The Effect of Time Pressure on Motion Economy and Smoothness of Interventional Radiology Trainee Performance in Simulated Central Venous Line Placement.

PURPOSE: To evaluate the effect of being under time pressure on procedural performance using hand motion analysis. MATERIALS AND METHODS: Eight radiology trainees performed central venous access on a phantom while recording video and hand motion data using an electromagnetic motion tracker. Each trainee performed the procedure six times: the first three trials without any prompts (control), while for the next three, they were asked to perform the task as fast as possible (time pressure). Validated hand motion metrics were analyzed, and two blinded and independent evaluators rated procedural performance using a previously validated task-specific global rating scale (GRS). Motion/time ratios and linear mixed-effect methods were used to control for time, and constants for both strategies were compared. RESULTS: Hand motion analysis showed that trainees completed the simulated procedure faster under time pressure (46 ± 18 s vs. 56 ± 27 s, p = 0.008) than during the control strategy. However, when controlling for time, trainees moved their hands 79 more centimeters (p = 0.04), made 15 more translational movements (p = 0.003) and 18 more rotational movements (p = 0.01) when under time pressure compared to at their own pace. CONCLUSION: Although trainees could perform the procedure faster under time pressure, there was a deterioration in hand motion economy and smoothness. This suggests that hand motion metrics offer a more comprehensive assessment of technical performance than time alone.

A thermophysical investigation of weakly coordinated metals in ionic liquids.

Ionic liquids can solvate metals without strongly coordinating them, which gives a rare opportunity to probe the complexity of weakly coordinated metals through characterisation of liquid properties. In this work we use bis(trifluoromethanesulfonyl)imide (i.e. bistriflimide; [NTf2]-) anions to prepare weakly coordinated metal containing ionic liquids (MILs) that are highly versatile because they are reactive with readily substituted ligands. Weakly coordinated metals are more than highly active catalysts. They are primed to create dynamic systems that are useful in other areas such as battery electrolytes, soft materials, and separations. However, very little is known about the properties of ionic liquids with weakly coordinated metals, so we present a wide scope analysis of nineteen 1-alkyl-3-methylimidazolium bistriflimide ILs with five different M[NTf2] n salts (M = Li, Mg, Zn, Co, Ni) in variable concentration to understand how metal cations influence thermophysical properties. We investigate short- and long-term thermal stability, decomposition kinetics, and decomposition mechanisms which provides operating windows and knowledge on how to improve stability. In particular, we find that all metals catalyse the elimination decomposition process, which severely compromises thermal stability. Alongside this, we present a detailed analysis of viscosities, densities, and heat capacities, the latter of which revealed that bistriflimide metal ILs are prone to drawing water from the air to form strong hydration spheres. Thermal parameters are affected to varying degrees, but desorption is possible under elevated temperatures - further justifying the need to know upper temperature limits. Altogether, this work provides a broad and methodical study to help understand solvent-solute interactions and thus design better systems for emerging applications that utilise weakly coordinated metals.

Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression.

Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue. Unbiased deconvolution of the spatial data identifies the following four distinct microenvironments: glomerular, immune, tubule and fibrotic. We describe the complex organization of microenvironments in health and disease and find that the fibrotic microenvironment is able to molecularly classify human kidneys and offers an improved prognosis compared to traditional histopathology. We provide a comprehensive spatially resolved molecular roadmap of the human kidney and the fibrotic process, demonstrating the clinical utility of spatial transcriptomics.

Analyzing the Evolution of Needle and Ultrasound Probe Manipulation Skills of Interventional Radiology Trainees With Time and Experience.

PURPOSE: To test the hypothesis that hand motion analysis can measure the progression of needle and ultrasound probe manipulation skills of interventional radiology trainees in central venous line placement. MATERIALS AND METHODS: An expert cohort of 6 interventional radiologists and 4 anesthesiologists and a trainee cohort of 6 novice trainees (<50 central lines) and 5 experienced trainees (>50 central lines) performed simulated central venous access. Four novices and 1 experienced trainee repeated the task 1 year later. An electromagnetic motion tracking system tracked the needle hand and ultrasound probe. Path length, translational, and rotational movements were calculated separately for the needle hand and probe sensor. These metrics were used to calculate motion metrics based scores on a scale of 0 to 3 for each sensor. Nonparametric statistics were used, and the data are reported as median ± interquartile range. RESULTS: Comparing novice and experienced trainees, there was a significant difference in probe scores (experienced vs. novice: 1 ± 2 vs. 0 ± 0, P = 0.04) but not in needle-hand scores (1 ± 1.5 vs. 0 ± 1, P = 0.26). Trainees showed a significant increase in probe scores at the 1-year follow-up (baseline vs. follow-up: 0 ± 1 vs. 2.5 ± 1.8, P = 0.003), but no significant difference was observed in the needle manipulation metrics. Experts differed significantly from experienced trainees for all metrics for both sensors (P < 0.05), with the exception of the path length of the probe. CONCLUSIONS: Acquisition of improved dexterity of the probe may occur before improvement in the dexterity with the needle hand for interventional radiology trainees.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Effectiveness of tailored talks between a cancer screening specialist and general practitioners to improve the uptake of colorectal cancer screening in Ancona (Italy) during the pandemic period.

BACKGROUND: Colorectal cancer (CRC) screening uptake in many countries has been low and further impacted by the COVID-19 pandemic. General Practitioners (GPs) are key facilitators, however research on their impact on organised CRC screening is still limited. OBJECTIVES: To evaluate the effectiveness of tailored talks with GPs to increase population uptake of the long-established CRC screening programme in Ancona province, Italy. METHODS: In this prospective cohort study, one-to-one tailored talks were organised in January 2020 between the GPs of one county of the province (with GPs from other counties as controls) and the screening programme physician-in-chief to discuss the deployment and effectiveness of organised screening. Data was extracted from the National Healthcare System datasets and linear regression was used to assess the potential predictors of CRC screening uptake. RESULTS: The mean CRC screening uptake remained stable from 39.9% in 2018-19 to 40.8% in 2020-21 in the 22 GPs of the intervention county, whereas it statistically significantly decreased from 38.7% to 34.7% in the 232 control GPs. In multivariate analyses, belonging to the intervention county was associated with an improved uptake compared to the control counties (+5.1%; 95% Confidence Intervals - CI: 2.0%; 8.1%). CONCLUSION: Persons cared for by GPs who received a tailored talk with a cancer screening specialist avoided a drop in CRC screening adherence, which characterised all other Italian screening programmes during the COVID-19 emergency. If future randomised trials confirm the impact of tailored talks, they may be incorporated into existing strategies to improve population CRC screening uptake.

Tailored talks on CRC screening were conducted between one cancer screening specialist and GPs.Even during the pandemic, CRC screening uptake was stable among persons cared for by GPs targeted by tailored talks.If confirmed by randomised trials, tailored talks may be employed to improve CRC screening uptake.

The effects of non-diagnostic information on confidence and decision making.

Many decision-making tasks are characterized by a combination of diagnostic and non-diagnostic information, yet models of responding and confidence almost exclusively focus on the contribution of diagnostic information (e.g., evidence associated with stimulus discriminability), largely ignoring the contribution of non-diagnostic information. An exception is Baranski and Petrusic's Journal of Experimental Psychology: Human Perception and Performance, 24(3), 929-945, (1998) doubt-scaling model, which predicts a negative relationship between non-diagnostic information and confidence, and between non-diagnostic information and accuracy. In two perceptual-choice tasks, we tested the effects of manipulating non-diagnostic information on confidence, accuracy and response time (RT). In Experiment 1, participants viewed a dynamic grid consisting of flashing blue, orange and white pixels and indicated whether the stimulus was predominantly blue or orange (using a response scale ranging from low-confidence blue to high-confidence orange), with the white pixels constituting non-diagnostic information. Increasing non-diagnostic information reduced both confidence and accuracy, generally slowed RTs, and led to an increase in the speed of errors. Experiment 2 replicated these results for a decision-only task, providing further support for the doubt-scaling model of confidence.

L1 Cell Adhesion Molecule (L1CAM) Expression and Molecular Alterations Distinguish Low-Grade Oncocytic Tumor From Eosinophilic Chromophobe Renal Cell Carcinoma.

Renal low-grade oncocytic tumor (LOT) is a recently recognized renal cell neoplasm designated within the "other oncocytic tumors" category in the 2022 World Health Organization classification system. Although the clinicopathologic, immunohistochemical, and molecular features reported for LOT have been largely consistent, the data are relatively limited. The morphologic overlap between LOT and other low-grade oncocytic neoplasms, particularly eosinophilic chromophobe renal cell carcinoma (E-chRCC), remains a controversial area in renal tumor classification. To address this uncertainty, we characterized and compared large cohorts of LOT (n = 67) and E-chRCC (n = 69) and revealed notable differences between the 2 entities. Clinically, LOT predominantly affected women, whereas E-chRCC showed a male predilection. Histologically, although almost all LOTs were dominated by a small-nested pattern, E-chRCC mainly showed solid and tubular architectures. Molecular analysis revealed that 87% of LOT cases harbored mutations in the tuberous sclerosis complex (TSC)-mTOR complex 1 (mTORC1) pathway, most frequently in MTOR and RHEB genes; a subset of LOT cases had chromosomal 7 and 19q gains. In contrast, E-chRCC lacked mTORC1 mutations, and 60% of cases displayed chromosomal losses characteristic of chRCC. We also explored the cell of origin for LOT and identified L1 cell adhesion molecule (L1CAM), a collecting duct and connecting tubule principal cell marker, as a highly sensitive and specific ancillary test for differentiating LOT from E-chRCC. This distinctive L1CAM immunohistochemical labeling suggests the principal cells as the cell of origin for LOT, unlike the intercalated cell origin of E-chRCC and oncocytoma. The ultrastructural analysis of LOT showed normal-appearing mitochondria and intracytoplasmic lumina with microvilli, different from what has been described for chRCC. Our study further supports LOT as a unique entity with a benign clinical course. Based on the likely cell of origin and its clinicopathologic characteristics, we propose that changing the nomenclature of LOT to "Oncocytic Principal Cell Adenoma of the Kidney" may be a better way to define and describe this entity.

Dancers Show More Accurate Trunk-Pelvic Joint Angle Reproduction While Wearing a Jacket Augmented With Elastic Bands.

Purpose: The Backalast® compression jacket is intended to improve posture and proprioception of the trunk and shoulder girdle for dancers and dance students during dance training by way of elastic bands in the rear of the garment (which include bands enclosing the inferior thorax). This study was intended to investigate whether there is evidence to support those objectives. Materials and Methods: Fifteen dance students participated (4 male, mean age 19.9 ± 1.4 years old). The dependent variables of trunk-pelvis angle and proximity of trunk axis to global vertical for each participant were measured using optical motion capture before and after the completion of a series of trunk movements. The Helen Hayes model, which we used to represent the trunk, includes the shoulder girdles as part of the trunk. We compared the effect of the type of garment (Backalast® or control compression shirt) worn upon the 2 dependent variables, within-subject with paired t-tests. The order of whether Backalast® or control compression shirt was worn first was alternated between participants. Results: The pre/posttest difference in trunk proprioception as represented by the construct of ability to reproduce trunk-pelvis angle wearing the Backalast® was 0.8° ± 0.8°, but for the control shirt, the difference was 1.8° ± 1.4°, P = .03. The difference between garments in vertical trunk alignment, measured after the series of trunk movements, was not significant. Conclusion: Our findings suggest that the Backalast® can help enhance trunk proprioception when compared to the control compression shirt, although it did not change the angle at which the participants' held their trunks while standing erect (proximity to global vertical).

The impact of alternate HPV vaccination and cervical screening strategies in Japan: a cost-effectiveness analysis.

Background: The Japanese 2020 cervical screening guidelines recommend conventional cervical cytology screening every 2-years for women aged 20-69 years. The nonavalent human papillomavirus (HPV) vaccine has also recently been approved in Japan. We therefore evaluated the cost-effectiveness of cervical cancer screening strategies alongside universal nonavalent HPV vaccination of girls (12-16 years). Methods: A cost-effectiveness analysis was performed using an age-specific Markov microsimulation model for Japan to evaluate total costs, quality adjusted life-years (QALYs) gained, incremental cost-effectiveness ratios (ICER), colposcopies, biopsies, precancer and cervical cancer treatments for 29 combined vaccination and screening strategies (conventional cytology, liquid-based cytology (LBC), HPV testing, and HPV self-collection). A cohort of 100,000 girls (12-16 years old) over a lifetime offered the nonavalent HPV vaccine was used (current vaccination coverage = 0.08%, current screening coverage = 43.7%). A discount rate of 3% was applied to costs and QALYs. Univariate and probabilistic sensitivity analysis was performed to assess robustness of the findings. Costs were reported in US dollars (2023). Findings: Compared with conventional cytology, evaluated strategies would incur an additional cost of US$839,280-738,182,669 and gain 62,755-247,347 quality-adjusted-life-years. HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be most cost-effective (ICER = US$7511 per QALY gained). At a willingness-to-pay (WTP) of 1-times gross domestic product (GDP) per capita, the probability of it being cost-effective was 70%. At historically high vaccination coverage (70%) ICERs decreased overall but did not affect the ranking of the most cost-effective strategy. While a 5-yearly interval became more cost-effective than a 3-yearly interval. Including HPV self-collection for under-screened women made all strategies more cost-effective. Interpretation: At current cervical screening participation (43.7%) and low vaccination coverage (<1.0%), HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be the most cost-effective screening strategy compared to conventional cytology (2-yearly). Funding: Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17H03589) and Grants of the National Cancer Center Japan (Gan Kenkyu Kaihatsuhi 31-A-20 and 2023-A-23).

Clinicopathologic Features of Antibrush Border Antibody Disease.

Introduction: Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management. Methods: We identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2, CUBN, and AMN. Follow-up data, including treatment(s), laboratory values, and outcomes, were available from 51 patients. Results: Patients with ABBA were predominantly male with a median age of 72 years. Median serum creatinine was 2.7 mg/dl, proteinuria was 2.8 g/day, and hematuria was present in two-thirds of the patients. Tubular injury with LRP2-positive tubular basement membrane (TBM) deposits were seen in 94.2% of patients. Thirty-eight patients (56.7%) had a second kidney disease, commonly glomerular diseases with high-grade proteinuria. These diseases included podocytopathies, membranous nephropathy (MN), IgA nephropathy, diabetic glomerulopathy, lupus nephritis (LN), crescentic glomerulonephritis (GN), tubulointerstitial nephritis, and involvement by lymphoma. The majority of patients were treated with immunosuppression. Of those patients with follow-up, 29.4% achieved remission, 70.6% had no response, and 52.8% required dialysis or were deceased. Untreated patients were at the highest risk. Conclusion: ABBA is a rare autoimmune kidney disease that often occurs with other kidney diseases. Although the overall prognosis of ABBA is poor, there is potential benefit from immunosuppression.

Unraveling the epigenetic code: human kidney DNA methylation and chromatin dynamics in renal disease development.

Epigenetic changes may fill a critical gap in our understanding of kidney disease development, as they not only reflect metabolic changes but are also preserved and transmitted during cell division. We conducted a genome-wide cytosine methylation analysis of 399 human kidney samples, along with single-nuclear open chromatin analysis on over 60,000 cells from 14 subjects, including controls, and diabetes and hypertension attributed chronic kidney disease (CKD) patients. We identified and validated differentially methylated positions associated with disease states, and discovered that nearly 30% of these alterations were influenced by underlying genetic variations, including variants known to be associated with kidney disease in genome-wide association studies. We also identified regions showing both methylation and open chromatin changes. These changes in methylation and open chromatin significantly associated gene expression changes, most notably those playing role in metabolism and expressed in proximal tubules. Our study further demonstrated that methylation risk scores (MRS) can improve disease state annotation and prediction of kidney disease development. Collectively, our results suggest a causal relationship between epigenetic changes and kidney disease pathogenesis, thereby providing potential pathways for the development of novel risk stratification methods.

Greater target or lure variability? An exploration on the effects of stimulus types and memory paradigms.

In recognition memory, the variance of the target distribution is almost universally found to be greater than that of the lure distribution. However, these estimates commonly come from long-term memory paradigms where words are used as stimuli. Two exceptions to this rule have found evidence for greater lure variability: a short-term memory task (Yotsumoto et al., Memory & Cognition, 36, 282-294 2008) and in an eyewitness memory paradigm (Wixted et al., Cognitive Psychology, 105, 81-114 2018). In the present work, we conducted a series of recognition memory experiments using different stimulus (faces vs. words) along with different paradigms (long-term vs. short-term paradigms) to evaluate whether either of these conditions would result in greater variability in lure items. Greater target variability was observed across stimulus types and memory paradigms. This suggests that factors other than stimuli and retention interval might be responsible for cases where variability is less for targets than lures.

Strategic Operational Redesign Improves Prior Authorization Access: A Validation Study.

Purpose: Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. We ask whether such a redesign may be replicable and adoptable across oncology centers. Materials and Methods: Our PA redesign strategy was based on a 3-tiered approach. Specifically, we (1) held payors accountable to legally backed timelines, (2) leveraged expertise on insurance policies and practices, and (3) updated the submission, appeal writing, and planning procedures for PA. Metrics were compared at the following 3 time points: 6 months before, at phase-in, and at 6 months after intervention. Results: In analyzing the impact of improving PA access to care, the percentage of approvals for commercial proton beam therapy improved by an absolute 30.6% postintervention (P < .001). The proportion of commercially insured patients treated with proton beam therapy also increased by 6.2%, and the number of new starts rose by 11.7 patients/mo. Overall patient census increased by 13 patients/d. Median authorization time was 1 week, and 90% of surveyed providers reported reduced PA burden and improved patient care. Conclusion: This is the first validated, comprehensive operational strategy to improve access to cancer therapy while reducing the burden of PA. This novel approach may be helpful for addressing barriers to PA in medical and surgical oncology because the redesign is predicated on laws that regulate PA across disciplines.

Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations.

Introduction: Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility, and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial, and vascular lesions evaluated semiquantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet's agreement coefficient (AC)1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (134 MCD, 194 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6-0.8) reproducibility. Mesangial hypercellularity scored as absent, focal, or diffuse had moderate reproducibility (AC1 = 0.58), but good reproducibility (AC1 = 0.71) when scored as absent or focal versus diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1 = 0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis, and tubular atrophy with estimated glomerular filtration rate, foot process effacement with urine protein/creatinine ratio, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery.

CureGN-Diabetes Study: Rationale, Design, and Methods of a Prospective Observational Study of Glomerular Disease Patients with Diabetes.

Glomerular diseases (GDs) represent the third leading cause of end-stage kidney disease (ESKD) in the US Diabetes was excluded from the CureGN Study, an NIH/NIDDK-sponsored observational cohort study of four leading primary GDs: IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). CureGN-Diabetes, an ancillary study to CureGN, seeks to understand how diabetes influences the diagnosis, treatment, and outcomes of GD. It is a multicenter, prospective cohort study, targeting an enrollment of 300 adults with prevalent type 1 or type 2 diabetes and MCD, FSGS, MN, or IgAN, with first kidney biopsy obtained within 5 years of enrollment in 80% (20% allowed if biopsy after 2010). CureGN and Transformative Research in DiabEtic NephropaThy (TRIDENT) provide comparator cohorts. Retrospective and prospective clinical data and patient-reported outcomes are obtained. Blood and urine specimens are collected at study visits annually. Kidney biopsy reports and digital images are obtained, and standardized pathologic evaluations performed. Light microscopy images are uploaded to the NIH pathology repository. Outcomes include relapse and remission rates, changes in proteinuria and estimated glomerular filtration rate, infections, cardiovascular events, malignancy, ESKD, and death. Multiple analytical approaches will be used leveraging the baseline and longitudinal data to compare disease presentation and progression across subgroups of interest. With 300 patients and an average of 3 years of follow-up, the study has 80% power to detect a HR of 1.4-1.8 for time to complete remission of proteinuria, a rate ratio for hospitalizations of 1.18-1.56 and difference in eGFR slope of 6.0-8.6 mL/min/year between two groups of 300 participants each. CureGN-Diabetes will enhance our understanding of diabetes as a modifying factor of the pathology and outcomes of GDs and support studies to identify disease mechanisms and improve patient outcomes in this understudied patient population.

Dupilumab-Associated Sweet Syndrome.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is characterized by the abrupt appearance of edematous and erythematous papules, plaques, or nodules on the skin that have a distinct histopathologic appearance. Several subtypes of SS exist, including classic (also referred to as idiopathic) and drug induced. Although multiple medications have been implicated as causative agents, we present a rare case of SS caused by dupilumab, a monoclonal antibody therapy, used in the treatment of severe eosinophilic asthma and other conditions. Clinicians should be aware of this potential adverse reaction, as prompt recognition and treatment are essential.

Metastatic solid tumors to the testis: a clinicopathologic evaluation of 157 cases from an international collaboration.

To elucidate the spectrum of metastatic solid tumors to the testis and their clinicopathologic features. The databases and files of 26 pathology departments from 9 countries on 3 continents were surveyed to identify metastatic solid tumors to the testis and to characterize their clinicopathologic features in detail. We compiled a series of 157 cases of metastatic solid tumors that secondarily involved the testis. The mean patient age at diagnosis was 64 years (range, 12-93 years). Most patients (127/144; 88%) had clinical manifestation of the disease, with testicular mass/nodule (89/127; 70%) being the most common finding. The main mechanism of testicular involvement was metastasis in 154/157 (98%) cases. Bilateral testicular involvement was present in 12/157 (8%) patients. Concurrent or prior extratesticular metastases were present in 78/101 (77%) patients. The diagnosis was made mainly in orchiectomy specimens (150/157; 95%). Different types of carcinomas (138/157; 87%), most commonly adenocarcinoma (72/157; 46%), were the most common malignancies. The most common primary carcinomas included prostatic (51/149; 34%), renal (29/149; 20%), and colorectal (13/149; 9%). Intratubular growth was identified in 13/124 (11%) cases and paratesticular involvement was found in 73/152 (48%) cases. In patients with available follow-up (110/157; 70%), more than half (58/110; 53%) died of disease. In this largest series compiled to date, we found that most secondary tumors of the testis represent metastases from the genitourinary and gastrointestinal tract carcinomas and typically occur in the setting of disseminated disease.