High spatial-density, cladding-pumped 6-mode 7-core fiber amplifier for C-band operation.

We present a C-band 6-mode 7-core fiber amplifier in an all-fiberized cladding-pumped configuration for space division multiplexed transmission supporting a record 42 spatial channels. With optimized fiber components (e.g. passively cooled pump laser diode, pump coupler, pump stripper), high power multimode pump light is coupled to the active fiber without any noticeable thermal degradation and an average gain of 18 dB and noise figure of 5.4 dB are obtained with an average differential modal gain of 3.4 dB.

Regulation of Activating Transcription Factor 4 (ATF4) Expression by Fat Mass and Obesity-Associated (FTO) in Mouse Hepatocyte Cells.

CONTEXT: Abnormally increased hepatic glucose production contributes to hyperglycemia in diabetes. Interventions that suppress hepatic gluconeogenesis should be beneficial in improving glycemic control in patients with diabetes. OBJECTIVES: It has been suggested that hepatic FTO is involved in glycemic control by regulating gluconeogenesis. Both FTO and activating transcription factor 4 (ATF4) positively regulate the expression of gluconeogenic genes in the liver, suggesting the possibility that ATF4 mediates the stimulatory effect of FTO on hepatic gluconeogenesis. The present study aimed to determine the effect of altered expression or activity of FTO on Atf4 and gluconeogenic gene expression in hepatocyte cells. METHODS: Mouse hepatocyte AML12 cells were treated with the FTO inhibitor rhein or transfected with an FTO-expressing plasmid. Levels of gluconeogenic glucose-6-phosphatase (G6pc) and Atf4 mRNA and protein were measured. RESULTS: Rhein treatment significantly reduced G6pc mRNA levels as well as Atf4 mRNA and protein levels. Conversely, enhanced FTO expression caused an increase in G6pc and Atf4 mRNA levels. CONCLUSIONS: These findings support the hypothesis that hepatic FTO participates in the regulation of hepatic gluconeogenic gene and ATF4 expression. Reducing the activity of the hepatic FTO-ATF4 pathway may be beneficial in reducing hepatic glucose production and ameliorating hyperglycemia in diabetes.

Performance of a modified three-level classification in stratifying open liver resection procedures in terms of complexity and postoperative morbidity.

BACKGROUND: Traditional classifications for open liver resection are not always associated with surgical complexity and postoperative morbidity. The aim of this study was to test whether a three-level classification for stratifying surgical complexity based on surgical and postoperative outcomes, originally devised for laparoscopic liver resection, is superior to classifications based on a previously reported survey for stratifying surgical complexity of open liver resections, minor/major nomenclature or number of resected segments. METHODS: Patients undergoing a first open liver resection without simultaneous procedures at MD Anderson Cancer Center (Houston cohort) or the University of Tokyo (Tokyo cohort) were studied. Surgical and postoperative outcomes were compared among three grades: I (wedge resection for anterolateral or posterosuperior segment and left lateral sectionectomy); II (anterolateral segmentectomy and left hepatectomy); III (posterosuperior segmentectomy, right posterior sectionectomy, right hepatectomy, central hepatectomy and extended left/right hepatectomy). RESULTS: In both the Houston (1878 patients) and Tokyo (1202) cohorts, duration of operation, estimated blood loss and comprehensive complication index score differed between the three grades (all P < 0·050) and increased in stepwise fashion from grades I to III (all P < 0·001). Left hepatectomy was associated with better surgical and postoperative outcomes than right hepatectomy, extended right hepatectomy and right posterior sectionectomy, although these four procedures were categorized as being of medium complexity in the survey-based classification. Surgical outcomes of minor open liver resections also differed between the three grades (all P < 0·050). For duration of operation and blood loss, the area under the curve was higher for the three-level classification than for the minor/major or segment-based classification. CONCLUSION: The three-level classification may be useful in studies analysing open liver resection at Western and Eastern centres.

ANTECEDENTES: Las clasificaciones tradicionales de la resección hepática abierta (open liver resection, OLR) por número de segmentos resecados, no siempre se asocian con la complejidad quirúrgica y la morbilidad postoperatoria. El objetivo de este estudio fue comprobar si una clasificación de 3 niveles para estratificar la complejidad quirúrgica en función de los resultados quirúrgicos y postoperatorios, ideada originalmente para la resección hepática laparoscópica, es superior a las clasificaciones basadas en una encuesta descrita previamente para estratificar la complejidad quirúrgica de los procedimientos de OLR, nomenclatura menor/mayor, o número de segmentos resecados. MÉTODOS: Se estudiaron pacientes sometidos a una primera OLR sin otros procedimientos quirúrgicos concomitantes en el hospital MD Anderson (cohorte de Houston) o en la Universidad de Tokio (cohorte de Tokio). Se compararon los resultados quirúrgicos y postoperatorios entre 3 grados: I (resección limitada para el segmento anterolateral o posterosuperior y seccionectomía izquierda); II (segmentectomía anterolateral y hepatectomía izquierda); III (segmentectomía posterosuperior, seccionectomía posterior derecha, hepatectomía derecha, hepatectomía central y hepatectomía ampliada izquierda/derecha). RESULTADOS: En ambas cohortes de Houston (n = 1.878) y Tokio (n = 1.202), el tiempo operatorio, las pérdidas estimadas de sangre, y el índice de complejidad integral (comprehensive complication index) variaba en los 3 grados (todos P < 0,05) y aumentaba paso a paso desde los grados I a III (todos P < 0,05). La hepatectomía izquierda se asociaba con mejores resultados quirúrgicos y postoperatorios que la hepatectomía derecha, hepatectomía derecha ampliada, y seccionectomía posterior derecha, aunque estos cuatro procedimientos fueron categorizados como de complejidad intermedia en la clasificación basada en la encuesta. Los resultados quirúrgicos de las OLRs menores también variaron en los 3 grados (todos P < 0,05). Para el tiempo operatorio y la pérdida sanguínea, el área bajo la curva fue mayor para la clasificación de 3 niveles en el estudio actual, que para la clasificación menor/mayor o la clasificación basada en los segmentos. CONCLUSIÓN: La clasificación en 3 niveles puede ser útil en estudios que analizan las resecciones hepáticas abiertas en centros occidentales y orientales.

Proposal for a new classification for perihilar cholangiocarcinoma based on tumour depth.

BACKGROUND: The T system for distal cholangiocarcinoma has been revised from a layer-based to a depth-based approach in the current American Joint Committee on Cancer (AJCC) classification. In perihilar cholangiocarcinoma, tumour depth in the staging scheme has not yet been addressed. The aim of this study was to propose a new T system using measured tumour depth in perihilar cholangiocarcinoma. METHODS: Patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2001 and 2014 were reviewed retrospectively. The vertical distance between the top of the tumour and deepest invasive cells was measured as invasive tumour thickness (ITT) by two independent pathologists. Log rank statistics were used to determine cut-off points, and the concordance (C) index was used to assess survival discrimination of each T system. RESULTS: ITT was measurable in all 440 patients, with a median value of 6·0 (range 0-45) mm. The median difference in ITT between observers was 0·6 (range 0-20) mm. Cut-off points for prognosis were 1, 5 and 8 mm. Five-year survival decreased with increasing ITT (P < 0·001): 67 per cent for ITT less than 1 mm (25 patients), 54·9 per cent for ITT 1 mm and over to less than 5 mm (138 patients), 43·4 per cent for ITT 5 mm and over to less than 8 mm (118 patients), and 32·2 per cent for ITT 8 mm and over (159 patients). The C-index of this classification was comparable to that of the current AJCC T classification (0·598 versus 0·589). CONCLUSION: ITT is a reliable approach for making a depth assessment in perihilar cholangiocarcinoma. A four-tier ITT classification with cut-off points of 1, 5 and 8 mm is an adequate alternative to the current layer-based T classification.

Clinical value of additional resection of a margin-positive distal bile duct in perihilar cholangiocarcinoma.

BACKGROUND: Little is known about the effect of additional resection for a frozen-section-positive distal bile duct margin (DM) in perihilar cholangiocarcinoma. METHODS: Patients who underwent surgical resection for perihilar cholangiocarcinoma between 2001 and 2015 were analysed retrospectively, focusing on the DM. RESULTS: Of 558 consecutive patients who underwent frozen-section examination for a DM, 74 (13·3 per cent) had a frozen-section-positive DM with invasive cancer or carcinoma in situ. Eventually, 53 patients underwent additional resection (bile duct resection in 44 and pancreatoduodenectomy in 9), whereas the remaining 21 patients did not. Ultimately, R0 resection was achieved in 30 of the 53 patients (57 per cent). No patient who underwent additional resection died from surgical complications. The 44 patients with additional bile duct resection had a 5-year overall survival rate of 31 per cent. Overall survival of the nine patients who had pancreatoduodenectomy was better, with a 10-year rate of 67 per cent. Survival of the 21 patients without additional resection was dismal: all died within 5 years. Multivariable analyses identified nodal status and additional resection as independent prognostic factors (lymph node metastasis: hazard ratio (HR) 2·26, 95 per cent c.i. 1·26 to 4·07; bile duct resection versus no additional resection: HR 0·32, 0·17 to 0·60; pancreatoduodenectomy versus no additional resection: HR 0·08, 0·02 to 0·29). CONCLUSION: Additional resection for frozen-section-positive DM in perihilar cholangiocarcinoma frequently yields R0 margins. It offers a better chance of long-term survival, and thus should be performed in carefully selected patients.

Benign hilar bile duct strictures resected as perihilar cholangiocarcinoma.

BACKGROUND: Differentiation between perihilar cholangiocarcinoma (PHCC) and benign strictures is frequently difficult. The aim of this study was to investigate the incidence and long-term outcome of patients with tumours resected because of suspicion of PHCC, which ultimately turned out to be benign (malignancy masquerade). METHODS: Patients who underwent surgical resection with a diagnosis of PHCC between 2001 and 2016 were reviewed retrospectively. RESULTS: Among 707 consecutive patients, 685 had PHCC and the remaining 22 (3·1 per cent) had benign biliary stricture. All patients with benign disease underwent major hepatectomy, with no deaths. Preoperative histological assessment using bile duct biopsy or aspiration cytology had a high specificity (90 per cent), low sensitivity (62 per cent) and unsatisfactory accuracy (63 per cent). Despite the increasing use of histological assessment, the incidence of benign strictures resected did not decrease over time, being 0·9 per cent in 2001-2004, 4·0 per cent in 2005-2008, 3·8 per cent in 2009-2012 and 2·9 per cent in 2013-2016. The final pathology of benign strictures included IgG4-related sclerosing cholangitis (9 patients), hepatolithiasis (4), granulomatous cholangitis (3), non-specific chronic cholangitis (3), benign strictures after cholecystectomy (2), and a benign stricture possibly caused by parasitic infection (1). The 10-year overall survival rate for the 22 patients with benign stricture was 87 per cent, without recurrence of biliary stricture. CONCLUSION: The incidence of benign strictures resected as PHCC as a proportion of all resections was relatively low, at 3·1 per cent. Currently, unnecessary surgery for suspected PHCC is unavoidable.

ANTECEDENTES: La diferenciación entre colangiocarcinoma perihilar (perihilar colangiocarcinoma, PHCC) y estenosis benignas es con frecuencia difícil. El objetivo de este estudio fue investigar la incidencia y el resultado a largo plazo de los tumores resecados con sospecha diagnóstica de PHCC, que finalmente resultaron ser benignos (malignidad enmascarada). MÉTODOS: Se revisaron retrospectivamente los pacientes con diagnóstico de PHCC que se sometieron a resección quirúrgica entre 2001 y 2016. RESULTADOS: Entre 707 pacientes consecutivos, 685 pacientes presentaban PHCC y los 22 restantes (3,1%) tenían una estenosis biliar benigna. Todos los pacientes con patología benigna se sometieron a una hepatectomía mayor, sin mortalidad. La evaluación histológica preoperatoria mediante biopsia de conducto biliar o citología por aspiración tuvo una alta especificidad (90%), una baja sensibilidad (62%) y una exactitud diagnóstica insatisfactoria (63%). A pesar del uso creciente de la evaluación histológica, la incidencia de estenosis benignas resecadas no disminuyó con el tiempo, con un 0,9% en 2001-2004, un 4,0% en 2005-2008, un 3,8% en 2009-2012 y un 2,9% en 2013-2016. La patología final de las estenosis benignas incluyó colangitis esclerosante relacionada con IgG4 (n = 9), hepatolitiasis (n = 4), colangitis granulomatosa (n = 3), colangitis crónica no específica (n = 3), estenosis benignas tras una colecistectomía (n = 2) y una estenosis benigna posiblemente causada por una infección parasitaria (n = 1). Los resultados a largo plazo de los 22 pacientes con estenosis benigna fueron mejores (tasa de supervivencia a 10 años; 87,4%) sin recidiva de la estenosis biliar. CONCLUSIÓN: La incidencia de pacientes con estenosis benignas resecadas como PHCC en comparación con todas las resecciones fue relativamente baja, del 3,1%. Actualmente, la cirugía "innecesaria" por sospecha de PHCC es inevitable.

Major hepatectomy with or without pancreatoduodenectomy for advanced gallbladder cancer.

BACKGROUND: The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. METHODS: Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). RESULTS: Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P = 0·015) and periaortic nodal metastasis (P = 0·006), but were less likely to receive adjuvant therapy (P = 0·006). HPD was associated with a high incidence of grade III or higher complications (P = 0·002) and death (P = 0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996-2006) (P = 0·002), pathological T4 disease (P = 0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P = 0·002) with longer overall survival. CONCLUSION: Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint.

Surgical resection for Bismuth type IV perihilar cholangiocarcinoma.

BACKGROUND: Bismuth type IV perihilar cholangiocarcinoma has traditionally been categorized as unresectable disease. The aim of this study was to review experience with a resection-based strategy in patients who have type IV perihilar cholangiocarcinoma. METHODS: Medical records of consecutive patients with a diagnosis of type IV perihilar cholangiocarcinoma between 2006 and 2015 were reviewed retrospectively. Primary outcomes assessed were surgical results and long-term survival. RESULTS: Of the 332 patients with type IV tumour, 216 (65·1 per cent) underwent resection. Left hepatic trisectionectomy was the most common procedure (112 patients). Combined vascular resection was performed in 131 patients. Median duration of operation was 607 (range 356-1045) min, and blood loss was 1357 (209-10 349) ml. Complications of Clavien-Dindo grade III or more developed in 90 patients (41·7 per cent) and four (1·9 per cent) died from complications within 90 days. Survival rates were better for the 216 patients whose tumours were resected than for the 116 patients with unresected tumours (32·8 versus 1·5 per cent at 5 years; P < 0·001). Patients with pN0 M0 disease after resection had a favourable 5-year survival rate of 53 per cent. Percutaneous transhepatic biliary drainage, blood transfusion, lymph node metastasis and distant metastasis were identified as independent negative prognostic factors for survival. CONCLUSION: Although resection for type IV tumour is technically demanding with high morbidity, it can be performed with low mortality and offers better survival probability in selected patients.

Ethanol ablation for refractory bile leakage after complex hepatectomy.

BACKGROUND: Only a few reports exist on the use of ethanol ablation for posthepatectomy bile leakage. The aim of this study was to assess the value of ethanol ablation in refractory bile leakage. METHODS: Medical records of consecutive patients who underwent a first hepatobiliary resection with bilioenteric anastomosis between 2007 and 2016 were reviewed retrospectively, with special attention to bile leakage and ethanol ablation therapy. Bile leakage was graded as A/B1/B2 according to the International Study Group of Liver Surgery definition. Absolute ethanol was injected into the target bile duct during fistulography. RESULTS: Of the 609 study patients, 237 (38·9 per cent) had bile leakage, including grade A in 33, grade B1 in 18 and grade B2 in 186. Left trisectionectomy was more often associated with grade B2 bile leakage than other types of hepatectomy (P < 0·001). Of 186 patients with grade B2 bile leakage, 31 underwent ethanol ablation therapy. Ethanol ablation was started a median of 34 (range 15-122) days after hepatectomy. The median number of treatments was 3 (1-7), and the total amount of ethanol used was 15 (3-71) ml. Complications related to ethanol ablation included transient fever (27 patients) and mild pain (13). Following ethanol ablation, bile leakage resolved in all patients and drains were removed. The median interval between the first ablation and drain removal was 28 (1-154) days. CONCLUSION: Ethanol ablation is safe and effective, and may be a treatment option for refractory bile leakage.

Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases.

BACKGROUND: Although perihepatic lymph node metastases (PLNMs) are known to be a poor prognosticator for patients with colorectal liver metastases (CRLMs), optimal management remains unclear. This study aimed to determine the risk factors for PLNMs, and the survival impact of their number and location in patients with resectable CRLMs. METHODS: Data on patients with CRLM who underwent hepatectomy during 2003-2014 were analysed retrospectively. Recurrence-free (RFS) and overall (OS) survival were calculated according to presence, number and location of PLNMs. Risk factors for PLNM were evaluated by logistic regression analysis. RESULTS: Of 1485 patients, 174 underwent lymphadenectomy, and 54 (31·0 per cent) had PLNM. Ten patients (5·7 per cent) who had lymphadenectomy and 176 (13·4 per cent) who did not underwent repeat hepatectomy. Survival of patients with PLNM was significantly poorer than that of patients without (RFS: 5·3 versus 13·8 months, P < 0·001; OS: 20·5 versus 71·3 months; P < 0·001). Median OS was significantly better in patients with para-aortic versus hepatoduodenal ligament PLNMs (58·2 versus 15·5 months; P = 0·011). Patients with three or more PLNMs had significantly worse median OS than those with one or two (16·3 versus 25·4 months; P = 0·039). The presence of primary tumour lymph node metastases (odds ratio 2·35; P = 0·037) and intrahepatic recurrence requiring repeat hepatectomy (odds ratio 5·61; P = 0·012) were significant risk factors for PLNM on multivariable analysis. CONCLUSION: Patients undergoing repeat hepatectomy and those with primary tumour lymph node metastases are at significant risk of PLNM. Although PLNM is a poor prognostic factor independent of perihepatic lymph node station, patients with one or two PLNMs have a more favourable outcome than those with more PLNMs.

Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation.

BACKGROUND AND PURPOSE: To establish and validate diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony-stimulating factor 1 receptor (CSF1R) mutation. METHODS: We developed diagnostic criteria for ALSP based on a recent analysis of the clinical characteristics of ALSP. These criteria provide 'probable' and 'possible' designations for patients who do not have a genetic diagnosis. To verify its sensitivity and specificity, we retrospectively applied our criteria to 83 ALSP cases who had CSF1R mutations (24 of these were analyzed at our institutions and the others were identified from the literature), 53 cases who had CSF1R mutation-negative leukoencephalopathies and 32 cases who had cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with NOTCH3 mutations. RESULTS: Among the CSF1R mutation-positive cases, 50 cases (60%) were diagnosed as 'probable' and 32 (39%) were diagnosed as 'possible,' leading to a sensitivity of 99% if calculated as a ratio of the combined number of cases who fulfilled 'probable' or 'possible' to the total number of cases. With regard to specificity, 22 cases (42%) with mutation-negative leukoencephalopathies and 28 (88%) with CADASIL were correctly excluded using these criteria. CONCLUSIONS: These diagnostic criteria are very sensitive for diagnosing ALSP with sufficient specificity for differentiation from CADASIL and moderate specificity for other leukoencephalopathies. Our results suggest that these criteria are useful for the clinical diagnosis of ALSP.

ABCC3 genetic variants are associated with postoperative morphine-induced respiratory depression and morphine pharmacokinetics in children.

Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux) affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1.28-4.37, P=0.0061) and 3.7 (95% CI 1.47-9.09, P=0.0050) times increase in odds of prolonged RD, respectively. These clinical associations were supported by increased formation clearance of morphine glucuronides in children with rs4148412 AA and rs4973665 CC genotypes in this cohort, as well as an independent spine surgical cohort of 67 adolescents. This is the first study to report association of ABCC3 variants with opioid-related RD, and morphine metabolite formation (in two independent surgical cohorts).

Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation.

BACKGROUND AND PURPOSE: The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. METHODS: Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation sheet to standardize the data. RESULTS: In all, 122 cases from 90 families with CSF1R mutations were identified. The mean age of onset was 43 years (range 18-78 years), the mean age at death was 53 years (range 23-84 years) and the mean disease duration was 6.8 years (range 1-29 years). Women had a significantly younger age of onset than men (40 vs. 47 years, P = 0.0006, 95% confidence interval 3.158-11.177). There was an age-dependent penetrance that was significantly different between the sexes (P = 0.0013). Motor dysfunctions were the most frequent initial symptom in women whose diseases began in their 20s. Thinning of the corpus callosum, abnormal signalling in pyramidal tracts, diffusion-restricted lesions and calcifications in the white matter were characteristic imaging findings of ALSP. The calcifications were more frequently reported in our case series than in the literature (54% vs. 3%). Seventy-nine per cent of the mutations were located in the distal part of the tyrosine kinase domain of CSF1R (102 cases). There were no apparent phenotype-genotype correlations. CONCLUSIONS: The characteristics of ALSP were clarified. The phenotype of ALSP caused by CSF1R mutations is affected by sex.

Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma.

BACKGROUND: Several gene variants identified in bronchial asthmatic patients are associated with a decrease in pulmonary function. The effects of this intervention on pulmonary function have not been fully researched. OBJECTIVE: We determined the effects of high-dose inhaled corticosteroids (ICSs) on decreased pulmonary function in asthmatic Japanese patients with variants of IL13 and STAT4 during long-term treatments with low to mild doses of ICS. METHODS: In this study, 411 patients with bronchial asthma who were receiving ICSs and living in Japan were recruited, were genotyped, and underwent pulmonary function tests and fibreoptic examinations. The effects of 2 years of high-dose ICSs administered to asthmatic patients who were homozygous for IL13 AA of rs20541 or STAT4 TT of rs925847 and who progressed to airway remodelling were investigated. RESULTS: High-dose ICS treatment increased the pulmonary function of patients homozygous for IL13 AA of rs20541 but not of patients homozygous for STAT4 TT of rs925847. The increased concentrations of the mediators IL23, IL11, GMCSF, hyaluronic acid, IL24, and CCL8 in bronchial lavage fluid (BLF) were diminished after high-dose ICS treatment in patients homozygous for IL13 AA of rs20541. CONCLUSION AND CLINICAL RELEVANCE: IL13 AA of rs20541 and STAT4 TT of rs925847 are potential genomic biomarkers for predicting lower pulmonary function. The administration of high-dose ICSs to asthmatic patients with genetic variants of IL13 AA may inhibit the advancement of airway remodelling. The genetic variants of STAT4 TT did not respond to high-dose ICSs. Therefore, using medications other than ICSs must be considered even during the initial treatment of bronchial asthma. These genetic variants may aid in the realization of personalized and phenotype-specific therapies for bronchial asthma.

Dynamic Stretching does not Change the Stiffness of the Muscle-Tendon Unit.

The purpose of this study was to identify changes in ankle range of motion and passive mechanical properties of the muscle-tendon unit after dynamic stretching. 12 healthy subjects participated in this study. Displacement of the muscle-tendon junction was measured using ultrasonography while the ankle was passively dorsiflexed at 1°/sec to its maximal dorsiflexion angle. Passive torque was also measured using an isokinetic dynamometer. Measurements were conducted pre-intervention, immediately after the intervention and 5, 10, 15 and 30 min post-intervention. The dynamic stretching consisted of four 30-s periods of ankle dorsiflexion and plantarflexion. Ankle range of motion was significantly increased immediately (from 18.3±1.8° to 21.4±1.7°) and 10 min (20.9±1.9°) after dynamic stretching, but this change disappeared within 15 min. However, stiffness of the muscle-tendon unit and displacement of the muscle-tendon junction at the submaximal dorsiflexion angle did not differ between the experimental conditions. These results demonstrate that dynamic stretching by contracting an antagonist muscle group increases ankle range of motion temporarily without changing the passive mechanical properties of the muscle-tendon unit. The increased range of motion of the ankle after dynamic stretching might be caused by enhanced stretch tolerance.

Impact of bacterial contamination of the abdominal cavity during pancreaticoduodenectomy on surgical-site infection.

BACKGROUND: Several risk factors for complications after pancreaticoduodenectomy have been reported. However, the impact of intraoperative bacterial contamination on surgical outcome after pancreaticoduodenectomy has not been examined in depth. METHODS: This retrospective study included patients who underwent pancreaticoduodenectomy and peritoneal lavage using 7000 ml saline between July 2012 and May 2014. The lavage fluid was subjected to bacterial culture examination. The influence of a positive bacterial culture on surgical-site infection (SSI) and postoperative course was evaluated. Risk factors for positive bacterial cultures were also evaluated. RESULTS: Forty-six (21.1 per cent) of 218 enrolled patients had a positive bacterial culture of the lavage fluid. Incisional SSI developed in 26 (57 per cent) of these 46 patients and in 13 (7.6 per cent) of 172 patients with a negative lavage culture (P < 0.001). Organ/space SSI developed in 32 patients with a positive lavage culture (70 per cent) and in 43 of those with a negative culture (25.0 per cent) (P < 0.001). Grade B/C pancreatic fistula was observed in 22 (48 per cent) and 48 (27.9 per cent) respectively of patients with positive and negative lavage cultures (P = 0.010). Postoperative hospital stay was longer in patients with a positive lavage culture (28 days versus 21 days in patients with a negative culture; P = 0.028). Multivariable analysis revealed that internal biliary drainage, combined colectomy and a longer duration of surgery were significant risk factors for positive bacterial culture of the lavage fluid. CONCLUSION: Intraoperative bacterial contamination has an adverse impact on the development of SSI and grade B/C pancreatic fistula following pancreaticoduodenectomy.

Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

OBJECTIVE: In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. METHODS: Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. RESULTS: High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. CONCLUSIONS: ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.

Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds in humans.

OBJECTIVE: Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. MATERIAL AND METHODS: One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. RESULTS: Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. CONCLUSIONS: The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders.

Off-resonance photoemission dynamics studied by recoil frame F1s and C1s photoelectron angular distributions of CH3F.

F1s and C1s photoelectron angular distributions are considered for CH3F, a molecule which does not support any shape resonance. In spite of the absence of features in the photoionization cross section profile, the recoil frame photoelectron angular distributions (RFPADs) exhibits dramatic changes depending on both the photoelectron energy and polarization geometry. Time-dependent density functional theory calculations are also given to rationalize the photoionization dynamics. The RFPADs have been compared with the theoretical calculations, in order to assess the accuracy of the theoretical method and rationalize the experimental findings. The effect of finite acceptance angles for both ionic fragments and photoelectrons has been included in the calculations, as well as the effect of rotational averaging around the fragmentation axis. Excellent agreement between theory and experiment is obtained, confirming the good quality of the calculated dynamical quantities (dipole moments and phase shifts).