Scanning electron microscopy and energy dispersive spectroscopy of Randall's plaque stones: an unexpected finding of monosodium urate crystals

Randall's plaques (RP) are located at the papillary tip, originating in the basement membranes of the thin loops of Henle, vasa recta and collecting ducts, and are associated with kidney stone retention. Disruption of the papillary epithelial layer exposes interstitial RP to calyceal urine, enabling calcium oxalate monohydrate (COM) overgrowth and papillary RP stone formation. This study aimed to analyze the surface and internal structures of RP stones using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Stones were collected from patients during percutaneous nephrolithotomy, ureteroscopy or both. Eighteen stones from nine patients were examined by stereoscopic microscopy, micro computed tomography (micro CT), SEM and EDS. Seven RP stones were sectioned for internal structure analysis. SEM revealed mineralized tubules potentially originating from thin loops, collecting ducts, ducts of Bellini, or vasa recta. These were frequently covered by collagen fibrils, and some were filled with dense or particulate mineral. Calcium phosphate (CaP) apatite was observed in various crystallized phases within RP regions. In three of the seven sectioned RP stones, monosodium urate monohydrate crystals were intercalated with RP, confirmed by EDS. Our multimodal imaging approach provides new insights into RP composition. This study suggests that sodium urate may precede RP formation in a subset of cases, potentially due to early, unexpected urinary pH shifts. Further studies are needed to validate this hypothesis and advance our understanding of RP stone pathophysiology, informing better diagnostic and therapeutic strategies for kidney stone disease

A matter of choice: a cross-sectional study examining the impact of the overturning of Roe v Wade on U.S. medical students' perceptions and career decisions

Background: In June 2022, the Dobbs decision by the U.S. Supreme Court overturned federal abortion protections. In states with restrictive abortion laws such as Indiana, which also has the country's largest medical school and the third worst maternal mortality rate, the impact of this ruling may have a significant impact on healthcare in the state. The purpose of this study was to analyze perceptions of medical students in Indiana in their third and fourth years of education after the Dobbs decision to assess if the state's current abortion restrictions impact their career choice. Methods: Between December 2022 and March 2023, an anonymous survey was carried out at Indiana University School of Medicine, which included questions about personal beliefs on abortion and the current abortion laws in Indiana, as well as priorities when choosing residency training and practice locations. Results: Our survey found that four-fifths of medical students in Indiana disagreed with the Dobbs decision. While most students (71.4%) had not considered state abortion laws when selecting a medical school, since the Dobbs decision, 66.3% of third-year and 40.3% of fourth-year students indicated that they would take abortion laws into account when choosing a residency program. 47.5% of women students stated that they will be seeking residency in a state where abortion is legal and 55.3% of single students were more likely to leave Indiana to practice medicine. Conclusion: Our research suggests that physicians who are more liberal in their views on abortion may now be much less likely to practice in conservative states which will compound the healthcare outcomes secondary to the Dobbs decision. We emphasize the role that abortion laws have in shaping the landscape of healthcare workforce and the need for a more nuanced understanding of how societal structures impact women's reproductive decisions and career paths in medicine

Corrigendum to “Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study” [eClinicalMedicine 73(2024) 102655]

[This corrects the article DOI: 10.1016/j.eclinm.2024.102655.]

Design and baseline characteristics of the Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) randomized trial

Background: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes in two phase 3 outcome trials. The Finerenone, in addition to standard of care, on the progression of kidney disease in patients with Non-Diabetic Chronic Kidney Disease (FIND-CKD) study investigates the effect of finerenone in adults with CKD without diabetes. Methods: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin:creatinine ratio (UACR) ≥200-≤3500 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-60 or <60 ml/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety. Results: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 ml/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%) and calcium channel blockers by 794 (50.1%). Sodium-glucose co-transporter 2 (SGLT2) inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 versus 46.8 ml/min/1.73 m2) and a slightly higher median UACR (871.9 versus 808.3 mg/g) compared with those not using SGLT2 inhibitors at baseline. Conclusions: FIND-CKD is the first phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology

Identifying anatomical subtypes of sporadic EOAD in LEADS via unsupervised clustering of MRI‐based regional atrophy patterns

Background: Neurodegeneration in sporadic early‐onset Alzheimer disease (EOAD) is topographically heterogeneous, as suggested by variability in syndromic presentation. We performed an unsupervised clustering analysis of structural MRI data to identify anatomical subtypes of EOAD. We hypothesized that distinct clusters will be present but will: (1) share areas of overlap focused around posterior regions of our newly developed EOAD signature of cortical atrophy (Touroutoglou et al., 2023), including the posterior default mode (DMN) and frontoparietal control networks (FPN) of the cerebral cortex; and (2) show non‐overlapping topography inclusive of nodes of other networks including dorsal attention (DAN) and visual association (VIS) networks. Methods: We analyzed structural MRI data from 183 individuals with EOAD and 88 cognitively unimpaired (CU) participants from the Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS). MRI data were processed using FreeSurfer v6.0 to estimate vertex‐wise cortical thickness, which was converted to W‐scores (i.e., Z‐scores relative to CU participants adjusted for age and sex). We then performed an agglomerative hierarchical clustering analysis on a between‐patients similarity matrix computed from rank‐ordered whole‐cortex W‐scores. Results: Analysis yielded 2 major clusters, with subordinate clustering failing to delineate additional unique topographies. One cluster (n=54) exhibited prominent atrophy in the anterior DMN (medial prefrontal cortex, anterior lateral temporal cortex) and rostral FPN (rostral middle and superior frontal gyri). The other cluster (n=129) showed prominent atrophy in the DAN (superior parietal lobule, caudal superior frontal gyrus, posterior temporal cortex) and VIS (posterior inferior temporal/occipital cortex, posterior parietal cortex). Both clusters showed atrophy in the posterior DMN (posterior cingulate cortex, precuneus, posterior inferior parietal lobule, mid lateral temporal cortex) and the FPN (middle and superior frontal gyri, anterior inferior parietal lobule, mid inferior temporal cortex). The clusters did not differ with respect to age, sex, education, APOE status, or clinical measures of disease severity. Conclusions: Our sample of sporadic EOAD patients comprised 2 principal anatomical subtypes, commonly overlapping with the posterior DMN and FPN that constitute the EOAD signature, one subtype uniquely overlapped with the anterior DMN/rostral FPN and the other with the DAN/VIS network. Anatomical differences between the subtypes likely correspond to aspects of phenotypic heterogeneity

Social, Demographic, and Behavioral Determinants of Prolonged Hospital Stay and Readmissions of Postoperative Complications in an Urban Acute Care Hospital

Background and Hypothesis The correlation between postoperative complications and social determinants of health (SDOH) is a prominent focus in medical literature due to its implications for healthcare quality and hospital outcomes. In evaluating hospital performance, extended hospital stays (LOS) and readmissions (RA) are critical indicators, prompting initiatives like the Hospital Readmission Reduction Program. Despite efforts, disparities affecting surgical outcomes among urban patients remain underexplored. This study aims to investigate how SDOH influence readmissions and prolonged hospital stays among urban patients experiencing postoperative complications. Conducted through a Community-Based Participatory Research (CBPR) collaboration between Indiana University School of Medicine (IUSM) and Power Health in Northwest Indiana, the research addresses gaps in understanding healthcare disparities in urban settings. Methods This retrospective study analyzed a dataset sourced from SMMC via EPIC™, focusing on SDOH, demographic profiles, health behaviors, and outcomes of adult inpatients who experienced prolonged hospital stays or 30-day readmissions after surgical procedures at an urban hospital between January 2021 and April 2024. Data analysis utilized SPSS 29.0, employing methods like frequency analysis, Chi-Square tests (p<0.05), binary logistic regression (p<0.05), and linear logistic regression (p<0.05) tailored to the study population. The study received exemption from the Indiana University Human Research Protection Program (IRB # 14040) on 1/28/2022. Results The study included data from over 900 patients, with 565 readmissions (RA) and 337 extended LOS cases, primarily adults over 50 years old (81.8% RA, 81.4% LOS), White (69.4% RA, 86.3% LOS), and publicly-insured (74.8% RA, 74.7% LOS). Bivariate analysis revealed significant associations between postoperative complications and age (p < 0.001 for RA, p < 0.011 for LOS), veteran status (p = 0.022 for RA, p = 0.058 for LOS), insurance type (p < 0.001 for RA), smoking tobacco use (p < 0.001 for RA, p = 0.026 for LOS), and BMI (p = 0.002 for RA). Multivariate analysis showed that former smoking (OR = 2.144, p < 0.001), underweight BMI (OR = 4.131, p = 0.006), and publicly-insured status (OR = 3.295, p < 0.001) remained significant across all readmission durations. Specifically for 30-day readmission, public insurance (OR = 2.844, p = 0.021) and former smoking (OR = 1.875, p = 0.037) were significant factors. Potential Impact This research highlights various SDOH and health behaviors associated with increased risks of prolonged hospital stays and readmissions following postoperative complications among urban patients. Policy interventions addressing these factors before and after surgery could potentially mitigate readmissions and extended hospital stays due to procedural complications, thereby improving healthcare outcomes and reducing disparities in urban healthcare settings.This project was funded with support from the Indiana Clinical and Translational Sciences Institute, the National Institutes of Health, Indiana University School of Medicine – Northwest as well Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $100,000. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.​

Accelerated symptom improvement in Parkinson’s disease via remote internet-based optimization of deep brain stimulation therapy: a randomized controlled multicenter trial

Background: Deep brain stimulation (DBS) has emerged as an important therapeutic intervention for neurological and neuropsychiatric disorders. After initial programming, clinicians are tasked with fine-tuning DBS parameters through repeated in-person clinic visits. We aimed to evaluate whether DBS patients achieve clinical benefit more rapidly by incorporating remote internet-based adjustment (RIBA) of stimulation parameters into the continuum of care. Methods: We conducted a randomized controlled multicenter study (ClinicalTrails.gov NCT05269862) involving patients scheduled for de novo implantation with a DBS System to treat Parkinson's Disease. Eligibility criteria included the ability to incorporate RIBA as part of routine follow-up care. Ninety-six patients were randomly assigned in a 1:1 ratio using automated allocation, blocked into groups of 4, allocation concealed, and no stratification. After surgery and initial configuration of stimulation parameters, optimization of DBS settings occurred in the clinic alone (IC) or with additional access to RIBA. The primary outcome assessed differences in the average time to achieve a one-point improvement on the Patient Global Impression of Change score between groups. Patients, caregivers, and outcome assessors were not blinded to group assignment. Most of the data collection took place in the patient's home environment. Results: Access to RIBA reduces the time to symptom improvement, with patients reporting 15.1 days faster clinical benefit (after 39.1 (SD 3.3) days in the RIBA group (n = 48) and after 54.2 (SD 3.7) days in the IC group (n = 48)). None of the reported adverse events are related to RIBA. Conclusions: This study demonstrates safety and efficacy of internet-based adjustment of DBS therapy, while providing clinical benefit earlier than in-clinic optimization of stimulation parameters by increasing patient access to therapy adjustment

Mineralized tissue loss at the femoral ACL enthesis in young male ACL‐injured patients

Purpose: Primary anterior cruciate ligament (ACL) reconstruction graft failure remains a significant health concern in young patients. Despite the high incidence of poor graft integration in these patients and the resulting high failure rate, little consideration has been given to the quality of the bone into which the graft is anchored at reconstruction. Therefore, we investigated post ACL injury mineralized tissue changes in the ACL femoral entheses of young males and compared them to changes previously reported for young females. Methods: ACL femoral entheses and adjacent bone specimens were harvested from the injured knees of 51 young males during primary ACL reconstructive surgery and from 10 non-injured male cadaveric donors. The specimens were imaged via nano-computed tomography and analyzed for volumetric bone mineral density (vBMD) and architectural changes. Results: Male femoral ACL explant specimens had significantly lower cortical vBMD (p 0.05) to those of control specimens from male cadaveric donors. Cortical and trabecular bone loss increased significantly with time from ACL injury to reconstructive surgery (p's < 0.05). While cortical loss occurred in both males and females, significant trabecular loss occurred only in females (p = 0.009). Conclusion: Femoral entheseal bone loss occurs in males following ACL injury. This bone loss increases with time following ACL injury, with cortical bone loss occurring sooner after injury than trabecular bone loss. The effects of ACL injury and time from injury to surgery on trabecular bone microarchitecture differed between male and female patients

Navigating Automated Insulin Delivery for Type 1 Diabetes Management During Pregnancy

Achieving pregnancy-specific glucose targets is difficult in pregnant individuals with type 1 diabetes (T1D), and the rates of complications for mothers and their infants remain high. Currently marketed automated insulin delivery (AID) systems are hybrid closed-loop (HCL) systems in which basal insulin delivery (with or without automated correction boluses) is driven by algorithms, and users are required to initiate meal boluses. For non-pregnant people with T1D, HCL therapy has established benefits for glycemic outcomes and quality of life. While none of the currently available HCL systems were designed for pregnancy-specific glucose targets and outcomes, preliminary data suggest that the use of HCL systems may result in improved glycemia during pregnancy. There is an accumulating body of literature examining HCL systems in pregnancy, although there are still limited data regarding the impact of HCL systems on perinatal outcomes. Many individuals conceive while using clinically available HCL systems and may be hesitant to discontinue use during pregnancy, and clinicians may consider HCL therapy for pregnant individuals who are struggling to meet recommended glycemic levels during pregnancy. We therefore offer guidance on how to counsel patients on the risks and benefits of HCL therapy in pregnancy, how to identify appropriate candidates for HCL therapy in pregnancy, and how to manage commercially available HCL systems off-label throughout gestation