Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups

Preliminary independent reports of the Italian GIMEMA and the Spanish PETHEMA trials for newly diagnosed acute promyelocytic leukemia (APL) indicated a similarly high antileukemic efficacy in terms of complete remission and disease-free survival rates. To better investigate these studies and the prognostic factors influencing relapse risk, this study analyzed the updated results of 217 patients with PML/RAR alpha-positive APL enrolled in GIMEMA (n = 108) and PETHEMA (n = 109). All patients received identical induction (AIDA schedule) and maintenance. For consolidation, GIMEMA patients received 3 courses including idarubicin/cytarabine, mitoxantrone/etoposide, and idarubicin/cytarabine/thioguanine, whereas PETHEMA patients received the same drugs and dose schedule of idarubicin and mitoxantrone with the omission of nonintercalating agents. Depending on whether molecular relapses were classified as censored or uncensored events, the 3-year Kaplan-Meier estimates of relapse-free survival (RFS) for the combined series were 90 +/- 2% and 86 +/- 2%, respectively. Minor differences observed between the 2 patient cohorts were negligible. Multivariate regression analysis of RFS showed that initial leukocyte (WBC) and platelet counts were the only variables with independent prognostic value. The resulting predictive model for RFS demonstrated its capability of segregating patients into low-risk (WBC count 40 x 10(9)/L), intermediate-risk (WBC count 10 x 10(9)/L) groups, with distinctive RFS curves (P <.0001). The conclusions are that omission of nonanthracycline drugs from the AIDA regimen is not associated with reduced antileukemic efficacy and a simple predictive model may be used for risk-adapted therapy in this disease. (Blood. 2000;96:1247-1253)     

The role of graft reperfusion sequence in the development of non-anastomotic biliary strictures following orthotopic liver transplantation: A meta-analysis

Background

Liver transplant is a potential cure for liver failure and hepatic malignancy but there are many techniques which have been described for vascular reconstruction. This study was to compare the prevalence of non-anastomotic biliary stricture and other surgical complications based on Clavien-Dindo scoring system, in initial portal reperfusion (sequential) versus simultaneous or initial artery reperfusion.

Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to transplantation

BACKGROUND AND OBJECTIVES: Arsenic trioxide (ATO) has been reported to be a safe and effective treatment for relapsed acute promyelocytic leukemia (APL). The aim of this study was to evaluate the efficacy and toxicity as well as the eligibility to stem cell transplantation (SCT) in a series of 7 patients with relapsing APL, managed with ATO. DESIGN AND METHODS: Seven patients with relapsing APL while on maintenance treatment with all-trans-retinoic acid (ATRA) or who were ATRA refractory-received ATO at a dose of 10 mg daily by 2-hour intravenous infusion until complete remission (CR). After consolidation chemotherapy, patients were programmed to receive autologous or allogeneic stem cell transplantation (SCT) according to donor availability. The median age of the patients was 55 (21-71) years: 2 patients presented with concomitant extramedullary relapse. RESULTS: Six patients (86%) achieved CR after a median of 35 ATO doses (20-49) with negligible toxicity; one patient died from pneumonia. After consolidation with a four-day course of cytarabine at 1 g/m2 and mitoxantrone 6 mg/m2, two patients underwent allogeneic SCT, two received PML/RARa negative autologous peripheral blood stem cells collected after consolidation plus granulocyte colony-stimulating factor, one failed mobilization and received a second consolidation course. One elderly patient refused further treatment and relapsed 6 months later. After a median follow-up of 15 months from CR2 achievement, 5 patients are alive in continuous CR. INTERPRETATION AND CONCLUSIONS: The high CR rate and the mild toxicity confirm that ATO represents a valid alternative to salvage chemotherapy for patients relapsing while on ATRA treatment or who are ATRA-refractory. Allogeneic or autologous SCT after ATO-induced CR is feasible in the majority of patients.     

Prophylaxis for venous thromboembolism after resection of hepatocellular carcinoma on cirrhosis: Is it necessary?

AIM: To assess the safety and effectiveness of prophylaxis for venous thromboembolism (VTE) in a large population of patients with hepatocellular carcinoma (HCC) on cirrhosis.METHODS: Two hundred and twenty nine consecutive cirrhotic patients with HCC who underwent hepatic resection were retrospectively evaluated to assess whether there was any difference in the incidence of thrombotic or hemorrhagic complications between those who received and those who did not receive prophylaxis with low-molecular weight...     

Platelet-Large Cell Ratio and the extent of coronary artery disease: results from a large prospective study

Even though platelet volume has been supposed to be indicator of platelet activation, contrasting results have been reported on its relationship with the extent of coronary artery disease (CAD). No data have been so far reported on Platelet-Large Cell Ratio (P-LCR). Thus, the aim of the current study was to investigate whether P-LCR is associated with CAD. We measured P-LCR in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least 1 coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. The relationship between P-LCR and platelet aggregation was evaluated by PFA-100 and Multiplate. Patients with higher P-LCR were older (P = 0.038), with larger prevalence of diabetes (P < 0.0001), dilated cardiomyopathy or valvular heart disease (P = 0.004) and less often family history of CAD (P = 0.045), more often on statins (P = 0.002), and diuretics (P = 0.016). P-LCR was significantly associated with baseline glycaemia (P = 0.001) and RBC count (P < 0.001), but inversely related to platelet count (P < 0.0001). P-LCR was not associated with the prevalence of CAD (adjusted P = 0.3) or its severity. In addition, P-LCR was not related to Carotid IMT or platelet aggregation in patients with or without aspirin therapy. This study showed that P-LCR is not related to platelet aggregation, aspirin resistance, the extent of CAD and carotid IMT. Thus, P-LCR can not be considered as a marker of platelet reactivity or a risk factor for CAD.     

Nasogastric or nasointestinal feeding in severe acute pancreatitis

AIM:To assess the rate of spontaneous tube migration and to compare the effects of naso-gastric and nasointestinal(NI)(beyond the ligament of Treitz) feeding in severe acute pancreatitis(SAP).METHODS:After bedside intragastric insertion,tube position was assessed,and enteral nutrition(EN) started at day 4,irrespective of tube localization.Patients were monitored daily and clinical and laboratory parameters evaluated to compare the outcome of patients with nasogastric(NG) or NI tube.RESULTS:Spontaneous tube ...     

Prevalence, incidence and types of mild anemia in the elderly: the ��Health and Anemia�� population-based study

Background

Hemoglobin concentrations slightly below the lower limit of normal are a common laboratory finding in the elderly, but scant evidence is available on the actual occurrence of mild anemia despite its potential effect on health. The objectives of this study were to estimate the prevalence and incidence of mild grade anemia and to assess the frequency of anemia types in the elderly.

Design and Methods

This was a prospective, population-based study in all residents 65 years or older in Biella, Italy.

Results

Blood test results were available for analysis from 8,744 elderly. Hemoglobin concentration decreased and mild anemia increased steadily with increasing age. Mild anemia (defined as a hemoglobin concentration of 10.0–11.9 g/dL in women and 10.0–12.9 g/dL in men) affected 11.8% of the elderly included in the analysis, while the estimated prevalence in the entire population was 11.1%. Before hemoglobin determination, most mildly anemic individuals perceived themselves as non-anemic. Chronic disease anemia, thalassemia trait, and renal insufficiency were the most frequent types of mild anemia. The underlying cause of mild anemia remained unexplained in 26.4% of the cases, almost one third of which might be accounted for by myelodysplastic syndromes. In a random sample of non-anemic elderly at baseline (n=529), after about 2 years, the annual incidence rate of mild anemia was 22.5 per 1000 person-years and increased with increasing age.

Conclusions

The prevalence and incidence of mild anemia increase with age and mild anemia affects more than one out of ten elderly individuals. Unexplained anemia is common and may be due to myelodysplastic syndromes in some cases.     

Spatio-temporal population structuring and genetic diversity retention in depleted Atlantic Bluefin tuna of the Mediterranean Sea

Fishery genetics have greatly changed our understanding of population dynamics and structuring in marine fish. In this study, we show that the Atlantic Bluefin tuna (ABFT, Thunnus thynnus), an oceanic predatory species exhibiting highly migratory behavior, large population size, and high potential for dispersal during early life stages, displays significant genetic differences over space and time, both at the fine and large scales of variation. We compared microsatellite variation of contemporary (n = 256) and historical (n = 99) biological samples of ABFTs of the central-western Mediterranean Sea, the latter dating back to the early 20th century. Measures of genetic differentiation and a general heterozygote deficit suggest that differences exist among population samples, both now and 96–80 years ago. Thus, ABFTs do not represent a single panmictic population in the Mediterranean Sea. Statistics designed to infer changes in population size, both from current and past genetic variation, suggest that some Mediterranean ABFT populations, although still not severely reduced in their genetic potential, might have suffered from demographic declines. The short-term estimates of effective population size are straddled on the minimum threshold (effective population size = 500) indicated to maintain genetic diversity and evolutionary potential across several generations in natural populations.     

Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa

Gut microbial composition depends on different dietary habits just as health depends on microbial metabolism, but the association of microbiota with different diets in human populations has not yet been shown. In this work, we compared the fecal microbiota of European children (EU) and that of children from a rural African village of Burkina Faso (BF), where the diet, high in fiber content, is similar to that of early human settlements at the time of the birth of agriculture. By using high-throughput 16S rDNA sequencing and biochemical analyses, we found significant differences in gut microbiota between the two groups. BF children showed a significant enrichment in Bacteroidetes and depletion in Firmicutes (P < 0.001), with a unique abundance of bacteria from the genus Prevotella and Xylanibacter, known to contain a set of bacterial genes for cellulose and xylan hydrolysis, completely lacking in the EU children. In addition, we found significantly more short-chain fatty acids (P < 0.001) in BF than in EU children. Also, Enterobacteriaceae (Shigella and Escherichia) were significantly underrepresented in BF than in EU children (P < 0.05). We hypothesize that gut microbiota coevolved with the polysaccharide-rich diet of BF individuals, allowing them to maximize energy intake from fibers while also protecting them from inflammations and noninfectious colonic diseases. This study investigates and compares human intestinal microbiota from children characterized by a modern western diet and a rural diet, indicating the importance of preserving this treasure of microbial diversity from ancient rural communities worldwide.