Citations

Since the first successful kidney transplant in 1954, transplant medicine has advanced significantly, achieving favorable one-year outcomes. However, despite excellent short-term outcomes, long-term renal allograft survival remains sub-optimal, with acute rejection continuing to be a major contributor to death-censored allograft loss. Current approaches for post-transplant surveillance and rejection monitoring rely on either nonspecific markers that often detect injury late in their course or invasive procedures associated with procedural risks and complications. To address these limitations, numerous non-invasive biomarkers have been introduced into solid organ transplantation research with the goal of improving allograft surveillance, facilitating earlier detection of rejection and complementing existing diagnostic approaches. Although several biomarkers have demonstrated clinical promise, none currently possess sufficient accuracy to replace kidney allograft biopsy. Biomarkers under investigation include blood-, tissue- and urine-based specimens. Their development and validation as independent markers have been limited by smaller sample size, heterogenous targets, variable performance characteristics and suboptimal sensitivity and specificity. In response, the field has increasingly shifted toward multimodal approaches that combine biomarkers and incorporate artificial intelligence to improve diagnostic accuracy and outcomes prediction. This review summarizes current biomarkers, discusses their limitations and explores future directions for biomarker development and clinical implementation.

Gliomas are diffusely infiltrative, requiring accurate and sensitive diagnostic tools during surgical resection. Mutations in isocitrate dehydrogenase enzyme (IDH) alter its normal activity and result in accumulation of a unique oncometabolite, 2-hydroxyglutarate (2HG), in tumor cells. However, IDH-wild-type (IDH-wt) gliomas are more common and typically more aggressive. Here, 86 human brain samples were analyzed by syringe touch spray mass spectrometry to evaluate molecular alterations in gliomas. Tandem mass spectrometry (MS/MS) experiments were performed to minimize isobaric and isomeric interferences, and a ratiometric approach (using only signals for endogenous compounds) was employed to improve reliability of the measurements. Multiple ratios for pairs of metabolite signal intensities were found to differentiate tumor samples from nontumor tissue and they stratified glioma subtypes by IDH mutation status and by tumor grade, with several ratios showing 100% agreement with independent clinical assignments ( P < 0.0001, Mann–Whitney U test). Increased carnitine relative abundances were found across all glioma subtypes. Importantly, α-aminoadipate was significantly elevated in grade 4 glioma, which may correlate with increased tumor malignancy. Grade 3 gliomas showed markedly higher 2HG abundance than grade 4 samples. In addition, a selection of ratios showed a linear trend with varying tumor cell percentage. Overall, the multiple metabolic ratio alterations indicate a high degree of heterogeneity among glioma subtypes. Furthermore, there are metabolites that can differentiate glioma from nontumor tissue and this measurement can be made by a simple ratiometric method which has potential to be used intraoperatively for margin assessment without diverging from standard of care.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis of older adults and has traditionally been framed as an ophthalmologic emergency. Its most serious consequences, however, occur in the cardiovascular system, often years after inflammatory markers have normalized. In contemporary matched population cohorts, patients with GCA carry an approximately two-fold excess risk of aortic aneurysm; the historical Olmsted County cohort reported a 17-fold excess of thoracic aortic aneurysm with wide confidence limits, and the characteristic latency to aneurysm is five to ten years. Patients also face elevated risks of aortic dissection, myocardial infarction, stroke, venous thromboembolism, and heart failure that cluster within the first year of diagnosis, when vascular inflammation is most active. This narrative review, based on a structured search of PubMed/MEDLINE and Google Scholar through September 2026 with independent verification of every cited estimate, synthesizes current evidence on the full spectrum of cardiac and aortic complications of GCA, including aortitis, aneurysm and dissection, coronary arteritis, valvular disease, pericarditis, myocarditis, and conduction disease. We trace their common origin to the immunopathology of the arterial wall, where dendritic cell activation, Th1/Th17 polarization, and maladaptive vascular remodeling produce occlusion in medium-sized arteries and dilation in the aorta. We examine current diagnostic modalities, from the ultrasound-based fast-track clinic, which has reduced permanent visual loss by half or more in observational cohorts, to FDG-PET/CT, in which aortic uptake at diagnosis is associated with subsequent aortic dilation. We review treatment after the GiACTA and SELECT-GCA trials in the light of the 2025 European Alliance of Associations for Rheumatology (EULAR) recommendations, the unresolved role of antiplatelet and statin therapy, and the surgical and endovascular management of GCA-related aortopathy. We suggest that the organization of care, as well as the limitations of drug therapy, may contribute to the residual mortality of GCA, a hypothesis that has not been tested; distinguish recommendations that are supported by current guidelines from those that are our own proposals; and outline a cardio-rheumatology pathway in which baseline vascular phenotyping informs individualized aortic surveillance. GCA is a disease whose natural history often begins in the rheumatology clinic and ends in the cardiac operating room without prior surveillance.

Monoclonal gammopathy of renal significance (MGRS) encompasses renal lesions caused by nephrotoxic monoclonal immunoglobulins produced by small B-cell or plasma cell clones that do not meet criteria for overt hematologic malignancy. Diagnosis may be challenging when immune deposits are masked on routine immunofluorescence. We report a 63-year-old woman with hypertension, chronic kidney disease, peripheral neuropathy, venous thromboembolism, and progressive proteinuria who underwent kidney biopsy for worsening urinary abnormalities. Routine immunofluorescence on frozen tissue was negative; however, repeat immunofluorescence on protease-digested paraffin-embedded tissue demonstrated focal and segmental granular staining for IgG and kappa light chain with essentially negative lambda staining, consistent with proliferative glomerulonephritis with masked IgG-kappa dominant deposits. Congo red stain was negative. Bone marrow biopsy subsequently showed approximately 8% plasma cells with an abnormal kappa-excess plasma cell population, and serum immunofixation identified IgG-kappa monoclonal protein, supporting MGRS. Due to baseline peripheral neuropathy, bortezomib-based therapy was deferred, and the patient was treated with daratumumab, lenalidomide, and dexamethasone. Kidney function remained preserved, and proteinuria improved markedly from nephrotic-range level of 8.5–0.22 g/g. This case highlights the diagnostic importance of paraffin immunofluorescence when MGRS is suspected despite negative routine studies and illustrates that early clone-directed therapy can produce substantial renal response in masked monoclonal proliferative glomerulonephritis.

Abstract Background Immune checkpoint inhibitors (ICIs) directed against PD-1, PD-L1, and CTLA-4 augment antitumor immune responses but may also induce unintended immune activation, resulting in immune-related adverse events (irAEs). Cutaneous manifestations of irAEs are among the most common, ranging from mild eruptions to severe autoimmune blistering disorders (AIBDs). Although bullous pemphigoid (BP) is the most reported ICI-related autoimmune bullous disorder (irAIBD), data on the spectrum, and management of other ICI-associated AIBDs remain limited. Understanding these reactions is crucial to managing treatment interruptions and influencing oncologic outcomes. Objective This study aims to comprehensively characterize ICI-associated irAIBDs by examining demographics, clinical presentation, disease severity, therapeutic approaches, treatment responses, clinical outcomes, and mortality. Methods A single-institution retrospective chart review was conducted, using a text-based database search from 2011–2023. Adult patients (≥18 years) with biopsy-confirmed AIBDs attributed to ICIs were included. Demographic, oncologic, and immunotherapy details, as well as clinical, histopathologic, and immunofluorescence characteristics of AIBDs, were reviewed. Treatment approaches, outcomes, and mortality data were analyzed. Results Forty-four patients with irAIBDs were identified, predominantly representing males (29, 65.9%) with a mean age of 70.4 years (range: 62-80 years). Lung carcinoma (12, 27.2%) and melanoma (9, 20.4%) were the most frequent underlying malignancies, and pembrolizumab (25, 56.8%) was the most common agent. Bullous pemphigoid (BP) accounted for most cases (36, 81.8%), followed by lichen planus pemphigoides (LPP) (6, 13.6%), with one case each of mucous membrane pemphigoid (MMP) and linear IgA bullous dermatosis (LABD). Pruritus was reported in most (42, 9%) patients, and upper (36, 81.8%), lower (32, 72.2%) extremities and the chest (34, 77.2%) were most often involved. Eosinophilic infiltration was present in most (23, 81.8%) of BP cases, and linear IgG and C3 deposition were the predominant immunofluorescence patterns in BP. Most patients received topical (34, 77.2%) and/or systemic corticosteroids (32, 72.7%), while 16 required at least temporary ICI discontinuation. Four BP (4, 9.1%) patients were treated with dupilumab. Other systemic agents used included doxycycline (22, 50%), intravenous immunoglobulin (IVIG) (5, 11.3%), rituximab (6, 13.6%), dapsone (1, 2.2%), mycophenolate mofetil (1, 2.2%), methotrexate (1, 2.2%), and colchicine (1, 2.2%). Three cases with Grade 3 severity necessitated permanent ICI discontinuation. Clinical stabilization (24, 54.5%) or remission of the irAIBD (16, 36.3%) was achieved in most cases. One death (2.2%) was attributed to sepsis in a patient with severe irAIBD. Conclusion ICI-associated AIBDs are uncommon but clinically significant complications. Most patients in our cohort continued ICI therapy during management of their irAIBD, while others required temporary or permanent interruption. These findings highlight the importance of prompt recognition and multidisciplinary management of these uncommon toxicities.

Purpose To determine the incidence of cystoid macular edema (CME) within the first 6 months after endothelial keratoplasty (EK) in eyes that had previously undergone vitrectomy versus those without prior vitrectomy. Design Retrospective cohort study. Methods A retrospective cohort analysis of the TriNetX database was performed by querying all patients who underwent EK (Descemet stripping automated endothelial keratoplasty or Descemet membrane endothelial keratoplasty) with ≥ 6 months of follow-up between January 1, 2004, and August 30, 2024. Patients with a previous history of diabetic macular edema, uveitis, or retinal vascular occlusion were excluded. Cohorts were stratified based on a history of prior vitrectomy. Propensity score matching (PSM) between cohorts was conducted for age at index, sex, race, ethnicity, and diagnosis of Fuchs endothelial dystrophy. The outcome assessed was the incidence of postoperative CME within 6 months after EK in both groups. Odds ratios were calculated between cohorts. Results The final analysis included 1044 patients, divided into those with (n = 522) and without (n = 522) prior vitrectomy before EK. Patients who had undergone vitrectomy prior to EK were found to develop postoperative CME within 6 months at a significantly higher rate (32 of 522) compared to those who had not undergone vitrectomy (17 of 522) (P = 0.0282; OR 1.94, 95% CI 1.063–3.539). Conclusion Prior vitrectomy appears to be associated with a greater incidence of postoperative CME after EK.

Importance The development of artificial intelligence (AI) models for atherosclerotic cardiovascular disease (ASCVD) risk prediction has rapidly accelerated. However, despite reports of high predictive accuracy, evidence supporting clinical implementation remains limited. Objective This study aimed to evaluate the methodological rigor of AI-based ASCVD prediction models and assess whether reported algorithmic discrimination is associated with prespecified reporting and translational-evidence gaps. Data sources and study selection A systematic search of PubMed, Embase, Web of Science, Scopus, and Cochrane CENTRAL was conducted for original studies published between 1 January 2020 and 27 March 2026. Studies reporting the development or validation of AI and machine learning prognostic models for adult ASCVD outcomes were included. Data extraction and synthesis Following the PRISMA guidelines, a structured methodological audit was performed. Five binary reporting and translational-evidence gaps were independently extracted: absent calibration assessment, lack of external validation, absent decision-analytic utility evaluation, undefined temporal prediction horizons, and lack of reproducibility or accessibility artifacts. A prespecified minimum evidence proxy for translational evaluation was defined. Main outcomes and measures The primary outcomes were the cumulative methodological gap burden (range, 0–5) and its association with the primary discrimination metric (area under the receiver operating characteristic curve [AUC] or C-index). Results Among 101 primary models evaluated, the median discrimination performance was 0.790 (IQR, 0.734–0.833). However, a substantial cumulative gap burden was observed, with only 6.9% of the models meeting the prespecified translational-readiness proxy. Reported discrimination was not associated with methodological completeness; top-quartile models (AUC ≥ 0.833) exhibited high gap burdens at rates comparable to lower-performing models. Reporting and translational-evidence gaps systematically co-occurred, predominantly driven by the simultaneous absence of external validation, calibration assessment, and reproducibility or accessibility artifacts. The use of advanced algorithmic architectures (e.g., deep learning) and multimodal data integration did not independently reduce the reporting gap burden. Conclusion and relevance In AI-based ASCVD risk prediction, reported algorithmic discrimination is a poor surrogate for clinical readiness. The literature features models with high discrimination but critical methodological deficits. These findings suggest that evaluation frameworks should consider incorporating calibration, external validation, and formal decision-analytic utility assessment alongside discrimination metrics.

Objective Hospitalization, particularly for surgery, represents a period of heightened stress. We evaluated how frailty attenuates the association of rheumatoid arthritis (RA) with negative health outcomes after elective noncardiac surgery. Methods We conducted a cross‐sectional study using the National Inpatient Sample (2018 to 2020), including adults (aged ≥18 years) with elective hospitalizations with noncardiac surgery. Frailty was measured using the Hospital Frailty Risk Score (HFRS). Surgeries were categorized by risk level. Outcomes included discharge health resources need (DHRN), composite adverse clinical events (CACE), and death. Results Among 8,800,359 hospitalizations (2.14% among patients with RA), 73.36% underwent intermediate‐risk surgery and 62.25% had HFRS above 0. DHRN occurred in 28.9%, CACE occurred in 0.93%, and all‐cause mortality occurred in 0.17%. A 10‐point increase in HFRS was associated with a 3.8‐fold increased DHRN, 8.5‐fold increased CACE, and 22.8‐fold increased mortality. RA was not independently associated with CACE (adjusted odds ratio [aOR] 0.91; 95% confidence interval [CI] 0.82–1.01; P = 0.08) or death (aOR 0.90; 95% CI 0.71–1.15; P = 0.41) but was significantly associated with DHRN (aOR 1.28, 95% CI 1.25–1.31; P < 0.001) after adjusting for confounders and frailty. In sensitivity analysis, RA had 10% higher relative odds of DHRN following orthopedic (aOR 1.10; 95% CI 1.07–1.13; P < 0.001) but not nonorthopedic intermediate‐risk surgery (aOR 1.10; 95% CI 0.98–1.23; P = 0.11). Conclusion RA was associated with higher odds of DHRN after orthopedic intermediate‐risk surgery but not CACE or inpatient mortality. Moreover, HFRS was associated with DHRN, CACE, and death. These findings underscore the need for disease‐specific clinical considerations and highlight the potential utility of HFRS in discharge planning.