Objectives The fractional flow reserve (FFR) is an index of the severity of coronary stenosis that has been clinically validated in several studies. The instantaneous wave-free ratio (iFR) and the resting distal coronary artery pressure/aortic pressure (Pd/Pa) are nonhyperemic pressure-derived indices of the severity of stenosis. This study sought to examine the diagnostic accuracy of the iFR and resting Pd/Pa with respect to hyperemic FFR.

Methods Following an intracoronary injection of papaverine, the iFR, resting Pd/Pa, and FFR were continuously measured in 123 lesions in 103 patients with stable coronary disease.

Results The iFR and resting Pd/Pa values were strongly correlated with the FFR (R=0.794, p<0.001, R=0.832, p<0.0001, respectively). A receiver operator curve (ROC) analysis revealed that the optimal iFR cut-off value for predicting an FFR of <0.80 was 0.89 (AUC 0.901, sensitivity 84.1%, specificity 80.0%, positive predictive value 69.8%, negative predictive value 90.0%, diagnostic accuracy 81.3%), while the optimal resting Pd/Pa cut-off value was 0.92 (AUC 0.925, sensitivity 90.9%, specificity 78.5%, positive predictive value 70.2%, negative predictive value 93.9%, diagnostic accuracy 82.9%). The lesions with an iFR value of ≤0.89 and a Pd/Pa value of ≤0.92 were defined as double-positive lesions, while the lesions with an iFR value of >0.89 and a Pd/Pa value of >0.92 were defined as double-negative lesions. In these 109 lesions, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.3%, 82.9%, 75.0%, 95.1%, and 86.2%, respectively.

Conclusion This analysis demonstrated that the iFR and resting Pd/Pa were strongly correlated with the FFR and that the diagnostic accuracy of the iFR was similar to that of the resting Pd/Pa. The diagnostic accuracy can be improved with the use of both the iFR and the resting Pd/Pa.

Objective Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, dyslipidemia and type-2 diabetes mellitus. Bile acids (BAs) bind to the farnesoid X receptor (FXR) and G protein-coupled receptor 5 (TGR5), which are involved in lipid and glucose metabolism and energy expenditure. The present study aimed to determine associations between the circulating BAs and the skeletal muscle volume (SMV), and lipid and glucose metabolism in patients with NAFLD.

Methods Serum BAs and metabolic parameters were measured in 55 patients with NAFLD (median age, 55 years). The changes (Δ) in serum BA (ΔBA) and metabolic parameters were determined in 17 patients (male, n=10; female, n=7) who received nutritional counseling for 12 months.

Results Spearman's test revealed that the levels of 12α-hydroxysterol (12α-OH) BAs, including deoxycholic acid (DCA), were inversely correlated with the SMV of the upper and lower limbs and the total SMV. A multivariate analysis revealed that the level of DCA was correlated with a reduced total SMV, whereas non-12α-OH BAs, including chenodeoxycholic acid (CDCA), were correlated with an increased SMV of the lower limbs. Changes in CDCA were positively correlated with the ΔSMV of the lower limbs, and inversely correlated with the Δwaist-hip ratio and Δtotal cholesterol. Changes in the total non-12α-OH BA level were positively correlated with the ΔSMV of the lower limbs.

Conclusion Circulating BAs were associated with SMV. The 12α-OH BAs, including DCA were associated with reduced SMV levels, whereas non-12α-OH BAs including CDCA were associated with increased SMV levels. The molecular mechanisms underlying the association between the BA levels and the SMV remain to be explored.

Objective Emerging studies have focused on the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM in a Japanese middle-aged health check population.

Methods We conducted a 10-year observational study in a health checkup population of middle-aged Japanese men and women at Hidaka Hospital from 2004 to 2013. We excluded cases with an alcohol intake exceeding 20 g/day and those with impaired glucose tolerance. The remaining 1,544 men and 864 women were classified into fatty liver and non-fatty liver groups based on the findings of abdominal ultrasonography. Both groups were followed for the development of diabetes. A multiple regression analysis was performed for each variable to predict the risk of future diabetes.

Results The median age of the participants was 46.0 years at the entry, and the follow-up period was 10 years. The incidence of diabetes in the fatty liver group was 12.5% (29/232) in men and 26.3% (10/38) in women, whereas the incidence of diabetes in the non-fatty liver group was 2.5% (34/1,312) in men and 1.8% (15/826) in women. The relative risk of diabetes associated with fatty liver was 4.8 [95% confidence interval (CI) 3.0-7.8, p<0.0001] in men and 14.5 (95% CI 7.0-30.1, p<0.0001) in women.

Conclusion NAFLD was a significant predictor for future diabetes in a Japanese middle-aged health check population, especially in women.

Objective Two interferon-gamma release assays (IGRAs), the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT), are commercially available. The agreement between the two IGRAs in the screening of healthcare workers (HCWs) for latent tuberculosis is not well known.

Methods The QFT-GIT and T-SPOT tests were performed for the baseline tuberculosis screening of 654 HCWs who worked at Mie University Hospital in Japan. The results of the two tests were directly compared.

Results Nineteen (2.9%), 28 (4.3%) and 33 (5.0%) of the 654 HCWs were found to be positive by the QFT-GIT, T-SPOT, and the QFT-GIT and/or T-SPOT methods using cut-off values of 0.35 IU/mL (QFT-GIT) and 6 spots (T-SPOT). After excluding 4 cases with indeterminate results, there were 14 concordant positive (2.2%), 618 concordant negative (95.1%), and 18 discordant (2.8%) results using the cut-off values of 0.35 IU/mL (QFT-GIT) and 6 spots (T-SPOT). The agreement of the two IGRAs was 97.2% (κ=0.595). When cut-off values of 0.35 IU/mL (QFT-GIT) and 8 spots (T-SPOT) were applied, there were 11 concordant positive (1.7%), 626 concordant negative (96.3%), and 13 discordant (2.0%) results, with 98.0% agreement (κ=0.618). When the borderline criteria for the QFT-GIT (0.1 to <0.35 IU/mL) and T-SPOT (5-7 spots) were applied, there were 11 concordant positive (1.7%), 11 concordant borderline (1.7%), 586 concordant negative (90.2%), and 42 discordant (6.5%) results, with 93.5% agreement between the two methods (κ=0.538).

Conclusion When standard cut-off values were used, the agreement between the two IGRAs in the tuberculosis screening of Japanese HCWs was moderate to high. Importantly, some HCWs showed discordant results, especially those whose results were in the borderline zones.

Objective Coagulase-negative staphylococci are among the most frequently isolated microorganisms in blood cultures. The aim of this study was to assess [1] the clinical characteristics of methicillin-resistant, coagulase-negative staphylococci bacteremia and [2] the susceptibility of the isolated bacteria to glycopeptides.

Methods We retrospectively reviewed the medical records of 70 patients from whom methicillin-resistant coagulase-negative staphylococci had been isolated at Osaka City University Hospital between January 2010 and December 2013. We evaluated the patients' background, severity and prognosis of the disease, and the susceptibility of the isolated methicillin-resistant coagulase-negative staphylococci to glycopeptides.

Results Out of the 70 patients tested, 28 (40.0%) had leukemia, and 36 (51.4%) had been treated for febrile neutropenia. Infection with Staphylococcus epidermidis accounted for 78.6% of patients. Thirty-nine cases (55.7%) were related to intravascular catheters, and 39 (55.7%) were treated using teicoplanin as a first-line therapy. The 30-day mortality rate was 4.3%. Regarding susceptibility, 20% of all isolates were non-susceptible to teicoplanin. According to multivariate analyses, it was observed that premedication using glycopeptides was independently associated with teicoplanin non-susceptibility (p=0.03; hazard ratio = 5.64; 95% confidence interval, 1.16-26.76).

Conclusion Our results suggest that clinicians must use glycopeptides appropriately to prevent the development of further antibiotic resistance in methicillin-resistant coagulase-negative staphylococci.

We experienced two patients with serious arrhythmias associated with the administration of ledipasvir (LDV) and sofosbuvir (SOF). Neither patient took amiodarone, an agent for which concomitant use is prohibited. One patient was 82 years old and hypertensive; the other was 72 years old and had no cardiovascular risk factors such as hypertension or diabetes mellitus. The arrhythmias were both serious ventricular tachycardia (VT) that converted spontaneously to sinus rhythm, without treatment, and both patients had good outcomes. These cases suggest that LDV/SOF may be associated with an increased risk of heart-related events.

A 73-year-old man complained of sternoclavicular joint pain; blood tests revealed elevated C-reactive protein. The patient developed delirium; magnetic resonance imaging showed metastatic bone tumors. He died two weeks after admission. Autopsy revealed abdominal aortic intimal sarcoma with metastasis to the peritracheal lymph nodes and sternum. Peripheral arterial embolism and bone metastasis are common symptoms of aortic intimal sarcoma, which implies a place for aortic intimal sarcoma in differential diagnoses of embolism or bone tumors of unknown origin.

We report a rare case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with amyotrophic lateral sclerosis (ALS). A 69-year-old man was admitted to our hospital with sustained hyponatremia. Hyposmolality with elevated urinary osmolality and sodium excretion was observed, which indicated SIADH. The treatment for SIADH was challenging; the patient developed carbon dioxide narcosis, which led to the diagnosis of ALS. After the initiation of noninvasive positive-pressure ventilation, the patient's serum sodium concentration normalized and became stable. Thus, ALS should be recognized as a possible cause of SIADH in the clinical setting.

We herein report the case of a hemodialysis patient whose response to an erythropoiesis-stimulating agent (ESA) improved following the resection of thyroid cancer. Her hemoglobin level remained below 7 g/dL, despite the use of ESA. During the search for the causes of her hyporesponsiveness to ESA, papillary thyroid cancer and aceruloplasminemia were found. The existence of other potential causes, such as iron deficiency, infectious disease, severe hyperparathyroidism and malnutrition were ruled out. Following the resection of the thyroid cancer tumor, her hemoglobin level increased to 10.2 g/dL over a period of 4 months. This is the first report to demonstrate the resolution of hyporesponsiveness to ESA following the resection of a malignant tumor.

A 55-year-old man developed rapidly progressive glomerulonephritis and nephrotic syndrome. A kidney biopsy specimen showed diffuse proliferative and crescentic glomerulonephritis with monoclonal IgG1κ, humps, and nephritis-associated plasmin receptor, indicating infection-associated proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID). Despite dialysis-dependent renal failure, symptomatic therapy resulted in spontaneous recovery of the renal function, mimicking post-infectious glomerulonephritis (PIGN). A heterozygous complement factor H mutation was detected by comprehensive genetic testing of alternative pathway regulatory genes, which might lead to persistent infection-triggered alternative pathway activation and account for severe glomerulonephritis. Post-infectious PGNMID and PIGN might share common clinical presentations and pathogenesis related to the complement pathway.

A 51-year-old man was admitted to have a nodule evaluated using chest computed tomography (CT). Shortly after curetting and transbronchial biopsies via bronchoscopy, hypotension, bradycardia, unconsciousness, and left hemiplegia appeared and resolved within one hour. Head CT showed cerebral air embolism. The following day, lower left quadrant pain developed. Pneumatosis intestinalis on abdominal CT and elevation of creatine kinase and troponin T levels indicated air embolism in the mesenteric and coronary arteries. Some reports have documented cerebral air embolism alone after bronchoscopy; however, we should consider systemic air embolism, even when encountering a patient without specific symptoms related to any organ.

Pulmonary artery sarcoma is highly malignant and easily metastasizes to the systemic organs. Both the introduction of novel diagnostic procedures and the development of new treatment modalities are required to achieve long-term survival. Several studies have shown that platelet-derived growth factor receptor α (PDGFRα) gene amplification is frequently observed in pulmonary artery sarcoma. PDGFRα is known to be involved in cell proliferation in certain malignancies. PDGFRα may become a potential biological marker in pulmonary artery sarcoma. We report a case in which a diagnosis of pulmonary artery sarcoma overexpressing PDGFRα was made using endovascular catheter biopsy following positron emission tomography with integrated computed tomography (PET/CT) scans.

We herein report the case of a 52-year-old woman who consulted us because of a 2-month history of a fever, anorexia and weight loss. A physical examination was unremarkable. The blood count showed mild anemia and lymphopenia, and lactate dehydrogenase was elevated. Creatinine clearance was normal and proteinuria was undetectable. CT showed enlarged kidneys. A bone marrow biopsy was normal. PET-CT showed an intense uptake of ¹⁸fluorodeoxyglucose in both kidneys. A kidney biopsy provided the diagnosis of intravascular large B-cell lymphoma (IVLBCL). Kidney-limited IVLBCL without an impairment in the renal function or proteinuria has not been described. We analyzed the 38 published cases of IVLBCL involving the kidney to describe the main features of this entity.

A 76-year-old Japanese man was admitted to our hospital because of the occurrence of multiple nodules on the shaft of his penis. He was diagnosed with diffuse large B cell lymphoma (DLBCL). His lymphoma was located only in his penis. He received immunochemotherapy and involved-field radiotherapy, and achieved complete response (CR). About two years later, he complained of a poor appetite. Magnetic resonance imaging showed a mass lesion in the pituitary stalk. Biopsy of this mass revealed the recurrence of DLBCL. He received whole-brain radiotherapy, and achieved CR. This is the first case of an isolated pituitary stalk relapse of primary penile lymphoma.

Fabry disease (FD) is an inherited lysosomal disorder caused by an X-linked α-galactosidase A deficiency. We report the case of a 50-year-old male FD patient on hemodialysis who presented with macroglossia-related speaking difficulty and gastrointestinal symptoms. An endoscopic analysis revealed multiple gastric ulcers, and a histological examination led to a diagnosis of amyloid light-chain amyloidosis. Serum free light-chain and bone marrow analyses detected multiple myeloma (MM). Treatment with bortezomib and dexamethasone significantly improved the patient's symptoms. This is the first case to demonstrate a potential pathogenic relationship between FD and MM. The similar gastrointestinal manifestations might have contributed to the diagnostic difficulty.

A 55-year-old man presented to our department with diarrhea, weight loss, fatigability, and polyarthralgia. Blood tests revealed elevated soluble interleukin-2 receptor levels and IgG-type M protein positivity, without any findings that were suggestive of collagen disease. After computed tomography (CT) detected enlarged lymph nodes in the abdominal para-aortic region, lymphoma was suspected. CT-guided needle biopsy of the lymph node did not help to achieve a definitive diagnosis; however, a bone marrow test showed the pathological features of B-cell lymphoma. A genetic examination detected a MYD88 L265P mutation; the mutation analysis was valuable in diagnosing lymphoplasmacytic lymphoma in a IgM-type M protein-negative patient.

A 73-year-old man was admitted to our hospital with disturbance of consciousness, fever and headache. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with neutrophil predominance, increased protein and low glucose. CSF and blood cultures yielded negative results. Antibiotics and antituberculous drugs were started for meningitis. An antimycotic was also added. The patient died from transtentorial hernia 99 days after admission. Autopsy revealed meningitis, ventriculitis and brain abscess, and Nocardia araoensis was detected in pus from the left lateral ventricle. This appears to represent the first report of N. araoensis meningitis complicated by ventriculitis and brain abscess.

An 81-year-old man was admitted to our hospital with abdominal distension due to refractory ascites of unknown origin. He subsequently died of aspiration pneumonia. Autopsy revealed a diagnosis of biphasic malignant peritoneal mesothelioma (MPM) containing both epithelioid and sarcomatous components. The diagnosis of MPM is often difficult because serum tumor markers, imaging studies, and the cytology of ascites may not provide enough information. Accordingly, peritoneal biopsy is necessary in order to diagnose MPM based on the histological and immunohistochemical findings.

Chromosome 22q11.2 deletion syndrome (22q11.2 DS) has a very wide phenotypic spectrum that includes dysmorphic features, cardiac anomalies, and hypocalcemia arising from hypoparathyroidism. We herein describe an adult case of 22q11.2 DS with associated hypoparathyroidism and anomalies of the aortic arch. Because the patient had been diagnosed with primary hypoparathyroidism at another hospital, a diagnosis of 22q11.2 DS had been overlooked. A chest X-ray examination revealed widening of the mediastinum caused by a high-positioned right aortic arch, and we subsequently confirmed a diagnosis of 22q11.2 DS using fluorescence in situ hybridization. Because primary hypoparathyroidism is a rare disorder, physicians should be aware of the variable phenotypic features of 22q11.2 DS.