Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy

Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.     

Association of antibiotics with status epilepticus

The objective of this study is to evaluate clinical picture, radiological findings and response to treatment in patients with antibiotic associated status epilepticus (SE). In a retrospective review, 12 out of 117 (10%) patients with SE had temporal association with antibiotic administration. Their medical history, clinical findings, and duration and type of SE were recorded. Serum chemistry, blood counts, cranial MRI, EEG and CSF examination were carried out. The offending antibiotics were withdrawn and the patients were treated with phenytoin, lorazepam, sodium valproate or midazolam. The response to treatment was recorded and death during hospital stay noted. The median age of the patients was 36 (18 and 74) years and 5 were females. Eight patients had convulsive and four nonconvulsive SE. The median duration of status was 12 h. The antibiotics related to SE included intravenous cephalosporin (ceftazidime 5, amoxyclavulenic acid 2, piperacillin 2, cefepime 1) and quinolones (levofloxacin 3, ofloxacin 1, ciprofloxacin 2) in isolation or in combinations. Five patients had hepatic (41.7%) and 6 (50%) renal failure; the later received higher than the recommended dose of antibiotics. Cranial MRI was abnormal in 7 out of 9 (77.8%) patients that include cortical lesion in one, corticosubcortical in three and subcortical in three. SE responded to first antiepileptic drug in four and to second in five patients. Three patients (25%) had refractory SE. Eight (66.7%) patients died and death was related to SE in 2 patients. 10% SE patients may be related to antibiotics. Hence the antibiotic should be carefully chosen in patients with hepatic and renal failure, and the dose should be modified.     

Utility of Sonoclot analysis and tranexamic acid in tetralogy of Fallot patients undergoing intracardiac repair

Sonoclot analysis is a point of care test to monitor the coagulation process, presenting a comprehensive evaluation of the clot formation and retraction as well as platelet function. This randomized double-blinded study was designed to investigate the utility of Sonoclot analysis in monitoring the coagulation profile as also the antifibrinolytic effects of tranexamic acid administered in patients with tetralogy of Fallot undergoing intracardiac repair. Eighty of a total 94 patients were randomly divided into two groups of 40 each. In the study group, TA was administered thrice at a dosage of 10 mg/kg, i.e. before CPB, on CPB and after CPB, whereas in the control group, placebo was administered at the same time intervals. Sonoclot analysis and D-dimer measurement were performed at baseline and following heparin neutralisation. An additional variable, DR?? (diminishing rate of clot strength at 15 min postmaximal clot strength), was calculated from the Sonoclot graph and was compared with d-dimer levels as a measure of fibrinolysis. The three Sonoclot variables, i.e. activated clotting time, clot rate and platelet function, were deranged at baseline in all the patients. Post-CPB, the change in these variables was not significant. ACT, clot rate and platelet function showed no significant (P > 0.05) difference in both the groups at both the time intervals. DR?? and d-dimer values were comparable at baseline in both the groups. However, a significant (P < 0.05) difference was seen in these variables in the control group as compared with the TA group following heparin neutralisation. To conclude, Sonoclot analysis is a useful, point of care method for the monitoring of coagulation and fibrinolysis in patients with tetralogy of Fallot undergoing intracardiac repair.     

QRS characteristics fail to reliably identify ventricular tachycardias that require epicardial ablation in ischemic heart disease

Criteria for Epicardial Origin in Ischemic VT. Objectives: We tested proposed algorithms for idiopathic and nonischemic tachycardias for their ability to identify epicardial LV‐VT origins. Backgroud: Several ECG features have been reported to identify epicardial origins for left ventricular tachycardias (LV‐VTs) in the absence of myocardial infarction. Only limited data exist in postinfarction patients. Methods: The QRS features of 24 VTs that were ablated from the epicardium and 39 left ventricular VTs ablated from the endocardium were retrospectively analyzed for various 12‐lead ECG features previously reported. Results: No ECG feature consistently predicted an epicardial LV‐VT origin in infarct‐related tachycardias, with epicardial VTs showing slightly longer QRS durations (189 ± 32 ms in epicardial vs 179 ± 37 ms in endocardial, P = 0.28). Pseudo‐delta duration was 38 ± 27 versus 47 ± 27 ms (P = 0.2), intrinsicoid deflection time 93 ± 35 versus 86 ± 32 ms (P = 0.4), shortest RS 97 ± 38 versus 99 ± 32 ms (P = 0.77), and median deflection index 0.82 ± 0.25 versus 0.87 ± 0.22 (P = 0.43). The finding of a Q wave in lead I and the absence of a Q wave in the inferior leads failed to predict an epicardial origin in superior LV‐VT sites. Q waves in any inferior lead and aVR/aVL‐ratio<1 were not specific for an epicardial origin in inferior sites (all P = ns). Furthermore, all inferior LV‐VTs showed a Q wave in the inferior leads which correlated with pre‐existing Q‐waves in sinus rhythm (P = 0.045). Conclusion : Proposed 12‐lead ECG features for differentiation of epicardial versus endocardial sites for nonischemic LV‐VTs do not reliably identify VTs that require ablation from the epicardium. Endocardial mapping should be the first approach to catheter ablation for VTs in patients with ischemic heart disease. (J Cardiovasc Electrophysiol, Vol. 23, pp. 188‐193, February 2012)     

Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women

Postmenopausal women with elevated serum sex steroids have an increased risk of breast cancer. Most of this risk is believed to be exerted through binding of the sex steroids to their receptors. For the first time, we investigate the association of estrogen receptor (ER) and androgen receptor (AR) serum bioactivity (SB) in addition to hormone levels in samples from women with breast cancer collected before diagnosis. Two hundred postmenopausal women participating in the UK Collaborative Trial of Ovarian Cancer Screening who developed ER-positive breast cancer 0.6-5 years after sample donation were identified and matched to 400 controls. ER and AR bioassays were used to measure ERα, ERβ, and AR SB. Androgen and estrogen levels were measured with immunoassays. Subjects were classified according to quintiles of the respective marker among controls and the associations between SB and hormones with breast cancer risk were determined by logistic regression analysis. ERα and ERβ SB were significantly higher before diagnosis compared with controls, while estrogens showed no difference. Women had a twofold increased breast cancer risk if ERα SB (odds ratio (OR), 2.114; 95% confidence interval (CI), 1.050-4.425; P=0.040) was in the top quintile >2 years before diagnosis or estrone (OR, 2.205; 95% CI, 1.104-4.586; P=0.029) was in the top quintile <2 years before diagnosis. AR showed no significant association with breast cancer while androstenedione (OR, 3.187; 95% CI, 1.738-6.044; P=0.0003) and testosterone (OR, 2.145; 95% CI, 1.256-3.712; P=0.006) were significantly higher compared with controls and showed a strong association with an almost threefold increased breast cancer risk independent of time to diagnosis. This study provides further evidence on the association of androgens and estrogens with breast cancer. In addition, it reports that high ER but not AR SB is associated with increased breast risk >2 years before diagnosis.     

The Personal Patient Profile-Prostate decision support for men with localized prostate cancer: A multi-center randomized trial

ObjectiveThe purpose of this trial was to compare usual patient education plus the Internet-based Personal Patient Profile-Prostate, vs. usual education alone, on conflict associated with decision making, plus explore time-to-treatment, and treatment choice.MethodsA randomized, multi-center clinical trial was conducted with measures at baseline, 1-, and 6 months. Men with newly diagnosed localized prostate cancer (CaP) who sought consultation at urology, radiation oncology, or multi-disciplinary clinics in 4 geographically-distinct American cities were recruited. Intervention group participants used the Personal Patient Profile-Prostate, a decision support system comprised of customized text and video coaching regarding potential outcomes, influential factors, and communication with care providers. The primary outcome, patient-reported decisional conflict, was evaluated over time using generalized estimating equations to fit generalized linear models. Additional outcomes, time-to-treatment, treatment choice, and program acceptability/usefulness, were explored.ResultsA total of 494 eligible men were randomized (266 intervention; 228 control). The intervention reduced adjusted decisional conflict over time compared with the control group, for the uncertainty score (estimate ?3.61; (confidence interval, ?7.01, 0.22), and values clarity (estimate ?3.57; confidence interval (?5.85,?1.30). Borderline effect was seen for the total decisional conflict score (estimate ?1.75; confidence interval (?3.61,0.11). Time-to-treatment was comparable between groups, while undecided men in the intervention group chose brachytherapy more often than in the control group. Acceptability and usefulness were highly rated.ConclusionThe Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized CaP. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a CaP treatment that is consistent with the patient values and preferences.     

Echocardiographic Assessment of Right Atrial Pressure in a Pediatric and Young Adult Population

Right atrial pressure (RAP) reflects right-sided cardiac hemodynamics and is useful in management of patients with cardiac and systemic disease. Studies in older adults demonstrated that inferior vena cava (IVC) diameter, IVC collapsibility index, hepatic vein systolic filling fraction (SFF), and right atrial volume (RAV) correlated with mean RAP at catheterization. This study aimed to assess the utility of echocardiographic parameters for assessment of RAP in children and young adults. Patients with pulmonary hypertension or heart transplantation undergoing right heart catheterization were recruited for this prospective observational pilot study. Transthoracic echocardiographic assessment of RAP was performed simultaneously with catheterization. For each parameter, three consecutive cardiac cycles were recorded. Long- and short-axis images of the IVC were obtained. RAV was assessed by area–length and biplane methods. IVC diameters and RAV were indexed to body surface area (BSA)^0.5 and (BSA)^1.4, respectively. Relationships between echocardiographic parameters and mean RAP were correlated using “Pearson’s r.” Fifty subjects aged 0.3–23 years (median 13, mean 12.3 ± 7 years) were enrolled. Mean RAP correlated modestly with RAV (r = 0.51, p < 0.001). Long-axis IVC_max (r = 0.30, p < 0.05) and tricuspid E wave velocity (r = 0.36, p < 0.01) also correlated with mean RAP. RV free wall tissue Doppler velocities, IVC collapsibility index, and hepatic vein SFF had no relation to mean RAP. In a pediatric and young adult population with pulmonary hypertension or heart transplantation, echocardiographic assessment of RAV and long-axis IVC_max provided a reasonable estimate of mean RAP. IVC collapsibility index and hepatic vein SFF demonstrated no association with mean RAP.     

Routine Postoperative Monitoring after Bariatric Surgery in Morbidly Obese Patients with Severe Obstructive Sleep Apnea: ICU Admission is not Necessary

Background and Study Aim

Obstructive sleep apnea (OSA) occurs in 70–80 % of bariatric surgery patients. Patients with severe OSA (apnea/hypopnea index (AHI) >30/h) are postoperatively admitted to an intensive care unit (ICU) for continuous monitoring, to prevent complications. The aim of this study was to assess the necessity of routine postoperative monitoring at an ICU of severe OSA patients after bariatric surgery, attempting to prevent and detect cardiorespiratory complications.

Methods

Patients undergoing bariatric surgery from November 2010 to July 2013 were entered into a database. Minimal follow-up was 1 month. Poly(somno)graphy (P(S)G) was routinely performed. Patients with severe OSA were admitted to the ICU for the first postoperative night. Oxygen saturation was continuously measured. The database was reviewed regarding patient characteristics, CPAP use, re-intubations, desaturations (saturation <90 % and severe <85 %), and complications.

Results

Severe OSA was present in 151 of the 794 patients, and all 151 were admitted to the ICU. Thirty who underwent revisional surgery were excluded. Forty-seven percent was male, median age was 51 years (27.0–68.0), and median body mass index (BMI) was 46.6 (kg/m²) (34.0–77.6). No deaths, re-intubations, or cardiopulmonary complications occurred. Eighty-two (67.8 %) patients used continuous positive airway pressure (CPAP). Twenty-one (17.4 %) patients experienced desaturations with a median of 2.0 (1–8). Six patients (5.0 %) had one episode of severe desaturation.

Conclusion

Patients with severe OSA and adequate CPAP use are at low risk of cardiopulmonary complications after (laparoscopic) bariatric surgery. Routine admission to an ICU might be superfluous. However, continuous digital oximetry remains essential.

     

Role of HLA B27 in diagnosis of seronegative spondyloarthropathies

Seronegative Spondyloarthropathies (SSA) is a very common problem in our area. The main aim of present study was (1) to find the HLA B27 positivity in patients presenting with sacroileitis (2) to see the correlation of B27 positivity on haematological, radiological and extra articular manifestations. Total 110 patients of SSA were studied between July 2004 to June 2005. Routine haematological and immunological test were done by standard method. Total positivity of B27 in SSA was 43.63%, HLA B27 positivity was higher in children (68.75%). Sex wise analysis of B27 positive cases showed that 81.81% B27 positive patients were males. In HLA B27 positive cases lower spine, hip, sacroiliac, shoulder and knee joints were more involved (77.08%, 79.16%, 79.16%, 37.50% and 50.00% respectively). Urinary tract infection (UTI), diarrhoea and constipation were more common in B27 positive cases. Leukocytosis of neutrophilic type (33.33%), raised ESR (77.55%)., CRP positivity (63.63%) and anaemia (65.00%) were seen more frequently in B27 positive cases. In bilateral sacroiliitis diagnosed by X-ray, only 69.23% patient were B27 positive. Our study concludes that HLA B 27 positivity is higher in SSA seen in childhood and in young adult males. B27 positive patients have more severe disease and systemic manifestation Hence, male patients specially young adolescent or young adults with sacroileitis must be subjected for B27 typing.