Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function

Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration.

Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group.

Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

Objective Immunomodulatory drugs and proteasome inhibitors are therapeutic options for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. This study aimed to evaluate the efficacy and safety of the combination of ixazomib, lenalidomide, and dexamethasone (IRd) for POEMS syndrome.

Methods Six consecutive patients with POEMS syndrome who were treated with the IRd regimen at Chiba University Hospital between April 2018 and August 2021 were included. Serum M-protein and serum vascular endothelial growth factor (sVEGF) levels, overall neuropathy limitation scales (ONLS), clinical symptoms, and adverse events were assessed.

Results Of the six patients, five had received prior treatments. Patients received a median of 5 cycles (range, 3-28 cycles) of IRd. Following treatment, serum M-protein disappeared in two patients, sVEGF levels returned to normal in two patients, two patients showed a reduction in the ONLS of 1, and clinical symptoms improved in four patients. The median level of sVEGF decreased from 2,395 pg/mL (range, 802-6,120 pg/mL) to 1,428 pg/mL (range, 183-3,680 pg/mL) in three months. Adverse events, including rash, neutropenia, sensory peripheral neuropathy, and nausea, were observed in three patients, which necessitated dose reduction or discontinuation of treatment.

Conclusion IRd can be a therapeutic option for POEMS syndrome, albeit with careful monitoring of adverse events.

Objective To investigate the efficacy of home-based gait training using the wearable Stride Management Assist (SMA) exoskeleton in people with moderately advanced Parkinson's disease.

Methods This was a single-center, open-label, parallel, randomized controlled trial. We included outpatients with idiopathic Parkinson's disease who were capable of walking independently with or without walk aids and had Hoehn and Yahr stage 2-4 in the ON state. Patients were randomly assigned (1:1 ratio) to receive either SMA gait training (SMA group) or control gait training (control group). All participants underwent gait training for approximately 30 min. These training sessions were conducted 10 times for 3 months. We measured clinical outcomes at baseline and post-intervention. The between-group difference of distance in the three-minute walk test was the primary outcome.

Results Of the 15 randomly assigned participants, 12 (five in the SMA group) completed this study. The between-group difference was a mean of 13.7 meters (standard error of the mean: 7.8) in the 3-minute walk test (p=0.109). The distance traversed increased from 141.4 m to 154.7 m in the SMA group (p=0.023), whereas there was no marked change in the control group. In addition, although there was a decrease in the physiological cost index from 0.29 to 0.13 in the SMA group (p=0.046), it remained unchanged in the control group.

Conclusion These findings suggest that home-based SMA gait training may increase the exercise endurance in people with moderately advanced Parkinson's disease.

Objective Left ventricular (LV) thrombus is a rare condition in acute cerebral infarction. The prevalence and features of cerebral infarction with LV thrombus are unclear. We explored the features of cerebral infarction due to LV thrombus.

Methods In this single-center retrospective study, we investigated consecutive patients with acute ischemic stroke admitted within seven days of the onset who had LV thrombus found by transthoracic echocardiography (TTE). First, we calculated the prevalence of LV thrombus in patients with cardioembolic stroke (CES). Second, we investigated the baseline characteristics, including the TTE findings and features of cerebral infarction due to LV thrombus.

Results From June 2012 to January 2019, a total of 5,693 patients were enrolled. Of these, 1,408 (25%) patients were diagnosed with CES. Of these 1,408 patients with CES, 13 (0.9%) had LV thrombus indicated by TTE, with dilative cardiomyopathy, subacute myocardial infarction, and old myocardial infarction present in 1 (8%), 2 (15%), and 10 (77%), respectively. The ejection fraction (EF) was 48.9% (25.3-64.7%). The maximum longitudinal size of LV thrombus was 13.4 (0.97-38.1) mm, and there was no correlation between the size of the LV thrombus and the EF. Regarding the features of cerebrovascular infarction, major vessel occlusion was observed in 10 (77%) patients. Six (46%) patients were found to have good outcomes (modified Rankin Scale 0-2) at 90 days after the onset.

Conclusion LV thrombus was seen in 0.9% of patients with CES. Many of the patients with LV thrombus had major vessel occlusion.

Von Hippel-Lindau (VHL) disease is a rare inherited familial syndrome complicated with various neoplasms, including neuroendocrine tumors (NETs). We herein report the first case of multiple gastric NETs in a 45-year-old man with VHL. He had multiple gastric polyps, and several endoscopic resected lesions were diagnosed as NETs. The serum gastrin level was elevated because he was taking a proton pump inhibitor (PPI). We suspected that gastrin had played a role in the development of NETs, and the remaining polyps were followed up with discontinuation of the PPI. The NETs gradually reduced in size until they became hard to notice on endoscopy and have remained nearly invisible for over eight years.

We herein report an 80-year-old man diagnosed with immunoproliferative small intestine disease (IPSID) via small bowel endoscopy with a biopsy. He developed persistent diarrhea and subsequently presented with hypoproteinemia and moderate anemia. Transanal double-balloon endoscopy showed prominent villous edema in the middle and lower ileum, while a histological examination showed high lymphocyte/plasma cell infiltration in the mucosal layer. Furthermore, an immunostaining analysis showed that Cluster of differentiation (CD) 3 and CD20 were partially positive, while CD138 was diffusely positive. Immunoglobulin A positivity was also observed. He was diagnosed with IPSID and received a nutritional agent and minocycline. After three months, the patients' symptoms improved.

We herein report a 61-year-old man who sustained injury after a 2-m fall and developed mediastinitis. He presented to another hospital two days after the fall and was transferred to our hospital four days after the fall with a fever and dysphagia. Computed tomography revealed osteophytes on the second and third thoracic vertebrae and free air in the mediastinum, indicating esophageal perforation. Emergent surgery was performed. Intraoperatively, a longitudinal esophageal tear was identified. We stress the importance of being aware of the possibility of osteophyte-related esophageal perforation in patients with a history of a fall. A delayed diagnosis affects the prognosis.

Chronic enteropathy associated with solute carrier organic anion transporter family, member 2A1 (SLCO2A1) (CEAS) is a rare autosomal recessive hereditary disease characterized by chronic persistent anemia and hypoproteinemia. Its diagnosis typically requires a genetic analysis. The efficacy of immunohistochemical staining with SLCO2A1 polyclonal antibody as a pre-diagnostic tool for CEAS has been previously reported. We herein report a patient with CEAS in whom immunohistochemical staining confirmed SLCO2A1 protein expression. The immunopositive results may have been due to nonsense-mediated RNA decay. As immunohistochemical staining of SLCO2A1 protein may show immunopositive results, a genetic analysis should also be performed when CEAS is strongly clinically suspected.

A 65-year-old man had a history of cholecystectomy and treatment for cholelithiasis with a common bile duct incision. Owing to frequent cholangitis, he underwent choledochojejunostomy. Twenty years after the surgery, he was hospitalized for cholangitis and was suspected of having hilar cholangiocarcinoma based on imaging findings. Percutaneous transhepatic cholangioscopy using a SpyGlass™ DS (Boston Scientific, Marlborough, USA) showed gallstones and bile sludge in the bile ducts, but no tumors were noted. Electrohydraulic shockwave lithotripsy with double-balloon enteroscopy enabled complete stone removal; a direct visual biopsy with peroral cholangioscopy showed no malignancy in the bile duct.

We herein report a case of encephalitis in a 42-year-old woman with hepatocellular carcinoma following atezolizumab plus bevacizumab therapy. After two weeks of treatment, she was admitted for a high fever, impaired consciousness, and convulsive seizure refractory to diazepam. Magnetic resonance imaging revealed a hyperintense splenial lesion. A cerebrospinal fluid test excluded malignancy and infection. These findings were highly suggestive of a diagnosis of encephalitis due to atezolizumab, an immune-related adverse event. Steroid pulse therapy improved the fever and seizure. However, her incomplete right-sided paralysis and aphasia persisted. This is the first case report of encephalitis caused by atezolizumab plus bevacizumab therapy for hepatocellular carcinoma.

Myocarditis is being increasingly reported as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccines. We herein report a case of myocarditis following COVID-19 mRNA vaccination in a man. Cardiac magnetic resonance imaging (CMRI) revealed an area of high signal intensity on short T1 inversion recovery (STIR) and late gadolinium enhancement (LGE), which are characteristic of myocarditis. Follow-up CMRI performed six months later revealed improvement in the myocardial edema and LGE findings. CMRI is a useful non-invasive imaging modality for making an initial diagnosis as well as for follow-up in cases of myocarditis after COVID-19 mRNA vaccination.

Pancytopenia due to malnutrition sometimes occurs after gastric bypass but is rare after sleeve gastrectomy. A 35-year-old patient underwent sleeve gastrectomy for severe obesity. Twelve months after the operation, rapid progression of macrocytic anemia with leukopenia and thrombocytopenia occurred, and a decrease in some vitamins and trace elements due to an insufficient food intake was also detected. Haptoglobin decreased, suggesting the presence of hemolysis. In addition, IgM antibody against parvovirus B19 was detected, followed by IgG antibody. Parvovirus B19 infection was suggested to be involved in the rapid progression of anemia in this malnourished patient after bariatric surgery.

A 69-year-old man was diagnosed with immunoglobulin (Ig) G4-related disease (IgG4-RD) at 62 years old. At that time, he had high serum IgG4 levels and bilateral submandibular gland swelling on CT; thus, a gland biopsy was performed. Because a reticular shadow was found on chest CT, a lung surgical biopsy was also performed. The specimens revealed usual interstitial pneumonia (UIP) pattern interstitial pneumonia with some IgG4-positive cells. The patient was subsequently followed up without treatment. His forced vital capacity and radiological findings progressively deteriorated, consistent with UIP pattern interstitial lung disease but different from a lung lesion of IgG4-RD.

Endobronchial aspergilloma is a rare disease. A 64-year-old man with severe diabetes mellitus developed a cough and fever and was referred to our hospital. He was diagnosed with obstructive pneumonia associated with endobronchial aspergilloma, underwent interventional bronchoscopy, and was treated with antifungals. While the optimal treatment has not been established, interventional bronchoscopy along with systemic antifungals may improve the outcome in such cases.

Cryptogenic bilateral fibrosing pleuritis is a rare condition, and its pathogenesis and clinical course are poorly understood, with no established therapy available. A 61-year-old man presented with bilateral pleural thickening and lymphocytic exudative effusions. The patient was diagnosed with fibrosing pleuritis with no evidence of a known etiology on a surgical pleural biopsy. Within 16 months from the onset of respiratory symptoms, restrictive ventilatory impairment progressed rapidly, resulting in hypercapnic respiratory failure requiring home oxygen and non-invasive positive pressure ventilation therapies.

A 74-year-old man was admitted to our hospital because of systemic lymphadenopathy, weight loss, and a fever at night that had persisted for approximately 1 month. Blood tests revealed extreme peripheral blood plasmacytosis and hypergammaglobulinemia. A lymph node biopsy showed angioimmunoblastic T-cell lymphoma (AITL). Based on the history of methotrexate (MTX) administration, the established diagnosis was MTX-associated lymphoproliferative disorder (MTX-LPD). After MTX was discontinued, the lymphadenopathy spontaneously regressed and the plasmacytosis disappeared. He had no disease progression for three years. We found that AITL as an MTX-LPD can cause plasmacytosis, and the prognosis of this disease may not be poor.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by the infiltration of foamy histiocytes into multiple organs. We herein report a case of ECD with central nervous system (CNS) involvement in a 63-year-old man who also presented a positive result for Toxoplasma gondii nested polymerase chain reaction testing of cerebrospinal fluid. Since anti-Toxoplasma treatment proved completely ineffective, we presumed latent infection of the CNS with T. gondii. This case suggests the difficulty of distinguishing ECD with CNS involvement from toxoplasmic encephalitis and the possibility of a relationship between the pathogeneses of ECD and infection with T. gondii.

A 63-year-old woman who presented for orofacial dystonia showed cortical ribboning, a typical MRI finding in sporadic Creutzfeldt-Jakob disease (sCJD). However, real-time quaking-induced conversion (RT-QuIC), the most sensitive method for an early diagnosis of sCJD, was negative. She developed sCJD six months later, at which time RT-QuIC became positive. The cerebral blood flow showed a decrease in the cerebral cortex (especially in the supramarginal gyrus) consistent with cortical ribboning, but an increase in the basal ganglia, probably involved in orofacial dystonia. Cortical ribboning on MRI might be a better biomarker than RT-QuIC in the prodromal phase of sCJD.

Pleural effusion is a rare manifestation in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, which is characterized by the presence of osteoarticular lesions and dermatological involvement. We herein report a 71-year-old man with pleural effusion resulting from SAPHO syndrome. He was successfully treated using corticosteroids and has experienced no recurrence for one year. We should consider SAPHO syndrome when encountering cases of anterior chest pain and pleural fluid.

A 66-year-old man was admitted to our hospital for gastrointestinal perforation. He had a history of surgery and chemotherapy for colorectal cancer and had a subcutaneously implanted central venous port catheter. After surgery for gastrointestinal tract perforation, he developed an intra-abdominal abscess, which was treated with broad-spectrum antimicrobial agents and improved. Following this improvement, Rhodotorula spp. was detected in a blood culture and at the catheter tip. He was asymptomatic despite having fungemia. His condition improved after the removal of the catheter and the administration of antifungal drugs. Fungemia due to Rhodotorula spp. is rare, and asymptomatic fungemia is even rarer.

There are few cases describing the association of eosinophilia with hypercalcemia, and drug-induced eosinophilia with hypercalcemia has not been reported. A 74-year-old man had been diagnosed with asthma 4 months earlier. He was admitted due to eosinophilia with hypercalcemia. Chest computed tomography showed a nodule in the left lung and mediastinal lymphadenopathy. By obtaining a detailed medical history, clopidogrel was suspected as the prime cause of eosinophilia. After the discontinuation of clopidogrel, the eosinophilia with hypercalcemia, lung nodule and mediastinal lymphadenopathy improved. Clopidogrel-induced eosinophilia can potentially cause hypercalcemia. Obtaining a detailed clinical history is important in diagnosing the cause of eosinophilia.

Kikuchi disease, also called histiocytic necrotizing lymphadenitis, is an idiopathic and generally self-limiting disease affecting young adults and children. Kikuchi disease does not commonly manifest neurological complications at its initial presentation. We herein report two cases of Kikuchi disease that initially presented with aseptic meningitis and encephalitis rather than the more common signs of lymphadenopathy, rash, and arthritis. A 15-year-old boy presented with aseptic meningitis with an extremely high intracranial pressure. A 28-year-old man presented with dysesthesia of the right lower extremity, coinciding with abnormal magnetic resonance imaging findings. In both cases, painful cervical lymphadenopathy was observed following the central nervous system symptoms. Both patients improved after treatment with steroids. Kikuchi disease occasionally affects the central nervous system, to which lymphadenitis may be observed subsequently. A repeated, careful physical examination of the cervical lymph nodes may be helpful for the diagnosis.