Association of Medication Profiles, Including Polypharmacy, Guideline-Directed Medical Therapy, and Potentially Inappropriate Medications, With All-Cause Mortality in Older Adults With Heart Failure, With or Without Frailty and Disability.

Background: Polypharmacy, driven by guideline-directed medical therapy (GDMT) and medications for comorbidities, including potentially inappropriate medications (PIMs), is common in older adults with heart failure (HF). Although medication profiles affect survival, the effects of frailty and disability status remain underexplored.

Methods And Results: This retrospective study assessed polypharmacy (≥5 medications), the use of GDMT, and PIMs based on the Beers Criteria.

Causes of applying Long-Term Care Insurance certification for patients with heart failure with systolic dysfunction.

Aim: The number of patients with heart failure with disability and the use of Long-Term Care Insurance (LTCI) has been increasing in the Japanese aging society. This study investigated the main causes of LTCI demands for better care management.

Methods: We carried out a retrospective study including patients with heart failure with reduced ejection fraction in seven hospitals in Niigata City from 2011 to 2016.

Repeated inhalation of GM-CSF by nonhuman primates induces bronchus-associated lymphoid tissue along the lower respiratory tract.

Background: Repeated inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently approved in Japan as a treatment for autoimmune pulmonary alveolar proteinosis. However, the detailed physiological and pathological effects of repeated inhalation in the long term, especially at increasing doses, remain unclear.

Methods: In this chronic safety study, we administered 24 cynomolgus monkeys (Macaca fascicularis) aged 2-3 years with aerosolized sargramostim (a yeast-derived recombinant human GM-CSF [rhGM-CSF]) biweekly for 26 weeks across four dosing groups (0, 5, 100, and 500 µg/kg/day).

Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes.

Methods: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks.

Validation of a Cox prognostic model for tooth autotransplantation.

Objectives: This study aimed to validate our Cox proportional hazards prognostic model for autotransplantation of teeth with complete root formation using prognostic index (PI) and determine whether the prognosis can be predicted.

Patients And Methods: The Protocol group, as a training data set for validation, consisted of 259 autotransplanted teeth to create a PI using the Cox model, as described previously. The Pre-protocol group, as the first validation data set, consisted of 95 autotransplanted teeth treated without a protocol.

Relationship Between Medical Therapy, Long-Term Care Insurance, and Comorbidity in Elderly Patients With Heart Failure With Systolic Dysfunction.

Background: Although guideline-directed medical therapy (GDMT), including β-blockers, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), improves survival and quality of life, most patients with heart failure with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction are treated with inadequate medications. We investigated the prescription patterns of GDMT in elderly patients with HFrEF and HFmrEF and their characteristics, including the certification of long-term care insurance (LTCI), which represents frailty and disability.

Methods and results: This retrospective cross-sectional study analyzed 1,296 elderly patients with symptomatic HFrEF and HFmrEF with diuretic use (median age 78 years; 63.

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

Background: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets.

Methods: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed.

Urinary A- and C-megalin predict progression of diabetic kidney disease: an exploratory retrospective cohort study.

Aims: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD).

Methods: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation.

Reduced-dose WBRT combined with SRS for 1-4 brain metastases aiming at minimizing neurocognitive function deterioration without compromising brain tumor control.

Background And Purpose: To minimize cognitive decline without increasing brain tumor recurrence (BTR) by reduced-dose whole-brain radiotherapy (RD-WBRT) (25 Gy, 10 fractions) + stereotactic radiosurgery (SRS) in patients with ≤ 4 brain metastases.

Materials And Methods: Eligible patients with ≤ 4 brain metastases on contrast-enhanced MRI and Karnofsky Performance Status ≥ 70. The primary endpoint was the non-inferiority of BTR at distant sites in the brain (BTR-distant)-free survival at 6 months compared to that of the standard dose (SD)-WBRT (30 Gy, 10 fractions) + SRS arm in a randomized clinical trial (JROSG99-1) of SRS with/without SD-WBRT.

Incidence and Risk Factors of Future Need for Long-Term Care Insurance in Japanese Elderly Patients With Left Ventricular Systolic Dysfunction.

Background: Heart failure in elderly people causes physical and cognitive dysfunction and often requires long-term care insurance (LTCI); however, among patients with left ventricular (LV) systolic dysfunction, the incidence and risk factors of future LTCI requirements need to be elucidated.

Methods and results: The study included 1,852 patients aged ≥65 years with an echocardiographic LV ejection fraction (LVEF) ≤50%; we referred to their LTCI data and those of 113,038 community-dwelling elderly people. During a mean 1.

Low-dose Droperidol Reduces the Amplitude of Transcranial Electrical Motor-evoked Potential: A Randomized, Double-blind, Placebo-controlled Trial.

Background: Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes.

Methods: Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.

Placebo-Controlled, Double-Blind Study of Empagliflozin (EMPA) and Implantable Cardioverter-Defibrillator (EMPA-ICD) in Patients with Type 2 Diabetes (T2DM): Rationale and Design.

Introduction: Type 2 diabetes (T2DM) is associated with cardiovascular death, including sudden cardiac death due to arrhythmias. Patients with an implantable cardioverter-defibrillator (ICD) are also at high risk of developing a clinically significant ventricular arrhythmia. It has been reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular deaths; however, the physiological mechanisms of this remain unclear.

Novel scoring system for differentiating parechovirus-A3 and enterovirus infection in neonates and young infants.

Background: Parechovirus-A3 (PeV-A3) and the enteroviruses (EVs) are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants; however, differences in the clinical presentations of two infections are not well described.

Objectives: To describe the clinical presentations of PeV-A3- and EVs-related diseases and develop a novel scoring system to differentiate two diseases.

Study Design: This prospective study used real-time PCR and genetic sequencing to evaluate viral etiologies of febrile neonates and infants <4 months with suspected sepsis or meningoencephalitis in Niigata area, Japan, in 2014-2016.

Rice Endosperm Protein Administration to Juvenile Mice Regulates Gut Microbiota and Suppresses the Development of High-Fat Diet-Induced Obesity and Related Disorders in Adulthood.

Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear.

Does maternal autoantibody that transfer to newborn cause disease?

Autoimmune pulmonary alveolar proteinosis (aPAP) is associated with excess amount of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody (GMAb) in the lung and blood. We experienced a female case with severe aPAP who could continue her pregnancy under home oxygen therapy and delivered a newborn by caesarean section. Maternal serum GMAb remained high level for up to one year after the delivery, although aPAP entered remission by whole lung lavage.

Inhaled GM-CSF for Pulmonary Alveolar Proteinosis.

Background: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear.

Memory B cell pool of autoimmune pulmonary alveolar proteinosis patients contains higher frequency of GM-CSF autoreactive B cells than healthy subjects.

The IgG-type neutralizing GM-CSF autoantibody (GMAb) is known to be the causative agent for autoimmune pulmonary alveolar proteinosis (APAP). Previous studies report that serum levels of IgG-GMAb are approximately 50-fold higher in APAP patients than in healthy subjects (HS). Serum levels of IgM-GMAb are also higher in APAP patients than in HS, but this has been assumed to be an etiological bystander.

Incidence of autoimmune pulmonary alveolar proteinosis estimated using Poisson distribution.

The incidence and prevalence of autoimmune pulmonary alveolar proteinosis in Japan were previously estimated to be 0.49 and 6.2 per million, respectively.