Urokinase (uPA) and urokinase plasminogen activator receptor (uPAR/PLAUR) mediate fibrinolysis and matrix remodeling. Liberation of monocyte/macrophage (MO/Mφ)-bound soluble uPAR (suPAR) occurs after infection with coronaviruses (CoVs) such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), correlating with systemic inflammatory stress and end-organ injury severity. How suPAR liberation from MO/Mφs occurs after CoV infection, and whether suPAR induction is exclusive to coronavirus infection or occurs from other clinically significant coagulopathy-inducing pneumotropic viral infections such as influenza A (IAV), is unknown. We noted increased PLAUR transcripts in peripheral blood mononuclear cells (PBMCs) from SARS-CoV-2-positive and IAV-positive patients. Elevated suPAR liberation was observed after murine CoV infection but not IAV infection-both of which led to increased MO/Mφ mRNA and cell-bound uPA and uPAR, and increased secreted uPA activity. uPA knockdown in MO/Mφs abrogated suPAR liberation and blunted tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 induction post-CoV, suggesting that targeting co-regulators of uPAR and uPA may be beneficial in attenuating coronavirus-driven inflammatory cytokine responses, and treating diseases characterized by suPAR release from Mφs.

Introduction: Preeclampsia (PreE) is a hypertensive disorder of pregnancy diagnosed after 20 weeks of gestation. While broadly characterized by hypertension (HTN), systemic inflammation, and end-organ injury, PreE varies in severity and presentation, and its impact on maternal brain health remains unclear. Small studies show increased neuronal injury biomarkers in women with PreE, suggesting potential neuronal damage. This study evaluated serum neurofilament light chain (NfL), a marker of axonal injury, and phosphorylated tau-217 (ptau217), a marker elevated in Alzheimer’s disease (AD), to assess brain injury in PreE. Hypothesis: We hypothesized that neuronal injury occurs during PreE and that NfL and ptau217 would be elevated. Methods: A cohort of 184 pregnant patients (32 ± 6 y) were enrolled. Blood samples were collected between 18–40 weeks of gestation. PreE patients (N=85) were compared to non-PreE controls (N=99). Serum concentrations of NfL and ptau217 were measured by ELISA and analyzed by PreE status. Results: NfL was elevated in PreE patients during both the 2nd trimester (p<0.01) and 3rd trimester (p<0.001) versus controls, suggesting axonal injury. Unexpectedly, ptau217 was significantly lower in PreE patients during the 3rd trimester (p<0.001) compared to controls. Conclusion: Women with PreE demonstrated elevated NfL levels, consistent with neuronal injury. However, contrary to our hypothesis, ptau217 levels were decreased. One explanation may be that healthy neonates have high ptau217 levels critical for early brain development, and PreE may disrupt this maternal-fetal transfer. This is the first study to investigate ptau217 in pregnant women. These biomarkers may reflect maternal neuronal damage (NfL) and possible fetal effects (ptau217). Given the growing recognition that hypertensive disorders of pregnancy increase risk for later cognitive decline and vascular dementia, longitudinal studies are critical. Biomarkers may aid in identifying women at higher risk for cerebrovascular and neurodegenerative disease following adverse pregnancy events.

OSA is a prevalent chronic condition characterized by repetitive upper airway collapse that promotes the occurrence of gas exchange abnormalities reflected as intermittent hypoxia (IH) along with heightened risk for the occurrence of end-organ morbidity. Here, we examine the molecular and cellular mechanisms driving OSA-induced morbidity. We describe the maladaptive responses to chronic IH, including stress programs, primarily driven by bursts of reactive oxygen species (ROS) that overwhelm antioxidant defenses and trigger robust, NF-κB-mediated inflammatory cascades (e.g. TNF-α, IL-6). These responses, strikingly different from the adaptive responses to sustained hypoxia, lead to systemic consequences, including endothelial dysfunction, hypertension, and profound metabolic dysfunction with insulin resistance. Understanding this pathophysiology is complicated by marked cellular and tissue heterogeneity, with different cell populations (e.g. endothelium, adipose tissue or different brain regions) exhibiting divergent, context-dependent responses to IH (i.e. inflammation versus repair). Traditional bulk-tissue analyses and clinical metrics, such as the AHI or hypoxic burden, fail to capture in their entirety this cellular and tissue heterogeneity and the critical kinetics of IH, particularly during reoxygenation. Critical knowledge gaps remain, including the need to standardize IH exposure metrics (capturing cycle frequency, hypoxic depth, and reoxygenation kinetics), integrate circadian context and other OSA-related stressors (e.g. episodic hypercapnia, fragmented sleep), account for key biological modifiers (sex, age, genetic background, comorbidities), and determine the potential reversibility of IH-induced injury. Addressing these gaps will be essential to advance OSA diagnostic and therapeutic approaches. Integrating multi-omics profiling and physiological modeling within standardized IH paradigms offers a pathway toward patient-tailored interventions.

Background:Failure of cerebrovascular reserve is a fundamental determinant of ischemic vulnerability, yet the mechanisms by which vascular smooth muscle dysfunction compromises reserve and predisposes the brain to injury remain incompletely defined. We therefore tested whether a pathogenic smooth muscle mutation produces a baseline failure of cerebrovascular reserve sufficient to render the brain vulnerable to hypoperfusion, even in the absence of fixed arterial occlusion.Methods:We examined cerebrovascular structure, hemodynamics, and reserve in a genetically defined mouse model of ACTA2-associated multisystemic smooth muscle dysfunction syndrome with systemic or brain-restricted expression of the mutant allele. Cerebral artery morphology was assessed using magnetic resonance angiography and black ink angiography. Vascular smooth muscle phenotype was evaluated by immunohistochemistry and proliferation assays. Blood pressure reactivity and cerebral blood flow (CBF) were measured simultaneously using femoral arterial catheterization and laser speckle flowmetry during vasoactive challenges and controlled hypotension. Cerebrovascular stress responses were tested using unilateral common carotid artery occlusion. Downstream brain effects were assessed by histology, resting state functional connectivity imaging, and behavioral testing.Results:Impaired smooth muscle contractility drove rectification and narrowing of major cerebral arteries, downregulation of contractile markers, and increased vascular cell proliferation. These structural changes produced a distinct physiological phenotype: mutant mice exhibited blunted vasoreactivity, diminished spontaneous vasodynamic activity, and a downward shift in the blood pressure-CBF relationship across a wide range of arterial pressures, consistent with loss of cerebrovascular reserve. As a result, CBF was reduced at baseline and could not be maintained during hypotension or acute vascular stress. During carotid occlusion, mutant mice showed impaired compensatory perfusion, greater physiological instability, and worse behavioral outcomes. Chronic reserve failure coincided with white matter loss, reduced neuronal density, disrupted large-scale functional connectivity, and deficits in locomotion, anxiety-related behavior, and working memory.Conclusions:Pathogenic smooth muscle dysfunction caused by ACTA2 mutation produces a baseline failure of cerebrovascular reserve that renders the brain vulnerable to hypoperfusion and stress-induced ischemic injury. These findings establish cerebrovascular reserve failure as a central physiological mechanism linking vascular dysfunction to end-organ brain injury and identify reserve preservation as a critical, potentially actionable determinant of brain health in hypotension-prone vascular disease.

Hemoglobin Binders Reduce Inflammation and Tissue Injury from Hemolysis in Venovenous Extracorporeal Circulation.

ObjectivesThis study hypothesizes that induced hypothermia (IH) can safely extend aortic cross-clamp (ACC) time, significantly reducing metabolic burden and end-organ injury, thereby enabling more comprehensive aortic arch reconstructions and offering distinct advantages.MethodsIn this experimental animal research, 62 New Zealand white rabbits were randomized into normothermia (39°C) and mild hypothermia (35°C) groups. Animals in each group underwent proximal aortic arch (PAA) clamping for 20, 30, or 40 minutes. Serial blood samples measured biochemistry, oxidative stress biomarkers, arterial and mixed venous blood gases, and lactate levels. Kidney and liver tissues were harvested for histopathological evaluation of ischaemic changes.ResultsNormothermic rabbits experienced significant increases in oxidative stress, metabolic acidosis, and end-organ injury (renal, hepatic, and exclusively, spinal cord injury) with prolonged clamping. Conversely, IH markedly attenuated these adverse effects, preserving acid-base balance and reducing histological injury. Notably, the metabolic burden and end-organ injury observed after 30 minutes of hypothermic ischaemia were comparable with those after 20 minutes of normothermic ischaemia, suggesting a substantial extension of safe clamping time.ConclusionsInduced hypothermia during ACC provides significant protection against ischaemia-reperfusion injury by minimizing oxidative damage, preserving antioxidant capacity, and maintaining metabolic balance, thereby enhancing haemodynamic function post-surgery. This approach allows for safely extended ACC times, with a safety margin appearing to correspond to 30 minutes under hypothermia, facilitating complex aortic arch reconstructions and enabling safer surgical training. Clinical trials are warranted to confirm these findings in humans.

Hypotension is a frequent complication after induction of general anaesthesia leading to end-organ injury, for which elderly and multimorbid patients are particularly susceptible. The extent of hypotension depends, among other factors, on the dose and rate of propofol administration. Target-controlled infusion systems are widely used to administer short-acting anaesthetics such as propofol and remifentanil. Commonly, induction is started with a fixed effect-site concentration. Titration, an alternative method of induction using an incremental augmentation of propofol, leads to a reduced induction dose and rate of propofol. We hypothesise that the titration method improves haemodynamic stability compared with conventional induction. This multicentre, expertise-based randomised controlled trial takes place at four Swiss hospitals. Patients ≥55 years of age undergoing non-cardiac surgery under general anaesthesia using propofol target-controlled infusion are randomised to either a conventional or a titrated anaesthesia induction method. Patients, statisticians and, if resources allow, outcome assessors will be blinded. The primary endpoint is the mean arterial pressure under the individual baseline mean arterial pressure (area under threshold) during the first 30 min after start of induction. Secondary endpoints include the maximum deviation from baseline mean arterial pressure, haemodynamic rescue methods, propofol consumption and neurocognitive recovery after regaining consciousness.A total of 320 patients are required to have an 80% chance of observing superiority of titration for the area under the threshold as significant at the 5% level, assuming a true difference of 100 mm Hg*min. The area under threshold and the maximum deviation will be compared between arms using mixed linear regression models. Ethical approval has been obtained from all responsible ethics committees (BASEC2025-01007). The results will be presented at international meetings and published in peer-reviewed journals and may contribute to a change in clinical practice for anaesthesia induction using target-controlled infusion systems with propofol. clinicaltrials.gov (NCT06980688) and www.humanforschung-schweiz.ch (HumRes67022).

Background: Aspartate aminotransferase (AST) and alanine transaminase (ALT) are commonly used to assess liver function, but they also increase in acute myocardial infarction (AMI) as a result of myocardial injury and hemodynamic compromise. ALT is relatively specific for hepatocellular injury, whereas AST is also present in cardiac tissue and rises during cellular necrosis. Therefore, the AST/ALT (De Ritis) ratio has been proposed as a potential marker for end-organ ischemic injury. This study aimed to evaluate the prognostic value of the De Ritis ratio in AMI patients undergoing percutaneous coronary intervention (PCI). Methods: A retrospective cohort study was conducted on patients with STEMI and NSTEMI undergoing PCI. Blood samples were taken upon emergency department admission to measure AST and ALT, and the De Ritis ratio was calculated. Major adverse cardiovascular events (MACE) were assessed during hospitalization and up to 30 days after discharge. Receiver operating characteristic analysis determined the optimal cutoff, while Kaplan–Meier and Cox regression analyses were used for outcome evaluation. Results: Among 278 patients, in-hospital MACE occurred significantly more often in those with a De Ritis ratio ≥2.03 (p = 0.014). A high De Ritis ratio was an independent predictor of in-hospital MACE (HR = 1.842, p = 0.001), along with pre-procedural TIMI flow, hs-troponin, and NLR. However, the De Ritis ratio was not an independent predictor of 30-day MACE (HR = 2.208, p = 0.557). Conclusion: The De Ritis ratio independently predicts in-hospital MACE in AMI patients undergoing PCI.

Introduction: Hypertension is a leading global health concern, characterised by chronic low-grade inflammation and oxidative stress that drive a vicious cycle of vascular dysfunction, endothelial damage, and end-organ injury. Aim: This study evaluated serum levels of inflammatory and oxidative stress biomarkers among hypertensive adults in Port Harcourt, Nigeria, to examine the variation in these biomarkers between untreated and treated hypertensive subjects. Methods: This cross-sectional study enrolled 150 participants aged 25-65 years, divided into three groups: 50 treated hypertensives on medication, 50 newly-diagnosed untreated hypertensives, and 50 normotensive controls. All participants underwent anthropometric and blood pressure measurements. Venous blood (5mL) was collected for the laboratory quantification of serum levels of inflammatory markers: C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α), and oxidative stress biomarkers: malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). Results: Findings reveal that study participants were relatively age-matched across the groups. Our data show significantly elevated body mass index (BMI), MDA, CRP and TNF among the treated hypertensive subjects compared to both the untreated hypertensive and normotensive controls (p<0.05). Conversely, we observed significantly reduced levels of GSH, GPx, CAT and SOD among the treated and untreated hypertensive groups compared to the normotensive control (p<0.05). Conclusion: The current study demonstrates that hypertension is characterised by chronic immuno-inflammatory dysregulation mediated by reactive oxygen species (ROS), which drives endothelial dysfunction and arterial stiffness. The persistence of these inflammatory and oxidative stress markers in treated patients underscores the need for adjunct antioxidant and immunomodulatory supplementation to improve vascular outcomes in hypertension.

Pediatric cardiac surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest is associated with global myocardial ischemia-reperfusion (IR) injury, leukocyte activation, and a systemic inflammatory response that contributes to early postoperative morbidity and mortality. The mechanisms for acute myocardial dysfunction and end-organ injury after pediatric heart surgery are complex and incompletely understood. This study aimed to: (1) investigate the contributions of the toll-like receptor-4 (TLR-4) pro-inflammatory and the pro-survival hypoxia-inducible factor-1α/phosphatidylinositol 3-kinase (HIF-1α/PI3K) pathways to global myocardial IR injury and inflammation, and (2) evaluate the impact of nicorandil, a coronary vasodilator and anti-ischemic agent, on TLR-4 and HIF-1α/PI3K signaling and end-organ dysfunction in a neonatal piglet model of CPB and cardioplegic arrest.Piglets (4-5 weeks old, N = 12) were randomly assigned to IR or IR + nicorandil. After initiation of CPB with cardioplegic arrest, hearts were reperfused on partial CPB, followed by complete separation from CPB. Left ventricular (LV) systolic and diastolic pressures were continuously recorded, and serial blood and terminal tissue samples were collected to measure inflammation, oxidant stress (OS), and apoptosis.CPB with cardioplegic arrest transiently and significantly impaired both LV contractility (p = 0.01) and diastolic relaxation (p = 0.001) associated with a 39-fold increase in cardiac TLR-4 expression (p = 0.034), a 3-fold increase in IL-6 production (p = 0.01), and significant increases in plasma markers for end-organ injury, but without the expected upregulation in the HIF-1α/PI3K pro-survival pathway. Nicorandil pre-treatment significantly augmented LV systolic (p = 0.004) and diastolic (p = 0.002) functional recovery associated with attenuated upregulation of TLR-4 signaling pathways, augmented HIF-1α/PI3K pro-survival signaling, and reduced inflammation, OS, apoptosis, and end-organ injury.Our piglet model of CPB with cardioplegic arrest demonstrates that the TLR-4 pro-inflammatory signaling pathway plays an essential role in myocardial IR-induced cardiac dysfunction, inflammation, OS, apoptosis, and multi-organ injury. Nicorandil pre-treatment attenuates these effects. Nicorandil also upregulates the HIF-1α/PI3K pro-survival signaling pathway. These results suggest that nicorandil should be studied further to assess its potential therapeutic effects after CPB in children.

Adverse events after durable left ventricular assist devices (LVADs) pose a challenge to survival. However, there are limited risk stratification approaches. Plasma cell-free DNA (cfDNA) offers potential as a biomarker for assessing end-organ injury and risk stratification. The study included a multicenter prospective cohort of patients with heart failure with and without LVAD (cohort 1), a separate cohort of patients with heart failure with paired samples before and after LVAD (cohort 2) implantation, and a comparator group of healthy controls. Nuclear cfDNA (ncfDNA) and mitochondrial cfDNA were quantified by digital droplet polymerase chain reaction. Tissue-specific cfDNA was identified using whole-genome bisulfite sequencing. Differences in cfDNA levels by LVAD use were assessed with the Wilcoxon rank-sum test or the paired t test. Outcomes (hemocompatibility-related adverse event-free survival and infection-free survival) by cfDNA tertiles were compared by log-rank tests. Cohort 1 had 76 patients with LVAD and 144 without LVAD. Cohort 2 had 40 patients with LVAD with samples before and after LVAD. ncfDNA levels were 4-fold higher (9794 versus 2386 copies/mL; P<0.001), and mtDNA was 1.5-fold higher (134 707 versus 82 054 copies/mL; P=0.01) in cohort 1 compared with healthy controls (n=48). Patients without LVAD had higher ncfDNA levels compared with those with LVAD in cohort 1 (11 423 versus 7912 copies/mL; P=0.019). After LVAD placement in cohort 2, ncfDNA nearly halved (18 980 versus 10 228 copies/mL; P<0.001), with significant reductions in innate immune, vascular endothelium, gastrointestinal, and liver cfDNA levels. The highest pre-LVAD tertile of ncfDNA was associated with worse infection-free (hazard ratio, 2.94 [95% CI, 1.31-6.56]; P=0.006) and hemocompatibility-related adverse event-free (hazard ratio, 3.24 [95% CI, 1.03-10.3]; P=0.034) survival. LVAD implantation was associated with reductions in systemic and tissue-specific cfDNA levels. cfDNA levels offer promise for improving risk stratification of LVAD candidates for post-LVAD outcomes.

Cholesterol crystal embolization syndrome: Systemic and end-organ injury.

Perioperative Normoxia vs Hyperoxia in Neonates With Cyanotic Heart Disease Undergoing Cardiac Surgery: A Randomized Controlled Trial.

BackgroundHypertensive disorders of pregnancy remain a leading cause of preventable maternal and perinatal mortality, particularly in low‑ and middle‑income countries (LMICs). Eclampsia, the most severe manifestation, is responsible for a disproportionate share of maternal deaths in sub‑Saharan Africa, yet contemporary data from Tigray, Ethiopia are scarce.ObjectiveTo determine the prevalence, clinical presentation, and factors associated with adverse feto‑maternal outcomes among women managed for eclampsia at Ayder Comprehensive Specialized Hospital (ACSH), Tigray, Ethiopia, between 1 January 2017 and 31 December 2021.MethodsWe conducted a retrospective cross‑sectional review of all women with a discharge diagnosis of eclampsia. A piloted extraction tool, adapted from recent studies, was used to abstract socio‑demographic, obstetric, clinical, laboratory, management, and outcome variables from medical charts. EpiData v4.6 was used for data entry, and data were analysed with Stata v16. Descriptive statistics summarised prevalence and presentation. Multivariate logistic regression identified independent predictors of (i) maternal end‑organ injury and (ii) perinatal death, reporting adjusted odds ratios (aOR) with 95% confidence intervals (CI). Model fitness was assessed with the Hosmer–Lemeshow test (p > 0.05).ResultsOf 23,090 deliveries during the study period, 252 women (1.1%, 95% CI 1.0–1.2%) were diagnosed with eclampsia; 240 charts were analysed. The case‑fatality rate was 3.3% and perinatal mortality 20.1%. Antepartum eclampsia accounted for 63.8%, intrapartum 9.6%, and postpartum 26.7%. Headache (77.5%), visual disturbance (53.8%), and epigastric/right‑upper‑quadrant pain (46.3%) were the most frequent prodromal symptoms. Independent predictors of maternal end-organ injury were referral from another facility (aOR 4.9, 95% CI 1.8–13.9) and having perinatal death (aOR 2.7, 95% CI 1.2–6.1). Vaginal delivery (aOR 5.5, 95% CI 2.3–13.3), and pregnancies complicated with postpartum haemorrhage (aOR 3.2, 95% CI 1.2–8.3), acute respiratory distress syndrome (aOR 3.2, 95% CI 1.1–9.3), and dialysis‑requiring acute kidney injury (aOR 24.7, 95% CI 5.6–109.9) were independent predictors of perinatal death.ConclusionsEclampsia prevalence at ACSH remains high and is associated with substantial maternal and perinatal mortality. Strengthening antenatal surveillance, streamlining referral pathways, and ensuring timely definitive delivery are critical to improving outcomes. Context-specific quality‑improvement initiatives should prioritise the prevention and aggressive management of hypertensive disorders of pregnancy.

Abstract Background: One of the key risk factors for the severity of cardiovascular nontransmitted diseases such as renal failure, coronary heart disease, and stroke is hypertension. Only stable patients with no indications or symptoms of end-organ injury experience asymptomatic hypertension. Objectives: To estimate the incidence rate of asymptomatic hypertension among early middle age people. Materials and Methods: A cross-sectional design was utilized and a nonprobability (convenience approach) sampling technique with a size of sample 270 subjects who visited Merjan and AL Imam AL Sadiq teaching hospitals from December 1, 2022, to March 30, 2023. Data was gathered by two techniques, an interview, and a questionnaire, and taking two different blood pressure readings by a mercury Sphygmomanometer for every participant. Results: Overall incidence rate of asymptomatic hypertension was 16.584% with rates for females 9.52% and males 7.063%. There is a high percentage of women aged 46 and more (32.9) in urban areas (67.4) with low monthly income (41.4) additionally housewives (46.3) and primary school graduates (32.9) and there hve a family history of hypertension (92.9%) and had not diabetes mellitus, renal disease and heart disease. A high percentage of using mixed drugs (53.4) including contraceptives, herbs, and NSAIDs with high percentage cholesterol and triglyceride levels. Conclusion: High incidence rate of asymptomatic hypertension and it is more common in females than males among early middle age people.

Alcohol misuse is a leading modifiable risk factor for disease burden across the lifespan. Alcohol-mediated end organ injury results from a combination of pathophysiological processes including oxidative stress, mitochondrial dysfunction, cell death, endoplasmic reticulum stress, extracellular matrix remodeling, and epigenomic adaptations. Alcohol's multi-systemic physiological impact causes direct cellular damage and impairs an individual's capacity to adapt or recover from additional health insults, thereby amplifying overall disease burden. While the impact of alcohol on liver and brain physiological mechanisms is the most studied, the adverse effects of alcohol extend to multiple other organ systems, and though frequently underappreciated, contribute to several comorbidities. This review focuses on alcohol-associated pathophysiological effects on the gastrointestinal, cardiovascular, immune systems, and energy metabolism that contribute to multiorgan injury and disease burden. Understanding the pathophysiological effects of alcohol on the different organ systems will significantly help inform therapeutic modalities to help reduce alcohol-associated comorbidities.

Cardiogenic shock and cardiac arrest are associated with high risk of mortality despite advances in resuscitation techniques and supportive care. A growing body of evidence implicates a systemic inflammatory response syndrome (SIRS) in the pathogenesis of post-arrest vasoplegia and end-organ injury. Methylene blue (MB), a nitric oxide pathway inhibitor, has shown efficacy in vasoplegic and septic shock, yet its role in cardiogenic shock or cardiac arrest is not well established. We conducted a systematic review of peer-reviewed studies examining methylene blue in cardiogenic shock or cardiac arrest. Electronic databases MEDLINE, EMBASE, CENTRAL, Scopus, and Web of Science were searched in March 2025. Preclinical randomised trials and clinical studies in adult humans or animal models were included. Out of 676 screened records, seven studies met inclusion criteria: six preclinical randomised animal studies and one retrospective human cohort study. Early porcine studies using electrically induced ventricular fibrillation and continuous MB infusion during CPR demonstrated improved survival, haemodynamic profile, and neurologic outcomes. In contrast, more recent, well conducted bolus-only studies using infarct-induced models reported minimal or no benefit associated with MB administration. The single human study lacked a comparator group and provided limited cardiogenic shock-specific outcome data. This systematic review highlights the lack of data available for MB in cardiogenic shock and cardiac arrest, especially in humans. There was a potential therapeutic signal for methylene blue in some animal models of cardiogenic shock and cardiac arrest. Prospective studies with clinically relevant models of cardiac injury are warranted to determine whether MB can improve outcomes in this high-risk population.

Background: The liver being the largest and central organ of nutrient metabolism is at a high risk of injury from the toxic metabolites of ingested materials. This invariably leads to rising incidence of chronic liver disease. This study investigated the ability of the aqueous extract of Citrus reticulata leaf to reverse carbon tetrachloride induced acute liver injury. Methods: Mild, moderate and severe liver injuries were induced in three sets of animals with each consisting of three groups. Subsequently, low (200 mg/kg) and high (400 mg/kg) doses of the leaf extract were administered orally once daily to six of the groups for 28 days. At expiration, blood samples were collected for biochemical analyses. Liver and kidney were harvested from the animals for histopathological evaluation. Results: The standardized weights of the liver as well as those of the kidney were similar across the groups. The blood protein level was elevated in all the groups that had the extract but depressed in the liver injured groups that did not receive the extract. Low dose of the extract elevated the globulin level. The globulin: albumin ratio was greater than one in all the groups. The alanine aminotransferase (ALT) level of the high extract dose with severe liver injury group was similar to that of the general control but remarkably lower than that of its counterpart control (ie the group with severe liver injury but did not receive the extract). The aspartate aminotransferase and alkaline phosphatase levels were similar in pattern to that of ALT. The histological architecture of both the liver and the kidney were preserved. Conclusion: Oral administration of the aqueous extract of Citrus reticulata (tangerine) leaf reversed the organ damage potentiated by the administration of carbon tetrachloride (chemical). Low dose of C. reticulata leaf extract may improve immune status.

Emergency medicine updates: Managing the patient with return of spontaneous circulation.

Sepsis and septic shock are leading causes of maternal morbidity and mortality. Sepsis complicates an estimated 1 in 1,000 pregnancies and is responsible for 24% of in-hospital maternal deaths. Because most cases occur outside of the hospital, it is crucial to educate patients about warning signs to seek early medical care and for clinicians to engage in critical listening and evaluation of patient concerns. In the hospital, screening patients for vital sign aberrancy, followed by bedside and laboratory evaluation for signs of end-organ injury, prompt antibiotic therapy, and restoration of perfusion (through fluid resuscitation and vasopressor administration), is critical for optimal outcomes. Long-term sequelae are common and include psychological sequelae, cognitive dysfunction, and weakness. Screening for these long-term effects and referrals for treatment are key to patient recovery.