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Introduction: Robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (PLND) represents the gold standard surgical treatment for high-risk localized prostate cancer. PLND carries the risk of lymphocele formation, which can lead to complications such as deep vein thrombosis (DVT), infection, and voiding dysfunction. Many techniques have been described to minimize lymphocele formation, yet no method has seen widespread use or been described as sutureless. The objective of this study is to describe the novel, sutureless peritoneal window (PWIN) technique and assess its efficacy in lymphocele prophylaxis for extended PLND. Methods: This was a retrospective review of patients with high-risk prostate cancer undergoing RARP with extended PLND by a single surgeon from 2018 to 2024. PLND was carried out in the usual manner with bipolar cautery. PWIN technique is performed by excising a 3 × 5 cm PWIN over the lymphadenectomy bed to maintain lymphatic communication with the abdominal cavity. The primary outcome was a comparison between the incidence of symptomatic lymphoceles (SLs) with PWIN vs standard technique. SLs were defined as lymphoceles presenting with pain, DVT, voiding dysfunction, or infectious symptoms. Patients with asymptomatic lymphoceles were excluded. Results: Our study included 199 patients who underwent RARP with extended PLND. There were 46 patients (23.1%) in the standard approach group and 153 patients (76.9%) in the PWIN group. We identified 5/46 (10.9%) SLs in the standard technique, which were significantly higher than the 3/153 (2.0%) observed in the PWIN group (p = 0.017). There was no difference between the standard and PWIN cohorts regarding symptomology or treatment of their lymphocele. Conclusion: This study describes a novel, sutureless PWIN technique that significantly decreases SL after extended PLND. This technique offers a practical, time-efficient, and cost-effective alternative for lymphocele prevention. Future prospective studies are warranted to validate these findings.

Background: Periarticular local infiltration analgesia has become an important mainstay of multimodal analgesia after elective total hip arthroplasty (THA). However, the role of novel motor-sparing fascial plane blocks—with or without periarticular local infiltration analgesia—has not been fully elucidated for patients undergoing THA. The authors conducted a network meta-analysis evaluating the relative analgesic effectiveness of motor-sparing fascial plane blocks (quadratus lumborum, erector spinae, and pericapsular nerve group blocks) and periarticular local infiltration analgesia for adult patients undergoing THA. Methods: Randomized trials examining single-injection quadratus lumborum, erector spinae, or pericapsular nerve group blocks, or periarticular local infiltration analgesia, for THA were sought. The primary outcome was area under the curve (AUC) rest pain scores during the period from 0 to 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; postoperative function at 6, 12, and 24 h; analgesic consumption at 0 to 24 h; incidence of opioid-related side effects; and incidence of block-related complications. Network meta-analysis was performed using a frequentist approach. Results: A total of 44 trials (3,579 patients) evaluating the quadratus lumborum block, erector spinae block, pericapsular nerve group block, or periarticular local infiltration analgesia for THA were considered. Network meta-analysis was used to derive the probability of each intervention being the most effective as compared to the others (P score). For AUC 0 to 24 h rest pain, periarticular local infiltration analgesia was the most effective intervention, as demonstrated by a P score of 89%. For postoperative analgesic consumption, the quadratus lumborum block was the most effective intervention, with a P score of 88%. This was followed by the pericapsular nerve group block (74%), the erector spinae block (38%), and periarticular local infiltration analgesia (42%). Conclusions: Periarticular local infiltration analgesia alone provides the most consistent improvements in postoperative rest pain, analgesic consumption, and functional recovery after THA. The addition of a quadratus lumborum block or pericapsular nerve group block to periarticular local infiltration may further improve analgesic outcomes.

ABSTRACT Background Sulfa antibiotic allergy labels (SALs) are encountered frequently in kidney transplant recipients (KTs). This often results in patients receiving second‐line prophylaxis for both Pneumocystis jiroveci and urinary tract infections (UTIs). The effect of SAL on outcomes including UTIs after KT is unclear. Methods In our single‐center retrospective cohort study, we investigated the effect of SALs on bacteriuria after KT. We identified patients with pre‐KT SALs from 2011 to 2022. A matched cohort was then created using KT with no pretransplant SALs. The groups were compared using proportional analysis and univariable and multivariable Cox proportional regression models. The primary outcome of interest was the proportion of individuals experiencing one or more episodes of bacteriuria within 1 year posttransplant. Secondary outcomes included bacteremic UTIs, acute kidney injury, and opportunistic infections. Results We found that the proportion of individuals experiencing bacteriuria within the first‐year posttransplant was significantly greater in the SAL group versus the control group ( n = 21, 28% vs. n = 22, 14.7%, p = 0.012). This result was also seen in univariable and multivariable survival analysis. In addition, episodes of UTI with associated bacteremia ( n = 11, 14.7% vs. n = 5, 3.3%, p = 0.002) were statistically significantly higher in the SAL group. Conclusion There was a significantly greater number of episodes of bacteriuria in the first‐year posttransplant in subjects with pretransplant SAL. Based on our findings, we suggest that all KTs with pretransplant SALs undergo evaluation and intervention prior to transplantation. image

CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months. For the 97 treated patients, median OS was 60.7 months (95% CI, 41.9 to not estimable). One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative (at least 10 −5 threshold) and imaging-negative at year 5 or later after cilta-cel. Baseline characteristics, including the presence of high-risk cytogenetics and extramedullary disease, were generally comparable for the 32 patients who were progression-free for ≥5 years versus patients who had progressive disease by year 5. A trend of lower baseline tumor burden, higher fraction of naïve T-cells in the cilta-cel drug product, higher T cell-to-neutrophil ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio were associated with ≥5-year progression-free status. The safety profile of cilta-cel remained consistent with previous reports. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.

Abstract Multiple myeloma (MM) is an incurable malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment. To investigate immune factors driving treatment response and resistance, we conducted multi-omics profiling including CD138 neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138 pos bulk RNA and whole-genome sequencing from 209 samples. Longitudinal analyses revealed that interferon gamma signaling impairs T cell memory after autologous stem cell transplant, while naïve B cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48, p = 2.3e -4 ). At disease progression, MM cells upregulated cancer-testis antigens and immune effector genes, with concurrent B cell depletion, enrichment of myeloid-derived suppressor cell genes in monocytes, and T cell exhaustion. These findings highlight dynamic immune-tumor interactions, identifying naïve B cell reconstitution as a biomarker of durable response, and cancer-testis antigens as potential targets for high-risk disease at progression. Statement of Significance Longitudinal profiling of multiple myeloma and the immune microenvironment revealed dynamic immune-tumor interactions across the disease course. Dysfunctional CD8⁺ T cells limited memory formation post-transplant, while naïve B recovery associated with sustained treatment response. At progression, cancer-testis antigen expression associated with immunosuppression, revealing novel mechanisms of immune escape.

7540 Background: The combination of a proteasome inhibitor (PI) with lenalidomide (R) and dex (d) has been a common initial therapy for newly diagnosed myeloma (NDMM). We designed a randomized phase 3 trial to examine if carfilzomib (K), a next generation PI, improved progression free survival (PFS) compared with bortezomib (V) when either is combined with Rd for initial treatment of NDMM. Initial analysis at a median follow up of 15.3 months (mos) showed comparable PFS for both triplets. We present the long-term results of the trial with ~70 months median follow up. Methods: Patients (Pts) with NDMM, were randomized 1:1 to receive VRd or KRd for 36 weeks followed by a 2 nd randomization (1:1) to indefinite versus 2 yrs of R maintenance. Pts without del17p, t(14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included V 1.3 mg/m 2 on days(d) 1, 4, 8, and 11 (d1, 8 for cycles 9-12), R 25 mg d1-14, and d 20 mg d1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received K 36 mg/m 2 d1, 2, 8, 9, 15, 16 with R 25 mg daily on d1-21 and d 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance used 15 mg R d1-21 q4 wks. Results: The study accrued 1087 pts (VRd=542, KRd=545). Median age was 65y; baseline characteristics including intent to transplant were similar across the arms. Median induction duration (mos; IQR) was 7.2 (3.4-8.9) and 8.4 (5.1-9.1) for VRd and KRd, respectively; 59.8% in VRd and 45.3% in KRd did not proceed to Step 2. Median PFS (mos) was VRd=41.9 and KRd=44.6; HR = 0.89 (0.76-1.04). Toxicity data, PFS sensitivity analyses and OS probabilities are as in the table. Conclusions: In this randomized trial, with median follow up of nearly 6 years, KRd and VRd had comparable PFS and OS in an intent to treat analysis. While similar numbers proceeded to SCT in the 2 arms, more did so during induction in the VRd arm while more patients in the KRd arm went to SCT later. VRd remains a standard triplet induction regimen in standard and intermediate risk NDMM, and a suitable backbone for 4 drug combinations. Clinical trial information: NCT01863550 . N (%) VRd(n=527) KRd(n=526) SCT anytime 186 (34.3) 183 (33.6) SCT without Step 2 registration 146 112 Median Time to SCT (mos; range) 7.7 (3.5-83.9) 10.6 (3.7-70.6) Grade 3-4 Treatment-Related Toxicity 315 (59.8) 344 (65.4) Grade 5 Treatment-Related Toxicity 2 (0.4) 9 (1.7) Grade 5 All Events 11 (2.1) 20 (3.8) Survival outcomes HR Median (95% CI) Median (95% CI) PFS Primary: PD or death within 3 months of last evaluation as events 0.89(0.76-1.04) 41.9(35.7, 50.3) 44.6(38.2, 51.9) PFS Sensitivity: All deaths as events, 0.87(0.75-1.02) 39.5(34.9, 46.0) 42.8(37.4, 49.7) PFS Sensitivity: Censor at alternate Rx 0.83(0.69-0.99) 35.0(31.3, 42.6) 38.7(34.7, 49.0) PFS Sensitivity: Event at alternate Rx 0.84(0.73-0.97) 18.0(14.2, 23.0) 24.4(20.9, 27.9) Overall survival 0.92(0.75-1.12) 119(100, NE) 118(103-NE)

Background: Varicose veins (VVs) of the lower limbs, characterized by palpable, dilated, and tortuous veins, affect 2–73% of the global population. Artificial intelligence (AI) offers significant potential to enhance healthcare efficiency and decision-making, particularly in managing VVs through improved risk factor identification, diagnosis, and treatment planning. Objective: This abstract explores the role of AI in VV management, focusing on its applications in risk detection, image analysis, treatment planning, and surgical interventions, while addressing challenges to its widespread adoption. Methods: AI leverages advanced techniques such as computer vision and deep learning to analyze patient data, including medical history, symptoms, physical examinations, and imaging (e.g., ultrasounds, venography). It identifies patterns in large datasets to support personalized treatment plans, early risk detection, and disease severity assessment. Results: AI demonstrates promise in automating VV detection and classification, assessing disease severity, and aiding treatment planning. It enhances surgical interventions through preoperative planning, intraoperative navigation, and recurrence risk prediction. However, its adoption is limited by a lack of large-scale studies, concerns over accuracy, and the need for regulatory and ethical oversight. Conclusion: AI has the potential to revolutionize VV management by improving diagnosis, treatment precision, and patient outcomes. Further research, validation, and integration are critical to overcoming current limitations and fully realizing AI’s capabilities in clinical practice.

Abstract RATIONALE: Chronic kidney disease (CKD) is common in the general population and is associated with inflammation and compromised immune function. Since these mechanisms are hypothesized to promote severe COVID-19, we tested associations of pre-pandemic CKD with incident COVID-19 hospitalization or death in a large, multi-ethnic, US general population-based meta-cohort of adults. METHODS: Data were harmonized and pooled from 9 NIH-funded longitudinal cohorts participating in the Collaborative Cohort of Cohorts for COVID-19 Research (C4R). CKD was classified by KDIGO 2024 CKD guideline (Low Risk, Moderately Increased Risk, High Risk, Very High Risk) using pre-pandemic urinary albumin-to-creatinine ratio (uACR) and estimated glomerular filtration rate using creatinine (eGFRcr). Incident COVID-19 hospitalization or death was ascertained over 2020−2023 via self-report and active surveillance, with medical record adjudication in a subset. In our primary analysis, we assessed associations between CKD stages and incident COVID-19 hospitalization or death. A secondary analysis examined joint association of CKD stages and the number of comorbidities (obesity, hypertension, diabetes, and cardiovascular disease) with the severe COVID-19. Multivariable hazard ratios (HRs) were estimated by cause-specific Cox regression, adjusting for socio-demographics and smoking. RESULTS: Among 26,039 multi-ethnic adult participants (mean age 66.1±14.8, 60.6 % female, 28.6% Whites, 3.2% Asians, 20.6% Blacks, 41.3% Hispanics, 6.3% American Indians) with a median follow-up of 550 days since the onset of the pandemic (baseline: March 1, 2020), there were 734 incident COVID-19 hospitalizations or deaths. The mean time since CKD markers were measured before the baseline was 6.5 years. The cumulative incidence of severe COVID-19 was 2.3, 3.5, 6.5, and 7.3% across CKD risk stages, and similar patterns were observed within variant types (Figure 1). Compared to participants with Low Risk of CKD, there was a graded increased hazards of severe COVID-19 across CKD stages, with HRs (95% CIs) of 1.27 (1.03−1.55) for Moderately Increased Risk, 2.33 (1.77−3.06) for High Risk, and 2.72 (1.89−3.92) for Very High Risk. In a joint analysis, both increased CKD risk and a higher number of comorbidities were associated with a higher risk of severe COVID-19, showing the highest HR of 12.29 (5.75−26.27) in Very High Risk individuals with four comorbidities compared to Low Risk individuals with none. CONCLUSIONS: Higher CKD stages were associated with a greater risk of COVID-19 hospitalization or death and the risk is substantially heightened with additional comorbidities. These results suggest that adults with CKD and related comorbidities may merit enhanced COVID-19 risk mitigation.

Importance A subset of Union for International Cancer Control ( UICC )/ American Joint Committee on Cancer ( AJCC ) eighth edition TNM stage I and II human papillomavirus–positive oropharyngeal carcinoma has undesirable outcomes, which might have contributed to a lack of success in phase III deintensification trials. Refining clinical stage groups, especially in the overabundant cN1/stage I group, has become important for treatment selection. Objective To assess the prognostic importance of pretreatment lymph node (LN) characteristics to optimize case distribution and outcome homogeneity within the N classification system. Design, Setting, and Participants This is an international multi-institutional retrospective prognostic cohort study. Analysis of human papillomavirus–positive oropharyngeal carcinoma treated curatively from 4 institutions (International Collaboration of Oropharyngeal Cancer Network for N-Classification [ICON-N] dataset) provided a refined clinical staging proposal; an independent dataset (Centre Hospitalier de l’Université de Montréal [CHUM] dataset) validated the proposal. Neuroradiologists reviewed pretreatment computed tomography and/or magnetic resonance imaging for nodal features, including presence or absence of abnormal LN(s), retropharyngeal LN, laterality, number of abnormal LN, and imaging-detected extranodal extension (iENE). Data were collected from February to May 2023, and data were analyzed from June to July 2023. Exposures Definitive chemoradiotherapy/radiotherapy or definitive surgery with or without postoperative chemoradiotherapy/radiotherapy. Main Outcomes and Measures The primary end point was overall survival. A Cox proportional hazards multivariable model was used to estimate adjusted hazard ratios (AHRs) and to derive an optimal clinical TNM stage classification (AHR-stage schema) incorporating the strongest prognostic nodal features within the UICC/AJCC eighth edition TNM framework after confirming the prognostication of iENE status. The performance (according to overall normalized scores and ranking) of the AHR-stage schema against the current UICC/AJCC eighth edition TNM staging system was evaluated for hazard consistency, hazard discrimination, prognostic importance, and sample size balance. Validation was performed in the CHUM dataset. Results The ICON-N dataset comprised 2053 patients, including 1898 (92.5%) with cN-positive disease and 155 (7.5%) with cN0 disease; a total of 298 (14.5%) were female, and the mean (SD) age was 60.6 (9.3) years. iENE-positive disease was identified in 710 of 1898 patients with cN-positive disease (37.4%). The median (range) follow-up was 5.1 (0.1-14.7) years. iENE was the strongest prognostic nodal feature in multivariable analysis; the AHR for iENE-positive vs iENE-positive disease was 2.43 (95% CI, 1.96-3.03) in the ICON-N dataset and 2.04 (95% CI, 1.28-3.23) in the CHUM dataset (n = 451). Reclassifying iENE-positive cases 1 stratum higher for N categorization without altering iENE-negative cases yielded an AHR-stage schema that outperformed the current TNM staging system in disease-free and overall survival with a lower (ie, better) overall normalized score (2 vs 3). Conclusions and Relevance In this study, reclassifying each N category 1 stratum higher for iENE-positive disease resulted in better disease-free and overall survival. The proposed new classification outperformed the currently TNM staging system in risk stratification and may facilitate future clinical trial design, outcomes research, and patient care.