Extended Computed Tomography Angiography for the Successful Diagnosis of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA: Study Protocol for a Randomized Controlled Trial.

INTRODUCTION: Cardiac imaging is one of the main components of the etiological investigation of ischemic strokes. However, basic and advanced cardiac imaging remain underused in most stroke centers globally. Computed tomography angiography (CTA) of the supra-aortic and intracranial arteries is the most frequent imaging modality applied during the evaluation of patients with acute ischemic stroke to identify the presence of a large vessel occlusion. Recent evidence from retrospective observational studies has shown a high detection of cardiac thrombi, ranging from 6.6 to 17.4%, by extending a CTA a few cm below the carina to capture cardiac images. However, this approach has never been prospectively compared against usual care in a randomized controlled trial. The Extended Computed Tomography Angiography for the Successful Screening of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA (DAYLIGHT) prospective, randomized, controlled trial evaluates whether an extended CTA (eCTA) + standard-of-care stroke workup results in higher detection rates of cardiac and aortic source of embolism compared to standard-of-care CTA (sCTA) + standard-of-care stroke workup. METHODS: DAYLIGHT is a single-center, prospective, randomized, open-blinded endpoint trial, aiming to recruit 830 patients with suspected acute ischemic stroke or transient ischemic attack (TIA) being assessed under acute code stroke at the emergency department or at a dedicated urgent stroke prevention clinic. Patients are randomized 1:1 to eCTA versus sCTA. The eCTA expands image acquisition caudally, 6 cm below the carina. All patients receive standard-of-care cardiac imaging and diagnostic stroke workup. The primary efficacy endpoint is the diagnosis of a cardioaortic thrombus after at least 30 days of follow-up. The primary safety endpoint is door-to-CTA completion time. The diagnosis of a qualifying ischemic stroke or TIA is independently adjudicated by a stroke neurologist, blinded to the study arm allocation. Patients without an adjudicated ischemic stroke or TIA are excluded from the analysis. The primary outcome events are adjudicated by a board-certified radiologist with subspecialty training in cardiothoracic radiology and a cardiologist with formal training in cardiac imaging. The primary analysis is performed according to the modified intention-to-diagnose principle and without adjustment by logistic regression models. Results are presented with odds ratios and 95% confidence intervals. CONCLUSION: The DAYLIGHT trial will provide evidence on whether extending a CTA to include the heart results in an increased detection of cardioaortic thrombi compared to standard-of-care stroke workup.

Antidiabetic activity of Berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats.

Medicinal plants play a key role in protection of chronic non-communicable ailments like diabetes, hypertension and dyslipidemia. Berberis brandisiana Ahrendt (Berberidaceae) is traditionally used to treat diabetes, liver problems, wounds, arthritis, infections, swelling and tumors. It is also known to be enriched with multiple phytoconstituents including berbamine, berberine, quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, m-coumaric acid and ferulic acid. The efficacy of B. brandisiana has not been established yet in diabetes. This study has been planned to assess the antidiabetic activity of B. brandisiana in high fat diet and streptozotocin (HFD/STZ)-induced diabetes using animals. Administration of aqueous methanolic extract of B. brandisiana (AMEBB) and berbamine (Berb) for 8 weeks caused a dose dependent marked (p < 0.01) rise in serum insulin and HDL levels with a significant decline (p < 0.01) in glucose, triglycerides, glycosylated hemoglobin (HbA1c), cholesterol, LDL, LFTs and RFTs levels when compared with only HFD/STZ-administered rats. AMEBB and Berb also modulated inflammatory biomarkers (TNF-α, IL-6) and adipocytokines (leptin, adiponectin and chemerin). AMEBB (150 mg/kg and 300 mg/kg) and Berb (80 mg/kg and 160 mg/kg) treated rats showed a marked increase (p < 0.001) in catalase levels (Units/mg) in pancreas (42.4 ± 0.24, 47.4 ± 0.51), (38.2 ± 0.583, 48.6 ± 1.03) and liver (52 ± 1.41, 63.2 ± 0.51), (57.2 ± 0.58, 61.6 ± 1.24) and superoxide dismutase levels (Units/mg) in pancreas (34.8 ± 1.46, 38.2 ± 0.58), (33.2 ± 0.80, 40.4 ± 1.96) and liver (31.8 ± 1.52, 36.8 ± 0.96), (30 ± 0.70, 38.4 ± 0.81),respectively while a significant (p < 0.01) decrease in serum melondialdehyde levels (nmol/g) in pancreas (7.34 ± 0.17, 6.22 ± 0.22), (7.34 ± 0.20, 6.34 ± 0.11) and liver (9.08 ± 0.31,8.18 ± 0.29), (9.34 ± 0.10, 8.86 ± 0.24) compared to the data of only HFD/STZ-fed rats. Histopathological studies of pancreas, liver, kidney, heart and aorta revealed restoration of normal tissue architect in AMEBB and Berb treated rats. When mRNA expressions of candidate genes were assessed, AMEBB and Berb showed upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17. These findings suggest that AMEBB and Berb possess antidiabetic activity, possibly due to its effect on oxidative stress, glucose metabolism, inflammatory biomarkers and adipocytokines levels. Further upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17, demonstrated its potential impact on glucose homeostasis, insulin resistance and chronic inflammatory markers. Thus, this study provides support to the medicinal use of B. brandisiana and berbamine in diabetes.

Caryopteris odorata and its metabolite coumarin attenuate characteristic features of cardiometabolic syndrome in high-refined carbohydrate-high fat-cholesterol-loaded feed-fed diet rats.

Caryopteris odorata (D. Don) B.L. Robinson (Verbenaceae family) is an aromaric shrub traditionally used to treat diabetes and related pathologies (diabetic foot ulcer), cancer/tumors, wound healing, and inflammation. It is enriched with flavonoids and phenolics like coumarins, quercetin, gallic acid, coumaric acid, stigmasterol, α-tocopherol, and iridoids. C. odorata has been reported as having α-glucosidase, anti-inflammatory, and anti-oxidant properties. Its effectiveness in preventing cardiometabolic syndrome has not yet been assessed. This study aims to investigate the potential efficacy of C. odorata and coumarin for characteristic features of cardiometabolic syndrome (CMS), including obesity, dyslipidemia, hyperglycemia, insulin resistance, and hypertension by using high-refined carbohydrate-high fat-cholesterol (HRCHFC)-loaded feed-fed rats. Chronic administration of C. odorata and coumarin for 6 weeks revealed a marked attenuation in body and organ weights, with a consistent decline in feed intake compared to HRCHFC diet fed rats. The test materials also caused a significant reduction in the blood pressure (systolic, diastolic, and mean) and heart rate of HRCHFC-diet fed rats. Improved glucose tolerance and insulin sensitivity tests were also observed in test material administered rats compare to only HRCHFC-diet fed rats. C. odorata and coumarin-treated animals produced a marked decline in serum FBG, TC, TG, LFTs, and RFTs, while an increase in serum HDL-C levels was noticed. C. odorata and coumarin also significantly modulated inflammatory biomarkers (TNFα, IL-6), adipokines (leptin, adiponectin, and chemerin), and HMG-CoA reductase levels, indicating prominent anti-inflammatory, cholesterol-lowering, and anti-hyperglycemic potential. Administration of C. odorata and coumarin exhibited a marked improvement in oxidative stress markers (CAT, SOD, and MDA). Histopathological analysis of liver, heart, kidney, pancreas, aorta, and fat tissues showed a revival of normal tissue architecture in C. odorata and coumarin-treated rats compared to only HRCHFC-diet fed rats. These results suggest that C. odorata and coumarin possess beneficial effects against the characteristic features of CMS (obesity, insulin resistance, hypertension, and dyslipidemia) in HRCHFC feed-administered rats. These effects were possibly mediated through improved adipokines, glucose tolerance, and insulin sensitivity, the attenuation of HMG-CoA reductase and inflammatory biomarkers, and modulated oxidative stress biomarkers. This study thus demonstrates a rationale for the therapeutic potential of C. odorata and coumarin in CMS.

Magnetic Resonance Left Ventricle Mass-Index/Fibrosis: Long-Term Predictors for Ventricular Arrhythmia in Hypertrophic Cardiomyopathy-A Retrospective Registry.

Objective: We aimed to study the long-term association of LV mass index (LVMI) and myocardial fibrosis with ventricular arrhythmia (VA) in a population of patients with confirmed hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance imaging (CMR). Methods: We retrospectively analyzed the data in consecutive HCM patients confirmed on CMR referred to an HCM clinic between January 2008 and October 2018. Patients were followed up yearly following diagnosis. Baseline demographics, risk factors and clinical outcomes from cardiac monitoring and an implanted cardioverter defibrillator (ICD) were analyzed for association of LVMI and LV late gadolinium enhancement (LVLGE) with VA. Patients were then allocated to one of two groups according to the presence of VA (Group A) or absence of VA (Group B) during the follow-up period. The transthoracic echocardiogram (TTE) and CMR parameters were compared between the two groups. Results: A total of 247 patients with confirmed HCM (age 56.2 ± 16.6, male = 71%) were studied over the follow-up period of 7 ± 3.3 years (95% CI = 6.6-7.4 years). LVMI derived from CMR was higher in Group A (91.1 ± 28.1 g/m2 vs. 78.8 ± 28.3 g/m2, p = 0.003) when compared to Group B. LVLGE was higher in Group A (7.3 ± 6.3% vs. 4.7 ± 4.3%, p = 0.001) when compared to Group B. Multivariable Cox regression analysis showed LVMI (hazard ratio (HR) = 1.02, 95% CI = 1.001-1.03, p = 0.03) and LVLGE (HR = 1.04, 95% CI = 1.001-1.08, p = 0.04) to be independent predictors for VA. Receiver operative curves showed higher LVMI and LVLGE with a cut-off of 85 g/m2 and 6%, respectively, to be associated with VA. Conclusions: LVMI and LVLGE are strongly associated with VA over long-term follow-up. LVMI requires more thorough studies to consider it as a risk stratification tool in patients with HCM.

Stress Perfusion Cardiac Magnetic Resonance Imaging With a 3.0-Tesla Scanner for Myocardial Viability in a Patient With a Conditional Pacemaker.

Cardiac magnetic resonance (CMR) imaging provides images with high spatial and temporal resolution, with high diagnostic and prognostic performance. An abundance of data indicate the safety and efficacy of noncardiac magnetic resonance imaging at both 1.5 Tesla (T) and 3T in patients with cardiac implantable electronic devices (CIEDs). Safety and efficacy have also been evaluated for stress perfusion (SP)-CMR for pateints with CIEDs, using 1.5T scanners, but no previous reports have been made of SP-CMR using 3T scanners. Herein, we report a case of a patient with a CIED who successfully and safely underwent SP-CMR imaging using a 3T scanner.

L'imagerie par résonance magnétique cardiaque (IRMC) procure des images à haute résolution spatiale et temporelle en plus d'offrir une capacité diagnostique et pronostique élevée, mais une multitude de données mettent en lumière l'innocuité et l'efficacité de l'imagerie non cardiaque réalisée au moyen d'appareils d'IRM produisant un champ magnétique de 1,5 ou de 3 teslas (T) chez des patients porteurs d'un dispositif cardiaque électronique implantable (DCEI). L'innocuité et l'efficacité de l'évaluation de la perfusion à l'effort (EPE) par IRMC ont aussi été évaluées chez des patients porteurs d'un DCEI au moyen d'appareils produisant un champ magnétique de 1,5 T, mais pas au moyen d'appareils produisant un champ magnétique de 3 T. Nous rapportons ici le cas d'un patient porteur d'un DCEI ayant subi avec succès et en toute sécurité une EPE par IRMC réalisée au moyen d'un appareil produisant un champ magnétique de 3 T.

Non-operative treatment of hepatic trauma: A changing paradigm. A Six year review of liver trauma patient in a single institute.

OBJECTIVE: To review the managing strategies of adult patients with liver trauma in a tertiary care hospital during a six years period. METHODS: The medical records of all patients admitted with a diagnosis of liver trauma from January 2012 to December 2017 in the Aga Khan University Hospital were retrospectively reviewed. The details of demographic, clinical, and outcome variables including morbidity and mortality rates were noted. RESULTS: A total of 182 patients were admitted at AKUH with liver trauma between January 2012 and December 2017. Twenty-two patients were excluded according to our study criteria. Of 160 patients, 139 were male and 21 were female. One hundred twenty seven (79.4%) patients were less than 45 years of age. Most patients (89.4%) had no comorbids and 48 (44%) arrived at the hospital within 4 hours of injury. Majority, 101 (63.1%) of the patients had blunt trauma and 142 (89%) met with road accidents. A total of 109 (68.1%) patients were stable at arrival and 77 (48.1%) had abdominal signs present on examination. FAST ultrasound was done on 75 (46.9%) patients and CT scan abdomen on 145 (90.6 %) patients. Liver injuries were associated with other abdominal or systemic injuries in 139 (86.6%) patients. Low grade (Grade I & II) liver injuries were found in only 41 (25.6%) patients, with the remainder being high grade (Grade III- 41 patients, Grade IV-42 patients and Grade V-2 patients). Conservative treatment was offered to 68 (41.9%) patients, of which 57 (85.1%) remained stable and were eventually discharged. Of these, 2 expired and 3 required intervention. There were a total of 92 (57.2%) interventions done of which 60 patients were cured, 14 expired and 18 readmitted. Interventions included perihepatic packing (n=18), hepatorraphy (n=3), angioembolization (n=12) and hepatectomy (n=1). There were 16(10%) deaths in which liver haemorrhage and sepsis were the most common cause of mortality. Mean hospital stay in our study population was 8.9 days. Second admission was observed in 28 (17.5%) patients (n=28). Morbidity rate in our patients was 17.5% (n=28). The most common complication noted was that of a liver abscess, developing in 2 (1.3%) patients. Other significant problems were intra-abdominal collections (n=2) and biliary complications (n=3). Unstable haemodynamic status at arrival and prolonged stay in high dependency unit were noted to be independent risk factors for mortality. CONCLUSIONS: Conservative treatment was found successful in most of our patients with an intervention rate of 57.5% and overall mortality rate of 10%. So, NOMLI can be safely offered to liver trauma patients, even in high grade injuries.

Segment IV hepatic artery in potential donors for living related liver transplantation: Evaluation with multi-detector CT.

OBJECTIVE: To assess segment IV hepatic arterial anatomy and its variation on multi-detector computed tomography in potential liver donors. METHODS: The retrospective study was conducted at Shifa International Hospital, Islamabad and comprised data of potential liver transplant donors related to the period between January 2012 and June 2017. Computed tomography scans were performed using multi-detector scanners. Images were transferred to work station for postprocessing and were analysed regarding the origination and variation of the arteries by two independent experienced radiologists. RESULTS: Of the 455 patients whose records were evaluated, 299(65.7%) were males and 156(34.3%) were females. Six types of segment IV artery were defined based on their points of origin: left hepatic artery 285(62.6%), right hepatic artery 111(24.4 %), proper hepatic artery 9(1.8 %), common hepatic artery 29(6.4%), gastro duodenal artery 3(0.7 %), and dual 18(4.1 %).313 of total cases (68.8%) had normal anatomy with no variation. Those with aberrant/variant anatomy constituted 142(31.2%) of the total. CONCLUSIONS: Multi-detector computed tomography angiography was found to be a fast, reliable and non-invasive technique that could evaluate normal as well as anatomical variants of segment IV arteries.

Lymphoepithelioma-Like Carcinoma of the Esophagus: A Rare Tumor.

Lymphoepithelioma-like carcinoma of esophagus is a rare tumor with about 20 cases reported worldwide. It can involve the salivary gland, esophagus, stomach, thymus, thyroid, breast, lung, uterus, cervix, urinary bladder, and the skin. Its association with Epstein Barr virus has been postulated. We report the case of a 45-year female who had been treated for hepatitis C and esophageal tuberculosis and recovered fully from these conditions. She presented with dysphagia of 2-3 month duration. Endoscopic examination revealed narrowing of the esophageal lumen with a fungating mass at the lower end of esophagus with no extension into the stomach. ACTscan confirmed a mass at the lower end of esophagus with multiple enlarged mediastinal lymph nodes. Histological and immunohistochemistry of esophageal biopsy sample showed lymphoepithelioma-like carcinoma. She was managed with chemotherapy comprising of capecitabine, epirubicin and cisplatin followed by esophagectomy and made full recovery.

Validation of ethnopharmacological uses of Murraya paniculata in disorders of diarrhea, asthma and hypertension.

BACKGROUND: Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems. METHODS: Aqueous-ethanolic extract of Mp.Cr was tested using in vitro techniques on isolated tissue of rabbit (jejunum, trachea and aorta) to detect the possible presence of spasmolytic activity. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system. RESULTS: Application of the extract of Mp.Cr relaxed spontaneous and high K(+) (80mM)-induced contraction in rabbit jejunum preparation. Because it shifted the CRCs (Calcium response curve) towards the right side so the possible blockade was of calcium channel similar to verapamil. In rabbit trachea, extract of Mp.Cr produced relaxation of carbachol and high K(+) induced contractions. When plant extract was checked further on isolated aorta for its possible vasodilator effect, it caused relaxation of phenylephrine and high K(+)-induced spastic contractions at different doses. CONCLUSION: These results indicate that Murraya paniculata shows anti-spasmodic, bronchodilator and vasodilator activity facilitated through Ca(++) antagonist mechanisms.