Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL

We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10(-3) or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n = 43) over the MRD-based risk groups differed significantly from that of precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk group compared to only 11% of patients with precursor B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points.     

Management of 350 aneurysmal subarachnoid hemorrhages in 22 Italian neurosurgical centers

OBJECTIVE: To collect information on clinical practice and current management strategies in 22 Italian neurosurgical hospitals for patients with aneurysmal subarachnoid hemorrhage. DESIGN AND SETTING: Observational 6-month study for prospective data collection. PATIENTS: 350 cases of aneurysmal subarachnoid hemorrhage. MEASUREMENTS AND RESULTS: Each center enrolled from 4-36 patients. Neurological deterioration (24%) was more frequent in patients with higher Fisher classification, and with pretreatment rebleeding and it was associated with an unfavorable outcome (46%, 36/78, vs. 33%, 83/251). Aneurysms were mainly secured by clipping (55%, 191/350). An endovascular approach was utilized in 35% (121/350). The more frequent medical complications were fever, recorded in one-half of cases, pneumonia (18%), sodium disturbances (hyponatremia 22%, hypernatremia 17%), cardiopulmonary events as neurogenic pulmonary edema (4%) and myocardial ischemia (5%). Intracranial hypertension was experienced in one-third of the patients, followed by hydrocephalus (29%) and vasospasm (30%). Cerebral ischemia was found in an about one-quarter of the cohort. To identify the independent predictors of outcome we developed a model in which the dichotomized Glasgow Outcome Scale was tested as function of extracranial and intracranial complications. Only high intracranial pressure and deterioration in neurological status were independent factors related to unfavorable outcome. CONCLUSIONS: Our data confirm that in every step of care there is extreme heterogeneity among centers. These patients are complex, with comorbidities, immediate risk of rebleeding, and delayed risk of intracranial and medical complications. Following SAH early treatment and careful intensive care management requires the careful coordination of the various clinical specialties.     

Atrial tachyarrhythmia recurrence temporal patterns in bradycardia patients implanted with antitachycardia pacemakers

INTRODUCTION: New-generation pacemakers allow continuous atrial tachyarrhythmia (AT) monitoring that provides accurate information about AT type, frequency, burden, and temporary evolution. METHODS AND RESULTS: We performed a prospective multicenter study to describe AT temporal patterns in patients with sinus bradycardia and AT. Two hundred forty patients (123 men; age 71 +/- 8 years) were implanted with a DDDRP pacemaker (model AT500, Medtronic Inc.). All patients were followed for 13 months. The first-month stabilization period of all patients was discarded from analysis. Seventy percent of patients had AT recurrences. Mean time to first AT recurrence (48.2 days, 95% confidence interval [CI] 37.0-59.5 days) was significantly longer than the time between first and second AT episode (10.3 days, 95% CI 6.7-13.9 days, P < 0.01). A minority of patients had a uniform time distribution of AT recurrences: <25% of patients had AT episodes in more than 6 of the 12 months considered in the study. The probability density function of consecutive sinus rhythm days between AT episodes was calculated for each of 40 patients who experienced >25 AT episodes and fitted by power law and exponential functions. The best fit was obtained by power law function in 60% of patients, by exponential function in 10%, and the two models gave comparable results in 30% of patients. CONCLUSION: In our population of patients with a history of sinus bradycardia and AT who were implanted with a new device equipped with atrial pacing therapies, 30% did not experience AT recurrences in the 12-month study period. Analysis of interevent time showed that in 60% of patients AT recurrences do not follow a uniform or random distribution. These findings bring into question the use of cross-over design and time to first AT recurrence as a clinical outcome in trials for AT therapy in this patient population.     

Results of “elephant trunk” total aortic arch replacement using a multi-branched,collared graft prosthesis

We report on our experience with a simplified elephant trunk (ET) procedure with a multi-branched prosthesis (Vascutek^® Siena? Collared Graft). It consists of a proximal portion (20 cm) with prefabricated side branches, a collar and a distal portion (30 cm). The collar, which can be trimmed into any desired diameter, constitutes the suture portion to the descending aorta. Radiopaque markers in the distal portion indicate the landing zone. Between January 2011 and June 2013, 20 consecutive patients (10 women; mean age, 66 ± 9.3 years) underwent ET procedure, including 6 re-do cases. Underlying aortic diseases were acute dissection (n = 6), chronic dissection (n = 4), aneurysm (n = 8) and PAU (n = 2). Mean preoperative diameter of the descending aorta was 49.1 ± 12.9 mm (range 74.7–29.7 mm). Concomitant procedures included ascending aortic replacement in 16 patients; root replacement in 2; AVR in 2, CABG in 3 and mitral repair in 1 patient. CPB time was 263 ± 94 min; mean duration of ACP was 65 ± 14 min. Two patients died on POD 8 and 78, respectively. Major adverse events included stroke (n = 1), resternotomy for bleeding (n = 2), renal failure requiring temporary dialysis (n = 1) and recurrent nerve paresis (n = 2). After a mean follow-up of 10 ± 8 months, all discharged patients were alive. Seven patients underwent stent-graft implantation of the descending aorta and one patient underwent open descending aortic replacement. The last generation of multi-branched arch prosthesis and especially the Vascutek^® Siena? Collared Graft make ET procedure a reasonable treatment option even in patients with acute aortic dissection.     

Effects of nifedipine GITS and diuretics in isolated systolic hypertension--a subanalysis of the INSIGHT study

Aims: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study. Major findings: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups. Mean BP fell by 29/10 mmHg in the nifedipine and 30/10 mmHg in the diuretic group to a mean BP of 144/78 mmHg and 143/79 mmHg, respectively, at endpoint. The percentage of primary outcomes in patients with ISH was not significantly different between the two treatment groups (nifedipine GITS 6.0%, co-amilozide 6.6%). The number of ISH patients with composite secondary outcomes was 90 (12.2%) in the nifedipine GITS group and 110 (14.5%) in the co-amilozide group (not significant). The incidence rates of primary and secondary outcomes were similar in patients without ISH. Conclusion: In patients with ISH, nifedipine GITS and co-amilozide had similar effects on clinical outcomes and BP lowering. They lend support to international guidelines for the treatment of hypertension recommending the use of long-acting dihydropyridine calcium-channel blockers as one treatment option for patients with ISH.     

MTHFR (methylenetetrahydrofolate reductase: EC 1.5.1.20) SNPs (single-nucleotide polymorphisms) and homocysteine in patients referred for investigation of fertility

Journal of Assisted Reproduction and Genetics - MTHFR, one of the major enzymes in the folate cycle, is known to acquire single-nucleotide polymorphisms that significantly reduce its activity,...     

European consensus table 2006 on botulinum toxin for children with cerebral palsy

An interdisciplinary group of experienced botulinum toxin users and experts in the field of movement disorders was assembled, to develop a consensus on best practice for the treatment of cerebral palsy using a problem-orientated approach to integrate theories and methods. The authors tabulated the supporting evidence to produce a condensed but comprehensive information base, pooling data and experience from nine European countries, 13 institutions and more than 5500 patients. The consensus table summarises the current understanding regarding botulinum toxin treatment options in children with CP.     

Modulation of H reflexes in human tibialis anterior muscle with passive movement

Significant movement-induced gain changes in H reflexes have been observed in soleus muscle following passive movement of the lower limb. Hypotheses from these concepts were tested on magnitudes of H reflexes in tonically contracted tibialis anterior. From eleven subjects at rates of 20 and 60 r.p.m. passive leg movement, statistically significant attenuation from controls and phasic modulation occurred. The results make more general the conclusions from soleus H reflexes. However, the functional effect should be much smaller, as tibialis anterior H reflexes are smaller compared to those in soleus.