De novo acute myeloid leukemia with multilineage dysplasia: treatment results and prognostic evaluation from a series of 44 patients treated with fludarabine,cytarabine and G-CSF (FLAG)

OBJECTIVES: To evaluate therapeutic results and prognostic factors from a series of 44 patients affected by de novo acute myeloid leukemia with multilineage dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G-CSF (FLAG). METHODS: Forty-four patients with de novo MD-AML were treated with the FLAG regimen. The median age was 61 yr (range 31-75 yr). Induction therapy consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine. Patients with a compatible donor and aged less than 55 yr were programmed to receive allogeneic bone marrow transplantation (BMT), while in those without a donor and aged less than 65 yr autologous transplantation with peripheral blood stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone marrow harvest was performed in poor mobilizers. RESULTS: Complete remission (CR) was achieved in 28 out of 44 patients (64%). Death in induction occurred in four patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of consolidation was negligible. Most patients aged less than 60 yr and achieving CR were eligible for transplantation procedures, the main reason of exclusion being early relapse. Median overall survival and disease free survival were 16 and 22 months, respectively. Unfavorable cytogenetics was the only parameter significantly related to inferior clinical outcome following multivariate analysis. CONCLUSION: Multilineage dysplasia per se is not an adverse prognostic factor in AML patients treated with the FLAG regimen. Favorable results are obtained in patients with intermediate karyotype, while in those with adverse cytogenetics new approaches are clearly needed. The toxicity of the regimen is also acceptable in the elderly, and following induction/consolidation, most patients may be submitted to transplantation procedures.     

ECMO criteria for influenza A (H1N1)-associated ARDS: role of transpulmonary pressure

Purpose

To assess whether partitioning the elastance of the respiratory system (E _RS) between lung (E _L) and chest wall (E _CW) elastance in order to target values of end-inspiratory transpulmonary pressure (PPLAT_L) close to its upper physiological limit (25?cmH₂O) may optimize oxygenation allowing conventional treatment in patients with influenza A (H1N1)-associated ARDS referred for extracorporeal membrane oxygenation (ECMO).

Methods

Prospective data collection of patients with influenza A (H1N1)-associated ARDS referred for ECMO (October 2009?CJanuary 2010). Esophageal pressure was used to (a) partition respiratory mechanics between lung and chest wall, (b) titrate positive end-expiratory pressure (PEEP) to target the upper physiological limit of PPLAT_L (25?cmH₂O).

Results

Fourteen patients were referred for ECMO. In seven patients PPLAT_L was 27.2?±?1.2?cmH₂O; all these patients underwent ECMO. In the other seven patients, PPLAT_L was 16.6?±?2.9?cmH₂O. Raising PEEP (from 17.9?±?1.2 to 22.3?±?1.4?cmH₂O, P?=?0.0001) to approach the upper physiological limit of transpulmonary pressure (PPLAT_L?=?25.3?±?1.7?cm H₂O) improved oxygenation index (from 37.4?±?3.7 to 16.5?±?1.4, P?=?0.0001) allowing patients to be treated with conventional ventilation.

Conclusions

Abnormalities of chest wall mechanics may be present in some patients with influenza A (H1N1)-associated ARDS. These abnormalities may not be inferred from measurements of end-inspiratory plateau pressure of the respiratory system (PPLAT_RS). In these patients, titrating PEEP to PPLAT_RS may overestimate the incidence of hypoxemia refractory to conventional ventilation leading to inappropriate use of ECMO.     

Selection of patient for cardiac resynchronization therapy: role of QT corrected dispersion

Aims : About 30 to 50% of patients undergoing cardiac resynchronization therapy (CRT) may not show clinical or echocardiographic improvement, despite fulfilling guidelines recommendations for CRT. For this reason, we need a more accurate method to assess CRT eligibility. The aims of this study were to verify, on a 12‐month follow‐up, the usefulness of QT corrected dispersion (QTcD) in a patient's selection for CRT. Methods : We stratified 53 patients who underwent CRT, into two groups based on the estimation of QTcD, that is, QTcD > 60 ms and QTcD ≤ 60 ms. In all patients were performed New York Heart Association (NYHA) class determination, six‐minute walking test, QtcD, and QRS measurements, and complete echocardiographic assessment at 1, 3, 6, and 12 months after implantation. Results : At baseline, there were no significant differences in clinical, echocardiographic, and electrocardiographic parameters duration between two groups. At 12‐month follow‐up between the two groups, there were significant differences in NYHA (1.2 ± 0.4 vs 2 ± 0.6; P < 0.01), six‐minute walking distance (422 ± 68 vs 364 ± 68; P < 0.01), left ventricular (LV) ejection fraction (34 ± 7% vs 28 ± 6%; P < 0.01), LV end‐diastolic diameter (57 ± 7 vs 63 ± 8; P < 0.01), and LV intraventricular dyssynchrony (24 ± 14 vs 39 ± 23; P < 0.01). Conclusion: This study suggests that QTc dispersion in addition to QRS duration could improve the sensitivity of electrocardiogram in a patient's selection for CRT. (PACE 2012;1–6)     

Morphological and functional evaluation of the bioresorption of the bioresorbable everolimus-eluting vascular scaffold using IVUS, echogenicity and vasomotion testing at two year follow-up: a patient level insight into the ABSORB A clinical trial

The aim of this study was to describe vaso-reactivity (by Acetylcholine and Methergine tests) at 2 year follow-up in parallel with the individual changes in the echogenicity characteristics of the polymer struts of the everolimus eluting bioresorbable vascular scaffold (BVS), from post-treatment to 2 year follow-up, in patients enrolled in the ABSORB Cohort A study. Intravascular ultrasound assessment was performed with a phased array catheter (EagleEye, Volcano Corporation, Cordova, CA, USA) with automated pullback at 0.5 mm per second. The % ratio at 6 months and 2 years [(Scaffold Area post PCI- Lumen Area)/Scaffold Area post PCI] was calculated as a measure of scaffold shrinkage. The % change of hyperechogenicity was defined as: ([post-procedural hyperechogenicity] - [2 year follow up hyperechogenicity])/[post-procedural hyperechogenicity]) × 100. The vasomotion test with intracoronary acetylcholine (10(-6) M) or intravenous methergine (0.4 mg) was performed at 2 years. Overall nine patients received all these analyses and were enrolled in the present analysis. A 50-96% reduction in hyperechogenicity was observed between baseline and 2 years, which corresponded to a change in vasoreactivity between 2 and 22%. A vasoconstriction of the scaffolded segment was observed in the 5 patients, who underwent the methergine test, with a mean decrease in lumen diameter after methergine of 9 ± 7% (P = 0.06), while vasodilatation occurred in the 4 patients who underwent the acetylcholine test with a mean increase in lumen diameter after acetylcholine of 8 ± 5% (P = 0.125). Bioresorption of the BVS is accompanied by re-establishment of both endothelial and non-endothelial dependent vasomotion.     

Long-term clinical outcomes following sirolimus-eluting stent implantation in patients with acute myocardial infarction. A meta-analysis of randomized trials

Objectives

The aim of this study was to perform a meta-analysis of randomized trials, evaluating the long-term outcomes of sirolimus-eluting stents (SES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).

Background

Despite short-term outcomes of patients with STEMI undergoing primary percutaneous coronary intervention indicate a benefit of SES in terms of reintervention, several concerns remain on the long-term safety and efficacy of SES.

Methods

A systematic literature search of electronic resources, through October 2011, was performed using specific search terms. Included trials were randomized studies comparing SES to BMS in STEMI patients, with a follow-up ≥3?years.

Results

Seven trials were included, with a total of 2,364 patients. At a median follow-up of 3?years, SES significantly reduced the risk of target-vessel revascularization when compared with BMS [odds ratio (OR), 0.44; 95?% confidence interval (CI), 0.34–0.57; p?<?0.0001], without increasing the risk of mortality (OR 0.78; 95?% CI, 0.57–1.08; p?=?0.14), reinfarction (OR 0.91; 95?% CI, 0.61–1.35, p?=?0.64) and early to late stent thrombosis (OR 0.77; 95?% CI, 0.49–1.20; p?=?0.25). However after the first year, SES did not further reduce target-vessel revascularization (OR 1.06; 95?% CI, 0.64–1.74; p?=?0.83) and increased the risk of very late stent thrombosis (OR 2.81; 95?% CI, 1.33–5.92; p?=?0.007).

Conclusions

At long-term follow-up, SES compared to BMS use in STEMI patients reduces the risk of target-vessel revascularization, without increasing the risk of death and reinfarction. However, the strong SES efficacy is counterbalanced by a significant risk of very late stent thrombosis.     

Fibrinogen as a predictor of mortality after acute myocardial infarction: a forty-two-month follow-up study.

BACKGROUND: Several studies suggest that fibrinogen may be considered an independent risk factor for coronary artery disease, but it is still on debate if we need its evaluation during an acute myocardial infarction (AMI) to prevent future fatal or non-fatal cardiovascular events. Therefore, we decided to investigate this field. METHODS: We studied 92 male patients with AMI, evaluating at admission age, body mass index, systolic blood pressure, cigarette smoking, ejection fraction, plasma levels of total cholesterol, triglycerides, fibrinogen, glycemia, and white blood cell count. All patients were followed up for 42 months to evaluate total mortality and cardiovascular morbidity. RESULTS: During the follow-up 5 patients died and 64 had one or more non-fatal cardiovascular events: angina (n = 78), heart failure (n = 17), re-AMI (n = 3), stroke (n = 3), or revascularization procedure (n = 16). A multivariate analysis revealed that fibrinogen plasma levels at admission (r = +0.213, p < 0.05) were independently associated with mortality, while systemic thrombolysis was negatively associated (r = -0.447, p < 0.0001). CONCLUSIONS: Plasma fibrinogen levels were the only independent predictor of mortality in a 42-month follow-up post-AMI. This finding, together with other observations from recent studies, suggest that fibrinogen evaluation during AMI may be useful in identifying patients at higher risk of acute event recurrence.     

Pediatric onset Crohn's colitis is characterized by genotype-dependent age-related susceptibility

BACKGROUND: Pediatric onset Crohn's disease (CD) is associated with more colitis and less ileitis compared with adult onset CD. Differences in disease site by age may suggest a different genotype, or different host responses such as decreased ileal susceptibility or increased susceptibility of the colon. METHODS: We evaluated 721 pediatric onset CD patients from 3 cohorts with a high allele frequency of NOD2/CARD15 mutations. Children with isolated upper intestinal disease were excluded. The remaining 678 patients were evaluated for interactions between age of onset, NOD2/CARD15, and disease location. RESULTS: We found an age-related tendency for isolated colitis. Among pediatric onset patients without NOD2/CARD15 mutations, colitis without ileal involvement was significantly more common in first-decade onset patients (P = 4.57 x 10(-5), odds ratio [OR] 2.76, 95% confidence interval [CI] 1.72-4.43). This was not true for colonic disease with ileal involvement (P = 0.35), or for isolated colitis in patients with NOD2/CARD15 mutations (P = 0.61). Analysis of 229 patients with ileal or ileocolonic disease and a NOD2/CARD15 mutation disclosed that ileocolitis was more prevalent through age 10, while isolated ileitis was more prevalent above age 10 (P = 0.016). NOD2/CARD15 mutations were not associated with age of onset. CONCLUSIONS: In early-onset pediatric CD, children with NOD2/CARD15 mutations demonstrate more ileocolitis and less isolated ileitis. Young children without NOD2/CARD15 mutations have an isolated colonic disease distribution, suggesting that this phenotype is associated with genes that lead to a specific phenotype of early-onset disease.     

Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study

BACKGROUND AND AIM: Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up. METHODS: Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG. RESULTS: During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 +/- 30.14 min at baseline and 92.10 +/- 24.52 min at the end of follow-up) and without AN (135.14 +/- 17.09 min and 92.68 +/- 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho - 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values. CONCLUSIONS: Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control.     

Modern imaging of Crohn's disease using bowel ultrasound

Technological advancement of ultrasound (US) equipments and understanding of bowel appearances with high resolution US during the last decade has led to consideration of this imaging procedure as an important tool for inflammatory bowel diseases assessment. In particular, Crohn's disease (CD) for its pathologic characteristics (that is, inflammatory infiltration of the entire bowel wall with possible extension to the surrounding mesentery) is the disease entity which has mainly taken advantage from this non-invasive, radiation-free technique. Beside correctly defining anatomic location and extension of CD lesions within the bowel in the majority of cases, US also shows perigut abnormalities and may demonstrate complications such as fistulas and abscesses. With the help of Power Doppler function, some additional information may be obtained about the local activity of the disease which is particularly useful in the presence of strictures. New US technologies (such as those using intravenous bolus contrast agents or oral nonabsorbable anechoic solutions) may further improve diagnostic capability of US in this context, thus probably revolutioning the diagnostic approach to this disease in the near future, particularly during follow-up in CD of the small bowel.