Quasi-periodic X-ray eruptions years after a nearby tidal disruption event.

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks1-5. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities6-8 or interacting with a stellar object in a close orbit9-11. It has been suggested that this disk could be created when the SMBH disrupts a passing star8,11, implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions13,14. TDEs and QPEs also occur preferentially in similar galaxies15. However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE16. We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs.

First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase I dose exploration.

BACKGROUND: Homozygous deletion of methylthioadenosine phosphorylase (MTAP) occurs in ∼10%-15% of solid tumors. AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumor cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors. PATIENTS AND METHODS: In this first-in-human, multicenter, open-label, phase I study, patients with advanced CDKN2A-deleted and/or MTAP-deleted solid tumors received AMG 193 orally [once (o.d.) or twice (b.i.d.) daily] continuously in 28-day cycles. Primary objectives were safety and tolerability assessed by dose-limiting toxicities and determination of the maximum tolerated dose; secondary objectives included pharmacokinetics and preliminary antitumor activity measured by RECIST v1.1. RESULTS: As of 23 May 2024, 80 patients in dose exploration received AMG 193 at doses 40-1600 mg o.d. or 600 mg b.i.d. The most common treatment-related adverse events were nausea (48.8%), fatigue (31.3%), and vomiting (30.0%). Dose-limiting toxicities were reported in eight patients at doses ≥240 mg, including nausea, vomiting, fatigue, hypersensitivity reaction, and hypokalemia. The maximum tolerated dose was determined to be 1200 mg o.d. Mean exposure of AMG 193 increased in a dose-proportional manner from 40 mg to 1200 mg. Among the efficacy-assessable patients treated at the active and tolerable doses of 800 mg o.d., 1200 mg o.d., or 600 mg b.i.d. (n = 42), objective response rate was 21.4% (95% confidence interval 10.3% to 36.8%). Responses were observed across eight different tumor types, including squamous/non-squamous non-small-cell lung cancer, pancreatic adenocarcinoma, and biliary tract cancer. At doses ≥480 mg, complete intratumoral PRMT5 inhibition was confirmed in paired MTAP-deleted tumor biopsies, and molecular responses (circulating tumor DNA clearance) were observed. CONCLUSIONS: AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP-deleted solid tumors was observed based on objective response rate and circulating tumor DNA clearance.

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study.

BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.

Molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.

OBJECTIVE: This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea. METHOD: Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions. RESULTS: The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group. CONCLUSION: Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.

Enabling ultra-low-voltage switching in BaTiO3.

Single crystals of BaTiO3 exhibit small switching fields and energies, but thin-film performance is considerably worse, thus precluding their use in next-generation devices. Here, we demonstrate high-quality BaTiO3 thin films with nearly bulk-like properties. Thickness scaling provides access to the coercive voltages (<100 mV) and fields (<10 kV cm-1) required for future applications and results in a switching energy of <2 J cm-3 (corresponding to <2 aJ per bit in a 10 × 10 × 10 nm3 device). While reduction in film thickness reduces coercive voltage, it does so at the expense of remanent polarization. Depolarization fields impact polar state stability in thicker films but fortunately suppress the coercive field, thus driving a deviation from Janovec-Kay-Dunn scaling and enabling a constant coercive field for films <150 nm in thickness. Switching studies reveal fast speeds (switching times of ~2 ns for 25-nm-thick films with 5-µm-diameter capacitors) and a pathway to subnanosecond switching. Finally, integration of BaTiO3 thin films onto silicon substrates is shown. We also discuss what remains to be demonstrated to enable the use of these materials for next-generation devices.

Lifetime risks of hip fracture in patients with type 2 diabetic: Taiwan Diabetes Study.

This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. INTRODUCTION: The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. METHODS: A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30-100 years old and participated in the National Diabetes Case Management Program in 2002-2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. RESULTS: Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. CONCLUSIONS: The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

Association of fine-particulate and acidic-gas air pollution with premenstrual syndrome risk.

OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.

Competing risk analysis on visit-to-visit glucose variations and risk of depression: The Taiwan Diabetes Study.

AIM: Patients with diabetes have higher rates of depression than does the general population, but diabetes management mainly aims to maintain glucose stability. For this reason, our study assessed the relationship between 1-year variations in fasting plasma glucose (FPG) and risk of depression in Chinese patients with type 2 diabetes (T2D). METHODS: This retrospective cohort study was conducted on 32,829 patients aged ≥30 years who were diagnosed with T2D and who participated in the National Diabetes Case Management Program in Taiwan. Their 1-year FPG variation as a predictor was determined by coefficient of variation (CV), whereas depressive events were analyzed by Cox's proportional hazards models. RESULTS: During a mean 8.23 years of follow-up, 1041 new cases of depression were diagnosed. When patients were grouped based on quartiles of FPG-CV, incidence rates were 3.23, 3.49, 3.96 and 4.80 per 1000 person-years in the first, second, third and fourth quartile subgroups, respectively. After adjusting for traditional risk factors, baseline fasting glucose and HbA1c levels, and diabetes complications, FPG-CV was independently linked with incident depression. Hazard ratios of depression for FPG-CV in the fourth vs first quartile subgroups was 1.33 (95% CI: 1.11-1.59), respectively. CONCLUSION: Patients whose 1-year FPG variations were>42.6% had an increased risk of depression, thus suggesting that FPG variations may be a predictor of depression in patients with T2D. Also, glucose variation during outpatient visits may be an indicator for individualized diabetes management in clinical practice.

Visit-to-visit blood pressure variability and hip fracture risk in older persons.

We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. INTRODUCTION: Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. METHODS: We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients' 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. RESULTS: There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00-1.40) for the third tertile compared with the first tertile. CONCLUSIONS: Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.

Impact of Positive Donor-Specific HLA Antibodies Crossmatch on Graft Survival in ABO-Incompatible Liver-Kidney Transplantation: A Case Report.

We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.

Cost Analysis and Determinants of Living Donor Liver Transplantation in Taiwan.

BACKGROUND: Liver transplantation (LT) has become established therapy for end-stage liver disease and small-cell hepatocellular carcinoma (HCC), relying mainly on living donor LT (LDLT) in Taiwan. The cost of LDLT varies in different countries depending on the insurance system, the costs of the facility, and staff. In this study we aimed to investigate cost outcomes and determinants of LDLT in Taiwan. METHODS: From January 2014 to December 2015, 184 LDLT patients were enrolled in a study performed at the Kaohsiung Chang Gung Memorial Hospital. Patients' transplantation costs were defined as expense from immediately after surgery to discharge during hospitalization for LDLT. Antiviral therapy and hepatitis B immunoglobulin (HBIG) for prevention of hepatitis B virus (HBV) were included, but direct-acting antiviral (DAA) therapy for hepatitis C (HCV) was excluded. RESULTS: The median total, intensive care unit (ICU), and ward costs of LT were US$64,250, $43,357, and $16,138 (currency ratio 1:30), respectively. HBV significantly increased the total cost of LT, followed by postoperative reintubation and bile duct complications. CONCLUSION: The charges associated with anti-HBV viral therapy and HBIG increase the cost of LDLT. Disease severity of liver cirrhosis showed less importance in predicting cost. Postoperative complications such as reintubation or bile duct complications should be avoided to reduce the cost of LT.

Diffusion-Weighted Magnetic Resonance Imaging in Liver Graft Rejection.

OBJECTIVE: The purpose of this study is to evaluate the use of diffusion-weighted magnetic resonance imaging (DWMRI) in the assessment of graft rejection after liver transplantation (LT). METHODS: From June 2017 to January 2018, 32 patients were included in the study with a mean age of 52.3 years. All patients underwent LT. The DWMRI was performed using the apparent diffusion coefficient map and measuring the different b-values (b-400, b-600, b-800, and b-1000). These measurements were compared with the histopathology results. Statistical analysis included t test, analysis of variance, and area under the curve for receiver operating characteristic (ROC). RESULTS: There were 17 patients without rejection and 15 patients with liver graft rejection diagnosed by histopathology. The mean (SD) results between the nonrejection and rejection groups were as follows: b-400 = 1.568 (0.265) vs 1.519 (0.119) (P = .089), b-600 = 1.380 (0.181) vs 1.284 (0.106) (P = .039), b-800 = 1.262 (0.170) vs 1.170 (0.086) (P = .035), b-1000 = 1.109 (0.129) vs 1.098 (0.078) (P = .095); B-values × 10-3 mm2/s. Only b-600 (P = .04) and b-800 (P = .04) values have significant differences between the 2 groups. B-600 showed 90.48% sensitivity and 83.33% specificity (ROC area under the curve = 0.784; P < .001), and b-800 showed 90.38% sensitivity and 83.03% specificity (ROC area under the curve = 0.816; P < .001). The values obtained with the apparent diffusion coefficient in b-800 were clearly differentiated between the mild, moderate, and severe degrees of rejection (P < .001). CONCLUSION: Measurement of b-600 and b-800 values using DWMRI may be used for the diagnosis of graft rejection after LT.

Donor-Transmitted Bacterial Infection in Deceased Donor Liver Transplantation: Experience of Southern Taiwan Medical Center.

BACKGROUND: Bacterial Infection is the most important source of mortality and morbidity in liver transplantation recipients. Donor transmitted bacterial infection is rare but one of the most important infection sources. This kind of infection is difficult to identify, causing treatment dilemma. PATIENTS AND METHODS: In this article, we retrospectively reviewed our deceased donor liver transplants performed from January 2014 to December 2016. Forty-two recipients in Kaohsiung Chang Gung Memorial Hospital receiving liver grafts from 35 deceased liver donors were evaluated. The demography, donor transmitted infection, and outcomes were evaluated. RESULT: Two patients had probable donor transmitted bacterial infection and 1 patient died of suspected transmitted infection. CONCLUSION: Early identification of donor infection and adequate antibiotic treatment for the donor and recipient are the keys to preventing donor transmitted bacterial infection. Donor infection is not an absolute contraindication for organ donation in the area of organ shortage. Organ procurement organizations or similar authorities may establish the platform for sharing the data about donor and recipient infections.

Intervention of Online Percent Coefficient of Variation Reporting System Reduces the Variability of Tacrolimus Trough Concentration in Kidney Transplant Recipients.

BACKGROUND: The online percent coefficient of variation reporting system could monitor the variation of tacrolimus trough level (T0) and identify kidney transplant recipients (KTRs) with a higher percent coefficient of variation (%CV) instantly. Consequently, transplant doctors and pharmacists could take actions to improve drug variability. The purpose of this study was to determine the efficacy of the system for higher intrapatient variability of T0 in KTRs. METHODS: The T0 data were collected with KTRs routinely followed up at an outpatient clinic between June 2016 and November 2016. The %CV was calculated with T0 data within 6 months before and after the index date. The last outpatient clinic visit date was before December 1, 2016. The KTRs with %CV of T0 greater than 22% were enrolled. RESULTS: The study consisted of 183 KTRs (96 male, 87 female), the median age was 50 years (interquartile range [IQR], 41.0-57.0), and the median years post-kidney transplantation was 7 years (IQR, 3.0-12.4). The median T0 and creatinine level at baseline were 6.09 ng/mL (IQR, 4.80-7.52) and 1.33 mg/dL (IQR, 1.03-1.72), respectively. After the intervention, the median %CV of T0 was significantly lower than before, 32% (IQR, 26%-42%) vs 22% (IQR, 15%-33%), P < .001. The average improvement of %CV was also significantly better in KTRs with %CV ≥ 30% (median, from 41% to 25%) than KTRs with %CV between 22% and 30% (median, from 26% to 20%), P < .001. CONCLUSIONS: The results of this study indicate that continuously aggressive intervention with an online %CV reporting system effectively improves intrapatient variability of T0 in KTRs.

The association between septicemia and the risk of multiple sclerosis: a nationwide register-based retrospective cohort study in Taiwan.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Few studies focused on the relationship between septicemia and MS. AIM: To evaluate the potential impact of septicemia on risk for MS. DESIGN: Two cohorts of patients with septicemia and without septicemia were followed up for the occurrence of MS. METHODS: Patients of 482 790 with septicemia was enrolled from the National Health Insurance Research Database between 2001 and 2011 as the study group to match the 1 892 820 individuals, as the control group, by age and gender. Incidence of MS in both groups was calculated. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR) for MS between groups. RESULTS: Septicemia patients had a 3.06-fold (95% CI: 2.16-4.32, P < 0.001) greater risk of developing MS than the matched group. In addition, higher severity of septicemia was associated with higher risk of developing MS (moderate: HR = 4.03, 95% CI: 2.53-6.45, P < 0.001; severe: HR = 11.1, 95% CI: 7.01-17.7, P < 0.001). Similar results also occurred in both male and female patients with septicemia (male: HR = 4.06, 95% CI: 2.17-7.58, P < 0.001; female: HR = 2.72, 95% CI: 1.79-4.11, P < 0.001). Patients without counterpart comorbidities had a significantly higher risk of MS than the controlled group (HR = 3.02, 95% CI: 2.10-4.35, P < 0.001). CONCLUSION: The results indicated septicemia is linked to an increased risk for MS. Aggressively preventing and treating septicemia may be warranted for one of precautionary strategies of MS.

Risk score prediction model for dementia in patients with type 2 diabetes.

BACKGROUND AND PURPOSE: No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients. METHODS: The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50-94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system. RESULTS: The average follow-up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3-, 5- and 10-year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively. CONCLUSIONS: The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.

Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.

Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. Results: A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials.gov (NCT 01287585).

Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan.

BACKGROUND: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS: Selected by computerized random sampling from all 19 counties in Taiwan. MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.