Citations

Background: The impact of multiple substance use on the risk of pancreatitis remains underexplored. Objective: To systematically review peer-reviewed observational studies assessing the association of multiple substance use with the risk of acute pancreatitis (AP) or chronic pancreatitis (CP) in adults. Design: We conducted a systematic review informed by the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Data sources and methods: EMBASE, MEDLINE, and PsycINFO were searched up to March 2024. Reference lists of included studies were reviewed. From 5205 records identified, 181 relevant records were evaluated in full text. Studies evaluating the association of ⩾2 substances, including tobacco, alcohol, cannabis, and illicit substances, with AP or CP were included. Data were extracted by one reviewer, with quality control by a second reviewer. Quality assessments were independently conducted by two reviewers, with differences resolved by a third. Results: Of 11 included studies, 6 investigated AP as the outcome and 5 examined CP. Among AP studies, 5 comparing smoking and alcohol to alcohol-only use showed high heterogeneity ( I 2 = 90.9%), with relative risks (RRs) from 1.40 to 11.40. One study examining cannabis and alcohol versus alcohol found a lower risk of AP in cannabis users. Among CP studies, four comparing smoking and alcohol to alcohol-only use were heterogeneous ( I 2 = 81%) with odds ratios 1.21–31.50. Where examined, smoking increases the risk of AP and CP in a dose-dependent fashion. Heavy alcohol users demonstrated a significant increase in CP risk across all smoking categories in one study. Conclusion: Combined alcohol and tobacco use increases pancreatitis risk compared to single substance use, despite heterogeneity in RRs and exposure definitions. Evidence suggests a dose-dependent impact of smoking on pancreatitis risk when added to alcohol. Studies on the impact of a combination of other substance use on pancreatitis risk are needed. Trial registration (PROSPERO): CRD42024503677.

ABSTRACT Background ASP‐1929 photoimmunotherapy—cetuximab conjugated to IRDye 700DX and red light (690 nm) for localized drug activation—results in rapid, selective cell killing. Methods This phase Ib/II open‐label study evaluated ASP‐1929 photoimmunotherapy plus pembrolizumab in patients with recurrent/metastatic HNSCC (≥ 1 accessible lesion, PD‐L1 combined positive score ≥ 1, ineligible for standard locoregional therapy). Primary objectives were safety/tolerability and objective response rate (ORR). Secondary objectives included overall survival (OS) and progression‐free survival (PFS). Results Eighteen patients (median age 63 years, 74% male) comprised the photoimmunotherapy‐evaluable population. The confirmed ORR was 27.8% (95% CI 9.7–53.5); four of five responders had complete responses (95% CI, 6.4–47.6). Median OS was 25.6 months (95% CI, 14.6–not evaluable); median PFS was 2.9 months (95% CI, 1.4–14.6). The most common serious adverse reactions were dysphagia and tongue edema (each n = 2; 10.5%). Conclusions ASP‐1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC.

Abstract Oral commensals such as Parvimonas micra are increasingly implicated in sporadic colorectal cancer (CRC). Several findings support an emerging notion that alterations in host DNA methylation constitute a mechanism by which P. micra adapts to the host microenvironment and contributes to pathogenic processes. However, multiple limitations hinder definitive conclusions, including the correlative nature of the human studies and the absence of human microbiota in mouse models. Here, we investigated how a complex human microbiome influences the adaptation and oncogenic potential of P. micra in a spontaneous mouse model of polyposis. Adult mice, following antibiotic conditioning, received fecal microbiota transplants (FMT) from a healthy human donor, with or without supplementation of P. micra. P. micra caused significant reshaping of the gut microbial community and altered co-occurrence network structures, which however largely recovered within 21 days post FMT. Despite the transient nature of these changes, P. micra caused a marked increase in both the number and invasive potential of intestinal polyps. Epigenomic profiling of polyp crypts revealed global DNA hypomethylation alongside gene-specific hypermethylation, accompanied by transcriptional changes in key oncogenic pathways. Affected pathways included Wnt signaling, epithelial-to-mesenchymal transition, circadian rhythm regulation, and host–microbe interactions. These findings demonstrate that P. micra exerts a profound influence on microbial ecology, host epigenetic programming, and tumorigenesis in a genetically predisposed host, highlighting its role as a microbial driver of intestinal carcinogenesis.

ABSTRACTIntroductionUpper and lower gastrointestinal (GI) dysfunctions frequently coexist, potentially mediated by gastrocolonic or cologastric neural reflexes. This study aims to assess the prevalence of impaired gastric accommodation (GA) and delayed gastric emptying (GE) among patients with slow colonic transit (CT), dyssynergic defecation (DD), and to evaluate relationships between CT or DD with impaired GA and delayed GE.MethodsWe reviewed records of 178 adult patients at Mayo Clinic (2005–2025) with documented slow CT or DD (respectively based on scintigraphy and high‐resolution anorectal manometry [ARM] and balloon expulsion [BE]) who underwent 99mTc‐SPECT measurement of GA and scintigraphic GE of 320‐kcal, 30% fat egg meal. Slow CT was defined by geometric center (GC) at 48 h < 2.1 for males and < 1.9 for females. Abnormal GA ratio was assessed as reduced < 2.62 or increased > 3.85, and delayed GE % < 75% at 4 h. Correlations were assessed using Spearman rank test.ResultsReduced GA was found in 23.7% with DD and 26.7% with slow CT, while increased GA was observed in 30.1% and 24.4%, respectively. Delayed GE was present in 20.5% DD patients and 35.6% slow CT patients. GC 48 h and 24 h were positively correlated with GE% 4 h (Rs = 0.279, and Rs = 0.294 respectively, both p < 0.001) suggesting slow CT retards GE. GC 48 h was moderately correlated with resting anal pressure (Rs = 0.259, p < 0.001) and negatively with the rectoanal pressure gradient (Rs = −0.166, p = 0.027). No significant correlations were observed between CT and GA.ConclusionSlow CT is associated with slower GE, suggesting cologastric reflex inhibition, but not with GA. There is a high prevalence of impaired GA and delayed GE in slow CT and DD.

Abstract Background Multiple guideline-based surgical treatment options for Peyronie’s disease (PD) exist, including penile plication and plaque incision or excision and grafting. Surgical incision type may differ depending upon location and severity of curve, planned concomitant procedures, and surgeon preference. Aim To evaluate postoperative wound complications comparing outcomes between ventral and subcoronal incisions in patients undergoing tunica albuginea plication (TAP) and plaque incision or partial excision and grafting (PG) for PD. Methods A single-surgeon, single-center retrospective chart review was conducted on all patients undergoing TAP or PG from 2019 to 2023. Patient demographics, including previous PD treatments, were recorded. A Mann–Whitney U test was utilized to determine differences in wound complication rate, median curvature improvement, and remaining postoperative curvature between ventral and subcoronal approaches. Outcomes Wound complication was classified as any dehiscence and/or wound exudate suspicious for infection within the first 3 months postoperatively. A secondary analysis was performed comparing these outcomes between TAP and PG. Results In the analysis, 189 patients were included, including PD straightening surgery, including 125 patients who underwent TAP (66%) and 64 patients (34%) who underwent PG. Among all cases, 49.7% underwent ventral incision (N = 94) and 50.3% (N = 95) underwent subcoronal incision. A total of 12 patients (6.3%) experienced a wound-related complication postoperatively (range 3-23 days), including 9/94 (9.6%) in the ventral incision cohort and 3/95 (3.2%) in the subcoronal cohort (P = 0.081). All the patients were treated with oral antibiotics and two patients required closure under local anesthesia (both in the ventral incision cohort). Secondary analysis did not reveal any significant difference in outcomes between TAP and PG cohorts with respect to wound complications. Clinical Implications While we did not identify a statistically significant difference, most of our wound complications, including infection and/or dehiscence, were seen in those undergoing a ventral penile raphe incision. Despite this, the rate of wound complications with either incisional approach as low. Strengths and Limitations Our report represents a large cohort of patients treated with surgical straightening for PD, and to our knowledge is one of the first to compare wound complications between ventral and subcoronal incisions. Limitations include the retrospective single-surgeon series without randomization, lack of power analysis, and heterogenous classification of wound complications. Conclusion Both ventral penile raphe and subcoronal (degloving) incisions can be considered for penile straightening procedures to correct PD curvature deformity with a low risk for serious wound-related complications.

Abstract Background Breast cancer genome-wide association studies (GWAS) have identified more than 200 susceptibility loci, but most studies are dominated by European and East Asian populations. Methods We analyzed breast cancer GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR), and Hispanic/Latina (H/L) samples (159,297 cases and 212,102 controls). We estimated logit-scale SNP-based heritability, polygenicity, and cross-ancestry genetic correlation, partitioned heritability across functional annotations, and integrated GWAS results with the Tabula Sapiens single-cell atlas using scDRS+. Results The logit-scale heritability of breast cancer ranged from ℎ 2 =0.47 (SE = 0.07) in EAS to AFR ℎ 2 =0.61 (SE = 0.10), with no significant differences across ancestries (p=0.63). The estimated number of susceptibility markers in a sparse normal-mixture effects model also varied from 4,446 (SE = 3,100) in EAS to 8,308 (SE = 2,751) in AFR, but differences were not significant across ancestries (p=0.55). Cross-sample genetic correlations varied, with the strongest correlation between EUR and EAS (𝜌 = 0.79, SE = 0.08) and weakest between AFR and H/L (𝜌 = 0.26, SE = 0.24). Regulatory annotations were enriched for breast cancer heritability across samples. Integration with single-cell expression profiles implicated ancestry-shared associations with innate immune, secretory epithelial, and stromal cell types. Conclusion These results indicate substantial cross-ancestry sharing of breast cancer polygenic architecture, highlight a consistent contribution of regulatory variation, and identify convergent cellular contexts that motivate functional follow-up and inform expectations for the transferability and attainable performance of common-variant risk prediction across populations.

Rubella is typically a mild viral illness, but it can lead to severe complications when contracted during pregnancy, such as pregnancy loss or developmental defects in the fetus (congenital rubella syndrome). Therefore, it is crucial to develop and maintain protective immunity in women of childbearing age. In this study, we assessed the transcriptional factors associated with rubella-specific immune outcomes (IgG binding antibody and avidity, neutralizing antibody, and memory B cell ELISpot response) following a third MMR vaccine dose in women of reproductive age to identify key factors/signatures impacting the immune response. We identified baseline (Day 0) and differentially expressed (Day 28–Day 0) genes associated with several RV-specific immune outcomes, including the transferrin receptor 2 (TFR2), which is an important factor regulating iron homeostasis and macrophage functional activity, and a close functional homolog of TFR1, the cellular receptor of the New World hemorrhagic fever arenaviruses. We also identified enriched KEGG pathways, “cell adhesion molecules”, “antigen processing and presentation”, “natural killer cell-mediated cytotoxicity”, and “immune network for IgA production”, relevant to immune response priming and immune activation to be associated with RV-specific immune outcomes. This study provides novel insights into potential biomarkers of rubella-specific immunity in women of childbearing age.

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity.

Abstract Objectives To enable users with modest technical background to perform biomedical natural language processing (NLP). Materials and Methods We developed medspacyV using the Python graphical programming tkinter library, following the model-view-controller (MVC) design pattern. The interface wraps around a rule-based pipeline for sentence splitting, section segmentation, concept identification, and negation detection. Results The primary window allows the user to configure the project and NLP rules, execute the pipeline, and save the outputs into a table. A separate annotation viewer window can be launched to inspect the immediate or previous NLP outputs. Discussion We developed medspacyV with three rationales: controllability, explainability, and economy. The rule-based approach is sufficient for many NLP use cases. Conclusion The medspacyV program is publicly available at https://github.com/medspacy/medspacyV, targeting use by healthcare professionals and researchers in their NLP projects.