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Presenting symptoms of sporadic Creutzfeldt-Jakob disease (sCJD) are variable, and as imaging and EEG may be normal in the early to middle stages of the disease process, serial testing is vital when there is clinical suspicion for sCJD. We present a case of probable Heidenhain variant of sCJD (HvCJD) with notable rapid progression. A 72-year-old woman presented with neurological decline following new-onset visual changes. Over the course of 3 weeks, she developed ataxia followed by paranoia, memory impairment, and visual hallucinations. An extensive workup from 1 week prior at an outside hospital was unrevealing and included two magnetic resonance imaging (MRI) studies read as normal and an EEG without periodic sharp wave complexes. Repeat of imaging at our hospital showed cortical restricted diffusion in the right occipital lobe. In combination with new periodic sharp wave complexes visualized on prolonged EEG, concern was raised for sCJD. Palliative care was consulted early in the hospitalization, and the patient was transitioned to comfort care and discharged 3 days after admission. She declined quickly and passed away at home within a week, one day before her send out CSF sample resulted with a positive real-time quaking-induced conversion (RT-QuiC) and markedly elevated T-tau protein and 14-3-3 gamma. As there is no treatment for this fatal disease, palliative engagement and discussion of goals of care in cases of CJD is critical in providing compassionate care for the patient and their family. High clinical suspicion warrants discussion of comfort care measures even prior to confirmation with RT-QuiC., Competing Interests: Rahul Gaini has nothing to disclose. Julia Denniss has nothing to disclose. Elijah Lackey has received compensation for advisory boards from EMD Serono, Sanofi, and Doximity., (Copyright © 2024 Rahul Gaini et al.)

Background: Health care utilization is higher in individuals with multiple sclerosis (MS) than in the general population. However, there are limited data on the reasons for their hospital admissions. Our primary objective is to analyze the reasons for the hospitalization of individuals with MS with the goal of identifying preventable causes., Methods: We conducted a retrospective analysis of a cohort of adults with a confirmed diagnosis of MS admitted to Duke University Hospital between January 2018 and January 2020. This yielded a cohort of 210 individuals. Data were analyzed using descriptive statistics., Results: The most common reason for admission was urinary tract infection (UTI; 10.3%). The average length of stay was 6.1 days for the individuals with MS vs 5.5 days for the general population. The 30-day readmission rates were 14.9% and 15.5%, respectively. A significant number of admitted patients were not on any disease-modifying therapy (DMT), and no difference in median age was identified between those with a DMT vs those without., Conclusions: Length of stay and readmission rates were similar to those of the general population in this contemporary cohort. Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS. Though we now have more treatment options for MS, many individuals with the highest health care utilization are not on a DMT. Future research is needed to identify the factors that can be addressed to support these patients and reduce preventable hospitalizations., (© 2024 Consortium of Multiple Sclerosis Centers.)

Neurosarcoidosis, a rare granulomatous disease, causes inflammation and damage to the central nervous system (CNS). A major diagnostic challenge in neurosarcoidosis is the absence of well-defined biomarkers. The need for biopsy to make the diagnosis can lead to delays and misdiagnosis if histopathology is inaccessible or indeterminate, highlighting the need for more accessible diagnostic indicators. The current gold standard for a "definite" neurosarcoidosis diagnosis requires biopsy of CNS tissue revealing non-caseating granulomas. However, such biopsies are inherently invasive and carry associated procedural risks. Notably, angiotensin-converting enzyme (ACE), commonly associated with systemic sarcoidosis, is recognized as a poor biomarker for neurosarcoidosis due to its lack of accuracy in the context of CNS involvement. Furthermore, imaging in neurosarcoidosis, while widely utilized and important for narrowing the diagnosis, lacks specificity. Decades of research have yielded molecular and immunologic biomarkers-soluble interleukin-2 receptor (IL-2R), serum amyloid A1, the CD4/CD8 ratio, neopterin, interferon-gamma (IFN-γ), and chemokine ligand 2 (CCL2)-that hold potential for improving diagnostic accuracy. However, these biomarkers are not yet established in clinical care as they may be difficult to obtain and are derived from small studies. They also suffer from a lack of specificity against other inflammatory and infectious central nervous system diseases. New biomarkers are needed for use alongside those previously discovered to improve diagnosis of this rare disease. This review synthesizes existing literature on neurosarcoidosis biomarkers, aiming to establish a foundation for further research in this evolving field. It also consolidates information on biomarkers of systemic sarcoidosis such as IL-8 and soluble CD40L that have not yet been studied in neurosarcoidosis but hold potential as markers of CNS disease., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Sarcoidosis is a disease characterized by non-caseating granulomas that can involve the central nervous system as neurosarcoidosis. This challenging disease is currently managed with high dose steroids, and sometimes the addition of infliximab. Other TNA-alpha inhibitors have not been studied as rigorously. We discovered ten neurosarcoidosis patients who were on an alternative TNA-alpha inhibitor, adalimumab. Eight patients had a positive response clinically and radiographically to adalimumab., Competing Interests: Declaration of competing interest The authors declare no relevant disclosures or competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Purpose of Review: Neurosarcoidosis is a rare manifestation of sarcoidosis that is challenging to diagnose. Biopsy confirmation of granulomas is not sufficient, as other granulomatous diseases can present similarly. This review is intended to guide the clinician in identifying key conditions to exclude prior to concluding a diagnosis of neurosarcoidosis., Recent Findings: Although new biomarkers are being studied, there are no reliable tests for neurosarcoidosis. Advances in serum testing and imaging have improved the diagnosis for key mimics of neurosarcoidosis in certain clinical scenarios, but biopsy remains an important method of differentiation. Key mimics of neurosarcoidosis in all cases include infections (tuberculosis, fungal), autoimmune disease (vasculitis, IgG4-related disease), and lymphoma. As neurosarcoidosis can affect any part of the nervous system, patients should have a unique differential diagnosis tailored to their clinical presentation. Although biopsy can assist with excluding mimics, diagnosis is ultimately clinical., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Family caregivers of people with dementia often experience negative impacts including stress and burden. Psychoeducational programs can reduce these negative outcomes., Objective: To evaluate whether this virtual caregiver education program changes caregiver confidence, self-efficacy, and burden relative to controls., Methods: This was a pre-post comparison of a five-week, synchronous, virtual caregiver education program delivered by a clinician and caregiver support specialist covering aspects of dementia, including changes in cognition, behavior, functional abilities, caregiver-care recipient roles, communication, and caregiver self-care. Caregivers (n = 90) were surveyed at baseline, at completion of intervention, and three months thereafter; controls (n = 44) were surveyed at two points six weeks apart. We compared validated measures of caregiver confidence, self-efficacy, and burden using generalized estimating equations., Results: Participants' confidence and self-efficacy increased over follow-up compared with controls (p < 0.01 for intervention*time in regression models). There was no difference in burden. All participants (100%) reported perceived increased knowledge, 97% perceived increased confidence, and 95% perceived increased ability to manage dementia-related behaviors after the course., Conclusion: This virtual caregiver education program was effective in improving caregiver confidence and self-efficacy and participants' self-reported impact was equivalent to those who had taken previous courses in person. Caregivers with greater confidence and self-efficacy have been shown to have better health outcomes and decreased stress and depressive symptoms. Health professionals, health care organizations, and public health agencies should consider using efficacious virtual caregiver education programs in rural and other community settings, during public health crises, or in standard practice as an alternative to in-person programs.

In health, the high-speed airflow associated with cough represents a vital backup mechanism for clearing accumulated mucus from our airways. However, alterations in the mucus layer in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) leads to the mucus layer adhered to the airway surfaces, representing the nidus of chronic lung infection. To understand what is different about diseased mucus and why cough clearance is defective, there is a need for techniques to quantify the strength of the interactions limiting the ability of airflow to strip mucus from the airway surface ( i.e ., adhesive strength) or tear mucus apart ( i.e ., cohesive strength). To overcome the issues with measuring these properties in a soft ( i.e ., low elastic modulus) mucus layer, we present here novel peel-testing technologies capable of quantifying the mucus adhesive strength on cultured airway cells and cohesive strength of excised mucus samples. While this protocol focuses on measurements of airway mucus, this approach can easily be adapted to measuring adhesive/cohesive properties of other soft biological materials., Competing Interests: Competing interests None for any authors listed.

Clearance of intrapulmonary mucus by the high-velocity airflow generated by cough is the major rescue clearance mechanism in subjects with mucoobstructive diseases and failed cilial-dependent mucus clearance, e.g., subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Previous studies have investigated the mechanical forces generated at airway surfaces by cough but have not considered the effects of mucus biophysical properties on cough efficacy. Theoretically, mucus can be cleared by cough from the lung by an adhesive failure, i.e., breaking mucus-cell surface adhesive bonds and/or by cohesive failure, i.e., directly fracturing mucus. Utilizing peel-testing technologies, mucus-epithelial surface adhesive and mucus cohesive strengths were measured. Because both mucus concentration and pH have been reported to alter mucus biophysical properties in disease, the effects of mucus concentration and pH on adhesion and cohesion were compared. Both adhesive and cohesive strengths depended on mucus concentration, but neither on physiologically relevant changes in pH nor bicarbonate concentration. Mucus from bronchial epithelial cultures and patient sputum samples exhibited similar adhesive and cohesive properties. Notably, the magnitudes of both adhesive and cohesive strength exhibited similar velocity and concentration dependencies, suggesting that viscous dissipation of energy within mucus during cough determines the efficiency of cough clearance of diseased, hyperconcentrated, mucus. Calculations of airflow-induced shear forces on airway mucus related to mucus concentration predicted substantially reduced cough clearance in small versus large airways. Studies designed to improve cough clearance in subjects with mucoobstructive diseases identified reductions of mucus concentration and viscous dissipation as key therapeutic strategies., Competing Interests: The authors declare no conflict of interest.

The National Cancer Institute (NCI)-supported adult cooperative oncology research groups (now officially Network groups) have a longstanding history of participating in international collaborations throughout the world. Most frequently, the US-based cooperative groups work reciprocally with the Canadian national adult cancer clinical trial group, NCIC CTG (previously the National Cancer Institute of Canada Clinical Trials Group). Thus, Canada is the largest contributor to cooperative groups based in the United States, and vice versa. Although international collaborations have many benefits, they are most frequently utilized to enhance patient accrual to large phase III trials originating in the United States or Canada. Within the cooperative group setting, adequate attention has not been given to the study of cancers that are unique to countries outside the United States and Canada, such as those frequently associated with infections in Latin America, Asia, and Africa. Global collaborations are limited by a number of barriers, some of which are unique to the countries involved, while others are related to financial support and to US policies that restrict drug distribution outside the United States. This article serves to detail the cooperative group experience in international research and describe how international collaboration in cancer clinical trials is a promising and important area that requires greater consideration in the future., (Copyright © 2015 Elsevier Inc. All rights reserved.)