Patients with Behçet's disease (BD) suffer from episodic ocular and mucocutaneous attacks, resulting in a reduced quality of life. The phenotype of Japanese BD has been changing over the past 20 years, and the rate of human leukocyte antigen (HLA)-B*51-positive complete type is decreasing while that of intestinal type is increasing. This phenotypical evolution may be related to changes in as-yet-unknown environmental factors, as the immigration influx in Japan is low. Mechanisms discovered by genome-wide association studies include ERAP1-mediated HLA class I antigen bounding pathway, autoinflammation, Th17 cells, natural killer cells, and polarized macrophages, a similar genetic architecture to Crohn's disease, ankylosing spondylitis, and psoriasis. As for treatments, management guidelines have been implemented, and the development of tumor necrosis factor (TNF) inhibitors is markedly improving the outcome of BD, but evidence supporting treatment for special-type BD is limited. The classification of BD into distinct clusters based on clinical manifestations and genetic factors is crucial to the development of optimized medicine.

Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk.

Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis.

Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT.

Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.

Objective To prevent the development of overt hepatic encephalopathy, the early intervention for minimal hepatic encephalopathy (MHE) based on an accurate diagnosis is essential. This study investigated whether or not magnetic resonance diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) could detect brain microstructure abnormalities in MHE. The aim was to confirm whether or not brain microstructure abnormalities detected by magnetic resonance (MR) imaging could be used for the diagnosis of MHE.

Methods Thirty-two subjects were prospectively examined with a 3-T MR scanner. Tract-based spatial statistics and region of interest analyses of diffusion imaging were performed to compare the mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values between patients with and without minimal hepatic encephalopathy. The diagnostic performance for the detection of MHE was assessed with a receiver operating characteristic analysis.

Results Ten subjects were diagnosed with MHE by neuropsychological testing. After the exclusion of unsuitable subjects, we analyzed 9 subjects with MHE and 14 without MHE. The patients with MHE had a reduced MK in the widespread white matter. We also found significant decreases in the MK in the caudate nucleus, putamen, globus pallidus, and/or thalamus in the subjects with MHE. The MK in the putamen showed the best diagnostic performance for differentiating the subjects with MHE from those without MHE (cut-off value, 0.74; sensitivity, 0.89; specificity, 0.86).

Conclusion DKI detects changes in the cerebral white matter and basal ganglia regions of patients with MHE more sensitively than DTI. The MK values in the putamen can be a useful marker for diagnosing MHE from cirrhotic patients without MHE.

Objective To assess the rate of successfully achieving treatment goals among Japanese men with hyperuricemia/gout and identify factors influencing the success rate.

Methods This cross-sectional study, conducted from January to December 2012, examined the serum uric acid (SUA) levels and clinical characteristics of 2,103 men with hyperuricemia/gout selected from an initial population of 136,770 individuals who participated in a workplace health checkup. The success rates (defined as SUA ≤6.0 mg/dL) were calculated, and a multivariate analysis was used to identify factors associated with "therapeutic failure" to achieve target SUA levels.

Results The rate of successfully achieving the target SUA level was 37.5%. The body mass index (BMI) was significantly associated with therapeutic failure [25.0≤ Category (C) 2<27.5, adjusted odds ratio (AOR) =1.35; 27.5≤C3<30.0, AOR=1.69; C4 ≥ 30.0, AOR=1.94; relative to C1<25.0]. A significant positive association was also observed between waist circumference (WC) and therapeutic failure (85≤C2<90, OR=1.29; 90≤C3<95, OR=1.41; 95≤C4, OR=2.28; relative to C1<85.0 cm). Those with higher BMI/WC measurements were significantly more likely to have higher SUA levels than those with lower such measurements. The ongoing intake of dyslipidemia medication was identified as a protective factor against therapeutic failure.

Discussion Our findings suggest a possible association between obesity and therapeutic failure, underscoring the importance of maintaining lipid profiles as part of managing SUA levels. Better management of both obesity and dyslipidemia may prevent future cardiovascular disorders by ensuring healthier SUA levels.

Objective Renal arteriolosclerosis is a risk factor for acute reductions in the glomerular filtration rate (GFR) when renin-angiotensin system (RAS) inhibitors are administered. Renal arteriolosclerosis can be detected by an increase in the resistive index (RI) on Doppler ultrasonography. The purpose of the present study is to determine whether or not the RI can predict acute GFR reductions following RAS blockade in chronic kidney disease (CKD).

Methods We surveyed all CKD patients who were hospitalized in Otemae Hospital from January 2008 to December 2017. One hundred and eight patients who had been newly treated with RAS inhibitors were able to be followed for 14 weeks. The end point was an acute reduction in the GFR, defined as a decrease of ≥30%.

Results Twenty-three of the 108 patients presented with acute GFR reductions. The cumulative probability of acute GFR reductions was 3.3% and 53% in patients with RI ≤0.70 and RI >0.70, respectively (p<0.001). A univariate Cox proportional-hazards analysis showed that the RI, age, GFR, systolic blood pressure, urinary protein excretion, diabetic kidney disease, coronary artery disease, and use of diuretics were significant variables. Multivariate hazard ratios were calculated from the RI and three established variables (age, GFR, diuretics), and the RI and use of diuretics were shown to be significant risk factors for acute GFR reductions.

Conclusion These results suggest that an increase in the RI, as well as the use of diuretics, may be risk factors for acute GFR reductions following RAS blockade.

Objective The effects of partial pressure of arterial oxygen (PaO₂) after introducing long-term noninvasive ventilation (NIV) on the prognosis of patients with restrictive thoracic disease and chronic respiratory failure are not exactly known.

Methods Data from 141 patients with restrictive thoracic disease under long-term nocturnal NIV were retrospectively examined. We divided the patients into 2 groups according to the daytime PaO₂ value while breathing spontaneously with prescribed oxygen at 12 months after introducing NIV: PaO₂≥80 Torr group (n=76) and PaO₂<80 Torr group (n=65).

Results During the 4-year follow-up, the mortality was significantly higher in the PaO₂<80 Torr group than in the PaO₂≥80 Torr group (50.8% vs. 32.9%, p=0.03). Independent factors associated with the 4-year mortality after introducing NIV determined by a multivariate logistic regression analysis were a low body mass index [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.77 to 0.97; p=0.01], assisted mode with NIV (OR 4.11; 95% CI, 1.79 to 9.45; p=0.0009), hospitalization during the first year of introducing NIV (OR 1.72; 95% CI, 1.06 to 2.79; p=0.03), and daytime PaO₂<80 Torr at 12 months after introducing NIV (OR 2.30; 95% CI, 1.03 to 5.10; p=0.04).

Conclusion A low daytime PaO₂ at 12 months after introducing NIV was an independent risk factor for mortality. Keeping the daytime PaO₂≥80 Torr through the adjustment of the nocturnal NIV settings or increased diurnal supplemental oxygen may help improve the prognosis in patients with restrictive thoracic disease who are under NIV.

Objective Tracheoarterial fistula (TAF) is a rare but devastating complication of tracheostomy caused by pressure necrosis from the elbow, tip, or over-inflated cuff of the tracheostomy tube. The incidence of TAF is reportedly higher in patients with neurological disorders than in those without such disorders. To evaluate the incidence of and factors contributing to the misalignment of tracheostomy tubes in bedridden patients with chronic neurological disorders.

Methods We retrospectively assessed three-dimensionally reconstructed serial computed tomography (CT) images to see if the tip of the tube made contact with the tracheal wall and if the main arteries were running adjacent to the tube's elbow, tip or cuff.

Results The tip of the tube was in contact with the tracheal wall in 14 of the 30 patients assessed. Among them, the tip was adjacent to the innominate artery in eight, the aortic arch in three and an aberrant right subclavian artery in one. In one patient with the tube tip adjacent to the aortic arch and the other four patients, the cuff of the tube was adjacent to the innominate artery across the tracheal wall. Patients with the tube tip in contact with the anterior tracheal wall had a significantly greater cervical lordosis angle than those without contact (p<0.05).

Conclusion More than half of tracheostomized patients with chronic neurological disorders had a latent risk of TAF. The variability in the location of the innominate artery, anomalies of the aortic arch, and skeletal deformities may therefore be contributing factors.

Objective Hydroxychloroquine (HCQ) was not approved in Japan until 2015, and its therapeutic potential has not been explored in depth. We evaluated the additional therapeutic effect of HCQ in Japanese patients with systemic lupus erythematosus (SLE) on maintenance therapy.

Methods Patients with SLE who visited our hospital from 2015 to 2016 and were taking prednisolone (PSL) at <20 mg/day were retrospectively evaluated. All patients were divided into three groups according to their maintenance treatment regimen: PSL + immunosuppressant, PSL alone, and no treatment. We compared the changes in the SLE disease activity index (SLEDAI), PSL dose, and cumulative flare rate between patients who were and were not treated with HCQ.

Results Among the 165 patients evaluated, 35 (21.2%) were treated with HCQ. The mean period of observation did not differ markedly between patients who did and did not receive HCQ (p=0.3). The SLEDAI and PSL dose were significantly reduced in patients who received HCQ, regardless of their background treatment regimen. The cumulative flare rate was lower in patients who received HCQ than in those who did not in the PSL + immunosuppressant and no maintenance treatment groups (p=0.03 and 0.05, respectively).

Conclusion The addition of HCQ reduced the disease activity and allowed PSL dose reduction, regardless of background treatment, in Japanese patients with SLE.

Immunotherapy targeting programmed cell death-1 (PD-1) signaling is becoming the standard of care for advanced gastric cancer. We herein report a patient with gastric adenocarcinoma with peritoneal dissemination who was treated with nab-paclitaxel and ramucirumab following nivolumab and developed sclerosing cholangitis. Endoscopic retrograde cholangiography showed irregular narrowing and widening of the entire intrahepatic biliary system. Intriguingly, the patient receiving second-line chemotherapy with nab-paclitaxel plus ramucirumab prior to being administered nivolumab, however, he had experienced progressive disease. Thereafter, the administration of fourth-line chemotherapy with nab-paclitaxel and ramucirumab following nivolumab resulted in a clinical response. Nivolumab may enhance the efficacy of the subsequent chemotherapy regimens but also induce sclerosing cholangitis.

Even in the era of Helicobacter pylori eradication and proton pump inhibitors, peptic ulcer remains an important disease. Stricture due to a duodenal ulcer in the healing stage is a well-known etiology of benign gastric outlet obstruction. However, a duodenal ulcer-induced submucosal tumor-like change with gastric outlet obstruction is a very rare manifestation. We herein present a rare case of a patient with deteriorating symptoms of gastric outlet obstruction caused by an unusual manifestation of a lumen-occupying protruding duodenal ulcer mimicking a submucosal tumor.

Carcinosarcoma is a biphasic malignant tumor comprising both carcinomatous and sarcomatous components; its occurrence in the duodenum is very rare. We herein report the case of a 96-year-old woman with duodenal carcinosarcoma showing rapid growth within the past year. The tumor was found to be bulging into the lumen and predominantly comprised sarcomatoid components with focal positive staining for cytokeratin. Therefore, the tumor was diagnosed as duodenal carcinosarcoma. The clinical information of the present case and our literature review of the 12 cases reported to date will help physicians diagnose and treat this rare tumor.

Obstructive sleep apnea (OSA) is associated with the occurrence of various kinds of bradyarrhythmia and tachyarrhythmia. The activation of the autonomic nerve system is an important causative factor of the pathogenesis of the arrhythmia in OSA patients. Previous studies have shown that the R-R interval is an effective parameter for evaluating autonomic nerve activities. However, whether or not OSA can induce variations in the R-R interval and whether or not continuous positive airway pressure (CPAP) therapy can improve these variations in OSA patients are unclear. The present study explored whether or not CPAP therapy could improve the regularity of the R-R interval.

The natural course of myocardial calcification is unclear. We herein report a case of massive biventricular myocardial calcification associated with fulminant myocarditis and present its natural course. The patient was a 15-year-old boy. Massive calcification was detected in both ventricles on computed tomography several months after left ventricular assist device placement. Although the calcification gradually regressed, the patient's cardiac function did not recover, and he underwent heart transplantation after a waiting period of 3 years. A histological examination revealed severe fibrosis in both ventricles of the original heart. Myocardial calcification might suggest severe myocardial inflammation and injury in cases of fulminant myocarditis.

A 61-year-old man with essential thrombocythemia (ET) presented with acute myocardial infarction (AMI) and underwent primary percutaneous coronary intervention. After stent deployment from the left main (LM) to the left anterior descending artery, intravascular ultrasound revealed thrombi formation in the whole stent. Two days later, optical frequency domain imaging confirmed stent malapposition and thrombi remaining in only the LM. The stent malapposition and ET might have contributed to this phenomenon. He underwent an additional stent expansion and aggressive anti-thrombotic regimen. AMI complicated with ET carries increased risks of in-stent thrombi formation and requires careful revascularization and aggressive pharmacotherapy.

A 68-year-old Japanese man was admitted to our hospital with right eye pain, a sudden worsening of his eyesight, and a fever. He was diagnosed with endogenous bacterial endophthalmitis due to infectious endocarditis (IE) of Group B Streptococcus (GBS) on the day of admission. He recovered systemically, but his right eye became phthisical only with the administration of antibiotics. We conducted a review of the reported cases of IE caused by GBS complicated with endogenous bacterial endophthalmitis. IE should be considered when an undetermined etiology of endogenous endophthalmitis is encountered. The prompt diagnosis and treatment of IE will improve patients' outcomes.

This case report concerns a 22-year-old woman with large patent ductus arteriosus and atrial septal defect. She was referred to our hospital because of exertional dyspnea and was revealed to have advanced pulmonary arterial hypertension (PAH) with a mean pulmonary arterial pressure (PAP) of 79 mmHg. Although both shunts had bidirectional flow, based on the results of acute pulmonary vasoreactive testing, one-stage surgical closure was performed followed by up-front combination therapy for post-operative pulmonary hypertensive crisis and residual PAH. At 14 months after the surgery, her symptoms were markedly improved, and her mean PAP had dramatically decreased to 13 mmHg.

The patient was a 75-year-old man who was admitted to our hospital because of fatigue, leg edema and heavy proteinuria. Due to his cloudy urine and elevated triglyceride level in his urine, he was diagnosed with chyluria. Tests for infectious disease were negative, and lymphoscintigraphy showed no blockage in the lymphatic system. He was therefore diagnosed with idiopathic chyluria. Hypothyroidism was also found and his cloudy urine and heavy proteinuria disappeared without dietary modifications after starting levothyroxine treatment for hypothyroidism. The patient is currently being followed up in an outpatient clinic and is doing well, with no recurrence of chyluria.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a complication characterized by dyspnea, pulmonary hypertension, and occasionally sudden death. We encountered a man who developed PTTM and had an inhalation history of chemical herbicides and abnormal findings on chest computed tomography, mimicking chemical inhalation lung injury. He was diagnosed with PTTM with adenocarcinoma by a transbronchial lung biopsy and received chemotherapy and anticoagulant therapy. He survived for one month. An autopsy revealed primary gastric cancer with PTTM that can have a presentation similar to diffuse pulmonary diseases, including chemical inhalation lung injury. The examination of a biopsy specimen is crucial in such patients.

The push and slide method is a method of endoscopic bronchial occlusion using an endobronchial Watanabe spigot that facilitates occlusion of the target bronchus rapidly and accurately using a guidewire. We herein report the case of a man who was diagnosed with empyema forming bronchopulmonary fistulae that was successfully treated by endoscopic bronchial occlusion. Because of the multiple fistulae, balloon occlusion was not a favorable therapeutic approach. Instead, the push and slide method was used in order to detect the fistulae. Endoscopic occlusion, particularly that using the push and slide method, may be a valid treatment option for empyema with multiple bronchopulmonary fistulae.

A 63-year-old man presented with persistent cough and progressive dyspnea. Computed tomography showed irregular pleural thickening and fibrotic changes with volume loss in the upper lobes, and subtle reticulation in the lower lobes. Pleuroparenchymal fibroelastosis (PPFE) was diagnosed based on the findings of a surgical lung biopsy. Bronchiolar lesions, including proliferative bronchiolitis, constrictive bronchiolitis obliterans, and peribronchiolar metaplasia were evident on pathology. A usual interstitial pneumonia (UIP) pattern was also observed in the lower lobes. Three weeks after the biopsy, an acute exacerbation occurred. We herein describe a rare case of idiopathic PPFE with various bronchiolar lesions and a UIP pattern in which an acute exacerbation developed.

A 76-year-old Japanese woman with recurrent hepatocellular carcinoma presented with acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) after transcatheter arterial therapy using miriplatin. She had a history of preexisting IIP five years before presenting at our hospital. On day 4 after transcatheter arterial therapy, she complained of shortness of breath. Subsequently, she developed acute respiratory failure on day 11 after transcatheter arterial therapy. Chest computed tomography revealed extensive ground-glass opacity and traction bronchiectasis in bilateral lung fields; subsequently, she was diagnosed with AE-IIP triggered by transcatheter arterial therapy using miriplatin. Despite systemic administration of high-dose corticosteroid and cyclophosphamide, she died of respiratory failure on day 36.

Ewing's sarcoma (ES)/primitive neuroectodermal tumors (PNETs) are highly malignant neoplasms that usually affect the bones and soft tissues in children and young adults. ES/PNET of the lung is very rare and is associated with a poor prognosis. We herein report a case of ES/PNET of the left lung in a 45-year-old man. He was treated with neoadjuvant chemotherapy and pneumonectomy, but unfortunately his disease recurred 1.5 months after surgery. He was started on pazopanib, which resulted in a five-month progression-free survival. To our knowledge, this is the first demonstration of pazopanib efficacy in ES/PNET of the lung.

To explore non-motor comorbidities of myasthenia gravis (MG), we present two cases of thymoma-associated MG patients. Alopecia, pure red cell aplasia, and thymoma- associated multiorgan autoimmunity were observed in Case 1, and alopecia, thrombocytopenia, hypogammaglobulinemia and nephrotic syndrome were observed in Case 2. In both cases, autoreactive T lymphocytes inappropriately stimulated by thymus tissue may have played key roles in generating the various autoimmune-associated symptoms. Consequently, systemic immunological involvement due to the thymoma-associated breakdown of immunoregulations in both motor and non-motor systems should be considered in MG patients.

Cerebral embolism after left upper lobectomy caused by a thrombus in the pulmonary vein stump (PVS) is a serious complication. However, it is unclear if cerebral embolism can develop after other types of lobectomy. We present a case of a 68-year-old man with cerebral embolism after left lower lobectomy with a longer PVS than normal. There were no clinically suspected sources for the thrombus except for the PVS. This thrombus seemed to have formed in the PVS. The endovascularly removed thrombus contained scattered nuclear debris around neutrophils, suggesting a physiological response caused by tissue injury.

A 26-year-old woman with Takayasu's arteritis (TAK) experienced back and neck pain during tocilizumab (TCZ) treatment. The levels of C-reactive protein were normal, and ultrasonography revealed no significant changes. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement in the walls of several arteries. Contrast computed tomography showed arterial inflammation in the same lesion. After increasing the dose of prednisolone and TCZ, all signal enhancements decreased and continued to decrease, as observed on days 76 and 132. Thus, DWIBS may be a novel imaging modality for assessing the disease activity of TAK, particularly during follow-up.

Acute infectious endocarditis (IE) is a complex disease that presents as a serious clinical condition associated with a high mortality rate, especially due to intracranial hemorrhaging (ICH). The most common causative organism is Staphylococcus aureus. We herein report a patient with ICH following subacute IE with a positive blood culture for Cardiobacterium hominis. A review of the existing literature revealed that acute IE associated with Cardiobacterium has been reported to cause ICH in only seven previous cases. Prolonged culture-specific antibiotic therapy along with extended surveillance of blood culture is therefore essential for timely intervention.