Impact of Low Skeletal Muscle Mass on the Prognosis of Patients with Head and Neck Cancer Treated Nonsurgically.

INTRODUCTION: Sarcopenia, characterized by low skeletal muscle mass, and the outcome of cancer therapy are closely related based on recent research. This study aimed to evaluate the correlation between skeletal muscle mass and prognosis in head and neck cancer (HNC) patients. METHODS: In this study, 51 male patients with HNC treated nonsurgically between January 2016 and April 2018 at Shinshu University Hospital were evaluated. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and the skeletal mass index (SMI) was calculated to classify the patients. RESULTS: The low-SMI group had a significantly worse overall survival (OS) than the normal-SMI group (3-year OS: 72.0% vs. 93.0%, p = 0.014), and there was a trend toward worse progression-free survival (PFS) in the low-SMI group (3-year PFS: 49.6% vs. 79.3%, p = 0.064). Multivariate analysis also showed that low SMI (p = 0.04) and severe N stage (p = 0.009) were significantly associated with poorer OS. CONCLUSION: The pretreatment assessment of SMI using bioelectrical impedance analysis is useful for identifying patients with poor prognoses. To improve the treatment outcome in HNC, we need to think of the intervention, such as cancer rehabilitation and nutritional support, during or before treatment, especially for patients with low SMI.

Bilateral delayed endolymphatic hydrops evaluated by bilateral intratympanic injection of gadodiamide with 3T-MRI.

The purpose of this study was to assess the diagnostic performance of 3T MRI after intratympanic injection of gadodiamide for delayed endolymphatic hydrops (DEH), and assess the relationship between endolymphatic hydrops (ELH) and vestibular function in patients diagnosed with DEH and confirmed by 3T MRI. Nineteen patients clinically diagnosed with DEH (11 ipsilateral DEH, 8 contralateral DEH) participated in this study. Diluted gadodiamide was administered to the bilateral tympanic cavity by injection through the tympanic membrane. At 24 hours post-injection, the ELH was evaluated by MRI. Patient vestibular functions were evaluated by caloric testing and cVEMP. ELH was observed in all patients (19/19: positive rate 100%). The distribution patterns of ELH varied between the cochlear or vestibular region. Vestibular ELH was observed in the affected ear in all ipsilateral DEH patients. In the contralateral DEH patients, however, there were individual differences in the distribution patterns of ELH. Six patients (1 ipsilateral DEH, 5 contralateral DEH) had bilateral ELH. No obvious relationships were observed between ELH and vestibular function. ELH distribution was complicated, particularly in the contralateral DEH cases. It was difficult to identify the existence of ELH by vestibular functional testing alone; therefore, 3T MRI is thought to be useful for identifying the affected ear. A significant number of cases had "bilateral" DEH, particularly among the contralateral DEH cases, indicating that we should pay careful attention to this pathology when treating DEH.

WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis.

A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA6/14/38 and Wolfram-like syndrome. Massively parallel DNA sequencing of 68 target genes was performed in 2,549 unrelated Japanese HL patients to identify genomic variations responsible for HL. The detailed clinical features in patients with WFS1 variants were collected from medical charts and analyzed. We successfully identified 13 WFS1 variants in 19 probands: eight of the 13 variants were previously reported mutations, including three mutations (p.A684V, p.K836N, and p.E864K) known to cause Wolfram-like syndrome, and five were novel mutations. Variants were detected in 15 probands (2.5%) in 602 families with presumably autosomal dominant or mitochondrial HL, and in four probands (0.7%) in 559 sporadic cases; however, no variants were detected in the other 1,388 probands with autosomal recessive or unknown family history. Among the 30 individuals possessing variants, marked variations were observed in the onset of HL as well as in the presence of progressive HL and tinnitus. Vestibular symptoms, which had been rarely reported, were present in 7 out of 30 (23%) of the affected individuals. The most prevalent audiometric configuration was low-frequency type; however, some individuals had high-frequency HL. Haplotype analysis in three mutations (p.A716T, p.K836T, and p.E864K) suggested that the mutations occurred at these mutation hot spots. The present study provided new insights into the audiovestibular phenotypes in patients with WFS1 mutations.

Recurrent Stroke and Bleeding Events after Acute Cardioembolic Stroke-Analysis Using Japanese Healthcare Database from Acute-Care Institutions.

BACKGROUND: To understand the reality of patients who experienced a cardioembolic stroke (CES) is important because of the high incidence of recurrent stroke and the need to account for bleeding risk in relation to the need for anticoagulation treatment. We elucidated the current real-world medical care in patients who had a CES and identified the risk factors for recurrent stroke. METHODS AND RESULTS: The study comprised 9804 patients who were diagnosed with CES between April 2008 and September 2013 as identified in a healthcare database used by acute-care institutions in Japan. We analyzed the incidence and risk factors of stroke and bleeding events in CES patients. The incidence of stroke was 10.3% during the median observation period of 68 days, mainly consisting of recurrent CES (8.5%). The incidence of bleeding events and intracranial bleeding was 10.3% and 7.0%, respectively. The recurrence of ischemic stroke was significantly lower, and brain hemorrhage was significantly higher in the anticoagulation treatment group. The factors related to an increased risk of stroke were a history of cerebral infarction or transient ischemic attack, diabetes, and increase of CHA2DS2-VASc and CHADS2 scores. The risk factors for bleeding events were hypertension, renal dysfunction, and use of proton pump inhibitors (PPIs). CONCLUSIONS: The patients who experienced CES had a high rate of recurrent stroke or CES, mainly consisting of recurrent CES. Although anticoagulation may be beneficial for reducing recurrence of ischemic stroke, careful management is required given consideration of increased risk of brain hemorrhage during anticoagulation treatment, especially for patients with hypertension, renal dysfunction, and use of PPIs.

Etiology of single-sided deafness and asymmetrical hearing loss.

CONCLUSIONS: The present study revealed that various etiologies are involved in single-sided deafness (SSD), and that the cause of SSD and asymmetrical hearing loss (AHL) differed greatly between congenital/early-onset cases and adult cases. Clarification of the etiology is the first step toward providing appropriate intervention. OBJECTIVES: The study aimed to clarify the etiology of SSD and AHL patients. METHODS: The etiology of a total of 527 SSD or AHL patients who visited Shinshu University Hospital between 2006 and 2016 were analyzed by imaging as well as serological tests for mumps virus, and CMV DNA testing. RESULTS: In our cohort of congenital/early-onset SSD (n = 210), the most prevalent cause in children was cochlear nerve deficiency (43.7%; 87 of 199 patients undergoing CT and/or MRI), followed by CMV infection, mumps infection, anomalies of the inner ear, ANSD, and other rare etiologies. In contrast, half of the adult SSD patients presented with idiopathic sensorineural hearing loss, followed by various types of otitis media, cerebellopontine angle tumor and other rare etiologies.

Incidence of venous thromboembolism and bleeding events in patients with lower extremity orthopedic surgery: a retrospective analysis of a Japanese healthcare database.

BACKGROUND: Orthopedic surgeries of lower extremities such as total knee arthroplasty (TKA), total hip arthroplasty (THA), and hip fracture surgery (HFS) are widely considered to carry a high risk of developing deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE). Growing attention to epidemiological studies using a healthcare database led us to quantify the risks using a Japanese database to reveal recent medical care for such events. METHODS: The study comprised 36,947 patients who had undergone orthopedic surgeries of the lower extremities and whose medical information from April 2008 to September 2013 was available. The source population of the database was derived from 100 acute-care hospitals with Diagnosis Procedure Combination. The events were defined by diagnosis, medication, imaging, and laboratory tests. RESULTS: A breakdown of patients who underwent orthopedic surgeries by type of surgery showed 13.6% for TKA, 10.4% for THA, 56.8% for HFS, 1.5% for rupture of Achilles tendon, and 18.0% for simple fracture of lower extremities. The incidence for DVT, PTE, and bleeding events by type of surgery was 1.3, 0.2, and 1.0% for TKA; 0.9, 0.2, and 1.1% for THA; and 0.4, 0.1, and 1.8% for HFS, respectively. The population for risk factor analysis consisted of patients with similar background factors who underwent TKA, THA, or HFS. The statistically significant risk factors for PTE analyzed by the backward elimination procedure in a multivariate model were female sex, history of venous thromboembolism (VTE), thrombophilia, and varicose veins of lower extremity. CONCLUSIONS: The incidence of DVT, PTE, and bleeding events and the risk factors for DVT and PTE in patients by type of orthopedic surgeries of lower extremities found in our study are considered to be rational as they reflect evidence from real-world cases. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000012667.

Predictors of venous thromboembolism recurrence and the bleeding events identified using a Japanese healthcare database.

BACKGROUND: Treatment to prevent the recurrence of venous thromboembolism (VTE) and prevent bleeding events should be given to patients with VTE in an appropriate balance in relation to relevant predictors. We elucidated the current medical care in a real world setting and quantified predictors using a Japanese healthcare database. METHODS: The study included 3578 patients who were diagnosed with VTE between April 2008 and September 2013 at a Japanese acute-care hospital and included in the hospital database. Twenty-four patients who had a VTE event during the 180-day period after enrollment were excluded. We analyzed the incidence of recurrent VTE, incidence of bleeding events, and predictors in VTE patients. Events were defined by disease, medication, imaging, and laboratory testing, among other factors. RESULTS: The rate of recurrence of VTE events was 7.2 per 100 patient-years. The incidence rate of bleeding events was 8.3 per 100 patient-years. The presence of malignant disease, antipsychotic drugs, and nonsteroidal anti-inflammatory drugs increased the risk for recurrent VTE. The predictors for bleeding events were malignant disease, central venous catheterization, cancer chemotherapy, stroke, and diabetes. CONCLUSIONS: These findings obtained from healthcare database suggest predictors either for recurrent VTE and bleeding that should be considered when selecting treatment to reduce the risk of recurrent VTE and mitigate bleeding.

Usefulness of a healthcare database for epidemiological research in atrial fibrillation.

BACKGROUND: Big data are gaining attention as a valuable resource for providing insights into a range of issues and questions in healthcare. We evaluated the capacity of a Japanese healthcare database to conduct epidemiological research in non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: We examined data collected between April 2008 and September 2013 in a Japanese healthcare database. Prior to the risk factor analysis, we validated the criteria for defining the occurrence of a stroke, systemic embolic event (SEE), and intracranial bleeding event during the study period. The validity was considered appropriate based on the resulting high positive predictive values. The data of 18,998 NVAF patients demonstrated that the incidence rates of stroke, SEE, and any bleeding events were 2.2, 0.08, and 2.4 per 100 patient-years, respectively. In patients who had not been treated with an anticoagulant, incidence of stroke significantly increased in higher CHADS2 or CHA2DS2-VASc score, 1.7 and 1.5 fold by 1 point increase, respectively. The use of a proton pump inhibitor (PPI) was also identified as an independent risk factor for stroke. In patients who had been treated with an anticoagulant, the independent risk factors for any bleeding events were hypertension, renal dysfunction, hepatic failure, medical history of stroke, older age (≥65 years), use of nonsteroidal anti-inflammatory drug, and PPIs. CONCLUSION: The data obtained in this study were comparable with results obtained in prospective cohort studies conducted in Japan.

Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompanied by macrophage-activation syndrome.

We report a 57-year-old female case of intractable adult-onset Still's disease (AOSD). Initial high-dose prednisolone therapy was ineffective, and macrophage-activation syndrome (MAS) manifested after one session of additional tocilizumab therapy. After successful treatment for MAS with lipo-dexamethasone and cyclosporin, tocilizumab therapy aided in the rapid reduction of the therapeutic steroid dose. Tocilizumab may be useful for maintenance therapy for AOSD, although its efficacy is unclear for the highly active phase of the disease.

Carcinosarcomatous malignancy, osteosarcoma and squamous cell carcinoma, in giant cell tumor of the right distal femur.

We report a new type of secondary malignant giant cell tumor of bone, the malignancy of which was assigned to a carcinosarcoma, i.e., osteosarcoma and squamous cell carcinoma. It occurred 25 years after curettage and bone graft surgery under the diagnosis of giant cell tumor of the right distal femur. Although secondary malignant giant cell tumor is known as a sarcoma arising at the site of a previously diagnosed giant cell tumor, this case should be regarded as a new type of secondary malignant giant cell tumor of bone.

Perfluoropentacene: high-performance p-n junctions and complementary circuits with pentacene.

We report the synthesis and characterization of perfluoropentacene as an n-type semiconductor for organic field-effect transistors (OFETs). Perfluoropentacene is a planar and crystalline material that adopts a herringbone structure as observed for pentacene. OFETs with perfluoropentacene were constructed using top-contact geometry, and an electron mobility of 0.11 cm2 V-1 s-1 was observed. Bipolar OFETs with perfluoropentacene and pentacene function at both negative and positive gate voltages. The improved p-n junctions are probably due to the similar d-spacings of both acenes. Complementary inverter circuits were fabricated, and the transfer characteristics exhibit a sharp inversion of the output signal with a high-voltage gain.

Mean corpuscular volume (MCV) and the risk of colorectal adenoma in menopausal women.

BACKGROUND/AIMS: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume is increased under these conditions. We have reported that the mean corpuscular volume was higher in patients with adenoma than without adenoma in middle-aged men. The aim of this study was to assess the association between mean corpuscular volume and risk of colorectal adenoma in menopausal women. METHODOLOGY: The subjects were 415 menopausal women who underwent both barium enema examination and total colonoscopy, and their blood samples were analyzed. The subjects were divided into two groups with or without adenoma, and were divided into four groups according to the mean corpuscular volume value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The mean corpuscular volume was higher in patients with adenoma than without adenoma (P = 0.002). As for the mean corpuscular volume value, the odds ratio (95% CI) of patients with adenoma was 1.00 (referent); (mean corpuscular volume (fl) < 90), 1.50 (0.93-2.07); (> or = 90 but < 92.5), 1.52 (0.97-2.07); (> or = 92.5 but < 95) and 2.87 (2.25-3.45); (> or = 95). CONCLUSIONS: Mean corpuscular volume > or = 95 may be used as an index of the risk for colorectal adenomas in menopausal women.

[Long-term efficacy of transjugular intrahepatic portosystemic shunt for the treatment of refractory ascites].

Eighteen patients with refractory ascites (Child-Pugh score 9.9) defined by our criteria were treated with transjugular intrahepatic portosystemic shunt (TIPS). The long-term efficacy of the treatment was studied in these patients. The complete and partial response rate of refractory ascites was 73% at 6 months, 90% at 1 year and 100% at 2 years. The cumulative survival rate was 89% at 6 months, 78% at 1 year and 48% at 2 years. A statistically significant(p < 0.05) increase was observed in performance status score following TIPS: Mean performance status score prior to TIPS was 43%, as opposed to 62% at 3 months after TIPS and 85% at 2 years. Child-Pugh score and liver function tests showed no significant change. During follow-up, shunt stenosis was noted in 14 patients, requiring shunt revision. Ascites recurrence was observed in 70% of patients with shunt stenosis and shunt revision resulted in good control of ascites. Post-TIPS encephalopathy was seen in 15 patients during follow-up. In conclusion, TIPS is effective on the treatment of refractory ascites and results in an improvement in quality of life. TIPS also may improve survival of the patients with refractory ascites. However, shunt stenosis and encephalopathy are common and require careful follow-up and adequate treatment.

Chylomicronemia caused by lipoprotein lipase gene mutation related to a hyper-response of insulin secretion to glucose.

A 39-year-old man with lipoprotein lipase (LPL) deficiency (height 177.7 cm, body weight 67 kg, and body mass index 21.2 kg/m2) showed severe hypertriglyceridemia (2,032 mg/dl). LPL activity and concentration were markedly low in postheparin plasma. LPL gene analysis revealed a homozygous mutation, Asp204 --> Glu in exon 5. Fasting plasma glucose (81 mg/dl) and insulin (2.7 microU/ml) levels were normal. Plasma glucose pattern during oral glucose (75 g) tolerance test was normal, however 30 minutes after glucose-loading the insulin secretion unexpectedly increased to 89.4 microU/ml. These data suggested that chylomicronemia might be related to a hyper-response of insulin secretion to glucose without obesity.

Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice.

BACKGROUND: Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subsequently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice. METHODS: Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8h. Mice were administered 95% ethanol 24h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined. RESULTS: Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment. CONCLUSIONS: Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant.

A randomized clinical trial comparing transjugular intrahepatic portosystemic shunt with endoscopic sclerotherapy in the long-term management of patients with cirrhosis after recent variceal hemorrhage.

The aim of this study was to compare the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with that of endoscopic sclerotherapy (ES) in the long-term management of patients with cirrhosis after variceal bleeding. Seventy-eight consecutive cirrhotic patients with recent variceal bleeding were randomly allocated to either TIPS (n=38) or ES (n=40). All patients were in good condition at randomization. The mean follow-up was 1116+/-92 days in the TIPS group and 1047+/-102 days in the ES group. Differences in rebleeding from any source (18.4% vs. 32.5%) and esophageal variceal rebleeding (15.7% vs. 27.5%) were not significantly different between the two groups (P>0.05). The mortality rates were similar in both treatment groups. Shunt dysfunction was noted in 27 patients (71%) in the TIPS group. There were more numbers of rehospitalization during follow-up in the TIPS group than in the ES group (2.6+/-0.4 vs. 1.1+/-0.2) (P<0.01). TIPS and ES are equally effective in the prevention of variceal rebleeding. However, TIPS is associated with high incidence of shunt dysfunction, which lead to more rehospitalization. Therefore, TIPS may not be a first-line treatment for the prevention of variceal rebleeding in cirrhotic patients who are in stable condition.