Complication rates in managing hepatic trauma: a cross-sectional study stratifying their outcomes

Background: Liver trauma is the most commonly observed injured organ in abdominal trauma. The objectives of this study was to determine and evaluate the rates of complication in the management of liver traumaMethods: This cross-sectional observational study using non-probability convenient sampling technique was done at surgical unit of Liaquat University of Medical and Health Sciences, Jamshoro, for 06 months. After ethical approval from Institute’s Institutional Review Board (IRB), patients presenting to surgical emergency of the hospital between ages 16 to 60 years having blunt or penetrating liver trauma within 04 hours of incident, either road traffic accident, sustaining a fall, sporting injury, knife or stab wound were include while patients of liver trauma conservatively managed or had severe co-morbid, not fit for anesthesia, with multiple organs lesions (polytrauma) and all hepatic injury patients that were hemo-dynamically stable were excluded. SPSS version 23 was used for data analysis keeping p-value <0.05 as significant.Results: Among 136 patients with mean age 32.33±11.23 years, 120(88.2%) were males. 122(89.7%) of the patients were admitted due to liver trauma of blunt variety while 14(10%) with penetrating liver injury. Overall mean duration of hospital stay was 13.1±4.58 days. 41(30%) patients reported intra-abdominal sepsis, followed by recurrent hemorrhage in 33(24%) of patients while in 22(16%) of patients, biliary leakage was observed. An insignificant difference persisted in either surgical intervention in terms of the complication rates.Conclusions: Higher complication rates were observed in patients with peri-hepatic packing, however outcome of both surgical techniques in terms of complication rates were found to be insignificant. Further studies are needed to shed light upon the findings or this study

Outcomes of surgical management of liver trauma at LUMHS Jamshoro

Background: Mortality from liver trauma remains high despite surgical advancements. The objective of this study was to determine the outcomes of surgical management of liver trauma at LUMHS Jamshoro.Methods: A cross-sectional observational study using non-probability convenient sampling technique was done at department of surgery LUMHS Jamshoro for 18 months. Patients between 14 to 50 years with blunt hepatic trauma presenting to the E.R. within 04 hours of incident were included and hepatic trauma patients managed conservatively, having multiple trauma and hemo-dynamically stable were excluded. SPSS version 20 was used for data analysis with mean and SD reported for qualitative and frequency and percentages for quantitative variables. Chi-square test was applied keeping p-value of < 0.05 as statistically significant.Results: From 136 patients with mean age of 32.33±1.23 years, 120 (88%) were male. 122 (89.7%) were admitted due to blunt trauma and 14 (10.3%) due to penetrating trauma. Peri-hepatic packing was performed in 116 (85.2%) and suture hepatorrhaphy in 20 (14.8%). Intra-abdominal sepsis was seen in 41 (30%) of patients followed by recurrent hemorrhage in 33 (24%) while 30 (22%) of patients died. Substantial differences (p < 0.001) were observed in terms of surgical technique and each of the complication i.e. sepsis, bile leak and recurrent hemorrhage among alive patientsConclusions: The most common post-operative complication was intra-abdominal sepsis followed by recurrent haemorrhage and bile leak. Significant mortality was observed in between type of complication as well as surgical technique

B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus

Background: Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities. The purpose of this study was to determine the role of B cells and/or autoantibodies in the pathogenesis of murine NPSLE. Methods: We evaluated neuropsychiatric manifestations, brain pathology, and cytokine expression in constitutively (JhD/MRL/lpr) and conditionally (hCD20-DTA/MRL/lpr, inducible by tamoxifen) B cell-depleted mice as compared to MRL/lpr lupus mice. Results: We found that autoantibody levels were negligible (JhD/MRL/lpr) or significantly reduced (hCD20-DTA/MRL/lpr) in the serum and cerebrospinal fluid, respectively. Nevertheless, both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice showed profound depression-like behavior, which was no different from MRL/lpr mice. Cognitive deficits were also observed in both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice, similar to those exhibited by MRL/lpr mice. Furthermore, although some differences were dependent on the timing of depletion, central features of NPSLE in the MRL/lpr strain including increased blood-brain barrier permeability, brain cell apoptosis, and upregulated cytokine expression persisted in B cell-deficient and B cell-depleted mice. Conclusions: Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE

Yield of facility-based targeted universal testing for tuberculosis with Xpert and mycobacterial culture in high-risk groups attending primary care facilities in South Africa

DATA SHARING : Individual participant data that underlie the results reported in this article, after de-identification, the data dictionary, study protocol, statistical analysis plan, and analytic code will be made available to investigators whose proposed use of the data has been approved by an independent review committee to achieve aims in the approved proposal. Proposals should be submitted to N. A. M. ([email protected]). To gain access, data requestors will need to sign a data access agreement.BACKGROUND : We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups. METHODS : Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture. We report the proportion positive for Mycobacterium tuberculosis. Data were analyzed descriptively. The unadjusted clinical and demographic factors’ relative risk of TB detected by culture or Xpert were calculated and concordance between Xpert and culture is described. RESULTS : A total of 30 513 participants had a TB test result. Median age was 39 years, and 11 553 (38%) were men. The majority (n=21734, 71%) had HIV, 12 492 (41%) reported close contact with a TB patient, and 1573 (5%) reported prior TB. Overall, 8.3% were positive for M. tuberculosis by culture and/or Xpert compared with 6.0% with trace-positive results excluded. In asymptomatic participants, the yield was 6.7% and 10.1% in symptomatic participants (with trace-positives excluded). Only 10% of trace-positive results were culture-positive. We found that 55% of clinic attendees with a sputum result positive for M. tuberculosis did not have a positive TB symptom screen. CONCLUSIONS : A high proportion of clinic attendees with specific risk factors (HIV, close TB contact, history of TB) test positive for M. tuberculosis when universal testing is implemented.The Bill & Melinda Gates Foundation, the National Institutes of Health, all laboratory testing was paid for by the Government of South Africa.https://academic.oup.com/cidam2024Family MedicineSDG-03:Good heatlh and well-bein

Point Mutations in Aβ Result in the Formation of Distinct Polymorphic Aggregates in the Presence of Lipid Bilayers

A hallmark of Alzheimer's disease (AD) is the rearrangement of the β-amyloid (Aβ) peptide to a non-native conformation that promotes the formation of toxic, nanoscale aggregates. Recent studies have pointed to the role of sample preparation in creating polymorphic fibrillar species. One of many potential pathways for Aβ toxicity may be modulation of lipid membrane function on cellular surfaces. There are several mutations clustered around the central hydrophobic core of Aβ near the α-secretase cleavage site (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These point mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy (CAA) to typical Alzheimer's disease pathology with plaques and tangles. We investigated how these point mutations alter Aβ aggregation in the presence of supported lipid membranes comprised of total brain lipid extract. Brain lipid extract bilayers were used as a physiologically relevant model of a neuronal cell surface. Intact lipid bilayers were exposed to predominantly monomeric preparations of Wild Type or different mutant forms of Aβ, and atomic force microscopy was used to monitor aggregate formation and morphology as well as bilayer integrity over a 12 hour period. The goal of this study was to determine how point mutations in Aβ, which alter peptide charge and hydrophobic character, influence interactions between Aβ and the lipid surface. While fibril morphology did not appear to be significantly altered when mutants were prepped similarly and incubated under free solution conditions, aggregation in the lipid membranes resulted in a variety of polymorphic aggregates in a mutation dependent manner. The mutant peptides also had a variable ability to disrupt bilayer integrity

Anti-α-Internexin Autoantibody from Neuropsychiatric Lupus Induce Cognitive Damage via Inhibiting Axonal Elongation and Promote Neuron Apoptosis

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major complication for lupus patients, which often leads to cognitive disturbances and memory loss and contributes to a significant patient morbidity and mortality. The presence of anti-neuronal autoantibodies (aAbs) has been identified; as examples, anti-NMDA receptors and anti-Ribsomal P aAbs have been linked to certain pathophysiological features of NPSLE.In the current study, we used a proteomic approach to identify an intermediate neurofilament alpha-internexin (INA) as a pathogenetically relevant autoantigen in NPSLE. The significance of this finding was then validated in an expanded of a cohort of NPSLE patients (n = 67) and controls (n = 270) by demonstrating that high titers of anti-INA aAb was found in both the serum and cerebrospinal fluid (CSF) of ∼50% NPSLE. Subsequently, a murine model was developed by INA immunization that resulted in pronounced cognitive dysfunction that mimicked features of NPSLE. Histopathology in affected animals displayed cortical and hippocampal neuron apoptosis. In vitro studies further demonstrated that anti-INA Ab mediated neuronal damage via inhibiting axonal elongation and eventually driving the cells to apoptosis.Taken together, this study identified a novel anti-neurofilament aAb in NPSLE, and established a hitherto undescribed mechanism of aAb-mediated neuron damage that could have relevance to the pathophysiology of NPSLE

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

Morphology-Tailored Dynamic State Transition in Active-Passive Colloidal Assemblies

Mixtures of active self-propelled and passive colloidal particles promise rich assembly and dynamic states that are beyond reach via equilibrium routes. Yet, controllable transition between different dynamic states remains rare. Here, we reveal a plethora of dynamic behaviors emerging in assemblies of chemically propelled snowman-like active colloids and passive spherical particles as the particle shape, size, and composition are tuned. For example, assembles of one or more active colloids with one passive particle exhibit distinct translating or orbiting states while those composed of one active colloid with 2 passive particles display persistent “8”-like cyclic motion or hopping between circling states around one passive particle in the plane and around the waist of 2 passive ones out of the plane, controlled by the shape of the active colloid and the size of the passive particles, respectively. These morphology-tailored dynamic transitions are in excellent agreement with state diagrams predicted by mesoscale dynamics simulations. Our work discloses new dynamic states and corresponding transition strategies, which promise new applications of active systems such as micromachines with functions that are otherwise impossible