Causes of death after first time venous thromboembolism.

BACKGROUND: Causes of death after first time community-acquired venous thromboembolism (VTE) diagnosed in unselected patients at the emergency department (ED) was investigated. MATERIALS AND METHODS: The study consists of all patients > 18 years of age who had a visit for any medical reason to any of 5 different ED in Stockholm County, Sweden from 1st January 2016 to 31st December 2017. We have identified all patients with a first registered incident VTE; deep vein thrombosis (DVT) and/or pulmonary embolism (PE) during the study period. Cox regression models were used to estimate hazards ratios (HR) with 95% confidence intervals (CIs) for all-cause mortality and cause-specific death in patients with DVT or PE using all other patients as the reference group. RESULTS: In total, 359,884 patients had an ED visit during the study period of whom about 2.1% were diagnosed with VTE (DVT = 4,384, PE = 3,212). The patients with VTE were older compared to the control group. During a mean follow up of 2.1 years, 1567 (21%) and 23,741(6.7%) patients died within the VTE and reference group, respectively. The adjusted risk of all-cause mortality was nearly double in patients with DVT (HR 1.7; 95% CI, 1.5-1.8) and more than 3-fold in patients with PE (HR 3.4; 95% CI, 3.1-3.6). While the risk of cancer related death was nearly 3-fold in patient with DVT (HR 2.7; 95% CI, 2.4-3.1), and 5-fold in PE (HR 5.4; 95% CI, 4.9-6.0 respectively). The diagnosis of PE during the ED visit was associated with a significantly higher risk of cardiovascular death (HR 2.2; 95% CI, 1.9-2.6). CONCLUSION: Patients with VTE have an elevated risk of all-cause mortality, including cardiovascular death.

Sociodemographic factors associated with IgG and IgM seroprevalence for human cytomegalovirus infection in adult populations of Pakistan: a seroprevalence survey.

BACKGROUND: The seroprevalence of human cytomegalovirus (HCMV) infection ranges from 30 to 90 % in developed countries. Reliable estimates of HCMV seroprevalence are not available for Pakistan. This study determined the seroprevalence and sociodemographic factors associated with HCMV infection in adult populations of Karachi, Pakistan. METHODS: A seroprevalence survey was conducted on 1000 adults, including residents of two semi-urban communities, and visitors to a government and a private hospital. Questionnaire-based interviews were conducted. Sera were analysed for HCMV-specific IgG and IgM. Chi-square or Fisher's exact test was used for comparing sociodemographic variables against seropositivity of HCMV-IgG or IgM. Multiple logistic regression modeling was performed for IgG seroprevalence and adjusted odds ratios were computed. RESULTS: The seroprevalence of HCMV-IgG and IgM was 93.2 and 4.3 % respectively. 95.3 % of individuals who were IgM seropositive were also seropositive for IgG. Around 6 % (15/250) of women of childbearing age remained uninfected and were therefore susceptible to primary infection. HCMV-IgG seroprevalence was associated with being female (p = 0.001), increasing age (p = 0.002) and crowding index (p = 0.003) and also with lower levels of both education (p < 0.001) and income (p = 0.008). Seroprevalence also differed significantly by marital status (p = 0.008) and sampling location (p < 0.001). A logistic regression model for HCMV-IgG seroprevalence showed associations with being female (OR = 1.89; 95 % CI: 1.10-3.25), increasing age (OR = 3.95; 95 % CI: 1.79-8.71) and decreasing income (OR = 0.72; 95 % CI: 0.54-0.96). A strong association was observed between increased seroprevalence of HCMV-IgM and decreasing household size (p = 0.008). CONCLUSIONS: Seroprevalence of HCMV is very high in Pakistan, although 6 % of women of childbearing age remain at risk of primary infection. The IgM seropositivity observed in some individuals living in small household size (1-3 individuals) with persistent HCMV infection could have resulted from a recurrent HCMV infection. Future longitudinal research in pregnant women and neonates is required to study the trends in HCMV seroprevalence over time in Pakistan for the development of a potential HCMV prevention and vaccination programme.

Cytotoxic effects of aflatoxin B1 on human brain microvascular endothelial cells of the blood-brain barrier.

Aflatoxins are mycotoxins produced by Aspergillus spp. Although AFB1 is implicated as a carcinogen in hepatocellular carcinoma, brain autopsies in affected areas have revealed its presence in 81% of cases. Given its haematogenous spread, here we determined the cytotoxic effects of AFB1 on primary human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier, human umbilical vein endothelial cells (HUVEC) as well as immortalized epithelial cells of human hepatocellular carcinoma (Huh7). The cell types were exposed to AFB1 (3-32 nM) for 24 h and release of lactate dehydrogenase was measured as cell cytotoxicity marker. Furthermore, DNA was collected from both cell types and DNA adduct formation was determined by immunoblot using anti-AFB1-DNA adduct antibody. At 32 nM, AFB1 killed >85% HBMEC, while controls showed minimal effects (P < .05). Similar concentrations of AFB1 showed 22% cell death of HUVEC, while the same concentration did not kill Huh7. At low concentrations, in other words, 3.2 nM, AFB1 produced DNA adduct formation in HBMEC, while high concentration (32 nM) did not form DNA adducts. For HUVEC, 16 nM and 32 nM exhibited DNA adduct formation. For Huh7, 3.2 nM did not form DNA adducts, while 32 nM exhibited DNA adduct formation. For the first time, we report that AFB1 affected the viability of primary endothelial cells but not immortalized Huh7 cells. Cytotoxicity of brain endothelial cells suggests extra-hepatic complications post-AFB1 exposure.

Rosuvastatin inhibits TIMP-2 and promotes myocardial angiogenesis.

BACKGROUND: Angiogenesis is usually driven by inflammation. Matrix metalloproteinases MMP-3 and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 are implicated in vascular remodeling. TIMP-2 exhibits antiangiogenic properties. Statins show benefits that are additional to lipid lowering including pro- and antiangiogenic properties. Atherosclerotic lesions in the coronary arteries have been well studied, but less is known about the fine terminal branches of the myocardial vasculature. METHODS: To examine this, we studied rosuvastatin (RSV) treatment in ApoE knockout (ApoE(-/-)) mice fed a high cholesterol (HC) diet. Hearts from ApoE(-/-) mice on a normal diet, HC diet and HC diet with RSV were harvested to determine MMP-3, MMP-9, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF)-A and estrogen receptor-α (ER-α) mRNA. RESULTS: RSV inhibited TIMP-1 and TIMP-2 expression and enhanced myocardial VEGF-A and ER-α expression, independently of plasma lipid level changes, but had no effect on MMP-3 and MMP-9 expression. CONCLUSIONS: These modulations of TIMPs, VEGF and ER-α expression induced by RSV may act as local stimulating factors for arteriolar growth in the myocardium.

Life-Threatening Thrombosis After Large Amounts of Nitrous Oxide Use.

This case report highlights the development of severe, life-threatening thrombotic complications after chronic recreational use of large quantities of nitrous oxide in a 21-year-old patient. In young patients presenting with thromboembolism and nitrous oxide abuse, swift identification of symptoms and management is critical.

Adductor Canal Block Versus Local Infiltration Analgesia for Postoperative Pain Management in Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a common surgical procedure for patients with knee osteoarthritis, often associated with postoperative pain. Effective pain management strategies are essential for improving patient outcomes and satisfaction. This study aimed to compare the efficacy of two analgesic modalities, local infiltration analgesia (LIA) and adductor canal block (ACB), in providing postoperative pain relief for patients undergoing TKA. METHODS: This prospective randomized comparative study included 60 patients undergoing TKA for knee osteoarthritis under subarachnoid block (spinal anaesthesia). Patients were divided into two groups: LIA group (local wound infiltration with periarticular injection of bupivacaine 0.125% + dexmedetomidine 1 mcg/kg) and ACB group (ACB with bupivacaine 0.125% + 1 mcg/kg dexmedetomidine). Pain relief was assessed using the Numerical Rating Scale (NRS) score, time to first rescue analgesic requirement (NRS > 3), and total amount of analgesic needed in the first 24 hours post-surgery. RESULTS: The time to first perception of pain with NRS > 3 was 11.30±0.8 hours in the ACB group and 9.40 ± 1.1 hours in the LIA group, with a statistically significant difference (p < 0.001). Additionally, the total number of rescue analgesic doses given in the first 24 hours post-operatively differed significantly between the two groups (p = 0.046). CONCLUSION: The study concludes that ACB is an effective postoperative analgesic modality, superior to local infiltration analgesia, for patients undergoing TKA.

Neutrophil-to-Lymphocyte Ratio and Blood Eosinophil Levels As Inflammatory Indicators in Smoker and Non-smoker Young Adult Patients With Chronic Obstructive Pulmonary Disease at a Tertiary Care Hospital.

Background Inflammatory markers are elevated in chronic obstructive pulmonary disease (COPD) and can be quantified to detect severity, prognosis, mortality risk, and response to treatment. However, the estimation costs are high. The blood neutrophil-to-lymphocyte ratio (NLR) and eosinophil levels are emerging as biomarkers in COPD, yet there is a paucity of data. Aim and objectives This study was designed to elucidate the roles of the NLR and eosinophil levels in smokers and non-smokers with stable COPD male subjects, correlating them with lung functions. Materials and methods A prospective observational clinical study was conducted from January to June 2023, after receiving approval from the Institutional Ethics Committee, on 73 COPD patients aged 30-60 years who gave voluntary informed consent. Complete blood counts and spirometry were performed. Patients with a forced expiratory volume in one second (FEV1) % predicted <70% and an FEV1/forced vital capacity (FVC) % <70% based on the pulmonary function test (MIR Spirolab) were included. They were further divided into mild (n=10), moderate (n=27), severe (n=26), and very severe (n=10) categories as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Subjects were also categorized into smoker (n=45) and non-smoker (n=28) groups. The complete blood count was analyzed using an automated analyzer (Beckman Coulter). Analysis was also carried out with an NLR of more or less than three. A P-value of less than 0.05 was considered significant. Results Smokers constituted 61.65% (n=45) of the subjects, and non-smokers 38.35% (n=28). Among smokers, 17.78% had very severe airflow obstruction. In all COPD subjects (n=73), lymphocytes, eosinophils, and lung functions were lower in the group where the NLR was greater than three. NLR in smokers (3.52±1.43) was higher than in non-smokers (3.39±0.94). In non-smokers (n=28), blood eosinophils and lymphocytes were elevated. In smokers (n=45), blood neutrophils, monocytes, and basophils were increased. Smokers showed a non-significant increase in RBC, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Neutrophils, monocytes, eosinophils, and NLR increased with disease severity. NLR negatively correlated with FEV1 (r=-0.350, p=0.034) and positively with pack-years (r=0.546, p<0.001) in smokers. NLR negatively correlated with eosinophils, FVC, FEV1/FVC, and FEV1 % predicted. In all COPD subjects (n=73), NLR negatively correlated with blood eosinophils (r=-0.184, p=0.12), BMI, and lung functions. Conclusion NLR is elevated in COPD subjects and can serve as a marker of inflammation and a predictor of the risk and severity of airflow limitation. NLR correlates both positively and negatively with pack-years and lung functions, respectively.

Association of Sensory Nerve Action Potential Amplitude and Velocity With Type 2 Diabetic Peripheral Neuropathy.

BACKGROUND: There is ongoing controversy regarding the predominant type of nerve injury in diabetic peripheral neuropathy, whether it is demyelination or axonal degeneration. OBJECTIVE: This study aimed to investigate the association between nerve conduction study parameters, specifically nerve conduction velocity and the amplitude of the action potential, with diabetic peripheral neuropathy and determine their potential as early indicators of the condition. METHODS: A cross-sectional study was conducted involving diagnosed type 2 diabetes mellitus patients, who were divided into two groups: Group I (n = 111) with symptomatic diabetic peripheral neuropathy and Group II (n = 109) without clinically detectable peripheral neuropathy. Age and sex-matched healthy controls (n = 100) were also included. Nerve conduction velocity measurements were performed on both upper and lower limbs, with motor nerve conduction study focusing on the dominant side using the median and posterior tibial nerves and sensory nerve conduction study using the median and sural nerves. RESULTS: The nerve conduction studies revealed significantly lower sensory nerve action potential amplitudes and compound muscle action potential amplitudes in the median, posterior tibial, and sural nerves of the diabetic groups compared to the control subjects. Furthermore, these changes were more prominent in patients with peripheral neuropathy. Among the 220 diabetic patients analyzed, 135 (61.36%) exhibited nerve conduction abnormalities. The highest rate of abnormality was observed in the sural nerve, followed by the posterior tibial and median nerves. The most common abnormality detected in diabetic patients was a decrease in sensory nerve action potential, followed by a decrease in sensory nerve conduction velocity. CONCLUSION: The study findings suggest an association between reduced sensory nerve action potential amplitude and diabetic peripheral neuropathy. These results highlight the potential of sensory nerve action potential and velocity as a sensitive indicator of peripheral neuropathy in diabetic patients.

Association of coronary angiographic lesions and mortality in patients over 80 years with NSTEMI.

OBJECTIVE: Coronary angiography (CA) and percutaneous coronary intervention (PCI) is of great importance during non-ST-segment elevation myocardial infarction (NSTEMI) management. Coronary artery lesions and their association to mortality in elderly patients with NSTEMI was investigated. METHODS: Patients >80 years of age who underwent CA at index NSTEMI during 2011-2014 were included. Data were collected from the Swedish Coronary Angiography and Angioplasty Registry and Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registries. Coronary lesions were categorised into; one vessel disease (1VD), multi-vessel disease (MVD) and left main disease (LMD) and 0%-49% stenosis grade were considered as controls.Cox regression was used to estimate HRs for all-cause mortality associated with coronary lesions. Survival benefit was determined after PCI and in relation to if revascularisation was complete or incomplete and any complications in the Cath lab was assessed. RESULTS: Five thousand seven hundred and seventy patients with history of CA and PCI were included, 10% had normal coronary arteries, 26% had 1VD, 50% MVD and 14% LMD. Mortality was higher in patients with 1VD, MVD and LMD: HR 1.8 (1.3-2.5), HR 2.2 (1.6-3.0) and HR 2.8 (2.1-3.9), respectively. PCI were treated in 84% of 1VD, 73% MVD, and 54% in LMD. Survival was higher with PCI HR 0.85 (0.73-0.99). MVD had lower adjusted mortality HR 0.71 (0.58-0.87) compared with patients with MVD who did not undergo PCI. Complications and mortality were higher in patients with LMD both during CA and PCI, HR 2.9 (1.1-7.6) and HR 4.5 (1.6-12.5). CONCLUSION: Coronary lesions (>50% stenosis) are strong predictors of mortality in elderly patients with NSTEMI. MVD is common and PCI treatment is associated with increased survival.

Estrogen receptors do not influence angiogenesis after myocardial infarction.

BACKGROUND: There is controversy on whether estrogen receptors are present and functioning in the myocardium. Aims. To explore if after myocardial infarction (MI) estrogen receptors α (ERα) and ß (ERß) are upregulated in myocardial tissue and to explore if the presence/ absence of ERα or ERß influences angiogenesis after MI. METHODS: MI was induced by ligation of the left anterior descending artery in knockout (KO) mice, ERαKO and ERßKO, respectively, and non-KO littermate-controls, C57Bl/6 mice. The hearts were harvested after 12 days. A part of the periinfarct tissue was collected for ERα and ERß mRNA expression determination by real-time polymerase chain reaction. Using immunohistochemistry, ERα and ERß protein expression and capillary and arteriolar densities were blindly determined in the periinfarct area. RESULTS: In myocardium disrupted mRNA was upregulated in both ERαKO and ERßKO, (p < 0.005) and did not change after MI. There was no change in mRNA expression of ERα or ERß in wild type mice after MI. Expression of ERß in ERαKO and of ERα in ERßKO did not change. Following MI ERα or ERß could not be demonstrated by immunohistochemistry in either wild type or ERαKO or ERßKO. The capillary and arteriolar densities after MI did not differ between the groups in the periinfarct area. CONCLUSIONS: Although disrupted ER mRNA is upregulated in myocardium of ER knockout mice, no change in these or native receptors occurs following MI. At least in this model ER therefore seems not to have a role in myocardial arteriogenesis and angiogenesis after MI.

Early Risk of Stroke in Patients Undergoing Acute Versus Elective Cardioversion for Atrial Fibrillation.

Background Electrical cardioversion (ECV) is routinely used to restore sinus rhythm in patients with symptomatic atrial fibrillation. The European guidelines have been updated in recent years. Current information on differences in the risk for stroke after acute versus elective ECV is lacking. Methods And Results All patients with a first-time acute or elective ECV in the Stockholm regional health care data warehouse from 2011 to 2018 were included. Cox regression analyses were performed evaluating ischemic or unspecified stroke within 30 days after ECV with adjustments for the CHA2DS2-VASc score, medical treatment, and year of inclusion. The study included 9139 patients, 3094 after acute and 6045 after elective ECV. The mean age was 65.9±11.3 years, 69.5% were men, and the mean CHA2DS2-VASc score was 2.4±1.7. Before the intervention, 49.6% of patients with an acute ECV and 96.4% of those with an elective ECV had claimed an oral anticoagulant prescription. Ischemic or unspecified stroke occurred in 26 (0.28%) patients within 30 days. The unadjusted risk was higher after acute compared with elective ECV (hazard ratio [HR], 2.29; 95% CI, 1.06-4.96), whereas there was no difference after multivariable adjustments (adjusted HR, 0.99; 95% CI, 0.36-2.72). Both non-vitamin K oral anticoagulants (adjusted HR, 0.28; 95% CI, 0.08-0.98) and warfarin (adjusted HR, 0.17; 95% CI, 0.05-0.53) were associated with a lower risk for stroke compared with no anticoagulation. Conclusions Acute ECV was associated with a higher unadjusted risk for stroke than elective ECV, but the risk was similar after adjustment for anticoagulant treatment. This study indicates the importance of anticoagulation before ECV according to recent European guidelines.

Statin Therapy and Intensity: Prognosis in Patients with Myocardial Injury.

BACKGROUND: No guideline-directed pharmacological therapy has been established for patients with myocardial injury without type 1 myocardial infarction. We investigated the impact of statin treatment in patients with myocardial injury. METHODS: Patients with myocardial injury (nonischemic acute and chronic myocardial injury), type 2 myocardial infarction, and type 1 myocardial infarction with at least 1 emergency department visit for chest pain from 2011 to 2014 were included. Dispensed prescriptions of all types of statins with dosage within 180 days from the index visit were collected. In total, 2054 patients were divided into 3 groups: 1) acute myocardial injury (type 2 myocardial infarction, acute nonischemic myocardial injury), 2) chronic myocardial injury, and 3) type 1 myocardial infarction. We estimated the adjusted hazard ratio with 95% confidence interval for death with low- (reference), moderate-, and high-intensity statin therapy. RESULTS: The mean follow-up was 4.2 ± 1.8 years. Only 13% of patients with acute and chronic myocardial injury and 30% with type 1 myocardial infarction were treated with high-intensity statins. Adjusted mortality rates were higher in patients with acute and chronic myocardial injury than in those with type 1 myocardial infarction across all statin intensity categories. In patients with type 1 myocardial infarction, the adjusted mortality risk was 20% (hazard ratio, 0.80; 95% confidence interval, 0.36-1.77) lower in patients with high-intensity therapy. Point estimates in the adjusted models indicated similar associations between statin intensity and mortality risk in patients with acute and chronic myocardial injury. CONCLUSION: Patients with myocardial injury may benefit from high-intensity statin treatment, but the associations were not statistically significant when adjusting for confounders.

Treatment With Cardiovascular Medications: Prognosis in Patients With Myocardial Injury.

Background There is no clinical guidance on treatment in patients with non-ischemic myocardial injury and type 2 myocardial infarction (T2MI). Methods and Results In a cohort of 22 589 patients in the emergency department at Karolinska University Hospital in Sweden during 2011 to 2014 we identified 3853 patients who were categorized into either type 1 myocardial infarction, T2MI, non-ischemic acute and chronic myocardial injury. Data from all dispensed prescriptions within 180 days of the visit to the emergency department were obtained concerning ß-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins, and platelet inhibitors. We estimated adjusted hazard ratios (HR) with 95% CI for all-cause mortality in relationship to the number of medications (categorized into 0-1 [referent], 2-3 and 4 medications) in the groups of myocardial injury. In patients with T2MI, treatment with 2 to 3 and 4 medications was associated with a 50% and 56% lower mortality, respectively (adjusted HR [95% CI], 0.50 [0.25-1.01], and 0.43 [0.19-0.96]), while corresponding associations in patients with acute myocardial injury were 24% and 29%, respectively (adjusted HR [95% CI], 0.76 [0.59-0.99] and 0.71 [0.5-1.02]), and in patients with chronic myocardial injury 27% and 37%, respectively (adjusted HR [95% CI], 0.73 [0.58-0.92] and 0.63 [0.46-0.87]). Conclusions Patients with T2MI and non-ischemic acute or chronic myocardial injury are infrequently prescribed common cardiovascular medications compared with patients with type 1 myocardial infarction. However, treatment with guideline recommended drugs in patients with T2MI and acute or chronic myocardial injury is associated with a lower risk of death after adjustment for confounders.

Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats.

Berberis vulgaris is a widely used plant for the treatment of urolithiasis. To evaluate its antiurolithic potential, the crude aqueous-methanol extract of Berberis vulgaris root bark (Bv.Cr) was tested in an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol in drinking water. Bv.Cr (50 mg/kg) inhibited CaOx crystal deposition in renal tubules and protected against associated changes including polyuria, weight loss, impaired renal function and the development of oxidative stress in kidneys. Activity-guided fractionation revealed the concentration of antiurolithic constituent(s) mainly in the aqueous fraction. These data, indicating the presence of antiurolithic activity in Berberis vulgaris root bark, rationalize its medicinal use for the treatment of urolithiasis.

Outcome of Percutaneous Coronary Intervention During Non-ST-Segment-Elevation Myocardial Infarction in Elderly Patients With Chronic Kidney Disease.

Background There is a paucity of data on the benefit of revascularization by percutaneous coronary intervention (PCI) during non-ST-segment-elevation myocardial infarction in patients aged >80 years with concurrent chronic kidney disease. Methods and Results Patients aged >80 years with chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 with non-ST-segment-elevation myocardial infarction, during 2011 to 2014 in Sweden retrieved from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) Registry. Cox regression was used to estimate adjusted hazard ratios with 95% CIs for all-cause mortality in patients with PCI versus no PCI treatment, stratified for eGFR. Logistic regression was used to evaluate adjusted odds for reinfarction and bleeding during hospitalization. Propensity score weighting analysis was also done as sensitivity analysis. In total, 12 821 patients were included, of whom 47%, 45%, and 8% had an eGFR of >60, 30 to 60, and 15 to <30 mL/min per 1.73 m2, respectively. Patients with eGFR 30 to 60 and 15 to <30 mL/min per 1.73 m2, 22%, and 10%, respectively, underwent PCI, compared with 36% among patients with eGFR >60 mL/min per 1.73 m2. During a mean follow-up of 3.2 years, the absolute risk of death was 42%, 56%, and 76% in patients with eGFR >60, 30 to 60, and 15 to <30 mL/min per 1.73 m2, respectively. Patients who underwent PCI had a lower risk of death in all groups of eGFR (0.47 [95% CI, 0.42-0.53], 0.50 [95% CI, 0.45-0.56], and 0.44 [95% CI, 0.33-0.59], respectively). Patients with eGFR 15 to <30 mL/min per 1.73 m2 had a higher risk of bleeding with PCI. Propensity score weighting showed similar outcomes for mortality risk as the unweighted analysis in all the eGFR groups. Conclusions PCI is rarely used in non-ST-segment-elevation myocardial infarction elderly patients with chronic kidney disease, and it appears to offer a survival benefit.

Causes of Death in Patients With Acute and Chronic Myocardial Injury.

BACKGROUND: Information about causes of death in patients with myocardial injury is limited. The purpose of this study was to explore causes of death in patients with myocardial injury. METHODS: In a cohort of 22,589 patients, 3853 patients with myocardial injury were identified and categorized into: type 1 myocardial infarction, type 2 myocardial infarction, and nonischemic acute and chronic myocardial injury. We included all 1466/3853 (38%) patients who died during follow-up (3.9 ± 2 years). We estimated rates and adjusted odds ratio (OR) with 95% confidence interval (CI) for causes of death in the 4 categories of myocardial injury using patients without myocardial injury 819/17,932 (4.6%) who died as reference. RESULTS: The study cohort included 2285 patients. The proportion of cardiovascular deaths was higher in patients with type 1 myocardial infarction (48%), acute (43%), and chronic (45%) myocardial injury and type 2 myocardial infarction (39%) compared with patients without myocardial injury (25%). Adjusted rates for cardiovascular death were similar in patients with myocardial injury. Type 1 myocardial infarction, acute, and chronic myocardial injury was associated with a 77% (OR: 1.77, 95% CI 1.29-2.41), 40% (OR: 1.40, 95% CI: 1.07-1.84), and 36% (OR: 1.36, 95% CI: 1.05-1.76) higher risk of cardiovascular death. CONCLUSIONS: Patients with type 1 myocardial infarction and acute or chronic myocardial injury have similar proportions and high risks for cardiovascular death. We believe that these findings stress the need for investigating patients without known heart diseases who present with nonischemic myocardial injury, or type 2 myocardial infarction.

Diagnostic Accuracy in Acute Venous Thromboembolism: Comparing D-Dimer, Thrombin Generation, Overall Hemostatic Potential, and Fibrin Monomers.

Introduction For acute venous thromboembolism (VTE), a biomarker with higher specificity than D-dimer would be of great clinical use. Thrombin generation and overall hemostatic potential (OHP) reflect the hemostatic balance by globally assessing multiple coagulation factors and inhibitors. These tests discriminate between healthy controls and patients with a prothrombotic tendency but have yet to be established as clinical biomarkers of VTE. Objective This study compares endogenous thrombin potential (ETP) and OHP to D-dimer and fibrin monomers (FM) in outpatients with suspected VTE. Methods A cross-sectional diagnostic study where 954 patients with suspected pulmonary embolism or deep venous thrombosis were recruited consecutively from the medical emergency department at Karolinska University Hospital. D-dimer, FM, OHP, and ETP were analyzed in a subpopulation of 60 patients with VTE and 98 matched controls without VTE. VTE was verified either by ultrasonography or computed tomography and clinical data were collected from medical records. Results Compared with healthy controls, both VTE and non-VTE patients displayed prothrombotic profiles in OHP and ETP. D-dimer, FM, ETP area under the curve (AUC), and ETP T lag were significantly different between patients with VTE and non-VTE. The largest receiver-operating characteristic AUCs for discrimination between VTE and non-VTE, were found in D-dimer with 0.94, FM 0.77, and ETP AUC 0.65. No useful cutoff could be identified for the ETP or the OHP assay. Conclusion Compared with D-dimer, neither ETP nor OHP were clinically viable biomarkers of acute venous thrombosis. The data indicated that a large portion of the emergency patients with suspected VTE were in a prothrombotic state.

Modulations of cell cycle checkpoints during HCV associated disease.

BACKGROUND: Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC). This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. METHODS: Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1) with significant changes in mRNA levels (> 2-fold, p-value < 0.05) were selected, and their protein expressions were examined in the liver biopsies of 38 chronic hepatitis C patients. RESULTS: In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. CONCLUSION: Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development.

Frequency of hepatitis C and D super infection in patients with hepatitis B related complex liver disorders.

OBJECTIVE: To determine the frequency of super infection of hepatitis C and D in patients with hepatitis B related complex liver disorders and the distribution of HBV genotypes in these patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Gastroenterology Unit of PMRC in JPMC, Karachi, from July 2006 to June 2007. METHODOLOGY: All patients registered for HBV associated infections were selected. Blood was drawn from 180 patients who fulfilled the inclusion criteria. Those with an incomplete test profile were excluded. All clinical conditions were investigated through liver function tests, coagulation profile, and findings at abdominal ultrasonography, upper gastrointestinal endoscopy and liver biopsy. Liver cirrhosis and hepatocellular carcinoma (HCC) were diagnosed either on the basis of histology, or on a combination of radiological, endoscopic and laboratory data. Hepatitis B virus DNA was extracted from serum, and subjected to a nested PCR using the type specific primers for HBV genotype. Descriptive statistics were used for frequency and mean determination. RESULTS: The 129 patients finally selected for statistical analysis included 108 (84%) males and 21 (16%) females. The age ranged from 6- 68 years (mean=31.5 +/-12.39 years). There were 70 (54.2%) patients of non-cirrhotic, chronic hepatitis (CLD), 38 (29.4%) carriers, 12 (9.3%) cirrhotics and 9 (6.9%) HCC patients. Among the 129 patients, 45 (34.9%) were positive for double infection with HDV. These included 35 CLD cases, 7 cirrhotic and 3 carriers, 4 (3.1%) patients were positive for double infection with HCV including one with CLD, 2 with cirrhosis and one with HCC. Triple infection with HBV/HDV/HCV was present in 4 (3.1%) patients who had CLD. Approximately 59% (n=76) patients were not coinfected, though 9 had developed HCC. The genotype distribution of HBV was observed as D in 98 (76%) patients, A in 24 (18.6%), and AD mix in 7 (5.4%). Genotypes B, C, E or F were not found. Accordingly, genotype D strains were the predominant strains among all categories. CONCLUSION: The frequency of super infection of hepatitis C and D was found to be highest in HBV cirrhosis patients compared to patients having chronic liver disease (non-cirrhotics) and carriers. Genotype D of hepatitis B virus was found dominant in all hepatitis B related complex liver disorders.