Objective The aim of the present study is to assess the difference in the detection rates of small-bowel lesions in chronic abdominal pain (CAP) patients with irritable bowel syndrome (IBS) and non-IBS.

Patients Ninety-nine CAP patients who were scheduled to undergo capsule endoscopy (CE) to investigate their abdominal symptoms were included in this study. Among the subjects, 34 patients fulfilled the Rome III criteria for IBS (IBS group); the remaining 65 patients were categorized as the non-IBS group. CE was performed in both groups and the total enteroscopy achievement rate, small-bowel lesion detection rate, and the presence of small-bowel lesions were evaluated. We also evaluated the patients' blood test results and the rate at which abdominal symptoms improved following internal medication.

Results Total enteroscopy was achieved in 62% (21/34) and 86% (56/65) of the IBS and non-IBS patients, respectively. The total enteroscopy achievement rate was significantly higher in non-IBS patients. The small-bowel lesion detection rates were 3% (1/34) and 19% (12/65), respectively, and the detection rate was significantly higher in the non-IBS patients. In the non-IBS patients, mean C-reactive protein (CRP) was significantly higher in the patients with small-bowel lesions. The abdominal symptoms of 12 (92%) of the CAP patients with small-bowel lesions were improved by internal medication.

Conclusion CE may be considered for non-IBS CAP patients with high levels of CRP.

Objective To detect the aggressive phenotype (AP) of non-alcoholic fatty liver disease (NAFLD) based on the initial laboratory data and clinical characteristics.

Methods We enrolled 144 patients with histologically proven NAFLD. For the first analysis, 24 NAFLD patients underwent repeat biopsy to establish a discriminant formula for predicting the AP of NAFLD (D-APN). The AP was defined by NAFLD that had been maintained or progressed to a fibrotic stage beyond stage 2. In the second analysis, we analyzed the distribution of the AP in each stage of disease and the incidence of the PNPLA3 rs738409 GG genotype in AP in 120 other patients.

Results After the analysis, the following function was found to discriminate the disease phenotype: z=0.150×body mass index (kg/m²)+0.085×age (years)+1.112×ln (AST) (IU/L)+0.127×ln (m-AST)-12.96. A positive result indicates the AP of NAFLD. The discriminant functions had a positive predictive value of 94% and a negative predictive value of 71%.

The distribution of the AP and the incidence of the PNPLA3 GG genotype in the AP in each stage of the disease among the 120 patients were as follows: non-alcoholic fatty liver, 30%/33%; non-alcoholic steatohepatitis (NASH) stage 1, 53%/26%; stage 2, 71%/70%; stage 3, 92%/57%; and stage 4, 93%/64%; there was a significant increase in the incidence of the AP as the disease progressed (p<0.001).

Conclusion The new discriminant formula was useful for predicting disease progression potential in NAFLD patients and the incidence of the PNPLA3 GG genotype was elevated according to the distribution of AP.

Objective To investigate the relationship between patient characteristics and morning glycemic variability.

Methods We retrospectively evaluated 106 patients with type 2 diabetes who underwent continuous glucose monitoring during admission. The highest postprandial glucose level (within 3 hours after breakfast; 'highest level'), the time from the start of breakfast to the highest postprandial glucose level ('highest time'), the difference between the pre-breakfast and highest postprandial breakfast glucose level ('increase'), the area under the curve (AUC; ≥180 mg/dL) for the glycemic variability within 3 hours after breakfast ('morning AUC'), and the post-breakfast glucose gradient ('gradient') were calculated. We analyzed the associations between these factors and nocturnal hypoglycemia and the patients' characteristics by using a regression analysis.

Results After stepwise multivariate adjustment, significant independent associations were found between 'highest level' and high age, low BMI, and high HbA1c; 'highest time' and high HbA1c, low C-peptide immunoreactivity (CPR), and low fasting plasma glucose (FPG); the 'increase' and high age, low BMI, high HbA1c, low FPG and hypoglycemia; 'morning AUC' and high age, high HbA1c and hypoglycemia; and 'gradient' and long duration of diabetes and low BMI.

Conclusion Higher age and lower BMI are associated with higher 'highest' and 'increase' levels. Higher HbA1c levels were linked to a longer 'highest time', and longer durations of the diabetes, while lower BMI values were related to a higher 'gradient'.

Objective This study aimed to examine the association between the changes in an overall healthy lifestyle, as quantified by the number of unhealthy lifestyle factors and obesity status, and the incidence of proteinuria in the general Japanese population.

Methods A retrospective cohort study was conducted among 99,404 (men, 36.9%) participants aged from 40-74 years of age who underwent two health check-ups with a 1-year interval in Japan between 2008 and 2009. Any participants with chronic kidney disease at baseline were excluded. The smoking status, body mass index, physical activity, alcohol consumption, and healthy eating habits were combined into a simple overall healthy lifestyle score ranging from 0 to 5. The changes in overall healthy lifestyle scores from baseline (range, -5 to +5) and the incidence of proteinuria, defined by a dipstick urinalysis (score ≥1+), were assessed at the second check-up. A logistic regression analysis was used to examine the association between the changes in overall healthy lifestyle scores and the incidence of proteinuria.

Results After one year of follow-up, 3.9% of men and 2.4% of women developed proteinuria. Each increase (or decrease) in the changes in overall healthy lifestyle scores was associated with a reduced (or increased) risk of proteinuria in both men (odds ratio (OR) 0.87; 95% confidence interval (CI), 0.81-0.94) and women (OR 0.87; 95%CI, 0.80-0.94) after adjusting for age, baseline lifestyle scores, hypertension, diabetes mellitus, and hypercholesterolemia. Stratified analyses based on age, the presence or absence of hypertension, or diabetes mellitus revealed similar results.

Conclusion Overall lifestyle changes, even within a year, were found to influence the incidence of proteinuria.

Objective Pulmonary nocardiosis frequently develops as an opportunistic infection in patients with malignant tumor and is treated with steroids. This study was performed to clarify the clinical features of pulmonary nocardiosis in Japan.

Methods The patients definitively diagnosed with pulmonary nocardiosis at our hospital between January 1995 and December 2015 were retrospectively investigated.

Results Nineteen men and 11 women (30 in total) were diagnosed with pulmonary nocardiosis. Almost all patients were complicated by a non-pulmonary underlying disease, such as malignant tumor or collagen vascular disease, or pulmonary disease, such as chronic obstructive pulmonary disease or interstitial pneumonia, and 13 patients (43.3%) were treated with steroids or immunosuppressors. Gram staining was performed in 29 patients, and a characteristic Gram-positive rod was detected in 28 patients (96.6%). Thirty-one strains of Nocardia were isolated and identified. Seven strains of Nocardia farcinica were isolated as the most frequent species, followed by Nocardia nova isolated from 6 patients. Seventeen patients died, giving a crude morality rate of 56.7% and a 1-year survival rate of 55.4%. The 1-year survival rates in the groups with and without immunosuppressant agents were 41.7% and 59.7%, respectively, showing that the outcome of those receiving immunosuppressants tended to be poorer than those not receiving them.

Conclusion Pulmonary nocardiosis developed as an opportunistic infection in most cases. The outcome was relatively poor, with a 1-year survival rate of 55.4%, and it was particularly poor in patients treated with immunosuppressant agents. Pulmonary nocardiosis should always be considered in patients presenting with an opportunistic respiratory infection, and an early diagnosis requires sample collection and Gram staining.

Objective Several studies have shown an increased prevalence of right-to-left shunt (RLs) in migraine patients, particularly those with aura. However, the prevalence of RLs and its relation to Japanese patients with migraine are unknown. We investigated the prevalence of RLs in Japanese patients with migraine.

Methods In total, 112 consecutive patients with migraine were recruited from our headache outpatient clinic. Migraine with aura (MA) and migraine without aura (MWOA) were diagnosed according to the International Classification of Headache Disorders, 3rd edition (beta-version). Contrast transcranial Doppler ultrasound was used to detect RLs, including patent foramen ovale (PFO). Then, the associations between RLs and patients' backgrounds and presence of aura were assessed.

Results The overall prevalence of RLs and PFO in migraine patients was 54.5% and 43.8%, respectively. The prevalence of RLs and PFO in the MA group were significantly higher than in the MWOA group (RLs, 62.9% vs. 44.0%, p=0.046; PFO, 54.8% vs. 30.0%, p=0.008). There were no marked differences in the prevalence of large, middle and small shunts between MA and MWOA patients. Compared with the MWOA patients, the MA patients were younger (p=0.013) and had early onset age (p=0.013) and increased prevalence of photophobia (p=0.008).

Conclusion RLs were found in over half of the Japanese patients with migraine. Our study suggests a possible link between RLs and MA.

Objective Lifestyle changes may play an important role in the incidence reduction and delay of onset age of amyotrophic lateral sclerosis (ALS) in the Koza/Kozagawa/Kushimoto (K) area. The aim of this study was to evaluate recent lifestyle changes in the K area and to investigate the relationships between lifestyle and oxidative stress among the residents.

Methods We conducted a medical checkup for elderly residents in the K area and the control area and evaluated the urinary 8-OHdG levels, cognitive function test scores and metal contents in serum and scalp hair, coupled with a lifestyle questionnaire survey between 2010 and 2015.

Results Recent lifestyle changes among the K residents, including a decrease in the Japanese pickle consumption, increase in fresh vegetable consumption and decrease in farm work, were evaluated in this study. Low consumption of Japanese pickles, high consumption of fresh vegetables, rare farm work and low levels of 8-OHdG/creatinine were all associated with high scores in the cognitive function tests. Frequent farm work and consumption of Japanese pickles was associated with high contents of transition metals, such as Mn, Al and V, in the scalp hair.

Conclusion These lifestyle changes among residents in the K area may be associated with their oxidative stress.

Objective To examine the characteristics of the communication skills of medical students, we observed their performance during introductory medical interview training with simulated patients (SPs).

Methods The subjects of the present study included fifth-year medical students (male, n=180, female, n=99) who were undergoing clinical training in Japan from 2012 to 2014. Each student was assigned to one of four 10-minute clinical scenarios, which was conducted with an SP. Three or four teachers observed and assessed the performance of each of the students. The overall performance was rated on a 10-point scale, and nine basic communication skills that were common to each of the scenarios were rated using a four-point scale. The students also assessed their own performance on these items. The SPs assessed the students' performance from a patient's perspective on four items.

Results There were significant correlations between the teacher and student scores. However, the students tended to score themselves significantly lower than the teachers. The female students were rated significantly higher by the teachers on the following four items; 'eye contact and appropriate attitude,' 'nodding and back-channeling,' 'giving empathic verbal responses,' and 'acquisition of patient's psychosocial information.' However, the self-assessments of the female students were only significantly higher than the male students in one item, 'acquisition of patient's psychosocial information.' In contrast, self-assessments of the male students were significantly higher in two items; none of their items was scored higher by the teachers. There was no significant gender difference in the assessments made by the SPs.

Conclusion There were significant gender differences in the communication skills of the medical students during introductory training, suggesting the possibility that there were gender-specific traits and gender-based differences in the students' degrees of readiness.

A 95-year-old Japanese woman presented to our hospital with intermittent vomiting and several episodes of melena. Abdominal computed tomography revealed intussusception of the gastric tumor into the duodenum. After endoscopic reduction, endoscopic ultrasonography identified a hypoechogenic lesion limited to the submucosal layer. Endoscopic resection was performed as a localized treatment for the prevention of recurrent gastroduodenal intussusception. To our knowledge, there have been no other reports describing a gastric gastrointestinal stromal tumor presenting with gastroduodenal intussusception and treated using an endoscopic submucosal dissection technique.

Localized small rectal neuroendocrine tumors (NETs) without any vascular involvement rarely metastasize, and their resection alone is considered curative. We herein report a case of localized rectal NET (10×8 mm) without vascular involvement. Although resected initially, it recurred as liver metastasis 30 years later. For rectal NETs smaller than 10 to 20 mm, surveillance for 12 months is considered sufficient. However, this case suggests that such tumors can recur even 30 years after curative resection. The interval of recurrence is the longest among reported cases.

Succinic acid cibenzoline (CZ) is an antiarrhythmic agent often used for the treatment of tachyarrhythmia. However, hypoglycemia should be avoided in the treatment of diabetes. We herein report two late-stage elderly subjects who experienced a severe and prolonged hypoglycemic coma after the usage of CZ. These cases suggest that, when CZ is administered to elderly subjects with renal dysfunction and/or frailty, we should be aware of the possibility that this medicine may induce hypoglycemia and should adjust the dose as appropriate and monitor the concentration of CZ to avoid severe hypoglycemia.

Two elderly patients (a 76-year-old man and a 75-year-old woman), who had been previously diagnosed with familial hypercholesterolemia (at 58 and 48 years of age, respectively) underwent long-term treatment with oral therapy and low-density lipoprotein (LDL) apheresis. As their LDL cholesterol levels remained high (>150 mg/dL and >120 mg/dL, respectively) and their familial hypercholesterolemia was complicated with angina pectoris, we added evolocumab to their prescription. Thereafter, their LDL cholesterol levels decreased rapidly, and the patients were successfully weaned from LDL apheresis. Evolocumab therapy should thus be considered when LDL apheresis cannot achieve the target LDL cholesterol levels, though the prognosis of such treatment remains unclear.

Low birth weight (LBW) has been known to increase the susceptibility to renal injury in adulthood. A 26-year-old woman developed proteinuria in early pregnancy; she had been born with very LBW. The clinical course was progressive, and an emergency Caesarean section was performed at 36 weeks due to acute kidney injury. A renal biopsy provided a diagnosis of post-adaptive focal segmental glomerulosclerosis. Increased demand for glomerular filtration during early pregnancy appeared to have initiated the renal injury. This report highlights the fact that pregnancy might be a risk factor for renal injury in women born with LBW.

A 61-year-old Japanese man developed nephrotic syndrome (NS) due to idiopathic membranous glomerulonephritis (MGN). He received immunosuppressive therapy for two years, including prednisolone, cyclophosphamide, and cyclosporine A, but the NS persisted. Low-density lipoprotein apheresis (LDL-A) was initiated at a frequency of twice a month and continued for 9 years (203 sessions in total). His proteinuria reduced to less than 1 g daily after 9 years. LDL-A was stopped, and the NS has not relapsed for five years. This case suggests that long-term LDL-A therapy may be a treatment option for idiopathic MGN refractory to immunosuppressive therapy or short-term LDL-A.

Small cell lung cancer (SCLC) is a neuroendocrine tumor, and the median age of onset is about 70 years old. A 20-year-old non-smoking man with known systemic sclerosis presented with discomfort in his left chest. Chest X-ray showed a mass shadow in the left upper zone. A transbronchial lung biopsy revealed small cell carcinoma, and imaging studies reached the diagnosis of extensive disease small cell lung cancer. He had concurrent interstitial lung disease with a non-specific interstitial pneumonia pattern and anti-Scl-70 antibodies. He died eight months after the diagnosis during fifth-line chemotherapy. We herein report the youngest case to date of SCLC with systemic sclerosis.

As an idiopathic interstitial pneumonia, desquamative interstitial pneumonia (DIP) is an uncommon form of interstitial lung disease and is considered to be a smoking- or dust inhalation-related interstitial pneumonia in the majority of cases. However, the details regarding immunoglobulin G4 (IgG4)-related lung disease remain unclear and controversial. We herein report the first case of DIP complicated with IgG4-related lung disease. Even if a patient has a smoking history, we emphasize the importance of exploring the association between DIP and IgG4-related lung disease to clarify the pathogenesis of these two disorders.

Interstitial pneumonia is a common and major comorbidity affecting the prognosis of patients with systemic sclerosis (SSc). However, there are few reported cases of SSc-rheumatoid arthritis (RA) overlap-associated interstitial pneumonia. We herein report a case in which the clinical behavior and histopathology of interstitial pneumonia with SSc-RA overlap syndrome was followed over a long clinical course. When clinicians are deciding on the treatment strategy for patients with SSc-RA overlap syndrome-associated interstitial pneumonia, a pathological examination of a surgical lung biopsy may be useful.

As a treatment for superficial transitional cell carcinoma, Bacillus Calmette-Guerin (BCG) intravesical instillation can rarely cause unpredictable systemic side effects. We describe a patient admitted due to continuous pyrexia and general fatigue. He was previously treated with intravesical BCG. Laboratory data indicated a hepatic disorder, and chest computed tomography revealed extensive bilateral miliary nodules. Transbronchial lung biopsy specimens showed several small noncaseating granulomas. The diagnosis was unsolved on the basis of acid fast staining, polymerase chain reaction and microbiological cultures, so we considered the possibility of BCG side effect-induced granuloma. Two months after treatment with antituberculous agents and corticosteroids, his clinical symptoms were improved.

A 65-year-old man who had been diagnosed with transient global amnesia (TGA) 15 years previously was admitted to hospital with complaints of amnesia and headache. His symptoms improved on day-2. The initial brain MRI and electroencephalography findings were normal. He was diagnosed with a recurrence of TGA and discharged. However, he returned with right leg weakness and complained of a thunderclap headache. MRI demonstrated subarachnoid hemorrhage and multifocal segmental narrowing of the left posterior cerebral artery (PCA) and large intracranial arteries, and he was diagnosed with reversible cerebral vasoconstriction syndrome (RCVS). He was discharged on day-30 without any neurological deficits. This case suggested that TGA should be interpreted as one of the symptoms of RCVS or a prodromal symptom of RCVS.

True renal lupus vasculitis (TRLV), a vascular lesion usually associated with proliferative lupus nephritis (LN), is resistant to conventional treatments. The expression of P-glycoprotein (P-gp) on activated lymphocytes causes drug resistance. We herein report a patient with TRLV, minimal change LN, overexpression of P-gp on peripheral B cells, and accumulation of P-gp⁺ B cells at the site of TRLV. High-dose corticosteroids combined with intravenous cyclophosphamide pulse therapy resulted in clinical remission and the long-term normal renal function.

A 35-year-old woman with discoid lupus erythematosus (DLE) was admitted at 11 weeks' gestation with a persistent fever. Laboratory studies revealed pancytopenia, elevated liver enzymes, and hyperferritinemia. Bone marrow aspiration confirmed the diagnosis of hemophagocytic syndrome (HPS). She had no findings of infection or active systemic lupus erythematosus. The administration of high-dose corticosteroids resolved the clinical and laboratory findings. She delivered a healthy baby at 35 weeks' gestation. This case suggests that DLE can be a predisposing factor for pregnancy-induced HPS.

Biologics used in the treatment of rheumatoid arthritis (RA) rarely cause eosinophilia. We herein report a patient with RA being treated with infliximab, adalimumab, and tocilizumab who developed eosinophilia with skin symptoms. Interestingly, the marked eosinophilia and skin symptoms did not reappear after the patient's medication was switched to golimumab. In this case, the presence of biologics-specific antibodies suggested that immunogenicity caused the eosinophilia. Therefore, switching to a biologic with a lower immunogenicity was effective. These findings may be helpful for clinicians treating patients with biologics-induced eosinophilia.

We herein report a rare case of miliary tuberculosis-associated hemophagocytic syndrome (HPS) complicated with respiratory failure. A 19-year-old Japanese woman with a fever, general malaise, and chest radiograph abnormalities was referred to our hospital. After admission, she developed respiratory failure with pancytopenia. A histological examination of lung and bone marrow biopsy samples revealed noncaseating granulomas without evidence of acid-fast bacilli or lymphoma. In addition, a bone marrow biopsy showed marked histiocyte hyperplasia with hemophagocytosis, and a bronchoalveolar lavage fluid culture grew Mycobacterium tuberculosis. Therefore, a diagnosis of miliary tuberculosis-associated HPS was made. The patient was successfully treated with antituberculous therapy.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease caused by a novel Bunyavirus with a high mortality rate. We herein report a fatal case of an 86-year-old woman with SFTS complaining of a fever, fatigue, and bicytopenia. Her condition deteriorated with rapid progression of bleeding tendency, disturbance of consciousness, and multiple organ failure leading to death on Day 6 of her illness. The histopathological findings in the autopsy revealed marked infiltration of macrophages with hemophagocytosis in the bone marrow, liver, and spleen leading to a diagnosis of hemophagocytic lymphohistiocytosis (HLH). HLH might be a critical pathogenesis in fatal cases of SFTS.