Initiation of noninvasive ventilation in patients with amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Noninvasive ventilation (NIV) has been shown to improve survival and symptom burden in patients with amyotrophic lateral sclerosis (ALS). However, limited data exist regarding the clinical and physiological parameters at the time of NIV initiation. This study aimed to describe the clinical characteristics and respiratory physiological markers in a cohort of ALS patients with chronic respiratory failure. METHODS: This is a single-center retrospective cohort study of patients with ALS assessed for NIV initiation between February 2012 and January 2021. NIV was initiated based on insurance eligibility criteria: daytime hypercapnia, defined by partial pressure of carbon dioxide (PaCO2) >45 mm Hg using diurnal transcutaneous CO2 (TcCO2) as a surrogate, a maximal inspiratory pressure (MIP) <60 cmH2O or forced vital capacity (FVC) <50% predicted normal. RESULTS: We identified 335 patients with ALS and chronic respiratory failure referred to an outpatient home ventilation clinic for NIV initiation. The mean age was 64 years ±11; 151 (45%) were female, 326 (97%) were white, and 100 (29%) had bulbar-onset ALS. At the time of NIV initiation, the mean FVC was 64% ± 19%, the mean MIP; 41 cmH2O ± 17, and diurnal TcCO2; 40 ± 6 mmHg. The most common reasons for NIV initiation were MIP <60 cmH2O (58%) and multiple concomitant indications (28%). Within 1 year of NIV initiation, 126 (37%) patients were deceased. DISCUSSION: We found that impairment in inspiratory force was the most common reason for NIV initiation and often preceded significant declines in FVC.

Correction: Different cadences and resistances in sub-maximal synchronous handcycling in able-bodied men: Effects on efficiency and force application.

[This corrects the article DOI: 10.1371/journal.pone.0183502.].

Quality of participants' relationships to peer recovery support specialists as a function of perceived similarities: An exploratory analysis.

Background: A growing evidence base supports the value of peer recovery support specialists (PRSS), particularly due to shared lived experience with participants (recipients of PRSS services). However, little research has examined whether congruence on certain aspects of "peerness" (e.g., demographics, experiences) matters for PRSS-participant relationships. Methods: Through a pilot study under the NIDA-funded Initiative for Justice and Emerging Adult Populations (JEAP), adults who had recently received PRSS services (N=100) were interviewed. Participants completed a modified version of the Scales for Participant Alliance with Recovery Coach (SPARC), a measure of PRSS-participant relationship quality, and rated themselves as different/similar to their PRSS in several domains using a six-point scale. Results: Participants had met with their PRSS for a median of 10 sessions over two months. SPARC scores were unrelated to participant demographics or lived experiences. However, better-quality relationships were reported by participants who believed their PRSS was similar to them in relationships with family (p=.004), spirituality/religion (p=.001), age (p<.001), and overall recovery pathway (p<.001). Total SPARC scores were not significantly correlated with perceived PRSS-participant similarities on gender, race/ethnicity, substances of choice, and history of incarceration or substance use treatment. Discussion: Results from this pilot study suggest that PRSS-participant alignment on past experiences (e.g., prior incarceration, choice of drugs) may not be needed to establish good-quality working relationships. However, similarities on factors related to current life stage (e.g., age, family relationships) and/or recovery process (e.g., overall pathway, spirituality) may be more important. Future research should employ mixed-methods approaches to elucidate these unique findings.

Long-Term survival across breslow thickness categories: Findings from a Population-Based study of 210,042 Australian melanoma patients.

The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the four AJCC 8th Edition T-categories by analyzing Australian registry data for 210,042 melanoma patients diagnosed from 1982-2014. The 30-year incidence rates of death due to melanoma and non-melanoma causes (with 95% confidence intervals) were 7.1% (CI 6.9-7.3%) and 32.8% (CI 32.3-33.3%), respectively. For T2 melanomas, the corresponding rates were 21.6% (CI 21.0-22.3%) and 35.6% (CI 34.7-36.6%), for T3 melanomas 34.2% (CI 33.4-35.1%) and 39.6% (CI 38.5-40.8%), and for T4 melanomas 44.3% (CI 43.2-45.3%) and 39.6% (CI 38.3-41.0%). A plateau in melanoma-related deaths occurred in T4 patients after 20 years but there were ongoing melanoma-related deaths for the other T-categories beyond 30 years. A progressive rise in the risk of death from other causes occurred across all T-categories.

Evaluation of the long-term protection conferred by an organosilicon-based disinfectant formulation against bacterial contamination of surfaces.

AIMS: The aim of this work was to evaluate the efficacy of an organosilicon-based, commercially available antimicrobial formulation in the My-shield® product line against bacterial surface contamination. METHODS AND RESULTS: The antimicrobial product was tested in vitro for its long-term persistence on surfaces and effectiveness against Staphylococcus aureus biofilms in comparison to 70% ethanol and 0.1% or 0.6% sodium hypochlorite. Field testing was also conducted over 6 weeks at a university athletic facility. In vitro studies demonstrated the log reductions achieved by the test product, 70% ethanol, and 0.1% sodium hypochlorite were 3.6, 3.1, and 3.2, respectively. The test product persisted on surfaces after washing and scrubbing, and pre-treatment with this product prevented S. aureus surface colonization for up to 30 days. In comparison, pre-treatment with 70% ethanol or 0.6% sodium hypochlorite was not protective against S. aureus biofilm formation after seven days. The field test demonstrated that weekly applications of the test product were more effective at reducing surface bacterial load than daily applications of a control product. CONCLUSIONS: The test product conferred greater long-term protection against bacterial growth and biofilm formation by S. aureus than ethanol and sodium hypochlorite. Even with less frequent applications, the test product maintained a high level of antimicrobial activity.

Associations of physical activity levels with fatigue in people with inflammatory rheumatic diseases in the LIFT trial.

Objectives: The overall aim of the current study was to quantify physical activity levels in inflammatory rheumatic diseases (IRDs) and to explore their role in fatigue. Methods: We conducted a secondary analysis of data from the Lessening the Impact of Fatigue in IRDs (LIFT) trial of the personalized exercise program (PEP) intervention for fatigue. Participants with IRDs were recruited from 2017 to 2019 and the current analysis used fatigue, measured by the Chalder Fatigue Scale (CFS) and the Fatigue Severity Scale (FSS), and accelerometer measured physical activity data collected at baseline and at the 6-month follow-up. Physical activity levels were quantified and associations with fatigue and effects of PEP investigated. Results: Of the 337 included participants, 195 (68.4%) did not meet the current recommendations for moderate-vigorous physical activity (MVPA). In baseline cross-sectional analysis, many dimensions of physical activity were associated with fatigue. After mutual adjustment, overall physical activity (vector magnitude) was associated with CFS [-0.88 (95% CI -0.12, -1.64)] and distribution of time spent at different activity intensities was associated with FSS [-1.16 (95% CI -2.01, -0.31)]. Relative to usual care, PEP resulted in an increase in upright time, with trends for increases in step count and overall physical activity. People who increased overall physical activity (vector magnitude) more had greater improvements in CFS and FSS, while those who increased step count and MVPA more had greater improvements in FSS. Conclusion: Increasing physical activity is important for fatigue management in people with IRDs and further work is needed to optimize PEPs to target the symptoms and impact of fatigue. Trial registration: ClinicalTrials.gov (http://clinicaltrials.gov), NCT03248518.

Drug-Induced Alopecia Areata From Upadacitinib.

This case report describes an unexpected occurrence of alopecia areata (AA) in a 55-year-old woman undergoing treatment with upadacitinib for atopic dermatitis. This patient developed AA approximately one year into her upadacitinib treatment for atopic dermatitis. This case highlights possible upadacitinib-induced AA, which has not been reported in the literature. Not only does this case demonstrate the typical timeline for drug-induced alopecia, but it also raises questions about whether upadacitinib can cause drug-induced alopecia.

ß2 integrins impose a mechanical checkpoint on macrophage phagocytosis.

Phagocytosis is an intensely physical process that depends on the mechanical properties of both the phagocytic cell and its chosen target. Here, we employed differentially deformable hydrogel microparticles to examine the role of cargo rigidity in the regulation of phagocytosis by macrophages. Whereas stiff cargos elicited canonical phagocytic cup formation and rapid engulfment, soft cargos induced an architecturally distinct response, characterized by filamentous actin protrusions at the center of the contact site, slower cup advancement, and frequent phagocytic stalling. Using phosphoproteomics, we identified ß2 integrins as critical mediators of this mechanically regulated phagocytic switch. Macrophages lacking ß2 integrins or their downstream effectors, Talin1 and Vinculin, exhibited specific defects in phagocytic cup architecture and selective suppression of stiff cargo uptake. We conclude that integrin signaling serves as a mechanical checkpoint during phagocytosis to pair cargo rigidity to the appropriate mode of engulfment.

IL-17A Levels and Progression of Kidney Disease Following Hospitalization with and without Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality and new or progressive chronic kidney disease (CKD). Inflammatory cells play an important role in acute organ injury. We previously demonstrated that serum IL-17A levels were significantly elevated in critically ill patients with AKI and independently associated with hospital mortality. We hypothesize that IL-17A levels are elevated in hospitalized patients with AKI at diagnosis, and sustained elevation after discharge is associated with subsequent CKD incidence or progression. METHODS: Observational convenience sampling study of hospital survivors of Stage 2 or 3 AKI and controls without AKI from the ASSESS-AKI study. Patients were classified as progression or non-progression based on a composite of CKD incidence, progression, or end-stage kidney disease. IL-17A levels were evaluated with S-Plex assay (MSD) at 0- (during hospitalization), 3- and 12-month post-discharge, and analyzed along with clinical and biomarker data up to 84 months following discharge. RESULTS: Among 171 AKI and 175 non-AKI participants, IL-17A levels were elevated in AKI vs. non-AKI patients at 0M, 3M and 12M timepoints (p<0.05 for all comparisons). Further, IL-17A levels were elevated in the progression vs. non-progression group at the 3- and 12-month timepoints for outcomes occurring at 3-6 months and 12-84 months, respectively (p<0.05 for both). In adjusted multivariable models, IL-17A levels were not independently associated with progression of kidney disease. IL-17A levels were positively correlated with kidney disease and immune activation biomarkers at all timepoints (p<0.001). CONCLUSIONS: IL-17A was higher in patients with AKI vs. without AKI during hospitalization and up to 1-year post-discharge. IL-17A was higher in patients with progression of kidney disease after hospitalization but not independently associated with subsequent progression of kidney disease in fully adjusted models.

Role of Locoregional Therapies in the Treatment of Thyroid Pathology: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

The role of locoregional therapy in the management of thyroid pathology is rapidly evolving. The Society of Interventional Radiology Foundation commissioned an international research consensus panel consisting of physicians from multiple disciplines with expertise in the management of benign and malignant thyroid disease. The panel focused on identifying gaps in the current body of literature to establish research priorities that have the potential to shape the landscape of minimally invasive thyroid interventions. The topics discussed were centered on the emerging role of ablation for malignant thyroid tumors and the treatment of large functioning nodules with embolization and ablation. Specifically, the panel prioritized identifying nodule characteristics, including size and location, that are associated with ideal outcomes following thermal ablation for papillary thyroid microcarcinoma through the development of an international registry or a prospective, multi-institutional trial. The panel also prioritized evaluating the role of locoregional therapy in Stage T1b papillary thyroid cancer through a sequence of two studies: a Phase I study of ablation followed by immediate resection of Stage T1b papillary thyroid cancer, which may lead to a Phase II prospective, multi-institutional study of ablation followed by biopsy for Stage T1b papillary thyroid cancer. Lastly, the panel prioritized investigating the treatment of large, functioning thyroid nodules greater than 20 ml in volume through a randomized clinical trial or prospective registry comparing embolization alone with embolization followed by ablation.

Robotic Removal of Spilled Gallstones After Laparoscopic Cholecystectomy: Resolving Chronic Abdominal Pain Using New Technology.

Spilled gallstones during laparoscopic cholecystectomy can potentially lead to serious complications in patients. We present a case of a patient with gallstone spillage during cholecystectomy who was found years later to have gallstones stuck in a difficult location, requiring robotic surgery. A robotic approach allows for greater visual angles compared to conventional laparoscopy. The patient tolerated the robotic procedure successfully, and no patient symptoms were reported during follow-up. This case addresses retained gallstones for difficult anatomical positions and confirms that a robotic abdominal approach is a safe, minimally invasive option.

Gaidropsarus mauritanicus (Gadiformes, Gaidropsaridae) a new three-bearded rockling from a deep-water coral ecosystem with a genetically verified biogeographical distribution of the genus and notes to its ecology and behavior.

Gaidropsarus mauritanicus sp. nov. is described from one specimen collected using a grab sample from the Tanoûdêrt Canyon (ca. 20° N) off Mauritania at a depth of 595 m. The new species was further observed during eight remotely operated vehicle (ROV) dives along the Mauritanian slope southwards down to the Tiguent Coral Mound Complex (~17° N) in a bathymetric range between 613 and 416 m. It can be distinguished from congeners by a combination of characteristics, including large eyes (38.1% head length [HL]), large head (25.8% standard length [SL]), elongated pelvic fins (35.7% SL), low number of vertebrae (44), and coloration (pinkish with a dorsal darker brownish hue and bright blotches along the dorsal-fin base). A species-delimitation analysis performed with available cytochrome c oxidase subunit 1 (COI) sequences affiliated to the genus Gaidropsarus additionally supported the validity of the new species. Video analyses showed a deep-water coral-associated and protection-seeking behavior, which may explain why the species has remained undescribed until now. Additional ROV footage from separate deep-water coral sites in the North Atlantic and Mediterranean Sea further highlights the ecological behavior and hidden diversity of bathyal three-bearded rocklings. Here, we additionally discuss the biogeographical distribution of all genetically verified Gaidropsarus spp. in combination with genetic data and morphological characters. G. mauritanicus sp. nov. is closely related to a species from Tasmania (43° S), a geographical point furthest among the studied samples, which may hint to an important influence of (paleo-) oceanography on the distributions of Gaidropsarus species.

Introduction of the donor centre virtual crossmatch in Eurotransplant.

On 24 January 2023, Eurotransplant has introduced the virtual crossmatch for kidney and pancreas allocation as a better alternative for the physical Complement Dependent Cytotoxicity (CDC) crossmatches at the donor centre, which were associated with a longer cold ischaemia time and false positive reactions. For the time being, the physical CDC crossmatch at the recipient centre will remain in place as the final histocompatibility check. While Eurotransplant is certainly not the first organ allocation organisation to introduce virtual crossmatching, several novel aspects have been introduced, such as calculation of the virtual panel reactive antibody (vPRA) on 11 loci at the second-field level in addition to the serological broad and split level, electronic HLA typing data transmission using Histoimmunogenetics Markup Language (HML) file format, and the actual virtual crossmatch based on ambiguous, second-field HLA typing of the donor on all 11 loci. This short communication will focus on these novel aspects of the virtual crossmatch in Eurotransplant.

Multicenter Retrospective Review of Ketamine Use in Pediatric Intensive Care Units (Ketamine-PICU Study).

Objective: Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs). Methods: Multicenter, retrospective, observational study in children <18 years who received CI ketamine between 2014 and 2017. Time spent in goal pain/sedation score range and daily cumulative doses of analgesics/sedatives were compared from the 24 hours (H) prior to CI ketamine to the first 24H and 25-48H of the CI. Adverse effects were collected over the first 7 days of CI ketamine. Results: Twenty-four patients from 4 PICUs were included; median (IQR) age 7 (1-13.25) years, 54% female (n = 13), 92% intubated (n = 22), 25% on CI vasopressors (n = 6), and 33% on CI paralytics (n = 8). Ketamine indications were analgesia/sedation (n = 21, 87.5%) and status epilepticus (n = 3, 12.5%). Median starting dose was 0.5 (0.48-0.70) mg/kg/hr and continued for a median of 2.4 (1.3-4.4) days. There was a significant difference in mean proportion of time spent within goal pain score range (24H prior: 74% ± 14%, 0-24H: 85% ± 10%, and 25-48H: 72% ± 20%; p=0.014). A significant reduction in median morphine milligram equivalents (MME) was seen (24H prior: 58 (8-195) mg vs. 0-24H: 4 (0-69) mg and p=0.01), but this was not sustained (25-48H: 24 (2-246) mg and p=0.29). Common AEs were tachycardia (63%), hypotension (54%), secretions/suctioning (29%), and emergence reactions (13%). Conclusions: Ketamine CI improved time in goal pain score range and significantly reduced MME, but this was not sustained. Larger prospective studies are needed in the pediatric population.

Ag20 Nanoclusters with Surface Azides as an Easily Functionalized Platform for Diverse Chemical Applications.

Modifying atomically precise nanocluster surfaces while maintaining the cluster core remains a key challenge. Herein, the synthesis, structure, and properties of two targeted Ag20 nanoclusters (NCs) with eight surface azide moieties, [CO3@Ag20(StBu)10(m-N3-C6H4COO)8(DMF)4] (1-m) and [CO3@Ag20(StBu)10(p-N3-C6H4COO)8(DMF)4] (1-p) are reported, where DMF is N,N-dimethylformamide. These AgNCs are designed to undergo cluster surface strain-promoted azide-alkyne cycloaddition (CS-SPAAC) reactions, introducing new functionality to the cluster surface. Reactivity is screened using model strained cyclooctynes. Reaction products and parent clusters are characterized by UV-vis, FT-IR, and NMR spectroscopies. The structure of the parent clusters and presence of surface azides is confirmed by single crystal X-ray diffraction (SCXRD) analysis. Clusters 1-m and 1-p are found to be amenable to CS-SPAAC reactions with retention of the NC frameworks, opening new routes for efficient modification of AgNC for applications.

Prevalence of steatotic liver disease, advanced fibrosis and cirrhosis among community-dwelling overweight and obese individuals in the USA.

BACKGROUND: There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study was to fill that gap in knowledge by prospectively determining the MRI-based prevalence of steatotic liver disease (SLD) and its subcategories, advanced fibrosis and cirrhosis among overweight and obese individuals residing in the USA. METHODS: This is a cross-sectional analysis of prospectively enrolled overweight or obese adults aged 40-75 years from primary care and community-based settings in Southern California. Participants were classified as having SLD if MRI proton density fat fraction ≥5%, and subclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-related liver disease (ALD) consistently with the new nomenclature guidance per AASLD-EASL-ALEH. Advanced fibrosis and cirrhosis were defined as magnetic resonance elastography (MRE) ≥3.63 kPa and MRE ≥4.67 kPa, respectively. RESULTS: The cohort included 539 participants with mean (±SD) age of 51.5 (±13.1) years and body mass index of 32.6 (±6.2) kg/m2, respectively. The prevalence of SLD, advanced fibrosis and cirrhosis was 75%, 10.8% and 4.5%, respectively. The prevalence of MASLD, MetALD and ALD was 67.3%, 4.8% and 2.6%, respectively. There was no difference in prevalence of advanced fibrosis and cirrhosis among subcategories. CONCLUSIONS: Using advanced MRI methods among community-dwelling overweight and obese adults, the prevalence of cirrhosis was 4.5%. Most common SLD subcategory was MASLD with 67% of individuals, whereas MetALD and ALD were less common. Systematic screening for advanced fibrosis among overweight/obese adults may be considered.