Citations

Background: Considering the pathophysiological importance of the intestine-passing microbiota, we hypothesized that the mutational and microbial profiles of colorectal cancer might gradually change along detailed anatomical locations and that these trends might differ by the age of diagnosis and the microsatellite instability (MSI) status. Methods: We assessed somatic mutations and selected bacterial species in colorectal carcinomas along the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum, utilizing targeted sequencing data ( N = 5685) from the Genetics and Epidemiology of Colorectal Cancer Consortium and tissue microbial data ( N = 1389) from the Health Professionals Follow-up Study and Nurses’ Health Study. Results: There were decreasing trends from the cecum to rectum in the prevalence of gene mutations in the IGF/PI3K, receptor tyrosine kinase (RTK)/RAS, TGFB, and WNT signaling pathways (all P trend < 0.0001), as well as high levels of Bacteroides fragilis ( P trend < 0.0001) and high levels of Fusobacterium nucleatum ( P trend = 0.0029) (but not enterotoxigenic Bacteroides fragilis or pks+ Escherichia coli ). Conversely, TP53 pathway mutations showed an increasing cecum-to-rectum trend ( P trend < 0.0001). Similar to later-onset cases diagnosed at ages 50 years and older, in early-onset cases diagnosed under the age of 50 years, we found generally decreasing cecum-to-rectum trends of IGF/PI3K, RTK/RAS, TGFB, and WNT pathway mutations and an increasing cecum-to-rectum trend in TP53 pathway mutations. By contrast, the cecum-to-rectum prevalence-changing trends in IGF/PI3K, RTK/RAS, TGFB, and TP53 pathway mutations were present in non–MSI-high tumors but not in MSI-high tumors (all P interaction < 0.0052). Conclusion: Non–MSI-high colorectal cancers exhibited decreasing cecum-to-rectum trends of IGF/PI3K, RTK/RAS, and TGFB pathway mutations (and an increasing trend of TP53 pathway mutations), in contrast to MSI-high tumors that demonstrated no such trends. Our study highlights the importance of detailed colorectal subsite information combined with tumor molecular and microbial characteristics in colorectal cancer research.

Background: Several special tests for detecting medial ulnar collateral ligament (MUCL) injuries of the elbow have been described, but data on the clinical utility of these tests are limited. Purpose: To determine the clinical utility of selected elbow special tests to detect MUCL injuries in an athletic population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 84 consecutive patients with sports-related elbow pain underwent a standardized clinical examination. Overall, 6 special tests (moving valgus stress test, static valgus stress test, modified valgus stress test, milking maneuver, pronation flexion resistance test, and temple/cheek press test) were performed. Sensitivity, specificity, accuracy, positive/negative predictive value, and positive/negative likelihood ratio (LR+ and LR–, respectively) were calculated for individual tests and combinations of tests to detect MUCL injuries. Higher values for the LR+ and lower values for the LR– represent stronger clinical utility. Results: For detecting MUCL injuries, the moving valgus stress test resulted in the highest sensitivity (98%) and accuracy (93%) with the lowest LR– (2%). The milking maneuver had the highest LR+ (5.1) with the second highest sensitivity (77%) and accuracy (79%). The pronation flexion resistance test and the temple/cheek press test had the lowest LR+ (1.5 and 1.8, respectively) and highest LR– (94% and 95%, respectively) in addition to the lowest sensitivity (16% and 9%, respectively) and accuracy (33% and 30%, respectively). No combination of tests resulted in increased clinical utility. Conclusion: The moving valgus stress test and milking maneuver demonstrated acceptable clinical utility in which the moving valgus stress test was better for ruling out MUCL injuries and the milking maneuver was better at ruling in MUCL injuries. There was no added value when combining the 2 tests together or with other maneuvers.

Type 2 diabetes mellitus is associated with an increased risk of several malignancies, prompting interest in the potential oncologic effects of antidiabetic therapies, particularly metformin. This study evaluated cancer-related adverse event reporting associated with metformin compared with other antidiabetic agents using real-world pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS) between Q1 2023 and Q4 2024. A disproportionality analysis was conducted on over 3.2 million reports, including 66,187 metformin cases and 55,257 comparator cases comprising GLP-1 receptor agonists, SGLT2 inhibitors, sulfonylureas, and insulin. Reporting odds ratios (ROR), proportional reporting ratios (PRR), information components (IC), and chi-squared tests were applied across twelve pre-specified cancer types.<br /> Metformin was associated with significantly lower reporting of hepatocellular carcinoma (ROR 0.377, 95% CI 0.181–0.782) and pancreatic carcinoma (ROR 0.669, 95% CI 0.493–0.908). In contrast, increased reporting signals were observed for prostate cancer (ROR 2.065, 95% CI 1.435–2.972), leukaemia (ROR 2.388, 95% CI 1.155–4.939), and breast cancer (ROR 1.404, 95% CI 1.023–1.926). Drug-specific comparisons indicated relatively lower overall cancer reporting for metformin compared with sitagliptin and empagliflozin, but higher reporting compared with insulin. Temporal analyses demonstrated variability in reporting patterns across study quarters.<br /> These findings represent disproportionality signals reflecting reporting associations rather than causal effects and may be influenced by reporting bias, residual confounding, and differences in healthcare utilization. Overall, the results suggest a heterogeneous, cancer-type-specific reporting profile for metformin and highlight the value of pharmacovigilance analyses in generating real-world safety signals. Further confirmation in prospective and mechanistic studies is required.

Abstract Background: Despite efficacy in metastatic clear cell renal cell carcinoma (ccRCC), immunotherapy currently has no role in the neoadjuvant setting. Suppressive tumor-associated macrophages (TAMs) are known to mediate resistance to immune checkpoint blockade (ICB) in ccRCC. In preclinical studies, IL-1β blockade reprograms TAMs toward an anti-tumor phenotype and promotes T cell activation, creating a tumor microenvironment (TME) more sensitive to ICB. To test this in patients, we conducted a correlative-rich neoadjuvant trial of IL-1β + PD-1 inhibition in localized ccRCC. Methods: SPARC-1 is a single-center, phase 1b study assessing the safety and feasibility of neoadjuvant canakinumab (αIL-1β) and spartalizumab (αPD-1) in patients with localized ccRCC (T1b-T4NanyM0 or TanyN1M0). All patients received 2 doses of canakinumab (300mg IV, Q4w) and spartalizumab (400mg IV, Q4w), 6 weeks (±7 days) prior to nephrectomy. The primary endpoint was safety and feasibility. Key secondary and exploratory endpoints included 12-month metastasis-free survival rate, pathologic response rate, and quantification of immune cell infiltration. To characterize immunologic reprogramming, fresh tumor specimens were collected at nephrectomy for single-cell RNA sequencing (scRNAseq) and multiparametric flow cytometry. Tissue from a treatment naïve cohort was collected for comparative analysis (n=16). Results: From August 15th, 2018, to January 30th, 2025, 14 patients were enrolled. There were no severe treatment-related adverse events (Grade ≥ 3) attributed to canakinumab or spartalizumab. At a median follow-up of 12.0 months (range, 6.3-12.0 months), the 12-month metastasis-free survival was 100%. Based on the ASSURE nomogram, the mean predicted 12-month recurrence risk was 16.7% (range, 4.7-46.5%). ScRNAseq revealed that treatment with αIL-1β + αPD-1 increased the frequency of TREM2+APOE+ TAMs (p=0.035), a population typically associated with immune suppression. However, these TAMs exhibited a phenotypic shift toward a less immunosuppressive state, with reduced IL-1β expression and increased CXCL9:SPP1 ratio, consistent with anti-tumor TAM polarization. Immune profiling revealed an increased CD8/CD4 T cell ratio (p=0.042) with modest enrichment of activated CD8+ T cells after treatment, supporting a more pro-inflammatory TME. Conclusions: The neoadjuvant combination of canakinumab (αIL-1β) and spartalizumab (αPD-1) is well-tolerated, feasible, and demonstrated promising clinical activity with no progression of disease observed in a localized ccRCC population at high risk of recurrence. Correlative analyses demonstrated that combined IL-1β and PD-1 blockade reprograms immunosuppressive TAMs, providing evidence that dual IL-1β and PD-1 inhibition can overcome myeloid-driven resistance in ccRCC. Clinical Trial Information: NCT04028245 Citation Format: Patrick J. McCann, Aleksandar Obradovic, Casey R. Ager, David H. Aggen, Catherine S. Spina, Chelsea L. Rahiman, Kaitlyn R. Campbell, Caroline Laplaca, Peyton C. Johnston, Amanda Kim, Katherine Gomez, Kriti Bagri Manjrekar, Mark N. Stein, Charles G. Drake, Karie Runcie, Matthew Dallos. Neoadjuvant IL-1β and PD-1 inhibition in localized clear-cell renal cell carcinoma: Clinical and correlative analyses of the phase 1b SPARC-1 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT017.

OBJECTIVE This study investigated the relationship between diabetes and the incidence of postoperative dysphagia following cervical spine surgery (CSS). METHODS A prospectively collected multi-institutional quality registry was retrospectively reviewed. Patients who underwent CSS were categorized on the basis of diabetes status, and correlations with preoperative and postoperative Eating Assessment Tool-10 (EAT-10) dysphagia questionnaire scores were assessed. Mixed-effects logistic regressions were performed to examine the impact of preoperative diabetes on postoperative dysphagia. RESULTS Of the 2001 patients who met the inclusion criteria, 400 (20%) had diabetes. Baseline dysphagia rates were not significantly different between groups (18% vs 14%, p = 0.08). Patients with diabetes had a significantly higher incidence of dysphagia at 1 month (66% vs 54%, p = 0.002), 3 months (39% vs 26%, p < 0.001), and 12 months (33% vs 24%, p = 0.004) after surgery compared to patients without diabetes. Including baseline dysphagia as a fixed effect, multivariable analysis indicated that diabetes was a significant predictor of postoperative dysphagia at 1 month (OR 1.46, p = 0.041) and 3 months (OR 1.63, p = 0.001) but not at 12 months (OR 1.21, p = 0.3). In patients with no baseline dysphagia, those with diabetes (329 of 400 [82.3%]) had a significantly higher incidence of new dysphagia than nondiabetics at 1 month (62% vs 50%, p = 0.003), 3 months (34% vs 21%, p < 0.001), and 12 months (27% vs 18%, p = 0.001). The mean change in EAT-10 scores between baseline and 12 months was significantly worse in patients with preoperative diabetes (2.440 ± 5.013 vs 1.688 ± 4.139, p = 0.025). Multivariable analysis indicated that diabetes was a significant predictor of new postoperative dysphagia at 1 month (OR 1.49, p = 0.040) and 3 months (OR 1.81, p < 0.001) but not at 12 months (OR 1.31, p = 0.2). CONCLUSIONS Diabetes is a significant risk factor for experiencing postoperative dysphagia following CSS. Diabetes correlated with higher incidence of dysphagia at all postoperative time points and was a strong independent predictor of postoperative dysphagia at 1 and 3 months.

Abstract Background Red cell alloimmunization complicates sickle cell disease (SCD) management despite current widespread prophylactic Rh/K matching in the United States (US). Regional antibody patterns remain poorly characterized. Study Design and Methods We conducted a retrospective analysis of 2965 SCD patients from 9 US sites (2010–2022). All hospitals prophylactically match for Rh and K antigens. Each site collected demographics, antigen status, antibody histories, and antibody screen results from their laboratory information system. Results Overall antibody prevalence was 29.7% with dramatic institutional variation (17.9%–56.0%). Alloantibody prevalence was 27.5%. Most autoantibody‐positive patients (74.23%) also had alloantibodies, identifying a high‐risk population. A third of patients with positive antibody histories had negative screens. Pediatric patients showed markedly different antibody profiles than adults. Hospitals’ antibody patterns clustered by patient age rather than geography. Rh and K antibodies were the most common and also most likely to co‐occur, followed by S, Fya, and Jkb antibodies. Antibodies against Jsa (1.82%), V (1.75%), and Kpa (1.69%) were more prevalent than anti‐Jka (1.28%). Despite regional antibody variation, antigen frequencies remained overall consistent. In antigen–antibody pairwise comparisons, 3.15% were antigen‐negative and antibody‐positive reflecting alloimmunization; 0.47% were both antibody‐ and antigen‐positive, suggesting partial/variant antigens. Discussion Substantial institutional variation in antibody prevalence suggests need for site‐specific approaches to testing and prophylactic matching. High co‐occurrence of auto‐ and alloantibodies, antibody immunogenicity patterns, and antigen–antibody discordances support the need for further research and consideration of refined testing and/or matching strategies beyond the current Rh and K standard.

BACKGROUND Guidelines and evidence related to antibiotic prophylaxis in dermatologic surgery have evolved since the authors' previously published advisory statement. OBJECTIVE To provide an updated advisory statement on antibiotic prophylaxis in dermatologic surgery as guided by updated recommendations from the American Heart Association and the American Dental Association with the American Academy of Orthopaedic Surgeons guidelines. METHODS A structured literature review was performed. A multidisciplinary team of specialists from dermatologic surgery, infectious diseases, and pharmacy were convened to review up-to-date data and develop updated comprehensive evidence-based recommendations. RESULTS Consistent with the previous advisory statement, prophylactic antibiotics are recommended for patients with high-risk cardiac or prosthetic joint conditions, when the dermatologic surgical site is infected or if the procedure breaches the mucosa. Significant changes were made for prophylaxis of surgical site infection. Updated recommendations were made regarding antibiotic selection in penicillin-allergic patients and intraoperative use of intraincisional clindamycin in the local anesthetic. LIMITATIONS Reviewed data are predominantly limited to retrospective data. CONCLUSION Recommendations regarding antibiotic prophylaxis around dermatologic surgery are evolving as new data and practices are introduced. The 2025 advisory statement provides the latest recommendations for appropriate use of antibiotic prophylaxis in dermatologic surgery.

Abstract Background: Adhering to 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations is reportedly associated with better survival among long-term colon cancer survivors (likely affected by immortal time bias). Thus, it is important to validate survival benefits by assessing adherence shortly after diagnosis, and further investigation is needed to examine its association with chemotherapy outcomes. Methods: Using an NCI-sponsored adjuvant chemotherapy trial conducted in patients with stage III colon cancer (CALGB/SWOG 80702; NCT01150045), we included 1,666 patients who returned valid Willett food frequency questionnaires (FFQ) at chemotherapy initiation and derived WCRF/AICR scores accordingly (higher score suggesting higher adherence). The primary outcome was disease-free survival (time from FFQ completion to recurrence or death), and secondary outcomes were reduced relative dose intensity (RDI; &lt;85% suggesting worse completion) and severe toxicities (grade ≥3 for any chemotherapy-related toxicity). To estimate the associations of WCRF/AICR scores (quartiles) with survival and chemotherapy outcomes, we conducted multivariable Cox proportional hazards regression for disease-free survival and multivariable logistic regression for reduced RDI and severe toxicities. Results: Compared to those in the lowest quartile of the WCRF/AICR score, patients in the highest quartile had significantly better disease-free survival (hazard ratio: 0.75 [0.58, 0.98], Ptrend = 0.02) and lower risk of reduced RDI (odds ratio [OR]: 0.74 [0.54, 1.00], Ptrend = 0.03), but not for severe toxicities (OR: 1.24 [0.93, 1.67], Ptrend = 0.11). Conclusions: In patients with stage III colon cancer, higher adherence to WCRF/AICR recommendations was associated with better survival and chemotherapy completion, but not for severe toxicities. Funding: https://acknowledgments.alliancefound.org Citation Format: En Cheng, Chao Ma, Qian Shi, Anthony F. Shields, Peter T. Campbell, Ardaman P. Shergill, Katherine A. Guthrie, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha S. Krishnamurthi, Kimmie Ng, Eileen M. O'Reilly, Justin C. Brown, Philip A. Philip, Jeffrey A. Meyerhardt. Associations of WCRF/AICR recommendations with survival and chemotherapy outcomes in colon cancer: CALGB/SWOG 80702 (Alliance) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5038.