florio® HAEMO: A Longitudinal Survey of Patient Preference, Adherence and Wearable Functionality in Central Europe.

INTRODUCTION: florio® HAEMO is a hemophilia treatment monitoring application (app) offering activity tracking and wearable device connectivity. Its use might support everyday activities for people with hemophilia. The aim of this study was to evaluate user satisfaction, long-term usage and the impact on data entry when pairing a wearable with a hemophilia monitoring app. METHODS: This is a follow-up of a two-part user survey conducted in Central Europe. People with hemophilia and parents/caregivers of children with hemophilia using florio HAEMO and who completed part one were invited to complete a second online questionnaire at least 4 months later. RESULTS: Fifty participants (83.3%) who completed part one of the survey continued to use the florio HAEMO app and completed part two. Of 14 participants who chose to use the app with a wearable, more than half (57.1%) were aged between 13 and 25 years. Overall, the results demonstrated that florio HAEMO is very easy or rather easy to use, especially for individuals pairing the app with a wearable. Most people using a wearable indicated that florio HAEMO was very or rather important in bringing certainty to daily activities (85.7%). Notably, 14 of 36 (38.9%) non-wearable users indicated that they would prefer to pair the app with a wearable in the future. CONCLUSIONS: Adherence to the florio HAEMO app is maintained over an extended period of use. Pairing the app with a wearable might enable easier access to app features, increase data entry motivation and provide more certainty about daily activities for people with hemophilia.

Changes in Nutritional Intake, Body Composition, and Handgrip Strength in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Retrospective Study.

Patients who undergo autologous hematopoietic stem cell transplantation (autoHSCT) often experience reduced oral intake and wasting. We examined their daily nutritional intake, assessed alterations in body composition and muscle strength, and explored associations between decreased nutritional intake and treatment outcomes. This retrospective study included 64 patients. Their food record charts and parenteral nutrition (PN) prescriptions from medical records were used to assess nutritional intake. Body composition and handgrip strength data were obtained from dietitian records. Patients consumed >75% of their nutritional requirements through an oral diet in 6.7 days, 50-75% in 4.8 days, 25-50% in 5.0 days, and <25% in 3.1 days. The average oral intake was 62% of the requirement and was partially supplemented with PN. Patients experienced a mean decrease in body weight of 2.9 ± 3.0 kg, with 2.3 ± 3.4 kg of lean mass, and a mean reduction in handgrip strength of 3.5 ± 3.6 kg. We found a positive correlation of caloric deficits with weight loss and handgrip strength reduction and negative correlation with time to neutrophil engraftment and duration of hospitalization. This study highlighted a notable reduction in oral nutritional intake following autoHSCT. While caloric deficits might affect outcomes, further investigation is warranted to explore this observation.

Maternal Fatigue after Postpartum Anemia Treatment with Intravenous Ferric Carboxymaltose vs. Intravenous Ferric Derisomaltose vs. Oral Ferrous Sulphate: A Randomized Controlled Trial.

(1) Background: Postpartum anemia is a common maternal complication and is recognized as a cause of impaired quality of life, reduced cognitive abilities, and fatigue. Efficient iron supplementation for the treatment of postpartum anemia is an essential component of high-quality maternal care. The optimal mode of iron supplementation has not been determined yet, whether oral or intravenous. The objective of this study was to compare postpartum anemia treatment with intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate. (2) Methods: A single-center, open-label, randomized controlled trial. Women with hemoglobin < 100 g/L within 48 h postpartum were randomly allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose, or oral ferrous sulfate. Intravenous iron was given in one or two doses, while ferrous sulfate was given as two 80 mg tablets once daily. The primary outcome was maternal fatigue measured by the Multidimensional Fatigue Inventory (MFI) six weeks postpartum. Hemoglobin, ferritin, and transferrin saturation levels were analyzed as secondary outcomes. A Kruskal-Wallis test was used for group comparison (p < 0.05 significant). (3) Results: Three hundred women were included. The MFI score at six weeks postpartum did not differ between groups (median 38 (inter-quartile range (IQR) 29-47) in the ferric carboxymaltose group, median 34 (IQR 26-42) in the ferric derisomaltose group, and median 36 (IQR 25-47) in the ferrous sulfate group; p = 0.26). Participants receiving oral iron had lower levels of hemoglobin (135 (131-139) vs. 134 (129-139) vs. 131 (125-137) g/L; p = 0.008), ferritin (273 (198-377) vs. 187 (155-246) vs. 24 (17-37) µg/L; p < 0.001) and transferrin saturation (34 (28-38) vs. 30 (23-37) vs. 24 (17-37) %; p < 0.001) than those receiving ferric carboxymaltose or ferric derisomaltose. (4) Conclusions: Intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate had similar impacts on maternal fatigue at six weeks postpartum despite improved laboratory parameters in the intravenous groups.

Management and Outcomes of Invasive Procedures in Individuals with Hemophilia A on Emicizumab Prophylaxis: A Single Center Experience.

Prophylactic treatment with emicizumab has become an important and effective bleeding prevention for people with hemophilia A (PwHA). Perioperative management of PwHA using emicizumab prophylaxis is still challenging due to a lack of experience. Medical records of perioperative management and outcomes were reviewed, and data were collected for adult PwHA receiving emicizumab and undergoing surgical procedures between August 2019 and July 2022 at the University Medical Center Ljubljana. Twelve surgical procedures were performed in eight PwHA (one with FVIII inhibitors) while on emicizumab prophylaxis. Three minor procedures included cataract surgery, cystoscopic lithotripsy, and percutaneous coronary intervention. Nine major surgeries included four osteosyntheses, necrectomy of chronic osteomyelitis with new ankle arthrodesis, two below-knee amputations, total knee replacement, and placement of ventriculostomy after a spontaneous intraventricular hemorrhage. No major bleeds, thrombotic events or deaths, or new inhibitors appeared. Our real-world experience demonstrates that minor and major surgeries can be performed safely in PwHA on emicizumab prophylaxis. Additional data are needed to optimize dosing/duration of additional hemostatic agents in diverse invasive procedures and complex clinical situations.

Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations.

INTRODUCTION: Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is complement-mediated due to the lack of complement inhibitors in the hemopoietic cell membranes, making complement inhibition the best approach to manage PNH. Three complement inhibitors are approved by the European Medicines Agency as targeted therapy for PNH: eculizumab and ravulizumab, two humanized monoclonal antibodies targeting the same complement 5 (C5) epitope, approved in 2007 and 2019, respectively, and the more recently approved cyclic peptide, the complement 3 (C3) inhibitor pegcetacoplan. Although national and international PNH treatment guidelines exist, they do not take into consideration the latest clinical trial evidence. Given the lack of evidence-based data for some clinical situations encountered in real life, we identified specific populations of patients who may benefit from switching to proximal C3 from terminal C5 inhibition. METHODS: The expert recommendations presented here were created using a Delphi-like process by a group of expert PNH specialists across Central Europe. Based on an initial advisory board meeting discussion, recommendations were prepared and reviewed as part of a Delphi survey to test agreement. RESULTS: Using a systematic approach, literature databases were searched for relevant studies, and 50 articles were reviewed by the experts and included as supporting evidence. CONCLUSION: Implementation of these recommendations uniformly across healthcare institutions will promote the best use of complement inhibition in managing PNH, and has the potential to positively impact patient outcomes in Central Europe and worldwide.

Applicability of the European Society of Cardiology Guidelines on the management of acute coronary syndromes to older people with haemophilia A - A modified Delphi consensus by the ADVANCE Working Group.

INTRODUCTION: As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population. AIM: To review the guidelines and propose relevant adaptations for PWHA without inhibitors who are treated with prophylaxis and present with ACS. METHODS: As part of the ADVANCE Group, 20 European haemophilia experts used a modified Delphi approach to develop and gain consensus on proposed adaptations of the ESC guidelines for PWHA without inhibitors. RESULTS: Of the 32 Class I recommendations across both guidelines, adaptions were considered necessary and proposed for 15. The adaptions highlight the need to provide sufficient FVIII trough levels at the time of antithrombotic treatment in people with haemophilia A (HA) without inhibitors. Patients receiving emicizumab prophylaxis and requiring oral anticoagulation therapy or combined single antiplatelet plus oral anticoagulation therapy will require additional FVIII replacement therapy. CONCLUSION: In the absence of high-quality clinical evidence, the combined expert opinion used to develop these adaptions to the current ESC guidelines may help to guide clinicians in their treatment decisions when a PWHA presents with ACS.

Sixth Åland Island Conference on von Willebrand disease.

INTRODUCTION: The sixth Åland Islands Conference on von Willebrand disease (VWD) on the Åland Islands, Finland, was held from 20 to 22 September 2018. AIM: The meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD. RESULTS AND DISCUSSION: The topics covered both clinical aspects of disease management, and biochemical and laboratory insights into the disease. The clinical topics discussed included epidemiology, diagnosis and treatment of VWD in different countries, management of children with VWD, bleeding control during surgery, specific considerations for the management of type 3 VWD and bleeding control in women with VWD. Current approaches to the management of acquired von Willebrand syndrome were also discussed. Despite significant advances in the understanding and therapeutic options for VWD, there remain many challenges to be overcome in order to optimise patient care. In comparison with haemophilia A, there are very few registries of VWD patients, which would be a valuable source of data on the condition and its management. VWD is still underdiagnosed, and many patients suffer recurrent or severe bleeding that could be prevented. Awareness of VWD among healthcare practitioners, including non-haematologists, should be improved to allow timely diagnosis and intervention. Diagnosis remains challenging, and the development of fast, simple assays may help to facilitate accurate and rapid diagnosis of VWD.

Changing paradigms of hemophilia care across larger specialized treatment centers in the European region.

Introduction: In early 2021, the European Collaborative Haemophilia Network (ECHN) conducted a survey to determine whether the paradigms of care across the European region have changed with the introduction of novel therapies for people with hemophilia. Methods: We conducted a survey in 19 ECHN centers from 17 countries in the European region. The aim was to track recent changes in the hemophilia treatment landscape, determine the impact of these changes on hemophilia treatment centers and comprehensive care centers in the region, and to look into the future of care as applied to people with hemophilia. The survey was structured to include three key areas: demographics and organization; current challenges and opportunities; and future directions. Discussion: Our survey provides a snapshot of the current approach to hemophilia treatment that highlights a move toward preventive, rather than reactive care, but that also raises a number of key concerns related to costs and accessibility (particularly as related to novel therapies), time limitations for clinical research, and ongoing issues regarding human resources (particularly in terms of new doctors entering the field) and availability of laboratory resources as the use of novel therapies (some with unique modes of action and unusual adverse events, some with specialized monitoring requirements) becomes commonplace. Conclusion: While our survey suggests that specialized care will continue to play a central role in the management of hemophilia, the standards and protocols, as well as the centers themselves, will have to continue to evolve if they are to continue to provide the highest level of care. To meet this requirement, there is a clear need for engaging, ongoing education programs for healthcare professionals working in the field of hemophilia that can be adjusted to the changing landscape of hemophilia therapy and monitoring.

First experience of a hemophilia monitoring platform: florio HAEMO.

Background: florio HAEMO is a new hemophilia treatment monitoring application consisting of a patient smartphone application (app) and a web-based dashboard for healthcare professionals, providing several novel features, including activity tracking, wearable connectivity, kids and caregiver mode, and real-time pharmacokinetic factor level estimation. Objectives: To assess intuitiveness, ease-of-use, and patient preference of florio HAEMO in Central Europe using a cross-sectional survey. Methods: This survey was conducted in six Central European countries between 9 December 2020 and 24 May 2021. The online questionnaire included 17 questions about overall satisfaction, ease-of-use, intuitiveness, and patient preference. Adults or children with hemophilia on regular prophylaxis and using the florio HAEMO app for a minimum of 1 week were invited to complete the online questionnaire by their treating physician. Results: Sixty-six participants took part in the survey. The median duration for all respondents using the florio HAEMO app was 3 to 4 weeks. Overall, 89.4% of users reported being very satisfied or rather satisfied after using florio HAEMO. Of the 23 respondents who had switched from another hemophilia app, 87.0% indicated that they strongly preferred or preferred using florio HAEMO. Most florio HAEMO users reported that the app was very easy or rather easy to use (97.0%) and intuitive (94.0%). florio HAEMO had a positive impact on daily living, with 78.8% of users reporting that the app was very important or rather important to them. Conclusions: This survey suggests that florio HAEMO is an easy-to-use and intuitive app to assist self-management of home prophylaxis.

Is It Possible to Predict Clonal Thrombocytosis in Triple-Negative Patients with Isolated Thrombocytosis Based Only on Clinical or Blood Findings?

JAK2, MPL, and CALR mutations define clonal thrombocytosis in about 90% of patients with sustained isolated thrombocytosis. In the remainder of patients (triple-negative patients) diagnosing clonal thrombocytosis is especially difficult due to the different underlying conditions and possible inconclusive bone marrow biopsy results. The ability to predict patients with sustained isolated thrombocytosis with a potential clonal origin has a prognostic value and warrants further examination. The aim of our study was to define a non-invasive clinical or blood parameter that could help predict clonal thrombocytosis in triple-negative patients. We studied 237 JAK2 V617-negative patients who were diagnosed with isolated thrombocytosis and referred to the haematology service. Sixteen routine clinical and blood parameters were included in the logistic regression model which was used to predict the type of thrombocytosis (reactive/clonal). Platelet count and lactate dehydrogenase (LDH) were the only statistically significant predictors of clonal thrombocytosis. The platelet count threshold for the most accurate prediction of clonal or reactive thrombocytosis was 449 × 109/L. Other tested clinical and blood parameters were not statistically significant predictors of clonal thrombocytosis. The level of LDH was significantly higher in CALR-positive patients compared to CALR-negative patients. We did not identify any new clinical or blood parameters that could distinguish clonal from reactive thrombocytosis. When diagnosing clonal thrombocytosis triple-negative patients are most likely to be misdiagnosed. Treatment in patients with suspected triple negative clonal thrombocytosis should not be delayed if cardiovascular risk factors or pregnancy coexist, even in the absence of firm diagnostic criteria. In those cases the approach "better treat more than less" should be followed.

Health-Related Quality of Life in Patients with Haemophilia and Its Association with Depressive Symptoms: A Study in Croatia and Slovenia.

BACKGROUND: There are only a few studies in patients with haemophilia (PWH) that examined both quality of life and depressive symptoms, with only few studies examining their association. Aim of this study was to examine the association between depressive symptoms and health-related quality of life (HRQoL) in PWH from Croatia and Slovenia. SUBJECTS AND METHODS: A total of 112 adult PWH on prophylactic (73%) or on-demand (27%) treatment were included in the study (median age 46 years, range 18-73 years). Depressive symptoms were assessed with BDI-II, HRQoL with SF-36v2, demographic and socioeconomic data were collected using a questionnaire, and clinical data were obtained from medical records. RESULTS: All HRQoL scores were significantly negatively correlated with BDI-II in the -0.42 to -0.70 range (all p<0.05). Socio-demographic and clinical variables explained 28-51% of HRQoL variance scores. Depressive symptoms explained additional variance for six HRQoL domain scores, with incremental variance being larger for mental domain scores (ranging between 10-27%), and for Mental Component Summary score (26%). CONCLUSIONS: This study's findings support that having depressive symptoms is associated with HRQoL of PWH, more so in the mental health than in the physical health domains.

Identification of Variants Associated With Rare Hematological Disorder Erythrocytosis Using Targeted Next-Generation Sequencing Analysis.

An erythrocytosis is present when the red blood cell mass is increased, demonstrated as elevated hemoglobin and hematocrit in the laboratory evaluation. Congenital predispositions for erythrocytosis are rare, with germline variants in several genes involved in oxygen sensing (VHL, EGLN1, and EPAS1), signaling for hematopoietic cell maturation (EPOR and EPO), and oxygen transfer (HBB, HBA1, HBA2, and BPGM) that were already associated with the eight congenital types (ECYT1-8). Screening for variants in known congenital erythrocytosis genes with classical sequencing approach gives a correct diagnosis for only up to one-third of the patients. The genetic background of erythrocytosis is more heterogeneous, and additional genes involved in erythropoiesis and iron metabolism could have a putative effect on the development of erythrocytosis. This study aimed to detect variants in patients with yet unexplained erythrocytosis using the next-generation sequencing (NGS) approach, targeting genes associated with erythrocytosis and increased iron uptake and implementing the diagnostics of congenital erythrocytosis in Slovenia. Selected 25 patients with high hemoglobin, high hematocrit, and no acquired causes were screened for variants in the 39 candidate genes. We identified one pathogenic variant in EPAS1 gene and three novel variants with yet unknown significance in genes EPAS1, JAK2, and SH2B3. Interestingly, a high proportion of patients were heterozygous carriers for two variants in HFE gene, otherwise pathogenic for the condition of iron overload. The association between the HFE variants and the development of erythrocytosis is not clearly understood. With a targeted NGS approach, we determined an actual genetic cause for the erythrocytosis in one patient and contributed to better management of the disease for the patient and his family. The effect of variants of unknown significance on the enhanced production of red blood cells needs to be further explored with functional analysis. This study is of great significance for the improvement of diagnosis of Slovenian patients with unexplained erythrocytosis and future research on the etiology of this rare hematological disorder.

Congenital erythrocytosis - A condition behind recurrent thromboses: A case report and literature review.

Congenital erythrocytosis (CE) is an extremely rare disease and an infrequent cause of heamoglobin and haematocrit elevation. Genetic testing of CE is not widely available. Patients in whom a cause of erythrocytosis is not identified are classified as idiopathic erythrocytosis (IE) patients. In some types of CE thrombotic events have been reported but there is little hard evidence to advise on management in asymptomatic patients. Similarly is true for patients with IE. We describe a young patient who suffered several thromboembolic complications before the diagnosis of CE type 4 was established.

Diagnosis and management of non-clonal erythrocytosis remains challenging: a single centre clinical experience.

Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb > 185 g/L and/or Hct > 0.52 in men and Hb > 165 g/L and/or Hct > 0.48 in women on two visits ≥ two months apart, thus confirming true erythrocytosis. Secondly, polycythaemia vera was excluded and secondary causes of erythrocytosis (SE) identified. Thirdly, idiopathic erythrocytosis patients (IE) were referred to next-generation sequencing for possible genetic background evaluation. Of the 116 patients, 75 (65%) are men and 41 (35%) women, with non-clonal erythrocytosis 34/116 (29%) had SE, 15/116 (13%) IE and 67/116 (58%) stayed incompletely characterized (ICE). Patients with SE were significantly older and had significantly higher Hb and Hct compared to patients with IE. Most frequently, SE was attributed to obstructive sleep apnoea and smoking. Phlebotomies were performed in 56, 53 and 40% of patients in the SE, IE, and ICE group, respectively. Approx. 70% of patients in each group received aspirin. Thrombotic events were registered in 12, 20 and 15% of SE, IE and ICE patients, respectively. Congenital erythrocytosis type 4 (ECYT4) was diagnosed in one patient. The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm.

Association between reported medication adherence and health-related quality of life in adult patients with haemophilia.

Background Medication adherence is an important issue, not just health-related, for patients with haemophilia. Poor medication adherence to long-term therapies limits the potential of effective treatments to improve patients' health-related quality of life. Objective The aim of this study was to investigate the association of reported medication adherence and health-related quality of life in patients with haemophilia. Setting Data were collected from patients at University Hospital Centre Zagreb, Croatia and at University Medical Centre Ljubljana, Slovenia. Method Adult male patients with severe or moderate haemophilia receiving prophylactic treatment were eligible for the study. Main outcome measure Implementation phase of medication adherence was assessed with the self-reported VERITAS-Pro instrument and health-related quality of life with SF-36v2. Results A total of 82 participants were included in the study (median age was 44.50, range 18-73 years). The majority of our participants reported being adherent to medication (83%). Participants showed better health in the mental health domains and Mental Component Summary than in the physical health domains and Physical Component Summary. After controlling for demographic, socioeconomic and clinical predictors, better reported medication adherence explained an additional 4-6% of better health variance in Bodily Pain and Social Functioning domains and Mental Component Summary. Conclusion We found that reported medication adherence can contribute to better health-related quality of life in patients with haemophilia. Since life with a chronic condition is demanding, it is an important finding that medication adherence to replacement therapy can improve life conditions for patients with haemophilia.

Genetic analysis of 39 erythrocytosis and hereditary hemochromatosis-associated genes in the Slovenian family with idiopathic erythrocytosis.

BACKGROUND: Erythrocytosis is a condition with an excessive number of erythrocytes, accompanied by an elevated haemoglobin and/or haematocrit value. Congenital erythrocytosis has a diverse genetic background with several genes involved in erythropoiesis. In clinical practice, nine genes are usually examined, but in approximately 70% of patients, no causative mutation can be identified. In this study, we screened 39 genes, aiming to identify potential disease-driving variants in the family with erythrocytosis of unknown cause. PATIENTS AND METHODS: Two affected family members with elevated haemoglobin and/or haematocrit and negative for acquired causes and one healthy relative from the same family were selected for molecular-genetic analysis of 24 erythrocytosis and 15 hereditary haemochromatosis-associated genes with targeted NGS. The identified variants were further analysed for pathogenicity using various bioinformatic tools and review of the literature. RESULTS: Of the 12 identified variants, two heterozygous variants, the missense variant c.471G>C (NM_022051.2) (p.(Gln157His)) in the EGLN1 gene and the intron variant c.2572-13A>G (NM_004972.3) in the JAK2 gene, were classified as low-frequency variants in European population. None of the two variants were present in a healthy family member. Variant c.2572-13A>G has potential impact on splicing by one prediction tool. CONCLUSION: For the first time, we included 39 genes in the erythrocytosis clinical panel and identified two potential disease-driving variants in the Slovene family studied. Based on the reported functional in vitro studies combined with our bioinformatics analysis, we suggest further functional analysis of variant in the JAK2 gene and evaluation of a cumulative effect of both variants.

Erythrocytosis: genes and pathways involved in disease development.

Erythrocytosis is a blood disorder characterised by an increased red blood cell mass. The most common causes of erythrocytosis are acquired and caused by diseases and conditions that are accompanied by hypoxaemia or overproduction of erythropoietin. More rarely, erythrocytosis has a known genetic background, such as for polycythaemia vera and familial erythrocytosis. The majority of cases of polycythaemia vera are associated with acquired variants in JAK2, while familial erythrocytosis is a group of congenital disorders. Familial erythrocytosis type 1 is associated with hypersensitivity to erythropoietin (variants in EPOR), types 2-5 with defects in oxygen-sensing pathways (variants in VHL, EGLN1, EPAS1, EPO), and types 6-8 with an increased affinity of haemoglobin for oxygen (variants in HBB, HBA1, HBA2, BPGM). Due to a heterogenic genetic background, the causes of disease are not fully discovered and in more than 70% of patients the condition remains labelled idiopathic.The transfer of next-generation sequencing into clinical practice is becoming a reality enabling detection of various variants in a single rapid test. In this review, we describe the current research on erythrocytosis gene variants and the mechanisms associated with disease development, along with the currently used diagnostic tests.

Detection and evaluation of haemophilic arthropathy: Which tools may be considered more reliable.

INTRODUCTION: Progressive arthropathy is the main cause of morbidity in patients with severe haemophilia. Diagnostic imaging can detect even subclinical arthropathy and impact prophylactic treatment. However, in most clinical settings the regular joint evaluation and follow-up are based on clinical evaluation and patient's personal reporting of problems, while diagnostic imaging is not regularly employed. AIM: The aim of our prospective study was to assess how ultrasound (US), clinical examination, patient's subjective assessment and certain laboratory biomarkers correlate with magnetic resonance imaging (MRI) for detection and evaluation of haemophilic arthropathy in order to determine which tool is the most reliable. METHODS: The study included 30 patients with severe haemophilia (age range 16-49 years). MRI (IPSG), US (HEAD-US), clinical examination (HJHS 2.1) and patient's subjective assessment of elbows, knees and ankles were performed; additionally, blood samples for laboratory analysis were taken (s-25-OH vitamin D, s-ferritin, s-C-terminal telopeptide of type I collagen, s-N-terminal propeptide of type I procollagen and s-cartilage oligomeric matrix protein). MRI results were used as a reference standard for joint status. Pearson's r was used to assess correlation of other methods with MRI. RESULTS: The correlation with MRI was the highest for US (r = .92), considerably higher than for clinical evaluation (r = .62) and patient's subjective assessment (r = .66). There was no correlation between the presence or degree of haemophilic arthropathy and any of the laboratory biomarkers. CONCLUSION: The results of our study warrant the inclusion of US into the regular follow-up of patients with severe haemophilia, where the equipment and staffing permit.

Feasibility and safety of exercise training and nutritional support prior to haematopoietic stem cell transplantation in patients with haematologic malignancies.

BACKGROUND: Prehabilitation with regular exercise and nutritional care for patients undergoing surgeries for malignant disease was recently introduced to increase physiologic reserve prior to the procedure, accelerate recovery and improve outcomes. This study aimed to investigate the feasibility and safety of combined exercise training and nutritional support in patients with haematologic malignancies prior to haematopoietic stem cell transplantation (HSCT). METHODS: In this single-arm pilot study, 34 HSCT candidates were enrolled at least two weeks before admission for the procedure. Patients performed aerobic exercises at least 4 days per week for 20-30 min and strength exercises 3 days per week for 10-20 min. They received daily supplements of whey protein (0.3-0.4 g/kg body weight) and oral nutritional supplements if needed. The primary endpoints were feasibility (acceptability > 75%, attrition < 20%, adherence > 66%) and safety. The secondary endpoints were fat-free mass (FFM), muscle strength, physical performance and health-related quality of life (HRQoL) at HSCT. RESULTS: The rate of acceptability, attrition and adherence to aerobic exercise, strength exercise and protein supplement consumption was 82.4, 17.8, 71, 78 and 80%, respectively. No severe adverse events were reported. Twenty-eight patients participated in the study for a median of 6.0 weeks (range, 2-14). They performed aerobic exercises 4.5 days per week for 132 min per week and strength exercises 3.0 times per week. Patients consumed 20.7 g of extra protein daily. At the end of the programme, we recorded increases of 1.1 kg in FFM (p = 0.011), 50 m in walking distance in the 6-min walking test (6MWT) (p < 0.001), 3.3 repetitions in the 30-s chair-stand test (30sCST) score (p < 0.001) and 2.6 kg in handgrip strength (p = 0.006). The EORTC QLQ-C30 scores improved by 8.6 (p < 0.006) for global health status, 8.3 (p = 0.009) for emotional functioning, and 12.1 (p = 0.014) for social functioning. There was less fatigue, nausea and insomnia (p < 0.05). CONCLUSIONS: Our study shows that a multimodal intervention programme with partially supervised exercise training combined with nutritional support prior to HSCT is feasible and safe. Patients showed improvements in FFM, physical performance and HRQoL. Additional research is needed to assess the possible positive effects of such interventions.