Surfactant-Free Formate/O2 Biofuel Cell with Electropolymerized Phenothiazine Derivative-Modified Enzymatic Bioanode.

A formate (HCOO-) bioanode was developed by utilizing a phenothiazine-based electropolymerized layer deposited on sucrose-derived carbon. The electrode modified with NAD-dependent formate dehydrogenase and the electropolymerized layer synergistically catalyzed the oxidation of the coenzyme (NADH) and fuel (HCOO-) to achieve efficient electron transfer. Further, the replacement of carbon nanotubes with water-dispersible sucrose-derived carbon used as the electrode base allowed the fabrication of a surfactant-free bioanode delivering a maximum current density of 1.96 mA cm-2 in the fuel solution. Finally, a separator- and surfactant-free HCOO-/O2 biofuel cell featuring the above bioanode and a gas-diffusion biocathode modified with bilirubin oxidase and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) was fabricated, delivering a maximum power density of 70 µW cm-2 (at 0.24 V) and an open-circuit voltage of 0.59 V. Thus, this study demonstrates the potential of formic acid as a fuel and possibilities for the application of carbon materials in bioanodes.

Combined pituitary hormone deficiency harboring CHD7 gene missense mutation without CHARGE syndrome: a case report.

BACKGROUND: Heterozygous loss-of-function mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene cause CHARGE syndrome characterized by various congenital anomalies. A majority of patients with CHARGE syndrome present with congenital hypogonadotropic hypogonadism (HH), and combined pituitary hormone deficiency (CPHD) can also be present. Whereas CHD7 mutations have been identified in some patients with isolated HH without a diagnosis of CHARGE syndrome, it remains unclear whether CHD7 mutations can be identified in patients with CPHD who do not fulfill the criteria for CHARGE syndrome. CASE PRESENTATION: A 33-year-old woman was admitted to our hospital. She had primary amenorrhea and was at Tanner stage 2 for both pubic hair and breast development. She was diagnosed with CPHD (HH, growth hormone deficiency, and central hypothyroidism), and a heterozygous rare missense mutation (c.6745G > A, p.Asp2249Asn) in the CHD7 gene was identified. Our conservation analysis and numerous in silico analyses suggested that this mutation had pathogenic potential. She had mild intellectual disability, a minor feature of CHARGE syndrome, but did not fulfill the criteria for CHARGE syndrome. CONCLUSIONS: We report a rare case of CPHD harboring CHD7 mutation without CHARGE syndrome. This case provides valuable insights into phenotypes caused by CHD7 mutations. CHD7 mutations can have a continuous phenotypic spectrum depending on the severity of hypopituitarism and CHARGE features. Therefore, we would like to propose a novel concept of CHD7-associated syndrome.

Exogenous insulin antibody syndrome in a patient with diabetes secondary to total pancreatectomy.

Exogenous insulin can induce insulin antibodies that have a low affinity/high binding capacity. Similar to what is observed in insulin autoimmune syndrome, these insulin antibodies can cause fasting hypoglycemia and postprandial hyperglycemia, a phenomenon known as "exogenous insulin antibody syndrome" (EIAS). Cases of EIAS in patients with type 1 and type 2 diabetes have been sporadically reported, mainly in Asia. However, there has been no report on EIAS in patients with diabetes secondary to total pancreatectomy treated with insulin analogs. A 74-year-old man with diabetes after total pancreatectomy had been treated with continuous subcutaneous insulin infusion using an insulin analog, lispro, and developed recurrent early morning hypoglycemia even after discontinuation of nocturnal basal insulin. His fasting serum lispro level was high even approximately 9 h after the last lispro dose. He had a high titer (72.7%) of insulin antibodies, and a Scatchard analysis revealed low affinity/high binding capacity. These findings suggested that the patient's recurrent early morning hypoglycemia was associated with insulin antibodies against lispro, and we, therefore, switched from lispro to another insulin analog, glulisine. His hypoglycemia improved, accompanied by a dramatic decrease in his insulin antibodies and serum glulisine levels. Early morning hypoglycemia in patients with diabetes secondary to total pancreatectomy may often be explained by high glycemic variability, malnutrition, and/or glucagon deficiency. However, in cases of recurrent early morning hypoglycemia, EIAS should be considered as a potential differential diagnosis.

Metformin-associated Lactic Acidosis with Hypoglycemia during the COVID-19 Pandemic.

Metformin-associated lactic acidosis (MALA) is an extremely rare but life-threatening adverse effect of metformin treatment. The lifestyle changes associated with the coronavirus disease 2019 (COVID-19) pandemic may increase the potential risk of MALA development in patients with diabetes. We herein report a 64-year-old Japanese man taking a small dose of metformin who presented with MALA accompanied by hypoglycemia secondary to increased alcohol consumption triggered by lifestyle changes during the pandemic. Physicians should prescribe metformin judiciously to prevent MALA development and pay close attention to lifestyle changes in patients at risk for MALA during the COVID-19 pandemic.

Coexistence of Renin-independent Aldosterone Secretion and Multiple Endocrine Neoplasia Type 1 Within a Family.

Primary aldosteronism (PA) is a state of renin-independent aldosterone secretion that can range from subclinical to overt. Some normotensive individuals for whom PA screening is not routinely recommended are reported to fulfill the loading test criterion used for the diagnosis of PA. Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the development of various endocrine tumors. Cases of PA associated with MEN1 have been reported; however, there has been no previous report on renin-independent aldosterone secretion within a family with MEN1. Herein, we present the case of a normotensive family presenting with both MEN1 and renin-independent aldosterone secretion. A 49-year-old man was admitted to our hospital for PA evaluation owing to the plasma aldosterone concentration/plasma renin activity ratio being greater than the screening cut-off value; the patient was normotensive. The patient had a history of left nephrectomy and adrenalectomy for left renal carcinoma and adrenal tumor at the age of 39 years. Subsequently, he was diagnosed with MEN1 concurrent with primary hyperparathyroidism, insulinoma, and novel MEN1 gene mutations (c.655-5_655-4insC and c.818delC). The loading tests for PA confirmation, including saline infusion, and furosemide upright and captopril challenge tests, yielded positive findings, confirming a case of renin-independent aldosterone secretion. The patient's mother, brother, and sister were also genetically or clinically diagnosed with MEN1. All of them were also normotensive and confirmed to have renin-independent aldosterone secretion. The coexistence of renin-independent aldosterone secretion and MEN1 within this family suggests a relationship between the 2 entities.

Medium-term Influence of the Coronavirus Disease 2019 Pandemic on Patients with Diabetes: A Single-center Cross-sectional Study.

Objective This study evaluated the lifestyle changes in patients with diabetes and their independent associations with glycemic and body weight control. In addition, the correlation between changes in mental health and lifestyles was evaluated. Methods This single-center cross-sectional study included 340 patients with diabetes who periodically visited our department. Changes in dietary habits, activities of daily living, and mental health before and during approximately six months after the onset of the coronavirus disease 2019 (COVID-19) pandemic were evaluated using a questionnaire, including the International Physical Activity Questionnaire-Short Form. Results Approximately 20%, 30%, and over 50% of patients had worsened dietary habits, decreased activities of daily living, and deteriorated mental health, respectively. A multiple regression analysis showed that irregular meal timing was significantly associated with change in HbA1c (ß=0.328, p=0.001), and decreased walking time was significantly associated with changes in body weight (ß=-0.245, p=0.025). The change in fear and anxiety was positively associated with changes in meal timing regularity (r=0.129, p=0.019) and carbohydrate consumption (r=0.127, p=0.021). Subsequently, the change in depressed mood was positively associated with changes in carbohydrate (r=0.142, p=0.010) and alcohol (r=0.161, p=0.037) consumption, and the change in psychological stress was positively associated with changes in carbohydrates (r=0.183, p=0.001) and snack (r=0.151, p=0.008) consumption as well as sedentary time (r=0.158, p=0.004). Conclusion The COVID-19 pandemic has had a considerable medium-term impact on the lifestyle and mental health of patients with diabetes. Lifestyle changes were associated with glycemic and body weight control, and mental health changes were associated with lifestyle changes. These findings may provide important information on diabetes care during the pandemic.

Case of slowly progressive type 1 diabetes mellitus with drastically reduced insulin secretory capacity after immune checkpoint inhibitor treatment for advanced renal cell carcinoma.

We encountered a 55-year-old Japanese man with advanced renal cell carcinoma and slowly progressive type 1 diabetes mellitus (SPT1DM), whose insulin secretory capacity was drastically reduced for a brief period after only one cycle of immune checkpoint inhibitor (ICI) treatment. The patient had been diagnosed with type 2 diabetes at the age of 53 years and was treated using oral hypoglycemic agents. However, 2 years later, he was diagnosed with SPT1DM and autoimmune thyroiditis, based on the presence of anti-glutamic acid decarboxylase antibodies (GADA) and thyroid autoantibodies, which was accompanied by advanced renal cell carcinoma. At that time, his insulin secretory capacity was preserved (CPR 2.36 ng/mL), and good glycemic control was maintained using only medical nutrition therapy (HbA1c 6.3%). He subsequently developed destructive thyroiditis approximately 2 weeks after the first cycle of ICI treatment using nivolumab (a programmed cell death-1 inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen-4 inhibitor) for advanced renal cell carcinoma. Three weeks later, his plasma glucose level markedly increased, and we detected absolute insulin deficiency and hypothyroidism. Human leukocyte antigen (HLA) analysis revealed haplotypes indicating susceptibility to type 1 diabetes mellitus (T1DM) or autoimmune thyroiditis (HLA genotype, DRB1-DQB1 *09:01-*03:03/*08:03-*06:01). He showed a good antitumor response and is currently receiving permanent insulin therapy and levothyroxine replacement with the ICI treatment. Based on this case and the available literature, patients with preexisting islet autoantibodies or SPT1DM/LADA, plus a genetic predisposition to T1DM, may have an extremely high risk of developing ICI-related T1DM for a brief period after starting ICI treatment.

Hypoglycemia during the Concomitant Use of Repaglinide and Clopidogrel in an Elderly Patient with Type 2 Diabetes and Severe Renal Insufficiency.

Hypoglycemia should be avoided when treating patients with diabetes. Repaglinide is an insulin secretagogue with a low hypoglycemic risk because of its rapid- and short-acting effects. However, its blood concentration has been reported to increase in combination with clopidogrel, an antiplatelet drug, and in patients with severe renal insufficiency. We herein report an elderly patient with type 2 diabetes mellitus and severe renal insufficiency who received repaglinide and hypoglycemia three days after starting clopidogrel. The concomitant use of repaglinide and clopidogrel can lead to hypoglycemia, especially in patients with severe renal insufficiency.

Impact of contrast-induced acute kidney injury on outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PURPOSE: The purpose of this study was to identify predictors of contrast-induced acute kidney injury (CI-AKI) and the effect of CI-AKI on cardiovascular outcomes after hospital discharge in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS AND MATERIALS: We retrospectively reviewed 194 STEMI consecutive patients who underwent primary PCI to evaluate the predictors for CI-AKI and 187 survivors to examine all-cause mortality and cardiovascular events. Outcomes were compared between patients with CI-AKI and those without CI-AKI, which was defined as an increase >50% or >0.5mg/dl in serum creatinine concentration within 48hours after primary PCI. RESULTS: CI-AKI occurred in 23 patients (11.9%). Multivariate analysis identified pre-procedural renal insufficiency as a predictor of CI-AKI, and this predictor was independent from hemodynamic instability and excessive contrast volume. Receiver-operator characteristics analysis demonstrated that patients with an estimated glomerular filtration rate (eGFR) of ≤43.6ml/min per 1.73m(2) had the potential for CI-AKI. Patients who developed CI-AKI had higher mortality and cardiovascular events than did those without CI-AKI (27.8% vs. 4.7%; log-rank P=.0003, 27.8% vs. 11.2%; log-rank P=.0181, respectively). Cox proportional hazards model analysis identified CI-AKI as the independent predictor of mortality and cardiovascular events [hazard ratio [HR]=5.36; P=.0076, HR=3.10; P=.0250, respectively]. CONCLUSIONS: The risk of CI-AKI is increased in patients with pre-procedural renal insufficiency, and eGFR is clinically useful in the emergent setting for CI-AKI risk stratification before primary PCI.

Noninvasive demonstration of dual coronary artery fistulas to main pulmonary artery with 64-slice multidetector-computed tomography: a case report.

Coronary artery fistulas, including coronary pulmonary fistulas, are usually discovered accidently among the adult population when undergoing invasive coronary angiographies. We report here a 58-year-old woman with dual fistulas originating from the left anterior descending coronary artery and right coronary sinus to the main pulmonary artery, demonstrating noninvasively with multidetector-computed tomography (MDCT) and transthoracic echocardiography (TTE).