Search

Traumatic intracranial cerebral artery dissection (ICAD) in the pediatric population is relatively rare. We report two traumatic ICAD cases in children. Case 1: A 13-year-old boy presented with headache and left hemiparesis after body contact while playing basketball. We found a cerebral infarction in the middle cerebral artery territory and dissection at the bifurcation of the right internal carotid artery and posterior communicating artery. Six days after onset, his right hemiparesis deteriorated, and the infarction progressed. Therefore, bypass surgery was performed. Three months later, he regained the ability to walk without a cane and resumed school. Case 2: A 10-year-old boy fell while skiing and experienced a severe headache several hours later. Neuroradiological examination revealed a subarachnoid hemorrhage in the basal cistern without aneurysm. Six days after admission, magnetic resonance angiography revealed stenotic changes and an irregularly shaped basilar artery (BA). On day 7, an angiogram confirmed BA dissection. The patient's headache gradually improved, and the irregular shape of the BA normalized 3 weeks later. He was discharged without any neurological deficits. Determining whether vascular reconstruction should be performed is challenging. However, we believe that therapeutic intervention should be performed promptly when symptoms or brain images deteriorate.

Abstract Haploinsufficiency of the transcriptional repressor ZBTB18/RP58 is associated with intellectual disability. However, the mechanisms causing this disability are unknown, and preventative measures and treatments are not available. Here, we assessed multiple behaviors in Zbtb18/Rp58 heterozygous-knockout mice, and examined local field potentials, DNA fragmentation, mitochondrial morphology, and performed histochemical and transcriptome analyses in the hippocampus to evaluate chronic inflammation. In wild-type mice, object location memory was present at a similar level at 2 and 4–5 months of age, and became impaired at 12–18 months. In contrast, Zbtb18/Rp58 heterozygous-knockout mice displayed early onset impairments in object location memory by 4–5 months of age. These mice also exhibited earlier accumulation of DNA and mitochondrial damage, and activated microglia in the dentate gyrus, which are associated with defective DNA repair. Notably, chronic minocycline therapy, which has neuroprotective and anti-inflammatory effects, attenuated age-related phenotypes, including accumulation of DNA damage, increased microglial activation, and impairment of object location memory. Our results suggest that Zbtb18/Rp58 activity is required for DNA repair and its reduction results in DNA and mitochondrial damage, increased activation of microglia, and inflammation, leading to accelerated declines in cognitive functions. Minocycline has potential as a therapeutic agent for the treatment of ZBTB18/RP58 haploinsufficiency-associated cognitive dysfunction.

Background: Despite providing valuable staging and prognostic information, the therapeutic benefit of pelvic lymph node dissection (PLND) remains uncertain. We sought to assess the effect of extended PLND (ePLND) on the biochemical recurrence (BCR) of patients with National Comprehensive Cancer Net (NCCN) high- or very high-risk prostate cancer treated via robot-assisted radical prostatectomy (RARP). Methods: We used a multi-institutional database (six centers) to assess 989 patients who underwent RARP from 2014 to 2022 with or without ePLND, among which 699 patients underwent BCR analysis. We performed 1:1 propensity score matching to account for potential differences between the two groups and compared them in terms of BCR-free survival. Cox's regression models were used to test the effect of ePLND on BCR. Results: A total of 585 patients underwent ePLND and 404 did not. A median of 19 lymph nodes was removed in the ePLND cohort. After propensity score matching, no significant differences in BCR-free survival were observed between the two cohorts (HR 1.108, 95% CI 0.776–1.582, p = 0.556). Multivariable Cox's regression models adjusted for the preoperative and postoperative tumor characteristics revealed that PLND was not an independent predictor of BCR. Conclusion: No significant differences in BCR-free survival were observed between NCCN high- or very high-risk prostate cancer patients who underwent PLND during RARP and those who did not. The therapeutic utility of PLND thus remains unclear.

Background Despite the high burden of diabetes and cardiovascular risk factors in American Indian communities in the United States, prospective studies of heart failure (HF) in this population group are scarce, and the generalizability of previous HF risk scales may be limited. We developed a parsimonious HF risk prediction equation that accounts for relevant risk factors affecting American Indian communities, focusing on diabetes and kidney damage. Methods and Results A total of 3059 participants from the SHS (Strong Heart Study) (56±8 years of age, 58% women) were included. Five hundred seven developed HF. Progressively adjusted Cox proportional hazards models were used to identify risk factors for HF and HF subtypes. Predictors of risk at 5 and 10 years included older age (hazard ratio [HR], 1.79 [95% CI, 1.43–2.25]; HR, 1.68 [95% CI, 1.44–1.95]), smoking (HR, 2.26 [95% CI, 1.23–4.13]; HR, 2.08 [95% CI, 1.41–3.06]), macroalbuminuria (HR, 8.38 [95% CI, 4.44–15.83]; HR, 5.20 [95% CI, 3.42–7.9]), microalbuminuria (HR, 2.72 [95% CI, 1.51–4.90]; HR, 1.92 [95% CI, 1.33, 2.78]), and previous myocardial infarction (HR, 6.58 [95% CI, 2.54–17.03]; HR, 3.87 [95% CI, 2.29–6.54]), respectively. These predictors, together with diabetes diagnosis and glycated hemoglobin were significant at 10 and 28 years. High discrimination performance was achieved (C index, 0.81 [95% CI, 0.76–0.84]; C index, 0.78 [95% CI, 0.75–0.81]; and C index, 0.77 [95% CI, 0.74–0.78] at 5, 10, and up to 28 years of follow up, respectively). Some associations varied across HF subtypes, although diabetes, albuminuria, and previous myocardial infarction were associated with all subtypes. Conclusions This prospective study of HF risk factors in American Indian communities identifies that smoking, body mass index, and indicators of diabetes control and kidney damage (glycated hemoglobin and albuminuria) are major determinants of HF. Our findings can improve HF risk assessment in populations with a high burden of diabetes.

Abstract Background X‐linked dystrophin‐deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles. Hypothesis/Objectives Identify deleterious genetic variants in DMD by whole‐genome sequencing (WGS) using a next‐generation sequencer. Animals One MD‐affected cat, its parents, and 354 cats from a breeding colony. Methods We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high‐impact variants by in silico analyses. Next, we confirmed the candidate variants by Sanger sequencing using samples from the parents and cats from the breeding colony. We used 2 genome assemblies, the standard felCat9 (from an Abyssinian cat) and the novel AnAms1.0 (from an American Shorthair cat), to evaluate genome assembly differences. Results We found 2 novel high‐impact variants: a 1‐bp deletion in felCat9 and an identical nonsense variant in felCat9 and AnAms1.0. Whole genome and Sanger sequencing validation showed that the deletion in felCat9 was a false positive because of misassembly. Among the 357 cats, the nonsense variant was only found in the affected cat, which indicated it was a de novo variant. Conclusion and Clinical Importance We identified a de novo variant in the affected cat and next‐generation sequencing‐based genotyping of the whole DMD gene was determined to be necessary for affected cats because the parents of the affected cat did not have the risk variant.

AbstractAlthough the clinical efficacy of tofacitinib has been reported in adult patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (Ab+) dermatomyositis, data on its use in refractory juvenile dermatomyositis (JDM) are scarce. We describe two female Japanese patients with anti-MDA5 Ab + JDM and rapidly progressive interstitial lung disease who achieved remission by adding tofacitinib to existing immunosuppressive drugs and present a literature review. While both patients received various immunosuppressive or anti-inflammatory treatments for induction therapy, remission could not be achieved. Subsequently, tofacitinib was administered to reduce the Krebs von den Lungen-6 level 5 months after diagnosis in one patient; the other patient received tofacitinib 4 months after diagnosis to reduce ferritin levels and skin manifestations. Subsequently, both patients achieved remission, and prednisolone was withdrawn. Tofacitinib reduced the interferon signature associated with dermatomyositis/JDM disease progression and exerted a therapeutic effect on dermatomyositis/JDM. We found six published cases from five articles of tofacitinib for refractory anti-MDA5 Ab + JDM. Except for one case of herpes simplex meningitis, the other cases, including ours, had improved disease activity without severe adverse events, and steroids and immunosuppressive medicines could be tapered. Tofacitinib could be considered an available therapy for refractory anti-MDA5 Ab + JDM.

BackgroundWhile large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries.ResultsAssociations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7).ConclusionsLow frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.

Backgrounds: Remote cardiac rehabilitation has proven useful in patients with cardiovascular disease; however, the methodology had not been fully validated. This study aimed to investigate the efficacy and safety of remote cardiac rehabilitation (RCR) with real-time monitoring and an ergometer using a bidirectional communication tool during the recovery phase of cardiovascular diseases. Methods: This multicenter, nonrandomized, interventional study was conducted at 29 institutions across Japan and enrolled patients with cardiovascular diseases who met indications for cardiac rehabilitation (CR) after receiving in-hospital treatment. The RCR group exercised at home using an ergometer and was monitored in real-time using interactive video and monitoring tools for 2–3 months. Educational instructions were provided concurrently through e-learning approaches. The safety of the RCR protocol and the improvement in peak oxygen consumption (VO2) were compared with those of the historical control group that participated in center-based CR. Results: Fifty-three patients from the RCR group were compared with 103 historical controls having similar background characteristics. No patients in RCR experienced significant cardiovascular complications while engaging in exercise sessions. After 2–3 months of RCR, the peak VO2 improved significantly, and the increases in the RCR group did not exhibit any significant differences compared to those in the historical controls. During follow-up, the proportion of patients whose exercise capacity increased by 10% or more was also evaluated; this finding did not indicate a statistically significant distinction between the groups. Conclusions: RCR during the recovery phase of cardiovascular diseases proved equally efficient and safe as center-based CR.

Introduction Prostatic urethral lift is a treatment option for benign prostatic hyperplasia, yet information on surgeries following this procedure is scarce. Case presentation A 71‐year‐old man with persistent urinary retention following prostatic urethral lift underwent a secondary holmium laser enucleation of the prostate. The morcellation procedure, complicated by the presence of implants from the previous surgery, broke the morcellator blade. The fragmented blade was successfully retrieved without any organ damage. Postoperatively, the patient encountered no complications and showed improvement in his urinary symptoms. Conclusion This case highlights the potential risk of device breakage when a secondary surgery, specifically the morcellation process, is performed following prostatic urethral lift. Care must be taken to prevent interaction between the implants and the morcellator. Our case demonstrates the efficacy of holmium laser enucleation of the prostate as a salvage surgical intervention for patients in whom prostatic urethral lift has failed.

BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P

Background Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. Methods and Results Apparently healthy adult participants (n=280) were randomized to an 8‐minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre−/post‐assessments of endothelial health including endothelium‐dependent vasodilation (reactive hyperemia index), circulating endothelial cell‐derived microparticles (CD62E+, CD31+/CD42−, and CD31+/Annexin V+) and circulating bone marrow‐derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell‐derived microparticles and endothelial progenitor cells from baseline to 40 minutes. Conclusions In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium‐dependent vasodilation.

Introduction: Hypertension affects approximately 50 % of patients with hypertrophic cardiomyopathy (HCM) but clinical course in adults with co-occurring HCM and hypertension is underexplored. Management may be challenging as routine anti-hypertensive medications may worsen obstructive HCM, the most common HCM phenotype. In this scoping review, we sought to synthesize the available literature related to clinical course and outcomes in adults with both conditions and to highlight knowledge gaps to inform future research directions. Methods: We searched 5 electronic databases (PubMed, CINAHL, Scopus, Embase, Web of Science) to identify peer-reviewed articles, 2011–2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guideline. Results: Eleven articles met eligibility. Adults with both conditions were older and had higher rates of obesity and diabetes than adults with HCM alone. Results related to functional class and arrhythmia were equivocal in cross-sectional studies. Only 1 article investigated changes in medical therapy among adults with both conditions. Hypertension was a predictor of worse functional class, but was not associated with all-cause mortality, heart failure-related mortality, or sudden-death. No data was found that related to common hypertension-related outcomes, including renal disease progression, nor patient-reported outcomes, including quality of life. Conclusions: Our results highlight areas for future research to improve understanding of co-occurring HCM and hypertension. These include a need for tailored approaches to medical management to optimize outcomes, evaluation of symptom burden and quality of life, and investigation of hypertension-related outcomes, like renal disease and ischemic stroke, to inform cardiovascular risk mitigation strategies.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Background: Acute respiratory failure has been reported one of the manifestations of hypertensive crisis in pheochromocytoma in human medicine. In dogs, no reports have been described acute respiratory failure following hypertensive crisis. Here, we report the clinical presentation, course, and treatment of acute respiratory failure following hypertensive crisis in a dog with presumed pheochromocytoma or paraganglioma. Case Description: A 12-year-old neutered male toy poodle was referred for the diagnostic evaluation of a right adrenal gland mass. The dog suddenly exhibited severe dyspnea with abnormal hypertension (systolic blood pressure > 200 mmHg) 15 minutes after recovery from the anesthesia for the computed tomography (CT) examination. Pulmonary CT and ultrasonography findings suggested acute onset of severe pulmonary edema. Pulmonary edema was treated with mechanical ventilation (pressure-support ventilation with continuous positive airway pressure) and negative fluid balance after the administration of furosemide. Weaning from mechanical ventilation was successful 24 hours after the onset of respiratory failure. Finally, the dog was discharged 3 days after weaning from ventilation without complications. Conclusion: This report outlines a case of acute respiratory failure following a hypertensive crisis requiring mechanical ventilatory management in a dog. The onset and progression of pulmonary edema were extremely rapid. However, improvement in pulmonary edema was also rapid. Hemodynamic stability, in addition to prompt diagnosis and aggressive therapeutic intervention, including mechanical ventilation, may have contributed to the good prognosis of pulmonary edema following hypertensive crisis in a dog, which we attribute to a catecholamine storm. [Open Vet J 2023; 13(11.000): 1465-1470]

Abstract Background The application of different approaches calculating the anthropogenic carbon net flux from land, leads to estimates that vary considerably. One reason for these variations is the extent to which approaches consider forest land to be “managed” by humans, and thus contributing to the net anthropogenic flux. Global Earth Observation (EO) datasets characterising spatio-temporal changes in land cover and carbon stocks provide an independent and consistent approach to estimate forest carbon fluxes. These can be compared against results reported in National Greenhouse Gas Inventories (NGHGIs) to support accurate and timely measuring, reporting and verification (MRV). Using Brazil as a primary case study, with additional analysis in Indonesia and Malaysia, we compare a Global EO-based dataset of forest carbon fluxes to results reported in NGHGIs. Results Between 2001 and 2020, the EO-derived estimates of all forest-related emissions and removals indicate that Brazil was a net sink of carbon (− 0.2 GtCO2yr−1), while Brazil’s NGHGI reported a net carbon source (+ 0.8 GtCO2yr−1). After adjusting the EO estimate to use the Brazilian NGHGI definition of managed forest and other assumptions used in the inventory’s methodology, the EO net flux became a source of + 0.6 GtCO2yr−1, comparable to the NGHGI. Remaining discrepancies are due largely to differing carbon removal factors and forest types applied in the two datasets. In Indonesia, the EO and NGHGI net flux estimates were similar (+ 0.6 GtCO2 yr−1), but in Malaysia, they differed in both magnitude and sign (NGHGI: -0.2 GtCO2 yr−1; Global EO: + 0.2 GtCO2 yr−1). Spatially explicit datasets on forest types were not publicly available for analysis from either NGHGI, limiting the possibility of detailed adjustments. Conclusions By adjusting the EO dataset to improve comparability with carbon fluxes estimated for managed forests in the Brazilian NGHGI, initially diverging estimates were largely reconciled and remaining differences can be explained. Despite limited spatial data available for Indonesia and Malaysia, our comparison indicated specific aspects where differing approaches may explain divergence, including uncertainties and inaccuracies. Our study highlights the importance of enhanced transparency, as set out by the Paris Agreement, to enable alignment between different approaches for independent measuring and verification.