Neoadjuvant Treatment with HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.

This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety. METHODS: A network meta-analysis was applied to estimate the risk ratios along with 95% confidence intervals (CIs) for pathological complete response (pCR) and serious adverse events (SAE). A mixed-effect parametric survival analysis was conducted to assess the disease-free survival (DFS) between treatments. RESULTS: Twenty-one RCTs with eleven regimens of neoadjuvant anti-HER2 therapy (i.e., trastuzumab + chemotherapy (TC), lapatinib + chemotherapy (LC), pertuzumab + chemotherapy (PC), pertuzumab + trastuzumab (PT), trastuzumab emtansine + pertuzumab (T-DM1P), pertuzumab + trastuzumab + chemotherapy (PTC), lapatinib + trastuzumab + chemotherapy (LTC), trastuzumab emtansine + lapatinib + chemotherapy (T-DM1LC), trastuzumab emtansine + pertuzumab + chemotherapy(T-DM1PC), PTC followed by T-DM1P (PTC_T-DM1P), and trastuzumab emtansine (T-DM1)) and chemotherapy alone were included. When compared to TC, only PTC had a significantly higher DFS with a hazard ratio (95% CI) of 0.54 (0.32-0.91). The surface under the cumulative ranking curve (SUCRA) suggested that T-DM1LC (91.9%) was ranked first in achieving pCR, followed by the PTC_T-DM1P (90.5%), PTC (74.8%), and T-DM1PC (73.5%) regimens. For SAEs, LTC, LC, and T-DM1LC presented with the highest risks (SUCRA = 10.7%, 16.8%, and 20.8%), while PT (99.2%), T-DM1P (88%), and T-DM1 (83.9%) were the safest regimens. The T-DM1PC (73.5% vs. 71.6%), T-DM1 (70.5% vs. 83.9%), and PTC_T-DM1P (90.5% vs. 47.3%) regimens offered the optimal balance between pCR and SAE. CONCLUSIONS: The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen. However, these results were based on a small number of studies, and additional RCTs assessing the efficacy of regimens with T-DM1 are still needed to confirm these findings.

Unusual Polyhydroxylated Steroids from the Starfish Anthenoides laevigatus, Collected off the Coastal Waters of Vietnam.

Four new polyhydroxylated steroids 1-4 were isolated along with two previously known related steroids 5 and 6 from the methanolic extract of the starfish Anthenoides laevigatus collected off the coastal waters of Vietnam. Structures of new compounds were substantially elucidated by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy and HRESIMS techniques. Heptaol 1 and hexaol 2 contain the common 5α-cholestane skeleton, while hexaol 3 and heptaol 4 have the rare among starfish steroid compounds 5ß-cholestane skeleton. Compounds 1, 5, and 6 do not show cytotoxic effects against normal JB6 Cl41 and cancer HT-29 and MDA-MB-231 cells, however they inhibit cell proliferation and colony formation of cancer HT-29 and MDA-MB-231 cells.

Predicting 3-year mortality based on the tumor necrosis factor alpha concentration in low-flux hemodialysis patients.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF-α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF-α concentration, ≥ 67.29 pg/mL). During the 36-month follow-up period, a total of 50 (15.7%) patients died from all causes. The Kaplan-Meier analysis revealed that the all-cause mortality in T3 was significantly higher compared to that in T1 and T2 (log-rank test, P < .001). The serum TNF-α level was a significant predictor for all-cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF-α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high-sensitivity C-reactive protein, and serum beta-2 microglobulin concentrations. The serum TNF-α concentration was a good predictor of the 3-year mortality in low-flux hemodialysis patients.

Parent-youth communication and concordance between parents and adolescents on reported engagement in social relationships and sexually intimate behaviors in Hanoi and Khanh Hoa Province, Vietnam.

PURPOSE: Parent-child communication is associated with positive outcomes for youths' engagement in sexual behaviors. Limited data are available regarding parent-child communication in transitional countries. We present data from Vietnamese parent-youth dyads on parent reproductive health (RH) knowledge, comfort of communication, frequency of talk, and discordancy between youths' reported and parents' perceptions for engagement in relationships and sexually intimate behaviors. METHODS: The cohort included 185 randomly selected parent-youth dyads in four communes in Hanoi and Khanh Hoa Province. Descriptive and comparative analysis included chi-squared tests, independent samples t-tests, and ANOVA. Linear regression analysis was used to assess relationships between parental knowledge, level of comfort, frequency of talk, and discordancy. RESULTS: Seventy-six percent of parents and 44% of youth were female. The mean age of youth was 17.2 years. The mean score for parental "RH knowledge" was 24.74 (SD, 3.84; range, 15-34). Lower parental RH knowledge was positively associated with lower levels of education (F = 2.983; df, 184; p = .014). Data indicate a linear model in which knowledge is related to "comfort" (ß = .17; p = .048), and "comfort" to frequency of "talk" (ß = .6; p < .0001). Frequency of "talk" is not related to parents' discordant perceptions regarding their child's reported involvement in relationships (ß = .002; p = .79) or sexual touching (ß = .57; p = .60). CONCLUSIONS: Parent and youth in Vietnam are engaged in limited communication about RH. There is a need for more data to assess the effect of these communication patterns on youths' engagement in sexual behaviors and for development of family-centered interventions to increase parental knowledge and skills for positive communication.

Highly pathogenic avian influenza (H5N1) in ducks and in-contact chickens in backyard and smallholder commercial duck farms in Viet Nam.

Scavenging ducks are thought to play an important role in the maintenance and transmission of highly pathogenic avian influenza (HPAI) H5N1 virus among domesticated and wild bird populations in South East Asia, but detailed field epidemiological results describing the infection status of domestic ducks and in-contact chickens have not been published. We conducted a longitudinal study, monitoring ducks and in-contact chickens in 80 flocks in the Mekong Delta of Viet Nam with bi-monthly testing from May 2007 until May 2008. Because H5 vaccination campaigns are conducted at regular intervals in poultry flocks in Viet Nam, both unvaccinated sentinel and H5 vaccinates were monitored. On each farm, a total of 10 birds were selected: 7 ducks (4 unvaccinated and 3 vaccinated) and 3 chickens (2 unvaccinated and 1 vaccinated) that were in close contact with the ducks. Blood samples were tested for H5 antibodies using the hemagglutination inhibition test, with H5 antibody titers ≥2(4) considered to indicate past exposure to H5 field or vaccine virus. Titers of vaccinated birds were analyzed for samples collected more than 3 weeks post-vaccination. Pooled oropharyngeal and cloacal swabs were assessed for H5 viral RNA using real-time PCR. Bird- and flock-level prevalences were estimated accounting for sampling fractions and clustering under the multi-stage sampling design with birds being sampled within flocks within villages in four different provinces. In total, serum and swab samples from 5409 birds-samplings were analyzed. Bird-level seroprevalence was 17.5% (95% CI: 14.1, 20.9) amongst unvaccinated ducks and 10.7% (95% CI: 7.4, 14.4) amongst unvaccinated in-contact chickens. Flock-level seroprevalence (proportion of flock-visits with at least one unvaccinated bird test positive) was 42.6% (95% CI: 38.0, 47.2) for ducks and 19.0% (95% CI: 13.6, 24.4) for chickens. Only 54.3% (95% CI: 39.2, 69.3) of vaccinated ducks and 55.5% (95% CI: 46.8, 64.2) of vaccinated in-contact chickens had H5 antibodies at more than 3 weeks post-vaccination. At about 40% and 48% of flock-visits, less than 50% of sampled vaccinated ducks and chickens, respectively, had positive titers. The flock-level virus prevalence (proportion of flocks with at least one bird positive for H5 virus of the vaccinated and unvaccinated birds tested) was 0.7% (95% CI: 0.0, 2.1). No HPAI outbreaks or mortality suspected to be due to HPAI occurred in study flocks during the observation period. Our results indicate that a substantial proportion of ducks and in-contact chickens were exposed to H5 virus during the study period. In the face of this widespread exposure to H5 virus, and despite only moderate proportions of birds developing positive titers post-vaccination, flocks were not affected by HPAI outbreaks during our study period. The higher bird-level seroprevalence in ducks compared to in-contact chickens may be due to greater durations of antibody persistence in ducks or greater rates of H5 virus exposure. These findings indicate that ducks are potentially an important source of H5 virus for other bird species.