Association between serum triglycerides and stroke type, severity, and prognosis. Analysis in 6558 patients.

BACKGROUND AND OBJECTIVES: Hypertriglyceridemia (HT) may increase the risk of stroke. Limited studies have shown that stroke severity and infarction size are smaller in patients with HT. We explored the relationship between triglyceride levels and stroke risk factors, severity and outcome in a large prospective database. DESIGN: Prospective Cross-sectional study. SETTING: We retrospectively interrogated the Qatar Stroke Database in all patients admitted between 2014-2022 with acute ischemic stroke and evaluated the relationship between triglyceride, diabetes, stroke severity (measured on NIHSS), stroke type (TOAST classification) and the short- (mRS at 90 days) and long-term outcomes (MACE at 1 year) in patients with HT. PARTICIPANTS: Six thousand five hundred fifty-eight patients ≥20 years were included in this study RESULTS: Six thousand five hundred fifty-eight patients with ischemic stroke [mean age 54.6 ± 12. 9; male 82.1%) were included. Triglyceride levels upon admission were low-normal (≤1.1 mmol/L) in 2019 patients, high-normal (1.2-1.7 mmol/L) in 2142 patients, borderline-high (1.8-2.2 mmol/L) in 1072 patients and high (≥2.3 mmol/L) in 1325 patients. Higher triglyceride levels were associated with stroke and increased likelihood of having diabetes, obesity, active smoking, and small vessel/lacunar stroke type. An inverse relationship was noted whereby higher triglyceride levels were associated with lower stroke severity and reduced likelihood of poorer outcome (mRS 3-6) at discharge and 90 days. Long-term MACE events were less frequent in patients with higher triglyceride levels. After adjusting age, gender, diabetes, prior stroke, CAD, and obesity, multivariate analysis showed that hypertension and triglyceride levels were higher in mild ischemic strokes patients. CONCLUSIONS: Increasing triglycerides are associated with higher risk of small vessel disease and requires further prospective cohort studies for confirmation.

Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity.

Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael's addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile.

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Comparative analysis of 5-year efficacy and outcomes of single anastomosis procedures as revisional surgery for weight regain following sleeve gastrectomy.

BACKGROUND: It is imperative to assess the results of revisional procedures following Sleeve Gastrectomy (SG), given the substantially growing population of patients who experience weight regain within a few years after undergoing this procedure. OBJECTIVE: Examine the comparative effectiveness of the Single Anastomosis Duodeno-Ileal Bypass (SADI-S) and the One Anastomosis Gastric Bypass (OAGB-MGB) as revisional procedures, with respect to their impact on weight loss, resolution of comorbidities, incidence of complications, and rates of reoperation in patients who had weight regain after SG with up to or more than 5 years of follow-up. SETTING: Hamad General Hospital, Academic tertiary referral center, Qatar. METHODS: This study retrospectively analyzed a database of patients who underwent the Single Anastomosis Duodeno-Ileal Switch (SADI-S) or the One Anastomosis Gastric Bypass - Mini Gastric Bypass- (OAGB-MGB) as revisional procedures for weight recidivism after a primary Laparoscopic Sleeve Gastrectomy (LSG). The follow-up period was at least 5 years, during which the impact of both procedures on weight loss, comorbidities, nutritional deficiencies, complications, and outcomes were compared. RESULTS: The study comprised 91 patients, with 42 and 49 in the SADI-S and OAGB-MGB groups, respectively. Significant weight loss (measured by total weight loss percentage, TWL%) was observed at the 5-year follow-up for the SADI-S group compared to the OAGB-MGB group (30.0 ± 18.4 vs. 19.4 ± 16.3, p = 0.008). Remission of comorbidities, specifically diabetes mellitus and hypertension, was more prevalent in the SADI-S group. Notably, the OAGB-MGB group had a higher incidence of complications (28.6% vs. 21.42%) and reoperations (5 patients vs. 1 in the SADI-S group). No mortality events were reported in either group. CONCLUSION: While both the OAGB-MGB and SADI-S have demonstrated efficacy as revisional procedures for weight regain following SG, the SADI-S exhibits superior outcomes compared to the OAGB-MGB with regard to weight loss, resolution of comorbidities, complication rates, and reoperation rates.

Clinical and Liver Biochemistry Phenotypes, and Outcome in 133 Patients with Anti-seizure Drug-Induced Liver Injury.

AIMS AND OBJECTIVE: Anti-seizure drugs that cause idiosyncratic drug-induced liver injury (DILI) are an important cause of morbidity and mortality in individuals exposed to these drugs. The clinical and demographic characteristics, the liver injury pattern, the outcome, and the agents responsible for hepatotoxicity have not been thoroughly studied. We investigated the aforementioned characteristics in a large cohort of DILI registry patients. METHODS: Patients with anti-seizure DILI were studied from a large single-center DILI registry between 1998 and 2021. DILI was defined by international working group criteria with at least a probable relation with RUCAM. Immunoallergic features and organ-specific contribution to outcome were investigated. RESULTS: Anti-seizure drugs accounted for 133 patients (12.5%) among 1067 patients with idiosyncratic DILI. Compared to other agents, patients with anti-seizure DILI were younger (31 vs 41 years; p = 0.31), were more often females (52% vs 46%; p = 0.19) and had a lower frequency of jaundice (41% vs 59%, p = 0.001), MELD score (14.5 vs 16.5; p = 0.02) and mortality (9.8% vs 15.7%, p = 0.03). Anti-seizure DILI exhibited a greater frequency of hypersensitivity skin rashes (75% vs 22%, p < 0.001), including DRESS (51% vs 13%, p < 0.001) and SJS/TEN (19% vs1%, p < 0.001). A total of 18 different anti-seizure agents were responsible for DILI, largely contributed by carbamazepine (n = 36), phenytoin (n = 71), phenobarbitone (n = 8) and valproate (n = 14) which accounted for 89% of cases and 85% of 13 deaths. CONCLUSIONS: Anti-seizure DILI are caused predominantly by first generation drugs. Newer agents account for < 10% of cases. Hypersensitivity reaction is the most common phenotypic presentation. Both severity and mortality are lower with anti-seizure DILI.

The influence of intra-aortic balloon counter pulsation on central venous blood oxygen saturation.

OBJECTIVES: We aim at identifying the changes in venous blood saturation values that associates intra-aortic balloon pump (IABP) in cardiac surgery patients with reduced left ventricular function (LVF). METHODS: A retrospective observational study was conducted in a cardiothoracic intensive care unit (CTICU) in a tertiary cardiac center over 5 years in Qatar. A total of 114 patients with at least moderate impairment of LVF with ejection fraction (EF) less than 40% were enrolled. According to the association of IABP, patients were segregated into two groups with and without IABP (groups 1, 40 patients and group 2, 74 patients). Sequential arterial and venous blood gases were analyzed. The primary outcome was to analyze the changes in the central venous saturation (ScvO2) in both groups and the secondary outcome was to analyze whether these changes affect the overall outcome in terms of intensive care unit (ICU) length of stay. RESULTS: There was no significant difference between both groups with regard to age, preoperative EF, hemoglobin, and arterial oxygen saturation (SaO2) in blood gases. Patients with IABP have a higher cScvO2 when compared to the other group (71.5 ± 12.5 vs 63.5 ± 9.3, 68.3 ± 12.6 vs 60.1 ± 9.5, 62.7 ± 10.8 vs 55.63 ± 8.1, and 60.6 ± 7.6 vs 54.9 ± 8.1; p = 0.04, 0.05, 0.03, and 0.5, respectively). However, generalized estimating equations (GEE) analysis showed that compared with the participants showing that there is a decreasing trend in mean levels within the groups during follow-ups, overall difference between both groups' mean levels was not statistically significant. CONCLUSIONS: In this study, we observed that after cardiac surgeries, patients with IABP had non-significant higher ScvO2 when compared with a corresponding group with moderate impairment of LVF. Further prospective studies are required to validate these findings.

Impact of application of queuing theory on operational efficiency of patient registration.

Background: Hospital administrators are often challenged with overcrowding at hospitals. The study hospital receives referred patients; however, they have to wait in long queues even for getting registered. This was a cause of concern for hospital administrators. The study was undertaken to find an amicable solution to the queues at registration using Queuing Theory. Method: This observational and interventional study was carried out in a tertiary care ophthalmic hospital. In the first phase, data of service time and arrival rate was collected. The queuing model was built using the coefficient of variation (CoV) of the observed times. Server utilization for new patient registration was found to be 1.21 and was 0.63 for revisit patients. Scenario-based simulation carried out using free software for optimal utilization of both types of servers. Recommendations made to combine the registration process and to increase one server were implemented.In the second phase, after one year, patient registration data were collected and compared for the number of patients registered using SPSS 17. Results: Number of patients registered within the registration timings increased whereas the number of patients registered after the registration timings decreased significantly at 95% CI with a p-value of less than 0.001. Queues finished early and more number of patients were registered in the same time. Conclusion: Using queuing theory, the bottleneck of the systems can be identified. Scenario and software-based simulations provide solutions to the problem of queues. The study is an application of Queuing Theory with a focus on efficient resource utilization. It can be replicated in an organization with limited resources facing the challenge of queues.

Idiosyncratic Drug-Induced Liver Injury Associated With and Without Drug Reaction With Eosinophilia and Systemic Symptoms.

INTRODUCTION: Immunoallergic drug-induced liver injury (DILI) presenting with features of drug reaction with eosinophilia and systemic symptoms (DRESS) is a distinct phenotype. We describe the clinical characteristics, hepatitis pattern, severity, complications, and implicated medications in DILI patients with and without DRESS. METHODS: Using established criteria, we analyzed DILI registry patients with and without DRESS from 1998 to 2021. RESULTS: DILI associated with DRESS (DwD) comprised 179 among 943 cases (19%) of DILI. Compared with the cohort without DRESS, patients with DwD are more often women and have shorter latency, lesser degrees of injury ( P < 0.01), and lower mortality (7.8%) than those without DRESS (16%). Antiepileptic drugs (36%), sulfonamides (19%), antituberculosis drugs (14%), antibiotics (10%), and antiretroviral drugs (8%) account for 87% of the cases of DwD. DISCUSSION: A limited number of drugs cause DwD, representing a fifth of patients with DILI. DwD is characterized by lesser degrees of liver injury and mortality likely because of earlier presentation.

Characteristics and comparisons of acute stroke in "recovered" to "active COVID-19 and "pre-pandemic" in Qatar database.

Understanding the relationship of COVID-19 to stroke is important. We compare characteristics of pre-pandemic stroke (PPS), cases in acute COVID infection (CS) and in patients who have recovered from COVID-19 infection (RCS). We interrogated the Qatar stroke database for all stroke admissions between Jan 2020 and Feb 2021 (PPS) to CS and RCS to determine how COVID-19 affected ischemic stroke sub-types, clinical course, and outcomes prior to, during and post-pandemic peak. There were 3264 cases admitted (pre-pandemic: 3111, stroke in COVID-19: 60 and recovered COVID-19 stroke: 93). Patients with CS were significantly younger, had more severe symptoms, fever on presentation, more ICU admissions and poor stroke recovery at discharge when compared to PPS and RCS. Large vessel disease and cardioembolic disease was significantly higher in CS compared to PPS or RCS. There was a significant decline in stroke mimics in CS. Stroke in RCS has characteristics similar to PPS with no evidence of lasting effects of the virus on the short-term. However, CS is a more serious disease and tends to be more severe and have a poor prognosis.

Allocation scheduling leads to optimum utilization of operation theater time.

Background: Cancellation of surgeries is a regular phenomenon in any hospital, and reasons may vary from clinical to managerial ones. The aim of the study is to suggest scheduling to address the problem of time over run related cancellations. This is an observational and descriptive study conducted in a tertiary care hospital with ophthalmology facilities. The sample size is calculated with 95% confidence interval using Epi Info 6 from the total surgeries performed in the last 5 years (n = 380). Simple random sampling technique was used. Methods: Surgical time for all types of ophthalmic surgeries (n = 582) was observed. Allocation of listed cases to the available operating rooms (ORs) was carried out using the observed time using LEKIN software. Results: The time over-run of 2 h and 6 h was noted for two units, whereas idle OR time was observed in other units. An average idle time of 19% was noted on each day. Reallocation of the cases to the ORs was carried out taking all the planned cases (of both the operating units of the day) as the number of jobs and all the available ORs as parallel machines using LEKIN software. All the planned cases could be accommodated; still, an average of 17% of the total available operation theater (OT) time was found idle on each day. Conclusions: Planning of cases using procedure time and scheduling on a daily basis using allocation models with simple algorithms can provide optimal utilization of OTs and can address the time over-run and related cancellations.

Prevalence of coronavirus disease 2019 in a multiethnic cohort of patients with autoimmune rheumatic diseases in Qatar.

BACKGROUND: Autoimmune rheumatic diseases (ARDs) are characterized by immune dysfunction and associated with an increased risk of infections, which were of significant concern during the coronavirus disease 2019 (COVID-19) pandemic. Variable rates of COVID-19 incidence have been reported in patients with ARDs; however, the true effect of this infection on this patient population is still unclear. We, therefore, aimed to evaluate the COVID-19 prevalence among a multiethnic cohort of patients with ARDs in Qatar. MATERIAL AND METHODS: We used telephonic surveys to collect demographic and clinical information of patients with ARD in Qatar between April 1 and July 31, 2020, including any close contact with a COVID-19 case at home or work and polymerase chain reaction (PCR)-confirmed COVID-19 diagnosis. An electronic medical records review was conducted to verify pertinent data collected through the surveys. Prevalence with 95% confidence interval (CI), Student's t-tests, and chi-square/Fisher's exact tests were used for univariate analyses, whereas multivariate logistic regression was used to identify factors associated with COVID-19. RESULTS: The study included 700 patients with ARD (mean age, 43.2 ± 12.3 years), and 73% were female. Until July 2020, 75 (11%, 95% CI 9%-13%) patients had COVID-19. Factors associated with COVID-19 included being a man (adjusted odds ratio [aOR] 2.56, 95% CI 1.35-4.88, p = 0.01) and having close contact with a COVID-19 case (aOR 27.89, 95% CI 14.85-52.38, p = 0.01). Disease severity and rheumatic medications had no significant association with the odds of contracting COVID-19. In the 86 patients with ARD having close contact, the frequency of hydroxychloroquine utilization was lower in patients who contracted COVID-19 than in those who did not (35% vs 72.5%, p = 0.01). CONCLUSIONS: In Qatar, patients with ARDs had an overall higher prevalence of COVID-19 than global estimates. Being male and having close contact with a COVID-19 case were strongly associated with COVID-19 as reported globally. The presence of comorbid conditions, disease-specific factors, and rheumatic medications had no significant effect on the risk of COVID-19 in our study suggesting alternative mechanisms to the increased prevalence.

Resistin induces cardiac fibroblast-myofibroblast differentiation through JAK/STAT3 and JNK/c-Jun signaling.

Cardiac fibrosis is characterized by excessive deposition of extracellular matrix proteins and myofibroblast differentiation. Our previous findings have implicated resistin in cardiac fibrosis; however, the molecular mechanisms underlying this process are still unclear. Here we investigated the role of resistin in fibroblast-to-myofibroblast differentiation and elucidated the pathways involved in this process. Fibroblast-to-myofibroblast transdifferentiation was induced with resistin or TGFß1 in NIH-3T3 and adult cardiac fibroblasts. mRNA and protein expression of fibrotic markers were analyzed by qPCR and immunoblotting. Resistin-knockout mice, challenged with a high-fat diet (HFD) for 20 weeks to stimulate cardiac impairment, were analyzed for cardiac function and fibrosis using histologic and molecular methods. Cardiac fibroblasts stimulated with resistin displayed increased fibroblast-to-myofibroblast conversion, with increased levels of αSma, col1a1, Fn, Ccn2 and Mmp9, with remarkable differences in the actin network appearance. Mechanistically, resistin promotes fibroblast-to-myofibroblast transdifferentiation and fibrogenesis via JAK2/STAT3 and JNK/c-Jun signaling pathways, independent of TGFß1. Resistin-null mice challenged with HFD showed an improvement in cardiac function and a decrease in tissue fibrosis and reduced mRNA levels of fibrogenic markers. These findings are the first to delineate the role of resistin in the process of cardiac fibroblast-to-myofibroblast differentiation via JAK/STAT3 and JNK/c-Jun pathways, potentially leading to stimulation of cardiac fibrosis.

Screening for antenatal depression and its determinants among pregnant women in Qatar: revisiting the biopsychosocial model.

BACKGROUND: Screening for antenatal depression and its determinants is highly recommended. However, there is no consensus on a standard conceptual framework to approach pregnant women in a primary health care setting. The prevalence of antenatal depression and significant determinants are unknown in Qatar, a gap that we propose to fill. METHODS: An analytical cross-sectional study with a probability sampling technique was employed. Enrolling eight-hundred participants from primary health care centers. The screening was performed through a valid and reliable screening instrument 'Edinburgh Postpartum Depression Scale.' In addition to the proposed Comprehensive Biopsychosocial Model, participants were asked about their predisposing profile, biological risk, and other suggested modifiable variables. RESULTS: Twenty-one percent reported minor depressive episodes (n = 167, 20.9%) at a 95% confidence interval [18.2-23.8]. Previous use of mental health medications, fear of giving birth, concern about appearance, low perceived social support, and low resilience level showed to be associated with antenatal depression. The logistic regression analyses revealed that the Comprehensive Biopsychosocial model forecast 89% of antenatal depression predictors provided Area Under the Receiver Operating Characteristic Curve of 0.89 at a 95% confidence interval [0.85 to 0.92]. CONCLUSIONS: Antenatal depression is common among pregnant women in Qatar, and preventive interventions must target the determinants revealed. From a clinical perspective, the use of the proposed model may aid in the standardization of the screening process.

Ethnic differences in out-of-hospital cardiac arrest among Middle Eastern Arabs and North African populations living in Qatar.

Aims: There are very few studies comparing epidemiology and outcomes of out-of-hospital cardiac arrest (OHCA) in different ethnic groups. Previous ethnicity studies have mostly determined OHCA differences between African American and Caucasian populations. The aim of this study was to compare epidemiology, clinical presentation, and outcomes of OHCA between the local Middle Eastern Gulf Cooperation Council (GCC) Arab and the migrant North African populations living in Qatar.Methods: This was a retrospective cohort study of Middle Eastern GCC Arabs and migrant North African patients with presumed cardiac origin OHCA resuscitated by Emergency Medical Services (EMS) in Qatar, between June 2012 and May 2015.Results: There were 285 Middle Eastern GCC Arabs and 112 North African OHCA patients enrolled during the study period. Compared with the local GCC Arabs, univariate analysis showed that the migrant North African OHCA patients were younger and had higher odds of initial shockable rhythm, pre-hospital interventions (defibrillation and amioderone), pre-hospital scene time, and decreased odds of risk factors (hypertension, respiratory disease, and diabetes) and pre-hospital response time. The survival to hospital discharge had greater odds for North African OHCA patients which did not persist after adjustment. Multivariable logistic regression showed that North Africans were associated with lower odds of diabetes (OR 0.48, 95% CI 0.25-0.91, p = 0.03), and higher odds of initial shockable rhythm (OR 2.86, 95% CI 1.30-6.33, p = 0.01) and greater scene time (OR 1.02 95% CI 1.0-1.04, p = 0.02).Conclusions: North African migrant OHCA patients were younger, had decreased risk factors and favourable OHCA rhythm and received greater ACLS interventions with shorter pre-hospital response times and longer scene times leading to better survival.

Psychosocial and Clinical Profiles of the Cases Visiting the Emergency Department Due to Accidental Self-harm and Suicide Attempts in Doha, Qatar: A Retrospective Study.

The aims of this study were to retrospectively assess the profiles of subjects with suicide attempts and self-harm in Doha, Qatar; and whether the available data were complete. We reviewed all the records of fatal and non-fatal suicides together with accidental self-ham cases seen in the major Emergency Department in Doha, over a one-year period. There was 37 completed suicide, mostly male expatriates in mid 30 s who died by hanging. In cases with suicide intent (N = 270), more males were admitted to Psychiatry than women. Overdose was the common method and the majority had mood disorders. In self-harm cases with no suicide intent (N = 150) the majority were not seen by Psychiatry. The profiles of suicide cases in Qatar are similar to those reported internationally. However, there is a major need to establish a comprehensive system to register and assess all self-harm patients in Qatar.

Characteristics and Comparison of 32 COVID-19 and Non-COVID-19 Ischemic Strokes and Historical Stroke Patients.

OBJECTIVES: The presence of COVID-19 infection may increase the risk of thrombotic events including ischemic strokes. Whilst a number of recent reports suggest that COVID-19 associated stroke tends to be severe, there is limited data on the effects of COVID-19 in prospective registries. MATERIAL AND METHODS: To determine how COVID-19 infection may affect cerebrovascular disease, we evaluated the ischemic stroke sub-types, clinical course and outcomes prior to and during the pandemic in Qatar. The Hamad General Hospital (HGH) stroke database was interrogated for stroke admissions during the last 4 months of 2019 and January-May 2020. RESULTS: In Qatar the number of confirmed cases of COVID-19 increased from only 2 in February to 779 in March, 12,628 in April and 45,501 in May. Stroke admissions to HGH declined marginally from an average of 97/month for six pre-COVID months to 72/month in March-May. There were 32 strokes that were positive for COVID-19. When compared to non-COVID-19 stroke during the three months of the pandemic, COVID-19 patients were younger with significantly lower rates of hypertension, diabetes and dyslipidemia. COVID-19 positive patients had more cortical strokes (34.4% vs 5.6%; p = 0.001), severe disease (NIHSS >10: 34.4% vs 16.7%; p = 0.001) prolonged hospitalization and fewer with good recovery (mRS 0-2: 28.1% vs 51.9%; p = 0.001). CONCLUSIONS: When compared to six pre-COVID-19 months, the number of ischemic stroke admissions during the three months of the pandemic declined marginally. COVID-19 positive patients were more likely to have a large cortical stroke with severe symptoms and poor outcome.

Factors predicting difficult spinal block: A single centre study.

BACKGROUND AND AIMS: Several factors determine the success of dural puncture. We aimed to assess the association of first puncture success and number of attempts with characteristics of the patient, provider, technique and equipment. MATERIAL AND METHODS: This prospective, observational study was performed in 1647 adult patients undergoing surgery under spinal anesthesia. Patient characteristics, anatomical landmarks, spinal bony deformity, provider experience, technique, skin punctures, needle redirections, subarachnoid space depth, and complications, if any, were noted. Difficult dural puncture was assessed by first puncture success and number of attempts (skin punctures plus needle redirections) required for successful needle placement. RESULTS: First puncture success was obtained in 872 (52.9%) patients. Failed dural puncture occurred in 4 (0.2%) of 1647 patients. Multivariate logistic regression analysis revealed that longer distance from C7 vertebral spine to tip of coccyx (P = 0.04), lower subarachnoid space depth (P = 0.001), good quality of bony landmarks (P = 0.001) and absence of crowded spine (P = 0.02) were associated with first puncture success. Male gender, poor or no spinal landmarks, presence of bony deformity and lower level of provider's experience predicted increased number of attempts for successful dural puncture. CONCLUSION: First puncture success of spinal block was influenced only by patient's anatomical factors, whereas the number of attempts required for successful block were predicted by both provider and patient factors.

FTO-Dependent N6-Methyladenosine Regulates Cardiac Function During Remodeling and Repair.

BACKGROUND: Despite its functional importance in various fundamental bioprocesses, studies of N6-methyladenosine (m6A) in the heart are lacking. Here, we show that the FTO (fat mass and obesity-associated protein), an m6A demethylase, plays a critical role in cardiac contractile function during homeostasis, remodeling, and regeneration. METHODS: We used clinical human samples, preclinical pig and mouse models, and primary cardiomyocyte cell cultures to study the functional role of m6A and FTO in the heart and in cardiomyocytes. We modulated expression of FTO by using adeno-associated virus serotype 9 (in vivo), adenovirus (both in vivo and in vitro), and small interfering RNAs (in vitro) to study its function in regulating cardiomyocyte m6A, calcium dynamics and contractility, and cardiac function postischemia. We performed methylated (m6A) RNA immunoprecipitation sequencing to map transcriptome-wide m6A, and methylated (m6A) RNA immunoprecipitation quantitative polymerase chain reaction assays to map and validate m6A in individual transcripts, in healthy and failing hearts, and in myocytes. RESULTS: We discovered that FTO has decreased expression in failing mammalian hearts and hypoxic cardiomyocytes, thereby increasing m6A in RNA and decreasing cardiomyocyte contractile function. Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is performed by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts, thus preventing their degradation and improving their protein expression under ischemia. In addition, we demonstrate that FTO overexpression in mouse models of myocardial infarction decreased fibrosis and enhanced angiogenesis. CONCLUSIONS: Collectively, our study demonstrates the functional importance of the FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.

Dengue hepatitis with acute liver failure: Clinical, biochemical, histopathological characteristics and predictors of outcome.

BACKGROUND: Hepatitis infection from non-hepatotropic viruses such as dengue virus (DENV) is increasing worldwide. There is increasing recognition of the changing epidemiology and atypical presentations of DENV infection including acute liver failure (ALF). There is paucity of data regarding incidence, disease characteristics, and markers of prognosis in patients who develop DENV-related ALF. METHODS: We aimed to study the incidence, clinical features, laboratory characteristics, and determinants of outcome in patients of DENV presenting with ALF. We reviewed all patients with DENV infection and focused on DENV-related ALF from 2014 to 2017. Diagnosis of DENV and ALF was confirmed by serological tests and standard criteria, respectively. RESULTS: Thirty-six patients (20 men, mean age 32.3) developed ALF among 10 108 patients with DENV infection (0.35%). Twenty-one patients died (58.3%). Although bilirubin, aspartate and alanine aminotransferase, and international normalized ratio were markedly elevated in all patients with DENV ALF, there was no statistically significant difference between survivors and non-survivors. Lactate levels, pH at admission, and model for end-stage liver disease (MELD) score were the only predictors of mortality. Lactate levels were significantly higher in non-survivors (11.5 ± 4.2 mmol/L) than survivors (6.3 ± 3.6 mmol/L) (P < 0.001). MELD score in non-survivors (26.7 ± 10.2) was significantly higher than in survivors (20 ± 7.2) (P = 0.039). Receiver operator characteristic curve showed lactate or pH to be a superior prognostic marker than MELD with an area under the curve of 0.80, 0.79, and 0.70, respectively. CONCLUSION: Dengue hepatitis progressed to ALF in 0.35%. Development of ALF was associated with a high mortality (> 50%). Lactate level, pH, and MELD score at admission were significant determinants of outcome.

The FASILA Score: A Novel Bio-Clinical Score to Predict Massive Blood Transfusion in Patients with Abdominal Trauma.

BACKGROUND: Early identification of patients who may need massive blood transfusion remains a major challenge in trauma care. This study proposed a novel and easy-to-calculate prediction score using clinical and point of care laboratory findings in patients with abdominal trauma (AT). METHODS: Patients with AT admitted to a trauma center in Qatar between 2014 and 2017 were retrospectively analyzed. The FASILA score was proposed and calculated using focused assessment with sonography in trauma (0 = negative, 1 = positive), Shock Index (SI) (0 = 0.50-0.69, 1 = 0.70-0.79, 2 = 0.80-0.89, and 3 ≥ 0.90), and initial serum lactate (0 ≤ 2.0, 1 = 2.0-4.0, and 2 ≥ 4.0 mmol/l). Outcome variables included mortality, laparotomy, and massive blood transfusion (MT). FASILA was compared to other prediction scores using receiver operating characteristics and areas under the curves. Bootstrap procedure was employed for internal validation. RESULTS: In 1199 patients with a mean age of 31 ± 13.5 years, MT, MT protocol (MTP) activation, exploratory laparotomy (ExLap), and hospital mortality were related linearly with the FASILA score, Injury Severity Score, and total length of hospital stay. Initial hemoglobin, Revised Trauma Score (RTS), and Trauma Injury Severity Score (TRISS) were inversely proportional. FASILA scores correlated significantly with the Assessment of Blood Consumption (ABC) (r = 0.65), Revised Assessment of Bleeding and Transfusion (RABT) (r = 0.63), SI (r = 0.72), RTS (r = - 0.34), and Glasgow Coma Scale (r = - 0.32) and outperformed other predictive systems (RABT, ABC, and SI) in predicting MT, MTP, ExLap, and mortality. CONCLUSIONS: The novel FASILA score performs well in patients with abdominal trauma and offers advantages over other scores.