Citations

Abstract Adrenal infections are considered clinically important but often go unrecognized, with a significant number of cases only diagnosed post-mortem. The limited evidence regarding imaging findings in the literature emphasizes the need to detect and diagnose these infections early in disease course to improve patient outcomes. A range of microorganisms, including fungi, viruses, parasites, and bacteria, can directly or indirectly affect the morphology and function of the adrenal glands. When evaluating a patient with adrenal infection, several immunological and hormonal factors should be considered, such as the status of the hypothalamic-pituitary-adreno cortical axis and the serum cortisol level. Moreover, certain microorganisms specifically target one of the zones of the adrenal glands or vascular supply, resulting in distinct imaging manifestations. The purpose of this article is to describe the fundamental clinical features and imaging manifestations associated with adrenal infections, enabling radiologists to make informed interpretations and contribute to accurate diagnostic assessments.

Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.

OBJECTIVE Spinal cord cavernous malformations (SCCMs) are rare vascular malformations with a capricious prognosis. Given the eloquent nature of the spinal cord, considerable surgical morbidity may be encountered. Therefore, conservative management has emerged as a valid alternative, especially for incidental lesions diagnosed on ubiquitous imaging. The aim of this systematic review and meta-analysis was to evaluate the safety and efficacy of surgical versus conservative management of SCCMs. METHODS Following PRISMA guidelines, this study included articles published in full-text form comparing the outcomes following conservative and surgical management of SCCMs. Collected variables included the total number of patients, spine level, resection, myelotomy, follow-up duration, bleeding, motor weakness, pain, bladder and/or bowel dysfunction, and neurological improvement or deterioration after discharge. The primary outcome of interest was long-term functional outcome. RESULTS Eleven articles comprising 515 patients were included, of whom 343 (66.6%) underwent resection and 172 (33.4%) were managed conservatively. Patients who underwent surgery were more likely to have preoperative motor deficits, hemorrhagic episodes, and bladder and/or bowel dysfunction, indicating increased disease severity. Resection was associated with significantly improved long-term functional outcomes (OR 3.27, 95% CI 1.72–6.24) compared with conservative management. There was no significant difference between the two groups regarding odds of long-term clinical deterioration (OR 1.03, 95% CI 0.35–3.03). However, the risk of hemorrhagic episodes during follow-up was higher in the conservative group (17.3%) compared with the surgical group (1.69%). The odds of hemorrhage during follow-up were lower in the surgical group, although not statistically significant (OR 0.24, 95% CI 0.05–1.05). CONCLUSIONS This study highlights that while surgical management of SCCMs is associated with better long-term functional outcomes and reduced risk of recurrent hemorrhage, treatment decisions must be carefully tailored to the individual patient, particularly given the potential risks associated with surgery. Conservative management, although less invasive, carries a nonnegligible risk of hemorrhage during follow-up, warranting close monitoring. These findings parallel management strategies used for brainstem cavernomas, for which surgery is reserved for cases with low surgical risk and worsening neurological symptoms. However, the limitations of current data, including selection bias and heterogeneity in reporting, emphasize the need for a multi-institutional registry to better define the natural history of SCCMs and inform future management strategies.

Background and Aims: Metabolic dysfunction–associated steatotic liver disease affects about a third of adults worldwide and is projected soon to be the leading cause of liver cirrhosis. It occurs when fat accumulates in hepatocytes and can progress to metabolic dysfunction–associated steatohepatitis, liver cirrhosis, and HCC. Metabolic dysfunction–associated steatotic liver disease pathogenesis is believed to involve a combination of genetic and environmental risk factors. Single nucleotide polymorphisms have been implicated, but non-syndromic monogenic causes are lacking. Approach and Results: We identified a novel genetic variant in a familial case of metabolic dysfunction–associated steatohepatitis and performed deep variant functional analysis, including protein modeling, dynamics, and cell-based assays to assess molecular mechanisms of dysfunction and altered cellular signaling. We analyzed exome sequencing data of 3904 individuals with steatotic liver disease (SLD) to identify additional cases and establish the link between specific gene variants and SLD diagnosis. We discovered and functionally validated the NM_000245.4:c.3505A>T; p.(Ile1169Phe) variant in the MET (mesenchymal-epithelial transition) kinase domain as a monogenic cause of SLD. Subsequently, we detected additional ultra-rare, previously uninterpreted, and likely deleterious variants in MET from screening sequencing data. Among individuals with confirmed SLD based on electronic record review, 1.1% (45/3904) had rare predicted deleterious MET variants. Eight of 45 (17.7%) individuals had predicted deleterious variants in the MET kinase domain confirmed to be functionally like the familial case variant. Conclusions: We report the first germline nonmalignant rare MET -driven disease, a monogenic form of SLD.