Objective Ascites becomes refractory to diuretics in cirrhotic patients, who then require repeated large-volume paracentesis or cell-free and concentrated ascites reinfusion therapy (CART). The objective of this study was to confirm the safety and efficacy of CART, evaluate the actual situations with respect to the prescription of diuretics and determine the role of diuretics after the introduction of CART.

Patients and Methods We recruited 34 cirrhotic patients who received CART with concomitant diuretics using furosemide (76.2%), spironolactone (48.5%), thiazide (4.0%) and tolvaptan (53.5%) from a post-marketing surveillance of CART.

Results CART improved the tested clinical indices, i.e., body weight, abdominal circumference, performance status, dietary intake, total protein and albumin. The intervals of CART sessions were significantly prolonged in patients who received tolvaptan (mean, 22.5 days) compared to those not receiving tolvaptan (mean, 10.8 days) (p<0.001). The drop-out rate was significantly decreased in patients receiving tolvaptan compared to those not receiving tolvaptan when drop-out was defined as paracentesis (p<0.05).

Conclusion We confirmed that CART is an effective treatment for refractory ascites occurring in cirrhotic patients. The administration of tolvaptan in combination with CART leads to a significantly reduced rate of ascites accumulation.

Objective Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in human immunodeficiency virus (HIV)-negative and HIV-positive populations. White matter lesions (WMLs) have been reported in both populations of CM patients; however, the mechanisms underlying WML formation remain unknown. We herein report the relationship between the intrathecal immune response and the development of WMLs in HIV-negative patients with CM.

Methods Eleven consecutive HIV-negative patients with CM who presented at one of three emergency hospitals in Japan from April 2001 to March 2018 were enrolled. For all patients, we retrospectively assessed the relationships between clinical and laboratory information and the presence of WMLs.

Results At presentation, 6 patients had WMLs on magnetic resonance imaging (MRI). The cerebrospinal fluid immunoglobulin G (CSF IgG) index was significantly higher in the patients with WMLs than in those without WMLs (mean, 1.34 vs. 0.70, p=0.017). The time from the symptom onset to initial neuroimaging was also significantly longer in the patients with WMLs than in those without WMLs (median, 31.5 vs. 7.0 days; p=0.008). The clinical outcome was comparable among the patients with and without WMLs.

Conclusion In HIV-negative patients with CM, a persistent, aberrant immune response to Cryptococcus, such as intrathecal IgG synthesis, may induce WML formation.

Objective Chest physicians often encounter patients with interstitial pneumonia with autoimmune features. However, there have so far been few reports of patients presenting with concurrent immune thrombocytopenia (ITP) and interstitial pneumonia. The prevalence of interstitial pneumonia in patients with ITP is less well known.

Methods We surveyed patients diagnosed with ITP and interstitial pneumonia at the departments of Hematology and Respiratory Medicine to evaluate the association between these diseases.

Results Among 73 patients with ITP, 7 patients (9.6%) presented with interstitial pneumonia, including 4 patients (2%) who developed ITP in the course of 204 patients with interstitial pneumonia. All 7 patients were men. Four patients were positive for some autoantibodies. Two patients had autoimmune diseases other than ITP. There were significant differences in age and gender between the ITP patients with and without interstitial pneumonia.

Conclusion The present study suggests the possibility that the development of ITP, other autoimmune diseases, and interstitial pneumonia may be mutually associated. Advanced age and male sex in ITP may be significant predisposing factors for interstitial pneumonia. Clinicians should be aware of the potential for the coexistence of these diseases.

A 70-year-old man was admitted to our hospital due to elevated levels of hepatobiliary and pancreatic enzymes. Computed tomography showed contrast-enhanced mucosal hypertrophy from the duodenal papilla to the distal bile duct. Endoscopic examinations revealed a laterally spreading granular tumor and ampullary swelling. After surgical resection, an examination revealed well-differentiated adenocarcinoma of the ampulla with tubular adenoma spreading from the distal common bile duct to the second part of the duodenum showing both bile duct and duodenal phenotypes. To our knowledge, this is the first case of a tumor spreading from the bile duct to the duodenum that exhibited multiple phenotypes.

An 80-year-old woman with rheumatoid arthritis presented with chest pain. Clinical examination revealed new-onset paroxysmal atrial fibrillation with symptomatic sinus pauses and worsening mitral regurgitation, which were both resistant to conventional therapies. Based on her skin lesions, an increase in pleural and pericardial effusion, possible myocardial involvement, and a positive finding for immune complex testing, rheumatoid vasculitis was diagnosed. Subsequent glucocorticoid therapy suppressed systemic inflammation, resulting in structural, functional, and electrical reverse remodeling of the left atrium with complete remission of atrial arrhythmias and also an improvement of mitral regurgitation. This case highlights the importance of evaluating the underlying disease activity in a case of de novo paroxysmal atrial fibrillation associated with systemic autoimmune disease.

A 30-year-old woman was referred to our hospital to undergo an evaluation for suspected Brugada syndrome. She showed no symptoms, but had a strong family history of sudden cardiac death. During observation, Holter electrocardiography (ECG), which had been performed to investigate her symptoms of occasional dizziness, showed a sinus node dysfunction with an occasional long sinus pause. An implantable cardioverter defibrillator (ICD) was therefore put in place, and bradycardia pacing from the ICD relieved those symptoms during the subsequent 18-month follow-up. The patient completed two pregnancies during the follow-up period. No symptomatic changes occurred during the pregnancies, but ECG indicated that an ST segment elevation in the right precordial leads was attenuated during the second and third trimesters of both pregnancies.

We herein report the first case of purulent pericarditis associated with aortic stent-graft infection in an 80-year-old Japanese man that was caused by methicillin-susceptible Staphylococcus aureus, which appropriate antibiotics failed to treat. The detailed clinical course and autopsy images revealed that purulent pericarditis associated with aortic stent-graft infection caused cardiac tamponade and eventually led to mortality. We therefore suggest that surgical procedures, including drainage, should be introduced for such cases.

During the malignant phase of hypertension in patients with primary aldosteronism complicated with severe renal failure, the plasma renin activity may markedly increase with a false negative screening result for primary aldosteronism, thus potentially leading to a missed diagnosis of primary aldosteronism. We herein report the case of 37-year-old man who presented with accelerated-malignant hypertension complicated with severe renal insufficiency. The plasma renin activity was markedly increased in the malignant phase of hypertension, which were atypical results for primary aldosteronism. However, a plain abdominal computed tomography scan revealed a left adrenal nodule, which was diagnosed as aldosterone-producing adenoma by adrenal venous sampling.

A 38-year-old woman who consulted a local doctor with chief complaints of sudden palpitations, headaches, and chest pain is herein presented. After admission, pheochromocytoma crisis was suspected. Since the patient had a history of acute heart failure and had once survived an episode of cardiac arrest, a rapid decrease in the catecholamine levels was needed. After resuscitation, pharmacological therapy with agents such as phentolamine and landiolol was administered, and continuous hemodiafiltration (CHDF) was performed to reduce the catecholamine levels. Elective surgery was then performed, and a positive outcome was achieved. This case suggests that the preoperative use of CHDF to control pheochromocytoma crisis may therefore be effective.

We herein report a rare case of a 41-year-old woman with painless thyroiditis who was positive for thyrotropin (TSH) receptor-blocking (TBAbs) and receptor-stimulating autoantibodies (TSAbs) in the thyrotoxic phase. Her serum thyroid hormone levels were high, and TSH was undetectable. The low uptake of ^99mTc led to the diagnosis of painless thyroiditis. M22-TRAb, TBAb and TSAb were detectable in the thyrotoxic phase. Three months later, she became severely hypothyroid. M22-TRAb and TBAb were still strongly positive, although the TSAb levels had decreased to just above the reference range. In this case, TBAb led to hypothyroidism.

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%. After two months, she was admitted to our hospital and finally diagnosed with prolactinoma. For the treatment of prolactinoma, bromocriptine 2.5 mg/day was started. After seven days, her post-prandial blood glucose levels, homeostasis model assessment of insulin resistance and plasma C-peptide levels were significantly improved. These results indicate that traditional bromocriptine can be an effective therapeutic alternative in patients with prolactinoma complicated with type 2 diabetes.

The safety and efficacy of anti-programmed cell death-1 (PD-1) antibodies in patients with granulomatosis with polyangiitis (GPA) still remain unclear. An 83-year-old man with GPA that was well controlled with immunosuppressive therapy was diagnosed with a postoperative recurrence of non-small cell lung cancer (NSCLC). Because the programmed cell death ligand 1 (PD-L1) tumor proportion score was 90%, pembrolizumab was administered. After 10 cycles, immune-related adverse events or GPA flare was not observed, and the patient showed an antitumor response. Anti-PD-1 antibody should therefore be considered a treatment option for PD-L1-high-expressing NSCLC patients with well-controlled GPA.

Patients with end-stage lung disease can undergo living-donor lobar lung transplantation (LDLLT), with survival rates improving every year. We herein report the 20-year follow-up findings of the first patient who underwent LDLLT in Japan. A 24-year-old woman with primary ciliary dyskinesia became ventilator-dependent after severe respiratory failure and right-sided heart failure following repeated respiratory infections. In 1998, she underwent LDLLT and received her sister's right lower lobe and her mother's left lower lobe. Although the patient required 21 hospitalizations and developed unilateral bronchiolitis obliterans syndrome, she is in good physical condition and lives without restriction at 20 years after undergoing LDLLT.

Dasatinib-related chylothorax is a rare adverse event, and the mechanism underlying its occurrence is still not fully understood. We herein report the case of a 73-year-old woman with chronic myeloid leukemia (CML) who developed dasatinib-related chylothorax refractory to conventional treatments, except for steroids. To the best of our knowledge, this is the first case of dasatinib-related chylothorax which was successfully controlled by combining diuretics with the Japanese herbal medicine "Goreisan." "Goreisan" is known to inhibit aquaporin channels and regulate the water flow. Our findings showed that "Goreisan" is an effective treatment option for uncontrollable dasatinib-related chylothorax.

Chylothorax is the accumulation of lipid pleural effusion. Few reports have described chylothorax caused by gastric cancer. A 45-year-old woman presented with progressive lymphedema and bilateral chylothorax. Although repetitive thoracentesis was performed to relieve her dyspnea, swelling of her axillary lymph nodes became significant. Positron emission tomography/computed tomography demonstrated the accumulation of ¹⁸F-fluorodeoxyglucose in these nodes, and a lymph node biopsy showed signet ring cell carcinoma. The primary site was a 0-IIc type lesion in the gastric body that was only detected by upper gastrointestinal endoscopy. The patient was diagnosed with advanced gastric cancer 3.5 months after presentation for chylothorax.

Chest computed tomography (CT) findings of minute pulmonary meningothelial-like nodules (MPMNs) usually show tiny nodules (2-5 mm in diameter) of ground-glass attenuation. However, diffuse, thin-walled cavities have rarely been reported. We herein report a 56-year-old woman with MPMNs showing diffuse, thin-walled cystic lesions on a thin-section chest CT scan. Clinicians need to be aware of the imaging characteristics of this conditions to guide appropriate management of lung diseases, as these CT findings may resemble certain metastatic lung neoplasias and primary adenocarcinoma of the lung.

A 53-year-old woman presented at our hospital due to nasal bleeding and petechiae with profound thrombocytopenia (0.4×10⁹/L). Her platelet count returned to the normal range immediately following a platelet transfusion. In this case, tea brewed from Taxus yunnanensis was the only suspected agent ingested prior to the onset of thrombocytopenia while all other etiologies for thrombocytopenia were excluded. A re-exposure test to Taxus yunnanensis resulted in the recurrence of acute thrombocytopenia. The association of thrombocytopenia with substances other than drugs has so far only been rarely described and to the best of our knowledge, this is the first reported case of thrombocytopenia caused by Taxus yunnanensis.

Peripheral nerve imaging techniques have recently increasingly revealed their usefulness. We herein describe a man who had a subacute progression of symptom, diffuse and prominent proximal demyelination and conduction block, suggesting a diagnosis of inflammatory demyelinating polyneuropathy. Additional nerve imaging techniques revealed homogeneous and prominent nerve hypertrophy without proximal accentuation and the findings implied inherited polyneuropathies. Intravenous immunoglobulin was administered, and both the symptoms of weakness and findings of nerve conduction studies (NCS) improved. Subsequent genetic testing unveiled Charcot-Marie-Tooth 1A. To diagnose peripheral nerve disorders, a careful history, physical examination and NCS are essential diagnostic tools, but the findings of this case suggest the importance of nerve imaging techniques in clinical situations.

A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on ^99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging.

A 44-year-old female with rheumatoid arthritis treated with methotrexate (MTX) and tocilizumab (TCZ) was admitted to our hospital with nasal pain. Nasal fiberscopy revealed septum perforation, while a membrane biopsy indicated granuloma and fibrinoid necrosis of the small artery. The patient was treated with prednisolone 30 mg/day after discontinuation of MTX and TCZ. Inguinal lymph node biopsy revealed diffuse infiltrations of atypical T-cells and Epstein-Barr virus-positive B cells. The patient was diagnosed with peripheral T-cell lymphoma due to MTX-associated lymphoproliferative disorder (MTX-LPD). We herein describe the case of a patient with nasal septum perforation due to MTX-LPD mimicking granulomatosis with polyangiitis.

Diffuse proliferative lupus nephritis (DPLN) is a serious organ complication. Drug resistance correlates with P-glycoprotein (P-gp) expression on activated lymphocytes. We encountered a refractory DPLN patient with expansion of peripheral CD69/CXCR3-co-expressing P-gp⁺CD4⁺ cells producing IL-2 and IL-6. Treatment with high-dose corticosteroid combined with biweekly intravenous cyclophosphamide pulse therapy (IVCY) failed to reduce the population of activated P-gp⁺CD4⁺ cells or control the disease activity. Methotrexate (MTX) with monthly IVCY reduced activated P-gp⁺CD4⁺ cells and improved the clinical symptoms, resulting in long-term remission and tapering of corticosteroids. MTX-IVCY combination therapy, which down-regulates the activated P-gp⁺CD4⁺ cell-mediated disease activity, may be useful for the treatment of refractory DPLN.

Human brucellosis, one of the most common zoonoses worldwide, rarely occurs in Japan, and only a few chronic cases have been reported. We herein report the case of a 39-year-old Japanese woman with chronic human brucellosis, considered a Brucella canis infection, that persisted for 19 years. Her medical history and fever pattern suggested chronic brucellosis, and the diagnosis was made based on the results of a serum tube agglutination test (SAT). After undergoing combination therapy with streptomycin and doxycycline, she achieved symptomatic relief and showed negative SAT results. Even in non-endemic areas, chronic brucellosis is an important differential diagnosis in patients with long-term persistent fatigue or a fever.

A 38-year-old Japanese man without any significant past medical history was referred to our clinic to undergo further examination for a "refractory infection in his joints". He suffered recurrent migratory polyarthritis starting from bilateral knees to his right elbow. Certain antibiotic therapies appeared to improve his symptoms, but the symptoms recurred due to the migratory nature of arthritis. A diagnosis of familial Mediterranean fever (FMF) was considered and diagnostic tests were performed. Not many differential diagnoses exist for migratory polyarthritis, particularly when it has a recurrent nature. The administration of antibiotics without sufficient diagnostic consideration can cause a delay in making an accurate diagnosis and thereby also cause a delay in administering appropriate treatment.

A 69-year-old Japanese woman was admitted to our hospital with progressive muscle weakness and dysphagia. She was taking pitavastatin for dyslipidemia. Her serum creatine kinase was 6,300 U/L. Pitavastatin was stopped, but her symptoms deteriorated, and cardiac congestion appeared. A muscle biopsy showed necrotizing myopathy (NM), and anti-signal recognition particle (SRP) antibody was positive. ¹⁸F-fluorodeoxyglucose-positron emission tomography showed an abnormal uptake, and magnetic resonance imaging showed abnormal gadolinium enhancement in the left ventricular wall. An endomyocardial biopsy revealed inflammatory cardiomyopathy. Steroid, tacrolimus, and intravenous immunoglobulins were effective against the symptoms. This is the first case of biopsy-proven secondary cardiomyopathy due to anti-SRP-positive NM.