Transfusion related acute lung injury-TRALI: a review

Acute pulmonary damage caused by transfusion is characterized by the sudden onset of respiratory distress in newly transfused patients within 6 hours after the transfusion, bilateral infiltrative changes in chest X-ray, PaO2/FIO2 <300 mmHg, absence of other risk factors for acute lung injury and absence of signs suggesting cardiogenic origin of pulmonary edema. Being one of the most serious complications of blood transfusion, plasma is the most involved factor, although all blood components can cause it, and is caused by antigen reactions/leukocyte antibody and lipid activity with ability to modify the biological response on primitive leukocytes. The diagnosis is based on the integration of clinical, radiological and gasometric elements, ruling out the rest of the possible causes of acute lung injury. Its differential diagnosis should include hemodynamic overload, anaphylactic reaction, bacterial contamination of transfused blood products and transfusion hemolytic reaction. The treatment is supportive measures based on the needs and does not differ from the treatment of acute lung injury secondary to other etiologies, severe cases require endotracheal intubation and mechanical ventilation while the non-severe can be managed with oxygen therapy

Factors in AIDS Dementia Complex Trial Design: Results and Lessons from the Abacavir Trial

OBJECTIVES: To determine the efficacy of adding abacavir (Ziagen, ABC) to optimal stable background antiretroviral therapy (SBG) to AIDS dementia complex (ADC) patients and address trial design. DESIGN: Phase III randomized, double-blind placebo-controlled trial. SETTING: Tertiary outpatient clinics. PARTICIPANTS: ADC patients on SBG for ≥8 wk. INTERVENTIONS: Participants were randomized to ABC or matched placebo for 12 wk. OUTCOME MEASURES: The primary outcome measure was the change in the summary neuropsychological Z score (NPZ). Secondary measures were HIV RNA and the immune activation markers β-2 microglobulin, soluble tumor necrosis factor (TNF) receptor 2, and quinolinic acid. RESULTS: 105 participants were enrolled. The median change in NPZ at week 12 was +0.76 for the ABC + SBG and +0.63 for the SBG groups (p = 0.735). The lack of efficacy was unlikely related to possible limited antiviral efficacy of ABC: at week 12 more ABC than placebo participants had plasma HIV RNA ≤400 copies/mL (p = 0.002). There were, however, other factors. Two thirds of patients were subsequently found to have had baseline resistance to ABC. Second, there was an unanticipated beneficial effect of SBG that extended beyond 8 wk to 5 mo, thereby rendering some of the patients at baseline unstable. Third, there was an unexpectedly large variability in neuropsychological performance that underpowered the study. Fourth, there was a relative lack of activity of ADC: 56% of all patients had baseline cerebrospinal fluid (CSF) HIV-1 RNA <100 copies/mL and 83% had CSF β-2 microglobulin <3 nmol/L at baseline. CONCLUSIONS: The addition of ABC to SBG for ADC patients was not efficacious, possibly because of the inefficacy of ABC per se, baseline drug resistance, prolonged benefit from existing therapy, difficulties with sample size calculations, and lack of disease activity. Assessment of these trial design factors is critical in the design of future ADC trials

The burden of 14 hr-HPV genotypes in women attending routine cervical cancer screening in 20 states of Mexico: a cross-sectional study

In Mexico, HPV vaccines available immunize against genotypes 16/18 and 16/18/6/11; however, there is limited surveillance about carcinogenic subtypes in different states of the country that allow evaluating the effectiveness of vaccination and cervical cancer screening programs. Here, we report the regional and age-specific prevalence of 14 hr-HPV genotypes as well as their prevalence in abnormal cytology (from ASCUS to cervical cancer) among Mexican women which were undergoing from cervical cancer screening in the Salud Digna clinics in 20 states of the country. This study includes women with social security from the majority of public health institutions (IMSS, ISSSTE, SEMAR, and PEMEX), and women without social security. For cervical cancer screening, we used the SurePath liquid-based cytology and the BD Onclarity HPV Assay. From December 1, 2016, to August 2, 2018, the hr-HPV prevalence among 60,135 women was 24.78%, the most prevalent types were HPV 16 (4.13%), HPV 31 (4.12%) and HPV 51 (3.39%), while HPV 18 (1.70%) was less prevalent among infected women. Interestingly, the genotypes not covered by current vaccines in Mexico were commonly found in precancerous lesions, evidencing their carcinogenic potential, so it is necessary to increase their surveillance and inclusion in cervical cancer screening triage.We gratefully acknowledge to Iromy Meza, Jessica Avitia, and Oswaldo Carrillo for their technical support in obtaining databases during this project. Also, we want to thanks the staff of the Salud Digna clinics and the National Reference Center of Salud Digna for their support during this work. This work was funding by Salud Digna

Extrahepatic Anomalies in Infants With Biliary Atresia: Results of a Large Prospective North American Multicenter Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100275/1/hep26512.pd

Baseline ultrasound and clinical correlates in children with cystic fibrosis.

Objective: To investigate the relationship between abdominal ultrasound (US) findings and demographic, historical and clinical features in children with CF. Study design: Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multi-center study of US to predict hepatic fibrosis. Consensus US patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and U.S. or Toronto CF registries. Chi-square or ANOVA were used to compare variables among US groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal US. Results: Findings in 719 subjects were normal (n=590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (p=0.0004), homogeneous (p<0.0001) and heterogeneous (p=0.03) were older than normal. More males were heterogeneous (p=0.001). More heterogeneous (15.0%, p=0.009) and cirrhosis (25.0%, p=0.005) ha

Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia

OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes

A panel of induced pluripotent stem cells from chimpanzees: A resource for comparative functional genomics

Comparative genomics studies in primates are restricted due to our limited access to samples. In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates, we must have access to faithful model systems for a wide range of cell types. To facilitate this, we generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To demonstrate the utility of comparative iPSC panels, we collected RNA-sequencing and DNA methylation data from the chimpanzee iPSCs and the corresponding fibroblast lines, as well as from 7 human iPSCs and their source lines, which encompass multiple populations and cell types. We observe much less withinspecies variation in iPSCs than in somatic cells, indicating the reprogramming process erases many inter-individual differences. The low within-species regulatory variation in iPSCs allowed us to identify many novel inter-species regulatory differences of small magnitude