Descriptive analysis of sepsis in a developing country

BACKGROUND: Most studies on sepsis were conducted in developed countries. The aim of this study is to report on a series of patients with sepsis in a tertiary hospital in a developing country. METHODS: Patients admitted through the emergency department of a single university-based institution between January 2008 and June 2012, with a final diagnosis of sepsis, bacteremia, or septic shock, were retrieved. A sample of 97 patients was selected. Vital signs at presentation, number of SIRS criteria, use of vasopressors and steroids, and in-hospital mortality were recorded. RESULTS: The mean age was 70.09 ± 16.82, ranging from 19 to 96 years; 48.5 % were females and 51.5 % were males; 42.3 % of the patients were found to be bacteremic. IV fluid requirement during the first 6 h was 1.75 ± 1.96 l. The time for antibiotic initiation was 3.43 ± 4.48 h, with 87.6 % of the antibiotics initiated in the emergency department. Norepinephrine was the most commonly used vasopressor (38.1 %) followed by dopamine (8.2 %), and the inotrope dobutamine (4.1 %); 45.3 % of the patients were admitted to the intensive care unit (ICU), and the remaining 54.7 % were managed on the general practice unit (GPU). A total of 30 (30.9 %) septic patients died. The 28-day mortality was 20.6 %. Deceased patients had greater vasopressor use, a longer stay in the ICU (p = 0.001), and a longer time to norepinephrine use (p = 0.004). CONCLUSIONS: This is the first study providing an in-depth analysis of sepsis patients in a developing country, looking at in-hospital mortality, SIRS criteria utility, and at the overall sepsis management.Gilbert Abou Dagher, Mothana Saadeldine, Rana Bachir, Dina Zebian and Ralphe Bou Cheb

Cynicism and other attitudes towards patients in an emergency department in a middle eastern tertiary care center

Background: A caring, compassionate practitioner of the medical arts is the idealized version of what makes a good doctor. If asked to think of a painting of a doctor we most likely conjure an image of a physician sitting at a patient's bedside checking the pulse with a concerned look on his face. The reality is however that cynicism, among other negative attitudes, is becoming more prominent among physicians and medical staff. The causes and extent of cynicism likely vary among medical departments and different cultures. In this study, we aimed to assess attitudes of medical students and physicians in an Emergency Department (ED) in Lebanon that accommodates both local patients and is also known to attract patients from around the Middle East. Methods: A total of 30 students, residents and attending physicians at the American University of Beirut Medical Center were invited to participate. All participants underwent semi-structured interviews that were recorded, transcribed and then analyzed for common themes. Results: More negative emotions were expressed among participants than positive ones. Negative emotions were more frequently expressed among medical students, interns and residents than attending physicians. Cynicism in the ED was commonly reported however, maintenance of professionalism and adequate patient care were underscored. While empathy was recurrently found among participants, a trend towards a decrease in empathy with career progression was noted among attending physicians. Further, negative feelings towards patient families were prominent. Participants tended to categorize patients based on willingness to cooperate, gender, age, case acuity, ethnic origins and social status. Conclusions: Cynicism emerged as a prominent theme among medical students and staff in our study. However, participants were also empathetic. These attitudes were generally attributed to the peculiar stressors associated with the Lebanese culture, low acuity cases and "VIP" patients. It is crucial to explore methods in order to decrease cynicism and improve patient care. Also, the implications of these attitudes on patient care remain to be discovered.Nicholas J. Batley, Zeina Nasreddine, Ali Chami, Dina Zebian, Rana Bachir and Hussein A. Abba

Cross-Dimensional Mapping of Number, Length and Brightness by Preschool Children

Human adults in diverse cultures, children, infants, and non-human primates relate number to space, but it is not clear whether this ability reflects a specific and privileged number-space mapping. To investigate this possibility, we tested preschool children in matching tasks where the dimensions of number and length were mapped both to one another and to a third dimension, brightness. Children detected variation on all three dimensions, and they reliably performed mappings between number and length, and partially between brightness and length, but not between number and brightness. Moreover, children showed reliably better mapping of number onto the dimension of length than onto the dimension of brightness. These findings suggest that number establishes a privileged mapping with the dimension of length, and that other dimensions, including brightness, can be mapped onto length, although less efficiently. Children's adeptness at number-length mappings suggests that these two dimensions are intuitively related by the end of the preschool years

Protein Glycosylation in Helicobacter pylori: Beyond the Flagellins?

Glycosylation of flagellins by pseudaminic acid is required for virulence in Helicobacter pylori. We demonstrate that, in H. pylori, glycosylation extends to proteins other than flagellins and to sugars other than pseudaminic acid. Several candidate glycoproteins distinct from the flagellins were detected via ProQ-emerald staining and DIG- or biotin- hydrazide labeling of the soluble and outer membrane fractions of wild-type H. pylori, suggesting that protein glycosylation is not limited to the flagellins. DIG-hydrazide labeling of proteins from pseudaminic acid biosynthesis pathway mutants showed that the glycosylation of some glycoproteins is not dependent on the pseudaminic acid glycosylation pathway, indicating the existence of a novel glycosylation pathway. Fractions enriched in glycoprotein candidates by ion exchange chromatography were used to extract the sugars by acid hydrolysis. High performance anion exchange chromatography with pulsed amperometric detection revealed characteristic monosaccharide peaks in these extracts. The monosaccharides were then identified by LC-ESI-MS/MS. The spectra are consistent with sugars such as 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Ac7Ac) previously described on flagellins, 5-acetamidino-7-acetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Am7Ac), bacillosamine derivatives and a potential legionaminic acid derivative (Leg5AmNMe7Ac) which were not previously identified in H. pylori. These data open the way to the study of the mechanism and role of protein glycosylation on protein function and virulence in H. pylori

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma.

Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for ACVR1-mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 (K d = 150 nmol/L) and reduce DIPG cell viability in vitro but has limited ability to cross the blood-brain barrier. In addition to mTOR, everolimus inhibited ABCG2 (BCRP) and ABCB1 (P-gp) transporters and was synergistic in DIPG cells when combined with vandetanib in vitro. This combination was well tolerated in vivo and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Four patients with ACVR1-mutant DIPG were treated with vandetanib plus an mTOR inhibitor, informing the dosing and toxicity profile of this combination for future clinical studies. SIGNIFICANCE: Twenty-five percent of patients with the incurable brainstem tumor DIPG harbor somatic activating mutations in ACVR1, but there are no approved drugs targeting the receptor. Using artificial intelligence, we identify and validate, both experimentally and clinically, the novel combination of vandetanib and everolimus in these children based on both signaling and pharmacokinetic synergies.This article is highlighted in the In This Issue feature, p. 275

Cylindrospermopsin, a blue-green algal toxin, inhibited human luteinised granulosa cell protein synthesis in vitro

Abstract not availableFiona M. Young, Dina Zebian, Suzanne Froscio, Andrew Humpag

Validity and reliability of the Arabic version of the Household Food Insecurity Access Scale in rural Lebanon

OBJECTIVE: To assess the validity and reliability of the Arabic version of the Household Food Insecurity Access Scale (HFIAS) in rural Lebanon. DESIGN: A cross-sectional study on a sample of households with at least one child aged 0-2 years. In a one-to-one interview, participants completed an adapted Arabic version of the HFIAS. In order to evaluate the validity of the HFIAS, basic sociodemographic information, anthropometric measurements of the mother and child, and dietary intake data of the child were obtained. In order to examine reproducibility, the HFIAS was re-administered after 3 months. SETTING: Rural Lebanon. SUBJECTS: Mother and child pairs (n 150). RESULTS: Factor analysis of HFIAS items revealed two factors: 'insufficient food quality' and 'insufficient food quantity'. Using Pearson's correlation, food insecurity was inversely associated with mother's and father's education levels, number of cars and electrical appliances in the household, income, weight-for-age and length-for-age of the child and the child's dietary adequacy. In contrast, mother's BMI and crowding index were positively associated with food insecurity scores (P < 0·05 for all correlations). Cronbach's α of the scale was 0·91. A moderate correlation was observed between the two administrations of the questionnaire (intra-class correlation = 0·58; P < 0·05). CONCLUSIONS: Our findings indicated that the adapted Arabic version of the HFIAS is a valid and reliable tool to assess food insecurity in rural Lebanon, lending further evidence to the utility of the HFIAS in assessing food insecurity in culturally diverse populations.Farah Naja, Nahla Hwalla, Talar Fossian, Dina Zebian and Lara Nasreddin