Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Influence of 12 weeks of basketball training on college students' heart function.

OBJECTIVE: This study aims to investigate the influence of 12 weeks of basketball training on college students' heart function. SUBJECTS AND METHODS: The subjects were 30 college male basketball players. Carry out 8-week interval training, monitor the training load and interval time of athletes, and strictly control the heart rate during the interval. Before and after training, we used safe and effective experimental instruments - without any damage to the athletes - to detect the relevant indicators of the athletes' physiological functions; hence we compared and analyzed the various indicators before and after training. RESULTS: The time domain indexes Root Mean Square of Successive Differences (RMSSD), Statistically Determined Spatial Drift (SDSD), percentage of NN50 in the total number of NN intervals (PNN50), and Standard Deviation of all NN intervals for all 5-min segment (SDNN) after training were significantly higher than those before training, and the differences were statistically significant (p<0.05). Average (Avag) and Statistically Determined Allocation Weights (SDAW) after training were significantly higher than those before training, the difference was statistically significant (p<0.05); Asymmetry (Asym) and Tension index (TI) were significantly lower than those before training, the difference was statistically significant (p<0.05), Application Information Index (ApInf) had no significant difference (p>0.05). There was no significant difference in shooting hit rate (p>0.05). The speed of the 8-character dribble in the whole field after training was significantly lower than that before training, and the differences were statistically significant (p<0.05). There was no significant difference in average jump height, maximum jump height, average time in the air, and best jump time in the air after training (p>0.05). For the test of athletes' explosive power, five vertical jumps in situ were selected for testing, and the jump height and time in the air of each vertical jump were counted to calculate the maximum and average values of five vertical jumps. The results showed that there was no significant change in the explosive force of the athletes' lower limbs after training. The reason may be that strength training needs to follow the principles of heavy load, specialization, exercise sequence and reasonable interval. The intermittent training method used during training is not specialized in strength training, and the reasonable interval of strength training was not considered in the training process. CONCLUSIONS: Intermittent training can increase the tension of the cardiac vagus nerve of college basketball players, increase the cardiac reserve function and the load that the heart can bear, so that the cardiac function can be improved well. It can improve the cardiopulmonary function and aerobic work ability of college basketball players. It can improve the adjustment ability of the heart, lungs, liver, and other organs of college basketball players. It also can increase the load intensity that the central nerve can bear and improve the function of the central nerve and autonomic nerve. The anti-fatigue ability of athletes can be improved. It can improve the speed quality of college basketball players.

Chronic rhinitis and stress: the possible culprits of midfacial segment pain.

BACKGROUND: Bilateral symmetrical pain in the midfacial region without evidence of sinonasal disease is termed midfacial segment pain (MSP), about which little is known. The present study explored the prevalence of facial pain and the risk factors for MSP. METHODS: We analysed cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES). Those who reported facial pain or pressure lasting at least three months with no evidence of a sinonasal disease on nasal endoscopy were considered to have MSP. The participants were categorised according to the presence of facial pain and chronic rhinosinusitis. Basic demographic data and medical conditions, including hypertension, diabetes mellitus, and dyslipidemia, were compared between subject groups. We also evaluated psychological stress, depressive episodes, and suicidal thoughts, as well as physician-diagnosed nasal diseases, including chronic rhinitis and symptomatic nasal septal deviation. Univariate and multivariate logistic regression analyses were performed to determine risk factors for MSP. RESULTS: Of 31,999 participants, the prevalence of facial pain was 0.59%. A total of 58 (0.18%) respondents had MSP, of whom 40 (73.5%) were female. On univariate analysis, female sex, chronic rhinitis, and psychological stress were more prevalent in the subjects with MSP than the control subjects. However, in the multivariate analysis, only chronic rhinitis and psychological stress remained significant, while the female sex exhibited only marginal significance. CONCLUSION: Chronic rhinitis and psychological stress may be significant risk factors for MSP.

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.

Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study.

BACKGROUND: The phase III FLAURA2 (NCT04035486) study will evaluate efficacy and safety of first-line osimertinib with platinum-pemetrexed chemotherapy versus osimertinib monotherapy in epidermal growth factor receptor mutation-positive (EGFRm) advanced/metastatic non-small-cell lung cancer (NSCLC). The safety run-in, reported here, assessed the safety and tolerability of osimertinib with chemotherapy prior to the randomized phase III evaluation. PATIENTS AND METHODS: Patients (≥18 years; Japan: ≥20 years) with EGFRm locally advanced/metastatic NSCLC received oral osimertinib 80 mg once daily (QD), with either intravenous (IV) cisplatin 75 mg/m2 or IV carboplatin target area under the curve 5, plus pemetrexed 500 mg/m2 every 3 weeks (Q3W) for four cycles. Maintenance was osimertinib 80 mg QD with pemetrexed 500 mg/m2 Q3W until progression/discontinuation. The primary objective was to evaluate safety and tolerability of the osimertinib-chemotherapy combination. RESULTS: Thirty patients (15 per group) received treatment [Asian, 73%; female, 63%; median age (range) 61 (45-84) years]. Adverse events (AEs) were reported by 27 patients (90%): osimertinib-carboplatin-pemetrexed, 100%; osimertinib-cisplatin-pemetrexed, 80%. Most common AEs were constipation (60%) with osimertinib-carboplatin-pemetrexed and nausea (60%) with osimertinib-cisplatin-pemetrexed. In both groups, 20% of patients reported serious AEs. No specific pattern of AEs leading to dose modifications/discontinuations was observed; one patient discontinued all study treatments including osimertinib due to pneumonitis (study-specific discontinuation criterion). Hematologic toxicities were as expected and manageable. CONCLUSIONS: Osimertinib-chemotherapy combination had a manageable safety and tolerability profile in EGFRm advanced/metastatic NSCLC, supporting further assessment in the FLAURA2 randomized phase.

Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV-infected Koreans.

OBJECTIVES: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV-infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS. METHODS: This retrospective analysis included adults living with HIV, seen at four university-affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T-cell count < 200 cells/µL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score-matched case-control study between the non-INSTI and INSTI groups was performed. RESULTS: The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB-IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre-ART CD4 T-cell count (< 30 cells/µL), higher pre-ART viral load (≥ 75 000 copies/mL), and TB-OI. CONCLUSIONS: The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer.

BACKGROUND: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. PATIENTS AND METHODS: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25-75 mg p.o. twice a day; continuous or intermittent), savolitinib (600-800 mg p.o. once a day), or durvalumab (3-10 mg/kg intravenous every 2 weeks). RESULTS: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm-diarrhea (75%), rash (58%), nausea (47%); savolitinib arm-nausea (67%), rash (56%), vomiting (50%); durvalumab arm-rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. CONCLUSION: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. CLINICAL TRIALS NUMBER: NCT02143466.

Validation of a nomogram to predict the risk of cancer in patients with intraductal papillary mucinous neoplasm and main duct dilatation of 10 mm or less.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.

ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.

Modification of a limestone solubility method and potential to correlate with in vivo limestone calcium digestibility.

Work was done to modify a limestone solubility assay to improve predictions of in vivo apparent ileal digestibility of Ca (AID Ca) in broilers and impacts on AID P. Limestones (LIME) were obtained from 3 commercial sources. LIME-1 (0.633 mm mean diameter, GMD); LIME-2 (ground sub-sample of LIME-1, GMD = 0.063 mm); LIME-3 (GMD = 0.326 mm), and LIME-4 (GMD = 0.831 mm). Solubility was determined at 5, 15, and 30 min of incubation using either a 0.2 N HCl (S1) or a pH 3 HCl (pH = 0.26) solution buffered with 3 M glycine (S2) to mimic gizzard and proventriculus pH. An AID trial was conducted with 320 Ross 708 male broilers. Treatments (Trt) were no added LIME, or added LIME-1, 2, 3, and 4 to achieve 0.67% Ca, to a basal diet (no added inorganic P, 0.07% Ca) with or without 1,000 U phytase/kg (36 h, 23 to 24 D of age, n = 8, 4 birds/n). Distal ileal digesta was collected from all birds and pooled by pen. Irrespective of interaction, LIME solubilized quicker and more completely with S1 vs. S2 at all time points (P < 0.05). LIME-2 solubilized the quickest, while LIME-3 had the lowest solubility through all incubation times (P < 0.05). The AID Ca was 66.30, 47.46, 19.93, and 66.33% for LIME-1, 2, 3, and 4, respectively (0 U/kg, P < 0.05). Phytase inclusion increased AID Ca by 15% on average (P < 0.05). The AID P dig was highest in no LIME added diet (74.91%) and adding LIME reduced (P < 0.05) AID P to 23.14, 12.78, 65.47, and 37.40%, for LIME-1, 2, 3, and 4, respectively in the absence of phytase. Regression showed that GMD, 15- and 30-min solubility were critical for AID Ca (R2 between 0.978 and 0.988). In conclusion, the solubility dynamics including speed and extend of solubilization, rather than a single timepoint, yield better predictions for in vivo Ca digestibility of LIME.

Relationship between Within-Visit Blood Pressure Variability and Skeletal Muscle Mass.

Sarcopenia, defined as loss of skeletal muscle mass and function with age, is an important health issue in aging society. We tried to investigate the relationship between blood pressure variability and skeletal muscle mass in nation-wide large population cohort. This cross-sectional study was based on data acquired in the Korea National Health and Nutrition Examination Survey (KNHANES), conducted from 2009 to 2011 by the Korean Centers for Disease Control and Prevention. We included 14,481 participants (age ≥ 20 years, male 6,302) for the analysis who had both blood pressure and whole-body dual energy X-ray absorptiometry (DXA) scan data. As an intra-individual within-visit blood pressure variability index, we calculated standard deviation (SD), coefficient of variation (CV), and maximum minus minimum BP difference (MMD) of systolic and diastolic blood pressure, which was measured 3 times. Appendicular skeletal muscle mass (ASM) was the sum of lean masses of both arms and legs. We adjusted ASM by body mass index. Significant inverse relationship was observed between blood pressure variability index (SD, CV, and MMD) and adjusted ASM. Blood pressure variability index were significantly higher in the lowest ASM quintile group both in male and female participants (p<0.001). In multivariate analysis, blood pressure variability index were significantly associated with ASM, even after adjusting confounding factors (p<0.001). In conclusion, hemodynamic influence may play an important role in the development of sarcopenia.

Effects of limestone particle size and dietary Ca concentration on apparent P and Ca digestibility in the presence or absence of phytase.

The present study evaluated the effects of limestone particle size and Ca concentration on apparent ileal digestibility (AID) of P and Ca in the presence or absence of a 6-phytase derived from Buttiauxella sp., expressed in Trichoderma. Treatment diets were corn-soybean meal (SBM) based with no added inorganic Ca or P. The design consisted of a factorial arrangement of 2 particle sizes of limestone from the same source (mean particle size: pulverized, PUV < 75 µm; particulate, PAR = 402 µm); 3 Ca (0.6, 0.8, and 1.0%) and 2 phytase levels (0 and 1,000 (FTU)/kg) plus the corn-SBM basal diet with no added Ca (0.14% Ca), resulting a total of 13 treatments (Trts, n = 9, 3 birds/n). Starting at 27 d of age, broilers were fed the mash diets for 32 h, then sampled for gizzard pH and distal ileal digestibility. Gizzard pH was 1.94 in birds fed diet without added Ca and was similar to those fed diet with PAR limestone regardless of phytase. Gizzard pH was increased in birds fed PUV limestone diets irrespectively of phytase inclusion compared to birds fed 0.14% Ca (P < 0.05), except in birds fed 0.60% Ca diet. In the absence of phytase, AID P was reduced as a result of increases in limestone inclusion (P < 0.05), with a greater effect seen in PUV as compared to PAR limestone. The AID Ca in birds fed PUV limestone diets was lower than that of those fed PAR limestone diets (22.1% vs. 28.2%; P < 0.05). In the presence of phytase, the AID P was not affected by increasing Ca concentration when PAR limestone was used as the Ca source (average = 64.3%), whereas AID P decreased from 66.9% (0.6% Ca) to 51.0% (1.0% Ca) when PUV limestone was used as the Ca source (P < 0.05). In summary, impact of Ca concentration on AID Ca and P was dependent on limestone particle size and phytase inclusion.

Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma

Purpose: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). Methods/patients: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). Results: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. Conclusions: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor

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Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma.

PURPOSE: We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). METHODS/PATIENTS: A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). RESULTS: During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. CONCLUSIONS: A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

Impacts of dietary calcium, phytate, and phytase on inositol hexakisphosphate degradation and inositol phosphate release in different segments of digestive tract of broilers.

A total of 720 straight-run Heritage 56 M × fast feathering Cobb 500F broiler chickens was fed from 11 to 13 d of age to determine the impacts of dietary calcium (Ca), phytate phosphorus (PP), and phytase concentrations on inositol phosphate (IP3-6) profile in different digestive tract (GI) segments. The experiment was a 2 × 2 × 3 randomized block design with 2 Ca (0.7 and 1.0%) and 2 PP (0.23 and 0.34%) concentrations and 3 doses of Buttiauxella sp. phytase (0, 500, and 1,000 FTU/kg). The experiment was replicated in time (block) with 3 replicates per treatment (Trt) of 10 birds per block. Concentrations of IP3-6 in the crop, proventriculus (Prov) plus (+) gizzard (Giz), and distal ileum, as well as the ileal IP6 and P disappearance were determined at 13 d of age. The detrimental impact of Ca on IP6 and P disappearance was observed only in the ileum, where 11% reduction in both IP6 and P disappearance was seen when Ca increased from 0.7 to 1.0% (P < 0.05). Higher IP5 and IP6 concentrations were seen in both the crop and Prov+Giz at 0.34% PP as compared to birds fed to 0.23% PP diets, regardless of Ca or phytase (P < 0.05), whereas IP3 and IP4 concentrations were not affected by PP (P > 0.05). Inclusion of phytase, at both 500 and 1,000 FTU/kg, resulted in lower IP6 and the accumulation of lower IP ester (IP3-5) concentrations in all GI segments (P < 0.05). Improved IP6 and P disappearance was seen as a result of phytase inclusion, despite the degree of improvement affected by PP (P < 0.05). On average, 5.5 and 6.7 times improvement in IP6 was observed with 500 and 1,000 FTU phytase/kg inclusion, respectively, resulting in 41 and 64% greater P digestibility, respectively. In conclusion, phytase can effectively degrade IP6 to lower esters and increase P utilization. However, the efficacy of phytase can be affected by diet Ca and PP concentrations.

Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study.

While cross-sectional studies suggest that patients with mood disorders have a higher ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) and lower levels of omega-3 PUFAs, it is unknown if a high n-6/3 ratio indicates vulnerability for depression. We tested this hypothesis in a 7-year follow-up study of young individuals with an ultra-high risk (UHR) phenotype. We conducted a secondary analysis of the Vienna omega-3 study, a longitudinal study of omega-3 PUFAs in individuals at UHR for psychosis (n=69). Levels of n-6 and n-3 PUFAs were measured in the phosphatidylethanolamine fraction of erythrocyte membranes at intake into the study. Mood disorder diagnosis was ascertained with the Structured Clinical Interview for DSM-IV-TR and confirmed by review of medical records and interviews of caregivers. A higher n-6/3 PUFA ratio at baseline predicted mood disorders in UHR individuals over a 7-year (median) follow-up (odds ratio=1.89, 95% CI=1.075-3.338, P=0.03). This association remained significant after adjustment for age, gender, smoking, severity of depressive symptoms at baseline and n-3 supplementation. Consistent results were obtained for individual PUFAs, including lower levels of eicosapentaenoic acid and docosahexaenoic acid. The predictive capacity of these findings was specific to mood disorders as no associations were found for any other psychiatric disorder. To our knowledge, our data provide the first prospective evidence that the n-6/3 PUFA ratio is associated with an increased risk for mood disorders in young people exhibiting an UHR phenotype. These findings may have important implications for treatment and risk stratification beyond clinical characteristics.

Erythrocyte glutathione levels as long-term predictor of transition to psychosis.

A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion 'low erythrocyte GSH' to the set of criteria used to identify individuals at risk of psychosis may be indicated.

Clinical impact of hyperglycemia on days 0-7 after allogeneic stem cell transplantation.

In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0-7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110-149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24). The median follow-up was 2.7 years. Patients in the moderate/severe hyperglycemia group had significantly worse characteristics. The cumulative incidences of 2-year non-relapse mortality (NRM) and the probabilities of 2-year overall survival (OS) in the normoglycemia, mild hyperglycemia and moderate/severe hyperglycemia groups were 7.5%, 19% and 29%, respectively (P<0.01), and 69%, 53% and 33%, respectively (P<0.01). In multivariate analyses, hyperglycemia was an independent predictor of high NRM (vs normoglycemia; mild hyperglycemia, hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.56-4.18; moderate/severe hyperglycemia, HR 4.46, 95% CI 1.92-10.3) and poor OS (vs normoglycemia; mild hyperglycemia, HR 1.54, 95% CI 1.14-2.07; moderate/severe hyperglycemia, HR 1.61, 95% CI 0.89-2.91). In conclusion, hyperglycemia on days 0-7 after allo-SCT was associated with inferior outcomes.