Citations

Abstract Introduction Brain abscess is a serious condition in children, leading to rapid deterioration, and permanent neurological damage associated with significant morbidity and mortality. Current management protocols for brain abscesses focus on intravenous antibiotics and surgical excision and drainage. Case Presentation A 12-year-old adolescent male who had headache and photophobia and was diagnosed with multiple brain abscesses and was refractory to conventional medical and neurosurgical intervention. A single dose of 10 mg vancomycin was administered through endo-ventricular drain, resulting in resolution of abscesses and alleviation of symptoms. Conclusion We describe the first instance of intraventricular vancomycin use in the pediatric age group for the treatment of multiple brain abscesses. Given the variability in dosing reported in the literature, our case report warrants further studies to standardize dosage for this rare intervention.

Background Heart failure self‐care can contribute to a high daily workload and treatment burden. The goal of this cohort study was to assess the characteristics and outcomes associated with burden of treatment (BoT). Methods Surveys comprising validated instruments to measure BoT and other constructs were mailed to patients with heart failure in Southeastern Minnesota. Participants were divided into tertiles by BoT scores. Associations of clinical variables with BoT were examined using multinomial logistic regression. Associations of BoT with mortality and hospitalizations were examined using Cox proportional hazard regression and Andersen–Gill models, respectively. Results A total of 609 participants (mean age 76.3 years, 60.3% men, 55.2% urban, 64.3% preserved ejection fraction) completed surveys. Higher BoT was associated with worse health status, more depressive symptoms, lower resilience, less social support, lower medication adherence, and worse health literacy. Mean±SD follow‐up was 14.4 (4.1) months. Estimated 1‐year mortality (8.3% [95% CI, 4.3%–12.1%], 11.0% [95% CI, 6.5%–15.2%], 16.0% [95% CI, 10.8%–21.0%]) and 1‐year mean cumulative hospitalizations (0.57 [95% CI, 0.45–0.72], 0.83 [95% CI, 0.66–1.05], 1.15 [95% CI, 0.93–1.42]) increased across patients reporting low, medium, and high BoT, respectively. Adjustment for health status eliminated any significant association of BoT with risks of death and hospitalization (adjusted hazard ratio [HR], 1.10 [95% CI, 0.58–2.07] and 1.09 [95% CI, 0.74–1.61], respectively, highest versus lowest BoT tertile). Conclusions BoT in heart failure varies by clinical and psychosocial factors. Higher BoT identifies patients at increased risk of adverse health outcomes due to their worse health status. These findings can serve as a foundation for interventions to minimize workload and improve quality of life.

ABSTRACTBackgroundMagnetic resonance elastography (MRE) quantifies tissue viscoelasticity, offering insights into intracranial meningiomas. MRE‐derived parameters, including the storage modulus (G') and the magnitude of the complex modulus (|G*|), may aid neurosurgical planning, but their repeatability remains unexplored in brain tumors.Purpose/HypothesisTo evaluate the repeatability of G' and |G*| in meningiomas, the influence of tumor volume and spatial location on variability, and ranking stability across paired elastograms.Study TypeProspective.Population/SubjectsSeventeen paired MRE scans from 16 patients with meningiomas (mean age 64 ± 12 years, 10 females) scheduled for resection.Field Strength/SequenceMRE was performed on a 3 T system using a single‐shot spin‐echo echo‐planar imaging (SE‐EPI) sequence.AssessmentTumors were segmented on contrast‐enhanced T1‐weighted images; distance and volume metrics were extracted. Regions of interest were applied to G' and |G*| elastograms. Repeatability was evaluated using the coefficient of variation (CV%). Ranking stability was assessed by comparing median G' or |G*| values.Statistical TestsThe difference in CV% was assessed using the Wilcoxon signed rank test. Linear regression assessed the effect of tumor volume and distance from the external occipital protuberance (EOP) on CV%. The Wilcoxon signed‐rank test evaluated ranking stability and scan‐rescan CV%. Statistical significance was defined as p < 0.05.ResultsThe difference in CV% G' (14.89 ± 12.32) and CV% |G*| (13.88 ± 12.60) was not significant (p = 0.61). Tumor volume inversely correlated with CV% (G': β = −0.75 |G*|: β = −0.59). Tumor‐EOP distance had no significant effect (G': p = 0.58, |G*|: p = 0.23). Rankings remained stable (G': p = 0.82, |G*|: p = 0.71).Data ConclusionMRE‐derived parameters are repeatable in intracranial meningiomas, with G' and |G*| being equally stable. Larger tumors yielded more consistent estimates. Preserved ranking stability supports the use of MRE in preoperative planning.Evidence Level2.Technical EfficacyStage 2.

Abstract While adrenal androgen production is primarily regulated by ACTH, some data suggest a less common association between hyperprolactinemia and elevated dehydroepiandrosterone sulfate (DHEA-S). We describe 2 patients with this underrecognized connection. Patient 1, a 60-year-old male, was incidentally found to have bilateral adrenal masses on computed tomography during evaluation of gastrointestinal complaints. Further workup revealed elevated levels of DHEA-S and prolactin, with pituitary macroadenoma identified as the cause, given normalization of both prolactin and DHEA-S on cabergoline therapy. Patient 2, a 38-year-old male, presented with visual field defects, and subsequent pituitary magnetic resonance imaging confirmed a macroadenoma. He also had markedly elevated levels of DHEA-S and prolactin. Both patients were treated with cabergoline, leading to rapid normalization of both prolactin and DHEA-S levels. These cases demonstrate an association between hyperprolactinemia and elevated DHEA-S, supported by the normalization of levels with medical treatment of prolactinoma. Although hyperprolactinemia in the context of a prolactinoma is an uncommon cause of elevated DHEA-S, it should be considered once other etiologies have been excluded.

ABSTRACTPolycythemia vera (PV) is invariably associated with a JAK2 mutation, with over 50% of patients harboring additional non‐JAK2 mutations. In the current study, 319 patients with PV underwent NGS at diagnosis or in chronic phase PV (Group A: N = 270, 85%) or at the time of fibrotic (Group B; N = 37, 12%) or leukemic (Group C; N = 12, 4%) transformation. Mutational frequencies involving TP53/SRSF2/IDH1/U2AF1 were significantly (p < 0.05) different between patients in the mutually exclusive Groups A (2%/4%/2%/0.4%), B (8%/0%/0%/5%), and C (50%/25%/17%/8%). Analyses on phenotype/genotype associations and prognostic impact on overall (OS), leukemia‐free (LFS), and myelofibrosis‐free (MFFS) survival were limited to Group A patients. ASXL1MUT was associated with younger age (p < 0.01), SRSF2MUT with older age and leukocytosis (p < 0.01), and TP53MUT with leukocytosis (p < 0.01). Mutation co‐segregation was apparent between ASXL1 and IDH2 (p < 0.01) or SRSF2 (p < 0.01), SRSF2 and IDH2 (p < 0.01), and TP53 and NRAS (p = 0.01). Multivariable analysis identified SRSF2MUT (p < 0.01; HR, 4.2, 1.9–9.5), IDH2MUT (p = 0.01; HR, 5.3, 1.8–15.3), ASXL1MUT (p = 0.04; HR, 2.0, 1.1–3.7), leukocyte count ≥ 15 × 109/L (p < 0.01; HR 2.0, 1.3–3.1), and advanced age (p < 0.01) as risk factors for OS. Median OS in the presence (N = 235; 87%) or absence (N = 35; 13%) of any adverse mutation (i.e., SRSF2MUT, ASXL1MUT, or IDH2MUT) was 8.8 versus 17.8 years (p = 0.01; HR 1.8, 1.1–2.9). In addition, ASXL1MUT (p = 0.02; HR, 1.6–24.9), SRSF2MUT (p = 0.06; HR, 11.9, 1.1–126.2), and advanced age (p = 0.04) were associated with inferior LFS, and SRSF2MUT (p < 0.01; HR, 24.0, 5.5–103.8) and abnormal karyotype (p < 0.01; HR 3.8, 1.6–8.9) with inferior MFFS. The number of non‐JAK2 mutations was significant in predicting outcome in univariate but not multivariable analysis. The observations from the current study highlight the prognostic significance of non‐JAK2 mutations in PV and the prospect of their inclusion in future prognostic models.

Abstract Background Doxycycline is a frequently used alternative treatment for community-acquired pneumonia (CAP) in hospitalized patients; however, the evidence base is limited. We aimed to compare outcomes in CAP patients treated with doxycycline or azithromycin in combination with beta-lactams. Methods We evaluated patients with CAP admitted to Mayo Clinic hospitals from May 2018 to September 2022 and treated with either azithromycin or doxycycline in combination with a beta-lactam. Patients who received both antibiotics or were on either antibiotic as chronic therapy prior to admission were excluded. The primary outcome was mortality. Patients were 1-to-1 matched according to the presence of congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, human immunodeficiency virus infection, recent immunosuppressant use, and pneumonia severity index class. Results Among 8492 patients (5810 for azithromycin, 2682 for doxycycline), 2671 doxycycline-treated patients were matched with azithromycin-treated patients. In-hospital mortality was significantly lower in the azithromycin group than in the doxycycline group (odds ratio, 0.71; 95% confidence interval [CI], .56–.9), as was 90-day mortality (hazard ratio, 0.83; 95% CI, .73–.95). Patients on azithromycin also had significantly more hospital-free days (HFDs) than those on doxycycline (estimate, 1.37; 95% CI, .99–1.74). Conclusions Among hospitalized patients with CAP, azithromycin was associated with lower mortality and more HFDs compared with doxycycline in combination with beta-lactams. Randomized, controlled trials are needed to assess the effectiveness of each regimen and to compare their potential side effects.

Abstract Context Primary aldosteronism (PA) is a leading endocrine cause of secondary hypertension. Objective To support the development of the Endocrine Society Clinical Practice Guideline on managing PA. Data Source MEDLINE, Embase, Scopus, and others were searched on October 4, 2024. Study Selection Studies were selected by pairs of independent reviewers. Data Extraction Data were extracted and appraised by pairs of independent reviewers. Data Synthesis We included 95 studies (7 randomized trials and 88 observational studies). We did not identify trials that evaluated the outcomes of PA screening. One observational study suggested that screening was associated with higher rates of using PA-specific medical therapies and better blood pressure control. Patients managed with adrenal venous sampling (vs computed tomography alone) may have a better post-adrenalectomy biochemical cure rate, but with an increased risk of adrenal hemorrhage. Two small observational studies suggested that PA-specific medical or surgical therapy was likely associated with better blood pressure control than nonspecific therapy. Small randomized trials suggested that surgical therapy may be associated with better blood pressure control than medical therapy, with a lower number and dosage of antihypertensive medications. Compared to eplerenone, spironolactone may be associated with better control of hypokalemia and a lower number and dosage of antihypertensive agents. Unsuppressed plasma renin activity was associated with better control of hypokalemia, while suppression was associated with higher risk of mortality, atrial fibrillation, and stroke (very low certainty). Conclusion This systematic review addresses various aspects of managing PA and will support the development of the Endocrine Society guidelines.

ABSTRACT Background and hypothesis Podocytopathy associated with likely pathogenic/pathogenic variants of Transient receptor potential cation channel subfamily C member 6 (TRPC6) (TRPC6-AP) has been recognized for about 20 years. As a result of its rarity however, the spectrum of clinical phenotypes and genotype–phenotype correlation of TRPC6-AP remains poorly understood. Here, we characterized clinical, histological and genetic correlates of familial and sporadic patients with TRPC6-AP. Methods In this multicentre observational study, an online questionnaire followed by a systematic literature review was performed to create a cohort with comprehensive data on genetic and clinical outcomes [age of onset, clinical presentation, treatment response, kidney biopsy findings and progression to kidney failure (KF)]. Logistic regression, Cox proportional hazards model and Kaplan–Meier analyses investigated the associations between genetic variants and disease progression. Results Among 87 families (96 familial and 45 sporadic cases), 31 distinct missense TRPC6 variants (including 2 novel) were identified, with c.2683C&gt;T p.(Arg895Cys) and c.523C&gt;T p.(Arg175Trp) the commonest variants. Proteinuric kidney disease/nephrotic syndrome was the most common clinical presentation (83.7%), while focal segmental glomerulosclerosis was the most common histological finding (89.4%). By 33 (interquartile range 17–40) years, 48.9% (69/141) of patients had progressed to KF. Sporadic TRPC6-AP demonstrated an earlier progression to KF than familial cases (P = .001) and were more likely to present with nephrotic syndrome [odds ratio 4.34 (1.85–10.15); P = .001]. Gain-of-function TRPC6 variants were more frequent in familial than sporadic TRPC6-AP (70.8% vs 44.4%; P = .004). Compared with patients with other TRPC6 variants, patients with TRPC6 p.R175W and p.R895C variants progressed to KF earlier [median kidney survival of 21 years, hazard ratio 2.985 (95% confidence interval 1.40–5.79); and 38 years, hazard ratio 1.65 (95% confidence interval 1.01–2.81), respectively, log-rank P = .005]. Conclusion Our study shows unique clinical and genetic correlations of TRPC6-AP, which may enable personalized care and promising novel therapies.

Background: Osteochondral allograft transplant and autograft transplant for femoral head defects have emerged as promising treatments for concomitant cartilage and subchondral bone injuries in young patients. Purpose: To evaluate the clinical and radiological outcomes of patients who underwent osteochondral allograft or autograft transplant for femoral head defects and identify any risk factors that may lead to conversion to total hip arthroplasty (THA). Study Design: Case series; Level of evidence, 4. Methods: All patients who underwent osteochondral allograft or autograft transplant for femoral head defects across 2 institutions were analyzed. Clinical outcomes were assessed at final follow-up with the modified Harris Hip Score (mHHS), Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool (iHOT-12). Complications and reoperations were recorded. Patients were assessed radiographically preoperatively and at final follow-up for osteoarthritis using Tönnis grading. Results: A total of 27 patients were included in this study (19 osteochondral allograft transplant, 8 osteochondral autograft transplant). The mean follow-up for the allograft and autograft cohorts was 2.8 and 9.5 years, respectively. The mean defect size for patients who underwent allograft and autograft transplant was 2.8 × 2.1 cm and 1.6 × 1.0 cm, respectively. The mean mHHS, HOS-ADL, HOS-SSS, and iHOT-12 for the allograft cohort were 86.7, 92.8, 81.4, and 79.0, respectively, and for the autograft cohort were 87.6, 92.7, 83.1, and 82.0, respectively. No significant difference in outcomes was noted for patients who underwent femoral head allograft versus nonorthotopic femoral condyle allograft transplant. For the allograft cohort, 4 patients (21.1%) underwent conversion to THA at a mean of 1.9 years. Of the remaining 15 allograft patients, only 1 patient (6.7%) had radiographic osteoarthritis progression. None of the patients in the autograft cohort underwent conversion to THA. Conclusion: Osteochondral allograft and autograft transplant for femoral head defects demonstrated overall favorable clinical outcomes and rates of conversion to THA. Additionally, nonorthotopic femoral condyle allografts demonstrated similar outcomes to femoral head allografts. Both osteochondral allograft and autograft transplant should be considered for patients with focal femoral head defects.

ABSTRACT Objective There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence. Methods Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted. Results A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low‐flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized. Conclusion Skull base reconstruction and post‐ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences.