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Importance Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive disease caused by misfolded transthyretin (TTR), occurs as wild-type (ATTRwt-CM) or variant (ATTRv-CM) forms. p.Val142Ile is the most common variant in the US, linked to rapid progression and increased mortality. Acoramidis achieves near-complete (≥90%) TTR stabilization and showed clinical benefit in the 30-month ATTRibute-CM trial and through month 42 in the ongoing open-label extension (OLE). Objective To evaluate the efficacy of acoramidis in ATTRwt-CM, ATTRv-CM, and variant subgroups (p.Val142Ile and non-p.Val142Ile). Design, Setting, and Participants This international, multicenter, phase 3, randomized placebo-controlled study took place from April 2019 to May 2023 with ongoing OLE (month 42). ATTRibute-CM enrolled 632 participants with ATTR-CM; 611 of 632 were included in the modified intention-to-treat (mITT) population. There were 380 participants who continued into the OLE. These data were analyzed from January 2025 to July 2025. Interventions Oral acoramidis, 712 mg, or placebo twice daily for 30 months, followed by 12 months of open-label treatment. Main Outcomes and Measures All-cause mortality (ACM), cardiovascular-related hospitalizations (CVH), serum TTR, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, and N-terminal pro B-type natriuretic peptide in participants with ATTRwt-CM and ATTRv-CM. Post-hoc analyses were conducted in variant subgroups, including p.Val142Ile. Results Overall, 552 participants with wild-type ATTR-CM (mean [SD] age, 78 [6.3] years; 92.0% male and 8.0% female) and 59 participants with variant ATTR-CM (mean [SD] age, 73 [7.7] years; 77.3% male and 22.7% female) were randomized (mITT population), including 35 with p.Val142Ile. Consistent efficacy was observed in wild-type and variant subgroups for ACM/CVH through month 30 and ACM through month 42. At month 30, acoramidis reduced the risk of ACM/first CVH vs placebo by 31% in ATTRwt-CM (hazard ratio [HR], 0.69; 95% CI, 0.52-0.90; P = .007) and by 59% in ATTRv-CM (HR, 0.41; 95% CI, 0.21-0.81; P = .01). ACM was reduced through month 42 with HRs of 0.70 (95% CI, 0.50-0.98; P = .04) and 0.41 (95% CI, 0.19-0.93; P = .03) in the ATTRwt-CM and ATTRv-CM groups, respectively. Consistent treatment benefit was observed in participants with ATTRwt-CM and ATTRv-CM for secondary end points. Within variant subgroups (p.Val142Ile vs non-p.Val142Ile), consistent treatment benefits were observed for ACM/CVH through month 30 and ACM through month 42. Conclusions and Relevance The beneficial effect of acoramidis was observed consistently in ATTRwt-CM and ATTRv-CM groups. These hypothesis-generating results indicate that further studies are warranted to better characterize the therapeutic benefit of acoramidis in variant subgroups. Trial Registration ClinicalTrials.gov Identifiers: NCT03860935 ; NCT04988386

Background: Acute postoperative major salivary gland adenitis is a rare complication characterized by swelling of the salivary glands, most commonly associated with skull base neurosurgical procedures. Its occurrence following supratentorial non-skull base craniotomies is uncommon and may be overlooked. Case Description: We report a 45-year-old man who developed ipsilateral parotid gland inflammation within 24 h after undergoing a frontal interhemispheric craniotomy for resection of a craniopharyngioma. The procedure was performed in the supine position with 90° head rotation and 45° neck flexion. Postoperative imaging confirmed acute parotitis without abscess or hematoma. The patient was treated conservatively with hydration, warm compresses, and empiric antibiotics, leading to complete resolution of swelling without airway compromise. Conclusion: Acute postoperative parotitis can occur after supratentorial non-skull base procedures, particularly in cases involving extreme and prolonged head positioning. Although we presented a rather mild case of postoperative parotitis following a non-skull base craniotomy, acute major salivary gland adenitis after craniotomy may cause significant morbidity and early recognition and conservative management are essential to prevent airway compromise and other complications. Awareness of this rare entity may help neurosurgeons implement preventive measures during surgery.

Purpose of review The diuretic agents are commonly used in ICUs for various purposes. Despite the widespread utilization of diuretics, there remains substantial ambiguity regarding their indications, ICU-related changes in their pharmacodynamics and pharmacokinetics, dosing, form, and timing of administration, the differences in their utilities based on each organ failure, and their monitoring and safety issues. Recent findings In the recent past, there have been several clinical trials and large registries or systematic reviews with a focus on the use of diuretic agents in ICUs. Summary In this review article, we outline the essential changes in drug behavior during critical illnesses and organ failures, describe the indications of their use in ICUs (management of fluid overload, electrolyte imbalances, or diagnostic or prognostic tests), assess the impact of different organ failures on the utility and effectiveness of diuretics, review major recent clinical trials related to diuretic comparison, use of multiple classes of diuretics, and monitoring and safety of their use. We also provide some information regarding the safety and adverse effects of diuretic use in the ICU and outline the importance of individualizing their use during critical illnesses.

BACKGROUND AND OBJECTIVES: The Patient-Generated Subjective Global Assessment (PG-SGA) is a standardized tool for assessing malnutrition in patients with cancer. The primary aim of this study was to assess the impact of preoperative nutritional status as measured by PG-SGA on survival in patients requiring surgical intervention and/or radiotherapy for spinal metastases. METHODS: Patients with spinal metastases who underwent surgery and/or radiation therapy for symptomatic spinal metastases were enrolled in the AO Spine Metastatic Tumor Research and Outcomes Network, a prospective international multicenter research registry, between September 2017 and August 2022. Using the PG-SGA, nutritional status was classified into 3 categories: A, well nourished; B, moderately malnourished; and C, severely malnourished. RESULTS: A total of 589 patients met the inclusion criteria; 362 were classified as well nourished (61%), 159 were moderately malnourished (27%), and 68 were severely malnourished (12%). The median survival was 491 days, 328 days, and 117 days for well-nourished, moderately malnourished, and severely malnourished patients, respectively. In the multivariate analyses, severe malnourishment (HR 2.5 95% CI 1.4-4.3, P < .01) and an ECOG performance status of 3 or 4 (HR 2.7 95% CI 1.2-6.0) remained associated with significantly worse survival. CONCLUSION: Malnutrition as measured by the PG-SGA demonstrated to be significantly and independently associated with postoperative survival. The PG-SGA is a simple and useful tool to identify spinal metastases patients at risk of early postoperative mortality, and inclusion in the preoperative evaluation of these patients should be considered.

Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction often coexist with overlapping clinical features, they are usually studied separately. The SPIROMICS HF (Subpopulations and Intermediate Outcome Measures in COPD and Heart Failure Study) is testing hypotheses that new computed tomography emphysema subtypes are associated with specific cardiovascular phenotypes (eg, cor pulmonale , cor pulmonale parvus ), common airway branch variants are associated with right heart dysfunction, and symptomatic tobacco-exposed persons with preserved spirometry have signs of increased left ventricular afterload. METHODS: SPIROMICS is a multicenter observational study of COPD with extensive pulmonary phenotyping of participants with ≥20 pack-years smoking and nonsmoking controls. COPD and COPD severity were defined by standard spirometric criteria and symptomatic tobacco-exposed persons with preserved spirometry by ≥20 pack-years, normal spirometry, and COPD Assessment Test score >10. SPIROMICS HF selected all participants in SPIROMICS visit 5 at major sites. Its comprehensive speckle-tracking echocardiography, which included physiological perturbations of leg raise and low-intensity exercise, was harmonized prospectively with the Multi-Ethnic Study of Atherosclerosis Early Heart Failure and HeartSHARE (Combining Omics, Deep Phenotyping, and Electronic Health Records for Heart Failure Subtypes and Treatment Targets) studies. The cardiopulmonary magnetic resonance imaging protocol with gadolinium administration included myocardial fibrosis sequences, pulmonary angiography, time-resolved 3-dimensional cine magnetic resonance imaging (4-dimensional flow) of venous return, and metronome-paced tachypnea to induce dynamic hyperinflation. Coronary artery calcium was assessed on computed tomography scans. The Kansas City Cardiomyopathy Questionnaire was administered. RESULTS: Of the final sample of 753 participants, 57% had COPD (15% mild, 27% moderate, and 15% severe), 18% had symptomatic tobacco-exposed persons with preserved spirometry, 16% were smoking controls, and 8% were nonsmoking controls. Reproducibility of the main measures from speckle-tracking echocardiography (intraclass correlation coefficient, 0.83–0.99), exercise echocardiography (intraclass correlation coefficient, 0.71–0.99) and magnetic resonance imaging (intraclass correlation coefficient, 0.57–0.99) were good-to-excellent, including in severe COPD. CONCLUSIONS: SPIROMICS HF aims to characterize and understand cardiopulmonary interactions in COPD and COPD-related phenotypes to inform targeted treatments for combined cardiopulmonary failure.