Citations

ABSTRACT The alpha 1 and 2 chains of type IV collagen, encoded by the COL4A1 (MIM 120130) and COL4A2 (MIM 120090) respectively, play essential roles in the vascular basement membranes. Pathogenic variants in COL4A1 / COL4A2 are associated with autosomal dominant cerebral angiopathies. The clinical manifestations of COL4A1 / COL4A2 ‐related disorders include: aneurysms, intracerebral hemorrhage, polymicrogyria, porencephaly, heterotopia, periventricular leukomalacia, epilepsy, and neurodevelopmental disorders. COL4A1 pathogenic variants that are in exons 24 and 25 have been associated with hereditary angiopathy, nephropathy, aneurysms, and cramps. The multisystemic phenotypes of COL4A1 / COL4A2 ‐related disorders are increasingly being studied. Animal models have suggested that COL4A2 ‐related disorders may also manifest with a variable combination of multisystemic abnormalities affecting the eyes, muscles, and kidneys. Okano and colleagues recently reported a case of recurrent episodes of rhabdomyolysis in a 2‐year‐old with COL4A1 ‐related disorder raising fundamental questions on mechanisms of COL4A1 / COL4A2 variants in muscle homeostasis. To date, rhabdomyolysis has not been associated with COL4A2 ‐related disorder in humans. Rhabdomyolysis is a medical emergency, where there is elevated creatine kinase (CK) level in the blood and increased excretion of myoglobin in urine, due to skeletal muscle damage and release of intracytoplasmic proteins into systemic circulation. Rhabdomyolysis is a serious medical condition. It require intensive care management due to an increased risk of some life‐threatening complications [including disseminated intravascular coagulation, renal failure, and severe hyperkalemia]. Herein, we report a case of rhabdomyolysis in an adult with COL4A2 ‐related structural brain malformations (including polymicrogyria and heterotopia).

Stroke remains a leading cause of global disability and mortality despite advancements in acute interventions. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique, has primarily been studied for its effects on cortical excitability, with limited exploration of its neuroprotective and hemodynamic benefits. This review examines the role of tDCS in stroke, with a focus on neuroprotection in acute settings and cerebral blood flow (CBF) modulation in both acute and chronic phases. tDCS offers rapid, localized delivery to salvageable ischemic tissue, exerting pleiotropic effects that address a broader spectrum of pathological processes compared to pharmacological agents. Cathodal tDCS shows promise in acute ischemic stroke for neuroprotection in small-scale clinical studies, enhancing CBF and promoting vessel recanalization, while anodal tDCS demonstrates stronger effects on CBF, particularly in chronic stroke and hypoperfusion cases. Bihemispheric stimulation may offer additional benefits, with evidence suggesting a dose-dependent relationship between stimulation parameters and therapeutic outcomes. Further research is warranted to optimize stimulation protocols, evaluate safety and feasibility, and explore the potential of tDCS to promote neuroplasticity and functional recovery across different stroke populations and stages. By addressing these gaps, tDCS could emerge as a valuable adjunctive therapy in stroke management, complementing current interventions and expanding therapeutic windows.

Background: Syncope is a common presenting complaint in the outpatient setting and requires a thoughtful and meticulous approach to history-taking skills. This is crucial in discerning cardiac versus non-cardiac etiologies, underscoring the pivotal role of healthcare professionals in the diagnostic process. Case Report: This is a case of a 76-year-old male who presented to the primary care clinic following an episode of syncope with abrupt loss of consciousness. Given the presentation, there was a high suspicion of cardiac etiology, and further testing was pursued. An electrocardiogram (ECG) demonstrated normal sinus rhythm with a pre-existing first-degree atrioventricular (AV) block. The Holter monitor was without sustained arrhythmias. A dobutamine stress echocardiogram was negative for myocardial ischemia, though a resting transthoracic echocardiogram demonstrated findings consistent with cardiac amyloidosis. Further evaluation with cardiology confirmed the diagnosis of transthyretin (ATTR) cardiac amyloidosis. He was initiated on appropriate treatment and underwent a dual chamber implantable cardioverter defibrillator (ICD) given his presentation. The patient ultimately succumbed to his disease 5 years after his diagnosis. Conclusion: If the cardiac etiology of syncope is suspected, further cardiac structural evaluation is necessary. Cardiac amyloidosis, although rare, is a cause of cardiogenic syncope that should not be overlooked. It should be considered in the differential diagnosis in the appropriate clinical setting, highlighting the need for a broad and comprehensive approach to diagnosis.

Abstract Aims To evaluate clinical outcomes, echocardiographic features, and the efficacy and safety of sacubitril/valsartan compared to valsartan across age groups in the PARAGON-HF trial. Methods and results A total of 4796 participants ≥50 years of age with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) ≥45% were divided into three age groups: <65 years (n = 825), 65–74 years (n = 1772), and ≥75 years (n = 2199). Echocardiograms of 1097 patients were analysed in a standardized fashion at a core imaging laboratory. The primary composite outcome was total HF hospitalizations and cardiovascular (CV) death. Older patients were more likely to experience primary composite outcomes (compared to patients <65 years, adjusted rate ratio [aRR] for ≥75 years: 1.39, 95% confidence interval [CI] 1.21–1.61), total HF hospitalization (aRR 1.27, 95% CI 1.09–1.49), and CV death (adjusted hazard ratio [aHR] 2.04, 95% CI 1.44–2.87). Age did not modify the effect of sacubitril/valsartan compared to valsartan on primary composite endpoint (pinteraction = 0.79) in the overall population or in those with LVEF ≤57%. Older adults randomized to sacubitril/valsartan were more likely to develop hypotension compared to those receiving valsartan (pinteraction = 0.026). Older patients had smaller left ventricular chamber sizes, higher LVEF, and were more likely to have abnormal measures of diastolic function. Conclusion Older patients with HF with preserved ejection fraction had higher event rates than younger patients, more adverse events overall, and more hypotension when treated with sacubitril/valsartan; however, the treatment benefits of sacubitril/valsartan were retained in older patients.

AbstractObjectiveTo compare reflux symptoms, Zenker's diverticulum recurrence, and clinical outcomes in patients with and without a history of hiatal hernia who underwent Zenker's diverticulotomy (ZD).Study DesignSingle institution retrospective review.SettingTertiary care academic hospital.MethodsA retrospective review of patients with and without a history of hiatal hernia who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler, or harmonic scalpel technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, reflux symptoms, and rates of adverse events and symptomatic recurrence.ResultsA total of 426 patients were included in the study, 97 (22.8%) of which had a history of hiatal hernia. Eleven patients (11.3%) with a history of hiatal hernia had undergone Nissen fundoplication prior to ZD. Patients with a history of hiatal hernia showed less symptomatic improvement postoperatively. Significant differences were noted in the change in the Eating Assessment Tool (EAT‐10) (P < .01) and Reflux Symptom Index (RSI) (P = .03) where patients without a history of hiatal hernia improved more than hiatal hernia patients. Despite these differences in symptom relief, rates of postoperative complications and rates of recurrence did not significantly differ between groups. The median time to recurrence was similar for both groups.ConclusionPatients without a history of hiatal hernia had significantly larger improvements in EAT‐10 and RSI scores compared to patients with a history of hiatal hernia. However, these differences in scores may not represent clinically meaningful differences. There were no significant differences in postoperative adverse events or in recurrence of the Zenker's diverticulum between groups.

AbstractObjectiveThe extent of parotidectomy for benign tumors has de‐escalated in the United States. We aim to define modern benchmarks for operative time and hospital length of stay (LOS) in parotidectomy and identify risk factors that may prolong these benchmarks.Study DesignThis is a retrospective cross‐sectional study of all adults who underwent parotidectomy for a primary parotid neoplasm between January 2011 and December 2021 using the American College of Surgeons National Surgical Quality Improvement Program database.MethodsThe extent of parotidectomy was defined using Current Procedural Terminology codes. Prolonged operative time and LOS were defined as above the 75th percentile (longer than 194 minutes and more than 1 day, respectively). Multivariable logistic regression was used to identify patient and surgical risk factors that predict prolonged operative time or LOS.ResultsBenign parotidectomies are mostly performed as outpatient procedures in the United States (average LOS <1 day). Prolonged operative time was independently associated with malignant tumors versus benign tumors (adjusted odds ratio [aOR]: 2.7, 95% confidence interval [CI]: 2.4‐3.0), total parotidectomy with facial nerve sacrifice versus lesser extent of parotidectomy (aOR: 2.3, 95% CI: 1.7‐3.0), and simultaneous reconstructive procedures versus none (P < .001 for all). These features were similarly independently associated with prolonged LOS (P < .001 for all). Complication rates were universally low.ConclusionThe majority of superficial parotidectomies in this country are performed as outpatient procedures requiring <3 hours of operative time, with low complication rates. Malignant tumors, greater extent of parotidectomy, and simultaneous procedures were independently associated with prolonged operative time and LOS. These national benchmarks can inform operating room and hospital bed resource assignments.

Abstract Dilated cardiomyopathy (DCM) is extensively discussed in numerous expert consensus documents and international guidelines, with differing recommendations. To support clinicians in daily practice and decision-making, we conducted a systematic review of key guidelines and recommendations concerning the diagnosis and clinical management of DCM. Our research encompassed MEDLINE and EMBASE databases for relevant articles published, as well as the websites of relevant scientific societies. We identified two guidelines and one scientific statement that met stringent criteria, thereby qualifying them for detailed systematic analysis. Our review revealed consensus on several key aspects: the definition of DCM, the use of B-type natriuretic peptides and high-sensitivity troponin in laboratory testing, the essential role of multimodality cardiovascular imaging for initial diagnosis, genetic counselling, and the management of advanced disease. Nonetheless, notable areas of variation included the formation of multidisciplinary management teams, the role of cascade genetic testing, pathways for arrhythmic risk stratification, and the criteria for prophylactic defibrillator implantation. Significant evidence gaps persist, particularly regarding the clinical trajectory of genetic, non-genetic and gene-elusive forms of DCM, the use of cardiovascular magnetic resonance in phenotype-negative family members with genotype-positive probands, and the development of potential aetiology-oriented therapies. Addressing these gaps could enhance clinical outcomes and inform future research directions and guideline development.