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Donor-specific HLA antibodies (DSAs) are well-established mediators of antibody-mediated rejection (AMR), but growing evidence suggests that non-HLA antibodies may also contribute to kidney allograft dysfunction. However, the clinical utility of non-HLA antibody testing remains limited due to assay variability and undefined pathogenic thresholds. In this longitudinal study, we evaluated 167 deceased-donor kidney transplant recipients at UCSF using a multiplex Luminex assay to quantify IgG reactivity against 88 non-HLA antigens in paired pre- and post-transplant serum samples (n = 334). Patients were stratified by HLA-DSA status and graft outcome. The non-HLA panel reactive antibody (PRA) percentage was defined as the proportion of positive beads among the 88 tested antigens. Global non-HLA PRA declined significantly from pre- to post-transplant (9% to 6%; = 0.0010) only among recipients with functioning grafts, driven by reduced reactivity to signaling, cytoskeletal, and immune-related antigens. Elevated pre-transplant non-HLA PRA was associated with prior sensitization, IgA nephropathy, and African American ancestry, but was independent of age, ABO type, and HLA cPRA. AMR occurred primarily in recipients with both preformed and DSA, while no rejection was observed in DSA-negative recipients. Death-censored graft survival varied across groups, and neither preformed nor DSA consistently predicted outcomes. These findings suggest that longitudinal trajectories of non-HLA PRA, rather than staticmeasurements or DSA status alone, may influence graft loss. The dynamic nature of non-HLA antibody responses and supports integration of non-HLA antibody profiling into longitudinal immune monitoring frameworks. Larger multicenter studies are needed to define clinically meaningful threshold and estabilish the utility of non-HLA PRA testing across diverse transplant populations.

Conversion of glass slides to digital images is necessary to capitalize on advances in computational pathology and could potentially transform our approach to primary diagnosis, research, and medical education. Most slide scanners have a limited maximum scannable area and utilize proprietary tissue detection algorithms to selectively scan regions that contain tissue, allowing for increased scanning speed and reduced file size compared to scanning the entire slide at high resolution. However, very small and faintly stained tissue fragments may not be recognized by these algorithms, leading to loss of fidelity in the digital image compared to the glass slides. Cavitron ultrasonic surgical aspirator (CUSA) is frequently used in brain tumor resections, resulting in highly fragmented specimens that are used for primary diagnosis. Here we evaluated the rate of loss of fidelity in 296 digital images from 40 CUSA‐resected brain tumors scanned using a Philips Ultra Fast Scanner. Overall, 54% of the slides (at least one from every case) showed loss of fidelity, with at least one tissue fragment not scanned at high resolution. The majority of the missed tissue fragments were small (<0.5 mm), but rare slides were missing fragments greater than 5 mm in greatest dimension. In addition, 19% of the slides with missing tissue showed no indication of loss of fidelity in the digital image itself; the missing tissue could only be appreciated upon review of the glass slides. These results highlight a potential liability in the use of digital images for primary diagnosis in CUSA‐resected brain tumor specimens. Loss of fidelity in scanned whole‐slide images (WSI) is frequent for brain tumors resected using the cavitron ultrasonic surgical aspirator (CUSA), and cannot always be appreciated without review of the glass slide.

Instrumental work diagnostic examinations can be used for capability assessment in evaluating work suitability, job selection, complex and occupational rehabilitation, and career counselling. According to the literature, assessments performed with work simulators and the International Classification of Functioning, Disability and Health (ICF) are suitable for monitoring changes in functional capacity. We propose that instrumental work diagnostic measurements - specifically, measurements conducted on the ErgoScope work simulator - along with the ICF, can be effectively used for the objective assessment of functional capacity and tracking changes over time. At the request of an insurance company, a targeted examination was performed using the ErgoScope work simulator to determine the extent of force exertion. The measurement plan, evaluation of results, and ICF coding were prepared based on a methodology developed in our previous research with qualified assessors. The measurement results were recorded in an examination report. The examined individual was able to complete all tasks. If there was a difference in exertion between the two hands, the right hand/arm was always weaker. Based on our experience, determining ICF qualifiers requires not only measurement data but also precise, documented observations from the examiner. Our study suggests that the measurement results obtained from ErgoScope work simulator examinations, along with ICF categories assigned by qualified assessors, are suitable for tracking changes in functional capacity. This methodology supports medical professionals in insurance medicine and occupational health services in making objective, data-driven decisions.

BackgroundProliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain–restricted immunoglobulin and is rarely reported in children.MethodsWe characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition.ResultsEach patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-λ, two showed IgG3-κ, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course.ConclusionsOur study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID.

An impairment of an endothelial anticoagulation pathway in severe meningococcal disease. Neisseria meningitidis is the leading infectious cause of death in children in developed countries and is a cause of disability resulting from extensive skin damage and loss of limbs. 1 , 2 Severe meningococcal sepsis is characterized by marked inflammatory-cell activation, disseminated intravascular coagulation, and vascular compromise. 3 – 5 As compared with other forms of septic shock, the coagulopathy and microvascular thrombosis that develop in this type of sepsis are particularly severe. Purpura fulminans occurs in 10 to 20 percent of cases 6 , 7 and in severe cases involves thrombosis of the large vessels with infarction of the digits and limbs. 6 , 8 This disorder . . .

Coronary atherosclerosis with occlusive thrombosis is the major cause of acute myocardial infarction. Although plaque rupture is usually hypothesized to be the predisposing event in coronary thrombosis, the possibility cannot be excluded that local changes in the anticoagulant properties of the endothelium overlying the plaque contribute to this process. It is evident that thrombomodulin and the endothelial cell protein C receptor are critical players in the control of the thrombogenic process. This study examined whether thrombomodulin and the endothelial cell protein C receptor are down-regulated on endothelial cells overlying the atherosclerotic plaque in coronary arteries and thus could potentially favor local thrombus formation. Sections of archival left and right coronary arteries ( n = 18 each) with severe atherosclerosis from the native heart of six patients who underwent heart transplantation were immunostained for CD31, CD34, endothelial cell protein C receptor, and thrombomodulin using a streptavidin-biotin-peroxidase method. Controls included left and right coronary arteries from autopsy cases with no atherosclerosis ( n = 6), and also from cases with mild atherosclerosis ( n = 5). The apparent density of all of these proteins was much higher in control than in atherosclerotic arteries. Our findings support the hypothesis that both endothelial cell protein C receptor and thrombomodulin are down-regulated in coronary arteries with atherosclerosis. These changes would be expected to result in reduced inhibition of thrombogenic and anti-inflammatory activity on the endothelium overlying atherosclerotic regions and thus could contribute to coronary thrombosis.

There is an urgent need to develop and implement low cost, high-throughput standardized methods for routine molecular assessment of transplant biopsies. Given the vast archive of formalin-fixed and paraffin-embedded (FFPE) tissue blocks in transplant centers, a reliable protocol for utilizing this tissue bank for clinical validation of target molecules as predictors of graft outcome over time, would be of great value. We designed and optimized assays to quantify 19 target genes, including previously reported set of tissue common rejection module (tCRM) genes. We interrogated their performance for their clinical utility for detection of graft rejection and inflammation by analyzing gene expression microarrays analysis of 163 renal allograft biopsies, and subsequently validated in 40 independent FFPE archived kidney transplant biopsies at a single center. A QPCR (Fluidigm) and a barcoded oligo-based (NanoString) gene expression platform were compared for evaluation of amplification of gene expression signal for 19 genes from degraded RNA extracted from FFPE biopsy sections by a set protocol. Increased expression of the selected 19 genes, that reflect a combination of specific cellular infiltrates (8/19 genes) and a graft inflammation score (11/19 genes which computes the tCRM score allowed for segregation of kidney transplant biopsies with stable allograft function and normal histology from those with histologically confirmed acute rejection (AR; = 0.0022, QPCR; = 0.0036, barcoded assay) and many cases of histological borderline inflammation (BL). Serial biopsy shaves used for gene expression were also processed for hybridization (ISH) for a subset of genes. ISH confirmed a high degree of correlation of signal amplification and tissue localization. Target gene expression amplification across a custom set of genes can identify AR independent of histology, and quantify inflammation from archival kidney transplant biopsy tissue, providing a new tool for clinical correlation and outcome analysis of kidney allografts, without the need for prospective kidney biopsy biobanking efforts.

We present here the case of a 39-year-old man with metastatic pancreatic carcinoma receiving chemotherapy with the combination of gemcitabine and nab-paclitaxel as part of a clinical trial. Despite an impressive response to therapy, he ultimately developed profound anasarca, renal insufficiency, progressive cytopenias, and malignant hypertension 6 months into his treatment course. The diagnosis of gemcitabine-associated thrombotic microangiopathy (G-TMA) was made based on renal biopsy, and receipt of the anti-C5 monoclonal antibody eculizumab proved successful at reversing his deteriorating clinical course and improving his laboratory parameters. This case illustrates the importance of recognizing this rare but serious complication, and highlights one potential therapeutic option that can be used in the appropriate clinical context.

Examining possible psychosocial maladjustments should be an integral part of fertility care. For the early detection of vulnerability, the present study aimed to adapt and test the reliability and validity of the Hungarian version of SCREENIVF against the Fertility Quality of Life Questionnaire (FertiQoL) in a cross-sectional on subfertile women (n = 60, age 34.6 ± 5.2 years, BMI 24.2 ± 4.9 kg/m2) at a university linked fertility clinic in South-Hungary. A confirmatory factor analysis (CFA) was conducted to investigate the construct validity. For the reliability testing, Cronbach alpha values were calculated. Spearman’s rank correlation tested the criterion validity. Discriminant validity was applied using Mann–Whitney U-test and Kruskal–Wallis test. The Edinburgh Framework and COSMIN checklist were applicable for the analysis using SPSS 27.0; significance was set at p < 0.05. The confirmatory factor analysis indicated a good fit; all dimensions were reliable (α ≥ 0.70). Cronbach’s alpha was excellent (0.825–0.904). Strong correlations were found between the total scale (FertiQoL) and anxiety (R = −0.507, p < 0.001), depression (R = 0.554, p < 0.001), and helplessness cognitions (R = −0.747, p < 0.001) and moderate or no correlation with acceptance cognitions (R = 0.317, p = 0.015) and social support (R = 0.230, p = 0.082). The Hungarian version of SCREENIVF proved a valid and reliable tool to measure psychological maladjustment before ART. A longitudinal, randomized, controlled trial involving the partners could further strengthen the results, which is among our long-term plans.

The study aimed at a quantitative evaluation of macular vasculature after primary repair of rhegmatogenous retinal detachment (RRD) in correlation with the elapsed postoperative time. Optical coherence tomography angiography (OCT-A) was performed in 66 eyes of 33 patients in a retrospective case-control study: superficial and deep retinal vessel density (VD) of the whole image, fovea, parafovea, non-flow area, and foveal avascular zone (FAZ) were measured. Data of eyes with RRD were compared to the healthy fellow eyes in 3 groups according to the elapsed time after surgery: RD1: 6–12 months (n = 10), RD2: 1–2 years (n = 10), and RD3: 2–10 years (n = 13). In RD1 VD was significantly lower in the superficial parafoveal, deep parafoveal, and deep whole area compared to the fellow eyes. In RD3 VD was significantly lower in the superficial fovea, parafovea, whole image, and deep fovea, the non-flow area was significantly enlarged. OCT-A demonstrated a significant reduction in the superficial and deep regions of the macular vasculature after the repair of RRD. The deep area is more affected in the early postoperative period and the superficial region and the extent of the non-flow area are more involved after a longer postoperative time.