METHODS: This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD.
RESULTS: We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3-101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0-13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77-3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03-5.32), hypertension (HR = 2.81, 95% CI 1.16-6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01-1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84-7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19-5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57-3.16).
CONCLUSION: In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.
METHODS: In this study, we investigated the response of cartilage to the trauma sustained during extraction and determined the time needed for the cartilage to stabilize. Explants were extracted aseptically from bovine metacarpal-phalangeal joints and cultured for up to 17 days.
RESULTS: The cell viability, cell number, proteoglycan content, and collagen content of the harvested explants were analyzed at 0, 2, 10, and 17 days after explantation. A high percentage of the cartilage explants were found to be viable. The cell density initially increased significantly but stabilized after two days. The proteoglycan content decreased gradually over time, but it did not decrease to a significant level due to leakage through the distorted peripheral collagen network and into the bathing medium. The collagen content remained stable for most of the culture period until it dropped abruptly on day 17.
CONCLUSION: Overall, the tested cartilage explants were sustainable over long-term culture. They were most stable from day 2 to day 10. The degradation of the collagen on day 17 did not reach diseased levels, but it indicated the potential of the cultures to develop into degenerated cartilage. These findings have implications for the application of cartilage explants in pathophysiological fields.
PATIENTS AND METHODS: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned.
RESULTS: Overall (N = 55), median PFS was 4.9 months versus 4.4 months [stratified HR, 0.67; 90% CI, 0.35-1.28] with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR, 0.13; 90% CI, 0.04-0.43) and overall survival (OS; HR, 0.10; 90% CI, 0.02-0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 months versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range, 1.1-56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib and five (71.4%) had chemotherapy.
CONCLUSIONS: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
PATIENTS AND METHODS: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts.
RESULTS: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004).
CONCLUSION: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.
METHODS: We formulated body capacitive index (BCI), C(BMI) (capacitance × height(2)/weight), body resistive index (BRI), R(BMI) (resistance × weight/height(2)), and CH(2) (capacitance × height(2)). We also studied H(2)/R, R/H, and reactance of a capacitor/height (X(C) /H). There are 3 components in this study design: (1) establishment of normal values in a control Malaysian population, (2) comparison of these with a CAPD population, and (3) prediction of survival within a CAPD population. We initially performed a BIA study in 206 female and 116 male healthy volunteers, followed by a prospective study in a cohort of 128 CAPD patients [47 with diabetes mellitus (DM), 81 non-DM; 59 males, 69 females] for at least 2 years. All the parameters during enrolment, including BIA, serum albumin, peritoneal equilibrium test, age, and DM status, were analyzed. Outcome measurement was survival.
RESULTS: In healthy volunteers, both genders had the same BCI (2.0 nF kg/m(2)). On the contrary, female normal subjects had higher BRI than male normal subjects (median 15 642 vs 13242 Ω kg/m(2), p < 0.001) due to higher fat percentage (35.4% ± 0.4% vs 28.0% ± 0.6%, p < 0.001), resulting in a lower phase angle (mean 5.82 ± 0.04 vs 6.86 ± 0.07 degrees, p < 0.001). Logistic regression showed that BCI was the best risk indicator in 128 CAPD patients versus 322 normal subjects. In age- and body mass index (BMI)-matched head-to-head comparison, BCI had the highest χ(2) value (χ(2) = 102.63), followed by CH(2) (or H(2)/X(C); χ(2) = 81.00), BRI (χ(2) = 20.54), and X(C)/H (χ(2) = 20.48), with p value < 0.001 for these parameters. In comparison, phase angle (χ(2) = 11.42), R/H (χ(2) = 7.19), and H(2)/R (χ(2) = 5.69) had lower χ(2) values. 35 (27.3%) patients died during the study period. Univariate analysis adjusted for DM status and serum albumin level demonstrated that non-surviving patients had significantly higher CH(2) (245 vs 169 nF m(2), p < 0.001) and BCI (4.0 vs 2.9 nF m(2)/kg, p = 0.005) than patients that survived. CH(2) was the best predictor for all-cause mortality in Cox regression analysis, followed by BCI, phase angle, and X(C)/H.
CONCLUSION: Measures that normalize, such as BCI and CH(2), have higher risk discrimination and survival prediction ability than measures that do not normalize, such as phase angle. Unlike phase angle, measurement of BCI overcomes the gender effect. In this study, the best risk indicator for CAPD patients versus the general population is BCI, reflecting deficit in nutritional concentration, while CH(2) reflects total nutritional deficit and thus is the major risk indicator for survival of CAPD patients.
OBJECTIVE: The present study aims to investigate the effects of a standardized raw extract of C. asiatica (RECA) on hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in neural-like cells derived from mouse embryonic stem (ES) cell line.
METHODS: A transgenic mouse ES cell (46C) was differentiated into neural-like cells using 4-/4+ protocol with addition of all-trans retinoic acid. These cells were then exposed to H2O2 for 24 h. The effects of RECA on H2O2-induced neural-like cells were assessed through cell viability, apoptosis, and reactive oxygen species (ROS) assays, as well as neurite length measurement. The gene expression levels of neuronal-specific and antioxidant markers were assessed by RT-qPCR analysis.
RESULTS: Pre-treatment with H2O2 for 24 hours, in a dose-dependent manner, damaged neural-like cells as marked by a decrease in cell viability, substantial increase in intracellular ROS accumulation, and increase in apoptotic rate compared to untreated cells. These cells were used to treat with RECA. Treatment with RECA for 48 h remarkably restored cell survival and promoted neurite outgrowth in the H2O2- damaged neurons by increasing cell viability and decreasing ROS activity. RT-qPCR analysis revealed that RECA upregulated the level of antioxidant genes such as thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1) of treated cells, as well as the expression level of neuronal-specific markers such as Tuj1 and MAP2 genes, suggesting their contribution in neuritogenic effect.
CONCLUSION: Our findings indicate that RECA promotes neuroregenerative effects and exhibits antioxidant properties, suggesting a valuable synergistic activity of its phytochemical constituents, thus, making the extract a promising candidate in preventing or treating oxidative stress-associated Alzheimer's disease.
METHODS: We performed a retrospective analysis of 1043 consecutive patients submitted to CRS in a single institution. Potential risk factors for AL and GP, both related to patient overall condition, disease status and surgical technique were reviewed.
RESULTS: Anastomotic leaks were identified in 5.2% of patients, and GPs in 7.0%. The independent risk-factors for AL were age at surgery (OR1.40; CI95% 1.10-1.79); peritoneal cancer index (PCI) (OR1.04, CI95% 1.01-1.07); Cisplatin dose >240 mg during HIPEC (OR3.53; CI95% 1.47-8.56) and the presence of colorectal (CR) or colo-colic (CC) anastomosis (OR5.09; CI95% 2.71-9.53, and 4.58; CI95% 1.22-17.24 respectively). Male gender and intraoperative red blood cell transfusions were the only independent risk factors for GP identified (OR1.70; CI95% 1.04-2.78 and 1.06; CI95% 1.01-1.12, respectively). Regarding 30-day and 90-day postoperative mortality, independent risk-factors were mainly related to patient's overall condition.
CONCLUSION: Gastrointestinal leaks are a frequent source of postoperative morbidity, mainly at the expense of GP. A careful and systematic intraoperative revision of all potential gastrointestinal injuries is equally critical to perfecting anastomotic fashioning techniques to decrease gastrointestinal complication rates. We identified multiple risk-factors for AL and GP related to disease status and patient condition. Our study suggests that patient-related conditions are of paramount relevance, highlighting the importance of patient selection and preoperative patient optimization.