BACKGROUND This study investigated the impact of systemic inflammation on bleeding risk in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOAC).Methods and ResultsWe conducted a single-center prospective registry of 2,216 NVAF patients treated with DOAC the DIRECT registry (UMIN000033283). High-sensitivity C-reactive protein (hsCRP) was measured ≤3 months before (pre-DOAC hsCRP) and 6±3 months after initiation of DOAC (post-DOAC hsCRP). Multivariate logistic regression model was used to assess the influence of systemic inflammation and conventional bleeding risk factors on major bleeding according to International Society on Thrombosis and Haemostasis criteria. Based on the findings, we created a new bleeding risk assessment score the ORBIT-i score, which included post-DOAC hsCRP >0.100 mg/dL and all components of the ORBIT score. A total of 1,848 patients had both pre- and post-DOAC hsCRP data (follow-up duration, 460±388 days). Post-DOAC hsCRP was associated with major bleeding (OR, 2.770; 95% CI 1.687-4.548, P0.100 mg/dL more frequently had major bleeding than those without (log-rank test, P less then 0.001). ORBIT-i score had the highest C-index of 0.711 (95% CI, 0.654-0.769) compared with the ORBIT and HAS-BLED scores. CONCLUSIONS Persistent systemic inflammation was associated with major bleeding risk. ORBIT-i score had a higher discriminative performance compared with the conventional bleeding risk scores.Objective Although acute coronary syndrome (ACS) is an uncommon entity in young patients, it constitutes an important problem due to the devastating effects of the disease on the more active lifestyle of young patients. At present, there are no guidelines regarding the prevention of ACS in young patients. Methods We performed a retrospective study of ACS patients between 2014 and 2017. Epidemiological data, clinical findings, and short-term outcomes were evaluated between young ACS patients (≤50 years old) and elderly ACS patients (>50 years old). Results Of a total of 361 consecutive ACS patients, 37 were young ACS patients (10.2%). Compared with elderly ACS patients, young ACS patients showed a higher prevalence of males (94.6% vs. 73.8%, p less then 0.001), current smoking (70.3% vs. 29.9%; p less then 0.001), and overweight persons (67.6% vs. 27.8%, p less then 0.001). The eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio was significantly lower in young ACS patients than in elderly ACS patients (0.17 [0.12-0.25] vs. 0.25 [0.18-0.37], p=0.002). The prevalence of cardio-pulmonary arrest and percutaneous cardiopulmonary support use was higher in young ACS patients than in elderly ACS patients (24.3% vs. 8.6%, p=0.003, 16.2% vs. 3.1%, p less then 0.001). Conclusion The features were markedly different between young ACS patients and elderly ACS patients. In young ACS patients, smoking, being overweight, and a low EPA/AA ratio were distinctive risk factors, and more serious clinical presentations were observed at the onset of ACS than in older patients.We herein report a 50-year-old woman who suffered from tubulointerstitial nephritis with antimitochondrial M2 antibody, distal renal tubular acidosis, and Fanconi syndrome. Our case also had interstitial pneumonia. After initially successful glucocorticoid therapy, tubulointerstitial nephritis and interstitial pneumonia relapsed. After the second successful round of glucocorticoid therapy, tubulointerstitial nephritis relapsed again and responded to glucocorticoid and azathioprine. This case might indicate (1) the association between pulmonary involvement and tubulointerstitial nephritis with antimitochondrial antibodies and (2) the need for a maintenance dose of glucocorticoid and immunosuppressants in tubulointerstitial nephritis with antimitochondrial antibodies.Objective Uremic toxins are known risk factors for cancer in patients undergoing hemodialysis (HD). Although adequate removal of uremic toxins might reduce the cancer risk by improving subclinical uremia, the relationship between the dialysis dose and risk of cancer death in patients undergoing HD remains unclear. Methods In this prospective observational study, 3,450 patients undergoing HD were followed up for 4 years. The primary outcome was cancer death. Patients were divided into quartiles according to their baseline Kt/V levels. The association between the Kt/V levels and risk of cancer death was estimated using the Kaplan-Meier method and Cox proportional-hazards model. Results A total of 111 patients (3.2%) died from cancer during the 4-year observational period. The 4-year survival rate decreased linearly with decreasing Kt/V. The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer death were 2.23 (95% CI, 1.13-4.56), 1.77 (0.88-3.63), and 1.89 (1.04-3.56) in quartile (Q) 1, Q2, and Q3, respectively, compared with patients in the highest Kt/V category (Q4) (P for trend = 0.06). Every 0.1 increase in Kt/V was associated with a reduction of 8% in cancer death (HR 0.92, 95% CI 0.85-0.99). Conclusion A lower dialysis dose might be associated with a higher risk of cancer death in patients undergoing HD. Kt/V is a simple indicator of dialysis dose used in clinical practice and might be a useful modifiable factor for predicting the risk of cancer death. Further basic and interventional studies are needed to confirm the apparent reduction in cancer death associated with increasing the dialysis dose.A 72-year-old woman was admitted to our hospital with bilateral pleural effusions. She had a 31-year history of systemic lupus erythematosus and had been treated with prednisolone and azathioprine. Pleural fluid culture revealed Salmonella enterica subsp. arizonae infection. This pathogen rarely infects humans but is commonly found in the gut flora of reptiles, especially snakes. Our patient had not come in contact with reptiles. Despite antibiotic therapies and negative pleural cultures, the pleural effusion persisted. Colon cancer was detected concomitantly, and she finally died. The autopsy revealed that the pleuritis was due to underlying diffuse large B cell lymphoma.Radiation recall dermatitis (RRD) is an inflammatory reaction that occurs at previously irradiated skin regions after drug administration. We herein report a patient with non-small-cell lung cancer treated previously with thoracic radiotherapy who developed severe RRD induced by atezolizumab (anti-programmed death 1 ligand 1 [PD-L1] antibody). Immunohistochemistry of the skin biopsy showed dermatitis with infiltration of CD8+ lymphocytes, suggesting that atezolizumab might provoke an immune-related inflammatory reaction at previously irradiated skin regions. When administering anti-PD-L1 antibody to patients who have undergone radiotherapy previously, physicians should carefully monitor the irradiated skin for the potential occurrence of RRD.We herein report the case of a 65-year-old woman diagnosed with myasthenia gravis (MG) after complaining of double vision. The patient had anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibody in her serum, although antibodies against the acetylcholine receptor and muscle-specific tyrosine kinase were not detected. Chest computed tomography showed an anterior mediastinal tumor with a high uptake on fluorodeoxyglucose-positron emission tomography. Endoscopic thymectomy successfully ameliorated her ocular symptoms and showed the lesion to be thymoma. The present case revealed that anti-LRP4 antibody-associated MG can be associated with thymoma, which has been regarded as a rare complication of this disease thus far.An 80-year-old man with a history of cutaneous squamous cell carcinoma (SCC) was referred to our department for a solitary lung nodule. The nodule was surgically resected and diagnosed as SCC. Because the lung lesion and a previous skin lesion showed similar histological findings, the origin of the lung tumor was uncertain. Next-generation sequencing using a targeted driver oncogene panel was applied for the further examination. The lung lesion was diagnosed as primary lung SCC, as the two tumors possessed distinct somatic mutations in TP53. Recent advances in clinical sequencing have enabled us to obtain an accurate diagnosis in pathologically challenging cases.Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease commonly observed around the Mediterranean basin presenting as recurrent febrile episodes. We herein describe a Japanese case of genetically-confirmed FMF, in which fever was lacking during attacks. An otherwise healthy 34-year-old man presented with frequent episodes of abdominal pain, which resolved spontaneously. During the attacks, the patient was afebrile, but the inflammatory marker levels in his blood were increased. Abdominal CT demonstrated enhancement of the jejunal membrane. After the initiation of colchicine therapy, the patient experienced no attacks for more than one year. The diagnosis of FMF was confirmed by a genetic analysis.We report an adult case of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, who had a tonsillectomy at 10 years old and relapsed later. An early 40’s-year-old man had been suffering from recurrent fever attack once in 1-2 months during childhood. He was accompanied by fever which was persist for several days, aphthous stomatitis, tongued tonsillitis with moss, pharyngitis, and submandibular lymphadenitis with tenderness. He was not doing well during fare-up. At the time of admission, CRP level was 12.5mg/dl and the remarkably increased expression of CD64 on neutrophils was found. Bacterial infections and collagen diseases were excluded by the several examinations. We suspected PFAPA syndrome, and treated with cimetidine, but cimetidine was not effective. At the time of flare up, administration of prednisolone was remarkably effective. We diagnosed PFAPA syndrome on the basis of clinical courses. Genetic analysis of responsible gene of familial Mediterranean fever, MEFV showed E148Q heterozygous mutation in exon 2.Since an adult case of PFAPA syndrome is likely to be made misunderstanding for infectious recurrent pharyngitis, it is important to note that we should consider PFAPA syndrome as a differential diagnosis when we meet with the adult patient of recurrent fever.BACKGROUND Cochineal dyes are used as additives in various foods for the purpose of red coloration. On the other hand, although it has been reported as a causative agent of immediate allergy, most of them are adult women. We report a case of an 8-year-old boy who developed a cochineal allergy.Current disease history He has been suffering from atopic dermatitis, bronchial asthma, and food allergies since childhood. At the age of seven, he experienced an unknown anaphylaxis reaction twice. When he was 8 years old, he ate a frankfurter containing hypoallergenic cochineal for the first time; cold sweat, intraoral discomfort, respiratory distress, and urticaria appeared throughout the body. His skin prick tests were positive, with a result of 2+to frankfurter and cochineal dyes (color value 0.1 and 0.01). In the immunoblot assay, binding of IgE antibody was observed with CC38K (the main component of cochineal) and a protein of approximately 80-200 kDa in the high molecular weight region. DISCUSSION We report a case of anaphylaxis with hypoallergenic cochineal onset in a school-age boy.