The aim of this study was to compare the sensitivity of nerve biopsy, fat aspirate, and skin biopsy in detecting amyloid in symptomatic hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN). We identified patients with ATTRv-PN (2012-2023) seen at one of the Mayo Clinic 3 sites in Minnesota, Florida, and Arizona. Patients with symptomatic PN confirmed by a neurologist or EMG, who underwent an abdominal fat aspiration, skin biopsy, or nerve biopsy, were included. All patients had a pathogenic TTR variant and either a positive tissue biopsy or a positive pyrophosphate cardiac scintigraphy scan. Demographic, clinical, laboratory, and pathologic data were reviewed. Of the 195 patients with symptomatic ATTRv-PN seen, 111 were included. The median age was 64.2 years (interquartile range 56.9-70.1), and 74.8% were male. Fat aspirate was positive for amyloid in 50 of 103 patients (sensitivity 48.5%, 95% CI 0.39-0.59), skin biopsy in 17 of 32 (sensitivity 53.1%, 95% CI 0.35-0.71), and nerve biopsy in 20 of 21 (sensitivity 95%, 95% CI 0.76-1.0). Skin biopsy yielded a higher sensitivity (60% vs 24%; p = 0.02, n = 25) in patients who underwent skin biopsy and fat aspirate. Nerve biopsies are more sensitive than fat aspirate or skin biopsy for tissue diagnosis in this retrospective cohort of patients with symptomatic ATTRv-PN. Skin biopsy was slightly more sensitive than fat aspirate. This study provides Class IV evidence that a nerve biopsy, fat aspirate, and skin biopsy can accurately diagnose hereditary transthyretin amyloidosis in patients presenting with polyneuropathy. Nerve biopsies are more accurate than fat aspirates or skin biopsies in identifying patients with hereditary transthyretin amyloidosis.

The HERMES-24 score recently demonstrated high accuracy for outcome prediction after large vessel occlusion (LVO) treatment in late time window patients from randomized clinical trials. In this study, we externally validate the score in a real-world patient cohort. Data from German Stroke Registry patients with LVO treated with endovascular therapy beyond 6 hours from symptom onset or last seen well were used. We performed a complete case analysis, excluding functionally dependent patients (premorbid modified Rankin Scale [mRS] >2/>3 for prediction of mRS ≤2/≤3, respectively). We assessed the HERMES-24 score for 90-day mRS prediction using bootstrap resampling and the c-statistic. The analyzed cohort comprised 2,117 patients (mean age 74 ± 13.3 years; 55.4% female; median admission NIH Stroke Scale (NIHSS) 14 (Q1-Q3: 9-18)). The HERMES-24 score achieved an area under the curve (AUC) of 0.876 (95% CI 0.859-0.889) for mRS ≤2 and 0.856 (95% CI 0.837-0.875) for mRS ≤3. Subgroup analysis for mRS ≤2 prediction showed lower performance in patients with NIHSS <18 (AUC 0.850, 95% CI 0.832-0.870). In our real-world cohort of late time window patients with LVO, the HERMES-24 score showed good discriminative performance, supporting its cautious clinical applicability, considering its lower performance than in trial populations, especially in patients with lower baseline NIHSS scores.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive metabolic disorder that can cause premature atherosclerosis and ischemic stroke in young adults. We report a 23-year-old man who had recurrent strokes even after patent foramen ovale (PFO) closure. Initial evaluation for his first cryptogenic stroke revealed a PFO with a high Risk of Paradoxical Embolism (RoPE) score, leading to closure. Three years later, he experienced a recurrent stroke with right M1 segment occlusion. High-resolution magnetic resonance vessel wall imaging demonstrated intracranial atherosclerotic plaque, prompting reconsideration of the etiology. Further history taking revealed chronic diarrhea since infancy and juvenile cataracts. Examination showed borderline intellectual functioning, bilateral ankle clonus, and Achilles tendon xanthomas. Brain MRI exhibited characteristic bilateral dentate nucleus hyperintensities. Genetic testing confirmed CYP27A1 pathogenic variants, consistent with a diagnosis of CTX. Through highlighting CTX underlying premature atherosclerosis and stroke in a young man, this case emphasizes the importance of rare metabolic disorders in stroke, even when a common cause such as PFO is identified. Early recognition enables targeted therapy and improves outcomes.

This study explores the role of liquidity management in enhancing corporate financial stability, focusing on cash reserves and tradable securities strategies. Effective liquidity management helps companies manage financial risks and take advantage of investment opportunities, especially in the face of economic uncertainty. This study uses a systematic literature review approach to analyze the relationship between liquidity, cash reserves, and tradable securities. Cash reserves serve as a financial buffer to deal with cash flow fluctuations and reduce dependence on external funding. Meanwhile, tradable securities provide additional financial flexibility through quick access to liquidity. This study shows that companies that manage their liquidity well tend to have better financial stability, reduce bankruptcy risk, and increase investor confidence. This study also identifies research gaps, including the effects of financial technology and macroeconomic conditions on liquidity strategies. The practical and theoretical implications of this study provide guidance for companies to manage their liquidity more effectively, ensure business continuity, and support long-term growth