Citations

Importance Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and is the most common inherited kidney disorder worldwide. ADPKD accounts for 5% to 10% of kidney failure in the US and Europe, and its prevalence in the US is 9.3 per 10 000 individuals. Observations ADPKD is typically diagnosed in individuals aged 27 to 42 years and is primarily caused by pathogenic variants in the PKD1 (78%) or PKD2 (15%) genes. Most persons with ADPKD have an affected parent, but de novo disease is suggested in 10% to 25% of families. More than 90% of patients older than 35 years have hepatic cysts, which may cause abdominal discomfort and occasionally require medical or surgical intervention. Hypertension affects 70% to 80% of patients with ADPKD, and approximately 9% to 14% develop intracranial aneurysms, which have a rupture rate of 0.57 per 1000 patient-years. Approximately 50% of individuals with ADPKD require kidney replacement therapy by 62 years of age. The severity of kidney disease can be quantified using the Mayo Imaging Classification (MIC), which stratifies patients based on total kidney volume adjusted for height and age and ranges from 1A to 1E. Patients with MIC 1C to MIC 1E have larger kidneys because of more rapid growth (6%-10% per year) compared with those with MIC 1A and 1B (1%-5% per year) and have earlier progression to kidney replacement therapy, which occurs at a mean age of 58.4 years for MIC 1C, 52.5 years for MIC 1D, and 43.4 years for MIC 1E. Optimal management of ADPKD includes systolic blood pressure lower than 120 mm Hg for most patients, but lower than 110/75 mm Hg for patients with MIC 1C to 1E who have an estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m 2 and are younger than 50 years, dietary sodium restriction (<2000 mg/d), weight management, and adequate hydration (>2.5 L daily). The vasopressin type 2 receptor antagonist tolvaptan reduces the annual rate of eGFR decline by 0.98 to 1.27 mL/min/1.73 m 2 and is indicated for patients with MIC 1C to 1E or an eGFR decline greater than 3 mL/min/1.73 m 2 per year to slow disease progression and delay the onset of kidney failure. Conclusion ADPKD is the most common genetic kidney disease worldwide and is characterized by progressive development of kidney cysts. Patients typically have hypertension and liver cysts, and 9% to 14% develop intracranial aneurysms. First-line treatment includes blood pressure control, dietary and weight management, and adequate hydration. Tolvaptan reduces the rate of eGFR decline for those at high risk of rapid progression to kidney failure.

Abstract Emphysema’s significant morbidity and mortality underscore the need for reliable outcome metrics in clinical trials. However, commonly accepted chronic obstructive pulmonary disease outcome measures do not adequately capture emphysema severity or progression. Computed tomography (CT) metrics have been validated as accurate indicators of pathological emphysema and predictors of chronic obstructive pulmonary disease progression, exacerbations, and mortality. This position paper reviews the evidence supporting CT densitometry as a biomarker for emphysema, establishes implementation standards, and highlights areas for future research. A systematic literature review addressed three key questions: whether CT densitometry can be used as a diagnostic biomarker of emphysema, whether CT densitometry can be used as a prognostic biomarker, and whether longitudinal change in densitometry can be used as a disease progression monitoring biomarker. Emphysema metrics, such as the percentage of low attenuation areas below −950 Hounsfield units, are validated, highly reproducible diagnostic and prognostic biomarkers. Volume-adjusted lung density is recommended for disease monitoring. Both metrics demonstrate a scan–rescan intraclass correlation coefficient of 0.99 with proper technique. The paper also discusses relevant CT physics, techniques, and sources of variation, including technical factors, physiological changes, and software analysis. Key recommendations for clinical trials include using standardized CT techniques, proper subject selection, and longitudinal evaluation with volume-adjusted lung density.

Context.— In 2018, an evidence-based guideline was published by the College of American Pathologists to develop recommendations for the testing, application, interpretation, and reporting of high-risk human papillomavirus and surrogate marker tests in head and neck carcinomas. Substantial new evidence has prompted a review, including data on human papillomavirus (HPV) in nonoropharyngeal anatomic sites, HPV global rates, p16 immunohistochemistry, and HPV testing performance in cytology specimens, and performance of p16 immunohistochemistry as a surrogate marker. Objective.— To assess research published since the release of the original 2018 guideline and to update evidence-based recommendations for HPV testing in head and neck carcinomas. Design.— The College of American Pathologists convened a panel of experts to update the guideline following the standards established by the National Academy of Medicine for developing trustworthy clinical practice guidelines. The expert panel defined the key questions and performed a systematic review of the literature. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, recommendations were updated on the basis of available evidence, certainty of that evidence, and key judgments. Results.— Seven strong recommendations, 4 conditional recommendations, and 5 good practice statements are offered in the guideline update. Conclusions.— The updated guideline statements provide direction on the nature of HPV testing in various head and neck specimens (including key updates based on new research on sinonasal squamous cell carcinoma) and expanded guidance on specific scenarios and practice settings. The goal is to improve and standardize, where possible, HPV testing across diverse pathology practice settings and different countries.

The heat shock protein B8 (HSPB8) is one of the small heat shock proteins (sHSP or HSPB) and is a ubiquitous protein in various organisms, including humans. It is highly expressed in skeletal muscle, heart, and neurons. It plays a crucial role in identifying misfolding proteins and participating in chaperone-assisted selective autophagy (CASA) for the removal of misfolded and damaged, potentially cytotoxic proteins. Mutations in HSPB8 can cause distal hereditary motor neuropathy (dHMN), Charcot–Marie–Tooth (CMT) disease type 2L, or myopathy. The disease can manifest from childhood to mid-adulthood. Most missense mutations in the N-terminal and α-crystallin domains of HSPB8 lead to dHMN or CMT2L. Frameshift mutations in the C-terminal domain (CTD), resulting in elongation of the HSPB8 C-terminal, cause myopathy with myofibrillar pathology and rimmed vacuoles. Myopathy and motor neuropathy can coexist. HSPB8 frameshift mutations in the CTD result in HSPB8 mutant aggregation, which weakens the CASA ability to direct misfolded proteins to autophagic degradation. Cellular and animal models indicate that HSPB8 mutations drive pathogenesis through a toxic gain-of-function mechanism. Currently, no cure is available for HSPB8-associated neuromuscular disorders, but numerous therapeutic strategies are under investigation spanning from small molecules to RNA interference to exogenous HSPB8 delivery.

BACKGROUND The clinical and radiological evolution of large capillary telangiectasias is largely unknown. OBSERVATIONS A 30-year-old female presented with progressive ataxia and nystagmus. She was found to have a large, diffuse enhancing pontomedullary lesion with associated hypointensity on susceptibility-weighted imaging consistent with a large capillary telangiectasia. In addition, she had a second capillary telangiectasia in the right frontal lobe, hypertrophic olivary degeneration (HOD), and multiple susceptibility lesions throughout the brain. The patient’s condition continued to deteriorate and she became nonambulatory over 8 years, with right-sided hemiparesis and hemiataxia, nystagmus, palatal myoclonus, and a left abducens palsy. Over the follow-up period, serial MR images showed increased cavitation of the lesion and significant brainstem atrophy. LESSONS Capillary telangiectasias are generally small, benign lesions composed of dilated capillaries. However, when large (≥ 1 cm), they can be symptomatic. The authors present the case of a diffuse capillary telangiectasia of the pons with HOD and a progressively declining course due to brainstem atrophy and enlarging cavitation of the lesion. The radiological evolution of an aggressive capillary telangiectasia has not been previously reported. https://thejns.org/doi/10.3171/CASE24746

Recurrent coarctation of the aorta (reCoA) can be treated via redo surgical or endovascular means with the latter option providing a shorter hospitalization, expedient recovery, and a lower incidence of early morbidity and mortality. A common barrier to endovascular repair with standard thoracic endografts is the proximity of the left subclavian artery (LSA) to the reCoA which has previously necessitated adjunctive open revascularization or additional off-label endovascular techniques. This case describes percutaneous endovascular repair of postsurgical reCoA and a poststenotic descending thoracic aortic aneurysm with an off-the-shelf thoracic branched endograft incorporating the LSA with successful resolution of aortic pressure gradient and complete aneurysm exclusion. Clinical Impact This case highlights the use of a commercially available, off-the-shelf endograft to treat thoracic aortic coarctation and associated aortic aneurysm. The paper highlights unique technical points for use of the Gore Thoracic Branch Endoprosthesis in the off-label treatment of thoracic aortic coarctation which is an ideal endovascular option for lesions in proximity to the left subclavian artery.

Background Over half of ICU survivors experience post intensive care syndrome (PICS). Few PICS clinics were operational in the United States at the onset of the COVID-19 pandemic. Here we describe early experience of such a clinic at a large academic medical center. Our objective was to describe the (a) model of care (b) clinic interventions (c) short-term cognitive, psychiatric, and functional outcomes (d) one-year outcomes of COVID-19 ICU survivors at the Cleveland Clinic post-ICU recovery clinic (PIRC). Methods We conducted a retrospective cohort study through a chart review of all patients seen in PIRC from April 2020 – December 2020. A total of 59 patients completed the visit with 49% being virtual, and 51% being in-person. The cohort was predominantly white (50.8%), and male (57.6%) with a median age of 58.2 years. We screened for cognitive and psychiatric impairments using several different validated questionnaires. Functional impairments were self-reported and detected after assessment by a physical therapist. Quantifiable clinic interventions were referrals, pharmacy medication reconciliation, and vaccine administration. One-year outcomes were health care utilization, and death. Results In our cohort, 36%, 39.6%, and 17% of patients screened positive for cognitive impairment, anxiety and/or depression, and PTSD respectively. 42.3% of patients had lower extremity mobility impairment. 57.6% of patients required at least one referral after clinic. Of the 67.9% of patients who were working and 93.9% driving prior to hospitalization, only 24.6% and 73.2% had returned to those activities, respectively. The most common pharmacy intervention was discontinuation of a medication no longer in use. By one year, 34% of patients had hospital re-admissions with 5% requiring the ICU. There were no deaths. Conclusions Adult survivors of COVID-19 critical illness have impairments in all PICS domains as well as high health care utilization in the first year after hospital discharge. MeSH Terms Post intensive care syndrome, COVID-19 Key Points/Summary Adult survivors of COVID-19 critical illness have impairments in all PICS domains as well as high health care utilization in the first year after hospital discharge. Post-ICU recovery clinics can help survivors with recovery.

Abstract Aims Functional tricuspid regurgitation (FTR) associated with degenerative mitral regurgitation (DMR) accentuates the severity of heart failure and is a marker of poor prognosis. Little is known about FTR associated with asymptomatic DMR. Methods and results The study included 1249 asymptomatic patients with moderate or severe DMR from the Mitral Regurgitation International Database-Quantitative (MIDA-Q) registry (mean age 64 ± 15 years, 25% female). Despite the asymptomatic status, absent/trivial FTR was noted in only 42%, mild in 34.5%, moderate in 11%, and severe FTR in 12.5%. Patients with higher FTR grades were older and more often female and had higher EuroScore II, larger left atrial volumes, and more atrial fibrillation (all P < 0.05). Patients with moderate or severe FTR had comparable 5-year survival (64 ± 4% and 65 ± 4%) and lower than patients with no/trivial FTR(96 ± 1%, P < 0.001). After adjustment for key prognostic factors, including age, left ventricular dilatation and dysfunction, DMR severity, left atrial dilatation, and pulmonary hypertension, ≥moderate FTR remained a strong predictor of mortality (HR = 2.08 [1.17–3.72], P = 0.013). Sensitivity analysis showed stable impact of ≥moderate FTR among patients with/without pulmonary hypertension, in women and men and for any other subset. For patients who underwent mitral valve surgery, post-operative survival rates were similar between those with no/trivial FTR and those with ≥moderate or severe FTR (P = 0.76), suggesting that surgery could reduce the excess mortality related to preoperative FTR. Conclusions Among asymptomatic patients with significant DMR, ≥moderate FTR is frequent and independently associated with higher mortality, independently of traditional guideline-based risk factors. These findings suggest that ≥moderate FTR should lead to consideration of early mitral surgery to improve outcomes.

AbstractEpilepsy syndromes are distinct electroclinical entities which have been recently defined by the International League Against Epilepsy Nosology and Definitions Task Force. Each syndrome is associated with “a characteristic cluster of clinical and EEG features, often supported by specific etiologic findings”. Syndromes often present in an age‐dependent manner, carry both prognostic and treatment implications, and are associated with a specific range of comorbidities. Syndromes are most commonly identified in young children and are less frequent in adults. Syndrome identification assists clinicians in selecting the highest yield investigations, the most effective therapies, and allows them to give more accurate prognoses both with regards to seizure control and potential remission as well as expected, associated comorbidities. This review outlines how syndromes are organized and defined, highlighting the characteristic features of the more common entities.Plain Language SummaryEpilepsy syndromes are identifiable entities that are characterized by specific seizure type(s) and EEG findings. Identification of an epilepsy syndrome often provides a clue to the underlying cause, helps clinicians select the most effective treatments, and provides information on the likely outcome.

ABSTRACTBackgroundEfficient discharge planning is crucial for improving hospital capacity and patient care. Multidisciplinary rounds (MDRs) have been shown to enhance communication and coordination, yet their impact on resident teaching teams’ discharge efficiency is less studied.AimsTo examine how embedding dedicated case managers (CMs) and social workers (SWs) into internal medicine (IM) resident teams impacts discharge efficiency.MethodsWe conducted a retrospective cross‐sectional study at The Queen's Medical Center comparing two resident multidisciplinary teaching (MDT) teams that included dedicated CMs and SWs with two resident standard care teams over an 8‐month period (October 18 2023–June 25 2024). The outcomes assessed included length of stay (LOS), expected discharge date (EDD) accuracy, readmission rates and the rate of conditional discharge orders placed.ResultsA total of 1944 patients were included. The MDT teams showed significantly improved EDD accuracy (72.0% vs 66.7%, P = 0.0120) and more frequently placed conditional discharge orders (61.7% vs 43.8%, P < 0.0001) compared to standard care teams. No significant difference was observed in LOS or readmission rates.ConclusionEmbedding dedicated CMs and SWs within resident teams improved EDD accuracy and the rate of conditional discharge orders placed, suggesting an opportunity to integrate MDRs as a standard within IM residency training to enhance discharge planning efficiency.