Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Busulfan-Based and Treosulfan-Based Myeloablative Conditioning for Allogeneic Transplantation in Children with Thalassemia Major: a Single-Center Experience From Southern Turkey.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant is the only curative treatment for patients with transfusion-dependent thalassemia major. In recent years, a number of novel approaches have improved patient outcomes and quality of life by minimizing the toxicity of conditioning regimens. The objective of this study was to compare the role of treosulfan- and busulfan-based conditioning in transfusion-dependent thalassemia. MATERIALS AND METHODS: Data were collected retrospectively on 121 children with beta thalassemia major who underwent hematopoietic stem cell transplant using treosulfan-based (n = 37) or busulfan-based (n = 84) conditioning regimens between 2012 and 2022. RESULTS: Two-year overall survival was 87.5% in the busulfan-based conditioning group and 91.1% in the treosulfan-based conditioning group.The group given the busulfan regimen compared with treosulfan regimen had significantly increased number of side effects (58.3% vs 21.6%, respectively; P < .001). When the busulfan-based regimen by level was evaluated, we observed no significant differences between the frequency of side effects according to drug serum levels. In addition, no significant differences were shown between the 2 regimen groups for cumulative incidence of acute and chronic graft-versus-host disease. CONCLUSIONS: The safety and effectiveness of a treosulfan-based myeloablative conditioning regimen has been confirmed by ourretrospective investigation of pediatric patients with beta thalassemia.

Effects of a supervised therapeutic exercise program on musculoskeletal health and gait in patients with haemophilia: A pilot study.

INTRODUCTION: Episodes of bleeding in patients with haemophilia (PwH) are associated with haemophilic arthropathy, limitations in physical performance, reduced quality of life (QoL), and gait disorders. AIM: This non-randomized, controlled, interventional, prospective, single-centre pilot study aimed to assess the effects of an 8-week supervised therapeutic exercise program on musculoskeletal health, gait kinematic parameters (GKP), functional capacity, and QoL in adult PwH. METHODS: Nineteen PwH were allocated to an exercise group (n = 10) or a control group (n = 9). The patients in the exercise group followed an 8-week supervised therapeutic exercise program. The Haemophilia Joint Health Score (HJHS), a two-dimensional video-based gait kinematic analysis (2D-GKA), the 6-min walking test (6MWT), and the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-Qol) were used as the outcome measures at baseline, after the exercise program (at the 8th week), and at the 6th-month follow-up. RESULTS: A significant improvement was observed in the exercise group in the HJHS-Total and Haem-A-Qol Total scores and the 6MWT value after the exercise program. Moreover, the 2D-GKA revealed improvement in most of the GKP (knee extension during the midstance and late swing phases, ankle dorsiflexion during the midstance phase, and ankle plantar flexion during the preswing phase). However, the gain obtained by the exercise program was not maintained at the 6th-month follow-up for the HJHS-Total and Hem-A-QoL-Total scores and GKP. CONCLUSION: The 8-week supervised therapeutic exercise program was successful in achieving improvement in joint health, GKP, functional capacity, and QoL in PwH.

The effects of manual therapy and exercises on pain, muscle strength, joint health, functionality and quality of life in haemophilic arthropathy of the elbow joint: A randomized controlled pilot study.

INTRODUCTION: Effective physiotherapy interventions are required for haemophilic arthropathy (HA) of the elbow due to its biomechanical differences and contribution to upper limb functionality. AIM: To investigate the effects of manual therapy & exercises on bleeding frequency, pain, range of motion (ROM), strength, joint health, functionality and quality of life (QoL) in HA of the elbow. METHODS: Seventeen participants with HA of the elbow were randomized as Manual Therapy & Exercises Group (MTEG = 9) and Home Exercises Group (HEG = 8). Soft tissue mobilization, joint traction (grade I-II) and Mulligan's mobilization with movement as manual therapy, and stretching/strengthening exercises were applied to MTEG, while HEG had only same exercises as home programme. The interventions lasted 3 days/weekly for 5 weeks. Bleeding frequency was evaluated with patients' records; pain with Numeric Pain Scale; ROM with goniometer; strength with digital dynamometer; joint health with HJHS; functionality with Quick-Disability of Arm, Shoulder and Hand questionnaire; and QoL with Oxford Elbow Score. RESULTS: Bleeding frequency and activity pain were decreased, while elbow ROMs and flexor strength were increased in MTEG (P Ë‚ 0.05). Also significantly improvements were seen in joint health, functionality and QoL in MTEG. HEG showed improvements in activity pain, QoL and some ROMs. MTEG had better results in ROMs, joint health and functionality (P Ë‚ 0.05). CONCLUSION: Manual therapy & exercises may be used without causing bleeding and pain to increase the functionality, joint health and QoL, and is superior to home exercise for joint health and functionality. Home exercises may be ameliorated in pain, QoL and some ROMs.

The effects of manual therapy on musculoskeletal system, functional level, joint health and kinesiophobia in young adults with severe haemophilia: A randomized pilot study.

INTRODUCTION: The effects of manual therapy (MT) on joint health and functional level in haemophilic arthropathy (HA) have relatively under-explored. AIM: To investigate the effects of MT in HA of lower limb joints on musculoskeletal system, functional level, Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS) and kinesiophobia. METHODS: Seventeen patients were randomized to the control group (CG = 9) and manual therapy group (MTG = 8). The number of haemarthrosis (NoH) was recorded from the diaries. Range of motion (ROM), strength and pain intensity were measured using goniometer, digital dynamometer and visual analogue scale, respectively. Joint health was evaluated with HJHS, functional independence with FISH, and kinesiophobia with Tampa Scale. Functional Reach (FR), Timed Up-Go (TUG) and 5-Times Sit-to-Stand (5*STS) tests were used to evaluate functional level. Home exercises were given to both groups. Additionally, myofascial release techniques and mobilizations were applied to MTG. Interventions were applied 3 d/weekly for 5 weeks. Assessments were performed at baseline and after treatment. RESULTS: ROM, strength, activity pain, HJHS and FISH were improved in MTG (p˂0.05). Ankle NoH, 5*STS and FR were developed in both groups (p˂0.05), but kinesiophobia, TUG and knee NoH were not significant. Although improvements were observed in favour of MTG in HJHS, FR, activity pain and ankle strength/ROM (p˂0.05), no significant difference was found in FISH, kinesiophobia, TUG, 5*STS, resting pain and knee strength. CONCLUSION: Reduction in ankle NoH indicated that both interventions were safe. The use of MT in HA of lower limb joints was an effective physiotherapy approach to improve functional level, joint health and functional independence.