Median Ferritin Levels Research Articles

Red blood cell distribution width is useful in discriminating adult onset Still's disease and sepsis within 24 hours after hospitalization.

Background/AimsRed blood cell distribution width (RDW) is a value representing the heterogeneity in the size of red blood cell, and it is usually used in distinguishing types of anaemia. Recently, it was reported that it could reflect the burden of inflammation in diverse diseases and their prognosis. Hence, in this study, we investigated whether RDW may contribute to discriminating adult onset Still’s disease (AOSD) from sepsis in serious febrile patients within 24 hours after hospitalization. MethodsWe reviewed the medical records and enrolled 21 AOSD patients, 27 sepsis patients and 30 matched healthy controls. We collected at least two laboratory results of variables including RDW within 24 hours after hospitalization, and we calculated their mean values. ResultsSepsis patients showed the significantly increased median white blood cell count, compared to AOSD patients (14,390.0/mm3 vs. 12,390.0/mm3 , p = 0.010). The median RDW in sepsis patients was higher than that in AOSD patients (15.0% vs. 13.3%, p = 0.001), and furthermore, the median RDW in both patient-groups was significantly higher than that in healthy controls. In contrast, the median ferritin level in sepsis patients was lower than that in AOSD patients (544.0 mg/dL vs. 3,756.6 mg/dL, p = 0.001). In multivariate analysis, RDW ≥ 14.8% (odds ratio, 17.549) and ferritin < 2,251.0 mg/dL (odds ratio, 32.414) independently suggested sepsis more than AOSD in patients initially presenting with fever requiring hospitalization. ConclusionsRDW might be a rapid and helpful marker for a differential diagnosis between AOSD from sepsis at an early phase.

Folate, vitamin B12, ferritin and haemoglobin levels among women of childbearing age from a rural district in South India

BackgroundLow folate and vitamin B12 levels have negative effect on pregnancy outcomes but there is paucity of data on their levels among Indian women. Ferritin and haemoglobin are associated with maternal mortality and low birth-weight. Our aim was to estimate the prevalence of deficiency of serum folate and vitamin B12, and low levels of serum ferritin and blood haemoglobin among women of childbearing age from a rural population of South India.MethodsWe conducted a community-based cross-sectional study among 15-35 year women in a rural district. We used multistage stratified random sampling. Trained staff interviewed women to collect socio-demographic information and draw blood samples. We analysed samples for serum folate, vitamin B12, ferritin and blood haemoglobin levels and computed means and medians. We computed the proportion of deficiency based on cut-offs recommended by WHO. We examined the association of levels with age, parity and current pregnancy or breastfeeding by multi-variable regression using Stata 13.0.ResultsWe recruited 979 women. One-fifth (185, 19%) were pregnant and one-fifth (196, 20%)were breastfeeding. Median serum folate levels were 2.5 ng/ml (IQR, 1.2-4.8), median vitamin B12 levels were 228.0 pg/ml (IQR, 121 - 390), median ferritin levels were 13.0 μg/l (IQR, 6.0 - 20.0) and median blood haemoglobin levels were 12.1 mg/dl (IQR, 10.7 – 13.6). Low levels of serum folate, vitamin B12, ferritin and haemoglobin were found in 57% (95% CI, 54-60%), 44% (95% CI, 41-48%), 46% (95% CI, 43-49%) and 28% (95% CI, 25-31%) respectively. Women with folic acid deficiency had two times higher prevalence of having vitamin B12 deficiency. In adjusted regression analysis folate levels were lower in older and breastfeeding women, but not associated with parity and were higher among pregnant women. Similar associations were not found with Vitamin B12 deficiency. Ferritin levels were higher in older women; but not associated with parity, pregnancy or breastfeeding. Haemoglobin levels were lower in pregnant and breastfeeding women.ConclusionOur findings suggest that folic acid, vitamin B12 and iron deficiency are important public health problems in India. We observed that half of the women of childbearing age were deficient in these nutrients. Folic acid and vitamin B12 deficiencies co-exist and should be supplemented together.

The Incidence of Ototoxicity in Patients Using Iron Chelators.

In this study, we aimed to detect the incidences of ototoxicity in patients with hemoglobinopathies taking deferoxamine (DFO), deferiprone, and deferasirox using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) scale to obtain more objective data. Fifty-five transfusion-dependent patients were evaluated in this study. The NCI CTCAE scale was used to assess ototoxicity levels. The average ferritin and hemoglobin levels, the type of iron chelator, and the duration of therapy of all the patients were recorded. Ototoxicity was observed in 15 patients (31.9 %), all of whom were taking DFO. The median age was 19.5 (6-43) in patients without ototoxicity and 29 (16-50) in those with ototoxicity; this difference was statistically significant (p<0.05). The median ferritin and pre-tx Hb levels were 1391 ng/mL and 9.06 mg/dL, respectively, in patients with ototoxicity and 986.7 ng/mL and 9.24 mg/dL, respectively, in those without ototoxicity; these differences were not significant (p>0.05). Ototoxicity was not observed in the eight patients who used only deferasirox and deferiprone. The ototoxicity incidence with DFO at doses below 50 mg/kg/day was 27.3%. Deferiprone and deferasirox were not associated with ototoxic effects in patients taking these drugs.

A Different Kind of Craving: Incidence and Treatment of Pica After Laparoscopic Roux-en-Y Gastric Bypass.

Iron deficiency can occur in patients after Roux-en-y gastric bypass due to altered absorption. Pica, the compulsive craving and intake of non-nutritive substances, is a rare and poorly understood presentation of iron deficiency. To our knowledge, the rate of pica after RYGB has never been reported. The medical records of patients who underwent laparoscopic RYGB from 2001 to 2011 were reviewed. Patients with pica or other abnormal cravings were identified. Pica was identified in 16/959 (1.7%) patients who underwent RYGB during the study period. The most common presenting sign was pagophagia. All patients with pica were female and had multiple risk factors for iron deficiency with 13/16 being premenopausal and 7/16 non-compliant with oral iron supplementation. Pica symptoms presented at a mean of 3.9±1.9years after RYGB. Iron deficiency was identified in all 16 patients, with a median ferritin level of 5.0ng/mL (range 2-27). All 16 patients received intravenous iron and pica symptoms resolved. Pica is a rare phenomenon associated with iron deficiency and can occur despite oral iron supplementation. In our experience, intravenous iron can relieve symptoms. Patients considering bariatric surgery should be counseled on pica. Patients with unusual cravings should be evaluated for iron deficiency.

Hyperferritinemia in Hemophagocytic Lymphohistiocytosis: A Single Institution Experience in Pediatric Patients.

Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition that may run a rapid fatal course and calls for prompt diagnosis. Early intervention with steroids and other immunosuppressive drugs can contain the disease process and favours positive outcome. Ferritin ≥500ng/ml is a HLH diagnostic criterion. We evaluated the diagnostic potential of admission ferritin, in children with HLH. Pediatric patients of a referral teaching hospital from Feb 2010-Oct 2013 having been investigated for ferritin on admission were included. HLH was confirmed when patients had clinical features and met 5/8 diagnostic criteria of the revised 2004 HLH guidelines. Ferritin was estimated on Cobas e411 by electrochemiluminiscence, with a measuring range of 0.5-2000ng/ml. Dilutions were made when linearity exceeded and absolute values were reported. 905 on-admission ferritin investigations were reviewed out of which 346 values ≥500ng/ml. Hyperferritinemia was seen in HLH/MAS(macrophage activation syndrome) [HLH group, median age 4year4month, 59% male] and in systemic lupus erythematosus, sepsis, juvenile idiopathic arthritis, impending HLH, haemolytic anemias and malignancy [non-HLH group, median age 4year6month, 60% male]. Of 346, 72 cases of hyperferritinemia were diagnosed with secondary HLH while one patient had primary HLH. 13/73 patients expired. The median ferritin level of the HLH group was significantly higher [6556 (2402-11,734)ng/ml] compared to non-HLH group [median 1175 (943-2000)ng/ml] (p<0.0001). Receiver operator characteristics curve analysis revealed optimal admission ferritin of 3120ng/ml as the cut-off with sensitivity of 70% and specificity of 88.9% for HLH diagnosis, exceeding the currently prescribed cut-off of 500ng/ml. Hyperferritinemia below 3120ng/ml has higher negative predictive value to rule out secondary HLH on admission in the study population of children predominantly diagnosed with infection associated HLH than the prescribed cut-off as per the 2004 guidelines. This may prove to be beneficial to alert physicians for prompt intervention which considerably decreases mortality in this often fatal condition.

Iron-chelating therapy with deferasirox in transfusion-dependent, higher risk myelodysplastic syndromes: a retrospective, multicentre study.

Iron chelation is controversial in higher risk myelodysplastic syndromes (HR-MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion-dependent, intermediate-to-very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty-six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000mg/day (range 375-2500mg) for a median of 11months (range 0·4-75). Eight patients (16%) showed grade 2-3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709μg/l at baseline to 1100μg/l after 12months of treatment (P=0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3months, median overall survival was 37·5months. The results of this first survey of DFX in HR-MDS are comparable, in terms of safety and efficacy, with those observed in lower-risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR-MDS patients.

Pregnancy in patients with thalassemia major: a cohort study and conclusions for an adequate care management approach.

An improvement in quality of life and survival occurred among thalassemia major (TM) patients: pregnancy in such patients has become a reality. Safe pregnancy and delivery require efforts to ensure the best outcomes. Between 2007 and 2016, 30 TM patients had 37 pregnancies. We analyzed the hematological parameters before, during, and after pregnancies and in 19 patients a cardiovascular magnetic resonance (CMR) T2* was performed. The mean age at first pregnancy was 30±4years; the current mean age is 35±5years. Twenty-four patients (80%) had a single pregnancy, five patients (17%) had two pregnancies, and one patient (3%) became pregnant three times. Seventeen pregnancies (46%) were spontaneous, 20 (64%) needed gonadotrophin-induced ovulation and/or reproductive technologies. All pregnancies resulted in live births. Seven were twin pregnancies (19%). The mean gestational hemoglobin was 9.2±0.5g/dl, lower than pre- and postpregnancy (9.8±1g/dl, p=ns and 9.6±1g/dl, p=0.02, respectively). Median ferritin levels increased progressively (1071, range 409-5724ng/ml, before pregnancy vs 2231, range 836-6918ng/ml, after pregnancy, p<0.0001). CMR before pregnancy showed a normal cardiac T2* (mean 35.34±8.90ms) and a mean liver iron concentration (LIC) of 3.37±2.11mg/g dry weight (dw). After pregnancy, the mean cardiac T2* was 31.06±13.26ms and the mean LIC was significantly increased (9.06±5.75mg/gdw, p=0.0001). Pregnancy is possible and safe in thalassemia major. During pregnancy, iron accumulates, especially in the liver; a prompt resumption of chelation after delivery is mandatory.

The challenge of defining and treating anemia and iron deficiency in pregnancy: A study of New Zealand midwives' management of iron status in pregnancy and the postpartum period.

Early recognition and management of low maternal iron status is associated with improved maternal, fetal, and neonatal outcomes. However, existing international guidelines for the testing and management of maternal iron-deficiency anemia are variable, with no national guideline for New Zealand midwives. Clinical management is complicated by normal physiological hemodilution, and complicated further by the effects of inflammation on iron metabolism, especially in populations with a high prevalence of obesity or infection. This study describes how midwives in one New Zealand area diagnose and treat anemia and iron deficiency, in the absence of established guidelines. Data on demographics, laboratory results, and documented clinical management were retrospectively collected from midwives (n=21) and women (n=189), from September to December 2013. Analysis was predominantly descriptive. A secondary analysis of iron status and body mass index (BMI) was undertaken. A total of 46% of 186 women, with hemoglobin testing at booking, did not have ferritin tested; 86% (of 385) of ferritin tests were not concurrently tested with C-reactive protein. Despite midwives prescribing iron for 48.7% of second trimester women, 47.1% still had low iron status before birth. Only 22.8% of women had hemoglobin testing postpartum. There was a significant difference between third trimester median ferritin levels in women with BMI ≥25.00 (14μg/L) and BMI <25.00 (18μg/L) (P=.05). There was a wide range in the midwives' practice. Maternal iron status was difficult to categorize, because of inconsistent testing. This study indicates the need for an evidence-based clinical guideline for New Zealand midwives and maternity care providers.

Association of Serum Ferritin with Diabetes and Alcohol in Patients with Non-Viral Liver Disease-Related Hepatocellular Carcinoma

Introduction: Non-alcoholic fatty liver disease is a leading cause for hepatocellular carcinoma (HCC) in Sri Lanka. Diabetes mellitus, alcohol abuse, and liver inflammation are known to increase the risk of HCC. The present study evaluates serum ferritin levels in a cohort of patients with non-viral HCC (nvHCC). Methodology: Consecutive patients with nvHCC presenting to the Colombo North Liver transplant Service, Ragama, from January 2012 to July 2013 were investigated. All were negative for hepatitis B and C. At registration, 5 mL of serum was separated into plain tubes, stored at -80°C and analysed for ferritin using an enzyme-linked immunosorbent assay. Correlation between the serum ferritin and patient risk factors, liver status, and tumour characteristics were analysed. Results: There were 93 patients with nvHCC (median age 65 [12-82] years; 82 [88.2%] males). The median ferritin level was 246.2 μg/L, and 38 (40.86%) patients had elevated ferritin. Non-diabetics (median 363.5 mg/L, p = 0.003) and alcohol abusers (median 261.2 mg/L, p = 0.018) had higher ferritin levels. On multiple-variable analysis, being non-diabetic (p = 0.013) and alcoholic (p = 0.046) was significantly associated with high serum ferritin. No association was found with body mass index, tumour stage, size, macrovascular invasion, number of nodules, alpha-fetoprotein, bilirubin, international normalized ratio, and survival. Conclusion: In patients with nvHCC, serum ferritin levels are higher in non-diabetics and alcoholics.

Prospective Evaluation of the Effect of Deferasirox on Hematologic Response in Transfusion-Dependent Patients with Low-Risk MDS and Iron Overload: The Rythmex Study

▪Background:Long-term blood transfusions remain the mainstay of supportive care in patients with low-risk myelodysplastic syndromes (MDS). Blood transfusions can result in iron overload, which can lead to impaired organ function, significant morbidity and mortality. Although debate exists around its use in patients with MDS, iron chelation therapy is recommended in patients with low-risk MDS to prevent iron-overload toxicities and to improve survival. In addition, hematologic improvement has been reported during chelation therapy (Jensen PD 1996, Gattermann N 2012). Here we report results from a prospective, observational study that evaluated a hematologic response to deferasirox in a large population of regularly transfused patients with low- or intermediate-1-risk MDS.Methods:inclusion criteria: Transfusion-dependent (at least 4 packed red blood cells (PRBC)/8 weeks) adult patients with IPSS low- or intermediate-1-risk MDS who had initiated or had been receiving chelation therapy for less than 3 months. Primary endpoint was reduction in transfusion requirements at 3 month, (i.e. the number of PRBC received during the 8 weeks before deferasirox initiation compared with the 8 weeks before month 3). Secondary endpoints included: hematologic improvement (HI; IWG 2006 criteria for erythroid [HI-E], platelet [HI-P] and neutrophil [HI-N]) at 3, 6 and 12 months, duration of response, serum ferritin levels and safety.Results: 70 patients were included, 57 were evaluable. Most exclusions (19%) were related to a low level of transfusion before inclusion. Median age was 78.3 years. The cytologic subtypes were: sideroblastic anemia, 31.6%; refractory anemia, 19.3%; refractory anemia with excess blasts-1, 17.5%; refractory cytopenia with multilineage dysplasia, 17.5%; 5q syndrome, 10.5%; unclassified SMD, 3.6%. Median time since diagnosis was 2.79 years (33 months). Before inclusion, 87% patients had received a treatment for MDS (erythropoiesis-stimulating agents, 72%; lenalidomide, 17%;G-CSF, 16%; azacitidine, 7%; thalidomide: 2%). Patients received a median of 5.8 ± 2.8 PRBC during the 8 weeks before inclusion. The mean number of PRBC received per month during the 6 months before inclusion was 2.11. The median serum ferritin level at inclusion was 1 543 ng/ml.The mean number of PRBC received in the whole population post inclusion (eight weeks before month 3) was 5.9, which was not significantly different from the number of PRBC given during the 8 weeks before inclusion (5.8). However at 3 months, 4 patients had a positive effect on transfusion requirement. At 6 and 12 months, positive effect occurred in 3 and 4 additional patients, respectively. 10 patients achieved HI-E during the study and according to Kaplan-meier analysis, the probability of HI-E was 12.7% at 6 months and 24.2% at 1 year. During the study, 17 patients (32%) achieved an erythroid response, i.e positive effect on transfusion requirement and/or HI-E; 19% had an erythroid response at month 12. Median duration of erythroid response was 123 days. 3.5%, 10%, 21% of patients had received a concomitant treatment with deferasirox at 3, 6, and 12 months, respectively. However,deferasirox was the sole specific treatment received in 12/17 patients with erythroid response. 27 patients experienced adverse events (AEs) related to deferasirox, among them 4 patients with grade > 2 . 32 patients underwent deferasirox dosing modifications, and 20 patients had discontinued treatment by 3 months ( median duration of treatment 11.3 months). In patients receiving deferasirox for more than 9 months, the median serum ferritin level at 12 months was 1 438 ng/ml . In contrast, the median serum ferritin level at 12 months was 2247 ng/ml in the whole group. There were no predictive factors of erythroid response (cytologic classification, time since diagnosis, level of ferritin at inclusion, the number of PRBC transfused before inclusion), but the number of responders was low.Conclusions: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused low risk MDS patients. However, deferasirox could induce 19% of specific erythroid response at 12 months. These results suggest that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a small subset of patients with MDS and iron overload. DisclosuresRose:Genzyme, Novartis, Celgene: Honoraria, Research Funding. Beyne-Rauzy:Celgene, Novartis: Honoraria. Dreyfus:Novartis: Honoraria.

Long-Term Therapy with Deferasirox in Young Pediatric Patients with Transfusional Hemosiderosis Completing up to 5 Years of Treatment in the Observational E.N.T.R.U.S.T. Study

▪Introduction:Regular supportive transfusion therapy from an early age is common practice in young children with β thalassemia major (βTM), sickle-cell disease (SCD) and Diamond-Blackfan anemia (DBA). Patients consequently accumulate iron that can affect organ function and delay growth/development. As such, iron chelation therapy is often necessary from an early age, with lifelong requirements for patients who cannot be cured with hematopoietic stem cell transplantation. Deferasirox, a once-daily oral iron chelator, has demonstrated efficacy and safety in adult and pediatric patients with chronic iron overload. Long-term evaluation of deferasirox in young pediatric patients with transfusional hemosiderosis is valuable, as conducted in the 5-yr multinational, observational ENTRUST study. Here, we report safety and efficacy outcomes in pediatric patients with transfusional hemosiderosis receiving up to 5 yrs of continuous deferasirox treatment in clinical practice.Methods:Patients aged 2-<6 yrs at enrolment were prescribed deferasirox according to local labels, with recommendations to adjust dose based on serum ferritin levels, therapeutic goals, tolerability and weight gain. Patients were followed prospectively for 5 yrs in this observational study. Safety was evaluated by regular monitoring and recording of adverse events (AEs) in all patients who received ≥1 dose of deferasirox and had ≥1 post-baseline safety assessment (safety set). Serum ferritin levels were also analyzed (as a surrogate marker for body iron) in all patients who received ≥1 dose of deferasirox (full analysis set; FAS).Results:267 patients (mean age 3.2 yrs: 61.4% <4 yrs, 38.6% ≥4 yrs) with βTM (n=176, 65.9%), SCD (n=52, 19.5%), DBA (n=12, 4.5%), and other anemias (n=27, 10.1%) were enrolled and received ≥1 deferasirox dose. Overall mean ± SD deferasirox exposure was 44.1 ± 21.2 (range 1.2-65.6) months and mean ± SD dose was 25.8 ± 6.5 mg/kg/day. Dose was generally aligned with weight, though initial doses were suboptimal to manage iron intake and adjustments based on weight gain were delayed. 130 patients (49.8%) received deferasirox for ≥60 months. 122 patients (45.7%) patients discontinued treatment prematurely, most commonly (>5% of patients) because of loss to follow-up (n=19, 7.1%) and AEs (n=18, 6.7%; most commonly increased alanine or aspartate aminotransferase [ALT/AST], n=7 each). The number of patients discontinuing treatment because of AEs declined year on year; n=10 in Yr 1, n=4 in Yr 2, n=2 in Yr 3, and n=1 in Yrs 4 and 5, respectively. From Yr 3 onwards, there were no discontinuations due to an increase in ALT or AST. Change from baseline in serum ferritin by duration of deferasirox exposure (FAS) is summarized (Table). In the 130 patients exposed to deferasirox for 5 yrs, median serum ferritin levels decreased from 1777 (range 509-5804) ng/mL at baseline to 1414 (range 166-7030) ng/mL, a median change from baseline of -425 (range -4131-5576) ng/mL (Table).145 patients completed 5 yrs of follow-up and had data on AEs collected during this entire period. The most frequently occurring AEs with suspected relationship to study drug (occurring in ≥4 patients) were increased ALT (n=29, 20.0%), increased AST (n=12, 8.3%), vomiting (n=9, 6.2%), rash (n=6, 4.1%) and increased blood creatinine (n=6, 4.1%). Overall, there was a gradual decrease in the number of patients experiencing drug-related AEs in the safety set with each year of deferasirox exposure (Figure).Conclusions:This long-term, observational study of deferasirox in pediatric patients supports previous findings indicating favorable safety and efficacy. Approximately half the patients completed the 5-yr study, with many patients discontinuing for reasons unrelated to study drug, indicating good acceptance of treatment. Patients remaining on deferasirox benefited from sustained improvements in iron load, though this was not immediate, likely because of delayed increases in dose based on weight gain and ongoing iron intake. Among patients who continued on deferasirox tolerance was increasing over time as indicated by yearly decreasing numbers of AEs. In patients followed for up to 5 yrs, AEs were consistent with the known deferasirox safety profile, with no progressive increases in the incidence of renal-related AEs. These data therefore support the long-term use of deferasirox in young iron overloaded patients in everyday clinical practice. [Display omitted] [Display omitted] DisclosuresVichinsky:Novartis, ApoPharma Inc. and ARUP Laboratories: Research Funding; Novartis: Consultancy. El-Beshlawy:Novartis, ApoPharma Inc: Research Funding. Bruederle:Novartis Pharmaceuticals Corporation: Employment. Han:Novartis: Employment.

Children with Thalassemia Major Display Abnormal Renal Tubular Function

Introduction. Chronic hypoxia, transfusional iron overload and chelation therapy are all contributing factors to the deterioration of renal function in thalassemia major (TM ) patients. Among chelators, deferasirox (DFX) is considered the most toxic drug for kidneys: increment of more than 30% of serum creatinine levels is used for dosage modulation or interruption. Recently tubular abnormalities have also been described. We have observed renal toxicity in nine children affected by TM and treated with DFX or deferiprone (DFP) and described the differences in glomerular or tubular function between the two oral chelators.Material and methods. Nine children, 4 males and 5 females, aged 3-17 years (median 7 y), were retrospectively evaluated. They were regularly transfused every 2-3 weeks, receiving a median of 260 g erythrocytes concentrates/kg/year. The median serum ferritin level at baseline before starting oral chelation was 1763 ug/L (range 1127-4198).Four patients (pts) received only one type of chelator (1 DFP and 3 DFX). Five pts received both DFX or DFP in different periods. Overall 8 DFX treatments (dosage 15-30 mg/kg, for 18-112 months, mean 40) and 6 DFP treatments (dosage 75-130 mg/kg for 14-54 months, mean 24) were administered. Three pts had previously received deferoxamine; 3/8 DFX pts and 1/6 DFP pts were naïf to chelation before first renal evaluation.The following renal indices were considered:− glomerular function: serum creatinine and cystatine C levels, estimated glomerular filtration rate (eGFR), according to modified Schwartz formula; urine albumin to creatinine ratio (ACR), urine protein excretion.− tubular function: glycosuria, urinary N-acetyl-beta-D-glucosamidase activity/u-creatinine (u-NAG/u-cr), (index of acute tubular damage); urine daily Beta2 microglobulin (B2MG) and Alfa1 microglobulin (A1MG) excretion (both indices of chronic tubular damage).Analyses were performed at different intervals, according to clinical conditions and patients' age, with different frequency among children.Creatinine impairment was defined as an increase over 30% of basal level. All indices were graded according to local laboratory range. Toxicity was considered significant when the tests were abnormal in at least 25% of evaluations.Results. Initial renal function was normal in all patients (median eGFR 209 ml/min/1.73 m2, range 157-295) and eGFR remained stable over time in all cases. A total of 5 pts with DFX and 3 pts with DFP showed an increase of creatinine over 30% of basal levels. Increase of ACR > 30 mg/g cr was seen in 6/8 pts (75%) in DFX and in 1/6 pts (17%) in DFP; 2 pts (1/8 in DFX and 1/6 in DFP) had macroalbuminuria (ACR >300 mg/g creatinine). No association was found between cumulative DFP dose and eGFR over time (Pearson coefficient, r = 0.06), while a moderate association was found with DFX (r = 0.5; p = 0.06).Symptomatic acute tubular toxicity was observed in 2 pts, with tubular acidosis, glycosuria and abnormal acute tubular indices (u-NAG/u-cr). A1MG and B2MG were also altered, suggesting a chronic injury substrate. Both pts were in DFX group (receiving a dose of 20 and 40 mg/kg/day, respectively) and had experienced a fast reduction in ferritin levels over a short period of time. No signs of concomitant infection were detected.u-NAG/u-cr was always abnormal in all children in both groups; mean values were 2.8 U/mmol for DFX and 2.4 U/mmol for DFP. B2MG was altered in 6/8 DFX pts and in 2/6 DFP pts (75% vs 33%). Median values were 3.0 mg/24 h for DFX and 0.5 mg/24 h for DFP, respectively. A1MG was altered in 4/8 DFX pts and 3/6 DFP pts, with median values of 164 mg/24 h for DFX and 55 mg/24 h for DFP, respectively.Conclusions. Patients withTM can experience abnormalities in renal function, especially as regards tubular damage. Acute tubular damage indices were altered in all chelated pts, whereas tests for chronic damage were abnormal more often in the DFX group than in DFP-treated pts. Albeit the significance of our findings needs further confirmation in a longer follow up, these results suggest that extensive renal evaluation is needed, in particular in children whose life expectancy is open and long-term prognosis for multiple organ function is an important issue. DisclosuresNo relevant conflicts of interest to declare.

Facility Practice Variation to Help Understand the Effects of Public Policy: Insights from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Recent Centers for Medicare & Medicaid Services policies have used dialysis facility practice variation to develop public ratings and adjust payments. In the Dialysis Facility Compare star rating system (DFC SRS), facility-relative rates of performance-based clinical measures varied nearly two-fold for mortality (standardized mortality ratio; 10th/90th percentiles: 0.71, 1.34) and hospitalization (standardized hospitalization ratio; 10th/90th percentiles: 0.64, 1.37), and nearly four-fold for transfusion (standardized transfusion ratio; 10th/90th percentiles: 0.43, 1.65). Medicare claims data (from July of 2014) demonstrate that facility variation for the proportions of patients on hemodialysis hospitalized (10th/90th percentiles: 27%, 50%) and transfused (10th/90th percentiles: 3%, 17%) within 6 months that far exceeds relatively modest recent overall longitudinal trends. DFC SRS-rated facility variation is also substantial for fistula (10th/90th percentiles: 50%, 78%) and catheter use >90 days (10th/90th percentiles: 3%, 19%). By contrast, DFC SRS-rated facility distributions for adult hemodialysis Kt/V>1.2 (10th/90th percentiles: 84%, 97%) and total serum calcium >10.2 mg/dl (median, 1%; 75th/90th percentiles: 3%, 5%) are quite narrow and may be of questionable value. Likewise, variation in the US Dialysis Outcomes and Practice Patterns Study is over two-fold for facility median serum parathyroid hormone (10th/90th percentiles: 290 pg/ml, 629 pg/ml) and ferritin (10th/90th percentiles: 469 ng/ml, 1143 ng/ml) levels, and facility mean treatment time varies by 30 minutes (10th/90th percentiles: 204 minutes, 234 minutes). Rising serum parathyroid hormone and ferritin levels, and generally short dialysis treatment time, represent areas unchecked by existing policy; both overall trends and facility variation in these values may reflect unintended consequences of policy or reimbursement pressures and therefore raise concern. Additionally, outcomes in the transition period from advanced CKD to dialysis remain poor, and policy initiatives and performance accountability in this area remain insufficient. Innovative models of comprehensive care in advanced CKD and the early dialysis period which are more amenable to policy oversight are needed. In summary, facility variation is typically larger than prevailing longitudinal trends, and should not be overlooked. The combination of nationally representative observational databases (e.g., the Dialysis Outcomes and Practice Patterns Study) and ESRD registries can provide policy makers with additional tools to evaluate facility variation, develop policies, and monitor unintended effects.

Longitudinal MRI and Ferritin Monitoring of Iron Overload in Chronically Transfused and Chelated Children With Sickle Cell Anemia and Thalassemia Major.

Iron overload is an ineluctable complication in chronically transfused children warranting accurate assessment to avoid related morbidity. We investigated longitudinally the relationships between ferritin levels and hepatic and cardiac T2* magnetic resonance imaging (MRI) in a cohort of chronically transfused children receiving chelation therapy. Thirty children with sickle cell anemia (SCA) and 7 with thalassemia major (TM) chelated similarly by deferasirox were analyzed. Sex ratio, age, median duration of transfusion programs (5 y; range, 2 to 14 y), median transfusion iron intake 0.54 mg/kg/d (range, 0.27 to 0.74 mg/kg/d), and median ferritin level (1550 mg/L; range, 184 to 6204 mg/L) were comparable in TM and SCA. A significant relation was found between ferritin level and transfusion iron intake (P<0.001) despite chelation therapy. Analysis of 73 hepatic T2* MRI performed yearly demonstrated severe hepatic iron overload (≥14 mg/g) in 38.3% cases and a strong relationship between serum ferritin level and liver iron content both in SCA and TM (P<0.001). Analysis of 55 cardiac T2* MRI measurements found no cardiac overload in patients with SCA. Cardiac iron overload was moderate in 4 cases and severe in 1 case of TM. In almost half the cases, ferritin trend correctly predicted hepatic iron trend, both in patients with SCA and TM but failed to predict cardiac iron trend, notably in TM patients. Despite chelation therapy, iron burden in chronically transfused patients remains a threat. Ferritin levels are associated with liver iron overload in chelated children with SCA and TM, but iron burden should be best monitored with MRI whenever the setting allows it.

The Prognostic Significance of Elevated Serum Ferritin Levels Prior to Transplantation in Patients With Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation (autoHSCT): Role of Iron Overload.

Hematopoietic stem cell transplantation is a common and preferred treatment of lymphomas in many centers. Our goal was to determine the association between pretransplant iron overload and survival in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). A total of 165 patients with lymphoma, who underwent autoHSCT between the years of 2007 and 2014, were included in this study. Ferritin levels were used to determine iron status; the cut-off value was 500 ng/mL. The relationship between iron overload and survival was assessed by statistical analysis. The median ferritin level in the normal ferritin (ferritin< 500) group was 118 ng/mL (range, 9-494 ng/mL) and in the high-ferritin group (ferritin≥ 500), it was 908 ng/mL (range, 503-4549 ng/mL). A total of 64 (38.8%) patients died during follow-up. Of these patients that died, 52 (81.25%) were in the high-ferritin group, and 12 (18.75%) were in the normal ferritin group (P≤ .001). Twelve (14.1%) of 85 patients died in the normal ferritin group, and 52 (65.0%) of 80 patients died in the high-ferritin group. The overall mortality was significantly higher in the high-ferritin group (P< .001). The median overall survival was 42 months (range, 25-56 months) in the normal-ferritin group and20 months (range, 5-46) in the high-ferritin group. The difference between the groups was statistically significant (P< .001). The median disease-free survival was 39 months (range, 16-56) in the normal ferritin group and 10 months (range, 3-29) in the high-ferritin group. The difference between the groups was statistically significant (P< .001). Elevated serum ferritin levels might predict poorer survival in autoHSCT recipients.

A Score Based on IPSS-R, Ferritin and EPO Levels Predicts Erythroid Response to ESAs and Survival in Lower Risk Anemic MDS Patients with High Probability of Response to ESAs: Spresas Sub-Analysis from the GESMD

INTRODUCTIONAnemia is the most frequent cytopenia in lower-risk MDS. Erythropoietic-stimulating agents (ESAs) are commonly used in these patients. The use of ÒclassicalÓ parameters (EPO and ferritin levels) and the revised IPSS (IPSS-R) has been proposed1 (SantiniÕs score) to predict response to ESAs and overall survival (OS) among patients with lower risk MDS by IPSS and a favorable Nordic group score2.OBJECTIVESThe main objective of the study was to evaluate overall response rate (ORR) to ESAs and OS according to the proposed SantiniÕs score in an independent and large cohort of anemic lower risk MDS patients receiving treatment with ESAs.METHODSData from 530 anemic patients with low/int1 risk IPSS de novo MDS (according to FAB and WHO criteria) and sufficient follow-up data available were recorded in Spresas3 (SPanish Registry of Erythropoietic Stimulating Agents Study from GESMD). Two hundred and twenty six patients (42.6% of the patients) were selected according to specific criteria regarding the published SantiniÕs score1: Hb level </=10 g/dL, serum erythropoietin (EPO) <500 mU/mL and ESA (EPO alfa or B 40000-60000IU/week, or darbepoetin 150-300 ug/week). Applying 1 point to each of the following unfavorable variables for response to ESA, EPO>200mU/mL(=1), serum ferritin (SF) >350 ng/mL(=1) and IPSS-R very low=0, low=1, intermediate=2 and high=3) yielded a score ranging from 0 to 5. ESAs response rate and overall survival were analysed according to these score. Response to treatment was evaluated according to IWG 2006 response criteria and a multivariate logistic regression analysis was used to identify independent predictors of erythroid response (ER). OS were defined as the time between diagnosis and the corresponding event or last follow up (Feb 2015) and were analyzed using univariable and multivariable Cox proportional hazards regression methods.RESULTSMedian age was 77 years (interquartile range [IQR] 25%-75%: 71-83 y), median Hb level at start of treatment was 10 g/dL (IQR25-75: 9-10), median EPO level was 90 (IQR25-75: 27,25-108) and median ferritin level was 338,5 (IQR25-75: 146,5-568,75). Among 139 patients with this data available, 85 patients (61,1%) were RBC transfusion dependent before ESAs treatment. Median time from diagnosis to ESAs treatment was 82 (IQR25-75: 27-353) days. According to the IPSS, 68.6% (N=155) and 31.4% (N=71) were in low and Int-1 risk groups, respectively. Regarding IPSS-R, 23% (N=52), 66.8% (N=151), 9.7% (N=22) and 0.4% (N=1) were in very low, low, intermediate and high risk, respectively. ORR to ESA treatment was 71.2% (N=161), with a median duration of response of 2.06 years. Prognosis factors of ER showed a trend toward to a higher ER among patients in the lower IPSS-R (P>0.05), low IPSS (p=0.039) and lower EPO levels (p<0.0001) while in multivariate analysis EPO level was confirmed as most significant variable associated to ER (p<0.001).According to SantiniÕs score, 11.5%(N=26), 42.9%(N=97), 25.8%(N=81), 8%(N=18) and 1.8%(N=4) of the patients were in the 0, 1, 2 3 and 4 score. Erythroid response was better for patients in the lower scores, with response rates of 73.1%, 82.5%, 65.4%, 50% and 0%, for patients in 0, 1, 2, 3 and 4 score, respectively (p<0.001, figure 1). After a median follow up of 3.1 years, median OS from diagnosis was 4.99 years. Interestingly, median OS from diagnosis was clearly related to SantiniÕs score (10.7 years, 6.7y, 4.9y, 3.7y and 6.7y for patients with 0, 1, 2, 3, and 4 points, respectively, p=0.041, Figure 2) whereas median OS from start of ESAs showed also some trend (p=0.26).CONCLUSIONSThe present study confirms that SantiniÕs score is useful to identify patients with a higher probability of response to ESAs and better OS among lower risk MDS patients with an expected favorable response to ESA according to Nordic group score.Spresas study was partly supported by Janssen1.-Santini et al, Blood 122(13), 2013.2.-Hellstršm-Lindberg, Br J Haematol 120(6), 2003.3.-D'ez Campelo, EHA 2015 meeting, P244. [Display omitted] [Display omitted] DisclosuresDíez Campelo:Novartis: Research Funding, Speakers Bureau; Janssen: Research Funding; Celgene: Research Funding, Speakers Bureau. Off Label Use: Use of erythropoietic stimulating agents for anemia in patients with myelodysplastic syndromes. Ramos:JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees; AMGEN: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Falantes:Celgene: Honoraria. Garcia:Celgene: Research Funding. Sanz:JANSSEN CILAG: Honoraria, Research Funding, Speakers Bureau.

Can iron overload in patients with lower-risk myelodysplastic syndromes be reduced using erythropoiesis-stimulating agents?

Iron overload (IOL) portends inferior outcome in myelodysplastic syndromes (MDS). Erythropoiesis-stimulating agents (ESA) may reduce red blood cell transfusion requirements. MDS patients receiving ESA were reviewed for characteristics, response to ESA by International Working Group 2006 criteria and ferritin levels. Forty-nine patients received an ESA, had ferritin levels available, and were not receiving iron chelation therapy. Baseline characteristics were not significantly different between ESA responders (ER) and non-responders (ENR; P = NS). The median ESA treatment duration was 6.7 (1.5-85.9) months. Twenty-one (43%) patients had an ESA response. Median ferritin level in ER was pre-ESA, 473 (range 91-2727) and post-ESA, 801 (130-11,164) ng/mL (P = 0.01), and in ENR pre-ESA, 672 (76-3285) and post-ESA, 1423 (431-6593) ng/mL (P < 0.0001). There was a significant association between ESA response, post-ESA hemoglobin ≥100g/L, and post-ESA ferritin <1000ng/mL (P = 0.0003 and 0.03, respectively). At a median follow-up of 28months, the 2-year overall survival for ER and ENR, respectively, were 80% and 86% (P = NS). In lower-risk MDS patients responding to ESA, although an expected decrease in ferritin levels over treatment was not seen, ferritin levels increased less than in non-responders. Whether IOL may be reduced by ESA over a longer treatment duration may require analysis of larger numbers of patients.

Comparison of three types of intervention to enhance placental redistribution in term newborns: randomized control trial.

To compare the effect of combined delayed cord clamping and umbilical cord milking to either of them had done alone, on hematological parameters at 6 weeks of age in term neonates. It was a randomized controlled trial, conducted during January to December 2014. Three hundred eligible neonates were randomly allocated to three parallel groups. Primary outcome was hemoglobin and serum ferritin at 6 weeks of age. Data were analyzed using analysis of variance and Kruskal-Wallis test. Baseline characteristics and hemodynamic parameters were comparable in all the three groups. The median serum ferritin level at 6 weeks was significantly higher in the group receiving both delayed cord clamping and milking the cut cord group (295.49 (233.5 to 346.54) ng ml(-1)) as compared with the group that received only milking of the cut cord (184.55 (131.22 to 256.5) ng ml(-1)) or only delayed cord clamping (268.8 (189.4 to 315.44) ng ml(-1)). Delayed cord clamping with milking the cut cord improved iron stores at 6 weeks of age in term infants, then either of the two interventions alone.

Factors associated with steatosis in liver biopsies of individuals with chronic hepatitis C infection in southern Brazil

Background and study aimsInfection by the hepatitis C virus (HCV) is associated with various metabolic disorders that are collectively referred to as dysmetabolic syndrome associated with HCV. Hepatic steatosis is a common finding in chronic HCV infection and has been reported in 30–70% of patients. Here, we determine the prevalence of steatosis in patients with HCV, identify the characteristics associated with the presence of steatosis in liver biopsies and assess the association between steatosis and the severity of liver disease. Patients and methodsThis analytic cross-sectional study evaluated HCV carriers (adults) at the Gastroenterology and Hepatology Outpatient Clinic of a public university hospital between July 2013 and June 2014 using retrospective data collection. The patients were divided into two groups according to the presence or absence of steatosis in their liver biopsies. The groups were compared for the presence of risk factors for steatosis and clinical, laboratory, virological and histological characteristics. ResultsOne hundred and four patients aged 49.5±9.3years were included in the study; 56.0% of the patients were men. Steatosis was observed in 65.4% of the liver biopsies. When comparing individuals with and without steatosis, patients with steatosis exhibited a higher proportion of non-1 genotype (43.9 vs. 20.7%; p=0.034), higher median triglyceride levels (101.0 vs. 75.0; p=0.034), ferritin levels (333.0 vs. 193.5; p=0.025) and gamma glutamyl transferase levels (2.92 xULN vs. 1.87; p=0.030). Multivariate analysis demonstrated that triglyceride levels were independently associated with the presence of steatosis (OR=1.016; 95% CI 1.002–1.031; p=0.026). ConclusionsHepatic steatosis was observed in 65.4% of individuals with HCV. We observed that elevated triglyceride levels were associated independently with the presence of hepatic steatosis; we did not demonstrate an association between hepatic steatosis and histological severity.

Thresholds of iron markers for iron deficiency erythropoiesis—finding of the Japanese nationwide dialysis registry

Reportedly, serum ferritin levels are much lower in Japanese hemodialysis (HD) patients than their Western counterparts. Therefore, the cutoff values of ferritin and transferrin saturation (TSAT) for iron deficiency might differ from other countries. We conducted a cross-sectional observational study using the Japanese nationwide registry data. We enrolled 142,339 maintenance HD patients and assessed the association between these markers, hemoglobin (Hb), and erythropoiesis-stimulating agent (ESA) resistance index (ERI) utilizing restricted cubic spline analyses. Median ferritin and TSAT levels were 73 (IQR: 31–158) ng/ml and 23.7 (16.8–32.0)%, respectively. These lower ferritin ranges may possibly stem from a lower inflammatory state in Japanese patients, as shown in median CRP of 1.0 mg/l. An adjusted nonlinear association between Hb and TSAT showed that Hb levels drop with the decrease in TSAT below 20%, regardless of serum ferritin levels, suggesting the absolute iron deficiency cutoff as 20% for TSAT. In patients with TSAT >20%, the association between Hb and ferritin levels is nearly flat, whereas in patients with TSAT <20%, ferritin <50 ng/ml was associated with low Hb. In long-acting ESAs-users with TSAT >20%, U-shaped relationship was observed between ERI and ferritin with the bottom of ERI around 100 ng/ml of ferritin, possibly because high ferritin levels reflected an inflamed state leading to hyporesponsiveness to ESA. The patient subgroup with TSAT <20% and ferritin >100 ng/ml had significantly higher ERIs compared with the subgroup with TSAT >20% and ferritin <100 ng/ml, implying that TSAT, rather than ferritin, should be a primary iron marker predicting ESA response.