Clinical analysis of etiology, risk factors and outcome in patients with acute kidney injury.

Acute kidney injury is characterized by a rapid loss of renal excretory function with the increase of nitrogen compounds in the blood and with different outcome. Objective: Since descriptions of the risk factors and sequelae of acute kidney injury (AKI) remain relatively limited, the objective of this study was to determine etiology and clinical characteristics of AKI, as well as risk factors for adverse outcome of renal function and death in AKI patients. Methods: We retrospectively studied a cohort of 84 adult AKI patients admitted to Nephrology Clinic in University Clinical Centre Sarajevo during period 2012-2014. Demographic, laboratory and clinical parameters were retrieved. The in-hospital and 6 months mortality were recorded. Renal function outcome was defined 3 months following discharge. Results: Majority of patients were older (median age 73.5 years) with great severity of AKI (Stage III in 78.5% of cases) and high burden of comorbidities (mean Charlson comorbidity index, CCI score 6.4±3.05). The most common causes of AKI were acute interstitial nephritis (16.7%), heart failure (15.5%), gastroenterocolitis (13.1%), and sepsis (12%). Renal function recovery was recorded in 48.8% of patients, with prevalence of 10.7% of intrahospital mortality and 37.3% of 6 months mortality. Risk factors for poor outcome of renal function and mortality in AKI patients were increasing age and higher CCI score, while protective factor was higher diuresis. Sepsis proved to be risk factor for deat

Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing

sorLA is a sorting receptor for amyloid precursor protein (APP) genetically linked to Alzheimer's disease (AD). Retromer, an adaptor complex in the endosome-to-Golgi retrieval pathway, has been implicated in APP transport because retromer deficiency leads to aberrant APP sorting and processing and levels of retromer proteins are altered in AD. Here we report that sorLA and retromer functionally interact in neurons to control trafficking and amyloidogenic processing of APP. We have identified a sequence (FANSHY) in the cytoplasmic domain of sorLA that is recognized by the VPS26 subunit of the retromer complex. Accordingly, we characterized the interaction between the retromer complex and sorLA and determined the role of retromer on sorLA-dependent sorting and processing of APP. Mutations in the VPS26 binding site resulted in receptor redistribution to the endosomal network, similar to the situation seen in cells with VPS26 knockdown. The sorLA mutant retained APP-binding activity but, as opposed to the wild-type receptor, misdirected APP into a distinct non-Golgi compartment, resulting in increased amyloid processing. In conclusion, our data provide a molecular link between reduced retromer expression and increased amyloidogenesis as seen in patients with sporadic AD

Treatment Outcomes and Costs at Specialized Centers for the Treatment of PTSD After the War in Former Yugoslavia

Objective: Posttraumatic stress disorder (PTSD) is a frequent consequence of war experience, and specialized centers have been established in some war-affected areas to provide treatment. This study assessed treatment costs and outcomes in such centers in former Yugoslavia. Methods: An observational study was conducted in four specialized treatment centers (in Serbia, Croatia, and Bosnia-Herzegovina). A total of 526 consecutive adult patients with war-related PTSD were assessed at the beginning of treatment, and 463 met inclusion criteria, including a diagnosis of PTSD on the Clinician-Administered PTSD Scale for DSM-IV (CAPS). For most patients seven years had elapsed between the traumatic experience and treatment at the specialized center. Service costs were also assessed. Outcomes measured at one year were the presence of a PTSD diagnosis and severity of symptoms as indicated by the CAPS score and subjective quality of life as measured by the Manchester Short Assessment of Quality of Life. Results: At 12 months 380 (82%) patients were followed up, and 325 (86%) met criteria for PTSD. Symptoms and quality of life showed overall small but statistically significant improvements. Treatment costs for patients with and without PTSD at 12 months did not significantly differ ((sic)307 and (sic)284, respectively). Conclusions: The recovery rate among patients treated in specialized centers for war-related PTSD several years after the war was poor (14%), and symptom improvements were small. The recovery rate was not linked to service costs. Improving recovery rates might require different treatment methods or different service models. (Psychiatric Services 61:598-604, 2010

Association of polygenic risk scores, traumatic life events and coping strategies with war-related PTSD diagnosis and symptom severity in the South Eastern Europe (SEE)-PTSD cohort

Objectives Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. Methods Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. Results The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. Conclusions The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk