Diabetes mellitus, especially type 2 diabetes, has been a major concern among health issues for Japanese policy requiring serious address. In this regard, the increasing number of people with diabetes in Japan over the past few decades has been regarded as a fundamental and evident problem. We herein clarify that the crude diabetes prevalence is likely to have increased mainly as a result of changes in the population distribution, namely, aging of the general population in Japan. We also predict the future trend for the number of people with diabetes according to available concrete evidence in this review.

Objective Patients with ulcerative colitis (UC) are at an increased risk for thromboembolic events, particularly in patients with extensive and active disease. To date, a few studies have been published on the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in UC. However, there are no reports in the literature investigating the effect of UC treatment on plasma TAFI levels.

Methods The plasma TAFI antigen levels were quantitatively determined using ELISA kits for 20 UC patients at activation and remission, along with 17 healthy controls. The association between the TAFI levels and inflammatory markers was assessed to determine UC activation. To predict and determine the activation of UC, the Truelove-Witts index and the endoscopic activation index (EAI) were used for each subject.

Results The plasma TAFI levels were higher in UC patients at activation of the disease compared with the remission state and in healthy controls. Spearman's correlation analyses revealed that the WBC (r: 0.586, p<0.001), hsCRP (r: 0.593, p<0.001) and EAI (r: 0.721, p<0.001) were significantly correlated with the TAFI levels. The overall accuracy of TAFI in determining UC activation was 82.5% with a sensitivity, specificity, NPV and PPV of 80%, 85%, 81% and 84.2%, respectively (cut-off value: 156.2% and AUC: 0.879).

Conclusion The present study demonstrates that the TAFI levels are elevated in the active state of UC. The assessment of TAFI levels in patients with UC in conjunction with other markers of inflammation may provide additional information for estimating UC activation and severity.

Objective Admission D-dimer and C-reactive protein (CRP) values have been reported to predict the short-term outcomes in acute aortic dissection (AAD). However, the association between D-dimer values and the long-term outcomes has not been investigated.

Methods The primary endpoints included events determined to be all-cause death, recurrence of aortic dissection, aortic rupture, and surgical intervention for the aortic aneurysm following the first hospital discharge. We performed a receiver operating characteristic analysis and determined the optimal cut-off levels of admission D-dimer, admission CRP and peak CRP values in terms of the sensitivity and specificity for predicting the presence of events. Using the optimal cut-off values, we performed a multiple Cox analysis and investigated the hazard ratio of admission D-dimer, admission CRP and peak CRP.

Patients We retrospectively identified 173 AAD patients hospitalized between January 2005 and December 2013.

Results A multiple Cox regression analysis revealed that the hazard ratios were 3.4 for admission D-dimer [95% Confidence Interval (CI) 1.5 to 7.3, p=0.004] and 2.7 for admission CRP (95% CI 1.2 to 5.5, p=0.014).

Conclusion Admission D-dimer and CRP values may predict the long-term outcomes in AAD. Moreover, admission D-dimer values may be a valuable marker to predict not only the short-term outcomes, but also the long-term outcomes in AAD.

Objective A fever is observed in approximately one-third of cases of acute aortic dissection (AAD); however, the causes remain unclear. We investigated the mechanism of a fever in AAD by measuring the serum concentrations of inflammatory markers, mediators of coagulation and fibrinolysis, and procalcitonin, a marker of bacterial infection.

Methods We retrospectively studied 43 patients with medically treated AAD without apparent infection. Patients were divided into those with (Group A; n=19) and without (Group B; n=24) a maximum body temperature >38°C. We established which patients fulfilled the criteria for systemic inflammatory response syndrome (SIRS), and its relationship with a fever was examined. Mediators of inflammation, coagulation and fibrinolysis were compared by a univariate analysis. Factors independently associated with a fever were established by a multivariate analysis.

Results The criteria for SIRS were fulfilled in a greater proportion of patients in Group A (79%) than in Group B (42%, p=0.001). There was no difference in the procalcitonin concentration between Groups A and B (0.15±0.17 ng/mL vs. 0.11±0.12 ng/mL, respectively; p=0.572). Serum procalcitonin concentrations lay within the normal range in all patients in whom it was measured, which showed that the fever was caused by endogenous mediators. On the multivariate analysis, there was a borderline significant relationship between a fever and the prothrombin time-International Normalized Ratio (p=0.065), likely reflecting the extrinsic pathway activity initiated by tissue factor.

Conclusion Our findings suggest that a fever in AAD could be caused by SIRS, provoked by endogenous mediators that influence the extrinsic coagulation pathway without elevating the serum procalcitonin concentration.

Objective To evaluate some risk factors for cardiovascular diseases in feeding and eating disorders, the degree of lipid abnormalities was investigated in a large Japanese cohort of different groups of feeding and eating disorders, according to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012).

Methods Participants in the current study included 732 women divided into four groups of feeding and eating disorders: anorexia nervosa, restricting type (AN-R); anorexia nervosa, binge-eating/purging type; bulimia nervosa (BN); and binge-eating disorder (BED). We measured the serum levels of total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglyceride in these participants. Low-density-lipoprotein (LDL) cholesterol and non-HDL cholesterol levels were also calculated.

Results The concentrations of LDL cholesterol and non-HDL cholesterol were widely distributed in all groups. When the LDL cholesterol risk was defined as ≥120 mg/dL and the non-HDL cholesterol risk as ≥150 mg/dL, according to the JAS Guidelines 2012, the proportion of LDL cholesterol risk ranged from 29.6% (BN) to 38.6% (AN-R), and the proportion of non-HDL cholesterol risk ranged from 17.8% (BN) to 30.1% (BED).

Conclusion The present findings suggest the existence of LDL cholesterol risk and non-HDL cholesterol risk in all groups of eating disorders. Given the chronicity of this condition, the development of elevated concentrations of LDL cholesterol and non-HDL cholesterol at an early age may increase the risk of cardiovascular diseases.

A 41-year-old man presented with abdominal fullness in late August 2012. Abdominal CT showed ileus caused by stenosis of the ileum and an enlargement of the ileocecal lymph nodes. Colonoscopy showed a steep elevated protruding tumor in the cecum, with multiple ulcerative lesions on top. A pathological analysis of the lesions confirmed chronic inflammatory infiltration and epithelioid granuloma. The findings of a tuberculin skin test and QuantiFERON-TB-Gold test were positive. As a result, we treated the patient for tuberculosis of the cecum. After 4 months of treatment, colonoscopy confirmed the disappearance of the tumor. In conclusion, intestinal tuberculosis should be considered in the differential diagnosis when protruding lesions appear in the cecum.

Two men, 48 and 54 years of age, were referred for medical checkups without any particular symptoms. Upper gastrointestinal endoscopy showed a normal gastric body, but white marbled appearance in the lesser curvature of the gastric angle and antrum. Biopsy specimens revealed relatively long and tightly coiled organisms. The two patients were diagnosed as having non-Helicobacter pylori helicobacter (NHPH) infection according to the findings of pathological and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. After triple therapy (amoxicillin, clarithromycin, and rabeprazole), endoscopy showed an improvement of the white marbled lesions and biopsy specimens showed no NHPH. The white marbled appearance limited to the gastric angle and antrum may be a potential characteristic finding of NHPH-infected gastritis.

A 76-year-old man was admitted to a community hospital due to a persistent high fever. He became afebrile after the administration of broad-spectrum antibiotics, but developed heart failure due to progressive aortic and mitral valve insufficiency and was transferred to our hospital. Although sequential blood cultures were negative, a broad-range polymerase chain reaction targeting the bacterial 16S-rRNA gene followed by the direct sequencing of whole blood revealed spa(+), mecA(-) and Panton-Valentine leukocidin (PVL)(+). He was finally diagnosed with infective endocarditis (IE) caused by PVL-producing methicillin-susceptible Staphylococcus aureus (MSSA), and underwent cardiac surgery. This is the first reported case of IE due to MSSA producing PVL.

A 69-year-old man was admitted to our hospital with cardiopulmonary arrest. Percutaneous cardio-pulmonary support (PCPS) using the right femoral artery and vein was initiated, because ventricular fibrillation continued. Although we succeeded in defibrillation after percutaneous coronary intervention (PCI), a chest radiograph indicated a pneumothorax in the right lung and a pulmonic contusion in the left lung caused by cardiopulmonary resuscitation. Two days after PCI, partial pressure of arterial oxygen (PaO₂) from the right radial artery suddenly decreased, and his cardiac function showed improvement on an echocardiogram. To avoid additional brain damage, we converted the treatment to veno-venous extracorporeal membrane oxygenation by changing the blood returning site of PCPS from the right femoral artery to the right jugular vein. Thereafter, the patient's PaO₂ level gradually improved.

The patient was a 25-year-old woman whose paternal family was Japanese, maternal grandfather was Filipino, and maternal grandmother was Chinese. Eleven days after delivery, she presented with excessive thirst and disturbed consciousness due to diabetic ketoacidosis. She was diagnosed as having fulminant type 1 diabetes associated with pregnancy (PF). The antibody concentration against glutamic acid decarboxylase was 1.2 (<1.5) U/mL, and human leukocyte antigen (HLA) class II haplotypes were DRB1*04:10-DQB1*03:02 and DRB1*15:02-DQB1*05:01. The present case had unique HLA class II haplotypes that have not been previously reported in association with PF.

A 46-year-old diabetic man underwent the removal of a hematoma caused by traumatic brain injury. After surgery, severe hyponatremia occurred. The subsequent administration of NaCl and fludrocortisone improved his laboratory findings. The patient was transferred to our hospital, and his insulin therapy was replaced by teneligliptin. One week later, ipragliflozin treatment was initiated and induced an immediate increase in the serum sodium levels. NaCl and fludrocortisone were therefore discontinued. However, hyponatremia recurred after ipragliflozin withdrawal due to a urinary tract infection. NaCl and fludrocortisone were initiated again, and the laboratory data improved. We herein report a case of serum sodium fluctuation related to ipragliflozin administration.

We herein present a case of relapsed sarcoidosis with a deteriorated renal function accompanied by hypercalcemia, nephrolithiasis, and a ureteral stone in a woman with a history of ocular sarcoidosis. The ocular involvement appeared to be well controlled for a long period of time with a topical ophthalmic steroid; however, we believe that the absence of apparent recrudescence could have led to the delay in our diagnosis of relapse of the disease during the follow-up period. The conundrums regarding longitudinal surveillance for both evaluating the disease activity and determining the necessity of therapeutics are also discussed.

We present the case of a non-dialyzed patient with chronic kidney disease and biopsy-proven calciphylaxis who presented with painful cutaneous ulcers on both legs. The skin ulcers drastically improved within 6 months after the initiation of hemodialysis, aggressive wound care, the control of a mineral and bone disorder, and the administration of sodium thiosulfate and hyperbaric oxygen therapy. Notably, the patient's serum levels of C-reactive protein and calciprotein particles decreased and her serum albumin and fetuin-A levels increased in parallel with the alleviation of her calciphylaxis. This case highlights the importance of applying combined medical treatment to calciphylaxis and suggests the possible involvement of calciprotein particles in the pathogenesis of calciphylaxis.

The risk of massive pulmonary thromboembolism (PTE) secondary to varicose vein surgery is very low. There are only two cases which have been reported regarding massive PTE occurring after varicose vein surgery. We herein present the case of a woman who had suffered from chest pain. A short period following her admission to the emergency department, she had cardiac arrest and was subsequently diagnosed with massive PTE. Thrombolytic therapy was administered and her clinical status dramatically improved thereafter. Massive PTE may occur after minor surgical procedures, and thrombolytic therapy can safely be administered after cardiopulmonary resuscitation.

A 58-year-old woman with a 1-month history of right hand clumsiness and speaking difficulty was admitted to our hospital. A neurological examination revealed sensory aphasia and right hemiparesis. Her laboratory tests showed elevated serum levels of IgG and IgG4, pancytopenia, and liver dysfunction. The results of the imaging studies of her abdomen were compatible with sclerosing cholangitis. Brain MRI showed extensive signal abnormalities in the left hemisphere on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, extending from left internal capsule to the cerebral peduncle with an irregularly enhancing lesion in the left parietal lobe. A brain biopsy revealed lymphocyte and plasma cell infiltration and reactive gliosis. Most of the plasma cells were IgG positive; however, IgG4-positive plasma cells were sparsely observed. After the initiation of betamethasone treatment, her symptoms and the brain MRI abnormalities showed significant improvement. The brain biopsy results did not meet the current criteria of IgG4-related disease. This is the first reported case of a tumefactive lesion of the brain parenchyma with serum IgG4 elevation, which was responsive to steroid treatment. The accumulation of a greater number of reports on the pathological investigation of cases of possible IgG4-related disease may help to elucidate the exact role of IgG4 in IgG4-related disorders.

In this case report, we describe a patient with myasthenia gravis (MG) and Miller Fisher syndrome (MFS) overlap. A 69-year-old woman presented with acute bilateral ptosis, ophthalmoplegia, ataxic gait, and areflexia. The MFS diagnosis was confirmed with by a positive anti-GQ1b IgG antibody test result. MG was diagnosed from electrophysiological, edrophonium, and serological test results. Although intravenous immunoglobulin therapy is effective for both diseases, two courses of the therapy did not improve the patient's symptoms. However, steroid therapy was effective. Although the overlap of MG and MFS is very rare, it should be considered in the differential diagnosis of neuro-ophthalmic diseases.

We occasionally observe long-term remission of cervical dystonia after several botulinum toxin treatments. However, botulinum toxin transiently acts on neuromuscular junctions. We herein report that a cervical dystonia patient with spinocerebellar ataxia type 1 could have long-term remission as a result of the depression of hypermetabolism in the bilateral putamen and primary sensorimotor cortex after botulinum toxin therapy. We suggest that botulinum toxin impacts the central nervous system, causing prolonged improvement through the normalization of basal ganglia circuits in addition to its effects at neuromuscular junctions.

Tocilizumab, an anti-human interleukin 6 receptor (IL-6R) monoclonal antibody, is widely used to treat rheumatoid arthritis (RA) and is expected to exhibit clinical efficacy when used to treat other autoimmune diseases. However, a risk of opportunistic infection is occasionally recognized. A 54-year-old woman had received an oral corticosteroid and methotrexate to treat RA. Despite receiving these treatments, she received additional treatment with tocilizumab due to poor control of the disease activity. She presented at our hospital with a high fever and epigastralgia 19 days after receiving this treatment. A laboratory evaluation revealed liver injury and cytomegalovirus (CMV) viremia. Abdominal ultrasonography and computed tomography (CT) revealed hepatosplenomegaly, but no ascites. Upper gastrointestinal endoscopy revealed gastric erosions induced by CMV, which were confirmed immunohistochemically. Hence, we diagnosed the patient with CMV reactivation-induced acute hepatitis and gastric erosions under tocilizumab treatment. She received an anti-cytomegalovirus drug, ganciclovir, for 14 days due to her viremia and impaired general condition, which was suggestive of a severe infection. Her general condition subsequently improved, the liver function test results normalized, and the gastric erosions disappeared. In conclusion, although tocilizumab is very useful for treating certain autoimmune and inflammatory diseases, and will be prescribed more widely in the future, associated CMV infections must be closely monitored, as these can be lethal.

A 68-year-old man on peritoneal dialysis (PD) was hospitalized with the clinical picture of peritonitis. The patient was diagnosed with peritonitis caused by nontuberculous mycobacteria (NTM) according to positive Ziehl-Neelsen staining and negative Mycobacterium tuberculosis polymerase chain reaction results. Oral levofloxacin and clarithromycin, and later intraperitoneal imipenem were started. According to the anti-NTM susceptibility test results, oral minocycline was administered. The patient was treated for 6 months. He recovered without PD catheter removal; thus, PD was successfully continued. A genetic analysis identified the isolate as Mycobacterium iranicum. This is the first report of PD-related peritonitis caused by M. iranicum.