It has become clear that sodium glucose cotransporter (SGLT)-2 inhibitors not only do not increase the incidence of cardiovascular events but they also reduce the duration of hospitalization for heart failure in type 2 diabetes mellitus (T2DM) patients. The administration of SGLT2 inhibitor in T2DM patients with hypertension and a fluid retention tendency lowers the blood pressure and mitigates fluid retention. It also reduces the heart rate in T2DM patients with a fast heart rate. As an explanation for the multifaceted effects of SGLT2 inhibitors on hemodynamics, we hypothesize that these agents act on the inter-organ communication pathway, which modulates the sympathetic nerve activity to the cardiovascular system.

Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.

Objective The feasibility of continuous geriatric assessments (GAs) has not been evaluated fully in elderly patients with cancer. We prospectively investigated this issue by administering a recommended-GA set (r-GA) repeatedly to patients undergoing chemotherapy for gastrointestinal cancer on an outpatient basis.

Methods We administered the r-GA before chemotherapy and every two months thereafter. Continuous GAs was defined as the completion of at least two assessments, including the pre-treatment evaluation. The r-GA included the Barthel Index [Basic Activities of Daily Living (BADL)], Mini-Mental State Examination-Japanese (MMSE-J), Instrumental Activities of Daily Living (IADL) scale, Vitality Index (VI), and Geriatric Depression Scale-15. We also used the Vulnerable Elders Survey (VES)-13 to screen overall vulnerability. We analyzed the correlations between each baseline GA score and the overall survival (OS) and the association between the OS and changes in each patient's GA scores over time.

Patients Patients ≥65 years of age who presented to our department for initial consultation were enrolled and followed between December 2012 and January 2017.

Results Twenty-one elderly patients (median age, 76 years old) were enrolled. GAs were completed within 20 minutes. In an age- and performance status (PS)-adjusted Cox proportional hazards analysis, the baseline BADL, MMSE-J, and VI scores correlated significantly with the OS (p=0.012, p=0.032, and p=0.012, respectively). During the clinical course, decreases in the MMSE-J and VES-13 scores were correlated with the OS (p=0.022 and p=0.019, respectively).

Conclusion Outpatient GA administration is feasible. Low baseline BADL, MMSE-J, and VI scores and decreased MMSE-J and VES-13 scores over time may prognosticate the OS.

Objective The frontal QRS-T angle on a 12-lead electrocardiogram (ECG) has recently become accepted as a variable of ventricular repolarization. We compared the effects of myocardial perfusion defect (MPD) on the frontal QRS-T angle between anterior and inferior myocardial infarction (MI) using single-photon emission computed tomography.

Methods The frontal QRS-T angle was defined as the absolute value of the difference between the frontal plane QRS axis and T-wave axis. A QRS-T angle more than 90° was considered abnormal.

Patients Forty-two patients with anterior MI and 42 age- and sex-matched patients with inferior MI were enrolled. For controls, 42 age- and sex-matched patients with no MPD were selected.

Results The mean frontal QRS-T angles in anterior MI, inferior MI and control subjects were 94.7±46.2°, 26.7±22.1° and 27.0±23.2°, respectively. Compared with controls, the frontal QRS-T angle was larger in anterior MI subjects (p<0.001), and similar in value to that in inferior MI subjects (p=0.69). An abnormal QRS-T angle was frequent in the anterior MI subjects than the inferior MI subjects (55% vs. 2%, p<0.001). In anterior MI subjects, MPD was significantly associated with the T-wave axis (ρ=0.46, p=0.002) and QRS-T angle (ρ=0.47, p=0.002), but was not with the QRS axis (ρ=0.07, p=0.66). In inferior MI subjects, there were no associations between MPD and the ECG variables.

Conclusion Our data suggest that the frontal QRS-T angle in inferior MI subjects is not increased as evidently as that in anterior MI subjects.

Objective The pharmacodynamic effect of warfarin varies among individuals, and its maintenance dose is widely distributed. Although many formulae for predicting the maintenance dose of warfarin have been developed, most of them are complex and not in practical use.

Methods and Materials Among 12,738 new patients visiting the Cardiovascular Institute between 2004 and 2009, we identified 127 patients (66.6±8.8 years, 89 men) with atrial fibrillation for whom warfarin was newly started with an initial dose of 2 mg/day and the international normalized ratio (INR) at 1 year after warfarin was started was within the therapeutic range. The prediction models for the maintenance dose were developed by an exponential equation and a first-order equation.

Results The initial response of the INR to the dose of 2 mg/day (initial INR) ranged from 1.00-3.24 (mean 1.43), while the maintenance dose of warfarin ranged from 0.5-14 mg (mean 3.8 mg). The maintenance dose showed an exponential correlation to the initial INR: (predicted maintenance dose) =5.522× (initial INR) ^−1.556 (R²=0.795, p<0.001). Excluding the patients with a poor response to the initial dose (initial INR <1.1, n=32) permitted a simple correlation with a first-order approximation: (predicted maintenance dose) =−2.009× (initial INR) +6.172 (R²=0.706, p<0.001).

Conclusion We developed a simple formula for predicting the maintenance dose of warfarin using the initial response of the INR to low-dose warfarin.

Objective To evaluate the effect of endovascular therapy (EVT) on the central blood pressure (CBP) and augmentation index (AIx) in patients with peripheral artery disease (PAD).

Methods The CBP and AIx were assessed by radial applanation tonometry the day before and the day after EVT. We compared the differences in the therapeutic effects between the stenotic and occlusive lesions and between the iliac and superficial femoral artery (SFA) lesions.

Patients We enrolled 60 consecutive patients with PAD who underwent EVT for de novo lesions.

Results Both the CBP and AIx were significantly decreased after EVT (125±22 mmHg to 112±22 mmHg; p=0.002 and 84%±16% to 73%±15%; p<0.001, respectively). The effects of EVT on the CBP and AIx were equivalent, regardless of whether the target lesion was the stenotic lesion or the occlusive lesion. There were no significant differences between the iliac and SFA lesions in the effects of EVT on the CBP and AIx.

Conclusion EVT improved the CBP and AIx in patients with PAD, regardless of the morphology or site of the lesions.

Objective Exercise therapy is used for glycemic control in type 2 diabetes mellitus (T2DM). We evaluated the effects of intensive health guidance using the Internet of things (IoT) among Japanese company workers with early T2DM.

Methods Fifty-three men (mean age: 54 years) with glycated hemoglobin (HbA1c) levels of >6.5% were enrolled in a 6-month exercise therapy program between August 2016 and January 2017. They used activity meters, scales, and sphygmomanometers connected to the Internet by Bluetooth. These devices automatically and continuously recorded daily information, and the participants simultaneously received health guidance from a public health nurse twice a month.

Results The number of daily steps significantly increased, whereas the amount of physical activity increased but was not significant. The mean decrease (±SD) in HbA1c levels after 3 and 6 months was estimated to be -0.40% (±0.45, p<0.0001) and -0.19% (±0.55, p=0.033), respectively, by a linear mixed model that included baseline HbA1c levels and age as covariates. The program failed to improve the body mass index and blood pressure of the participants. The percentage of active stage (action and maintenance stage) in stage of health behavior significantly increased from 48% to 68% (p=0.011).

Conclusion Intensive lifestyle intervention using a wearable monitoring system and remote health guidance improved diabetic control in middle-aged company workers.

Objective Oryeongsan (Goreisan), a formula composed of five herbal medicines, has long been used to treat impairments of the regulation of body fluid homeostasis. Goreisan has been revealed to have anti-inflammatory actions and inhibit a water channel, the aquaporin (AQP). We herein report the therapeutic effect of Goreisan on experimental autoimmune encephalomyelitis (EAE in, an animal model of inflammatory demyelinating diseases.

Materials and Methods EAE mice immunized with MOG_35-55 peptide were divided into Goreisan- and sham-treated groups. The clinical EAE score and histopathological finding of the central nervous system (CNS) were analyzed. For the proliferation assay, prepared spleen cells from immunized mice were cultured and analyzed for the [³H]-thymidine uptake and cytokine concentrations of the culture supernatant. The relative quantification of AQP4 mRNA in the CNS of EAE mice was analyzed quantitatively.

Results The EAE score of the Goreisan-treated mice was significantly lower than that of the sham-treated mice. The CD4-positive cell number in the CNS of Goreisan-treated mice was lower than that of sham-treated mice. In the recall response to MOG_35-55 peptide, the cell proliferation did not differ markedly between the spleen cells from Goreisan- and sham-treated mice. Furthermore, Goreisan decreased the mRNA level of AQP4 in the spinal cord during EAE.

Conclusion Goreisan prevented the disease activity of EAE by inhibiting the migration of pathogenic cells into the CNS by suppressing the AQP4 expression in the CNS. Goreisan may have a therapeutic effect on inflammatory demyelinating diseases.

We herein report a case with the rare combination of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the stomach, autoimmune gastritis (AIG), autoimmune thyroiditis, autoimmune hemolytic anemia (AIHA), and systemic lupus erythematosus. A 68-year-old woman was diagnosed with gastric MALT lymphoma associated with Helicobacter pylori (H. pylori) infection and AIG. Complete remission of the MALT lymphoma was achieved by H. pylori eradication and radiotherapy. Three years after the diagnosis of MALT lymphoma, the patient developed AIHA and anti-nuclear and anti-Smith autoantibody-positive lupus serositis, which were successfully managed with prednisolone administration.

Myotonic dystrophy is a progressive disorder mainly affecting the voluntary muscles. We herein report a rare case of myotonic dystrophy complicated with high-resolution manometry-defined achalasia, the pathology of which is absent relaxation of the smooth muscles of lower esophageal sphincter (LES). In the present case, achalasia was considered a complication of myotonic dystrophy instead of sporadic achalasia, as on performing high-resolution manometry, the finding of an impaired LES relaxation (myotonic phase) changed to a totally emaciated LES function (muscle weakness phase) as myotonic dystrophy progressed.

A 78-year-old man with chronic hepatitis C underwent hepatectomy for hepatocellular carcinoma (HCC) 11 years prior to presentation. He was diagnosed with multiple intrahepatic recurrences of HCC with portal vein invasion and received hepatic arterial infusion chemotherapy (HAIC) with cisplatin. He developed abdominal pain, diarrhea, and blood-stained stool following treatment. Computed tomography revealed significant bowel wall thickening throughout the colon. Colonoscopy revealed reddish edematous mucosa with a reduced vascular pattern without ischemic changes. Conservative treatment with total parenteral nutrition improved his condition and his imaging findings. This is the first report of severe colitis following HAIC with cisplatin.

A 37-year-old Wilson disease patient treated with D-penicillamine visited our hospital for the evaluation of his liver function. Laboratory data showed a low serum copper level and ceruloplasmin. The ratio of urinary copper to urinary creatinine in a spot urinary analysis after 4 days' cessation of D-penicillamine was under 0.1. We concluded that the copper chelation was excessive and changed D-penicillamine to zinc acetate. However, his liver function test results did not normalize. We performed a liver biopsy and discovered a high copper content. The liver dysfunction was improved after resuming chelating therapy. Accurate measurement of the hepatic copper content via a biopsy is important for the adequate management of this disease.

Mutations in the cardiac sodium channel SCN5A can cause phenotypic overlap syndrome of long QT syndrome and Brugada syndrome. However, Brugada-type ST elevations in patients with overlap syndrome are often concealed, which creates a diagnostic challenge. A 38-year-old man was admitted due to ventricular fibrillation (VF). The 12-lead electrocardiogram showed a prolonged QT interval and saddleback-type ST elevation. Pilsicainide administration induced coved-type ST elevation and VF triggered by a single premature ventricular contraction. A genetic analysis showed an SCN5A c.5350G>A p.E1784K mutation. The present case suggests the importance of a drug administration test being performed in the clinical management of overlap syndrome.

A 61-year-old man experienced chest oppression for 1 hour. He was positive for troponin T and underwent emergent coronary angiography (CAG), which did not reveal significant coronary stenosis. He was diagnosed with myocardial infarction with nonobstructive coronary arteries (MINOCA). We performed a spasm-provocation test, which revealed a focal spasm at the segment of the myocardial bridge. After receiving a calcium-channel blocker, he exhibited a good clinical course. Coronary spasm is considered an underlying cause of MINOCA; therefore, the presence of a myocardial bridge may help with the diagnosis.

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare condition caused by an excessive activation of the complement pathway based on genetic or acquired dysfunctions in complement regulation, leading to thrombotic microangiopathy (TMA). A complement-amplifying condition (CAC) can trigger aHUS occurrence along with complement abnormality. We herein report a case of severe TMA after laparoscopic myomectomy in a healthy woman. This case was eventually diagnosed as complement-mediated TMA secondary to surgical invasive stress as a CAC, with no definitive diagnosis of aHUS despite a genetic test. The patient fully recovered after several eculizumab administrations.

Two patients, a 76-year-old woman and 66-year-old woman, presented to our hospital with symptoms of lower respiratory tract infection. Both patients showed chest imaging findings of bilateral ground-glass opacities and consolidations. We initially suspected these patients of having influenza-associated pneumonia and cryptogenic organizing pneumonia, respectively, and performed bronchoalveolar lavage, but only human parainfluenza virus-1 infection was detected by multiplex polymerase chain reaction testing. These findings suggest that pneumonia due to human parainfluenza virus-1 should be included in the differential diagnosis of such cases.

Paraneoplastic syndromes are frequently observed in lung cancer, especially in small cell lung cancer (SCLC). Although there have been many reports on paraneoplastic syndromes, few reports have been published on SCLC that simultaneously produces antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH), and these reports described the prognosis of such cases as extremely poor. We herein present a rare case of a Japanese woman with SCLC accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Cushing's syndrome. The survival of the patient was prolonged by the long-term administration of amrubicin.

A 51-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia underwent a second cord blood transplantation followed by maintenance therapy with interferon-α. After 33 months, she developed cardiogenic shock caused by advanced atrioventricular block. Laboratory tests revealed increased myocardium enzymes, and ultrasonic cardiography demonstrated mild thickening of the left ventricular wall. She was diagnosed with myocarditis and successfully treated using prednisolone. Myocarditis after allogeneic stem cell transplantation is a rare but potentially fatal complication. However, it is important for physicians to be aware of this complication because all of the symptoms may be reversed with immunosuppressive treatment.

Isolated adrenocorticotropic hormone deficiency (IAD) is a cause of adrenal insufficiency (AI), which shows impaired secretion of adrenocorticotropic hormone (ACTH) with the preserved secretion of other anterior pituitary gland hormones. We herein report a case of IAD complicated by chronic thyroiditis presenting with neuropsychiatric symptoms without other signs indicative of AI that showed complete improvement of the cognitive function after the administration of corticosteroids. The clinical features of our case may be confused with autoimmune encephalopathies (AEs); however, IAD should be strictly differentiated from AEs, as it requires permanent hormone replacement without addition of immunosuppressive agents.

There have been a few reports on the administration of rituximab for relapsing-remitting multiple sclerosis (RRMS) in the acute phase. We report the case of a 62-year-old woman with an acute lesion of RRMS. Although corticosteroid therapy and plasmapheresis were not effective, the lesion improved with the administration of rituximab. We believe that the B cells were promptly depleted after the infusion of rituximab, and that the inflammatory reactions related to the B cells were suppressed. We suggest that the administration of rituximab can be considered as a treatment option for acute-phase RRMS when conventional therapies are not effective.

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by a recurrent fever and multiple serositis. In the present report, we discuss the case of a 42-year-old man diagnosed with FMF accompanied by recurrent aseptic meningitis (RAM). The patient experienced RAM at intervals of several years without any serositis or synovitis. We detected Mediterranean fever (MEFV) gene mutations (E148Q homozygotes) and diagnosed FMF in perfect accordance with clinical diagnostic criteria. FMF, in which RAM is a major symptom, has also been described in previous reports. Therefore, FMF should be considered in the differential diagnosis of causative diseases for RAM.

Recently, severe cases of infection due to hypermucoviscous Klebsiella pneumonia (hmKP) have been reported in Japan. The Amami Islands in Japan are also endemic regions for Strongyloides stercoralis. Disseminated strongyloidiasis strain often causes severe enterobacteria infection; however, whether or not chronic strongyloidiasis induces it remains unclear. We herein report a 71-year-old man who developed meningitis and liver abscess due to hmKP complicated with chronic strongyloidiasis. He died on the seventh hospital day. Strongyloides stercoralis were only found around the polyp in the cecum. Chronic strongyloidiasis can also induce severe infection due to enterobacteria, especially hypervirulent pathogens like hmKP, through the induction of mucosal rupture.