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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the world’s largest public health concern. This study evaluated COVID-19 transmission risks in people in group living environments. A total of 4550 individuals with a history of recent contact with patients at different places (dormitory/home/outside the residences) and levels (close/lower-risk) were tested for SARS-CoV-2 viral RNA using a nasopharyngeal swab test between July 2020 and May 2021. The test-positive rate was highest in individuals who had contact in dormitories (27.5%), but the rates were largely different between dormitories with different infrastructural or lifestyle features and infection control measures among residents. With appropriate infection control measures, the secondary transmission risk in dormitories was adequately suppressed. The household transmission rate (12.6%) was as high as that of close contact outside the residences (11.3%) and accounted for > 60% of the current rate of COVID-19 transmission among non-adults. Household transmission rates synchronized to local epidemics with changed local capacity of quarantining infectious patients. In conclusion, a group living environment is a significant risk factor of secondary transmission. Appropriate infection control measures and quarantine of infectious residents will decrease the risk of secondary transmission in group living environments.

Introduction: The characteristics of somatic symptoms seen at the first hospital visit in patients with psychogenic backgrounds remain poorly elucidated till date. Methodology: A total of 277 patients who visited the Department of General Medicine at a single university hospital with somatic symptoms were prospectively enrolled in this study. The eventual definite diagnoses were classified into the following three groups: non-psychogenic disease (n = 128), psychogenic symptoms (n = 131), and mental illness (n = 18). Subsequently, the chief complaints and other background information of the patient obtained at the first visit were compared among the three groups. Results: More than half of the patient with non-psychogenic diseases (60.2%) presented with a single complaint at their first hospital visit; contrarily, less than half of the patients with psychogenic symptoms (23.7%) or mental illnesses (22.2%) presented with a single complaint at the first visit. Approximately

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

The progressive patterns of neurological disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and the significance of clinical relapses to the progressions of neurological disability in these diseases have not been fully elucidated. In this study, to elucidate the impact of relapses to the progression of accumulated neurological disability and to identify the factors to affect the progression of neurological disability in MS and NMOSD, we followed 62 consecutive MS patients and 33 consecutive NMOSD patients for more than 5 years with the clinical symptoms, relapse occurrence, and Expanded Disability Status Scale (EDSS) in the chronic phase. All enrolled MS patients were confirmed to be negative for serum anti-myelin oligodendrocyte glycoprotein antibody. As a result, patients with NMOSD showed significantly severer neurological disability at 5 years from onset than MS patients. Progression in EDSS score was almost exclusively seen after clinical attacks in NMOSD, whereas progression could be observed apart from relapses in MS. Neurological disability did not change without attacks in NMOSD, whereas it sometimes spontaneously improved or deteriorated apart from relapses in MS (p

A 66‐year‐old man with a 2‐year history of suspected scalp eczema with excessive dandruff developed painful swollen joints in the extremities. Four months after developing polyarthritis and polydactylitis, eczema gradually spread to the face. He was referred to our hospital for intractable scalp and facial eczema and polyarthritis. Based on the appearance of the head and facial skin lesions, psoriasis was suspected. Treatment with apremilast (a phosphodiesterase‐4‐inhibitor) was initiated, which swiftly alleviated the skin lesions. The joint deformities persisted, but the pain in the joints disappeared. This case implies that psoriatic arthritis should be suspected even if psoriatic skin lesions are localized to the scalp., Psoriatic arthritis was observed in a middle‐aged man with the skin lesions localized to scalp area. Because a delayed diagnosis may result in irreversible joint deformity, close collaboration with dermatologists is essential for early diagnosis of psoriatic arthritis in patients with localized skin lesions remote from the site of arthritis or dactylitis.

Background A recent investigation reported that 92.7% Japanese family physicians have prescribed Kampo medicine (KM). KM can treat a wide variety of conditions from mental disorders to physical weaknesses. However, the characteristics and course of patients treated with KM at the Department of General Medicine remain unclear. Aims To investigate the characteristics and course of patients treated with KM in our hospital. Methods Data on medical history, complaints, course after Kampo treatment, and Hamilton Depression Rating Scale (HAM‐D) scores were retrogradely collected. The background of patients who received Kampo treatment was compared to that of patients who did not. Result Of 362 patients, 51 were treated with KM. Symptoms for which KM was prescribed included pain, general malaise, or sensory disturbance of extremities. All patients treated with KM were screened and initially diagnosed with a functional disorder or noncritical condition. KM including a crude drug of saiko such as hochuekkito, shigyakusan, shosaikoto, and yokukansan, was frequently prescribed for patients. Subjective symptoms showed improvement (53%) and no change (47%), while worsening was not observed in any patient. HAM‐D scores showed that patients treated with KM had higher anxiety levels and related symptoms as well as a higher frequency of mental disorders prior to presenting at the hospital. Conclusion Most complaints of the patients treated with KM were pain, general malaise, and sensory disturbance. KM is more likely to be prescribed in patients with health‐related anxiety or a history of mental disorders., Kampo medicine is more likely to be prescribed in patients with health‐related anxiety or a history of mental disorders who visit the Department of General Medicine.

We herein report the case of a 14-year-old girl who had been experiencing chronic fatigue, febricula, and social withdrawal for 20 months. No notable abnormalities were identified during routine checkups at a general pediatric hospital; symptomatic treatments did not affect her condition. She was diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Based on the concepts of Japanese traditional medicine, she was administered shosaikoto-based treatment. After several weeks of treatment, all of the symptoms had been dramatically alleviated, consequently resolving the issue of non-attendance at school. Shosaikoto-based medication may be a therapeutic option for treating ME/CFS in patients presenting with chronic febricula.

A 30‐year‐old man with severe hypoalbuminemia (serum albumin: 0.9 g/dL) was admitted with severe bilateral leg edema and unilateral pleural effusion. Serum anti‐SS‐A and SS‐B antibody levels were abnormally elevated, and his symptoms fulfilled the diagnostic criteria for Sjögren's syndrome. Technetium‐99m albumin scintigraphy revealed protein leakage from a large area of the small intestine. Immunohistochemistry revealed perivascular deposition of C1q, C3d, and immunoglobulin G in the duodenal mucosa. The patient was diagnosed with protein‐losing gastroenteropathy associated with Sjögren's syndrome. Within 2 months of treatment with oral prednisolone and mycophenolate mofetil, the clinical symptoms of hypoalbuminemia and Sjögren's syndrome disappeared completely., A middle‐age man with severe hypoalbuminemia and severe edema. The patient was diagnosed with Sjögren's syndrome associated with protein‐losing enteropathy by protein scintigraphy and pathological examination of colon. After treatment of immunosuppressant, the clinical symptoms disappeared completely.

A 51-year-old afebrile man visited the hospital with acute severe neck pain with stiff neck, but cervical CT showed no calcification around the odontoid process. Cervical MRI revealed prevertebral hyperintense area of edema at the C1-C5 vertebral bodies, providing the diagnosis of retropharyngeal calcific tendinitis. The patient was spared for lumbar puncture, and his symptoms swiftly disappeared only with oral NSAIDs.

Japanese herbal medicines (HMs) cause adverse drug reactions (ADRs); however, solid nodule formation is uncommon. In this report, we aimed to show that ADRs with HM can mimic lung cancer. A 63-year-old man complained of back pain. His physician prescribed a traditional Japanese HM, Keishikajutsubuto, which alleviated his symptoms. After 4 weeks, a chest radiograph showed multiple lung nodules that were absent 6 months earlier; the patient did not have cough, fever, or dyspnea. Computed tomography (CT) showed multiple, bilateral lung nodules; however, blood tests and lung biopsy showed no abnormalities, ruling out interstitial pneumonia and lung cancer. Three months after the HM was discontinued, CT showed resolution of the lesions. Interstitial pneumonia was reported as a side effect of HM; however, no such side effect was reported for Keishikajutsubuto. When a patient presents with multiple lung nodules, a side effect of HM should be considered as a differential diagnosis.

Purpose: The epithelial-to-mesenchymal transition, the major process by which some cancer cells convert from an epithelial phenotype to a mesenchymal one, has been suggested to drive chemo-resistance and/or metastasis in patients with cancer. However, only a few studies have demonstrated the presence of CD45/CD326 doubly-positive cells (CD45/CD326 DPC) in cancer. We deployed a combination of cell surface markers to elucidate the phenotypic heterogeneity in non–small cell lung cancer (NSCLC) cells and identified a new subpopulation that is doubly-positive for epithelial and non–epithelial cell-surface markers in both NSCLC cells and patients' malignant pleural effusions. Experimental Design: We procured a total of 39 patients' samples, solid fresh lung cancer tissues from 21 patients and malignant pleural effusion samples from 18 others, and used FACS and fluorescence microscopy to check their surface markers. We also examined the EGFR mutations in patients with known acquired EGFR mutations. Results: Our data revealed that 0.4% to 17.9% of the solid tumor tissue cells and a higher percentage of malignant pleural effusion cells harbored CD45/CD326 DPC expressing both epithelial and nonepithelial surface markers. We selected 3 EGFR mutation patients and genetically confirmed that the newly identified cell population really originated from cancer cells. We also found that higher proportions of CD45/CD326 DPC are significantly associated with poor prognosis. Conclusions: In conclusion, varying percentages of CD45/CD326 DPC exist in both solid cancer tissue and malignant pleural effusion in patients with NSCLC. This CD45/CD326 doubly-positive subpopulation can be an important key to clinical management of patients with NSCLC.

Increased intrarenal vascular resistance is suggested to accompany chronic kidney diseases (CKD), which is known to be closely associated with hypertension. However, there are few studies that have examined the relationship between blood pressure and intrarenal vascular resistance. Renal color Doppler ultrasonography is one method that can non-invasively evaluate intrarenal vascular resistance. In this study, we comprehensively studied the correlations between ultrasonic parameters and blood pressure indices to elucidate their relationships. In total, 162 patients with suspected CKD were enrolled for this study. Demographics, blood pressure, blood test, urine test, and renal color Doppler ultrasonography data were obtained. The ratio of diastolic to systolic blood pressure (D/S ratio) and pulse pressure were calculated. Our results indicated strong negative correlations between the renal resistive index (RI) values in all four of the studied kidney regions and the D/S ratio. The RI values also showed significant correlations with diastolic pressure and pulse pressure, but they were weaker. Partial correlation coefficients between pulse pressure, mean arterial pressure, D/S ratio, and RI showed that D/S ratio significantly correlated with RI, but pulse pressure or mean arterial pressure did not. Systolic blood pressure did not correlate with any of the studied ultrasonic values. The negative correlation between RI values and the D/S ratio was still observed in subjects without renal dysfunction or any medications. In conclusion, D/S ratio, rather than pulse pressure or mean arterial pressure, would be the most appropriate index to estimate/calculate/judge intrarenal vascular resistance.

Objective The definite diagnosis of esophageal achalasia is established using manometry, which is performed in patients with suspected achalasia based on the findings of screening examinations, such as upper gastrointestinal endoscopy, chest computed tomography (CT), or a barium swallow test. However, the exact values of test characteristics in these supportive diagnostic examinations remain unclear. Methods We estimated the sensitivity and specificity of characteristic findings in the supportive diagnostic examinations for achalasia by comparing the data of a large number of achalasia patients and others with digestive symptoms. Patients Achalasia patients (n=119) and non-achalasia patients with suspected achalasia and repeated feelings of chest discomfort (n=37) who were treated in a single university hospital. Results Characteristic findings on chest CT (i.e., dilated esophagus, air-fluid level formation) and barium swallow tests were observed in more than 80% of achalasia patients but in less than 10% of non-achalasia patients. In contrast, conventional characteristic findings of upper gastrointestinal endoscopy (i.e., intra-esophageal food debris, feeling of resistance at the esophagogastric junction) were seen in only 40-70% of achalasia patients. In particular, the feeling of resistance at the esophagogastric junction was observed by the examiner in only 30-50% of patients. Conclusion Intra-esophageal food debris or resistance at the esophagogastric junction on upper gastrointestinal endoscopy will be positive in only about half of patients with achalasia. Other supportive diagnostic examinations, such as chest CT or barium fluoroscopy, should therefore be included in order to avoid overlooking the disease.

Background Several types of physical examinations are used in the diagnosis of meningitis, including nuchal rigidity, jolt accentuation, Kernig's sign, and Brudzinski's sign. Jolt accentuation was reported to have sensitivity of nearly 100% and to be highly efficient for excluding meningitis, but more recent studies showed that a number of patients with meningitis may present negative in this test. Methods We systematically reviewed studies on the above‐mentioned physical examination tests and performed meta‐analysis of their diagnostic characteristics to evaluate the clinical usefulness. Nine studies, comprising a total of 599 patients with pleocytosis in the cerebrospinal fluid (CSF) and 1216 patients without CSF pleocytosis, were enrolled in the analysis. Results Jolt accentuation showed a decent level of odds ratio (3.62; 99% confidence interval (CI): 1.13‐11.60, P = 0.004) comparable to that in nuchal rigidity (2.52; 1.21‐5.27, P = 0.001) for the correct prediction of CSF pleocytosis among subjects with suspected meningitis. The estimated sensitivity was relatively high (40%‐60%) in nuchal rigidity or jolt accentuation tests. On the other hand, Kernig's and Brudzinski's signs exhibited relatively low sensitivity (20%‐30%). The estimated specificity was higher in Kernig's and Brudzinski's signs (85%‐95%) than in nuchal rigidity or jolt accentuation tests (65%‐75%). Conclusion Approximately half of the patients with meningitis may not present typical meningeal signs upon physical examination. Combining several examinations for the detection of meningeal signs may decrease the risk of misdiagnosis.

We present a report of a 29-year-old woman with non-dipper type refractory hypertension due to the vascular compression of the medulla oblongata. The patient was diagnosed with hypertension at 17 years of age and underwent emergency Caesarean section at 26 weeks of gestation during 2 pregnancies due to severe high blood pressure. We suspected medullary compression by the curved posterior inferior cerebellar artery as the cause of her intractable hypertension, and she underwent Jannetta's decompression surgery. After the surgery, her blood pressure swiftly decreased to almost within the normal range, and her blood pressure pattern normalized to dipper type.

In this report, we present the successful treatment of five consecutive cases of premenopausal women suffering from severe menstrual migraine with tokishakuyakusan (TSS). Two patients were complicated by tension‐type headache (TTH), and another patient was by medication overuse headache (MOH). The effects of triptans were limited in all of them. After starting TSS, they showed dramatic improvement in the severity and frequency of their attacks. The patients with TTH and MOH also showed dramatic improvement in their symptoms. TSS could be a promising alternative choice for patients with intractable menstruation–related headaches that are refractory to conventional treatments, including triptans.

Esophageal achalasia is a disease characterized by the impaired esophageal peristalsis and non-relaxation of the lower esophageal sphincter muscle with unknown causes. Clinical manifestation of the disease is nonspecific (e.g., weight loss, vomiting, and persistent cough); namely, early diagnosis of the disease is often difficult. Delayed diagnosis of the disease is known to impair the patients' quality of life. Identifying the diagnostic factors that could cause diagnostic delay is needed. In this study, we collected data from 38 patients with achalasia and searched for diagnostic factors associated with delayed diagnosis (i.e., ≥ 6 months from the first hospital visit to diagnosis). The enrolled patients, diagnosed with achalasia based on esophageal manometry findings, had undergone surgical myotomy. As a result, the diagnosis of achalasia was likely to be delayed when the physician who had first contacted the patient did not perform a barium swallow test (p < 0.0001) or chest CT scan (p < 0.01) in a timely fashion. Among the patients with a delayed diagnosis (n = 15), none underwent a barium swallow test or chest CT within 6 months from their first hospital visit. The estimated sensitivities of diagnostic examinations for achalasia based on the enrolled 38 patients were higher than 80% for the barium swallow test and chest CT scan, but only 50-81% for endoscopy. To avoid the delayed diagnosis of achalasia, performing a barium swallow test or chest CT scan in a timely fashion, in addition to routine endoscopy, appears to be highly important.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) colonization can lead to MRSA pneumonia or other infections in compromised hosts, and invasive MRSA infections lead to significant morbidity and mortality. The present observational study elucidated whether administration of hochuekkito (HET) can prevent MRSA colonization in the upper respiratory tract and support recovery in acute stroke patients.Methods: In this retrospective, observational study, 73 acute stroke patients admitted to Kenwakai Hospital between April 2007 and December 2019 who did not require emergency surgery during this period were enrolled. Conventional treatment was provided to all patients, depending on their condition, and 7.5 g/day of HET was administered to the patients who could take the medicine via nasogastric tube or orally in three divided doses for three months. Bacterial cultures from laryngeal swabs and sputum were evaluated every week. We evaluated the presence of MRSA infection or another infectious disease within 30 days of admission; modified Rankin Scale scores, which assesses the independent living skills after stroke at three months after admission; and blood biomarkers (white blood cell count, albumin levels, C-reactive protein levels, and hemoglobin levels).Results: In total, 73 patients (HET group, n = 41; non-HET group, n = 32) were enrolled in the study. MRSA detection was significantly less likely in the HET group than in the non-HET group (p = 0.0497). The incidence of infectious diseases was significantly lower in the HET group than in the non-HET group (p = 0.0096), and the modified Rankin Scale score at three months was also significantly lower in the HET group than in the non-HET group (p = 0.033). The white blood cell count, and serum C-reactive protein levels did not differ between those who were treated with HET and those who were not. However, serum albumin and hemoglobin levels improved slightly between month one and month three after admission only in those who were treated with HET.Conclusion: Our results indicate that the administration of HET may contribute to the prevention of MRSA colonization and promote rehabilitation in stroke patients.

Background Zinc is an essential micronutrient for maintaining biological activity. The level of zinc in the blood is known to decrease with age, especially in those over 75 years of age. In older adults patients with impaired functional status, aspiration pneumonia based on dysphagia often becomes problematic. However, the relationship between zinc deficiency and swallowing function has not been studied before. Methods A total of 52 older adults subjects (15 males and 37 females) living in a nursing home were enrolled for this study. At the time of enrollment, data of gender, age, body weight, serum zinc levels, serum albumin levels, and the time in a simple 2-step swallowing provocation test (S-SPT) were collected. In patients with serum zinc levels Results At the time of enrollment, serum zinc level was significantly correlated with serum albumin levels (Pearson’s R = 0.58, p p = 0.0219). Twenty-five of the 52 patients had zinc deficiency with a serum zinc level p p = 0.04) significantly improved. Meanwhile, serum albumin level (p = 0.48) or body weight (p = 0.07) did not significantly change following zinc supplementation. Zinc supplementation significantly improved swallowing function, especially in the older adults who had comorbid dysphagia and zinc deficiency. Conclusions Zinc deficiency is associated with compromised swallowing function in older adults patients with impaired general functions. Oral zinc supplementation can alleviate dysphagia in older adults patients with zinc deficiency even though this is a retrospective study. Further study will be needed to confirm this positive effect.

Background:Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune-related neurological disorder of the central nervous system. Most patients with NMOSD have serum anti-aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). In addition to optic neuritis and myelitis, other insidious symptoms such as depressive state and chronic fatigue in NMOSD are gradually being recognized.Methods: To elucidate the impact of low- to medium-dose oral prednisolone (PSL) as a relapse prevention therapy for psychiatric disturbances and chronic fatigue in NMOSD, we evaluated clinical data from 39 patients with AQP4-IgG-positive NMOSD, along with the details of present and cumulative oral PSL dosage.Results: Thirty-six of the 39 patients were treated with low- to medium-dose oral PSL, and the mean and standard deviation of the present daily dose of oral PSL were 7.9 ± 4.0 mg/day. None of the patients were treated with a daily PSL dose of >15 mg. As a result, the disease duration and the untreated period before starting oral PSL showed weak to moderate correlations with the subsequent severities of psychiatric disturbance and fatigue level. Meanwhile, none of the other treatment-related variables evaluated, such as the present oral PSL daily dose, cumulative PSL dose, months of oral PSL administration, previous courses of steroid pulse therapy, and coadministered immunosuppressants, were correlated with these insidious symptoms.Conclusion: Our results suggest that the use of long-term low- to medium-dose oral PSL ≤15 mg daily for relapse prevention in AQP4-IgG-positive NMOSD would not aggravate the psychiatric and fatigue conditions. On the contrary, early initiation of oral PSL for relapse prevention, together with significantly decreased relapse rate, alleviated the subsequent depressive state and fatigue from the disease.

Objective The aim of this study was to report the possible association between minor trauma to the eyes and the subsequent occurrence of optic neuritis in patients with serum anti‐aquaporin‐4 (AQP4) antibody‐positive neuromyelitis optica spectrum disorder (NMOSD). Methods Herein, we present three patients who developed acute optic neuritis with visual disturbances after accidental minor trauma to their eyes, without any fundus abnormality or orbital floor fractures present. Results Two of the three patients had a preceding history of neurological disturbances compatible with NMOSD (e.g., myelitis, area postrema syndrome) before the occurrence of trauma. One patient was rapidly treated with steroid pulse therapy and plasmapheresis, and he fully recovered visual acuity. The other two, who were left untreated in the acute phase, had sequelae of severe visual disturbances in the affected eyes. Conclusions These cases suggest possible association between minor trauma to the eyes and the subsequent occurrence of optic neuritis in patients with serum anti‐AQP4 antibodies. Avoiding ocular trauma and early administration of steroid pulse therapy in response to optic neuritis after trauma are desired in such cases., We present three cases with serum AQP4‐IgG who developed optic neuritis after minor traumas. All patients showed relapsing clinical course compatible with AQP4‐IgG‐positive NMOSD. One patient treated with steroid pulse therapy had full recovery, but other untreated patients did not.

In response to the COVID-19 pandemic caused by SARS-CoV-2 in 2020, we conducted drive-through nasopharyngeal swab testing for COVID-19 in Sendai city, Japan, since April 2020. All tested individuals were judged in advance by public health centers for the necessity of undergoing the test with possible contact history and/or symptoms suggestive of COVID-19. In this study, to identify the predictors of SARS-CoV-2 test positivity for more efficient and evidenced selection of suspected individuals, we enrolled 3,540 consecutive individuals, tested in the first 7 months of the testing program, with data regarding to the history of close contact with COVID-19 patients, including those involved in cluster outbreaks. This cohort included 284 foreign students (257 males and 27 females) from a vocational school involved in the largest cluster outbreak in the area. Close contact history was present in 952 (26.9%) of the participants. The reverse transcription-polymerase chain reaction (RT-PCR) test results showed that 164 participants (4.6%) were positive and 3,376 participants (95.4%) were negative for the SARS-CoV-2 nucleocapsid gene (N2). In the univariate and multivariate analyses, history of close contact with COVID-19 patients, higher age, cough symptoms, and non-native ethnicity were predictors for SARS-CoV-2 test positivity. However, the significance of age and foreign nationality disappeared or declined upon excluding the foreign students from the aforementioned largest cluster outbreak. In conclusion, a history of close contact with COVID-19 patients and the presence of cough symptoms are significant predictors of SARS-CoV-2 test positivity.

ObjectiveTo elucidate the differences in the source and in the level of intrathecal synthesis between anti–aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG).MethodsThirty-eight patients with MOG-IgG–associated disease and 36 with AQP4-IgG–positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients.ResultsEleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG–positive cases and 43.8% of AQP4-IgG–positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability.ConclusionsIntrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG–associated disease and AQP4-IgG–positive NMOSD.

The progression pattern of neurological disability among patients with anti-myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) was evaluated. Neurological disability was evaluated annually for 408 person-years in 50 patients. More than 30% of the patients had clinical relapses in the first 5 years. Disability progression independent of relapse activity (PIRA) was not seen, whereas a stepwise disability progression was observed after clinical attacks in some instances. Disability worsening was more frequent after relapses than after the onset episode (p 0.01). Similar to patients with anti-aquaporin-4 antibodies, attack-related stepwise disability progression without PIRA is typical in MOGAD, suggesting the importance of relapse prevention.

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune neurological diseases of the central nervous system, which are characterized by the presence of serum anti-aquaporin-4 autoantibodies (AQP4-IgG). An association between Sjogren syndrome (SjS) and AQP4-IgG-positive NMOSD has been proposed, but the rate of coexistence has not been determined. In this study, 4,447 patients suspected of having NMOSD with acute neurological episodes were evaluated for the positivity of serum AQP4-IgG, serum SS-A/Ro antibody, and the presence of SjS-related symptoms (dry eye, dry mouth). Of the 4,447 patients, 1,651 were positive for serum AQP4-IgG, and the remaining 2,796 were negative. A significantly higher proportion of AQP4-IgG-positive patients were positive for serum anti-SSA/Ro antibody (26.3 vs. 4.5%; p

Objective: The purpose of this study was to elucidate the rapid impact of high-dose intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) on the eventual visual prognosis in patients with serum anti-aquaporin-4 immunoglobulin G (AQP4-IgG)–positive neuromyelitis optica spectrum disorders (NMOSDs) who had an attack of optic neuritis (ON).Methods: Data from 32 consecutive NMOSD patients (1 male and 31 female) with at least one ON attack, involving a total of 36 ON-involved eyes, were evaluated. The following variables at ON onset were evaluated: sex, age at the first ON episode, visual acuity at nadir, visual acuity after 1 year, duration from ON onset to treatment for an acute ON attack, cycles of high-dose intravenous methylprednisolone pulse therapy for the ON attack, and cycles of plasmapheresis for the ON attack. Among the 36 ON-involved eyes, 27 eyes were studied using orbital MRI with a short-T1 inversion recovery sequence and gadolinium-enhanced fat-suppressed T1 imaging before starting treatment in the acute phase.Results: In univariate analyses, a shorter duration from ON onset to the initiation of high-dose intravenous methylprednisolone pulse therapy favorably affected the eventual visual prognosis 1 year later (Spearman's rho = 0.50, p = 0.0018). The lesion length on orbital MRI was also correlated with the eventual visual prognosis (rho = 0.68, p < 0.0001). Meanwhile, the days to steroid pulse therapy and lesion length on orbital MRI did not show a significant correlation. These findings suggest that the rapidness of steroid pulse therapy administration affects the eventual visual prognosis independent of the severity of ON. In multivariate analysis, a shorter time from ON onset to the start of acute treatment (p = 0.0004) and a younger age at onset (p = 0.0071) were significantly associated with better visual outcomes.Conclusions: Rapid initiation of high-dose intravenous methylprednisolone pulse therapy is essential to preserve the eventual visual acuity in patients with serum AQP4-IgG-positive NMOSD. Once clinicians suspect acute ON with serum AQP4-IgG, swift administration of steroid pulse therapy before confirming the positivity of serum AQP4-IgG would be beneficial for preserving visual function.

PURPOSE: To determine whether clinical features and visual outcomes of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) differ between subjects who are White compared with those who are Asian. DESIGN: Multicenter retrospective cohort. METHODS: Setting: Multicenter. Patient: 153 subjects who are White or Asian with history of adult-onset(age≥18years-old) optic neuritis and positive MOG-IgG serology by cell-based assay were enrolled from two unpublished cohorts(January 2017-November 2019) and nine published cohorts with case-level data available(2012-2018). Subjects with alternative etiologies of demyelinating disease and positive or lack of AQP-4-IgG serology result were excluded. Main outcome measures: Clinical features and final visual outcomes. RESULTS: One hundred and fifty-three subjects who are White(n=80) or Asian(n= 73) were included. 93(61%) were female, mean age of onset was 40.8±14.9 years-old, median follow up was 35.2(range1-432) months, which were all similar between White and Asian subjects. Subjects who are White were more likely to have recurrent optic neuritis(57(71%) vs. 20(27%);p=0.001) and extra-optic nerve manifestations(35(44%) vs. 8(11%);p=0.001). Optic disc swelling, neuroimaging findings, presenting visual acuity, treatment and final visual acuity did not differ according to subjects’ race. Despite the high prevalence of severe visual loss(20/40) at final examination(51(66%) of 77 subjects who are White vs. 52(74%) of 70 subjects who are Asian). CONCLUSION: Subjects with MOG-ON who are White were more likely to have recurrent disease and extra-optic nerve manifestations. Visual outcomes were similar between subjects who are White and those who are Asian.

Background Aciduria caused by urinary excretion of acidic metabolic wastes produced in daily life is known to be augmented in patients with chronic kidney disease (CKD). To evaluate the reno-protective effect of oral alkalizing agents for the improvement of metabolic acidosis and neutralization of intratubular pH in the patients with mild stages of CKD. Also, to identify reno-protective surrogate markers in the serum and urine that can closely associate the effect of urine alkalization. Methods In this single-centered, open-labeled, randomized cohort study, patients with CKD stages G2, G3a and G3b, who visited and were treated at Tohoku University Hospital during the enrollment period were registered. We administered sodium bicarbonate or sodium-potassium citrate as the oral alkalinizing agents. A total of 150 patients with CKD will be randomly allocated into the following three groups: sodium bicarbonate, sodium-potassium citrate and standard therapy group without any alkalinizing agents. The data of performance status, venous blood test, spot urine test, venous blood-gas test, electrocardiogram, renal arterial ultrasonography and chest X-ray will be collected at 0, 6, 12 and 24 weeks (short-term study) from starting the interventions. These data will be also collected at 1 and 2 years (long-term study). The samples of plasma and serum and early-morning urine at every visit will be acquired for the analysis of renal function and surrogate uremic biomarkers. The recruitment for this cohort study terminated in March, 2018, and the follow-up period for all the enrolled subjects will be terminated in December, 2020. The primary endpoint will be the development of originally-defined significant renal dysfunction or the occurrence of any cerebrovascular disease in the short-term study. The secondary endpoint will be the same endpoints as in the long-term study, or the patients with significant changes in the suggested the surrogate biomarkers. Discussion The findings of this study will address the importance of taking oral alkalizing agents in the patients with early stages of CKD, furthermore they could address any new surrogate biomarkers that can be useful from early stage CKD. Trial registration Registered Report Identifier: UMIN000010059 and jRCT021180043. The trial registration number; 150. Date of registration; 2013/02/26.

Predisposing factors before the onset of neuromyelitis optica spectrum disorders (NMOSD) have not been systematically evaluated by now. We investigated the detailed pre-onset history in consecutive NMOSD patients. Thirteen of the enrolled 53 NMOSD patients (24.5%) had accompanying autoimmune diseases, such as Sjogren's syndrome. History of malignancy was seen in 8 of the 53 patients (15.1%). Recent history of non-neurological clinical episodes, such as systemic allergic reaction, systemic infection, surgical operation, or traumatic injury, was seen in 23 of the 53 patients (43.4%). NMOSD patients are likely to have pre-onset history of other autoimmune diseases, malignancy, or recent non-neurological systemic conditions, which may predispose or trigger the onset of NMOSD.

Multiple sclerosis (MS) is a demyelinating neurological disease with unknown causes. In this study, we comprehensively studied blood cell counts in the early phase of MS and compared their values with eventual prognostic variables. We found that the blood monocyte count in the early phase of MS was robustly associated with the clinical severity of MS (rho = 0.64; p = 0.0002) but that the counts of the other blood cells were not associated with severity. This correlation between monocyte count and severity was not observed in neuromyelitis optica. In conclusion, blood monocytes could be a candidate for the prognostic prediction of MS.

Myelin oligodendrocyte glycoprotein (MOG) is localized at the outermost layer of the myelin sheath and is accessible for autoantibodies. Although experimental autoimmune encephalitis induced with MOG immunization has been studied for 30 years, the results of previous reports on MOG immunoglobulin G (IgG) detection with enzyme-linked immunosorbent assay and Western blot are confusing. However, after the development of human MOG-transfected cell-based assay to detect conformational-sensitive MOG-IgG, unique groups of patients have been found seropositive, and MOG-IgG-associated disease has become a hot topic in clinical neuroimmunology. Currently, the clinical spectrum of MOG-IgG-associated disease includes idiopathic optic neuritis, acute disseminated encephalomyelitis, encephalitides (brainstem and cerebral cortical), idiopathic myelitis, atypical multiple sclerosis, aquaporin-4 IgG-negative neuromyelitis optica spectrum disorders and others. MOG-IgG-associated disease occurs in both children and adults, and the female:male ratio is almost 1:1. Pleocytosis in the cerebrospinal fluids during acute exacerbation is often seen, but oligoclonal IgG bands are usually negative. T helper cell 17, B cells and neutrophil-related cytokines appear to be upregulated intrathecally. The pathology of acute lesions is characterized by active inflammation demyelination with deposition of immunoglobulins and complements. Just like aquaporin 4 IgG-positive neuromyelitis optica spectrum disorders, some disease-modifying drugs for multiple sclerosis seem to be inefficacious in MOG-IgG-associated disease, and chronic immunosuppression is required to prevent relapse, especially in patients persistently positive for MOG-IgG. Our understanding of this newly recognized disease remains insufficient, and the progress of research is much expected.

Distal symmetric polyneuropathy, represented by chronic inflammatory demyelinating polyneuropathy, is a popular neurological condition. Some cases are known to be associated with genetic mutations or serum auto-antibodies, but the exact mechanisms in most cases are unknown. Recently, osmotic factors have been suggested to trigger some neurological disorders, such as neuromyelitis optica. The aim of the present study was to assess the possible association of osmotic factors in the pathogenesis of distal polyneuropathy. We prospectively measured the serum levels of osmolality, electrolytes, total protein, albumin, blood urea nitrogen, glucose, and osmolality gap in the patients with acute distal polyneuropathy before treatments (n = 12) and those with other comprehensive neurological disorders such as multiple sclerosis and neurodegenerative diseases (n = 176). Then, we compared each osmotic fraction between the two groups. As a result, all of the 12 patients with acute distal polyneuropathy, including 4 patients with chronic inflammatory demyelinating polyneuropathy, showed abnormally high or low values of osmolality gap, compared to the others (p < 0.0001, F-test). In the patients with other diseases, there were 2 patients with abnormally high osmolality gap values, which were attributable to their hyperlipidemia or high titer of serum autoantibody unrelated to polyneuropathy. In conclusion, serum osmolality gap would be elevated or decreased in the acute phase of distal symmetric polyneuropathy. Osmotic imbalance between the serum and nerve cells, based on abnormal excess or deficit of some unidentified serum osmolytes, may be one of the mechanisms in symmetric polyneuropathy with unknown causes.

We compared the retinal thickness in the unaffected eyes among the following subtypes of unilateral optic neuritis (ON): multiple sclerosis (MS-ON), neuromyelitis optica spectrum disorder with anti-AQP4 autoantibody (AQP4-ON), patients with serum anti-MOG antibody (MOG-ON), and idiopathic ON. In the chronic phase, macular GCC and circum-papillary RNFL in the unaffected eyes were both atrophied in MS-ON and AQP4-ON, but were not atrophied in the others. Titers of anti-AQP4-Ab was suggested to be associated with such latent neurodegenerative process in AQP4-ON. Long-term follow up of OCT is recommended even in the unaffected side in MS-ON and AQP4-ON.

We evaluated the brain volume and rate of atrophy in 85 Japanese patients with multiple sclerosis (MS). The mean brain volume was smaller and the rate of atrophy appeared to be more rapid in MS patients than in normal subjects. The brain atrophy seemed to exist from the early stage of MS and was prominent in the grey matter. Patients with progressive MS showed severer atrophy. We show the existence of pathological brain atrophy in Japanese MS patients for the first time, although the rate of atrophy may be much slower than in Caucasian patients.

Clinical application of accumulated medical big data is a hot topic in medical informatics. Not only for suggesting possible diagnoses in each individual, large medical database can be possibly used for detecting undiagnosed patients in the general population. In this study, we tried to develop a computerized system of detecting overlooked undiagnosed patients with rare chronic diseases in the community population by utilizing the uniformed national medical insurance record database. A cumulative total of 489,823 hospital visits at one tertiary medical center were collected for this project. As the target disease, we selected esophagogastric junction outflow obstruction (EGJOO), including achalasia, which is known to be easily overlooked without performing a barium swallow test. Patient selection software automatically picked out 17,814 individuals with the given suspected diagnoses that could be misdiagnosed in patients with the target disease, from which the software further picked out 526 individuals who underwent upper endoscopy but did not undergo barium swallow test. Of them, the hospital medical records suggested that 39 people still suffered from prolonged symptoms lasting for more than 6 months after the first hospital visit. Among them, 16 individuals agreed to undergo the barium swallow test. One of them was confirmed to suffer from EGJOO, possibly based on some undiagnosed connective tissue diseases. An automated computerized detection system with uniform big medical data would realize more efficient and less expensive screening system for undiagnosed chronic diseases in the general population based on symptoms and previously performed examinations in each individual.

Background The central nervous system was previously thought to draw oxygen and nutrition from the arteries and discharge carbon dioxide and other metabolic wastes into the venous system. At present, the functional role of cerebrospinal fluid in brain metabolism is not fully known. Methods In this prospective observational study, we performed gas analysis on venous blood and cerebrospinal fluid simultaneously acquired from 16 consecutive preoperative patients without any known neurological disorders. Results The carbon dioxide partial pressure (pCO2) (p

Oxidative stress in renal mesangial cell causes diabetic glomerular changes. High glucose levels and angiotensin II (Ang II) are known to stimulate superoxide production in renal mesangial cells. However, it has been unclear whether Ang II stimulation and pre-conditioning with high glucose affects the same pathway of superoxide production in renal mesangial cells or not. In this study, we examined the levels of oxidative stress under Ang II stimulation in renal mesangial cells preincubated for six hours at various glucose levels. Intracellular levels of reactive oxidative species (ROS) were measured using dihydroethidium or 5′,6′-chloromethyl- 2′,7′ dichlorodihydro-fluorescein diacetate, which facilitates the detection of intracellular ROS under real-time fluorescent microscope. Ang II-induced elevated intracellular ROS levels were detected only when the cells were pre-incubated with high levels of glucose (13.5 mM, 27.8 mM), but was not detected under normal glucose condition (5.5 mM). Production of Ang II-induced intracellular ROS was higher under pre-treatment with 27.8 mM glucose compared to pretreatment with 13.5 mM glucose level. This ROS production in mesangial cells was induced within several minutes of the initiation of Ang II stimulation under high glucose levels. The production of intracellular ROS was significantly reduced in the presence of angiotensin II type1-receptor (AT1R) antagonist, whereas it was augmented in the presence of angiotensin II type2-receptor antagonist. In conclusion, Ang II-induced oxidative stress was augmented by high glucose levels and ROS levels were further alleviated in the presence of AT1R antagonists.

After a massive disaster, many residents in affected areas are forced to temporarily stay in evacuation shelters. The exact impact of the state of resource supply and infrastructure in evacuation shelters on the health status of evacuees has not been sufficiently studied. Two weeks after the 2011 Great East Japan Earthquake (GEJE), comprehensive surveillance related to the health status and hygiene level was performed for all evacuation shelters (328 shelters with 46,480 evacuees at the peak) in one of the most devastating medical zones after the tsunami hit the area (Ishinomaki City). The joint relief team regularly visited all evacuation shelters across the area to assess the situation of resource supply levels, infrastructural damage, rapid need of resources, and the health status of the evacuees. In this cross-sectional observational study, we evaluated the relationship between the resource supply levels and health status among evacuees in two time periods (days 14–19 and 20–25). Among the evaluated vital resources, clean tap water supply was among the most disrupted by the disaster, and was not fully restored in most shelters during the assessment period. The cross-sectional relationship between resource supplies and morbidity was inconsistent between the two assessment periods, reflecting the multifactorial nature of health status in evacuation shelters. The clean tap water supply level at the first assessment showed a strong negative correlation with the subsequent prevalence of respiratory or gastrointestinal infectious conditions at the second assessment. Restorations in the clean tap water supply and toilet hygiene correlated each other, and both correlated with a decrease in the prevalence of gastrointestinal infectious conditions. In conclusion, disrupted clean tap water supply and inadequate toilet hygiene after a massive disaster would jointly harm the health status of those in shelters. Prompt assessments using quick visual assessment and restorations of these key resources have validity with suppressed environmental health risks among evacuees., Disaster; Evacuation shelter; Infectious diseases; Toilet hygiene; Water supply.

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing neuroinflammatory disease associated with aquaporin-4 antibody. Since disabilities in patients with NMOSD accumulate with attacks, relapse prevention is crucially important for improving long-term outcomes. Corticosteroids are inexpensive and promising drugs for relapse prevention in NMOSD, but few studies have analysed the efficacy of corticosteroids in NMOSD, especially regarding the appropriate dosing and tapering regimens.A single-center, retrospective analysis of corticosteroid therapy in aquaporin-4 antibody-positive NMOSD patients fulfilling the 2015 international consensus diagnostic criteria was conducted.Medical records of a total of 89 Japanese patients with aquaporin-4 antibody-positive NMOSD seen at Department of Neurology, Tohoku University Hospital (2000~2016) were reviewed. At the last follow-up, 66% of the patients were treated with prednisolone (PSL) monotherapy, and the percentage of those receiving PSL monotherapy or a combination of PSL and other immunosuppressants increased from 17.5% in 2000 to 94.1% in 2016. On the other hand, annualised relapse rate (ARR) decreased from 0.78 (13 attacks in 200 person-months) in 2000 to 0.07 (5 attacks in 819 person-months) in 2016. Under PSL treatment, the mean ARR significantly decreased, and disabilities stabilized (PSL treatment vs no-medication; ARR: 0.21 vs 0.98, P0.01, Expanded Disability Status Scale score change: +0.02 vs +0.89, P0.01, observation periods: 60.1 vs 68.2 months, P=0.26). Using Kaplan-Meier curves, the 10-year relapse-free rate was 46.5% with PSL monotherapy and 7.1% with no medication (hazard ratio: 0.069, 95% confidence interval [CI] 0.024-0.199, P0.01). Rapid tapering of PSL (10 mg or less in one year and/or 5 mg or less in two years after clinical attacks) was associated with frequent relapses compared to gradual tapering (more than 10 mg in one year and more than 5 mg in two years after clinical attacks) (rapid vs gradual, 36.7% vs 17.7%, odds ratio 2.69, 95% CI 1.12-6.44, P = 0.02). However, even with PSL of 5 mg/day or less, the relapse rate was low after two years of acute treatment (before vs after, 53.8% vs 13.6%, odds ratio 0.12, 95% CI 0.03-0.50, P0.01). Nine patients needed additional immunosuppressants due to insufficient relapse prevention by PSL monotherapy. PSL monotherapy was generally well tolerated, but seven patients had severe adverse events, mainly bone fractures (5 with bone fracture, 1 with femoral capital necrosis and 1 with cerebral infarction).Our study suggests that PSL monotherapy is effective to prevent relapses in about half of patients with aquaporin-4 antibody-positive NMOSD if the doses are gradually reduced. Although it is important to have a treatment strategy tailored to each patient, this study provides evidence that PSL monotherapy can be an option for relapse prevention in some patients with NMOSD.

We compared the clinical features of optic neuritis (ON) that are frequently observed in various central nervous system demyelinating diseases, including multiple sclerosis (MS), anti-aquaporin 4 (AQP4) antibody- and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody-related diseases. Almost all the AQP4-ON patients were female, whereas half of the MOG-ON patients were male. The ON-onset age was younger in MS-ON and was older in AQP4-ON. The ON-lesion detected using optic MRI in the acute phase was longer in MOG-ON and showed severe swelling and twisting. The worst visual acuity was similar between the diseases; however, the final visual acuity was significantly worse in AQP4-ON.

The visual acuity prognoses of patients with neuromyelitis optica (NMO) are worse than those with optic neuritis (ON) caused by other diseases. Predicting the prognoses of ON at the time of onset is important for selecting treatments for NMO patients.Twenty-three consecutive anti-aquaporin-4 autoantibody-positive NMO patients who presented with ON and had contrast-enhanced optic MRIs in the acute phase of their first ON episode were examined. Optical coherence tomographies (OCTs) were also examined for 22 of them. The visual acuity at the final follow-up, as assessed with the logMAR scale more than three years after ON onset, served as the outcome measure. These variables were also collected from 12 patients with serum anti-myelin oligodendrocyte glycoprotein antibody (anti-MOG-Ab).The strongest predictor of visual prognosis was the axial ON lesion length in the acute phase (R=0.747, p0.0001), which was not observed in patients with anti-MOG-Ab. Specifically, the ON lesion length within the intra-orbit and canalicular segments exhibited the strongest correlation with visual prognosis (R=0.783, p0.0001). The ON onset age was also correlated with visual prognosis (R=0.435, p=0.0338). OCT data in the chronic phase also showed a correlation with visual prognosis, but they were much weaker than the ON lesion length in the acute phase.The ON lesion length in the acute phase was an important predictor of the visual prognoses of NMO patients.

This study aimed to determine the seasonal impact on the clinical onset of inflammatory neurological diseases of the central nervous system by analyzing the onset month with information on clinical manifestations in Japanese patients. As a result, patients with anti-aquaporin-4 antibodies (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSD) showed spring-summer predominance of the clinical onset. Conversely, patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease showed autumn-winter predominance of the clinical onset. Both seasonal variations were irrespective of the clinical manifestation. Environmental factors with seasonal variation influence the development of neurological conditions related to AQP4-IgG and MOG-IgG.

We present a case of a 71-year-old woman who accidently swallowed a large fish bone that penetrated into the pulmonary vein. She visited the hospital the next day with a complaint of mild chest discomfort with slight pain and fever of 37.4 °C. Contrast-enhanced chest computed tomography (CT) scan revealed a large fish bone with a length of 35 mm impacted in the middle esophagus. The bone had penetrated into the pulmonary vein, causing mediastinitis. Blood tests revealed elevation in the white blood cell count and C-reactive protein level. Because intractable bleeding from pulmonary vein after endoscopic removal can be lethal, endoscopic removal of the fish bone in an operating room under general anesthesia with cardiovascular surgical standby for possible emergency surgery was selected. After endoscopic removal, mediastinal hematoma was absent with a follow-up chest CT scan, and the mediastinitis was treated with intravenous antibiotics. The patient shortly became afebrile with normalized blood test findings. After confirming the normal findings on the follow-up chest CT scan and endoscopic inspection in the next week, she was discharged from the hospital 10 days after hospitalization without any complications. When the swallowed bone penetrates into the major pericardial vessels, unprepared endoscopic removal may result in fatal sequelae such as intractable mediastinal hemorrhage. Urgent consultation with cardiovascular or thoracic surgeons for a possible emergent surgery is needed before endoscopic removal is attempted., Medical imaging; Gastrointestinal system; Emergency medicine; Internal medicine; Radiology; Chest computed tomography, Endoscopic removal, Mediastinitis, Penetration, Pulmonary vein, Swallowed fish bone.

The association between routine laboratory findings, including cerebrospinal fluid biomarkers, and neurological outcomes in patients with multiple sclerosis (MS) has not been fully elucidated. In this study, we evaluated blood and cerebrospinal fluid (CSF) analysis results at diagnosis and before treatment in patients with MS and assessed their correlations with neurological outcomes.In this study, 38 consecutive patients with MS (36 with relapsing-remitting MS and 2 with primary progressive MS) were recruited. Before treatment, all patients underwent routine CSF analysis at the time of diagnosis, including evaluation of albumin and immunoglobulin G (IgG) levels. The association between laboratory data and neurological outcomes was comprehensively evaluated. Subsequent neurological outcome was assessed by using the Expanded Disability Status Scale (EDSS) score at 1 year and 5 years after diagnosis and relapse frequency in the first year and in the first 5 years.The IgG level in the CSF (rho = 0.46, p = 0.004), oligoclonal band count (rho = 0.61, p = 0.006), ratio of IgG and total protein in CSF (rho = 0.59, p0.0001), and ratio of IgG and albumin in CSF (rho = 0.67, p0.0001) showed moderate to strong correlations with the subsequent EDSS score 1 year after diagnosis. These variables still showed significant correlations with EDSS 5 years later. Albumin and lactate dehydrogenase levels in CSF did not correlate with the subsequent EDSS score. Relapse frequency did not correlate with any of the studied serum and CSF biomarkers.IgG levels in CSF at MS diagnosis are significantly correlated with the level of neurological disability independent of the relapse frequency. Markers of intrathecal IgG synthesis, such as the IgG index, are useful in estimating the present and subsequent clinical severity in patients with MS.

Introduction Progressive brain atrophy, development of T1-hypointense areas, and T2-fluid-attenuated inversion recovery (FLAIR)-hyperintense lesion formation in multiple sclerosis (MS) are popular volumetric data that are often utilized as clinical outcomes. However, the exact clinical interpretation of these volumetric data has not yet been fully established. Methods We enrolled 42 consecutive patients with MS who fulfilled the revised McDonald criteria of 2010. They were followed-up for more than 3 years from onset, and cross-sectional brain volumetry was performed. Patients with no brain lesions were excluded in advance from this study. For the brain volumetric data, we evaluated several parameters including age-adjusted gray-matter volume atrophy, age-adjusted white-matter volume atrophy, and T2-FLAIR lesion volume. The numbers of T1-hypointense and T2-FLAIR-hyperintense areas were also measured along the same timeline. The clinical data pertaining to disease duration, expanded disability status scale (EDSS), and MS severity score (MSSS) at the timing of volumetry were collected. Results Among the 42 patients with MS and brain lesions, the number of T1-hypointensity (rho = 0.51, p

Introduction Neuromyelitis optica spectrum disorder (NMOSD) is characterized by the presence of serum anti-aquaporin 4 (AQP4) antibody. However, the significance of changes in the serum titer as a marker of disease severity or relapse prediction is unknown. Methods We collected clinical data and serum antibody titers by cell-based assay from 45 NMOSD patients for whom more than one titer measurement taken in 6–12 month interval periods was available. The AQP4-IgG titer was measured by a live cell-based assay method, and the serum titer levels between the acute phase and preceding chronic phase were compared. In addition, we evaluated the correlation between the serum titer and relapse frequency while following the clinical course of the enrolled NMOSD patients. Results Serum AQP4-IgG titer was not elevated in the acute phase, compared to that of the preceding chronic phase, irrespective of the clinical phenotypes. Moreover, there was no correlation between the titer at onset and relapse frequency in 10 years post-onset or neurological disability at 5 and 10 years after onset. The titer was slightly elevated several months before relapses in about half of the cases, but the change was trivial and may not be applicable for clinical use. Conclusion Although evaluating the positivity of serum AQP4-IgG at the onset is necessary, the titer level does not reflect the ongoing disease activity or the following neurological prognosis. Repeated follow-up of titer levels may not be useful for the management of NMOSD patients.

We aimed in this study to elucidate the impact of serum AQP4-IgG titer before starting treatments to the clinical manifestation of neuromyelitis optica spectrum disorders (NMOSD). Serum titer at the onset, measured using live cell-based assay method, did not correlate to the subsequent relapse rate or neurological prognosis. Patients with optic neuritis as the first attack showed significantly higher serum titer than patients with acute myelitis or area postrema syndrome, although the titer did not correlate to the visual prognosis. The result implies that the pathological mechanism of optic neuritis and acute myelitis could be different in NMOSD.

Immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG) are detected in the serum of some patients with demyelinating diseases. These patients are known to show repeated clinical episodes of inflammatory demyelinating attacks in the central nervous system. Although the associated pathogenicity and mechanism of inflammatory demyelination remains inconclusive, it is known that patients with MOG-IgG antibodies have a different clinical spectrum from those with other demyelinating diseases, such as multiple sclerosis. Based on our database of 85 MOG-IgG positive (+) cases, the most frequently associated clinical episodes were isolated optic neuritis (67.5%), encephalitis (26.5%), and myelitis (19.3%). Optic neuritis in MOG-IgG (+) disease usually involves the long segment of optic nerves and sometimes happens bilaterally, but visual acuity usually recovers with proper treatment in the acute phase. Brain and brainstem lesions usually present vague and focal appearances with irregular margins, typically in subcortical or brainstem regions, but occasionally in the cortex or corpus callosum. Due to these characteristics, MOG-IgG (+) cases with brain or brainstem lesions are sometimes diagnosed with acute disseminated encephalomyelitis, meningitis, or symptomatic epilepsy. The myelitis in MOG-IgG (+) typically shows longitudinally extensive lesions as seen in neuromyelitis optica spectrum disorders. Acute treatment to reduce attack-related disability is recommended in MOG-IgG (+) disease, and long-term immunosuppression may be considered in patients with a high frequency of relapses and/or high risk of neurological disability.

Overlap of multiple mental disorders in each psychiatric patient has been emphasized and the style of assessment and intervention in each patient has been gradually changed. A new practical structured model that can comprehensively explain and assess the major mental disorders integratedly has been desired. In this report, the relationships between each of the major mental disorders and each neuropsychiatric component like personality, reward system, or reinforcement learning have been comprehensively reviewed to construct a new integrated structured model for assessing the overlapped mental conditions in primary care psychiatry. This new structured model contains the following three loops: "input-output-feedback loop" (external/environmental loop), "reward-learning loop" (learning loop), and "mood-reward sensitivity loop" (mood loop), which are connected by the functions of prefrontal cortex and basal ganglia. With this new concept, overlapped mental conditions in each psychiatric patient could be theoretically much simply and logically explained. In conclusion, with the proposed psychiatric structured model, we can simply explain and understand the overlapped mental disorders in each patient. Inventing and developing such basic psychiatric structured model would offer us new diagnostic and therapeutic tools to realize personalized medicine, especially in the field of primary care psychiatry.

Saltatory conduction is an essential phenomenon to facilitate the fast conduction in myelinated nerves. The conventional conductive models assumed electric circuits with local current along the axonal membrane to explain the nerve conduction in unmyelinated nerves. However, whether such models with local current can be also applied to the saltatory conduction in myelinated nerves is unknown. In this report, I propose a new model of saltatory conduction by focusing on the behavior of electric charges in the axoplasm, not limited to the membrane. In myelinated nerves, because of the large internodal length and the low ion channel density in the internodal segment, the whole cross-section of the internodal axoplasm would contribute to the signal conduction. Because the conducted signals originate from the sodium ion influx through the voltage-gated sodium (NaV) channel at the Ranvier's nodes, an individual conducted signal can be described as a single electrostatic compressional wave of positive charges in the internodal axoplasm. Based on this model, the total number of NaV channels in one Ranvier's node would regulate the strength of the wave. Also, the internodal length would be important for the faster conduction in larger myelinated axons. Based on the linear relationships between axonal diameter, internodal length, and conduction velocity, the internodal length would be inversely proportional to the ratio of the transmitted overall wave strength at a Ranvier's node to the original strength at the proximal adjacent node. This new mathematical model may have wide applicability and usability for the conduction in myelinated nerves.