Dynamic Graft-versus-Host Disease-Free,Relapse-Free Survival: Multistate Modeling of the Morbidity and Mortality of Allotransplantation

Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6%) through 4 years (37.4% versus 22.2%). Mean survival without failure events was .52 years (95% confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.     

Black Light Smokers: How Nicotine Intake and Carcinogen Exposure Differ Across Various Biobehavioral Factors

ObjectiveThe study objective was to identify biobehavioral variables associated with greater intake of nicotine and a tobacco carcinogen among Black light smokers who smoke 1 to 10 cigarettes per day (CPD).MethodsWe analyzed baseline data collected from 426 Black light smokers enrolled in Kick It at Swope III (KIS III), a smoking cessation trial for Black smokers. We examined differences in concentrations of tobacco biomarkers, including urinary total nicotine equivalents (TNE) and total 4-(methylnitrosamino)-1-(3)pyridyl-1-butanonol (NNAL; a human carcinogen), across gender, age, plasma nicotine metabolite ratio (NMR), CPD, and measures of tobacco dependence, including time to first cigarette (TFC), using ANOVA.ResultsTobacco biomarker levels were significantly higher among those who smoked more CPD (6–10 vs 1–5 CPD) and those with greater reported physical dependence on tobacco. Concurrently, those who smoked 1–5 CPD smoked each cigarette more intensely than those who smoked 6–10 CPD. While we found no gender differences overall, among those who smoked 1–5 CPD, women had higher NNAL levels compared to men. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, was not significantly related to TNE or NNAL levels.ConclusionAmong Black Light smokers, higher cigarette consumption and greater physical dependence—but not rate of nicotine metabolism, menthol use, or socioeconomic status—were associated with greater toxicant exposure and thus a likely increased risk of tobacco-related diseases. The lack of data on light smokers, and specifically on Blacks, make this observation important given the disproportionate burden of lung cancer in this population.     

Immunologic non-inferiority and safety of the investigational pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) 4-dose vial presentation compared to the licensed PHiD-CV 1-dose vial presentation in infants: A phase III randomized study

BackgroundTo support vaccination programs in developing countries, a 4-dose vial presentation of pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was developed. This study assessed immunologic non-inferiority and safety of the investigational PHiD-CV 4-dose versus licensed 1-dose vial presentation in infants.MethodsIn this phase III, mono-center, observer-blind study in Bangladesh, 6–10-week-old infants were randomized 1:1 to receive PHiD-CV primary vaccination (at ages 6, 10, 18 weeks) and a booster dose (at age 9 months) with a 4-dose vial (with preservative, 4DV group) or 1-dose vial (preservative-free, 1DV group). DTPw-HBV/Hib was (co)-administered per study protocol and polio, measles and rubella vaccines as part of the national immunization program. Non-inferiority of PHiD-CV 4-dose versus 1-dose vial for each vaccine pneumococcal serotype (VT) and vaccine-related serotype 19A in terms of antibody geometric mean concentration (GMC) was assessed (criterion: upper limit of 2-sided 95% confidence interval of antibody GMC ratios [1DV/4DV] <2-fold). Immune responses were measured. Solicited, unsolicited and serious adverse events (AEs) were evaluated.ResultsOf 320 infants (160 per group) vaccinated during the primary vaccination phase, 297 received a booster. Non-inferiority was demonstrated for each VT and 19A. One month post-primary vaccination, for most VT, ≥97.9% of infants in each group had antibody concentrations ≥0.2 μg/mL; for 19A ≥ 80.1% reached this threshold. Pneumococcal antibody responses and opsonophagocytic activity for each VT and 19A were within similar ranges between groups after primary and booster vaccination, as were anti-protein D responses. Booster immune responses were observed in both groups. Reported AEs were within similar ranges for both presentations.ConclusionImmunologic non-inferiority of PHiD-CV 4-dose vial (with preservative) versus PHiD-CV 1-dose vial (preservative-free) was demonstrated. Immune responses and reactogenicity following primary/booster vaccination were within similar ranges for both presentations. PHiD-CV 4-dose vial would help improve access and coverage in resource-limited countries.Clinical Trial Registry: NCT02447432.     

Comparative analysis of dental procedure mix in public and private dental benefits programs

BackgroundThere is little published research on whether public and private dental benefits plans affect the types of oral health care procedures patients receive. This study compares the dental procedure mix by age group (children, working-age adults, older adults), dental benefits type (Medicaid and Children’s Health Insurance Program, private), and level of Medicaid dental benefits by state (emergency only, limited, extensive).MethodsThe authors extracted public dental benefits claims data from the 2018 Transformed Medicaid Statistical Information System. To compare procedure mix with beneficiaries who had private dental benefits, the authors used claims data from the 2018 IBM MarketScan dental database. The authors categorized dental procedures into specific service categories and calculated the share of procedures performed within each category. They analyzed procedure mix by age, plan type (fee-for-service, managed care), and adult Medicaid benefit level.ResultsAside from orthodontic services, the dental procedure mix among children with public and private benefits is similar. Among adults with public benefits, surgical interventions make up a higher share of dental procedures than routine preventive services.ConclusionsChildren with public benefits have a procedure mix comparable with those with private benefits. There are substantial differences in procedure mix between publicly and privately insured adults. Even in states that provide extensive dental benefits in Medicaid, those programs primarily finance invasive surgical treatment as opposed to preventive treatment.Practical ImplicationsThere is a need to assess best practices in publicly funded programs for children and translate those attributes to programs for adults for more equitable benefit design and care delivery across public and private insurers.     

Baicalin suppresses iron accumulation after substantia nigra injury: relationship between iron concentration and transferrin expression

Previous studies have shown that baicalin prevented iron accumulation after substantia nigra injury, reduced divalent metal transporter 1 expression, and increased ferroportin 1 expression in the substantia nigra of rotenone-induced Parkinson's disease rats. In the current study, we investigated the relationship between iron accumulation and transferrin expression in C6 cells, to explore the mechanisms of the inhibitory effect of baicalin on iron accumulation observed in Parkinson's disease rats. Iron content was detected using inductively coupled plasma-atomic emission spectroscopy. Results showed that iron content decreased 41% after blocking divalent metal transporter 1 and ferroportin 1 proteins. After treatment with ferric ammonium citrate of differing concentrations(10, 50, 100, 400 μg/mL) in C6 glioma cells, cell survival rate and ferroportin 1 expression were negatively correlated with ferric ammonium citrate concentration, but divalent metal transporter 1 expression positively correlated with ferric ammonium citrate concentration. Baicalin or deferoxamine reduced divalent metal transporter 1 expression, but increased ferroportin 1 expression in the 100 μg/mL ferric ammonium citrate-loaded C6 cells. These results indicate that baicalin down-regulated iron concentration, which positively regulated divalent metal transporter 1 expression and negatively regulated ferroportin 1 expression, and decreased iron accumulation in the substantia nigra.     

Mash1 efficiently reprograms rat astrocytes into neurons简

To date, it remains poorly understood whether astrocytes can be easily reprogrammed into neurons. Mashl and Brn2 have been previously shown to cooperate to reprogram fibroblasts into neurons. In this study, we examined astrocytes from 2-month-old Sprague-Dawley rats, and found that Brn2 was expressed, but Mashl was not detectable. Thus, we hypothesized that Mashl alone could be used to reprogram astrocytes into neurons. We transfected a recombinant MSCV-MASH1 plasmid into astrocytes for 72 hours, and saw that all cells expressed Mashl. One week later, we observed the changes in morphology of astrocytes, which showed typical neuro- nal characteristics. Moreover, β-tubulin expression levels were significantly higher in astrocytes expressing Mashl than in control cells. These results indicate that Mashl alone can reprogram astrocytes into neurons.     

The relationship between preoperative nutritional state and adverse outcome following abdominal and thoracic surgery in children: Results from the NSQIP database

Introduction

Anthropometric measurements can be used to define pediatric malnutrition. Our study aims to: (1) characterize the preoperative nutritional status of children undergoing abdominal or thoracic surgery, and (2) describe the associations between WHO-defined acute (stunting) and chronic (wasting) undernutrition (Z-scores <?2) and obesity (BMI Z-scores > + 2) with 30-day postoperative outcomes.