Evaluation of cognitive function in systemic sclerosis patients: a pilot study

Clinical Rheumatology - To investigate cognitive dysfunction in adult patients with systemic sclerosis (SSc) who had no known clinical neurological manifestations and to relate it with other...     

Emergency endoscopic variceal band ligation in a COVID-19 patient presented with hematemesis while on mechanical ventilation

COVID-19, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), is now a global pandemic with serious health consequences. Currently, many strict control measures are applied in health care settings, including endoscopy units, in order to limit virus spread. Several recommendations called to limit endoscopic procedures to emergent endoscopies; however, several uncertainties still exist concerning patient safety, protective measures, and infection control methods in emergency endoscopic settings. In this case report, we present a case of successful endoscopic band ligation for bleeding esophageal varices in man with COVID-19 disease who presented with an acute attack of hematemesis while on mechanical ventilation (MV). Esophago-gastroduodenoscopy was performed in the ICU room after preparing the setting, and revealed large, risky esophageal varices. Endoscopic band ligation was done with successful control of bleeding. Third-level measures of medical protection were applied for the participating medical personnel, and patient monitoring was maintained all through the procedure. After the procedure, the bleeding stopped, and the patient was vitally stable and conscious. We conclude that emergency endoscopic interventions could be performed safely with appropriate arrangements in patients with confirmed COVID-19 on MV.     

Low calcium intake is associated with high plasma homocysteine levels in postmenopausal women

Nutritional interventions targeting homocysteine remain controversial, and further nutritional research is warranted. We thus sought to explore the determinants of plasma homocysteine other than B-group vitamins. This cross-sectional study surveyed the nutritional status of 713 Japanese postmenopausal women using a semiquantitative food frequency questionnaire. Associations between total energy, protein, fat, carbohydrate, and vitamin A and K intakes and homocysteine were insignificant. Mean homocysteine in the second (536.1 ± 34.7 mg/day) and third (712.9 ± 115.6 mg/day) tertiles of calcium intake were lower than in the first tertile (379.6 ± 76.6 mg/day) by ?0.57 nmol/mL (95 % confidence interval, ?1.10 to ?0.04, p = 0.04) and ?1.18 nmol/mL (?1.76 to ?0.60, p < 0.01), respectively, after adjustment for lifestyle and clinical factors (trend p < 0.01). Mean homocysteine in those with dietary calcium intake above the median (>536 mg/day) were lower regardless of the folic acid concentration; the differences were ?1.59 nmol/mL (?2.33 to ?0.85, p = 0.02) and ?0.75 nmol/mL (?1.37 to ?0.12, p < 0.01) for the high (<7.8 ng/mL) and low folic acid groups, respectively. There was no significant association between calcium and folic acid (p = 0.08). In conclusion, further prospective research to confirm our findings is needed for the development of nutritional inventions targeting homocysteine.     

Nardilysin prevents amyloid plaque formation by enhancing α-secretase activity in an Alzheimer's disease mouse model

Amyloid beta (Aβ) peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Alpha-cleavage of APP by α-secretase has a potential to preclude the generation of Aβ because it occurs within the Aβ domain. We previously reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances α-cleavage of APP, which results in the decreased generation of Aβ in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents Aβ deposition in the AD mouse model. The activity of α-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. However, reactive gliosis adjacent to the Aβ plaques, one of the pathological features of AD, was not affected by the overexpression of NRDc. Taken together, our results indicate that NRDc controls Aβ formation through the regulation of α-secretase.     

Third-generation Aromatase Inhibitor Improved Adult Height in a Japanese Boy with Testotoxicosis

In this study, we report a Japanese boy with testotoxicosis due to a heterozygous mutation [p. A572V] in the LH/CGR gene, who was the first boy treated with a third-generation aromatase inhibitor (AI) and reached his adult height in Japan. He showed accelerated growth and rapid penile growth from 3 yr of age and was diagnosed as having testotoxicosis. Combined treatment with anastrozole and spironolactone was started when he was 7 yr old and 145.8 cm (+4.45 SD) tall, at which point his bone age (BA) was 13.5 yr. His predicted adult height (PAH) was estimated to be 158.3 cm. The combined treatment was continued until he was 13 yr old and 166.5 cm tall, with his BA being 15.5 yr. He reached his adult height of 166.9 cm at 15 yr of age. Combined treatment with anastrozole and spironolactone successfully decelerated BA advancement, prolonged pubertal period and improved adult height.     

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, a relative decrease in lymphocytes and increase in neutrophils in TBRS individuals compared to unaffected controls. We were able to recapitulate these hematologic phenotypes in multiple murine models of TBRS and identified rare hematological and non-hematological malignancies associated with constitutive Dnmt3a mutation. We further show that loss of DNMT3A in TBRS is associated with an altered DNA methylation landscape in hematopoietic cells affecting regions critical to stem cell function and tumorigenesis. Overall, our data identify key hematopoietic effects driven by DNMT3A mutation with clinical implications for individuals with TBRS and DNMT3A-associated clonal hematopoiesis or malignancies.     

Obstetrical factors for death and brain injury among extremely-low-birth-weight infants

OBJECTIVE: To examine the obstetrical risk factors for death and brain injury among extremely-low-birth-weight (ELBW) infants (birth weight <1000 g). STUDY DESIGN: Study subjects were 121 ELBW infants born at a single tertiary perinatal center. Death among ELBW infants was considered to have occurred when subjects died within their corrected age of 40 weeks. In the sub-analysis of the 91 ELBW infants who survived their corrected age of 40 weeks, brain injury was defined as present when criteria based on ultrasound and/or MRI were substantiated. RESULTS: A birth weight of <800 g [adjusted odds ratio (OR), 14.57; 95% confidence interval (CI), 4.72-56.98], a younger gestational age of <26 weeks (adjusted OR, 4.64; 95% CI, 1.60-14.90), and a low Apgar score of <5 (adjusted OR, 3.88; 95% CI, 1.32-12.45) were significantly associated with death among ELBW infants. A maternal age of 30 years or older (adjusted OR, 3.71; 95% CI, 1.19-13.35) was only associated with brain injury among surviving ELBW infants. CONCLUSION: Obstetrical care should be aimed at preventing or predicting premature delivery especially at <26 weeks of gestation.     

Frequent scanning using flash glucose monitoring contributes to better glycemic control in children and adolescents with type 1 diabetes

Aims/IntroductionWe examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes.Materials and MethodsThe study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively.ResultsThe median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was <12 times/day were categorized as the low‐frequency group (n = 40), and those who carried out the scanning >12 times/day were categorized as the high‐frequency group (n = 45). Patients in the high‐frequency group were more likely to be treated with insulin pumps compared with those in the low‐frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high‐frequency group showed significantly greater TIR than the low‐frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high‐frequency group showed significantly lower HbA1c levels than the low‐frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P < 0.001).ConclusionsThese findings showed that patients with a higher scanning frequency had better glycemic control, with greater TIRs and lower HbA1c levels, compared with those with a lower scanning frequency. Scanning frequency of >12 times/day might contribute to better glycemic outcomes in real‐world practice in children with type 1 diabetes.