-large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. The BsAbs included mosunetuzumab (13 studies), epcoritamab (10 studies), blinatumomab (5 studies), glofitamab (5 studies), odronextamab (2 studies), and AFM11 (1 study). The median age of patients was 66 years, and patients had received a median of two prior lines of therapy. Median follow-up duration was 9.1 months. The prevalence of all-grade infections was 35% (95% CI: 0.33-0.38; I2 = 79%). For grade ≥3 infections, the prevalence was 16% (95% CI: 0.14-0.18, (I2 = 77%). There were higher rates of all-grade infections in the combination therapy cohort (41%, 95% CI: 0.36-0.47) compared with the monotherapy cohort (33%, 95% CI: 0.30-0.36). All-grade and grade ≥3 neutropenia occurred in 31% (95% CI: 0.29-0.34; I2 = 80%) and 22% (95% CI: 0.20-0.24, I2 = 61%) of patients. CRS was observed in 45% of patients (95% CI: 0.43-0.48, I2 = 85%). Grade ≥3 CRS occurred in only 2% of patients (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). ICANS occurred in 12% (95% CI: 0.10-0.14, I2 = 90%) while grade ≥3 ICANS was rare, at 3% (95% CI: 0.02-0.03, I2 = 0%, p = 0.99). Conclusions: BsAb is associated with nontrivial rates of infections and neutropenia. The rates of high grade CRS and ICANS are low. The heterogeneity of the findings could be attributed by an underreporting of TRAE and small sample sizes from various studies. These results highlight the need for vigilant practices to diagnose and treat infections early and consideration for antibacterial prophylaxis in this immunocompromised population.

Introduction: Achieving undetectable measurable residual disease (uMRD) following treatment has shown significant prognostic value in several hematological malignancies. In chronic lymphocytic leukemia (CLL), uMRD is associated with improved outcomes in the era of chemoimmunotherapy (CIT). However, the role of measurable residual disease (MRD) in the context of novel agents such as Bruton tyrosine kinase inhibitors (BTKi) and/or BCL2 inhibitors (e.g. venetoclax) is uncertain. To address this question, we conducted a systematic review of the literature and performed a comprehensive meta-analysis of trials that included novel agents to evaluate the association between MRD status after treatment and PFS in patients with CLL. Methods: We conducted a comprehensive search of PubMed, EMBASE, Scopus, and Web of Science focusing on CLL trials reporting MRD and its association with PFS. Results were independently screened by two reviewers. Inclusion criteria included prospective phase 3 trials involving a novel agent in one of the treatment arms, while studies with incomplete information on MRD status related to PFS, reviews, abstracts, and retrospective analyses were excluded. The initial search identified 185 studies in PubMed and 402 studies in EMBASE. After applying prespecified criteria, a total of 10 phase 3 trials were included in our analysis. We extracted sample size, patient age, follow-up time, time point and tissue of MRD assessment, MRD cut-off and rate, performance status and molecular status when available. We only considered treatment arms with complete MRD information. The comparison involved patients who achieved uMRD with those exhibiting detectable MRD. When available, hazard ratios (HR) and confidence intervals (CI) were used to evaluate the relationship between MRD status and PFS. If not, we used Kaplan-Meier (KM) curves from both uMRD and MRD subgroups and extracted the coordinates points of the curves using DigitizeIt software (version 2.5.10, I. Bormann) and using the number at risk provided we estimated the HRs and CIs. A meta-analysis was performed using a random effects model from the R package metafor (Viechtbauer, W. (2010). Conducting meta-analyses in R with the metafor package. Journal of Statistical Software, 36(3), 1-48). The pooled hazard ratio estimates, and the corresponding 95% CI and prediction intervals (PI) were reported. Funnel and Baujat plots were generated to assess study heterogeneity and bias. All analysis was performed using R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results: A total of 10 phase 3 trials, encompassing 14 treatment arms and involving 3152 patients, met the stringent inclusion criteria. All but one study used a uMRD cut-off of < 0.01%. Detailed information on the treatment arms and key trial characteristics is presented in Table 1. Notably, ten treatment arms were derived from first-line treatment trials, while the remaining arms pertained to the relapsed/refractory population. Only two trials (4 treatment arms) assessed MRD using next generation sequencing (NGS), while the rest used multicolor flow cytometry (MFC) (9 treatment arms) and allele-specific oligonucleotides polymerase chain reaction (ASO-PCR) (2 treatment arms). All but 3 trials assessed MRD in both bone marrow (BM) and peripheral blood (PB). One trial (2 treatment arms) was excluded from the met-analysis due to higher MRD cut-off. All studies included in the meta-analysis measured uMRD (<0.01) versus MRD. The PFS pooled HR estimate for achieving uMRD at 0.01 cut off from the meta-analysis was 0.32 (95% CI [0.22, 0.45]), with minimal bias observed on the Funnel Plot. Conclusions: In this comprehensive meta-analysis, comprising 9 phase 3 trials, achieving uMRD was strongly associated with PFS. These findings further establish the prognostic role of MRD in CLL management and its potential use as a surrogate marker in clinical trials. As the body of evidence on MRD in CLL continues to grow, it becomes imperative to standardize the optimal time point, methodology, and tissue for MRD assessment. Substantial heterogeneity in these aspects underscores the necessity for unified guidelines to ensure the accurate and consistent evaluation of MRD status in clinical practice.

Purpose: The purpose of this article was to appraise the various methods of reconstruction for meningomyelocele (MMC) defects. Methods: A systematic review of the literature was performed to evaluate all reconstructions for MMC. The method of reconstruction was categorized by: primary closure with and without fascial flaps, random pattern flaps, VY advancement flaps (VY), perforator flaps, and myocutaneous flaps. Perforator flaps were subsequently subcategorized based on the type of flap. Results: Upon systematic review, 567 articles were screened with 104 articles assessed for eligibility. Twenty-nine articles were further reviewed and included for qualitative synthesis. Two hundred seventy patients underwent MMC repair. The lowest rates of major wound complications (MWC) were associated with myocutaneous and random pattern flaps. A majority of MWC was in the lumbrosacral/sacral region (87.5% of MWC). In this region, random patterns and perforator flaps demonstrated the lowest rate of MWC (4.5, 8.1%). Conclusions: Plastic surgery consultation should be strongly considered for MMC with defects in the lumbosacral/sacral region. Perforator flaps are excellent options for the reconstruction of these defects.

PURPOSE We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)–based regimens. METHODS MEDLINE, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched for publications reporting the outcome of patients with early-stage dMMR CRC receiving NIT. The primary outcome measures were the complete response (CR) rate (clinical CR [cCR] or pathologic CR [pCR]) and the incidence of grade 3 or higher toxicities. RESULTS The search identified 37 publications that included 423 patients with colon (n = 326, 77%) and rectal (n = 97,23%) cancers aged 19-82 years; most patients had stage III CRC (88%). Approximately 67% of patients received monotherapy with anti–PD-1 agents; the rest received dual ICIs (ipilimumab plus nivolumab). The CR rate (pCR + cCR) in the overall population was 72% (305 of 423). The R0 resection and pCR rates were 99.3% and 70% among the patients undergoing surgery, respectively. Only four (0.9%) patients had primary resistance to NIT. After median follow-up periods ranging from 4 to 27 months, 3 (0.7%) patients progressed after an initial response. Grade 3 or higher toxicities were uncommon (6.3%), rarely delaying planned surgery. CONCLUSION NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile. The findings of the present systematic review support further investigation of NIT in patients with early-stage dMMR CRC, with a particular emphasis on the organ-preserving potential of this strategy.

Abstract Purpose This scoping review summarises five decades of research on gender bias in subjective performance evaluations of medical trainees. Method A medical librarian searched PubMed, Ovid Embase, Scopus, Web of Science and Cochrane DBSR in June 2020. Two researchers independently reviewed each abstract to determine if it met inclusion criteria (original research article investigating gender bias in subjective medical trainee evaluations by staff). References from selected articles were also reviewed for inclusion. Data were extracted from the articles, and summary statistics were performed. Results A total of 212 abstracts were reviewed, and 32 met criteria. Twenty (62.5%) evaluated residents, and 12 (37.5%) studied medical students. The majority of studies on residents were Internal Medicine ( n = 8, 40.0%) and Surgery ( n = 7, 35.0%). All studies were performed in North America and were either retrospective or observational. Nine (28.0%) were qualitative, and 24 (75.0%) were quantitative. The majority of studies were published in the last decade ( n = 21, 65.6%). Twenty (62.5%) studies documented gender bias, of which 11 (55%) found that males received higher quantitative performance evaluations and 5 (25%) found that females received higher evaluation scores. The remaining 4 (20%) reported gender differences in qualitative evaluations. Conclusions Most studies detected gender bias in subjective performance evaluations of medical trainees, with a majority favouring males. There is a paucity of studies on bias in medical education with a lack of standardised approach to investigating bias.