Failure of clopidogrel to reduce platelet reactivity and activation following standard dosing in elective stenting: implications for thrombotic events and restenosis

There is no information on long-term platelet reactivity and activation following elective stenting in patients treated with clopidogrel and aspirin. We measured platelet reactivity and activation at baseline and at 2 h, 24 h, 5 days and 30 days following coronary stenting (n = 94). Patients were treated with the standard aspirin (325 mg) and clopidogrel regimen (300 mg load/75 mg qd). Reactivity was measured by aggregation (5 and 20 microM ADP) and activation was determined by the expression of total and active GP IIb/IIIa. Reactivity and activation were defined as heightened when post-stent aggregation and receptor expression exceeded baseline levels, respectively. Prolonged heightened platelet reactivity was detected by both 5 and 20 microM ADP aggregation. Using 20 microM ADP aggregation, heightened reactivity occurred in 55% of patients at 2 h, 26% at 24 h, 21% at 5 days, and 15% at 30 days post-stenting. A high frequency of heightened platelet activation was detected by both total and active GP IIb/IIIa expression. Using expression of the active GP IIb/IIIa receptor as the marker, activation was greater than baseline in 27% of patients at 2 h, 20% at 24 h, 30% at 5 days, and 22% at 30 days post-stenting. This is the first report demonstrating that a significant percentage of patients receiving standard clopidogrel and aspirin therapy for coronary stenting will have post-drug platelet reactivity and activation above baseline that persists for 30 days after the procedure. These finding suggest insufficient platelet inhibition. The clinical importance of these findings should be further investigated to establish the potential link between insufficient platelet inhibition, stent thrombosis, and restenosis.     

A systematic review and meta‐analysis of the impact of the left atrial appendage closure on left atrial function

BackgroundLeft atrial (LA) appendage closure (LAAC) is effective in patients with atrial fibrillation who are not candidates for long‐term anticoagulation. However, the impact of LAAC on LA function is unknown. The aim of this study is to evaluate the impact of LAAC on atrial function.MethodsThis meta‐analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar for studies showing the effect of LAAC on the LA function from inception to November 20, 2021. The standardized mean difference (SMD) was calculated from the means and standard deviations.ResultsOf 247 studies initially identified, 8 studies comprising 260 patients were included in the final analysis. There was a significant increase in LA emptying fraction following LAAC compared with preoperative function (SMD: 0.53; 95% confidence interval [CI]: 0.04–1.01; p = .03; I ² = 75%). In contrast, there were no significant differences in LA volume (SMD: −0.07; 95% CI: −0.82–0.69; p = .86; I ² = 92%) peak atrial longitudinal strain (SMD: 0.50; 95% CI: −0.08–1.08; p = .09; I ² = 89%), peak atrial contraction strain (SMD: 0.38; 95% CI: −0.22–0.99; p = .21; I ² = 81%), strain during atrial contraction (SMD: −0.24; 95% CI: −0.61–0.13; p = .20; I ² = 0%), strain during ventricular systole (SMD: 0.47; 95% CI: −0.32–1.27; p = .24; I ² = 89%), strain during ventricular diastole (SMD: 0.09; 95% CI: −0.32–0.51; p = .66; I ² = 65%).ConclusionLAAC is associated with improvement in the left atrial emptying fraction, but did not significantly influence other parameters.     

Foodborne botulism: an international outbreak

We report an outbreak of fishborne botulism caused by type E Clostridium botulinum. The eight cases, six in Israel and two in New York City, resulted from the consumption of ribbetz or kapchunka, a freshwater whitefish soaked in brine and air-dried, that was processed commercially in New York. Half the cases were males; the age range was 9 to 77 years. Five of the victims were hospitalized; the oldest died, and two others required ventilatory assistance. Laboratory confirmation of botulism was obtained in three cases. Prolonged lack of refrigeration during transatlantic flight and packaging contributing to an anaerobic environment were felt to be contributing environmental factors in the Israeli cases. Rapid communication and full cooperation between Israeli and US health authorities limited the extent of the outbreak. Despite adequate understanding of how foodborne botulism may be avoided, outbreaks still occur, particularly among people consuming certain high-risk or ethnic foods.     

Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study.

OBJECTIVES: We investigated whether patients who suffered subacute stent thrombosis (SAT) have higher post-treatment reactivity than those who do not encounter stent thrombosis. BACKGROUND: High post-treatment platelet reactivity has been reported after coronary stenting after clopidogrel therapy and may be an important factor in the occurrence of SAT. METHODS: We identified patients with SAT treated at two tertiary care centers over a 1.5-year period. Light transmittance aggregation induced by adenosine diphosphate (ADP) and arachidonic acid, total and activated glycoprotein (GP) IIb/IIIa after stimulation with ADP, and vasodilator-stimulated phosphoprotein phosphorylation levels to measure P2Y12 receptor inhibition were determined (n = 20) and compared with an age-matched group of patients without SAT (n = 100). High post-treatment platelet reactivity was defined as >75th percentile ADP-induced aggregation in the group without SAT. RESULTS: The SAT patients had higher mean platelet reactivity than those without SAT by all measurements (p < 0.05): 49 +/- 4% versus 33 +/- 2% for 5 micromol/l ADP-induced aggregation and 65 +/- 3% versus 51 +/- 2% for 20 micromol/l ADP-induced aggregation (p < 0.001), 69 +/- 5% versus 46 +/- 9% for P2Y12 reactivity ratio (p = 0.03), and 138 +/- 19 mean fluorescence intensity (MFI) versus 42 +/- 4 MFI for stimulated GP IIb/IIIa expression (p < 0.001). Of patients with SAT, 60% had high platelet reactivity. CONCLUSIONS: High post-treatment platelet reactivity and incomplete P2Y12 receptor inhibition are risk factors for SAT. Measures to uniformly determine platelet reactivity after coronary stenting and treatment strategies to improve P2Y12 receptor inhibition in patients with high post-treatment platelet reactivity should be further investigated.     

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy

Pituitary - To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with...     

Implementation of functional imaging using 11C-methionine PET-CT co-registered with MRI for advanced surgical planning and decision making in prolactinoma surgery

Pituitary - To report the first experience of our multidisciplinary team with functional imaging using 11C-methionine positron emission tomography-computed tomography (11C-methionine PET-CT)...     

Oral surgery‐associated postoperative bleeding in haemophilia patients – a tertiary centre's two decade experience

Our goal in this research was to evaluate potential and targeted therapy, correlated with haemophilia severity and dental procedural risk, to reduce postoperative bleeding risk. Patients with haemophilia who were treated at the Oral and Maxillofacial Surgery Clinic at Sheba Medical Center between 1996 and 2012 comprised the study cohort. Data collected included disease history and severity, perioperative factor concentrate therapy, local haemostatic agent application, systemic tranexamic acid use and outcome. Bleeding was defined as excessive bleeding during or within 20 days following procedure. Dental procedures (n = 1968) of 125 patients were studied. Patients’ bleeding risk score was evaluated according to the severity of haemophilia with or without the presence of an inhibitor, presence of comorbid coagulopathy and the type of dental procedure. Thirty‐four patients undergoing a total of 880 high‐risk and 1088 low‐risk procedures suffered 40 postoperative bleeding events that necessitated further dental and/or haematological intervention. Among risk factors for delayed bleeding, the use of fibrin glue was significantly (P = 0.027) associated with the risk of postprocedural bleed probably as it was applied to high‐risk patients and procedures. Earlier treatment period (P = 0.055), postprocedure hospitalization (P = 0.039) and dental “high‐risk” procedures (P < 0.0001) also increased bleeding risk. Patients with haemophilia may be safely treated if meticulous haemostasis is applied, along with fibrin glue and systemic therapy as required. Factor transfusions are not mandatory and should be applied considering the procedure‐related risk and the patient's calculated haematological risk for bleeding.     

Rubber band ligation for 750 cases of symptomatic hemorrhoids out of 2200 cases

AIM： To study the results for the treatment of symptomatic hemorrhoids using rubber band ligation （RBL） method. METHODS： A retrospective study for 750 patients who came to the colorectal unit from June, 1998 to September, 2006, data was retrieved from archived files. RBL was performed using the Mc Gown applicator on an outpatient basis. The patients were asked to return to out-patient clinic for follow up at 2 wk, 1 mo, 6 mo and through telephone call every 6 mo for 2 years）. RESULTS： After RBL, 696 patients （92.8%） were cured with no difference in outcome for second or third degree hemorrhoids （P = 0.31）. Symptomatic recurrence was detected in 11.04% after 2 years. A total of 52 patients （6.93%） had 77 complications from RBL which required no hospitalization. Complications were pain, rectal bleeding and vaso-vagal symptoms（4.13%, 4.13% and 1.33% of patients, respectively）. At 1 mo there were a significant improvement in mean SF-36 scores over baseline in five items, while after 2 years there were improvement in all items over baseline, but not significant. No significant manometeric changes after band ligation. CONCLUSION： RBL is a simple, safe and effective method for treating symptomatic second and third degree hemorrhoids as an out patient procedure with significant improvement in quality of life. RBL doesn＇t alter ano-rectal functions.