Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

Atrial arrhythmia burden on long-term monitoring in asymptomatic patients late after atrial fibrillation ablation

Patients appearing free of atrial fibrillation (AF) based on limited electrocardiographic monitoring/clinical history late after ablation may still have a large silent AF burden and thus have failed ablations and may be at risk of thromboembolism. We evaluated long-term monitoring (LTM; 7 days or 1 year) in 203 patients off antiarrhythmic drugs who were clinically free of AF >1 year after ablation. A 7-day monitor was done in 186 and 17 had pacemakers in whom the most recent year was analyzed. Arrhythmia recurrence was >30 seconds of AF, flutter, or tachycardia. LTM was done 3.1 ± 1.3 years (range 1.1 to 7.3) after the last ablation. AF recurred in only 8 of 186 (4.3%) on 7-day monitoring. One had persistent AF. For the other 7, AF burden was 0.0075% to 3.34% with 3 of 7 having an AF burden ≤0.037%. AF recurred in 4 of 17 patients (23.5%) with pacemakers. The 4 patients with pacemakers and AF had a 1-year AF burden of 0.0037% to 0.16%. Given the longer duration of monitoring, pacemakers detected more AF than 7-day monitors (p <0.011). AF duration before ablation was the only predictor of AF recurrence on LTM (p = 0.01). In patients with symptomatic AF who appeared free of AF on clinical grounds an average of 3 years after ablation, AF burden on LTM was low. In conclusion, monitoring by implanted devices detects more AF than 7-day monitors, most patients exceeding the failure definition of >30 seconds have a small AF burden, and when using LTM for follow-up the definition of "ablation failure" may be better described by an AF burden >0.5% rather than a single 30-second arrhythmia recurrence.     

Geographic variation in the relationship between human Lyme disease incidence and density of infected host-seeking Ixodes scapularis nymphs in the Eastern United States

Prevention and control of Lyme disease is difficult because of the complex biology of the pathogen's (Borrelia burgdorferi) vector (Ixodes scapularis) and multiple reservoir hosts with varying degrees of competence. Cost-effective implementation of tick- and host-targeted control methods requires an understanding of the relationship between pathogen prevalence in nymphs, nymph abundance, and incidence of human cases of Lyme disease. We quantified the relationship between estimated acarological risk and human incidence using county-level human case data and nymphal prevalence data from field-derived estimates in 36 eastern states. The estimated density of infected nymphs (mDIN) was significantly correlated with human incidence (r = 0.69). The relationship was strongest in high-prevalence areas, but it varied by region and state, partly because of the distribution of B. burgdorferi genotypes. More information is needed in several high-prevalence states before DIN can be used for cost-effectiveness analyses.     

Parkinson’s disease: considerations for dental hygienists

Abstract: The prevalence of Parkinson’s disease (PD) is expected to double over the next 20 years owing to the increase in life expectancy. This progressive disease has several implications relating to oral health, and many are manageable with proper awareness and knowledge about the disease. This article reviews the epidemiology, pathophysiology, and characteristics of PD, as well as the treatments and oral health considerations to enable dental hygienists to undertake an informed approach to patient management strategies and provide optimal care.     

A Prospective Randomized Study Comparing Patients with Morbid Obesity Submitted to Sleeve Gastrectomy With or Without Omentectomy

Background

Increased visceral adipose tissue is a risk factor for the metabolic complications associated with obesity and promotes a low-grade chronic inflammatory process. Resection of the great omentum in patients submitted to a bariatric procedure has been proposed for the amelioration of metabolic alterations and the maximization of weight loss. The aim of the present study was to investigate the impact of omentectomy performed in patients with morbid obesity undergoing sleeve gastrectomy (SG) on metabolic profile, adipokine secretion, inflammatory status, and weight loss.

Methods

Thirty-one obese patients were randomized into two groups: SG alone or with omentectomy. Adiponectin, omentin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), blood lipids, fasting glucose, insulin, and insulin resistance were measured before surgery and at 7 days, and 1, 3 and 12 months after surgery.

Results

During the 1-year follow-up, body mass index (BMI) decreased markedly and comparably in both groups (p?<?0.001). Insulin, IL-6, and hs-CRP levels decreased significantly compared to baseline (p?<?0.05) in both groups with no significant difference between groups. Adiponectin and high-density lipoprotein cholesterol levels were significantly and similarly increased compared to baseline (p?<?0.001) in both groups. Omentin levels increased significantly (p?<?0.05) in the control group and decreased in the omentectomy group 1 year postoperatively. There was no significant change in TNF-α levels in either group.

Conclusions

The theoretical advantages of omentectomy in regard to weight loss and obesity-related abnormalities are not confirmed in this prospective study. Furthermore, omentectomy does not induce important changes in the inflammatory status in patients undergoing SG.