Key Clinical Message: This case report and literature review examine the use of a relatively novel agent in a transfusion-dependent beta-thalassemia patient with extramedullary hematopoiesis (EMH). It examines the benefits and risks associated with its use and reviews the available literature while highlighting the drug's results in our patient with a higher risk profile. Abstract: Beta thalassemia can be complicated by EMH, which causes different symptoms based on location and size. Luspatercept is a new agent approved for transfusion-dependent thalassemia and Non-transfusion-dependent thalassemia (NTDT). Still, its use in patients with EMH was not well studied, and literature showed an increased risk of EMH expansion or development of new masses after its use. We discuss, in this case, the results of luspatercept treatment in a patient with transfusion-dependent thalassemia who is considered high risk for its use due to the patient's specific characteristics (history of symptomatic intrathoracic EMH, previous splenectomy, refusal to use antithrombotic medications). While also highlighting the benefits of using luspatercept regarding decreasing the iron overload and improving hemoglobin levels and examining how it was used safely to manage a transfusion-dependent thalassemia patient with an extramedullary hematopoiesis mass with no adverse events of note.
This report documents the treatment of a 41-year-old male with sickle cell disease (SCD) and repeated stuttering priapism using crizanlizumab, which alleviated the priapism but induced a significant vaso-occlusive crisis during the second infusion. Encouragingly, no subsequent vaso-occlusive crises occurred. However, the potential for infusion-related adverse events warrants close supervision. Further research is necessary to explore its full benefits on priapism management.
Objectives: Treatment options for preventing vaso-occlusive crises among sickle cell disease patients are on the rise, especially if hydroxyurea treatment has failed. This economic analysis is conducted to assess the comparative clinical effectiveness, safety, and acquisition cost of l-glutamine and crizanlizumab for older adolescents and adults (⩾16 years old) with sickle cell disease in Qatar, with an emphasis on treatment costs and acute pain crises. Methods: We conduct a decision-tree model, where we compare the clinical and economic outcomes of two novel Food and drug administration (FDA)-approved medications which are available in Qatar; l-glutamine and crizanlizumab over a time horizon of 1 year in a hypothetical cohort of adult sickle cell disease patients from a Qatar healthcare perspective. The main outcome is incremental cost per sickle cell disease-related acute pain crises averted. Model clinical parameters were derived from individual drug randomized trials, published literature, whereas cost parameters from Qatar healthcare payer system (2020-2021). A sensitivity analysis was carried out, and the study results were robust around model inputs. Costs were converted to 2020 US dollars. Results: Study results showed that both treatment modalities' costs were the main driver of this analysis, with an average annual cost of the treatments per patient being $189,014 for crizanlizumab (5 mg/kg), $143,798 for crizanlizumab (2.5 mg/kg), and $74,323 for l-glutamine. The probability of no first-time sickle cell disease-related vaso-occlusive crises averted was 0.001/year for glutamine, 0.26/year for crizanlizumab (5 mg/kg), and 0.34/year for crizanlizumab (2.5 mg/kg). Lower dose crizanlizumab (2.5 mg/kg) dominated the higher one (5 mg/kg). The incremental cost-effectiveness ratio of crizanlizumab (2.5 mg/kg), when compared to l-glutamine was $81,265 per sickle cell disease-related vaso-occlusive crises averted. When comparing crizanlizumab (5 mg/kg) and l-glutamine, crizanlizumab (5 mg/kg) showed higher efficacy, yet the crizanlizumab incremental cost-effectiveness ratio was at $459,620 than l-glutamine. Conclusions: Crizanlizumab (2.5 mg/kg) may be a cost-effective intervention, yet it is not the approved dose for preventing vaso-occlusive crises in adolescents and adults with sickle cell disease. Crizanlizumab (5 mg/kg) was more cost-effective than the approved l-glutamine per sickle cell disease vaso-occlusive crisis prevented. Of note, we primarily focused on modeling acute vaso-occlusive pain, which limited our ability to consider other key outcomes in sickle cell disease.
BACKGROUND: Myeloproliferative neoplasms (MPNs) are hematological disorders characterized by abnormal production of myeloid cells due to genetic mutations. Since 2013, researchers have identified somatic mutations in the Calreticulin (CALR) gene, primarily insertions or deletions, in two Philadelphia chromosome-negative MPNs; essential thrombocytosis (ET) and primary myelofibrosis (PMF), and occasionally in chronic myelomonocytic leukemia (CMML). This study aims to identify the various types of CALR mutations and their impact on CALR-positive MPN patients' clinical manifestations and outcomes. METHODS: A single-center retrospective study was conducted. The data was collected from pre-existing records. The study was carried out on Philadelphia-negative MPN patients who were being followed up on at the NCCCR (National Center for Cancer Care and Research) to assess the clinical manifestation and outcome of disease treatment. All patients included, were followed in our center between January 1, 2008, and November 20, 2021. RESULTS: A total of 50 patients with CALR-positive MPN were reviewed with a median follow-up of three years (1-11). This cohort included 31 (62%) patients with ET, 10 (20%) patients with PMF, and 9 (18%) patients with prefibrotic myelofibrosis (pre-MF). The study involved 38 (76%) male and 12 (24%) female patients. There were 16 (32%) patients diagnosed before the age of 40, 24 (48%) patients diagnosed between the ages of 40 and 60; and 10 (20%) patients diagnosed after the age of 60. Molecular analysis showed 24 (48%) patients with CALR type 1, 21 (42%) patients with CALR type 2, and 5 (10%) patients with none Type 1, none Type 2 CALR mutations. Two patients have double mutations; 1(2%) with none Type 1, none Type 2 CALR and JAK2 mutations, and 1(2%) with CALR type 1 and MPL mutations. The thrombotic events were 3 (6%) venous thromboembolisms, 3 (6%) abdominal veins thromboses, 2 (4%) strokes, and 4 (8%) ischemic cardiac events. Only 4 (8%) patients progressed to Myelofibrosis and were carrying CALR 1 mutations, and 1 (2%) patient progressed to AML with CALR 2 mutation. CONCLUSION: The data shows a significant rise in CALR-positive MPN diagnoses in younger people, emphasizing the need for a better assessment tool to improve disease management and reduce complications.
Calreticulin , Mutation , Myeloproliferative Disorders , Tertiary Care Centers , Humans , Calreticulin/genetics , Male , Female , Myeloproliferative Disorders/genetics , Middle Aged , Adult , Retrospective Studies , Qatar/epidemiology , Aged
Understanding the major factors influencing groundwater chemistry and its evolution in irrigation areas is crucial for efficient irrigation management. Major ions and isotopes (δD-H2O together with δ18O-H2O) were used to identify the natural and anthropogenic factors contributing to groundwater salinization in the shallow aquifer of the Wadi Guenniche Plain (WGP) in the Mediterranean region of Tunisia. A comprehensive geochemical investigation of groundwater was conducted during both the low irrigation season (L-IR) and the high irrigation season (H-IR). The results show that the variation range and average concentrations of almost all the ions in both the L-IR and H-IR seasons are high. The groundwater in both seasons is characterized by high electrical conductivity and CaMgCl/SO4 and NaCl types. The dissolution of halite and gypsum, the precipitation of calcite and dolomite, and Na-Ca exchange are the main chemical reactions in the geochemical evolution of groundwater in the Wadi Guenniche Shallow Aquifer (WGSA). Stable isotopes of hydrogen and oxygen (δ18O-H2O and δD-H2O) indicate that groundwater in WGSA originated from local precipitation. In the H-IR season, the δ18O-H2O and δD-H2O values indicate that the groundwater experienced noticeable evaporation. The enriched isotopic signatures reveal that the WGSA's groundwater was influenced by irrigation return flow and seawater intrusion. The proportions of mixing with seawater were found to vary between 0.12% and 5.95%, and between 0.13% and 8.42% during the L-IR and H-IR seasons, respectively. Irrigation return flow and the associated evaporation increase the dissolved solids content in groundwater during the irrigation season. The long-term human activities (fertilization, irrigation, and septic waste infiltration) are the main drives of the high nitrate-N concentrations in groundwater. In coastal irrigation areas suffering from water scarcity, these results can help planners and policy makers understand the complexities of groundwater salinization to enable more sustainable management and development.
BACKGROUND: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. OBJECTIVE: The primary objective is to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013 - December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and overall survival. METHODS: A retrospective, descriptive study of consecutive cases was conducted at Qatar's NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. RESULTS: Between 2013-2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36-95 years; p<0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases respectively, though this difference was statistically insignificant (p=0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while Lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64% respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94% versus 82%) for HL and NHL, with 5-year OS of 67% and 60% respectively. HL demonstrated higher OS throughout the study period compared to NHL (p<0.001), though median OS remained unreached. CONCLUSIONS: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar's immigration patterns.
Biodegradable polymers have gained great interest as ecofriendly packaging materials. However, addition of suitable fillers to the polymer matrix enhances their barrier and mechanical properties besides gaining new features such as bactericidal activity. This work deals with investigation of mechanical, gas/water transport properties and biodegradability performance of films based on polycaprolactone (PCL) reinforced by 1wt% of reduced graphene oxide (RGO) or modified graphene (mRG). To achieve this goal, nanosheets of RGO were firstly prepared then their surfaces were modified through in situ polymerization of hyperbranched polyester (PES) to obtain mRG. Then PCL was loaded with both fillers, and the nanocomposite films were prepared by a casting technique. Studying of the thermal properties of the films showed that the addition of RGO or mRG had no influence on the crystallinity of the PCL matrix. Although the mechanical characteristics of the PCL did not change when either filler was added, there was an increase in permeability and diffusivity in the presence of the fillers regardless of their composition. Nevertheless, the nanocomposites demonstrated antimicrobial properties against S. aureus and E. coli as models for Gram-positive and Gram-negative bacteria, respectively. The biodegradability test performed on the prepared film PCL, and those containing 1% of the filler, PCL/RGO, and PCL/mRG, emphasized that the film degradation became pronounced after three months for all samples.
The management of chronic myeloid leukemia (CML) diagnosed during pregnancy is a rare and challenging situation. We report the treatment and outcome of 87 cases diagnosed in chronic phase from 2001-2022 derived from the largest international observational registry, supported by the European LeukemiaNet (ELN), of 400 pregnancies in 299 CML women. Normal childbirth occurred in 76% without an increased rate of birth abnormalities or life-threatening events, including in patients untreated or treated with interferon-α and/or imatinib in 2nd-3rd trimester. The low birth weight rate of 12% was comparable to that seen in the normal population. Elective and spontaneous abortions occurred in 21% and 3%, respectively. The complete hematologic response rate before labor was 95% with imatinib and 47% with interferon only. No disease progression during pregnancy was observed, 28% of the patients switched their therapy at varying times after delivery. Treatment options balance the efficacy and safety for mother and infant: interferon-α can commence in the 1st trimester and continued throughout in cases of good disease control and tolerability. Because of limited placental crossing, selected tyrosine kinase inhibitors (imatinib and nilotinib) seem to be safe and effective options in 2nd and 3rd trimester while hydroxycarbamide offers few benefits.
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Humans , Female , Pregnancy , Imatinib Mesylate , Protein Kinase Inhibitors/adverse effects , Placenta , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Interferon-alpha/therapeutic use , Treatment Outcome
This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022. Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75-10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.
Anemia, Sickle Cell , Humans , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/therapy , Blood Transfusion , Hospitalization
In a global context, trace element pollution assessment in complex multi-aquifer groundwater systems is important, considering the growing concerns about water resource quality and sustainability worldwide. This research addresses multiple objectives by integrating spatial, chemometric, and indexical study approaches, for assessing trace element pollution in the multi-aquifer groundwater system of the Al-Hassa Oasis, Saudi Arabia. Groundwater sampling and analysis followed standard methods. For this purpose, the research employed internationally recognized protocols for groundwater sampling and analysis, including standardized techniques outlined by regulatory bodies such as the United States Environmental Protection Agency (USEPA) and the World Health Organization (WHO). Average values revealed that Cr (0.041) and Fe (2.312) concentrations surpassed the recommended limits for drinking water quality, posing serious threats to groundwater usability by humans. The trace elemental concentrations were ranked as: Li < Mn < Co < As < Mo < Zn < Al < Ba < Se < V < Ni < Cr < Cu < B < Fe < Sr. Various metal(loid) pollution indices, including degree of contamination, heavy metal evaluation index, heavy metal pollution index, and modified heavy metal index, indicated low levels of groundwater pollution. Similarly, low values of water pollution index and weighted arithmetic water quality index were observed for all groundwater points, signifying excellent groundwater quality for drinking and domestic purposes. Spatial distribution analysis showed diverse groundwater quality across the study area, with the eastern and western parts displaying a less desirable quality, while the northern has the best, making water users in the former more vulnerable to potential pollution effects. Thus, the zonation maps hinted the necessity for groundwater quality enhancement from the western to the northern parts. Chemometric analysis identified both human activities and geogenic factors as contributors to groundwater pollution, with human activities found to have more significant impacts. This research provides the scientific basis and insights for protecting the groundwater system and ensuring efficient water management.
Environmental Monitoring , Groundwater , Trace Elements , Water Pollutants, Chemical , Groundwater/analysis , Groundwater/chemistry , Saudi Arabia , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Trace Elements/analysis
The packaging industry demands improved eco-friendly materials with new and enhanced properties. In this context, bio-nanocomposite films with antimicrobial and UV-shielding properties based on modified cellulose nanocrystals/polycaprolactone (MCNC/PCL) were fabricated via solution casting method, and then food packaging simulation was carried out. CNCs were obtained by acid hydrolysis followed by successful functionalization with Quaternary ammonium surfactant, confirmed by FTIR, XPS, XRD, TEM, and DLS analyses. Furthermore, the morphological, physical, antibacterial, and food packaging properties of all prepared films were investigated. Results showed that the mechanical, UV blocking, barrier properties, and antibacterial activity of all composite films were remarkably improved. Particularly, the addition of 3 wt% MCNC increased the tensile strength and elongation at break by 27.5 % and 20.0 %, respectively. Moreover, the permeability of O2, CO2, and water vapor dramatically reduced by 97.6 %, 96.7 %, and 49.8% compared to the Neat PCL. Further, the UV-blocking properties of the composite films were significantly improved. The antimicrobial properties of MCNC/PCL films showed good antimicrobial properties against S. aureus. Finally, cherry packaged with 1 and 3 wt% MCNC films exhibited satisfactory freshness after 22 days of preservation. Overall, the fabricated PCL nanocomposite films can be utilized in the food packaging industry.
Anti-Infective Agents , Nanocomposites , Nanoparticles , Polyesters , Food Packaging , Staphylococcus aureus , Cellulose/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Nanocomposites/chemistry
Introduction: Polycythemia vera (PV) is one of the myeloproliferative neoplasms (MPN) diagnosed by World Health Organization (WHO) criteria 2016, which requires the presence of 3 major criteria: high hemoglobin/hematocrit, bone marrow findings, and Janus Kinase 2 (JAK2) mutation or two major and one minor criteria, including erythropoietin (EPO) level. However, in clinical practice, difficulties in diagnosis can arise as it may be masked by secondary causes for erythrocytosis such as smoking or obstructive sleep apnea (OSA). Case Presentation: Here, we report a 55-year-old gentleman, morbidly obese with OSA on home continuous positive airway pressure (CPAP) machine, who was incidentally found to have polycythemia. Further evaluation confirmed the diagnosis of PV. Conclusion: PV can be masked by the assumption of secondary polycythemia based on history. This underscores the importance of screening such cohort through JAK2 and EPO testing to avoid missing PV.
Introduction: Chronic myeloid leukemia (CML) is characterized by the presence of the BCR::ABL1 fusion gene, and the advent of tyrosine kinase inhibitors (TKIs) has revolutionized its therapeutic landscape. Asciminib, a STAMP inhibitor, emerges as a promising option for patients unresponsive or intolerant to multiple conventional TKIs. However, the safety and efficacy of asciminib in individuals with chronic kidney disease remain understudied. Case Presentation: In this report, we detail the case of a 62-year-old patient with CML and stage 3 chronic kidney disease, who faced intolerance to traditional TKIs primarily due to fluid retention. The transition to asciminib therapy resulted in a profound molecular response and did not exacerbate renal function, effectively addressing the fluid retention issue. Conclusion: This case highlights the potential of asciminib as a viable therapeutic alternative for CML patients with chronic kidney disease, particularly those intolerant to standard TKIs. Further research is warranted to establish the broader safety and efficacy profile of asciminib in this patient population.
Groundwater salinization in coastal aquifers is a major socioeconomic challenge in Oman and many other regions worldwide due to several anthropogenic activities and natural drivers. Therefore, assessing the salinization of groundwater resources is crucial to ensure the protection of water resources and sustainable management. The aim of this study is to apply a novel approach using predictive optimized ensemble trees-based (ETB) machine learning models, namely Catboost regression (CBR), Extra trees regression (ETR), and Bagging regression (BA), at two levels of modeling strategy for predicting groundwater TDS as an indicator for seawater intrusion in a coastal aquifer, Oman. At level 1, ETR and CBR models were used as base models or inputs for BA in level 2. The results show that the models at level 1 (i.e., ETR and CBR) yielded satisfactory results using a limited number of inputs (Cl, K, and Sr) from a few sets of 40 groundwater wells. The BA model at level 2 improved the overall performance of the modeling by extracting more information from ETR and CBR models at level 1 models. At level 2, the BA model achieved a significant improvement in accuracy (MSE = 0.0002, RSR = 0.062, R2 = 0.995 and NSE = 0.996) compared to each individual model of ETR (MSE = 0.0007, RSR = 0.245, R2 = 0.98 and NSE = 0.94), and CBR (MSE = 0.0035, RSR = 0.258, R2 = 0.933 and NSE = 0.934) at level 1 models in the testing dataset. BA model at level 2 outperformed all models regarding predictive accuracy, best generalization of new data, and matching the locations of the polluted and unpolluted wells. Our approach predicts groundwater TDS with high accuracy and thus provides early warnings of water quality deterioration along coastal aquifers which will improve water resources sustainability.
Groundwater , Water Pollutants, Chemical , Environmental Monitoring/methods , Salinity , Water Pollutants, Chemical/analysis , Water Resources , Seawater
ß-Thalassemia is one of the most common monogenetic diseases worldwide, with a particularly high prevalence in the Middle East region. As such, we have developed long-standing experience with disease management and devising solutions to address challenges attributed to resource limitations. The region has also participated in the majority of clinical trials and development programs of iron chelators and more novel ineffective erythropoiesis-targeted therapy. In this review, we provide a practical overview of management for patients with transfusion-dependent ß-thalassemia, primarily driven by such experiences, with the aim of transferring knowledge to colleagues in other regions facing similar challenges.
Iron Overload , Thalassemia , beta-Thalassemia , Humans , beta-Thalassemia/therapy , beta-Thalassemia/drug therapy , Thalassemia/drug therapy , Blood Transfusion , Iron Chelating Agents/therapeutic use , Prevalence , Iron Overload/drug therapy
Innovations in sophisticated optoelectronic devices have increased interest in high-refractive index polymers. Herein, we report innovative nanocomposite films with high linear and nonlinear refractive indices prepared by casting chitosan (Cs) with polyvinyl alcohol (PVA) (50:50 wt%) along with different concentrations (10-50 wt%) of sodium montmorillonite (NaMMT) nanoclay. The refractive indices in addition to other optical parameters of homopolymers and hybrid materials were investigated by UV-Vis. spectroscopy and optical modeling to assess their potential applications in optics. Besides, the structure, morphology, and thermal stability of the prepared films were investigated by a multitude of experimental techniques including X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), and thermogravimetric analysis (TGA/DTG). The ATR-FTIR, XRD, SEM, and AFM measurements confirmed the complete exfoliation of NaMMT nanolayers in the Cs/PVA matrix. The TGA/DTG revealed an increase in the thermal stability of Cs/PVA film with increasing clay content. The UV-Vis. measurements revealed a decrease in the optical energy gap (Eg) and a substantial increase in the linear (nD) and nonlinear (n2) refractive indices as clay content increased. Additionally, the nanohybrids displayed low UV transmission and reflected about 80 % of UV rays, making them excellent candidates for UV protection. For the first time, the dissipation factor (tanδ) in the UV/Vis. region has been calculated and fitted with the Drude-Lorentz model to predict the plasma frequency (ωp), resonance frequency (ω0), and electron lifetime (τ) of pristine polymers and nanocomposites.
Chitosan , Nanocomposites , Chitosan/chemistry , Polyvinyl Alcohol/chemistry , Bentonite/chemistry , Clay , Nanocomposites/chemistry , Polymers
Chronic kidney disease (CKD) is a major global health concern, affecting millions of people worldwide. The progressive decline in kidney function often necessitates renal replacement therapy, such as hemodialysis (HD) or peritoneal dialysis (PD), to maintain a patient's health. Iron overload, which is common in CKD patients on dialysis, can lead to severe complications, including cardiovascular disease and infections where most of the existing iron chelators are deemed unsuitable due to their suboptimal clearance in patients with compromised renal function, it becomes a significant challenge to effectively manage iron overload. Deferasirox (DFX), an oral iron chelator, has emerged as a promising treatment option for managing iron overload in these patients. However, the use of DFX comes with its unique set of challenges, such as its cost, potential side effects, and the need for close monitoring of patients, as well as the noticeable scarcity of comprehensive and rigorous clinical studies confirming its efficacy and safety of DFX. In this review, we delve into both the promising prospects and the emerging challenges associated with DFX use in managing CKD patients on HD or PD, striving for a comprehensive understanding that informs better clinical practice and patient care.
Background: Sickle cell disease (SCD) is a rare genetic blood condition affecting millions worldwide. Oxidative stress is a key player in the pathogenesis of SCD and its comorbid consequences. Renal function impairment is a common complication of SCD in both pediatric and adult patients with serious consequences leading to increased risk of mortality. In this observational real-world study, we are reporting the long-term (120 weeks) renal function in 10 patients treated with L-glutamine. Methods: Ten patients (4 pediatric and 6 adults), with confirmed diagnoses of SCD (HbSS genotype), were enrolled, these included four patients from Qatar with Arab Indian haplotype and six patients from French Guiana with African haplotype. All patients were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 120 weeks. Clinical events and laboratory parameters (renal function, hemoglobin, reticulocytes, and lactate dehydrogenase [LDH]) were measured at baseline, 48, and 120 weeks. Results: The study showed that with L-glutamine treatment there were improvements in renal and hematological parameters with no vaso-occlusive crisis at both 48-and 120-week follow-up time points in all 10 patients. Improvements were seen in the albumin creatinine ratio (ACR) from baseline to 48 weeks (mean [Standard deviation SD] ACR: -4.19 [9.81] mg/g) and 120 weeks (mean [SD] ACR: -12.31 [21.09] mg/g). Mean (SD) increase in hemoglobin concentrations from baseline to 48 weeks and 120 weeks was 0.72 (1) g/dL and 1.41 (0.79) g/dL, respectively. Mean (SD) reticulocyte counts and LDH levels decreased from baseline to 48 weeks (mean [SD] change from baseline to 48 weeks, reticulocyte counts: -40.30 [101.58] × 109 cells/L; LDH levels: -259 [154.93] U/L) and 120 weeks (mean [SD] change from baseline to 120 weeks, reticulocyte counts: -58.30 [128.38] × 109 cells/L; LDH levels: -344.80 [274.63] U/L). Conclusion: This is one of the first studies that assessed the long-term renal outcomes in SCD using L-glutamine. L-glutamine improved the renal function in patients with SCD along with improvements in clinical outcomes and hemolysis, from 48 weeks and sustained through 120 weeks of treatment.
Glanzmann thrombasthenia is a bleeding disorder with a low incidence. It typically manifests as superficial bleeding episodes, which tend to be mild. Deep organ involvement is not uncommon but remains rare due to the rarity of the disease itself and the unusual association between platelet disorders and deep organ implications. A 17-year-old boy with Glanzmann thrombasthenia since infancy developed ankle pain after a minor trauma. His initial workup was negative, but he continued to experience ankle pain. A magnetic resonance imaging (MRI) done after four weeks suggested siderotic synovitis. The patient was lost to follow-up after that and returned after two years with recurrent left ankle pain. Imaging and studies have shown evidence of chronic arthropathy. A specialized orthopedic team assessed the patient. The patient underwent intra-articular steroid injection for pain relief and was referred to continue physical therapy. In conclusion, hemarthrosis is more common in hemophilia than in platelet disorders and has potential morbidity and quality-of-life implications.
Thrombocytopenia is a common and serious complication that can occur following hematopoietic stem cell transplantation (HSCT), and it contributes to increased morbidity and mortality. The mechanisms of post-HSCT thrombocytopenia are multifactorial and complex. There are no clear consensus and guidelines for managing thrombocytopenia post-HSCT. Recently, there has been promising use of thrombopoietin receptor agonists (TPO-RAs), particularly eltrombopag and romiplostim, as treatments for post-HSCT thrombocytopenia. Notably, that this indication is considered off-label, and data in this use are limited. Based on the existing body of evidence, romiplostim emerges as a safe and effective option for individuals with transfusion-dependent thrombocytopenia after HSCT. In this context, we present a summary of our experience at a single center, where romiplostim was used in the management of post-HSCT thrombocytopenia due to poor graft function. Notably, all four cases responded positively to romiplostim treatment, and no significant adverse events were observed.
Hematopoietic Stem Cell Transplantation , Thrombocytopenia , Humans , Qatar , Thrombocytopenia/drug therapy , Thrombocytopenia/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Receptors, Fc/therapeutic use , Thrombopoietin/adverse effects , Recombinant Fusion Proteins/adverse effects , Benzoates/adverse effects , Hydrazines/adverse effects
