Effect of experimental coronary sinus ligation on myocardial structure and function in the presence or absence of structural heart disease: an insight for the interventional electrophysiologist.

AIMS: To study the effect of coronary sinus (CS) occlusion on normal hearts and hearts with structural disease. METHODS AND RESULTS: We included 32 dogs, divided into 4 groups: (1) CS ligation (CSL): subjected to CSL; (2) control group: no intervention; (3) MI-CSL group: subjected to myocardial infarction (MI) induction followed by CSL after 1 week; and (4) MI-control group: subjected to MI induction, then open thoracotomy after 1 week without CSL. Electrocardiography, echocardiography, histopathology, and immunohistochemistry were done before and after CSL. In CSL group, there were no significant electrocardiographic or echocardiographic changes after CSL, although there was interstitial oedema that decreased after 1 week with the appearance of Thebesian vessels and positive staining for vascular endothelial growth factor. In MI-CSL group, there was significant increase in left ventricular (LV) end-systolic diameter (P = 02), decrease in LV fractional shortening (P = 0.0001), and LV ejection fraction (P = 0.002) in comparison with MI-control group, associated with severe myocardial degeneration. CONCLUSION: Acute CS occlusion could be compensated in normal hearts, but may be detrimental in the presence of structural heart disease.

Early Repolarization Pattern Is Associated with Increased Risk of Early Ventricular Arrhythmias during Acute ST Segment Elevation Myocardial Infarction.

BACKGROUND: Early repolarization (ER) and acute ST segment elevation myocardial infarction (STEMI) are sharing the pathophysiology of J wave syndromes. It is speculated that early ventricular arrhythmias (VAs) during STEMI may be predisposed by ER. Our aim was to study the association between ER pattern and risk of VAs during acute STEMI. METHODS: The study included 102 male patients with acute STEMI who were divided into two groups: cases and controls. Cases included 52 patients with sustained VAs during the first 48 hours from the onset of STEMI, while controls included 50 patients with no VAs. On 12-lead surface electrocardiogram, ER was defined as ≥ 1 mm elevation of J point in at least two inferior or lateral leads with or without ST segment elevation. RESULTS: Mean age was 48.44 ± 10.08 years and mean left ventricular ejection fraction (LVEF) was 42.25 ± 11.1%. ER pattern was more frequent in cases than controls (29 vs 14 patients, P = 0.008). Notched J wave (P = 0.0007) and horizontal ST segment (P = 0.033) were more frequent in cases than controls. On adjusted regression model, LVEF (OR: 0.95, 95% CI: 0.91-0.99, P = 0.015) and ER (OR: 3.39, 95% CI: 1.41-8.12, P = 0.006) could predict VAs, while QTc interval (P = 0.24) and QTd (P = 0.86) did not have predictive effect. Inferior/inferolateral and global ER pattern (P = 0.044 and 0.031 respectively), notched J wave (P = 0.001), increasing J wave amplitude (P = 0.042), and ST segment elevation (P = 0.001) were associated with a higher risk of VAs. CONCLUSIONS: ER is associated with increased risk of VAs in the setting of acute STEMI.

von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis.

von Willebrand disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding. Early diagnosis and treatment are important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cutoff values of von Willebrand factor antigen (VWF:Ag) and platelet-dependent von Willebrand factor (VWF) activity assays in the diagnosis of VWD. We searched Cochrane Central Register for Controlled Trials, MEDLINE, and Embase databases for eligible studies. We pooled estimates of sensitivity and specificity and reported patient-important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis. The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD vs removing the disease diagnosis in patients with VWF levels that have normalized with age. For the diagnosis of type 1 VWD, VWF sequence variants were detected in 75% to 82% of patients with VWF:Ag < 0.30 IU/mL and in 44% to 60% of patients with VWF:Ag between 0.30 and 0.50 IU/mL. A sensitivity of 0.90 (95% confidence interval [CI], 0.83-0.94) and a specificity of 0.91 (95% CI, 0.76-0.97) were observed for a platelet-dependent VWF activity/VWF:Ag ratio < 0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF:Ag and platelet-dependent activity are continuous variables that are associated with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio < 0.7 vs lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD.

Laboratory assays of VWF activity and use of desmopressin trials in the diagnosis of VWD: a systematic review and meta-analysis.

von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment are important to prevent and treat these symptoms. We systematically reviewed the accuracy of any von Willebrand factor (VWF) activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and the certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR, VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio, and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appear to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with suspected VWD type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD.

Bleeding assessment tools in the diagnosis of VWD in adults and children: a systematic review and meta-analysis of test accuracy.

Von Willebrand disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. We systematically reviewed diagnostic test accuracy results of BATs to screen patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using the revised tool for the quality assessment of diagnostic accuracy studies and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval, 66-83) and 54% (29-77), respectively. Certainty of evidence varied from moderate to high. This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates, will influence patient management.

Transient Asymptomatic Sinus Bradycardia and Sinus Pauses with Bevacizumab: Case Report and Literature Review.

Systemic side effects of anti-cancer therapy remain a major limiting factor for patients, even with targeted therapy. Bevacizumab is an example of targeted cancer therapy which targets the vascular endothelial growth factor receptor (VEGFR) that has been approved for the treatment of various cancers and has been evaluated in metastatic urothelial carcinoma (MUC). We report a case of MUC on bevacizumab containing regimen who developed temporary asymptomatic sinus bradycardia with sinus pauses. That adverse event was thought to be related to the bevacizumab in her cancer regimen. Her Holter monitoring recording for a total duration of 28 days and 14 h after discharge did not show recurrence of sinus pauses. This case indicates the necessity for observation for the cardiac conduction defects as side effects in patients receiving bevacizumab, especially since they might be asymptomatic and transient.

The benefits of a model of interval comprehensive assessments (MICA) in hereditary cancer Syndromes: Hereditary diffuse gastric cancer (HDGC) as an example.

A high percentage of individuals at risk for hereditary cancer syndromes are unaware of their risk. This is especially detrimental in syndromes such as hereditary diffuse gastric cancer due to a CDH1 germline mutation, for which lifesaving prevention is possible. Surveillance for diffuse gastric cancer in the syndrome is limited, hence the recommendation for prophylactic total gastrectomy for mutation carriers. Genetic counseling and testing is crucial in suspected families but initial contact could be limited, leading to the importance of an interval comprehensive review every 5-8 years to identify and screen additional high-risk individuals. Our contact with a hereditary diffuse gastric cancer family in Jordan in 2011 led to a number of family members receiving education and genetic counseling. Our model of interval comprehensive assessment (MICA) was constructed and implemented by conducting family information service, video call and emails to the high-risk individuals 7 years after initial contact. Using an updated family pedigree we reached out to an additional thirteen high-risk members in six different countries and provided them with genetic education, counseling, and testing. Six members agreed to CDH1 testing (46%). Four tested positive (66%) and one member (25%) underwent prophylactic total gastrectomy.

Docetaxel-Induced Stevens-Johnson Syndrome in a Patient with Metastatic Prostate Adenocarcinoma.

Docetaxel is a commonly used chemotherapeutic agent in a variety of cancer treatment regimens. We present a case of apparent docetaxel-induced Stevens-Johnson syndrome (SJS) in a patient recently treated for metastatic prostate cancer. This medication is not classically associated with the development of SJS but in our case, along with a number of other case reports, and a single phase II clinical trial, an association was recognized. We encourage clinicians who employ the use of this medication to be aware of this relationship.

A Case of Levamisole-Induced Agranulocytosis.

A sixty-eight-year-old male with a past medical history of recurrent cocaine use presented to the emergency department with recurrent diarrhea and was found to have a white blood cell (WBC) count of 1.9 × 109/L with agranulocytosis (absolute neutrophil count (ANC) of 95 cell/mm3). At admission, the patient disclosed that he used cocaine earlier during the day, and a urine drug screen tested positive for this. On hospital day one, the patient was found to have a fever with a maximum temperature of 313.6 K. After ruling out other causes and noting the quick turnaround of his neutropenia after four days of cocaine abstinence, the patient's neutropenia was attributed to levamisole-adulterated cocaine.

A new hereditary colorectal cancer network in the Middle East and eastern mediterranean countries to improve care for high-risk families.

Colorectal cancer (CRC) has a very high incidence in the western world. Data from registries in the Middle East showed that the incidence of CRC is relatively low in these countries. However, these data also showed that CRC incidence has increased substantially over the past three decades and that a high proportion of cases are diagnosed at an early age (<50 years). In view of these findings, more attention should be paid to prevention. Because of the often limited financial resources, focused screening of individuals with hereditary CRC, in particular those with Lynch syndrome, appears to be the most cost-effective strategy. During recent meetings of the Palestinian Society of Gastroenterology and the Mediterranean Task force for Cancer Control (MTCC) in Jericho, and the Patient's Friends Society of Jerusalem in Hebron the issue of hereditary CRC in the Middle East was discussed and the idea was conceived to establish a network on hereditary colorectal cancer (HCCN-ME) with the goal of improving care for high-risk groups in the Middle East and (Eastern) Mediterranean Countries.

Efficacy and Safety of Coronary Sinus Aspiration During Coronary Angiography to Attenuate the Risk of Contrast-Induced Acute Kidney Injury in Predisposed Patients.

BACKGROUND: The incidence of contrast-induced acute kidney injury is strongly related to the amount of the given contrast. Our objectives were to evaluate the efficacy and safety of coronary sinus aspiration (CSA) procedure to reduce the volume of the given contrast and attenuate the risk of contrast-induced acute kidney injury. METHODS AND RESULTS: The study included 43 patients with type 2 diabetes mellitus and renal impairment (creatinine 1.5-3 mg/dL) who were candidates for coronary angiography. Eighteen patients were subjected to CSA procedure during coronary angiography (CSA group), and 25 patients served as a control group. Periprocedural standard care was given. In CSA group, the coronary sinus was cannulated via subclavian or femoral venous approaches, and aspiration was done directly from a transseptal sheath (8 patients) or through a balloon occlusion catheter placed through the sheath (10 patients) simultaneously during each coronary injection. Estimated volume of aspirated contrast was calculated based on the percentage reduction in hematocrit value of the aspirate in relation to the patient's baseline hematocrit. Fraction of aspirated contrast was calculated by dividing estimated volume of aspirated contrast over the volume of injected contrast×100. Both study groups were matched in clinical and laboratory data, as well as volume of injected contrast. In CSA group, mean fraction of aspirated contrast was 39.35±10.47%. One patient in the CSA group, compared with 9 patients in the control group, developed contrast-induced acute kidney injury (P=0.028). CONCLUSIONS: CSA during coronary angiography could effectively remove more than one third of the given contrast and may reduce the incidence of contrast-induced acute kidney injury in selected patients.

Major hereditary gastrointestinal cancer syndromes: a narrative review.

Gastrointestinal cancer is one of the major causes of death worldwide. Hereditary gastrointestinal cancer syndromes constitute about 5-10% of all cancers. About 20-25% of undiagnosed cases have a possible hereditary component, which is not yet established. In the last few decades, the advance in genomics has led to the discovery of multiple cancer predisposition genes in gastrointestinal cancer. Physicians should be aware of these syndromes to identify high-risk patients and offer genetic testing to prevent cancer death. In this review, we describe clinical manifestations, genetic testing and its challenges, diagnosis and management of the major hereditary gastrointestinal cancer syndromes.