Khan, Muhammad Ali

703 Background: The association of circulating tumor DNA (ctDNA) reduction with treatment response has been investigated across multiple malignancies. This study aims to assess the impact of ctDNA response on survival outcomes in patients receiving enfortumab-pembrolizumab (EV-P). Methods: We identified 32 patients with advanced urothelial carcinoma who received EV-P and had ≥2 ctDNA assessments with ≥1 detectable level. Deep molecular response was defined as >2-log reduction from highest ctDNA detection. Radiographic progression was determined from radiology reports documenting progression by RECIST criteria. Kaplan Meier analyses were performed to compute Hazard Ratios (HR) with 95% confidence intervals (CI) for radiographic progression free survival (rPFS), defined as time from treatment start to radiographic progression or death and overall survival (OS) defined as time from treatment start to death were computed. Log-rank tests were performed to compare PFS and OS in patients with deep molecular response to those without response. A p-value <0.05 indicated a statistically significant association with response. Results: Thirty-two patients were included (median age 71 years; range 39–90). Median follow-up was 10.6 months. At cutoff (10/1/2025), 26 patients were alive and 6 had died. Seventeen (53%) achieved a ≥2-log ctDNA reduction (responders), while 15 (47%) did not (non-responders). Progression-free survival was significantly longer in responders (log-rank P < 0.001); median PFS was 5.9 months (95% CI 2.4–NR) in non-responders and not reached in responders (HR 0.09, 95% CI 0.02–0.44; P = 0.0026). Median overall survival was 12.7 months (95% CI 10.0–NR) in non-responders versus not reached in responders (log-rank P = 0.011; HR 0.11, 95% CI 0.01–0.88; P = 0.037). At cutoff, 94% of responders and 67% of non-responders were alive. Conclusions: Achieving a >2-log decrease in ctDNA during EV + Pembrolizumab therapy was significantly associated with improved progression free and overall survival. These findings support ctDNA kinetics as a potential early biomarker of response warranting prospective validation. Clinical outcomes by >2-log ctDNA reduction status. Endpoint > 2-log drop (n = 17 ≤ 2-log drop (n = 15) Log-rank p Median (mo) ≤ 2-log > 2-log HR (95% CI) P C-index PFS 2 events (12%) 10 events (67%) 0.0002 5.9 (2.4–NA) NR 0.09 (0.02–0.44) 0.0026 0.77 OS 1 event (6%) 6 events (40%) 0.011 12.7 (10.0–NA) NR 0.11 (0.01–0.88) 0.037 0.73

Background: Acute tubulointerstitial nephritis (ATIN) is a significant yet under-monitored cause of U.S. mortality, particularly among the elderly. This study anrackalyzed national trends and demographic disparities in age-adjusted mortality rates (AAMRs) from 1999 to 2020 to identify high-risk populations and inform public health policy. Methods: Using the CDC WONDER database, we conducted a retrospective analysis of 6872 ATIN-related deaths. AAMRs (per 100,000) were stratified by sex, race, and census region. Temporal shifts were quantified using Joinpoint regression to determine annual percentage changes (APC) and 95% confidence intervals (CIs). Results: The analysis revealed a distinct “V-shaped” mortality trend across the 22-year period. Following an initial decline from 1999 to 2013, AAMRs rose sharply through 2020. Males experienced a slightly steeper recent increase (9.90%) compared to females (9.50%). While Black/African American individuals initially had higher mortality rates, a significant surge in deaths among Non-Hispanic White individuals after 2013 (APC 10.42%) led to a convergence of mortality rates between the two groups by 2020. Geographically, the Midwest (APC 12.08%) and the South saw the most pronounced recent increases, whereas the West showed a sustained upward trend beginning as early as 2008. Conclusions: There has been a concerning reversal in ATIN-related mortality trends in the United States over the last decade. The convergence of racial mortality rates and significant regional variations suggest that shifting healthcare access, environmental factors, or medication exposure patterns (such as polypharmacy) warrant urgent investigation to mitigate this rising public health burden.

The indications for immune checkpoint inhibitor (ICI) use in cancer treatment continue to expand. This is attributable to their proven anticancer activity in addition to their tolerability and favorable toxicity profile as compared to conventional chemotherapeutic agents. ICIs work by blocking the inhibitory signals between tumor cells and T-cells, thereby enhancing the T-cell cytotoxic activity to inhibit tumor growth. Because of their immune-stimulating effect, ICIs are linked to adverse renal outcomes in both native and transplanted kidneys. The risk of kidney allograft rejection in the setting of ICI use has been reported to be around 40%, leading to an increased risk of graft loss. In this report, we review the literature examining outcomes in kidney transplant recipients receiving ICIs for various oncologic indications.

Background: Solid organ transplant (SOT) recipients are living longer and, consequently, more of them require elective total hip arthroplasty (THA) to restore mobility and improve quality of life. Because these patients are chronically immunosuppressed and often burdened by multiple comorbidities, their peri-operative risk profile may differ substantially from that of the general THA population. This study aimed to evaluate risk factors associated with acute medical and surgical complications, implant survivorship, and overall mortality in patients with a history of SOT who underwent THA. Methods: A total of 173 THA procedures were reviewed in patients with previous SOT. Among them, 64 had undergone liver transplantation (LT), 83 had received renal transplants (RT), and 26 had experienced more than one type of organ transplant (MT). Kaplan–Meier survival analysis was employed to estimate median survival. Complications were examined using univariate analysis through mixed-effects logistic regression, while Cox regression was utilized to assess mortality risk. The median follow-up period extended to 99 months. Results: The proportion of patients experiencing at least one acute medical event was 27% in the LT group, 33% in the RT group, and 38% in the MT group, with no statistically significant difference between groups (p = 0.5). American Society of Anesthesiologists Class (ASA) 4 (Odds Ratio (OR) = 28; p = 0.006) and treatment with bisphosphonates (OR = 2.25; p = 0.03) were associated with higher risk of acute medical complications. Increased age at the time of SOT was linked to a reduced likelihood of surgical complications (OR = 0.94, p = 0.008), as was older age at the time of undergoing THA (OR = 0.92, p = 0.001). The observed rates of reoperation and implant revision were 3% and 1%, respectively. The estimated patient survivorship rates at 1, 5, and 10 years were 98.6, 82, and 58.4%, respectively. Older age at SOT (Hazard Ratio (HR) = 1.06, p < 0.001), at THA (HR = 1.08, p < 0.001), ASA 4 at THA (HR = 7.57, p = 0.02), and atrial fibrillation (AFib) (HR = 3.13, p = 0.02) were associated with higher mortality. Conclusions: ASA 4 and bisphosphonates were associated with a higher risk of acute medical complications, whereas older age was associated with lower surgical complications. Additionally, older age, ASA 4, and AFib were associated with higher mortality.

Kidney transplantation remains the gold standard for managing end-stage kidney disease, providing superior survival and quality-of-life outcomes compared to dialysis. Despite the ongoing gap between organ availability and demand, it is inevitable that kidney transplantation will continue to grow. This is owed to broader organ sharing, increased comfort of transplant programs with marginal kidney utilization, and the expansion of paired exchange among living donor kidneys. The evolution of kidney transplantation could not have been possible without the availability of effective immunosuppressive regimens that prevent rejection and maintain graft function. Mycophenolic acid and calcineurin inhibitors continue to serve as the foundation of modern maintenance immunosuppression. While these agents have markedly reduced acute rejection rates, their long-term efficacy in graft survival remains suboptimal. Alternative immunosuppressive therapies, including belatacept and mammalian target of rapamycin inhibitors, have demonstrated potential benefits. However, concerns regarding an increased risk of rejection have limited their widespread adoption as primary treatment options. In addition to ongoing efforts to refine steroid- and calcineurin inhibitor-sparing strategies, the identification of practical and quantifiable biomarkers for predicting long-term graft survival remains a critical objective. This review evaluates contemporary immunosuppressive protocols, highlights existing challenges, and explores future directions for optimizing long-term transplant outcomes.