Mild Neurological Manifestations Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Children During the Omicron Wave in Singapore: A Retrospective Cohort Review.

BACKGROUND: Neurological complications with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant have been reported in adults; however, there are little data in the pediatric population. We aimed to report on the prevalence and clinical characteristics of children with neurological symptoms during the SARS-CoV-2 omicron wave. METHODS: This was a single-center, retrospective cohort review of children (<18 years old) hospitalized for SARS-CoV-2 infection from December 2, 2021, to June 30, 2022. RESULTS: During the study period, 455 children (mean age 4.8 years, range 0.67 to 18, male 58.9%) were hospitalized with SARS-CoV-2 infection. A total of 108 (23.7%) children experienced neurological symptoms; most common were seizures (62.0%), headaches (32.4%) and giddiness (14.8%). Seizures included febrile seizures (64.1%), acute symptomatic seizures (17.9%), and breakthrough seizures in known epileptics (17.9%). Children with neurological manifestations were older (7.3 vs 4.0 years, P < 0.00001), more likely to have underlying epilepsy (9.3% vs 1.2%, P = 0.0002) or neurodevelopmental disorders (17.6% vs 1.7%, P < 0.00001), and presented earlier in their illness (2.1 vs 2.8 days, P < 0.00001), compared with those without neurological manifestations. Neurological symptoms fully resolved in all but one patient at discharge. There were no mortalities and no difference in duration of hospitalization (3.1 vs 3.7 days, P = 0.5) between the groups. CONCLUSIONS: One in four hospitalized children with SARS-CoV-2 infection when omicron variant was dominant experienced mild neurological symptoms. Overall risk factors for neurological symptoms associated with SARS-CoV-2 included older age, pre-existing febrile seizures/epilepsy and neurodevelopmental disorders.

Non-Tuberculous Mycobacterial Cervicofacial Lymphadenitis in Children-10-Year Experience in a Tertiary Pediatric Center.

BACKGROUND: Lymphadenitis is the most common manifestation of non-tuberculous mycobacteria (NTM) infection in children. We describe the epidemiology and clinical characteristics of NTM lymphadenitis, determine diagnostic yield from tissue sampling, and review management and outcomes. METHODS: This was a 10-year retrospective review of children aged 0-16 years diagnosed with NTM cervicofacial lymphadenitis who were seen in a pediatric infectious disease clinic in a tertiary public hospital. Data relating to patient demographics, clinical features, surgical and antimicrobial treatment, complications, and outcomes were retrieved from patients' electronic medical records and analyzed. RESULTS: There were 48 episodes of NTM cervicofacial lymphadenitis in 45 children (17 males and 28 females). Of these episodes, 43.7% manifested as a unilateral single node, mostly parotid (39.6%) and submandibular (29.2%). All patients underwent diagnostic fine-needle aspiration or surgery. Surgical excision more frequently yielded positive histological findings (P = .016). NTM was identified in 22/48 episodes (45.8%) via culture or molecular sequencing. Mycobacterium abscessus was most commonly found (47.8%). Thirty-eight children (79.2%) received antibiotics. Outcomes in 43 episodes revealed full resolution in 69.8%, while 25.6% had de novo disease and 4.6% experienced recurrence at the same site. Overlying skin changes and multiple or bilateral nodal diseases were significantly associated with de novo disease or recurrence (P = .034 and .084, respectively). Complications occurred in 11/70 (15.7%) procedures. Antibiotic-associated adverse effects occurred in 14/38 (36.8%) episodes. CONCLUSIONS: NTM lymphadenitis remains a challenging condition. More aggressive management with surgical excision and antibiotics is recommended for those with overlying skin changes and extensive nodal disease.

Short-term effects of transcatheter aortic valve replacement on blood pressure and cardiac function in elderly patients with severe aortic stenosis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a standard treatment for elderly and high-risk patients with aortic valve stenosis (AS); however, its short-term effects on blood pressure (BP) and cardiac function are not clear. Therefore, we aimed to determine the short-term effects of TAVR in elderly patients (>75 years), who reflect the clinical situation in Japan. METHOD AND RESULTS: Twenty-eight consecutive elderly patients with severe AS and hypertension who underwent TAVR under general anesthesia were retrospectively investigated. All patients had hypertension that was well controlled with antihypertensive drugs. Serum brain natriuretic peptide level and peak velocity in the aortic valve were significantly reduced. TAVR induces an increase in BP that requires additional antihypertensive agents. There was no correlation between the change rate of SBP and stroke volume index (SVI), but there was a positive correlation between the rate of change in pulse pressure (PP) and SVI. This tendency was particularly observed in patients with low brachial-ankle pulse wave velocity (baPWV). CONCLUSION: We observed post-TAVR hypertension and required additional antihypertensive drugs. The increases in SVI and PP after TAVR resulted in post-TAVR hypertension. Moreover, post-TAVR hypertension is less likely to occur in elderly patients with a high baPWV, which indicates advanced arteriosclerosis.

SARS-CoV-2-Related Acute Necrotizing Encephalopathy of Childhood With Good Response to Tocilizumab in an Adolescent.

BACKGROUND: Acute necrotizing encephalopathy of childhood (ANEC) is a rare parainfectious neurological disorder. ANEC is associated with a high mortality rate and poor neurological outcomes. ANEC is postulated to arise from immune-mediated or metabolic processes driven by viral infections. Although there have been some case reports of acute necrotizing encephalopathy with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection in adults, paediatric cases are rare. METHODS: A single case report of SARS-CoV-2-related ANEC in an 11-year-old boy is presented through retrospective chart review. Literature search was performed using PubMed, Embase, Cochrane database, and Google Scholar to compare and analyze similar cases of parainfectious immune-mediated encephalopathies related to SARS-CoV-2 in children. RESULTS: An 11-year-old boy with acute SARS-CoV-2 infection presented with ophthalmoplegia, ataxia, and aphasia. Neuroimaging findings demonstrated significant swelling and signal changes in bilateral thalami, brainstem, and cerebellar hemispheres, consistent with ANEC. His high ANEC Severity Score indicated poor neurological prognosis. Treatment with a combination of early steroid therapy, intravenous immunoglobulin therapy, and targeted interleukin 6 (IL-6) blockade yielded good neurological improvements. Literature search identified 19 parainfectious immune-mediated neurological disorders related to SARS-CoV-2 in children. The only other pediatric ANEC case identified was postinfectious and thus not included. CONCLUSIONS: This is the first report of a pediatric case of SARS-CoV-2-related ANEC, which responded well to early immunotherapy, including IL-6 blockade. Early immunotherapy with IL-6 blockade can be considered as an adjunct in managing severe ANEC.

Vascular Endothelial Dysfunction in Myeloproliferative Neoplasms and Gene Mutations.

Essential thrombocythemia (ET) and polycythemia vera (PV), are common Philadelphia-negative myeloproliferative neoplasms (MPN). Patients with MPN have a high rate of cardiovascular complications and often have acquired JAK2V617F and CALR genetic mutations. In this study, we aimed to analyze vascular endothelial function in patients with MPN.We evaluated 27 outpatients, including 10 patients diagnosed with MPN, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilation (NMD), between September 2014 and August 2016. We measured serum adiponectin, which protects vascular endothelial function, and serum asymmetric dimethyl arginine (ADMA), which inhibits the production of adiponectin. The presence or absence of JAK2V617F and CALR mutations was evaluated in patients with MPN.Venous thrombosis was observed more frequently in patients with MPN than in those without. Seven MPN patients were diagnosed with PV, and 3 MPN patients were diagnosed with ET. JAK2V617F and CALR mutations were found in 5 and 3 MPN patients, respectively. FMD was significantly lower in JAK2V617F-positive MPN patients than in JAK2V617F-negative MPN patients, although NMD, adiponectin, and ADMA were similar in both groups. Adiponectin levels were higher and ADMA levels were lower in CALR-positive MPN patients than in CALR-negative MPN patients. There was no difference in FMD and NMD prevalence between the 2 groups. Furthermore, we had 3 representative MPN patients who were complicated with coronary spasm, possibly caused by MPN-related endothelial dysfunction.We found that patients with MPN presented with endothelial dysfunction, which was related to the presence of genetic mutations and was sometimes associated with cardiovascular disease.

Prolonged sinus arrest due to the obstruction of a sinus node branch after percutaneous coronary intervention of the right coronary artery.

Myocardial ischemia due to narrowing of the right coronary artery (RCA) may result in sinus arrhythmias, which usually present as transient sinus bradycardia with no hemodynamic instability. We report a rare case of sinus arrest with hemodynamic instability, which lasted for several months, and was caused by the occlusion of the sinus node (SN) artery following the RCA stenting. A 78-year-old woman with diabetes mellitus, hypertension, and dyslipidemia was referred to our hospital because of chest pain during activity. In her coronary angiogram, severe diffuse stenosis of the RCA was observed and intracoronary imaging using intravascular ultrasound revealed diffuse atherosclerotic plaque lesions with partial calcification and vulnerability. RCA was treated by inserting three zotarolimus-eluting stents. Immediately after these interventions, the SN artery originating from the RCA proximal to the lesion was occluded, which resulted in SN dysfunction. Significant bradycardia was observed on electrocardiogram along with low blood pressure, suggesting sinus arrest. Along with hemodynamic instability, sinus arrest lasted for several months, and permanent pacemaker implantation was needed. The plaque burden should be taken into consideration when choosing the appropriate percutaneous coronary intervention strategy because of the potential complication of sinus arrest after RCA stenting. .

Primary cardiac B cell lymphoma in an immunocompetent patient.

Primary cardiac lymphoma is a rare entity of extranodal lymphoma and is observed with increasing frequency in immunocompromised hosts. However, a considerable proportion of cardiac lymphomas still occur in immunocompetent patients. We report the case of a 55-year-old immunocompetent Japanese man with a large amount of pericardial fluid and the presentation of heart failure secondary to primary cardiac B cell lymphoma, which was diagnosed by cytological examination of pericardial fluid and imaging. The right atrium, right ventricle and pericardium were affected by the tumour, which encased the mid/distal portion of the right coronary artery (RCA). Pretreatment optical coherence tomography of the RCA demonstrated no tumour extension into the vascular structure but a focal mural thrombus. We initiated chemotherapy (steroid therapy then COP at half dose/R-CHOP/R-CHASE) [COP (C: Cyclophosphamide, O: Oncovin, P: Prednisolone) R-CHOP (R: Rituximab, C: Cyclophosphamide, H: Doxorubicin Hydrochloride, O: Oncovin, P: Prednisolone) R-CHASE (R: Rituximab, C: Cyclophosphamide, HA: high dose Cytarabine, S: Steroid, E: Etoposide)]with administration of low-dose aspirin to prevent possible ischaemic events. The patient had a good clinical course without adverse events except for transient pericarditis.

Primary Aldosteronism Associated with Multiple Adrenocortical Micronodules in a Patient with Renal Cell Carcinoma.

A 47-year-old woman with a history of diabetes mellitus (DM) and obesity was admitted to our hospital for glucose control. She was detected to have hypertension (HT) and diagnosed with primary aldosteronism (PA) based on the high level of aldosterone to renin ratio and the results of the upright furosemide-loading test according to the criteria of the Japanese Society of Hypertension (JSH) guidelines. Computed tomography revealed left renal tumor and adrenocortical adenoma. She underwent left nephrectomy and adrenalectomy. The pathological findings were clear-cell renal cell carcinoma (RCC) and nonfunctional adrenocortical adenoma. Her nonneoplastic adrenal tissue histologically revealed CYP11B2-positive multiple adrenocortical micronodules (MNs) and concomitant paradoxical hyperplasia of the zona glomerulosa. Therefore, MNs were thought to be responsible for PA in this patient. After surgery, HT was improved, and the result of upright furosemide-loading test after 12 months of surgery did not fulfill the criteria of PA according to the JSH guidelines. However, the adrenocorticotrophic hormone stimulation test was positive; considering the possibility of slight aldosterone overproduction from the right adrenal gland, the administration of spironolactone was started. Herein, we report a rare case of RCC in conjunction with PA histologically associated with MNs.

Prevalence and Determinants of Cognitive Impairment in Elderly Patients With Heart Failure　- Pilot Study in a Geriatric Hospital.

Background: Elderly patients admitted to hospital with heart failure (HF) often have cognitive impairment, but the association between these conditions is unclear. Methods and Results: We enrolled 43 patients admitted to a geriatric hospital with HF. We evaluated echocardiography, Mini Mental State Examination (MMSE), and extracellular water/total body water (ECW/TBW) ratio (Inbody S10). Mean age was 85.1±8.0 years (range, 60-99 years) and 44.2% of the patients were men. Mean MMSE score was 20.5±5.4, with 66.7% of the patients showing cognitive impairment (MMSE ≤23). There was a significant negative correlation of MMSE score with age (r=-0.344, P=0.032), regular alcohol drinking (r=0.437, P=0.007), uric acid level (r=0.413, P=0.010), and ECW/TBW ratio (r=-0.437, P=0.007). On stepwise regression analysis including these covariates, MMSE score was significantly associated with the ECW/TBW ratio (ß=0.443, P=0.009). When several echocardiography parameters (i.e., end-diastolic left ventricular volume, r=0.327, P=0.048; left atrial volume index, r=-0.411, P=0.012; and transmitral inflow A wave velocity, r=-0.625, P=0.001) were added to the model, MMSE score was found to be related to the A wave (P=0.001) and to atrial volume index (P=0.015), which are measures of diastolic function. Conclusions: In elderly patients with HF, cognitive function might be influenced by body water distribution and diastolic heart function.

Case report of non-ST-segment elevation myocardial infarction diagnosed in spectral detector-based computed tomography performed for the diagnosis of acute pulmonary embolism.

BACKGROUND: Contrast-enhanced spectral detector-based computed tomography (SDCT) allows for the comprehensive and retrospective analysis. We report a case of pulmonary thromboembolism (PE) accompanied by non-ST-segment elevation myocardial infarction (NSTEMI) diagnosed by SDCT. CASE SUMMARY: A 72-year-old man with diabetes mellitus, hypertension, and prostate cancer suddenly developed chest and back pain and had difficulty in breathing at rest. Electrocardiography showed a right bundle branch block without significant ST-segment change. The initial serum troponin I level was 0.05 ng/mL, and the d-dimer level was 14.7 µg/mL. Spectral detector-based computed tomography showed bilateral scattered PE. After admission, his chest pain persisted, and the serum troponin I level 3 h after admission was elevated to 0.90 ng/mL. Reconstruction of SDCT images showed a perfusion defect of the posterolateral left ventricle myocardium. A coronary angiogram showed total occlusion of the obtuse marginal branch (OM); percutaneous coronary intervention was performed. Furthermore, we administered him with oral anticoagulants (OACs) for PE. Spectral detector-based computed tomography tests performed 6 months after the treatment was initiated, until when the dual antiplatelet therapy and OAC therapy were continued, showed improvement in perfusion defects of both pulmonary fields and the myocardium. His treatment was deescalated to single antiplatelet therapy and OAC, and the patient has had a good course. DISCUSSION: Non-ST-segment elevation myocardial infarction is sometimes difficult to diagnose accurately, especially in the hyper-acute phase or in the OM branch. The reconstruction of spectral images from enhanced SDCT was helpful to diagnose this unique combination of PE and NSTEMI and may be useful for evaluating therapeutic effects in such patients.

The efficacy of tolvaptan in treating dasatinib-induced pleural effusions in patients with chronic myelogenous leukemia.

BACKGROUND: Cancer treatment has been developing significantly and cancer-related cardiovascular disease treatments such as various anticancer agents and molecular target drugs have been reported often in the era of oncocardiology. Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy. Dasatinib is a novel tyrosine-kinase inhibitor approved for CML with Philadelphia (Ph) chromosome and the most common adverse effects of dasatinib are peripheral edema and pleural effusion, which sometimes impose the interruption or reduction of dosage of dasatinib treatment, accompanied by diuretic and steroid use. The goal of CML treatment is maintaining hematological control in the long term by controlling these side effects. The aim of this study is to clarify the efficacy of tolvaptan in treating dasatinib-induced fluid retention. METHODS: We retrospectively analyzed six CML patients who received tolvaptan for dasatinib-induced fluid retention. RESULTS: The mean age of patients was 60.5±11.5 years old, and the mean dosage of dasatinib and tolvaptan were 58.3±20.4mg/day and 5.0±1.9mg/day, respectively. Tolvaptan was introduced 564.5±369.9 days after dasatinib was introduced. Ejection fraction (EF) by echocardiography and brain natriuretic peptide (BNP) levels did not change. However, the diastolic function significantly changed [E/e' of the septal side: from 20.3±2.3 to 16.5±4.2, of the lateral side: from 15.0±2.1 to 12.5±3.8 (p<0.05, respectively)]. New York Heart Association functional class was improved from 3.3±0.5 to 1.5 ± 1.2 (p<0.01) and the grades of fluid retention were also improved. Three patients discontinued dasatinib, and two patients could restart the administration of dasatinib after controlling fluid retention. Five patients could control fluid retention and they could continue with dasatinib therapy without any complications. CONCLUSIONS: Tolvaptan may be useful in fluid control in patients with CML treated with dasatinib.

Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy through non-left anterior descending septal perforators.

Percutaneous transluminal septal myocardial ablation (PTSMA) has become a significant treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) despite maximal medical therapy. The target septal arteries usually arise from the left anterior descending artery (LAD). However, when septal perforators do not originate from the LAD, non-LAD septal perforators should be included as candidate-target septal branches that feed the hypertrophic septal myocardium, causing left ventricular outflow tract (LVOT) obstruction. Data pertaining to the procedure remain limited. We aimed to investigate PTSMA through the non-LAD septal perforators in patients with HOCM. In this case series review, we evaluated the baseline characteristics, echocardiographic features, and angiographic features, as well as symptoms and pressure gradient before and after PTSMA through the non-LAD septal perforators. Among 202 consecutive patients who underwent PTSMA for HOCM with LVOT obstruction, 21 had non-LAD septal branches that fed the hypertrophic septal myocardium and received alcohol ablation. Non-LAD septal perforators could be used as an alternative route for PTSMA in patients who experienced ineffective ablation of the septal branch that arises from the LAD. This unique procedure may improve response rates and overall outcomes of patients with HOCM.

Effective alcohol septal ablation for left ventricular outflow tract obstruction in a patient with isolated dextrocardia.

Isolated dextrocardia is a congenital anomaly characterised by the normal position of the thoracic and abdominal viscera with a right cardiac apex. Left ventricular outflow tract obstruction (LVOTO) is a common structural manifestation of hypertrophic cardiomyopathy (HCM). A 65-year-old woman had worsening chest discomfort and dyspnoea on exertion. Chest CT angiography identified the isolated dextrocardia and HCM. Colour Doppler echocardiography showed mosaic flow in the LV outflow, indicating LVOTO. We performed alcohol septal ablation (ASA) under intracardiac echocardiography (ICE)-guided selective myocardial contrasting. This procedure improved provoked intra-LV pressure gradient by Valsalva manoeuvre and nitroglycerin injection from 136 to 50 mm Hg and her symptoms. The unique combination of isolated dextrocardia and left ventricular hypertrophy could have been involved in the formation of latent LVOTO. Even with the anomaly, contrast ICE made it possible to clarify the target septal left ventricular wall of ASA, and we could perform ASA safely.

Evaluation of myocardial glucose metabolism in hypertrophic cardiomyopathy using 18F-fluorodeoxyglucose positron emission tomography.

BACKGROUND: The purposes of this study were to assess the usefulness of myocardial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for evaluating myocardial metabolic status in hypertrophic cardiomyopathy (HCM) and the therapeutic efficacy of alcohol septal ablation (ASA) in hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Thirty HCM patients (64.4±10.5 years, 14 male, 12 hypertrophic non-obstructive cardiomyopathy [HNCM], 16 HOCM, and 2 dilated phase of HCM) underwent 18F-FDG-PET/CT. 18F-FDG uptake was semi-quantitatively evaluated using an uptake score in each 17 segment and the entire LV or regional standardized uptake value (SUV). RESULTS: 18F-FDG uptake was observed mostly in a hypertrophied myocardium in HNCM patients, whereas 18F-FDG was extensively accumulated beyond the hypertrophied myocardium in HOCM patients. There was a positive correlation between the summed uptake score of 18F-FDG and high-sensitive troponin T level in HNCM patients (r = 0.603, p = 0.049), whereas the score was positively correlated with brain natriuretic peptide level (r = 0.614, p = 0.011) in HOCM patients. In 10 patients who received ASA, the maximum SUV of the entire LV was significantly reduced from 5.6±2.6 to 3.2±2.1 (p = 0.040) after ASA. Reduction of that maximum SUV was particularly significant in the lateral region (from 5.5±2.6 to 2.9 ±2.2, p = 0.024) but not significant in the anteroseptal region (from 4.5±2.6 to 2.9±1.6, p = 0.12). CONCLUSION: Extensive 18F-FDG uptake beyond the hypertrophied myocardium was observed in HOCM. ASA attenuates 18F-FDG uptake in a remote lateral myocardium.

Tuberculous pericarditis treated with steroid in a dialysis patient.

Mycobacterium tuberculosis has spread worldwide and its mortality rate had been very high. The prevention technology and antituberculosis (TB) chemotherapy has improved its prognosis. However, immunocompromised patients, such as those who had HIV infection, older age and on haemodialysis, are still at high risk of TB infection. TB pericarditis is a common cause of constrictive pericarditis and its mortality remains high. Early diagnosis and initiation of appropriate therapy are critical to improve mortality. Additionally, detection of an elevation in the adenosine deaminase level in pericardial effusion is reported to be useful. We report the case of an immunocompromised patient with TB pericarditis, and steroid therapy could prevent him from progressing to constrictive pericarditis. The adenosine deaminase value of pericardial effusion was so helpful that we could promptly make clinical and therapeutic decisions.

Impact of age on left ventricular geometry and diastolic function in elderly patients with treated hypertension.

PURPOSE: Left ventricular (LV) remodelling is observed in numerous patients with hypertension and is a principal cause of heart failure in elderly patients. The aim of this study was to determine the relationships between age and structural/functional LV remodelling observed in elderly hypertensive patients. METHODS: A total of 557 elderly hypertensive patients (mean age: 74.0 ± 8.6 years) with preserved LV systolic function underwent echocardiography and 24-hour blood pressure (BP) measurement. RESULTS: Overall, 41.1% of patients had LV hypertrophy, 77.9% had increased relative wall thickness (RWT) defined as RWT >0.42, and 31.8% had both. Logistic analysis of the entire study population showed that increased RWT was associated with both 24-hour systolic BP (odds ratio (OR) 1.38, 95% confidence interval (CI) 1.12 to 1.70) and age (OR 1.32, 95%CI 1.08 to 1.61), whereas increased RWT was associated only with age (OR 1.61, 95%CI 1.23 to 2.11) after excluding patients with LV hypertrophy. Univariate and multivariate linear regression analyses of all patients showed that LV diastolic echocardiographic parameters were consistently associated with age (p ≤ .001) alone, even considering LV structural changes. CONCLUSIONS: Age was independently correlated with LV concentric/functional changes regardless of LV hypertrophy, suggesting that ageing is independently involved in the progression of LV remodelling.