Intensive chemotherapy,azacitidine, or supportive care in older acute myeloid leukemia patients: An analysis from a regional healthcare network

We assessed in a French regional healthcare network the distribution of treatments, prognostic factors, and outcome of 334 newly diagnosed acute myeloid leukemia patients aged 60 years or older over a 4‐year period of time (2007–2010). Patients were selected in daily practice for intensive chemotherapy (n = 115), azacitidine (n = 95), or best supportive care (n = 124). In these three groups, median overall survival was 18.9, 11.3, and 1.8 months, respectively. In the azacitidine group, multivariate analysis showed that overall survival was negatively impacted by higher age (P = 0.010 for one unit increase), unfavorable cytogenetics (P = 0.001), lymphocyte count <0.5 G/L (P = 0.015), and higher lactate dehydrogenase level (P = 0.005 for one unit increase). We compared the survival of patients treated by azacitidine versus intensive chemotherapy and best supportive care using time‐dependent analysis and propensity score matching. Patients treated by intensive chemotherapy had a better overall survival compared with those treated by azacitidine from 6 months after diagnosis, whereas patients treated by azacitidine had a better overall survival compared with those treated by best supportive care from 1 day after diagnosis. This study of “real life” practice shows that there is a room for low intensive therapies such as azacitidine in selected elderly acute myeloid leukemia patients. Am. J. Hematol. 89:E244–E252, 2014. © 2014 Wiley Periodicals, Inc.     

Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy

Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our center, we identified 32 patients (9.3%) with fever, very high ferritin levels, and marrow hemophagocytosis (i.e. patients with hemophagocytic lymphohistiocytosis). Compared to patients without hemophagocytic lymphohistiocytosis, these 32 patients had hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia. A microbial etiology for the hemophagocytosis was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. The treatment of hemophagocytic lymphohistiocytosis consisted of corticosteroids and/or intravenous immunoglobulins along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, which was significantly shorter than that of patients without hemophagocytic lymphohistiocytosis (22.1 months) (P=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failure, mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of patients with acute myeloid leukemia undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of the diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in patients with acute myeloid leukemia.     

Acquisition and consolidation of sequential footstep movements with physical and motor imagery practice

Sleep-dependent performance enhancement has been consistently reported after explicit sequential finger learning, even using motor imagery practice (MIP), but whether similar sleep benefits occur after explicit sequential gross motor learning with the lower limbs has been addressed less often. Here, we investigated both acquisition and consolidation processes in an innovative sequential footstep task performed either physically or mentally. Forty-eight healthy young participants were tested before and after physical practice (PP) or MIP on the footstep task, following either a night of sleep (PPsleep and MIPsleep groups) or an equivalent daytime period (PPday and MIPday groups). Results showed that all groups improved motor performance following the acquisition session, albeit the magnitude of enhancement in the MIP groups remained lower relative to the PP groups. Importantly, only the MIPsleep group further improved performance after a night of sleep, while the other groups stabilized their performance after consolidation. Together, these findings demonstrate a sleep-dependent gain in performance after MIP in a sequential motor task with the lower limbs but not after PP. Overall, the present study is of particular importance in the context of motor learning and functional rehabilitation.     

Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs

Growing evidence supports a link between inflammation and cancer; however, mediators of the transition between inflammation and carcinogenesis remain incompletely understood. Sphingosine-1-phosphate (S1P) lyase (SPL) irreversibly degrades the bioactive sphingolipid S1P and is highly expressed in enterocytes but downregulated in colon cancer. Here, we investigated the role of SPL in colitis-associated cancer (CAC). We generated mice with intestinal epithelium-specific Sgpl1 deletion and chemically induced colitis and tumor formation in these animals. Compared with control animals, mice lacking intestinal SPL exhibited greater disease activity, colon shortening, cytokine levels, S1P accumulation, tumors, STAT3 activation, STAT3-activated microRNAs (miRNAs), and suppression of miR-targeted anti-oncogene products. This phenotype was attenuated by STAT3 inhibition. In fibroblasts, silencing SPL promoted tumorigenic transformation through a pathway involving extracellular transport of S1P through S1P transporter spinster homolog 2 (SPNS2), S1P receptor activation, JAK2/STAT3-dependent miR-181b-1 induction, and silencing of miR-181b-1 target cylindromatosis (CYLD). Colon biopsies from patients with inflammatory bowel disease revealed enhanced S1P and STAT3 signaling. In mice with chemical-induced CAC, oral administration of plant-type sphingolipids called sphingadienes increased colonic SPL levels and reduced S1P levels, STAT3 signaling, cytokine levels, and tumorigenesis, indicating that SPL prevents transformation and carcinogenesis. Together, our results suggest that dietary sphingolipids can augment or prevent colon cancer, depending upon whether they are metabolized to S1P or promote S1P metabolism through the actions of SPL.     

Évaluation endoscopique des patients atteints de maladie coeliaque

Celiac disease is an autoimmune disorder of the small bowel triggered by the exposure to gliadine, a storage protein of wheat and similar grains, occurring in genetically predisposed patients. The diagnosis of celiac disease typically requires the presence of both anti-tissue transglutaminase antibodies in the serum and specific histological features on small bowel mucosal biopsies, such as villous atrophy. The goals of the endoscopist in the management of patients with known or suspected celiac disease is to obtain contributive histological samples, knowing that mucosal lesions may be patchy among the small bowel, and to diagnose potential complications, such as ulcerative jejunitis, refractory sprue, or enteropathy-associated T lymphoma. We reviewed the respective contribution of the various endoscopic diagnostic tools in the management of patients with celiac disease.     

Characteristics and prognosis of sudden cardiac death in Greater Paris

Purpose

Sudden cardiac death (SCD) is a major public health concern, but data regarding epidemiology of this disease in Western European countries are outdated. This study reports the first results from a large registry of SCD.

Methods

A population-based registry was established in May 2011 using multiple sources to collect every case of SCD in Paris and its suburbs, covering a population of 6.6 million. Utstein variables were recorded. Pre-hospital and in-hospital data were considered, and the main outcome was survival at hospital discharge. Neurologic status at discharge was established as well.

Results

Of the 6,165 cases of SCD recorded over 2 years, 3,816 had a resuscitation attempt and represent the study population. Most patients were male (69 %), the SCD occurred at home (72 %) with bystanders in 80 % of cases, and cardiopulmonary resuscitation (CPR) was performed in 45 % of cases. Initial rhythm was shockable in 26 % of cases. A total of 1,332 patients (35 %) were admitted alive to hospital. Among hospitalized patients, 58 % had a coronary angiogram, and the same proportion had therapeutic hypothermia. Finally, 279 patients (7.5 %) were discharged alive, of whom 96 % had a favorable neurological outcome. In multivariate analysis, bystander CPR (OR 2.1, 95 % CI 1.5–3.1) and initial shockable rhythm (OR 11.5, 95 % CI 7.6–17.3) were positively associated with survival at hospital discharge, whereas age (OR 0.97 per year, 95 % CI 0.96–0.98), longer response time (OR 0.93 per minute, 95 % CI 0.89–0.97), occurrence at home (OR 0.4, 95 % CI 0.3–0.6), and epinephrine dose greater than 3 mg (OR 0.05, 95 % CI 0.03–0.08) were inversely associated with survival.

Conclusion

Despite being conducted in the therapeutic hypothermia and early coronary angiogram era, hospital discharge survival rate of resuscitated SCD remains poor. The current registry suggests ways to improve pre-hospital and in-hospital care of these patients.     

Frey Procedure in Patients with Chronic Pancreatitis: Short and Long-term Outcome from a Prospective Study

Background

The aim of this prospective study was to determine the short- and long-term results of the Frey procedure in the treatment of chronic pancreatitis.

Methods

From September 2000 to November 2009, 44 consecutive patients underwent the Frey procedure. Patients were included in the study before surgery and followed prospectively with assessment of pain relief, weight gain and exocrine/endocrine insufficiency. Twenty-one patients (47.7?%) were followed for more than 5?years.

Results

This study included 40 men (91?%) and four women (9?%) (mean age: 49?years) with a mean follow-up of 51.5?months. The primary etiology of chronic pancreatitis was chronic alcohol abuse in 38 patients (86.4?%). The major indication for surgery was disabling pain (95.5?%). There was no postoperative mortality. Postoperative morbidity occurred in 15 patients (34.1?%), with specific surgical complications in 11 patients (25?%). The percentage of pain-free patients after surgery was 68.3?%. Eight patients (18.1?%) and seven patients (16?%) developed diabetes de novo and exocrine insufficiency, respectively. The Body Mass Index showed statistically significant improvement during follow-up. Similar beneficial results concerning pain relief and weight gain persisted after the initial 5-year follow-up.

Conclusions

The Frey procedure is an appropriate, safe and effective technique for management of patients with chronic pancreatitis in the absence of neoplasia, based on long-term follow-up.