Mowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS. In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

The aims of this study were (1) to assess the incidence of ventilator-associated pneumonia (VAP) in patients with traumatic brain injury (TBI), (2) to identify risk factors for developing VAP, and (3) to assess the prevalence of the pathogens responsible. The following data were collected prospectively from patients admitted to a 24-bed intensive care unit (ICU) during 2013/14: the mechanism of injury, trauma distribution by system, the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Abbreviated Injury Scale (AIS) score, the Injury Severity Score (ISS), underlying diseases, Glasgow Coma Scale (GCS) score, use of vasopressors, need for intubation or cardiopulmonary resuscitation upon admission, and presence of pulmonary contusions. All patients were managed with a standardized protocol if VAP was suspected. The Sequential Organ Failure Assessment (SOFA) score and the Clinical Pulmonary Infection Score (CPIS) were measured on the day of VAP diagnosis. Of the 144 patients with TBI who underwent mechanical ventilation for >48h, 49.3% did not develop VAP, 24.3% developed early-onset VAP, and 26.4% developed late-onset VAP. Factors independently associated with early-onset VAP included thoracic injury (odds ratio (OR) 8.56, 95% confidence interval (CI) 2.05-35.70; p=0.003), ISS (OR 1.09, 95% CI 1.03-1.15; p=0.002), and coma upon admission (OR 13.40, 95% CI 3.12-57.66; p<0.001). Age (OR 1.04, 95% CI 1.02-1.07; p=0.002), ISS (OR 1.09, 95% CI 1.04-1.13; p<0.001), and coma upon admission (OR 3.84, 95% CI 1.44-10.28; p=0.007) were independently associated with late-onset VAP (Nagelkerke r(2)=0.371, area under the curve (AUC) 0.815, 95% CI 0.733-0.897; p<0.001). The 28-day survival rate was 69% in the non-VAP group, 45.7% in the early-onset VAP group, and 31.6% in the late-onset VAP group. Acinetobacter spp was the most common pathogen in patients with early- and late-onset VAP. These results suggest that the extent of TBI and trauma of other organs influences the development of early VAP, while the extent of TBI and age influences the development of late VAP. Patients with early- and late-onset VAP harboured the same pathogens.

Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.

Objective: This paper aims to assess the impact of co-injuries and consequent emergency surgical interventions and nosocomial pneumonia on the 28-day mortality of patients with severe traumatic brain injuries (TBIs). Subjects and Methods: One hundred and seventy-seven patients with TBI admitted to the emergency trauma intensive care unit at the Clinical Center of Serbia for more than 48 h were studied over a 1-year period. On admission, the Glasgow Coma Scale (GCS), Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation II score (APACHE II) were calculated. At admission, an isolated TBI was recorded in 45 of the patients, while 44 had three or more co-injuries. Results: Of the 177 patients, 78 (44.1%) died by the end of the 28-day follow-up period. They had a significantly higher ISS score (25 vs. 20; p = 0.024) and more severe head (p = 0.034) and chest (p = 0.013) injuries compared to those who survived. Nonsurvivors had spent more days on mechanical ventilation (9.5 vs. 8; p = 0.041) and had a significantly higher incidence of ventilator-associated pneumonia (VAP) than survivors (67.9 vs. 40.4%; p < 0.001). A high Rotterdam CT score (OR 2.062; p < 0.001) and a high APACHE II score (OR 1.219; p < 0.001) were identified as independent predictors of early TBI-related mortality. Conclusion: Patients who had TBI with a high Rotterdam score and a high APACHE II score were at higher risk of 28-day mortality. VAP was a very common complication of TBI and was associated with an early death and higher mortality in the subgroup of patients with a GCS ≤8.

Objective: The aim of the study was to assess the impact of human papillomavirus (HPV) awareness and knowledge on physiological state and quality of life of women referred to colposcopy and/or HPV testing.Materials and Methods: A cross-sectional study was carried out at University Hospital, Belgrade, Serbia. The women with abnormal Pap test results obtained at the primary care centers requiring colposcopy and/or HPV testing were included. Before gynecological examination, participants filled the questionnaire on demographic characteristics, gynecological history, questionnaire for the evaluation of HPV awareness and HPV knowledge level, a set of self-report questionnaires assessing the anxiety level, quality of life, and concern about the smear and colposcopy results and perceived risk of developing cervical cancer.Results: Of 324 women, 196 (60.5%) were aware of HPV. They reported higher concern about test results (p< .001), perceived risk of developing cervical cancer (p< .001), and had significantly lower quality of life (p= .004) than women who did not hear anything about this virus. On contrary, better knowledge correlated with younger age (p< .001) and better quality of life (p< .0001) and was associated with lower anxiety, lower concern about smear test results, and lower perceived risk of developing cancer.Conclusions: Human papillomavirus awareness and knowledge have different impact on psychological state and quality of life. Being aware of HPV is not enough for reducing the stress and anxiety and increasing the coverage of screening. Therefore, it is necessary to increase women's knowledge through more detailed information about HPV in different public health messages and education programs.