Diagnostic blood loss from phlebotomy and hospital acquired anemia in patients with severe burns

PurposeThe study was performed to estimate the diagnostic blood loss (DBL) volume during hospitalization and investigate its relationship with the development of moderate to severe hospital acquired anemia (HAA) and increased number of red blood cell (RBC) transfusion following extensive burns.Materials and methodsThis was a retrospective study of adult burned patients with total body surface area (TBSA) burn larger than 40%, who were admitted to burn center of Changhai hospital between January 2005 and December 2017.ResultsWe included a final number of 157 patients in the present study. Moderate to severe HAA within the fourth week postburn was developed in 46 of 121 patients who stayed over 28-day hospitalization. Patients with moderate to severe HAA had both significantly higher total DBL volume [245 (IQR: 183.75, 325.25) mL vs 168 (119, 163) mL ; P = 0.001] and DBL volume per day [10.22 (IQR: 8.57, 12.38) mL vs 6.63 (5.22, 10.42) mL/day; P = 0.005]. Logistic regression analysis revealed that both DBL volume per day and TBSA burn were independent risk factors for the development of moderate to severe HAA.ConclusionsSeverely burned patients appear to be prone to develop HAA during hospitalization. The DBL volume contribute to the occurrence of moderate to severe HAA, which might be a modifiable target for preventing HAA.     

Survival among Breast Cancer Patients: Comparison of the U.S. Military Health System with the Surveillance,Epidemiology and End Results Program

IntroductionAccessibility to health care is important to cancer survival. The U.S. military health system (MHS) provides universal health care access. However, whether the universal care has been translated into improved cancer survival is unknown. We compared survival of patients with breast cancer in the MHS with that in the U.S. general population and assessed the differences in cancer stage at diagnosis and treatment receipt between the two populations.MethodsThe MHS patients (n = 31,548) were identified from the Department of Defense's (DoD) Automated Central Tumor Registry (ACTUR). Patients in the U.S. general population (n = 63,096) were identified from the Surveillance, Epidemiology, and End Results (SEER) program. The two populations were matched on age, race, and diagnosis year. Multivariable Cox regression hazard modeling was used to estimate hazard ratios (HRs) comparing ACTUR with SEER. Multivariable logistic regression was used to estimate odds ratios (ORs) comparing stage and treatment receipt.ResultsACTUR patients exhibited a 24% lower overall mortality than the SEER patients (HR = 0.76, 95% CI, 0.71-0.80). They were less likely to present with later stage compared to the SEER patients (OR = 0.61, 95% CI, 0.55-0.67 for stage IV tumors). The ACTUR patients with stages I-III tumors were more likely to receive surgery (OR = 1.35, 95% CI, 1.20-1.52) but less likely to receive radiation (OR = 0.91, 95% CI, 0.88-0.94). The survival advantage of ACTUR patients remained regardless of surgery or radiation receipt.ConclusionsBreast cancer patients with universal health care access had improved survival compared to patients in the general population.     

Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

Limited options are available for clozapine-resistant schizophrenia and intolerable side effects of clozapine. We conducted a systematic review of randomized-controlled trials (RCTs) to determine the efficacy and safety of aripiprazole augmentation of clozapine for schizophrenia. Electronic databases searched included PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. This review synthesized the data of four short-term (8–24 weeks), placebo-controlled trials (N = 347). The overall relative risk (RR, 95% confidence interval) of discontinuation rates was not significantly different between groups (RR = 1.41, 95% CI = 0.78 to 2.56). The pooled standardized mean differences (SMDs, 95% CIs) (Z-test; number of study; I²-index) suggested trends of aripiprazole augmentation benefits on overall psychotic [−0.40 (−0.87 to 0.07) (n = 3; Z = 1.68, p = 0.09; I² = 68%)], positive [−1.05 (−2.39 to 0.29) (n = 3; Z = 1.54, p = 0.12; I² = 94%)], and negative [−0.36 (−0.77 to 0.05) (n = 3; Z = 1.74, p = 0.08; I² = 54%)] symptoms. Despite of no benefit on three cardiometabolic indices (i.e., fasting plasma glucose, triglyceride, and high-density lipoprotein), aripiprazole augmentation was superior for weight change with a mean difference (95% CI) of −1.36 kg (−2.35 to −0.36) (n = 3; Z = 2.67, p = 0.008; I² = 39%) and LDL-cholesterol with a mean difference of −11.06 mg/dL (−18.25 to −3.87) (n = 3; Z = 3.02, p = 0.003; I² = 31%). Aripiprazole augmentation was not correlated with headache and insomnia but significantly associated with agitation/akathesia (RR = 7.59, 95% CI = 1.43 to 40.18) (n = 3; Z = 2.38, p = 0.02; I² = 0%) and anxiety (RR = 2.70, 95% CI = 1.02 to 7.15) (n = 1; Z = 2.00, p = 0.05). The limited short-term data suggested that aripiprazole augmentation of clozapine can minimize the cardiometabolic risk, causes agitation/akathesia, and may be effective in attenuating psychotic symptoms.     

Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation

Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC₅₀ of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.     

Neutralizing antibody activity,safety and immunogenicity of human anti-rabies virus monoclonal antibody (Ormutivimab) in Chinese healthy adults: A phase Ⅱb randomized,double-blind,parallel-controlled study

ObjectiveThis study was a randomized, double-blind, parallel-controlled trail to evaluate the rabies virus neutralizing activity（RVNA）, safety and immunogenicity of Ormutivimab + rabies vaccine in Chinese healthy adults.MethodsSubjects were randomly and equally assigned to 4 groups (20 IU/kg Omtv + vaccine, 40 IU/kg Omtv + vaccine, 20 IU/kg HRIG + vaccine, and placebo + vaccine). Subjects received vaccine as the WHO Essen regime combined with Omutivimab、HRIG or placebo on Day 0. The study lasted for 43 days.ResultsA total of 240 subjects were simultaneously assigned to both FAS and SS. Fifty subjects with baseline RVNA > 0.05 IU/ml (detection limit) were excluded, 190 were included into mITT.All the subjects from 40 IU/kg Omtv + vaccine group had a protection level of RNVA (≥0.5 IU/ml, WHO) on Day 14, and those in 20 IU/kg Omtv + vaccine group and placebo + vaccine group converted positive 100 % on Day 28. In contrast to 20 IU/kg HRIG + vaccine and placebo + vaccine, Ormutivimab + vaccine provided a higher RVNA during Days 0 to 7. And RVNA in 40 IU/kg Omtv + vaccine and 20 IU/kg Omtv + vaccine groups were always higher than 20 IU/kg HRIG + vaccine group during the whole study. Although anti-Omtv antibody were detected in some subjects, it did not influence the RVNA. The incidence of adverse reactions was significantly lower in 20 IU/kg Omtv + vaccine group (17.2 %) than in 40 IU/kg Omtv + vaccine (36.7 %) and 20 IU/kg HRIG + vaccine groups (40.3 %).ConclusionCompared with HRIG + vaccine and placebo + vaccine, Omtv + vaccine provided higher RNVA for earlier immune protection. The interference of Ormutivimab on the long-term immune protection induced by rabies vaccine is weaker than HRIG. At the same dose, the adverse reactions of Omtv + vaccine group were less than HRIG + vaccine group.Registration: ClinicalTrials.gov #NCT02559921.     

Acquisition of Streptococcus pneumoniae in South African children vaccinated with 7-valent pneumococcal conjugate vaccine at 6, 14 and 40 weeks of age

BackgroundSeven-valent pneumococcal conjugate vaccine (PCV7) was introduced into the South African immunization program using 6, 14 and 40 weeks dosing schedule (2 + 1), with no catch-up in older children since April 2009. We investigated pneumococcal colonization acquisition in children who received this schedule and also compared it to historical cohorts of PCV-naïve children (n = 123 in 2007) and children who received a 3 + 1 PCV7 schedule (n = 124 in 2005/06).MethodsTwo hundred and fifty children aged 6–12 weeks were enrolled from December 2009 to April 2010. Participants had nasopharyngeal swabs collected on eight occasions between enrolment and 2-years of age. Standard methods were undertaken for bacterial culture and Streptococcus pneumoniae were serotyped using the Quellung method. Pneumococcal and Staphylococcus aureus colonization in the present study was compared to colonization in two historical longitudinal cohorts.ResultsS. pneumoniae was identified in 1081 (61.4%) of 1761 swabs collected in the current cohort. Pneumococcal colonization peaked at 41-weeks of age (76.8%) and decreased to 62.8% by 2-years of age (p = 0.002); PCV7-serotype colonization decreased during the same period from 28.6% to 15.6% (p = 0.001). Children from the current cohort compared to PCV-naïve children were less likely to be colonized by PCV7-serotypes from 40-weeks to 2-years of age and acquired PCV7-serotypes less frequently. No differences in overall pneumococcal, PCV7-serotype and non-PCV7-serotype colonization or new serotype acquisitions were detected comparing the current cohort to the historical cohort who received the 3 + 1 PCV7 schedule. Staphylococcus aureus colonization was similar in all three cohorts.ConclusionA 2 + 1 PCV7 schedule implemented in South Africa was temporally associated with reduced risk of vaccine-serotype colonization compared to historically unvaccinated children. Also, vaccine-serotype acquisition rate using the 2 + 1 schedule was similar to that in the 3 + 1 dosing cohort, suggesting that similar indirect protection against pneumococcal disease could be derived from either schedule in South Africa.     

Relationship between miRNAs polymorphisms and peripheral blood leukocyte DNA telomere length in coke oven workers: A cross-sectional study

ObjectiveThe purpose of this study was to investigate the factors affecting telomere length (TL) in coke oven workers by analyzing the interaction between miRNAs polymorphisms and coke oven emissions (COEs) exposure.MethodsA total of 544 coke oven workers and 238 healthy controls were recruited. Peripheral blood was collected from the subjects, genomic DNA was extracted, leukocyte TL was detected by real-time quantitative polymerase chain reaction, and fifteen polymorphisms of eight miRNAs were genotyped by flight mass spectrometry.ResultsStatistical analysis showed that the peripheral blood DNA TL in the exposure group was shorter than that in the control group (P < 0.001). Generalized linear model found that COEs-exposure [β (95%CI) = -0.427 (−0.556, −0.299), P < 0.001], genotype CC+CT for miR-612 rs1144925 [β (95%CI) = −0.367 (−0.630, −0.104), P = 0.006], and the interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure [β (95% CI) = 0.564 (0.108, 1.020), P = 0.015] were associated with the shortened TL.ConclusionCOEs-exposure and miR-612 rs1144925 TT could promote telomere shortening in coke oven workers. The interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure could protect telomere. This provides clues for further mechanistic studies between miRNA and telomere damage.     

Effects of green coffee bean extract on C-reactive protein levels: A systematic review and meta-analysis of randomized controlled trials

Background & objective: The effects of green coffee bean extract (GCBE) supplementation on inflammatory biomarkers have been widely spread. The purpose of this article was to assess the impact of GCBE supplementation on C-reactive protein (CRP) levels.MethodsThe literature search was performed in four databases (Scopus, PubMed, the Cochrane Library, and Google Scholar) to identify studies that examined the influence of GCBE supplementation on CRP levels up to August 2019. Mean and standard deviation (SD) of the outcomes were used to estimate the weight mean difference (WMD) between intervention and control groups for the follow-up period.ResultsFive (5) studies, with 6 arms, reported CRP as an outcome. Statistically, the use of GCBE supplements resulted in a significant change in CRP levels (WMD: −0.017 mg/dL, 95 % CI: −0.032, −0.003, p = 0.018), whose overall findings were obtained from random-effects model. In addition, a significantly greater reduction in CRP was noted for studies with doses of GCBE supplements ≥ 1000 mg/d (WMD: −0.015 mg/dL, 95 % CI: −0.020, −0.010, p < 0.000), length of intervention < 4 weeks (WMD: -0.015 mg/dL, 95 % CI: −0.020, −0.010, p < 0.001), and for non-healthy subjects (WMD: −0.019 mg/dL, 95 % CI: −0.027, −0.011, p < 0.001). Dyslipidemia, hypertension and non-alcoholic fatty liver disease were the ailments of the studies that encompassed non-healthy patients.ConclusionsThis meta-analysis shows that the use of GCBE supplements resulted in a statistical decrease in CRP levels, mainly for non-healthy subjects. However, due to the limited number of studies, further randomized clinical trials are crucial in this regard.