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The introduction of the electronic health record was heralded as a technology solution to improve care quality and efficiency, but these tools have contributed to increased administrative burden and burnout for clinicians. Today, artificial intelligence is receiving much of the same attention and promises as electronic health records. Can healthcare learn from the failures of electronic health records to maximize the potential of artificial intelligence?

BackgroundArtificial intelligence (AI), more specifically large language models (LLMs), holds significant potential in revolutionizing emergency care delivery by optimizing clinical workflows and enhancing the quality of decision-making. Although enthusiasm for integrating LLMs into emergency medicine (EM) is growing, the existing literature is characterized by a disparate collection of individual studies, conceptual analyses, and preliminary implementations. Given these complexities and gaps in understanding, a cohesive framework is needed to comprehend the existing body of knowledge on the application of LLMs in EM. ObjectiveGiven the absence of a comprehensive framework for exploring the roles of LLMs in EM, this scoping review aims to systematically map the existing literature on LLMs’ potential applications within EM and identify directions for future research. Addressing this gap will allow for informed advancements in the field. MethodsUsing PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) criteria, we searched Ovid MEDLINE, Embase, Web of Science, and Google Scholar for papers published between January 2018 and August 2023 that discussed LLMs’ use in EM. We excluded other forms of AI. A total of 1994 unique titles and abstracts were screened, and each full-text paper was independently reviewed by 2 authors. Data were abstracted independently, and 5 authors performed a collaborative quantitative and qualitative synthesis of the data. ResultsA total of 43 papers were included. Studies were predominantly from 2022 to 2023 and conducted in the United States and China. We uncovered four major themes: (1) clinical decision-making and support was highlighted as a pivotal area, with LLMs playing a substantial role in enhancing patient care, notably through their application in real-time triage, allowing early recognition of patient urgency; (2) efficiency, workflow, and information management demonstrated the capacity of LLMs to significantly boost operational efficiency, particularly through the automation of patient record synthesis, which could reduce administrative burden and enhance patient-centric care; (3) risks, ethics, and transparency were identified as areas of concern, especially regarding the reliability of LLMs’ outputs, and specific studies highlighted the challenges of ensuring unbiased decision-making amidst potentially flawed training data sets, stressing the importance of thorough validation and ethical oversight; and (4) education and communication possibilities included LLMs’ capacity to enrich medical training, such as through using simulated patient interactions that enhance communication skills. ConclusionsLLMs have the potential to fundamentally transform EM, enhancing clinical decision-making, optimizing workflows, and improving patient outcomes. This review sets the stage for future advancements by identifying key research areas: prospective validation of LLM applications, establishing standards for responsible use, understanding provider and patient perceptions, and improving physicians’ AI literacy. Effective integration of LLMs into EM will require collaborative efforts and thorough evaluation to ensure these technologies can be safely and effectively applied.

BackgroundMissingness in health care data poses significant challenges in the development and implementation of artificial intelligence (AI) and machine learning solutions. Identifying and addressing these challenges is critical to ensuring the continued growth and accuracy of these models as well as their equitable and effective use in health care settings. ObjectiveThis study aims to explore the challenges, opportunities, and potential solutions related to missingness in health care data for AI applications through the conduct of a digital conference and thematic analysis of conference proceedings. MethodsA digital conference was held in September 2022, attracting 861 registered participants, with 164 (19%) attending the live event. The conference featured presentations and panel discussions by experts in AI, machine learning, and health care. Transcripts of the event were analyzed using the stepwise framework of Braun and Clark to identify key themes related to missingness in health care data. ResultsThree principal themes—data quality and bias, human input in model development, and trust and privacy—emerged from the analysis. Topics included the accuracy of predictive models, lack of inclusion of underrepresented communities, partnership with physicians and other populations, challenges with sensitive health care data, and fostering trust with patients and the health care community. ConclusionsAddressing the challenges of data quality, human input, and trust is vital when devising and using machine learning algorithms in health care. Recommendations include expanding data collection efforts to reduce gaps and biases, involving medical professionals in the development and implementation of AI models, and developing clear ethical guidelines to safeguard patient privacy. Further research and ongoing discussions are needed to ensure these conclusions remain relevant as health care and AI continue to evolve.

BackgroundGenerative artificial intelligence (AI) technologies are increasingly being utilized across various fields, with considerable interest and concern regarding their potential application in medical education. These technologies, such as Chat GPT and Bard, can generate new content and have a wide range of possible applications. ObjectiveThis study aimed to synthesize the potential opportunities and limitations of generative AI in medical education. It sought to identify prevalent themes within recent literature regarding potential applications and challenges of generative AI in medical education and use these to guide future areas for exploration. MethodsWe conducted a scoping review, following the framework by Arksey and O'Malley, of English language articles published from 2022 onward that discussed generative AI in the context of medical education. A literature search was performed using PubMed, Web of Science, and Google Scholar databases. We screened articles for inclusion, extracted data from relevant studies, and completed a quantitative and qualitative synthesis of the data. ResultsThematic analysis revealed diverse potential applications for generative AI in medical education, including self-directed learning, simulation scenarios, and writing assistance. However, the literature also highlighted significant challenges, such as issues with academic integrity, data accuracy, and potential detriments to learning. Based on these themes and the current state of the literature, we propose the following 3 key areas for investigation: developing learners’ skills to evaluate AI critically, rethinking assessment methodology, and studying human-AI interactions. ConclusionsThe integration of generative AI in medical education presents exciting opportunities, alongside considerable challenges. There is a need to develop new skills and competencies related to AI as well as thoughtful, nuanced approaches to examine the growing use of generative AI in medical education.

Detlef Zillikens, MD, director and chair of the Department of Dermatology at the University of Lübeck, Lübeck, Germany, died in September 2022, aged only 64. He dedicated his professional life to autoimmune blistering diseases (AIBDs) and built his department into one of the world’s leading centers for these diseases. Herein, his professional life and the impact on the field of AIBDs and the research landscape at the University of Lübeck are addressed. With his warm, integrative, open-minded, ever-optimistic attitude, he was a highly reliable colleague, mentor, and friend to many in the field including each of the authors. Combined with his in-depth knowledge of dermatology, interest in many fields of life science, and hard work, Detlef Zillikens initiated the founding of two independent research institutes, the Lübeck Institute of Experimental Dermatology and the Institute and Comprehensive Center for Inflammation Medicine. He was also instrumental in establishing the Center for Research on Inflammation of the Skin, where in a new research building, over 140 scientists pursue research questions related to skin inflammation. By inviting numerous researchers and clinicians to his department and hosting two large international meetings, he brought the field of AIBDs much closer together and inspired multiple national and international research initiatives. His ideas will live on and grow in many of his colleagues and mentees.

Blue nevus is a benign melanocytic lesion, typically asymptomatic and of unknown etiology. Several histologic and clinical variants have been distinguished, the most frequent being common blue nevus, cellular blue nevus, and combined blue nevus. Although melanocytic nevi with a satellite lesion are usually suggestive of locally advanced malignant melanoma, very few cases of blue nevi with satellite lesions have been reported. The diagnosis of common or cellular blue nevi is generally straightforward; however, the presence of structures such as irregular edges or satellitosis are highly suggestive for malignancy, and differential diagnoses such as locally advanced malignant melanoma and malignant blue nevus should be considered. Recurrent blue nevi can display atypical features not seen in the primary lesion, such as pleomorphism and mitotic activity. They usually tend to follow a benign course; however, in some cases, recurrence may indicate malignant transformation. We here report the unique case of a 64-year-old woman with a recurrent cellular blue nevus accompanied by satellite lesions. Such a biological behavior resulting in a clinical presentation as a melanoma-like lesion is a rarity in blue nevus and has not been described before.

Hereditary erythrocytosis is a rare hematologic disorder characterized by an excess of red blood cell production. Here we describe a European collaborative study involving a collection of 2,160 patients with erythrocytosis sequenced in ten different laboratories. We focused our study on the EGLN1 gene and identified 39 germline missense variants including one gene deletion in 47 probands. EGLN1 encodes the PHD2 prolyl 4-hydroxylase, a major inhibitor of hypoxia-inducible factor. We performed a comprehensive study to evaluate the causal role of the identified PHD2 variants: (i) in silico studies of localization, conservation, and deleterious effects; (ii) analysis of hematologic parameters of carriers identified in the UK Biobank; (iii) functional studies of the protein activity and stability; and (iv) a comprehensive study of PHD2 splicing. Altogether, these studies allowed the classification of 16 pathogenic or likely pathogenic mutants in a total of 48 patients and relatives. The in silico studies extended to the variants described in the literature showed that a minority of PHD2 variants can be classified as pathogenic (36/96), without any differences from the variants of unknown significance regarding the severity of the developed disease (hematologic parameters and complications). Here, we demonstrated the great value of federating laboratories working on such rare disorders in order to implement the criteria required for genetic classification, a strategy that should be extended to all hereditary hematologic diseases.

Schnitzler syndrome is a rare autoinflammatory disorder characterized by urticarial rash, joint pain, recurrent fever, leucocytosis, elevated C-reactive protein (CRP) and serum amyloid A (SAA), and monoclonal IgM or IgG gammopathy. According to the Strasbourg criteria, both urticarial rash and gammopathy are mandatorily required for the diagnosis of Schnitzler’s syndrome. However, incomplete variants lacking either skin symptoms or monoclonal gammopathy have also been described. Here, we report a case in which the diagnosis of Schnitzler-like syndrome was made despite the absence of gammopathy, based on neutrophilic dermal inflammation, episodic and excessive increase in inflammatory parameters, and prompt response to anakinra, a soluble IL1 receptor antagonist (sIL-1RA). In addition, we detected neutrophil epitheliotropism, which is highly suggestive of autoinflammatory disease. Using whole-exome sequencing, we were unable to find a causative pathogenic mutation but did find several mutations possibly related to the inflammatory processes in this patient. This and other cases highlight that the existing Strasbourg criteria are too strict to capture Schnitzler-like syndromes that may respond well and rapidly to IL1 inhibition. Recurrent episodes of disease with normalization of inflammatory symptoms in the interval, rapid response to anakinra, and neutrophilic epitheliotropism in a lesional skin biopsy may help confirm the diagnosis of Schnitzler-like syndrome.

In the 20th century, the models used to predict the motion of heavenly bodies did not match observation. Investigating this incongruity led to the discovery of dark matter—the most abundant substance in the universe. In medicine, despite years of using a data-hungry approach, our models have been limited in their ability to predict population health outcomes—that is, our observations also do not meet our expectations. We believe this phenomenon represents medicine’s “dark matter”— the features which have a tremendous effect on clinical outcomes that we cannot directly observe yet. Advancing the information science of health care systems will thus require unique solutions and a humble approach that acknowledges its limitations. Dark matter changed the way the scientific community understood the universe; what might medicine learn from what it cannot yet see?

The current credentialing process for physicians struggled to accommodate fluctuating regional demands for providers during the severe acute respiratory syndrome coronavirus 2 pandemic. This hurdle highlighted existing inefficiencies and difficulties facing healthcare systems across the world and led us to explore how credentialing can be improved using digital technologies. We explain how this is a critical moment to make the shift from physical to digital credentials by specifying how a digital credentialing system could simplify onboarding for providers, enable secure expansion of telehealth services, and enhance information exchange.

Introduction: The World Health Organization's (WHO) Basic Emergency Care Course (BEC) is a five day, in-person course covering basic assessment and life-saving interventions. We developed two novel adjuncts for the WHO BEC: a suite of clinical cases (BEC-Cases) to simulate patient care and a mobile phone application (BEC-App) for reference. The purpose was to determine whether the use of these educational adjuncts in a flipped classroom approach improves knowledge acquisition and retention among healthcare workers in a low-resource setting. Methods: We conducted a prospective, cohort study from October 2017 through February 2018 at two district hospitals in the Pwani Region of Tanzania. Descriptive statistics, Fisher's exact t-tests, and Wilcoxon ranked-sum tests were used to examine whether the use of these adjuncts resulted in improved learner knowledge. Participants were enrolled based on location into two arms; Arm 1 received the BEC course and Arm 2 received the BEC-Cases and BEC-App in addition to the BEC course. Both Arms were tested before and after the BEC course, as well as a 7-month follow-up exam. All participants were invited to focus groups on the course and adjuncts. Results: A total of 24 participants were included, 12 (50%) of whom were followed to completion. Mean pre-test scores in Arm 1 (50%) were similar to Arm 2 (53%) (p=0.52). Both arms had improved test scores after the BEC Course Arm 1 (74%) and Arm 2 (87%), (p=0.03). At 7-month follow-up, though with significant participant loss to follow up, Arm 1 had a mean follow-up exam score of 66%, and Arm 2, 74%. Discussion: Implementation of flipped classroom educational adjuncts for the WHO BEC course is feasible and may improve healthcare worker learning in low resource settings. Our focus- group feedback suggest that the course and adjuncts are user friendly and culturally appropriate. Keywords: Flipped classroom, online, Emergency care, Open access educational resources, Education, Point-of-care

Background: Onychomycosis numbers among the most common fungal infections in humans affecting finger- or toenails. Histology remains a frequently applied screening technique to diagnose onychomycosis. Screening slides for fungal elements can be time-consuming for pathologists, and sensitivity in cases with low amounts of fungi remains a concern. Convolutional neural networks (CNNs) have revolutionized image classification in recent years. The goal of our project was to evaluate if a U-NET-based segmentation approach as a subcategory of CNNs can be applied to detect fungal elements on digitized histologic sections of human nail specimens and to compare it with the performance of 11 board-certified dermatopathologists. Methods: In total, 664 corresponding H&E- and PAS-stained histologic whole-slide images (WSIs) of human nail plates from four different laboratories were digitized. Histologic structures were manually annotated. A U-NET image segmentation model was trained for binary segmentation on the dataset generated by annotated slides. Results: The U-NET algorithm detected 90.5% of WSIs with fungi, demonstrating a comparable sensitivity with that of the 11 board-certified dermatopathologists (sensitivity of 89.2%). Conclusions: Our results demonstrate that machine-learning-based algorithms applied to real-world clinical cases can produce comparable sensitivities to human pathologists. Our established U-NET may be used as a supportive diagnostic tool to preselect possible slides with fungal elements. Slides where fungal elements are indicated by our U-NET should be reevaluated by the pathologist to confirm or refute the diagnosis of onychomycosis.

Hereditary xerocytosis is a dominantly inherited red cell membrane disorder caused in most cases by gain-of-function mutations in PIEZO1, encoding a mechanosensitive ion channel that translates a mechanic stimulus into calcium influx. We found that PIEZO1 was expressed early in erythroid progenitor cells, and investigated whether it could be involved in erythropoiesis, besides having a role in the homeostasis of mature red cell hydration. In UT7 cells, chemical PIEZO1 activation using YODA1 repressed glycophorin A expression by 75%. This effect was PIEZO1-dependent since it was reverted using specific short hairpin-RNA knockdown. The effect of PIEZO1 activation was confirmed in human primary progenitor cells, maintaining cells at an immature stage for longer and modifying the transcriptional balance in favor of genes associated with early erythropoiesis, as shown by a high GATA2/GATA1 ratio and decreased α/β-globin expression. The cell proliferation rate was also reduced, with accumulation of cells in G0/G1 of the cell cycle. The PIEZO1-mediated effect on UT7 cells required calcium-dependent activation of the NFAT and ERK1/2 pathways. In primary erythroid cells, PIEZO1 activation synergized with erythropoietin to activate STAT5 and ERK, indicating that it may modulate signaling pathways downstream of erythropoietin receptor activation. Finally, we studied the in-vitro erythroid differentiation of primary cells obtained from 14 PIEZO1-mutated patients, from 11 families, carrying ten different mutations. We observed a delay in erythroid differentiation in all cases, ranging from mild (n=3) to marked (n=8). Overall, these data demonstrate a role for PIEZO1 during erythropoiesis, since activation of PIEZO1 - both chemically and through activating mutations - delays erythroid maturation, providing new insights into the pathophysiology of hereditary xerocytosis.

We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a ‘Gardos channelopathy’. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.

Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level 4 (P=0.05) and a hepcidin:ferritin ratio 2000 pg/mL and a hepcidin:ferritin ratio

Gaucher disease (GD) is an inherited deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in tissues such as the spleen, liver, and bone marrow. The resulting lipid-laden macrophages lead to the appearance of “Gaucher cells”. Anemia associated with an unexplained hyperferritinemia is a frequent finding in GD, but whether this pathogenesis is related to an iron metabolism disorder has remained unclear. To investigate this issue, we explored the iron status of a large cohort of 90 type I GD patients, including 66 patients treated with enzyme replacement therapy. Ten of the patients treated with enzyme replacement were followed up before and during treatment. Serum levels of hepcidin, the iron regulatory peptide, remained within the physiological range, while the transferrin saturation was slightly decreased in children. Inflammation-independent hyperferritinemia was found in 65% of the patients, and Perl’s staining of the spleen and marrow smear revealed iron accumulation in Gaucher cells. Treated patients exhibited reduced hyperferritinemia, increased transferrin saturation and transiently increased systemic hepcidin. In addition, the hepcidin and ferritin correlation was markedly improved, and, in most patients, the hemoglobin level was normalized. To further explore eventual iron sequestration in macrophages, we produce a Gaucher cells model by treating the J774 macrophage cell line with a glucocerebrosidase inhibitor and showed induced local hepcidin and membrane retrieval of the iron exporter, ferroportin. These data reveal the involvement of Gaucher cells in abnormal iron sequestration, which may explain the mechanism of hyperferritinemia in GD patients. Local hepcidin-ferroportin interaction was involved in this pathogenesis.

The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P

Gaucher disease is a rare inherited disease caused by a deficiency in glucocerebrosidase leading to lipid accumulation in cells of mononuclear-macrophage lineage known as Gaucher cells. Visceral enlargement, bone involvement, mild anemia and thrombocytopenia are the major manifestations of Gaucher disease. We have previously demonstrated that the red blood cells from patients exhibit abnormal properties, which indicates a new role in Gaucher disease pathophysiology. To investigate whether erythroid progenitors are affected, we examined the in vitro erythropoiesis from the peripheral CD34+ cells of patients and controls. CD34− cells were differentiated into macrophages and co-cultivated with erythroblasts. We showed an accelerated differentiation of erythroid progenitors without maturation arrest from patients compared to controls. This abnormal differentiation persisted in the patients when the same experiments were performed without macrophages, which strongly suggested that dyserythropoiesis in Gaucher disease is secondary to an inherent defect in the erythroid progenitors. The accelerated differentiation was associated with reduced cell proliferation. As a result, less mature erythroid cells were generated in vitro in the Gaucher disease cultures compared to the control. We then compared the biological characteristics of untreated patients according to their anemic status. Compared to the non-anemic group, the anemic patients exhibit higher plasma levels of growth differentiation factor-15, a marker of ineffective erythropoiesis, but they had no indicators of hemolysis and similar reticulocyte counts. Taken together, these results demonstrated an unsuspected dyserythropoiesis that was independent of the macrophages and could participate, at least in part, to the basis of anemia in Gaucher disease.

Background Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on these reductions/improvements have been limited to case reports and small studies.Design and Methods To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade® (EPIC) study using International Working Group 2006 criteria.Results Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.Conclusions This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.

Background β-thalassemia is a rare disease in France, encountered mainly in patients originating from Italy and North Africa. In the setting of the recent French plan for rare diseases, a National Registry for thalassemia has been developed since 2005. Epidemiological and clinical data have been collected on living patients with β-thalassemia major or intermedia, including those who underwent hematopoietic stem cell transplantation.Design and Methods A standardized questionnaire was sent to clinicians throughout the national professional networks involved in the management of thalassemic patients and data were updated every 18 months. A cross-sectional study was performed in February 2009.Results Data on 378 patients (267 with thalassemia major) with a median age of 20 were recorded. Hematopoietic stem cell transplantation was performed in 52 patients. Stature, rates of parenthood, splenectomy, and cholecystectomy were no different between non-transplanted thalassemia major and thalassemia intermedia patients, after adjustment for age. Among the 215 non-transplanted thalassemia major patients, the median serum ferritin level was 1240 ng/mL and the rates of iron-related complications were 10%, 6%, 10% and 48% for cardiac failure, diabetes, hypothyroidism, and hypogonadism, respectively. From 2005 to 2008, a dramatic switch in chelation treatment, from deferoxamine to deferasirox, was observed.Conclusions The rates of complications of iron overload in French thalassemia major patients appeared similar to those reported in other developed countries in which this condition is not endemic. There were no significant differences in height and parenthood rates between patients with the major and the intermedia forms of the disease, underlining the progress in clinical care. Future developments will focus on mortality and morbidity under oral chelation treatment.

Background Following a clinical evaluation of deferasirox (Exjade®) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (aged ≥2 years) with transfusional hemosiderosis from various types of anemia.Design and Methods The recommended initial dose was 20 mg/kg/day for patients receiving 2–4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline.Results The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (−264 ng/mL; P5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%).Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821).

We quantified and studied the impact of post transfusional iron overload alone in post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 μg/L. Liver iron content (LIC) was 117 μmoles/gdw. Correlation RBCs and ferritin was (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal ferritin group in terms of RBCs transfused (p