Purpose: Olfactory deficit has been studied in aging, amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD). Parkinson's disease (PD), dementia with Lewy bodies (DLB) and idiopathic REM-sleep behavior disorder (iRBD). Our aim was to investigate the usefulness of a simple test kit “ The Odor Stick Identification test for the Japanese ”(OSIT-J) in clinical practice. Methods: A total of 240 patients were enrolled in this study, including 44 cognitively normal subjects (NS), 31 patients with aMCI, 70 patients with mild AD (AD-mild), 28 patients with DLB, 31 patients with PD and 36 patients with iRBD. The OSIT-J consists of 12 types of odor sticks. The subjects were asked to select an odor from a list of 4 odors that were rubbed on the medicine wraping paper for each odor stick. The maximum score was 12. Results: The mean odor identification (OI) score decreased in the order of aMCI, iRBD, AD-mild, PD and DLB (NS: aMCI, P < 0.05, NS: AD-mild, DLB, PD and iRBD, P < 0.001, aMCI: DLB, P < 0.001, aMCI: PD, P < 0.01 (Kruskal-Wallis, Dunn’s test). The sensitivity and specificity in differentiating each disease from NS at a cutoff value of 8 was 96.8% and 79.5%, respectively, in PD, and 96.4% and 79.5% in DLB. An ageing effect was observed in NSs ( r=-0.453 (p < 0.01)). Conclusions: Olfactory deficit is a non-specific phenomenon. However, it is important to be aware of the underlying diseases or future development of diseases. The OSIT-J, which is a simple test, is useful for detecting OI abnormalities in daily clinical practice.

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Objective: Type 1 diabetes (T1D) is an organ-specific autoimmune disease triggered by both genetic and environmental factors. Adult-onset T1D in Japan is frequently associated with autoimmune thyroid disease (AITD), and more than half of the T1D cases are preceded by AITD. We investigated whether the human leukocyte antigen (HLA) class II (DR/DQ) gene, the major genetic risk factor for T1D, is useful in identifying individuals at high risk of developing T1D among Japanese AITD patients. Design/Patients: We genotyped the HLA class II (DR/DQ) gene in 82 patients with AITD complicated with T1D (AITD+T1D), 131 AITD patients without T1D (AITDw/oT1D), and 222 healthy subjects as controls. Results: Compared to the controls, the AITD+T1D group had a significantly higher rate of the T1D-susceptible haplotype DRB1^*0405-DQB1^*0401, but the AITDw/oT1D group did not. Compared to the controls, the T1D-protective haplotypes DRB1^*1501-DQB1^*0602/DRB1^*1502-DQB1^*0601 were significantly less frequent in the AITD+T1D patients but not in the AITDw/oT1D patients. In genotypes combining the DRB1-DQB1 haplotypes susceptible to T1D, only DR4/DR8 was signifi-cantly more frequent compared to the controls. We classified the haplotypes into three types (susceptible [S], protective [P] and neutral [N]) to examine their association with T1D development. Compared to the controls, the genotypes S/S and N/P were observed more and less frequently, respectively, in AITD+T1D. No difference in the frequency of those genotypes between AITDw/oT1D and controls was observed. Conclusions:The risk of the future development of T1D in Japanese patients with AITD could be stratified by an analysis of combinations of HLA DRB1-DQB1 haplotypes.

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Background: To assess laparoscopic distal gastrectomy (LDG) for gastric cancer (GC), the Japanese Operative Rating Scale (JORS) for LDG has been developed. This study evaluated the learning curve of the initial experience of LDG for GC using JORS-LDG. Methods: Thirty-one cases of LDG were performed by a trainee. The trainee and an instructor scored the surgical performance using JORS-LDG immediately after LDG. The 31 cases were evenly divided into early phase (EP), middle phase (MP), and late phase (LP). Results: The trainee successfully completed all cases of LDG without any complications. There were also no severe postoperative complications with Clavien–Dindo classification grade III or higher. The average JORS-LDG points were stable after 24 cases of experience in the CUSUM analysis. The median JORS-LDG points in EP were significantly lower than those in LP (EP: MP: LP = 43.5: 44.3: 45.5, P = 0.02). In operative data, procedure time, bleeding, and the drain fluid amylase level were correlated with the JORS-LDG points. Conclusion: The JORS-LDG scoring system is a practical tool to evaluate surgical performance in the initial LDG experience.

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Subclinical hypothyroidism is a condition characterized by a normal range of thyroid hormone [triiodothyronine (T₃) and thyroxine (T₄)] but with an elevated level of thyroid stimulating hormone (TSH) . It is also reported to be associated with hypertension. Since thyroid cysts could have a beneficial effect on the activation of thyroid hormone as reported in our previous study, their presence could influence the association between subclinical hypothyroidism and hypertension. To clarify those associations, a cross-sectional study of 1,724 Japanese within normal range of thyroid hormone (i.e., normal range of free T₃ and free T₄), aged 40-74 years, who participated in an annual health checkup in 2014 was conducted. Among the study population, 98 were diagnosed as having sublicnical hypothyroidism. For participants without a thyroid cyst, hypertension had a significant positive association with subclinical hypothyroidism, while for participants with a thyroid cyst, even though the power could not reach a significant value, an inverse tendency between hypertension and subclinical hypothyroidism was observed. The adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were 1.91 (1.08, 3.37) for participants without thyroid cysts and 0.63 (0.26, 1.55) for participants with thyroid cysts, respectively. The status of thyroid cysts could act as a determining factor in the association between subclinical hypothyroidism and hypertension among participants within normal range of thyroid hormone.

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A 56-year-old woman who was diagnosed with schizophrenia at 30 years old presented with acute exacerbation of psychiatric symptoms. She was treated with increasing doses of antipsychotics owing to suspicion of worsening schizophrenia. Thereafter, she rapidly developed pyrexia, marked sweating, tremors, myotonia/postural abnormalities, stupor with akinesia, and decreased blood pressure, suggesting neuroleptic malignant syndrome (NMS) caused by the increased dose of antipsychotics. As a differential diagnosis, we considered malignant catatonia caused by schizophrenia. In addition, because the patient showed atypical symptoms and an atypical course of schizophrenia, we considered malignant catatonia caused by an organic disease and performed an antibody test of her cerebrospinal fluid. Modified electroconvulsive therapy was performed to treat the NMS, and the patient’s psychiatric and somatic symptoms improved. During treatment, she exhibited positivity for anti-N-methyl-D-aspartate (NMDA) receptor antibodies. However, she did not meet the consensus criteria for anti-NMDA receptor encephalitis. Thus, as a final diagnosis, we considered NMS of atypical schizophrenia with anti-NMDA receptor antibody positivity. Anti-NMDA receptor encephalitis can be misdiagnosed as schizophrenia because of similar psychiatric symptoms. This case emphasizes the importance of testing for anti-NMDA receptor antibodies in patients with an atypical course of schizophrenia.

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The relationship between the severity of COVID-19, hyperinflammation, and intravascular coagulopathy is of critical importance. We report on a case of severe COVID-19 pneumonia treated with favipiravir during the earliest phase of the pandemic. The present case showed improvement in SARS-CoV-2 viral load and the presence of SARS-CoV-2 IgG with decreased radiological evidence of pulmonary infiltration. Moreover, the levels of serum IL-6 and TNF-α did not increase markedly. However, the hypoxia failed to recover, leading to the patient’s death due to possible pulmonary thrombosis, because D-dimer was markedly elevated, and an electrocardiogram showed typical changes. At present, the fact that some COVID-19 patients with mild to moderate symptoms suddenly die at home has become a major issue in Japan. These findings suggest that additional treatment with anti-coagulants should be considered in some COVID-19 patients at risk of hypercoagulation to prevent sudden death from pulmonary thrombosis

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Objective: Acute exposure to hypoxia generally increase the ventilation. However, some of COVID-19 patients who suffer from pneumonia are characterized by hypoxic ventilatory depression with loss of dyspnea which is called as happy hypoxia. This report describes the background and the clinical issues of happy hypoxia. Methods: The mechanisms to increase ventilation and dyspnea under hypoxia are explained. Further, clinical issues and characteristics in COVID-19 are reviewed. Results: Genetic factors are definitely concerned with chemosensitivity to hypoxia. Further disease factors including COVID-19 infection could influence the attenuation of the chemosensitivity. This can be attributed to either ventilatory depression due to the modulation of metabolic substrate, adenosine in the brain, or autonomic neuropathy including the dysfunction of the carotid body. Conclusions: COVID-19 patients must be carefully treated and/or monitored to avoid hypoxic ventilator depression. The clinical application of aminophylline will be an issue to be considered.

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