Citations

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management.

Abstract Background One in five adults aged 40 will develop heart failure (HF) during their lifetime. Risk factors (e.g., hypertension, diabetes mellitus, coronary artery disease, etc.) lead to structural and functional changes in cardiomyocytes, resulting in HF. At the cellular level, these changes consist of mis/over‐expression of genes that regulate cardiac identity (e.g., CamK2δ, PKC, Stat3, etc.). The current paradigm for treating HF is pharmacological or device‐based intervention; however, with few exceptions, the condition worsens with time. We are proposing to implement a change in HF treatment, shifting from a drug‐centric system to a cardiac target‐specific molecular approach that would reverse hypertrophy and adverse remodelling of affected cardiomyocytes. Methods A cardiomyocyte targeting peptide (CTP) was reversibly linked to miRNA106a for delivery to a mouse model of HF. Reversal of morphological, signalling, and physiological HF parameters was measured. Additionally, CTP‐miRNA106a was introduced into a human cardiomyocyte cell line to identify mechanism(s) at play for reversing HF characteristics (e.g., hypertrophy). Results Bio‐distribution studies showed that intravenously injected CTP‐miRNA106 delivered its cargo specifically to the heart within 30 min, followed by clearance of CTP from the heart to the kidneys, and to a lesser extent, the liver by 35 h with persistence of miRNA106a in cardiomyocytes until day 7 (the latest tested time‐point). CTP‐miRNA106a reversed angiotensin2/isoproterenol‐induced hypertrophy in 90% of the treated mice. We also identified two potential HF intracellular signalling pathways/mechanisms (PLCβ1/PKC/IP3 and NF‐κB) targeted by CTP‐miRNA106a that could benefit many pathophysiologies underlying HF, including inflammation. Conclusions CTP‐miRNA106a, a first‐of‐a‐kind cardiac‐specific drug, downregulates genes involved in cardiac hypertrophy and inflammation through the PLCβ1 and CamKIIδ kinase pathways. CTP delivery of miRNA106a cargo is specific to cardiomyocytes both in vitro and in vivo, and once delivered, many HF parameters, including hypertrophy, are reversed. Key points Cardiac Targeting Peptide (CTP) delivers, specifically to the heart, reversibly linked miRNA106a. MiRNA106a targets genes in various pathways known to cause heart failure when they are over/hyper activated returning their expression to normal levels. In vivo analyses using a mouse heart failure model resulted in reversal of heart failure parameters in 19/20 mice.

There is an increased clinical use of elbow orthoses. It is important to consider patient experiences in their use. Patient-reported outcome measures (PROMs) serve as essential tools for gathering patient perspectives. This review provides a comprehensive list of PROMs used in clinical trials of elbow orthoses, and documents their properties, uses, and quality. A systematic literature search across PubMed, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, and Web of Science identified 31 clinical trials of elbow orthoses that used PROMs as outcome measures. Subsequently, manual searches were conducted to report on each PROM's characteristics. A total of 15 different PROMs were used as outcome measurements in clinical trials that used an elbow orthosis as an intervention for 11 different conditions. Researchers can use this review to aid in making informed decisions about which PROMs to use for future clinical trials.

Background: Home telemetry has been shown to reduce 30-day readmissions in patients at high risk for readmission. It remains unclear whether this finding is due to the telemetry itself or the nurse contact that follows detection of an abnormal parameter. Purpose: This study was a subgroup analysis from a prior trial comparing patients on home telemetry for 30 days to usual care after discharge to determine if nurse contact affected readmission rates. Methods: Patients randomized to telemetry who had at least 1 nurse contact were compared to those who had none to see if the contact reduced the rate of readmissions. Results: Of 449 home telemetry patients, 292 (65.0%) received 1 or more nurse contacts. Single and multivariable logistic regression models exploring the association of contact with 30-day readmission did not find any statistically significant associations of nurse contact with readmission (all unadjusted P ≥ .13, all adjusted P ≥ .18). Conclusion: Our subset analysis did not show that the nurse contact was the factor that reduced readmission in patients on home telemetry.

Abstract The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease‐modifying therapies. Modern diagnostic approaches emphasize biological precision, early detection, and dynamic frameworks that adapt to treatment‐induced changes in disease biology. These frameworks enable opportunities for personalized interventions—encompassing pharmacological and non‐pharmacological strategies—and for enhanced clinical trial design. However, implementing these advancements globally is influenced by diverse cultural, infrastructural, and regulatory factors. The 2024 Alzheimer's Association International Conference Advancements: Modernizing Diagnosis, held in Japan, provided a unique platform to explore these global dynamics, particularly from an Asian perspective. This article highlights key discussions from the conference, exploring the role of biomarker‐based diagnostic frameworks in shaping the future of AD/ADRD research, diagnosis, and treatment. We highlight regional challenges and successes and emphasize ethical considerations and practical strategies needed to ensure equitable access to diagnostic and therapeutic innovations. Highlights Advances in biomarkers are reshaping Alzheimer's disease diagnosis and treatment. Modern diagnostic frameworks highlight biological precision, early detection, and dynamic frameworks. The 2024 Alzheimer's Association International Conference Advancements: Modernizing Diagnosis explored challenges and opportunities in global biomarker implementation. The conference explored geographic‐specific impacts, focusing on Asia.

Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β cells, resulting in permanent loss of glucose homeostasis. Islet transplantation is a promising potential cure that remains hindered by immune rejection. We previously showed that ST8Sia6 expression on tumors reduced immune surveillance and hypothesized that this sialyltransferase could protect β cells from autoimmune destruction. Here, we demonstrate that ectopic expression of ST8Sia6 in β cells of female nonobese diabetic mice (NOD βST) decreased the spontaneous incidence of diabetes by 90% and preserved β cell mass. NOD βST mice had comparable insulitis at 8 weeks of age that did not progress over time compared with littermate controls. β Cell–autoreactive B and T cells were present in NOD βST mice, indicating a peripheral rather than central mechanism of immune tolerance. The islets of NOD βST mice displayed a dampened type 1 immune response and reduced IL-12p35 expression in dendritic cells compared with those of littermate controls. The peripheral protection persisted even after removal of ST8Sia6 expression at 20 weeks of age, indicating that transient expression was sufficient for establishment of tolerance. These results demonstrate that ST8Sia6 protects β cells from immune-mediated attack and rejection, highlighting its therapeutic potential for autoimmune disorders.

Abstract Introduction This study investigated if acute alcohol exposure produces sex differences in aged rats compared to adult and adolescent rats on ataxia and nonspatial cognition. Materials and Methods Sex- and age-related differences were assessed by using aged, young adult, and adolescent Sprague–Dawley rats. For acute alcohol exposure, animals were administered either 1 or 2 g/kg alcohol via intraperitoneal injection before testing. To examine the effects of acute alcohol exposure on balance and motor control and nonspatial learning, animals underwent behavioral testing in the aerial righting reflex (ARR) and Morris water maze (MWM) tests. Blood alcohol levels were determined 60 min following administration of either 1.0 or 2.0 g/kg alcohol. Results Sex differences were found in the ARR, as aged females were significantly less sensitive to the effect of acute alcohol exposure compared to aged males. Age was also found to significantly affect ARR performance, where aged animals performed worse than younger animals in response to acute alcohol. However, these sex- and age-related differences were not found in the nonspatial MWM test or in blood alcohol concentrations. Conclusions These results indicate that the sex- and age-dependent effects of acute alcohol exposure are task specific. In conclusion, these findings highlight the importance of studying the effects of acute alcohol on the aged population.

Hepatic hydrothorax (HH) is a rare but serious complication of end-stage liver disease that is often refractory to conventional medical and procedural management. This case report describes a 75-year-old woman with HH secondary to cirrhosis from metabolic-associated steatotic liver disease. Her clinical course was marked by recurrent hospitalizations, refractory right-sided pleural effusion, and multiple unsuccessful interventions including diuretics, serial thoracenteses, an indwelling pleural catheter, and chemical pleurodesis. Notably, the persistence of pleural fluid despite resolution of ascites ultimately led to the formation of a thoracic fistula, with pleural drainage volumes exceeding 4 L/day. Further invasive procedures, such as transjugular intrahepatic portosystemic shunt or liver transplantation, were declined by the patient. She was enrolled in Mayo Clinic’s hospital-at-home (HaH) program, where continuous intravenous octreotide was initiated at a dose of 25 mcg/h. This resulted in a significant reduction in pleural output—from over 4000 mL to less than 100 mL daily. After clinical stabilization, the patient transitioned to subcutaneous octreotide and remained clinically stable for over 6 months, with improved quality of life and no significant adverse effects. To our knowledge, this is the first reported case of continuous intravenous octreotide infusion for HH administered safely in a home-based acute care setting. This case underscores the potential therapeutic role of octreotide in managing refractory HH and highlights the feasibility of delivering complex cirrhosis-related care through a HaH model with multidisciplinary collaboration. Further research is warranted to assess the long-term efficacy, safety, and cost-effectiveness of octreotide in this context and to explore broader application in home hospital environments.

Abstract Patients with cancer and venous thromboembolism (VTE) have higher complication rates of anticoagulation. However, studies supporting this data are relatively old reflecting the era of vitamin K inhibitors. To assess VTE recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB) in patients (March 1, 2013 to April 30, 2023) with cancer-associated VTE and patients without cancer, the prospective Mayo Clinic Thrombophilia Clinic Registry was analyzed. Over the study period, 4,711 patients with acute VTE were enrolled including 2,064 patients with cancer (mean age 62.5 ± 12.4, 46% female) and 2,647 patients without cancer (mean age 59.4 ± 16.0, 45% female). The most common cancers were gastrointestinal (n = 423, 21%), pancreatic (n = 287, 14%), and genitourinary (n = 198, 10%). Direct oral anticoagulants were used in 1,339 (65%) cancer and in 1,952 (74%) non-cancer patients. Among cancer patients, 12-month Kaplan–Meier probability of VTE recurrence was 2.4-fold greater (7.1% vs. 2.9%, p < 0.001) compared with the non-cancer group, including higher recurrent leg deep vein thrombosis (3.0% vs. 1.4%; p = 0.002) and pulmonary embolism (3.5% vs. 1.0%, p < 0.001). Patients with cancer also had 2.1-fold greater risk of major bleeding (6.3% vs. 3.0%; p < 0.001) including bleeding from the gastrointestinal tract (3.0 vs. 1.4, p = 0.01) compared with patients without cancer. Clinically relevant non-major bleeding events were similar between the groups. In this large prospective registry of VTE management, patients with cancer had significantly higher rates of VTE recurrence and major bleeding compared with patients without cancer, yet the rate of complications are substantially smaller relative to historic values of a prior vitamin K antagonist era.

ABSTRACT Background and Purpose Radiomics extracts imaging features that may not be detectable through conventional volumetric analyses. Given their role in multiple sclerosis (MS), we applied radiomics to thalamic nuclei and examined their associations with cognitive performance. Methods A total of 601 individuals were included (342 people with MS [PwMS] from two cohorts and 259 healthy controls [HC]). Radiomic features (RF) and volumes were extracted from the whole thalamus, five thalamic nuclei, and the putamen segmented on three‐dimensional T1‐weighted images. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) in PwMS and the Digit Symbol Substitution Test (DSST) in HC. In the first MS cohort, multivariate linear regression in a discovery set ( N = 103) identified thalamus‐derived RF associated with SDMT, which were retested in a replication set ( N = 63). Their associations with PASAT in a second MS cohort ( N = 176) and DSST in HC were also evaluated. We then tested whether the same RFs, when extracted from the putamen, was associated with SDMT. Least Absolute Shrinkage and Selection Operator (LASSO) models assessed the combined predictive value of RF and volumes. Results Twenty‐eight RF–region of interest (ROI) pairs were associated with SDMT in the replication set (false discovery rate [FDR] < 0.05). Of these, 24 were also associated with PASAT (FDR ≤ 0.03), and 2 with DSST. Only ventral nuclei volume showed replicated associations among volumetrics. Only four putamen‐derived pairs were associated with SDMT (FDR = 0.04). LASSO results confirmed RF outperformed volumes. Conclusion RF extracted from the thalamus is strongly associated with cognitive performance in PwMS, outperforming volumetric measures and supporting their potential as sensitive imaging biomarkers.