A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction.

Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative disorders. We have developed a real-time polymerase chain reaction assay for the detection and quantification of MPL mutations that is based on locked nucleic acid fluorescent probes. Mutational analysis was performed using DNA from granulocytes. Reference curves were obtained using cloned fragments of MPL containing either the wild-type or mutated sequence; the predicted sensitivity level was at least 0.1% mutant allele in a wild-type background. None of the 60 control subjects presented with a MPLW515L/K mutation. Of 217 patients with myelofibrosis, 19 (8.7%) harbored the MPLW515 mutation, 10 (52.6%) with the W515L allele. In one case, both the W515L and W515K alleles were detected by real-time polymerase chain reaction. By comparing results obtained with conventional sequencing, no erroneous genotype attribution using real-time polymerase chain reaction was found, whereas one patient considered wild type according to sequence analysis actually harbored a low W515L allele burden. This is a simple, sensitive, and cost-effective procedure for large-scale screening of the MPLW515L/K mutation in patients suspected to have a myeloproliferative disorder. It can also provide a quantitative estimate of mutant allele burden that might be useful for both patient prognosis and monitoring response to therapy

Fluctuations in warfarin dose response after heart valve surgery: implications for cardiac rehabilitation

In patients undergoing heart valve surgery (HVS) who require warfarin therapy, the maintenance of low variability in the level of anticoagulation early after operation is generally difficult. Aim of this study was to evaluate the time in therapeutic range (TTR) in HVS patients receiving oral anticoagulation therapy (OAT) during phase I-II of cardiac rehabilitation (CR), and, secondly, to identify clinical variables associated with inadequate anticoagulation. Methods: Observational study of consecutive in-hospital patients directly tracked from a cardiac surgery unit to a CR facility. OAT was monitored both in terms of administered warfarin doses and resulted INR values, from day 1 to day 15 after operation. Clinical variables were tested in a logistic regression model for the prediction of inadequate anticoagulation, defined as the presence of nontherapeutic INRs for ≥5 days between day 8 and 15. Results: Eighty-one patients (males 56%, age 62±19 yrs.), following valvuloplasty (37%), mechanical (17%), and bioprosthetic (45%) valve replacement were considered. The prescribed warfarin dosages were significantly higher from day 1 to day 7 than from day 8 to day 15 (4.6±3.6 and 3.0±1.1 mg respectively, p< 0.001). Overall, TTR was 6±3 days, while time with elevated and lower INRs accounted for 1.3±1.6 and 8.0±3.5 days respectively. At day 7, only 25% of patients (n= 20) showed a therapeutic INR value. Inadequate anticoagulation between postoperative day 8 and 15 was displayed in 41 (51%) patients, with hypertension as the only independent predictor (p< 0.001) at multivariate analysis. Conclusions: Despite intensive monitoring, half of patients have nontherapeutic INR values (mainly subtherapeutic) in the first two weeks after HVS while on warfarin. Giving the high risk of completing the hospitalization phase without a stable OAT in many patients, both cardiac surgeons and cardiologists should not miss the opportunity to improve patients education, and consider a direct track to anticoagulation management services after discharge

Primary Prophylaxis of Invasive Fungal Diseases in Allogeneic Stem Cell Transplantation: Revised Recommendations from a Consensus Process by Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Abstract This document updates and expands the recommendations on primary prophylaxis of invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe and evaluate current information and practice regarding risk stratification and primary antifungal prophylaxis during the pre-engraftment and postengraftment phases after allo-HSCT. The revised recommendations were based on the evaluation of recent literature including a large, prospective, multicenter epidemiological study of allo-HSCT recipients conducted among the GITMO transplantation centers during the period of 2008 to 2010. It is intended as a guide for the identification of types and phases of transplantation at low, standard, and high risk for IFD, according to the underlying disease, transplantation, and post-transplantation factors. The risk stratification was the critical determinant of the primary antifungal approach for allo-HSCT recipients

Direct Aortic CoreValve Implantation via Right Anterior Thoracotomy in a Patient with Patent Bilateral Mammary Artery Grafts and Aortic Arch Chronic Dissection

Direct aortic trans-catheter aortic valve implantation is an alternative approach to treat high risk for surgery patients affected by severe aortic stenosis and concomitant peripheral vascular disease. We describe a case of direct aortic CoreValve implantation made via a right anterior thoracotomy in a 78-year-old male affected by severe aortic stenosis and severe peripheral vasculopathy, who previously underwent coronary artery bypass grafting, with patent bilateral mammary artery grafts and chronic aortic arch dissection

Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation : the COPPS-2 randomized clinical trial

IMPORTANCE: Postpericardiotomy syndrome, postoperative atrial fibrillation (AF), and postoperative effusions may be responsible for increased morbidity and health care costs after cardiac surgery. Postoperative use of colchicine prevented these complications in a single trial. OBJECTIVE: To determine the efficacy and safety of perioperative use of oral colchicine in reducing postpericardiotomy syndrome, postoperative AF, and postoperative pericardial or pleural effusions. DESIGN, SETTING, AND PARTICIPANTS: Investigator-initiated, double-blind, placebo-controlled, randomized clinical trial among 360 consecutive candidates for cardiac surgery enrolled in 11 Italian centers between March 2012 and March 2014. At enrollment, mean age of the trial participants was 67.5 years (SD, 10.6 years), 69% were men, and 36% had planned valvular surgery. Main exclusion criteria were absence of sinus rhythm at enrollment, cardiac transplantation, and contraindications to colchicine. INTERVENTIONS: Patients were randomized to receive placebo (n=180) or colchicine (0.5 mg twice daily in patients 6570 kg or 0.5 mg once daily in patients <70 kg; n=180) starting between 48 and 72 hours before surgery and continued for 1 month after surgery. MAIN OUTCOMES AND MEASURES: Occurrence of postpericardiotomy syndrome within 3 months; main secondary study end points were postoperative AF and pericardial or pleural effusion. RESULTS: The primary end point of postpericardiotomy syndrome occurred in 35 patients (19.4%) assigned to colchicine and in 53 (29.4%) assigned to placebo (absolute difference, 10.0%; 95% CI, 1.1%-18.7%; number needed to treat\u2009=\u200910). There were no significant differences between the colchicine and placebo groups for the secondary end points of postoperative AF (colchicine, 61 patients [33.9%]; placebo, 75 patients [41.7%]; absolute difference, 7.8%; 95% CI, -2.2% to 17.6%) or postoperative pericardial/pleural effusion (colchicine, 103 patients [57.2%]; placebo, 106 patients [58.9%]; absolute difference, 1.7%; 95% CI, -8.5% to 11.7%), although there was a reduction in postoperative AF in the prespecified on-treatment analysis (placebo, 61/148 patients [41.2%]; colchicine, 38/141 patients [27.0%]; absolute difference, 14.2%; 95% CI, 3.3%-24.7%). Adverse events occurred in 21 patients (11.7%) in the placebo group vs 36 (20.0%) in the colchicine group (absolute difference, 8.3%; 95% CI; 0.76%-15.9%; number needed to harm\u2009=\u200912), but discontinuation rates were similar. No serious adverse events were observed. CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, perioperative use of colchicine compared with placebo reduced the incidence of postpericardiotomy syndrome but not of postoperative AF or postoperative pericardial/pleural effusion. The increased risk of gastrointestinal adverse effects reduced the potential benefits of colchicine in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT0155218

The usefulness of speckle tracking echocardiography in identifying subclinical myocardial dysfunction in young adults recovered from mild COVID-19

Background Myocardial strain assessed with speckle tracking echocardiography is a sensitive marker of cardiac dysfunction. Both left-ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were affected by severe SARS-CoV-2 infection. However, data about cardiac involvement in patients with asymptomatic/mild Coronavirus disease-19 (COVID-19) is still lacking. Aim To evaluate myocardial function using LV-GLS and RV-LS in patients with previous asymptomatic/mild COVID-19. Methods Forty young adults without previously known comorbidities/cardiovascular risk factors and with a confirmed diagnosis of asymptomatic or paucisymptomatic SARS-CoV-2 infection were retrospectively included. A 2D-transthoracic echocardiogram with speckle tracking analysis was performed at least 3 months after the diagnosis. Forty healthy subjects, matched for age, sex, and body surface area in a 1:1 ratio were used as the control group. Results Left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and RV-LS were comparable between the two groups. LV-GLS was significantly lower in the cases compared to the control group (-22.7 +/- 1.6% vs. -25.7 +/- 2.3%; p &lt; .001). Moreover, the prevalence of regional peak systolic strain below -16% in at least two segments was three times higher in patients with previous COVID-19 compared to controls (30% vs. 10%, p = .02). In multivariable logistic regression, previous COVID-19 infection was independently associated with reduced LV-GLS values (p &lt; .001). Conclusion SARS-CoV-2 infection may affect left ventricular deformation in 30% of young adult patients despite an asymptomatic or only mildly symptomatic acute illness. Speckle-tracking echocardiography could help early identification of patients with subclinical cardiac involvement, with potential repercussions on risk stratification and management