Citations

ABSTRACT The purpose of this 1‐year study was to assess the effect of osteogenic loading combined with melatonin on musculoskeletal health and well‐being in a population with osteopenia. Participants were randomized into one of four groups and received mock loading plus plant fiber as placebo (ML/Placebo), mock loading plus 5 mg melatonin (ML/Melatonin), osteogenic loading plus placebo (OL/Placebo), and osteogenic loading plus 5 mg melatonin (OL/Melatonin). The loading protocol was designed to deliver multiples of body weight (MOB; 1‐2 MOB for mock loading and 1.5–4.2 MOB for osteogenic loading) to the upper body (targeting the arm, chest, and shoulders), core (targeting the spine and core stability), lower body (targeting the legs and hip) and postural (targeting the spine and posture). Following these interventions, musculoskeletal health was measured by DXA and functional testing using timed‐up‐and‐go (TUG) and sit‐to‐stand (STS) assessments. Markers of bone health (e.g., P1NP, CTX, CRP, cortisol, and melatonin) were assessed in urine collected during the night (10 pm–6 am). Mental health assessments were conducted using PSS, CES‐D, STAI and QualiOst. Time‐dependent increases in the amount of force exerted (in lbs) were observed in the OL groups for all musculoskeletal systems targeted, compared to those participants receiving ML. Over 12mos, compared to baseline, participants in the OL/Melatonin group had statistically significant increases in lumbar spine T‐scores (mean difference [MD] = 0.13, standard deviation [SD] = 0.05, p = 0.015) and BMD (MD = 0.013, SD = 0.006, p = 0.021). No other statistically significant effects were noted for T‐scores, BMD, or FRAX scores. Additionally, no significant differences were observed when T‐scores were compared between groups. Functional assessments at 12mos revealed increases in TUG times (MD = −1.7, SD = 0.3, p = 0.002) from baseline and deterioration for STS (MD = 2.8, SD = 0.59, p = 0.004) from month 03 for ML/placebo group, which did not occur for the other interventions. Correlation analysis revealed negative associations between TUG performance and CTX levels starting at 3mos in the OL/Melatonin group ( r = −0.960, p = 0.04). The change in STS repetitions over a 12‐month period (12mo–0mo) was negatively associated with the P1NP:CTX ratio ( r = −0.978, p = 0.02) and positively associated with melatonin levels in the OL/Melatonin group ( r = 0.958, p = 0.04). No changes in nocturnal output of CRP or cortisol and subject‐reported outcomes were observed for any of the interventions within and between groups. The results from this study reveal that osteogenic loading combined with melatonin may be an alternative therapeutic intervention for those with osteopenia.

Abstract Nephrotic syndrome is a rare, heterogeneous kidney disorder characterized by proteinuria, hypoalbuminemia, and edema. To elucidate its genetic architecture, we conducted a large-scale, electronic health record (EHR)-linked, multi-ancestry genome-wide association study comprising 5,214 cases and 1,601,060 controls. We identified 37 distinct loci associated with disease risk, including novel associations at JAML and STPG2 , and confirmed prior signals at PLA2R1 , HMCN1 , and APOL1 . Fine-mapping of the major histocompatibility complex (MHC) revealed the strongest association at DRB103:01:01G in individuals of European ancestry (OR = 2.01, P = 1.4×10⁻²⁰), alongside nominal ancestry-specific associations in African ( DOA01:01:05 ) and Latino ( DPB1*14:01:01G ) populations. Transcriptome-wide association analysis (TWAS) identified 484 significant gene-tissue associations, including C4A in kidney cortex. Expression quantitative trait locus (eQTL) mapping revealed numerous cis-eQTLs in glomerular and tubular renal tissues, largely within the MHC region. We observed significant genetic correlation between adult and pediatric nephrotic syndrome (Rg = 0.63, P = 3.5x10 -11 ), suggesting shared genetic etiology. Pathway analyses implicated estrogen receptor signaling and histone modification. Mendelian randomization implicated APOM expression and apomorphine exposure with increased disease risk (OR = 4.93, P = 1.8x10 -19 ). These results expand the understanding of nephrotic syndrome pathogenesis and highlight ancestry-informed targets for therapeutic development.

Abstract Background Photon counting detector CT (PCD‐CT) has the potential to sort detected x‐ray photons into more than two energy bins to perform multi‐material decomposition using K‐edge materials without additional mathematical constraints/assumptions. The availability of multiple energy thresholds in PCD‐CT opens the possibility for unique clinical applications such as simultaneous multi‐contrast‐agent imaging. Purpose To evaluate the technical performance of a PCD‐CT system with four energy thresholds for conducting multi‐material decomposition of iodine, gadolinium, and water after a comprehensive system calibration procedure. Methods Experiments were performed on a commercial PCD‐CT scanner (NAEOTOM Alpha, Siemens Healthineers) using a research mode with four energy thresholds. Material calibration was performed by scanning contrast materials with known concentration placed in various sizes of cylindrical water‐equivalent phantoms at various tube currents and positions. From these data, per‐voxel contrast models were derived for each material by multiple linear regressions up to second order, where the predictor variables were combinations of tube current, phantom diameter, and distance to isocenter. After calibration, small (20 cm diameter) and large (30 cm × 40 cm) uniform multi‐energy CT phantoms and an anthropomorphic thorax phantom (31 cm × 39 cm), each containing bone, soft tissue, and several quantitative inserts of iodine (0.2–5.0 mg/ml), gadolinium (0.3–5.0 mg/ml), and a mixture of both (5.0 mg/ml each) were scanned using the four‐energy threshold mode at 140 kV with energy thresholds set at 20, 52, 75, and 82 keV. Images for each energy threshold were reconstructed with a filtered back‐projection algorithm and a quantitative kernel (Qr44). Subsequent image‐based material decomposition was performed on individual voxels of the energy threshold images using the models derived from the calibration process to generate water, iodine, and gadolinium basis images. Quantitative material concentrations and image noise magnitudes, and noise power spectra (NPS) were measured. Results Iodine and gadolinium concentrations above 1.25 mg/ml were visible in the material basis images in all phantoms. Averaged quantitative accuracy for iodine and gadolinium in the small, large, and thorax phantoms were 0.39 ± 0.30 mg/ml, 0.96 ± 0.53 mg/ml, and 0.53 ± 0.35 mg/ml, respectively. In the water basis images, accuracy was within 24 HU in all phantoms. Noise magnitudes in iodine and gadolinium basis images were 2.91 and 3.52 times that of the lowest energy threshold image for the small phantom, and were 6.92 and 7.17 times that of the lowest threshold image for the large phantom. Noise texture did not change between the energy threshold and material basis images for either size phantom as measured by the NPS. Conclusions After a comprehensive system calibration, a commercial PCD‐CT with four energy thresholds performed multiple material decomposition of iodine, gadolinium, and water for concentrations above 1.25 mg/ml in human‐sized phantoms. Noise amplification and quantitative accuracy from the decomposition greatly depended on object size.

Background Whistal (Whipple + Distal) is a rare parenchyma-preserving technique for select patients with disease in both the pancreatic head and tail, sparing a disease-free middle segment. It may also be used after prior partial pancreatectomy. Surgical resection remains the cornerstone of treatment for pancreatic diseases such as PDAC, RCC metastasis, and multifocal IPMN. Whistal may balance oncologic control with pancreatic function preservation. Though infrequent, it is practiced and reported in literature. Methods With IRB approval, a retrospective review of a prospective database (Aug 1999-Mar 2024) identified Whistal cases, categorized as staged Whistal (SW) or concomitant whistal (CW). Perioperative outcomes were assessed via Clavien-Dindo and ISGPS. A PubMed search identified reported middle segment pancreatectomy (Whistal) cases. Results Of 2008 resections (Aug 1999-Mar 2024), 5 were Whistals (3 CW, 2 SW) for PDAC (n = 3), RCC (n = 1), IPMN (n = 1), and bile duct stricture (n = 1). Rates for major morbidity, POPF, and DGE were each 40%. Literature review found 26 papers reporting 52 additional Whistal cases. Conclusion Whistal is safe for select patients, but wider adoption and long-term data are needed to confirm its efficacy.

Objective: To evaluate the efficacy of regional anesthesia (RA) in enabling arteriovenous fistula (AVF) creation in patients with small-caliber veins who would typically receive arteriovenous grafts (AVG), and to compare access outcomes between AVF and AVG cohorts. Methods: We conducted a retrospective analysis of a prospectively maintained database from 2018 through 2024 involving patients with chronic kidney disease (CKD) requiring access creation. Eligible patients were those aged 18 years or older with inadequate veins for AVF creation based on initial ultrasound vein mapping. All patients underwent RA prior to the access creation and had a repeated intraoperative vein mapping at least 30 min after RA. Patients whose veins were sufficiently dilated and met the criteria for AVF creation underwent AVF formation; otherwise, an AVG was created. Outcomes included access maturation, patency rates, access failure, abandonment, and mortality. Statistical analysis was performed using R software, with significance set at p < 0.05. Results: Of the 106 patients, 67 (63.2%) underwent AVF creation post-RA due to sufficient vein dilation, while 39 (36.8%) received AVGs. Baseline vein diameters and comorbidities were comparable between groups. AVF maturation was achieved in 83.6% of AVF patients, with longer times to successful cannulation compared to AVG (median 187.0 vs 80.0 days, p = 0.037). Kaplan-Meier analysis revealed no difference in primary patency ( p = 0.97), but AVF patients had superior primary assisted ( p = 0.015) and secondary patency ( p = 0.033), and lower access failure rates ( p = 0.034) compared to AVG patients. Access abandonment and mortality rates did not differ significantly between groups. Conclusions: RA-induced venodilation enables the use of veins previously deemed inadequate for AVF creation, leading to improved access outcomes compared to AVG placement. Implementing RA may increase AVF utilization and enhance patient outcomes in hemodialysis access surgery.

Despite efforts to improve donor heart allocation policies, geographic disparities, logistical challenges and patient criteria limit organ availability. However, recent surgical innovations offer potential solutions. These include partial heart transplantation and xenotransplantation. Partial heart transplantation is a new procedure with the potential to address several clinical challenges in treating congenital heart defects. Cardiac xenotransplantation involves the transplantation of genetically modified porcine hearts into humans, offering a potential solution to the shortage of donor organs. Although immunologic barriers and ethical concerns remain, ongoing research aims to mitigate the risks and optimize outcomes, providing hope for patients in need. These innovative surgical approaches offer promising avenues for addressing the critical shortage of donor hearts and with ongoing research, may hold the potential to revolutionize heart transplantation, and improve outcomes for patients facing terminal heart failure.

Abstract Background Pregnancy is a known trigger for thrombotic thrombocytopenia purpura (TTP); however, there is limited data on the impact of a TTP diagnosis on pregnancy outcomes. Study design We used retrospective data from the National Inpatient Sample database to identify all hospital admissions of pregnant patients (≥18 years), with and without TTP from 2012 to 2021 using ICD‐9/10 codes. To describe the impact of TTP on maternal and fetal morbidity, we identified different morbidity indicators using standard CDC definitions. Results We identified 7,397,411 pregnancy hospitalizations with a mean age of 29 years. Of these, 233 had TTP , with 73 receiving therapeutic plasma exchange ( TPE ) during admission, which was treated as a surrogate for active TTP . Severe maternal morbidity rates were several‐fold higher in women with TTP (133 per 100 admissions; 95% CI 112–155) compared to those without TTP (6.75 per 100 admissions; 95% CI 6.74–6.79) ( p < 0.001). This included significantly higher rates of acute myocardial infarction, acute renal failure, acute respiratory distress syndrome ( ARDS ), disseminated intravascular coagulation ( DIC ), pulmonary edema/acute heart failure, puerperal cerebrovascular disorders, sepsis, shock, air/thrombotic embolism, blood transfusion, and mechanical ventilation. Amongst fetal outcomes, fetal growth restriction (6.9% vs. 2.3%) was more common in TTP , while there was no statistical difference between the two groups in rates of preterm delivery. In the multivariate analysis, Charlson comorbidity index ( CCI ) ≥ 1 and age ≥ 35 years were associated with higher likelihood of morbidity. Conclusion Pregnancy associated with TTP is associated with inferior maternal and fetal health outcomes.

Background Approximately 20% of hospice patients in the US are discharged alive, often due to Medicare regulations. Such discharges are frequently perceived by caregivers as abandonment or expulsion, especially when they occur without follow-up or planning for care transition. Methods This study explored caregiver experiences with live hospice discharge through 2 narrative interviews and institutional data from a Midwest medical center (January 2020 through December 2022). Caregiver stories were analyzed thematically to identify emotional and logistical challenges. Retrospective patient data were also reviewed to provide descriptive statistics on patient volume. Results Of 1556 hospice patients discharged, 107 (6.9%) were discharged alive, with a mean length of stay of 205 days—substantially longer than that for the general hospice population. Most patients were women who were diagnosed with cerebrovascular or neurologic conditions and discharged from skilled-care facilities. One of the caregivers described discharge as distressing and poorly coordinated; the other reported a positive experience shaped by prior knowledge and financial resources. Both emphasized the importance of clear communication, care planning (eg, to avoid loss of durable medical equipment), and interdisciplinary support. The caregiver’s financial stability likely influenced discharge decisions and preparedness. Conclusions Live hospice discharge can cause emotional and practical disruption, especially when not accompanied by a care transition plan or access to durable medical equipment. This study highlights the need for team-based communication, sensitivity in language, and continued support. Engaging all members of the interdisciplinary team and ensuring access to essential resources may improve caregiver confidence and continuity of care.

ABSTRACT Objective Data on bone health in patients with mild autonomous cortisol secretion (MACS) are limited and heterogenous. We sought to assess the prevalence of osteoporosis and symptomatic fragility fractures in patients with adrenal adenomas and hypercortisolism, and explore associations with the degree of cortisol excess and frailty. Design This multicenter cross ‐sectional study involved prospective enrollment of adults with nonfunctioning adrenal adenomas (NFA), MACS, Cushing syndrome (CS) and referent subjects without adrenal disorders during the study period (January 2019–September 2022). All participants completed a bone health questionnaire at enrollment and had dual‐energy X ‐ray absorptiometry bone mineral density assessment within 12‐months. Final analyses were adjusted for age, sex, body mass index, smoking status, alcohol use. Results Participants included 117 with NFA (median age 62 years, 80% women), 191 with MACS (median age 63 years, 74% women), 62 with CS (median age 50 years, 92% women), and 101 referent subjects (median age 59 years, 47% women). Both patients with CS (OR: 3.0, 95% CI: 1.1–8.3) and MACS (OR: 2.2, 95% CI: 1.9–4.9) had a higher prevalence of osteoporosis when compared to referents. Among patients with MACS, only those with post 1‐mg dexamethasone suppression test (post‐1mg‐DST) cortisol > 83 nmol/L had a higher prevalence of osteoporosis when compared to referents (OR: 3.2, 95% CI: 1.4–7.5) and NFA (OR: 2.2, 95% CI: 1.1–4.4). For clinical fragility fractures, only patients with CS showed an increased prevalence when compared to referents (OR: 6.1, 95% CI: 1.7–26.4) and NFA (OR: 3.8, 95% CI: 1.3–11.2). Prevalence of clinical fragility fractures was similar to referents in patients with MACS (OR: 1.8, 95% CI: 0.6–6.9) and NFA (OR: 1.5, 95% CI: 0.4–6.1), and was not associated with post‐1mg‐DST cortisol or frailty in the MACS and NFA groups. Conclusion Patients with CS, and those with MACS and post‐1mg‐DST cortisol > 83 nmol/L, exhibited a higher burden of osteoporosis. However, only CS was associated with an elevated risk of symptomatic fragility fractures.