Improvement In Hemoglobin Levels Research Articles

Activation of the mTOR pathway by the amino acid l-leucine in the 5q- syndrome and other ribosomopathies

Patients with the 5q- syndrome and Diamond-Blackfan anemia (DBA) suffer from a severe macrocytic anemia. The 5q- syndrome and DBA are disorders of aberrant ribosome biogenesis (ribosomopathies) and haploinsufficiency of the ribosomal protein genes RPS14 and RPS19, respectively, underlies the anemia found in these disorders. Erythroblasts obtained from patients with the 5q- syndrome and DBA show impaired mRNA translation and this defect in translation may represent a potential therapeutic target in these ribosomopathies. There are some indications that the amino acid l-leucine, a translation enhancer, may have some efficacy in this group of disorders. Recent studies have shown that l-leucine treatment of zebrafish and murine models of the 5q- syndrome and DBA results in a marked improvement in the anemia. l-leucine treatment of RPS14-deficient and RPS19-deficient erythroblasts and erythroblasts from patients with the 5q- syndrome has been shown to result in an increase in cell proliferation, erythroid differentiation and mRNA translation in culture. l-leucine has been shown to improve hemoglobin levels and transfusion independence in a patient with DBA. l-leucine activates the mTOR (mammalian target of rapamycin) signaling pathway that controls cell growth and mRNA translation. There is evidence to suggest that the promotion of translation via the mTOR pathway by l-leucine is the mechanism that underlies the enhanced erythroid progenitor cell growth and differentiation observed in animal and cellular models of the 5q- syndrome and DBA treated with this amino acid. These data support the rationale for clinical trials of l-leucine as a therapeutic agent for the 5q- syndrome and DBA.

Oxidative damage and genotoxicity biomarkers in transfused and untransfused thalassemic subjects

Chronic anemia and tissue hypoxia increase intestinal iron absorption and mitochondrial impairment in thalassemic patients. Regular blood transfusions improve hemoglobin levels but determine an iron overload that induces reactive oxygen species (ROS) overproduction. The aim of this study was to assess cellular oxidative damage by detection of ROS, lipid peroxidation, 8-oxo-dG, and mitochondrial transmembrane potential (Δψm) in transfused and untransfused thalassemic patients. We have also evaluated genotoxicity by CBMN and comet assay. Our data show that ROS and lipid hydroperoxides are significantly higher in thalassemic patients than in controls, especially in untransfused thalassemia intermedia patients. Moreover, the latter have a significant decrease in Δψm that highlights the energetic failure in hypoxic state and the ROS overproduction in the respiratory chain. 8-OHdG levels are higher in thalassemics than in controls, but do not differ significantly between the two patient groups. Both genotoxicity biomarkers highlight the mutagenic potential of hydroxyl radicals released by iron in the Fenton reaction. Values for percentage of DNA in the comet tail and micronuclei frequency, significantly higher in transfused patients, could also be due to active hepatitis C virus infection and to the many drug treatments. Our biomonitoring study confirms the oxidative damage in patients with thalassemia major and shows an unexpected cellular oxidative damage in untransfused thalassemic patients. In addition to iron overload, the results highlight the important role played by hypoxia-driven mitochondrial ROS overproduction in determining oxidative damage in β-thalassemias.

Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia

BackgroundSevere aplastic anemia, which is characterized by immune-mediated bone marrow hypoplasia and pancytopenia, can be treated effectively with immunosuppressive therapy or allogeneic transplantation. One third of patients have disease that is refractory to immunosuppression, with persistent, severe cytopenia and a profound deficit in hematopoietic stem cells and progenitor cells. Thrombopoietin may increase the number of hematopoietic stem cells and progenitor cells.MethodsWe conducted a phase 2 study involving patients with aplastic anemia that was refractory to immunosuppression to determine whether the oral thrombopoietin mimetic eltrombopag (Promacta) can improve blood counts. Twenty-five patients received eltrombopag at a dose of 50 mg, which could be increased, as needed, to a maximum dose of 150 mg daily, for a total of 12 weeks. Primary end points were clinically significant changes in blood counts or transfusion independence. Patients with a response continued to receive eltrombopag.ResultsEleven of 25 patients (44%) had a hematologic response in at least one lineage at 12 weeks, with minimal toxic effects. Nine patients no longer needed platelet transfusions (median increase in platelet count, 44,000 per cubic millimeter). Six patients had improved hemoglobin levels (median increase, 4.4 g per deciliter); 3 of them were previously dependent on red-cell transfusions and no longer needed transfusions. Nine patients had increased neutrophil counts (median increase, 1350 per cubic millimeter). Serial bone marrow biopsies showed normalization of trilineage hematopoiesis in patients who had a response, without increased fibrosis. Monitoring of immune function revealed no consistent changes.ConclusionsTreatment with eltrombopag was associated with multilineage clinical responses in some patients with refractory severe aplastic anemia. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00922883.)

Vitamin A and Carotenoids During Pregnancy and Maternal, Neonatal and Infant Health Outcomes: a Systematic Review and Meta‐Analysis

Vitamin A (VA) deficiency during pregnancy is common in low-income countries and a growing number of intervention trials have examined the effects of supplementation during pregnancy on maternal, perinatal and infant health outcomes. We systematically reviewed the literature to identify trials isolating the effects of VA or carotenoid supplementation during pregnancy on maternal, fetal, neonatal and early infant health outcomes. Meta-analysis was used to pool effect estimates for outcomes with more than one comparable study. We used GRADE criteria to assess the quality of individual studies and the level of evidence available for each outcome. We identified 23 eligible trials of which 17 had suitable quality for inclusion in meta-analyses. VA or beta-carotene (βC) supplementation during pregnancy did not have a significant overall effect on birthweight indicators, preterm birth, stillbirth, miscarriage or fetal loss. Among HIV-positive women, supplementation was protective against low birthweight (<2.5 kg) [risk ratio (RR) = 0.79 [95% confidence interval (CI) 0.64, 0.99]], but no significant effects on preterm delivery or small-for-gestational age were observed. Pooled analysis of the results of three large randomised trials found no effects of VA supplementation on neonatal/infant mortality, or pregnancy-related maternal mortality (random-effects RR = 0.86 [0.60, 1.24]) although high heterogeneity was observed in the maternal mortality estimate (I(2) = 74%, P = 0.02). VA supplementation during pregnancy was found to improve haemoglobin levels and reduce anaemia risk (<11.0 g/dL) during pregnancy (random-effects RR = 0.81 [0.69, 0.94]), also with high heterogeneity (I(2) = 52%, P = 0.04). We found no effect of VA/βC supplementation on mother-to-child HIV transmission in pooled analysis, although some evidence suggests that it may increase transmission. There is little consistent evidence of benefit of maternal supplementation with VA or βC during pregnancy on maternal or infant mortality. While there may be beneficial effects for certain outcomes, there may also be potential for harm through increased HIV transmission in some populations.

A Hospital Policy Change Toward Delayed Cord Clamping is Effective in Improving Hemoglobin Levels and Anemia Status of 8-month-old Peruvian Infants

To assess the effectiveness of a hospital policy change toward delayed cord clamping on infant hemoglobin (Hb) levels and anemia status at 4 and 8 months of age. A cohort of Peruvian mothers and infants, originating from a pre/post study investigating a change in hospital policy from early to delayed cord clamping, was followed until 8 months postpartum. Infant hemoglobin levels and anemia status were measured at 4 and 8 months postpartum. Following the hospital policy change, adjusted mean infant Hb levels improved by 0.89 gdl(-1) [95% confidence interval (95% CI) 0.57-1.22] and anemia was significantly reduced (aOR = 0.38; 95% CI 0.19-0.78) at 8 months postpartum. A hospital policy change toward delayed cord clamping is effective in improving Hb levels and the anemia status of 8-month-old infants. Prior to scaling-up this intervention, issues related to training, monitoring, safety, additional long-term benefits and specific local conditions should be investigated.

A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis

To evaluate the clinical efficacy of silymarin in ulcerative colitis (UC) patients. A randomized double blinded placebo-controlled clinical trial was conducted in 80 UC patients whose disease had been documented and were in remission state between September 2009 and October 2010. Patients were assigned to silymarin group (42 cases) and placebo group (38 cases) using a random number table. Either silymarin (140 mg) or placebo (lactose mono-hydrate, corn starch magnesium stearate) tablets were given once daily for 6 months along with their standard therapy. The efficacies were assessed by disease activity index (DAI), frequency difference of the disease flare-up, and paraclinical data. Ten patients (4 in the silymarin group due to nausea and 6 in the placebo group due to disease flare-up and abdominal pain) discontinued the study. An improvement in hemoglobin level (11.8±1.6 g/dL vs. 13.4±1.2 g/dL,P<0.05) and erythrocyte sedimentation rate (23.7±11.5 mm/h vs.10.8±3.2 mm/h,P<0.05) was observed in the silymarin group but not in the placebo group. DAI significantly decreased in the silymarin group and reached from 11.3±3.5 to 10.7±2.8 (P<0.05). Thirty-five out of 38 patients in the silymarin group were in complete remission with no flare-up after 6 months as compared to 21 out of 32 patients in the placebo group (P=0.5000). Silymarin as a natural supplement may be used in UC patients to maintain remission.

Anemia in heart failure patients.

Heart failure is a very common disease, with severe morbidity and mortality, and a frequent reason of hospitalization. Anemia and a concurrent renal impairment are two major risk factors contributing to the severity of the outcome and consist of the cardio renal anemia syndrome. Anemia in heart failure is complex and multifactorial. Hemodilution, absolute or functional iron deficiency, activation of the inflammatory cascade, and impaired erythropoietin production and activity are some pathophysiological mechanisms involved in anemia of the heart failure. Furthermore other concomitant causes of anemia, such as myelodysplastic syndrome and chemotherapy, may worsen the outcome. Based on the pathophysiology of cardiac anemia, there are several therapeutic options that may improve hemoglobin levels, tissues' oxygenation, and probably the outcome. These include administration of iron, erythropoiesis-stimulating agents, and blood transfusions but still the evidence provided for their use remains limited.

Pump blood processing, salvage and re-transfusion improves hemoglobin levels after coronary artery bypass grafting, but affects coagulative and fibrinolytic systems

Cell saving systems are commonly used during cardiac operations to improve hemoglobin levels and to reduce blood product requirements. We analyzed the effects of residual pump blood salvage through a cell saver on coagulation and fibrinolysis activation and on postoperative hemoglobin levels. Thirty-four elective coronary artery bypass graft (CABG) patients were randomized. In 17 patients, residual cardiopulmonary bypass (CPB) circuit blood was transfused after the cell saving procedure (cell salvage group). In the other 17 patients, residual CPB circuit blood was discarded (control group). Activation of the coagulative, fibrinolytic and inflammatory systems was evaluated pre-operatively (Pre), 2 hours after the termination of CPB (T0) and 24 hours postoperatively (T1), measuring prothrombin fragment 1.2 (PF 1.2), plasmin-anti-plasmin (PAP), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). The cell salvage group of patients had a significant improvement in hemoglobin levels after processed blood infusion (2.7 ± 1.7 g/dL vs 1.2 ± 1.1 g/dL; p=0.003). PF1.2 levels were significantly higher after infusion (T0: 1175 ± 770 pmol/L vs 730 ± 237 pmol/L; p=0.037; T1: 331 ± 235 pmol/L vs 174 ± 134 pmol/L; p=0.026). Also, PAP levels were higher in the cell salvage group, although not significantly (T0: 253 ± 251 ng/mL vs 168 ± 96 ng/mL; p: NS; T1: 95 ± 60 ng/mL vs 53 ± 32 ng/mL; p: NS). No differences were found for PAI-1, IL-6, heparin levels or for red blood cell (RBC) transfusions. The cell salvage group of patients had increased chest tube drainage (749 ± 320 vs 592 ± 264; p: NS) and fresh frozen plasma transfusion rate (5 (29%) pts vs 0 pts; p<0.04). Pump blood salvage with a cell saving system improved postoperative hemoglobin levels, but induced a strong thrombin generation, fibrinolysis activation and lower fibrinolysis inhibition. These conditions could generate a consumption coagulopathy.

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG

Testosterone levels decrease with age. This decline is steeper during “critical illnesses”. Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as “acute postoperative frailty”. We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels.

Iron therapy in patients with chronic kidney disease

SUMMARYIron deficiency, both functional and absolute, is common in patients with chronic kidney disease and in those requiring dialysis. The Renal National Service Framework and National Institute for Health and Clinical Excellence advocate treatment of anemia in patients with chronic kidney disease. Oral iron is often both insufficient and slow to improve hemoglobin levels while intravenous supplementation replenishes and maintains iron stores more effectively. This leads to a reduction in the use of erythropoietin stimulating agents. This reduction in erythropoietin stimulating agents use may be potentially beneficial in certain cases in particularly reducing stroke risk. In contrast, intravenous iron has the potential to improve quality of life, reduce cardiovascular risk and produce cost savings. However, long‐term clinical data are needed to reassure one of the effectiveness of parenteral iron therapy and exclude potential long‐term cellular and systemic adverse effects.

An evidence-based review of the potential benefits of taliglucerase alfa in the treatment of patients with Gaucher disease

Gaucher disease is an inherited lysosomal storage disorder, characterized by deficient activity of glucocerebrosidase leading to storage of glucocerebroside in tissue macrophages. Type I disease, the most prevalent form, lacks central nervous system involvement but presents primarily with variable degrees of hepatosplenomegaly, cytopenia, and bone disease. Intravenous enzyme replacement therapy can reverse these manifestations. In addition to the two enzymes currently authorized for use, the newest enzyme, taliglucerase alfa, is at the late stages of clinical development. Taliglucerase alfa is a unique product, as it is the first plant cell–based recombinant enzyme therapy. This review considers the existing evidence for therapeutic efficacy of taliglucerase alfa in the treatment of the non-neuronopathic manifestations of Gaucher disease. Clinical studies encompass one phase I trial in healthy volunteers, one phase III trial, and preliminary results from both an extension study and a switch study. In the 9-month, randomized, double-blind phase III trial, treatment-naïve patients with type I Gaucher disease were treated with either 30 or 60 U/kg every 2 weeks. Dose-dependent improvements were achieved after 6 and 9 months of therapy, with reductions in spleen and liver volumes and improvements in hemoglobin levels. Platelet counts improved initially only in the higher-dose group, but preliminary results from the extension study also show significant increases in the lower-dose group. Bone marrow involvement, as assessed by magnetic resonance imaging, improved in almost all patients. Taliglucerase alfa has shown a good safety profile, with few patients experiencing hypersensitivity reactions and developing antibodies. An additional enzyme replacement therapy for Gaucher disease would enable the treatment of more patients and would provide backup for unexpected production problems. Furthermore, it is expected that this new treatment would reduce the costs of therapy. Taliglucerase alfa is a valuable new treatment modality for the non-neuronopathic manifestations of Gaucher disease.

Chemotherapy Plus Hematopoietic Growth Factor for Refractory Paroxysmal Nocturnal Hemoglobinuria: Diminishing PNH Clone and Stimulating Hematopoisis

Abstract 4376 BACKGROUNDEven complement inhibitor against C5 Eculizumab has been used in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) acting as a “dam” protecting PNH clone and storing higher risk of hemolysis. So we carried out a study to investigate the efficacy and safety of chemotherapy plus growth factors, a traditional treatment for malignant hematological diseases, aiming at diminishing PNH clone and stimulating hematopoisis, in patients with refractory and relapsed PNH. METHODS10 patients were enrolled in this study. These patients were admitted into General Hospital affiliated to Tianjin Medical University(TMU) between 2006 to 2010, receiving either DAG (DNR 40mg/d, d1–2; 20mg/d, d3; Ara-C 100mg/d, d1-5; G-CSF until WBC return normal) or HAG (HHT 2–3mg/d, d1-5; Ara-C 100mg/d, d1-5; G-CSF until WBC return normal) regimen chemotherapy intravenously every 4 weeks for several cycles. The primary end points were the improvement of hemoglobin levels, decreased proportion of PNH clone and dosage of corticosteroid. Biochemical indicators of intravascular haemolysis and adverse events were also assessed. RESULTSAll patients responded well. Overall improvement for anemia was achieved, transfusion independence(HB can keep more than 6g/L without transfusion) was achieved in 4 patients, hemoglobin levels reached normal gradually in 1 of them, 2 patients got prolonged transfusion interval, another 4 patients did not need transfusion all the time. Elevation of hemoglobin from (58.1±12.12) g/L to (90.20±21.55) g/L (P=0.000) was achieved for the 10 patients. The dosage of corticosteroid decreased significantly from (45.84±19.05)mg to (13.00±6.75)mg (P=0.000). The results of flow cytometry demonstrated that CD59− and CD55− erythrocytes and granulocytes in peripheral blood decreased significantly in 8 patients [(20.87±11.68)% vs (7.97±10.02)%, P=0.004 for CD59− erythrocytes; (63.76±25.36)% vs (28.44±23.50)%, P=0.002 for CD55− erythrocytes; (68.25±26.05)% vs (59.53±24.60)%, P=0.007 for CD59− granulocytes; (81.47±26.13)% vs (68.14±26.53)%, P=0.003 for CD55− granulocytes]. Indicators for haemolysis also improved. In 10 patients, apart from 1 patient with normal IBIL and TBIL all the time, IBIL decreased significantly from (36.8±29.2) U/L at baseline to (18.1±12.4) U/L (P= 0.015). Free hemoglobin level, Rous test, Ham ‘s test were carried out only in some of the patients and results of which were also encouraging. No patients died during chemotherapy; most common adverse events were infection, nausea, vomiting and fatigue. The duration of bone marrow depression ranged from 10 to 33 days. CONCLUSIONSDAG/HAG regimens Chemotherapy was an effective, safe and promising therapy for PNH. Disclosures:No relevant conflicts of interest to declare.

Eltrombopag Can Stimulate Trilineage Hematopoiesis with Transfusion Independence in Patients with Refractory Severe Aplastic Anemia: Results From a Phase II Trial

Abstract 54▪▪This icon denotes a clinically relevant abstractSevere aplastic anemia (SAA) is characterized by trilineage marrow hypoplasia and a paucity of hematopoietic stem cell (HSC) progenitors. SAA is treated with immunosuppressive therapy (IST) or allogeneic HSC transplantation (HSCT), with a successful outcome after either treatment in a majority of patients. However, 20–40% of patients without a suitable donor for HSCT and a suboptimal response to IST may have persistent severe thrombocytopenia. Thrombopoietin (TPO) is the principal regulator of platelet production, and it exerts its effects through binding the megakaryocyte progenitor TPO receptor mpl, which stimulates production of mature megakaryocytes and platelets. Several lines of evidence support the concept that signaling through mpl also influences expansion and maintenance of primitive HSCs and multi-potent progenitor cells. Eltrombopag, is a small molecule TPO receptor agonist that stimulates mpl, and increases platelet counts in patients with chronic immune thrombocytopenic purpura (ITP). It is approved for the treatment of chronic ITP (Promacta®). We conducted a non-randomized, pilot phase II study of eltrombopag in SAA patients who remained severely thrombocytopenic at least six months after one or more rounds of IST (clinical trials.gov identifier NCT00922883). Consecutive patients fulfilling the inclusion criteria received eltrombopag 50mg daily with dose escalation every two weeks to a maximum dose of 150mg daily. Primary end points assessed after three months of treatment were changes in peripheral blood counts (platelets, hemoglobin, absolute neutrophil counts), with hematologic response criteria defined a priori for each lineage. Secondary endpoints included the incidence of bleeding events, and health related quality of life. Patients who achieved hematologic responses were maintained on eltrombopag through an extended access protocol. We completed our planned accrual of twenty five patients, and 22 are evaluable for response to date. Median age was 45 years old (range 18–77 years), and the median time from the last course of IST was 13 months (range 6–54 months). Median follow up time was 9 months (range 1–24 months). Nine of twenty two patients (41%) achieved hematologic responses: seven of twenty-two patients (32%) achieved platelet responses with transfusion independence for eight weeks or greater; six patients had improved hemoglobin levels after starting treatment (mean hemoglobin increase of 3.8 g/dL) and 4 patients who were previously dependent on red blood cell transfusions have achieved transfusion-independence. Five neutropenic patients had increased neutrophil counts after treatment with eltrombopag (mean increase 660 cells/uL). Plasma TPO levels did not predict for hematologic response to eltrombopag. Serial bone marrow biopsies performed on patients with hematologic responses demonstrated normalization of trilineage hematopoiesis and cellularity in three of four responders receiving a year or more of therapy, with no increase in reticulin fibrosis (Figure 1). These results represent the first evidence that TPO stimulation can expand the HSC pool in humans, with clinically meaningful trilineage hematologic improvements in patients with SAA, resulting in transfusion-independence and improved quality of life with a simple daily oral regimen. Updated response data on the full 25 patients will be presented at the Society’s meeting. [Display omitted] Disclosures:Off Label Use: Eltrombopag for severe aplastic anemia.

Evaluation of the Hematological, Hypoglycemic, Hypolipidemic and Antioxidant Properties of &lt;i&gt;Amaranthus Tricolor&lt;/i&gt; Leaf Extract in Rat

Purpose: To investigate the effect of Amaranthus tricolor leaf extract on some biochemical parameters in diabetic and normal ratsMethods: A. tricolor aqueous extract was assayed for antioxidant properties using ferric reducing ability of plasma (FRAP) assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and phosphomolybdenum assay. The effect of the leaf extract on serum glucose and triglyceride, total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), elevated high density lipoprotein (HDL), body weight and hematological parameters were assessed in diabetic and normal rats. The extract doses used were 200 and 400 mg/kg body weight. Acute toxicity studies were also carried out Results: In the extract doses, 200 and 400 mg/kg, reduced blood glucose levels in a dose-dependant manner, from 168.0 &plusmn; 18.5 mg/dl at 0 h to 43.0 &plusmn; 9.3 mg/dl at the 12th hour and from 146.50 &plusmn; 22.1 mg/dl at 0 h to 37.250 &plusmn; 6.3 mg/dl at the 12th hour, respectively. Oral administration of 400 mg/kg of the extract for 21 days significantly reduced (p &lt; 0.001) serum glucose, serum triglyceride, total cholesterol, low density lipoprotein, and very low density lipoprotein, but elevated (p &lt; 0.05) high density lipoprotein in diabetic experimental rats, compared to diabetic control. The extract prevented a decrease in body weight in treated diabetic rats and promoted an improvement in haemoglobin levels. Total antioxidant activity assay revealed that 1 g of dry leaf powder was equivalent to 0.035g/ml of ascorbic acid. The extract showed no toxicity up to 2 g/kg body weight.Conclusions: This study shows that the aqueous extract of Amaranthus tricolor possesses some beneficial antidiabetic properties that warrant further research.Keywords: Amaranthus tricolor, Anti-hyperglycemia, Anti-hyperlipidemia; Amaranthus, Antioxidant activity, Phosphomolybdenum

A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania

BackgroundChildren with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately.Methods255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin.ResultsThere was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n = 22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI = 0.12, 1.10; p = 0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p < 0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n = 48; 2 cm, compared to 1 cm in the placebo group; 95% CI = 0.20, 1.70; p = 0.01; p for interaction by age group = 0.01).ConclusionsMultivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure.Clinicaltrials.gov IdentifierNCT00145184

Autoimmune Hemolytic Anemia and Interstitial Pneumonitis as the Initial Presentation of Systemic Lupus Erythematosus

immunologic destruction of erythrocytes and can be life-threatening. • AIHA may be idiopathic, however, it should prompt a work-up for secondary causes. • Evaluation consists of a reticulocyte count, LDH, haptoglobin, indirect bilirubin, direct and indirect Coombs tests, auto-antibody testing, and a peripheral smear for erythrocyte morphology, including microspherocytes, polychromasia, and schistocytes. • AIHA is not associated with a deficiency state; it is characterized by an elevated LDH and reticulocyte count, indirect hyperbilirubinemia, and a low haptoglobin. • A 48-year-old female from Hong Kong with no significant past medical history presented to the emergency department with a one-month history of progressive dry cough and fatigue. • On exam, she was noticeably icteric and had bibasilar coarse crackles. • Labs on presentation: hemoglobin 4.9 g/dL, indirect bilirubin 7.1 mg/dL, reticulocyte count 35%, LDH 468 U/L, haptoglobin 4 mg/dL. Direct Coombs test positive secondary to warm agglutinins. • Chest radiograph and CT scan revealed interstitial infiltrates. • An immunologic work-up revealed positive anti-nuclear antibody, rheumatoid factor, anti-SSA, anti-Smith, anti-RNP, and a low complement level. • High-dose intravenous corticosteroids were initiated, with a slow improvement in hemoglobin level as well as in the pulmonary infiltrates. • Treatment has now been tapered to low dose oral corticosteroids, and the patient’s hemoglobin remains within normal limits.

Effect of Micronutrient and Probiotic Fortified Yogurt on Immune-Function of Anti-Retroviral Therapy Naive HIV Patients

Background: Micronutrient supplementation has been shown to reduce the progression of HIV but does not have an effect on the intestinal barrier or the intestinal microbiota of HIV patients. Studies have suggested that probiotics could potentially complement micronutrients in preserving the immune-function of HIV patients. Objective: Assess the impact of micronutrient supplemented probiotic yogurt on the immune function of HIV patients. Design:We performed a randomized, double blind, controlled trial with CD4 count as primary outcome among HIV patients naïve to anti-retroviral treatment. Secondary outcomes included hematological parameters, incidence of diarrhea and clinical symptoms. A total of 112 HIV patients were randomized to receive a micronutrient fortified yogurt with (n = 55) or without additional probiotic Lactobacillus rhamnosus GR-1 (n = 57) for four weeks. Results:An average decline in CD4 count of −70 cells/μL (95% CI: −154 to −15) was observed in the micronutrient, probiotic group versus a decrease of −63 cells/μL (95% CI: −157 to −30) in the micronutrient control group (p = 0.9). Additional probiotic supplementation was well tolerated and not associated with adverse events. No difference between groups was detected in incidence of diarrhea or clinical symptoms. An improvement of hemoglobin levels was observed for all subjects, based upon a mean difference from baseline of 1.4 g/L (SD = 6) (p = 0.02). Conclusion:The addition of probiotics to a micronutrient fortified yogurt was well tolerated by HIV patients but was not associated with a further increase in CD4 count after one month.

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania

Patients with tuberculosis (TB) often suffer from profound malnutrition. To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. A total of 471 human immunodeficiency virus (HIV) positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months' TB treatment following enrollment. About 40% of HIV-positive and 47% of HIV-negative TB patients had body mass index (BMI) < 18.5 kg/m 2 at baseline, while about 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV- positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Fe- male sex, older age, low CD4 cell counts, previous TB infection and less money spent on food were independently associated with a smaller improvement in hemoglobin levels among HIV-positive patients during treatment. HIV-positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment.

Nuove frontiere nel controllo del sanguinamento intrae peri-operatorio nel trattamento delle lesioni neoplastiche del sistema muscolo-scheletrico

Anemia is a frequent condition in oncologic patients and influences patient survival rate. A good hemoglobin level is related to better patient conditions and improves the outcome of therapies. Authors report the possible mechanisms inducing anemia in bone oncology, as histotype, chemotherapy and radiotherapy, surgery, nutrition, discuss the problems transfusion related, and report the options of blood saving in the different times: before surgery, intraoperatively and postoperatively. In particular attention should be given to the preoperative administration of erythropoietin, to less invasive surgical technique for reducing transfusion and improving hemoglobin level.

Objetivos terapéuticos en la enfermedad de Gaucher

Gaucher's disease (GD) occurs because of deficiency of the enzyme beta-glucocerebrosidase that results in accumulation of this glycolipid compound in the cells of the macrophage-monocyte system. There are 3 types: type 1 is non-neuronopathic with primarily visceral signs and symptoms which range tremendously in severity; infantile-onset type 2 and later-onset type 3 involve the central nervous system. More than 300 mutations have been described in the gene, partially explaining phenotypic heterogeneity. Commercialization in 1991 of the first enzyme replacement therapy, alglucerase, resulted in a revolution in the management of patients with symptomatic GD (i.e., by improving the hematological and visceral signs and symptoms). Within the first 5 years of alglucerase, its safety and efficacy in improving hemoglobin levels and platelet counts, and in reducing splenic and hepatic enlargement were confirmed albeit recognizing its inability to impact neurological symptoms and signs because of its large molecular size. Recombinant imiglucerase soon replaced alglucerase as the standard of care for GD. The therapeutic targets recently defined as treatment goals were: normalization of cell counts; reduction of liver and spleen volume; elimination of the infiltration in the bone marrow to prevent the complications, and improvement in surrogate biomarkers.