ABSTRACT
BACKGROUND: The COVID-19 pandemic introduced challenges and disruption across healthcare, including apheresis medicine (AM). In this study, we report findings from a survey conducted among American Society for Apheresis Physician Committee (ASFA-PC) members to describe the impact of the COVID-19 pandemic on AM education practices. STUDY DESIGN AND METHODS: A voluntary, anonymous, 24-question, institutional review board-approved survey regarding AM teaching during the pandemic was distributed to ASFA-PC members in the United States between December 1, 2020, and December 15, 2020. Descriptive analyses were reported as number and frequency of respondents for each question. Free text responses were summarized. RESULTS: Responses were received from 14/31 (45%) of ASFA-PC members, of whom 12 practiced at academic institutions. Among these, 11/12 (92%) transitioned to virtual platform for AM trainee conferences during the pandemic. A variety of resources were employed to support independent AM learning. While 7/12 (58%) respondents did not change the informed consent process for AM procedures, others delegated this process or introduced remote alternatives. The most common method respondents used to conduct AM patient rounding was a hybrid in-person/virtual model. CONCLUSION: This survey describes the adaptations and changes AM practitioners made to trainee education in response to the early phase of the COVID-19 pandemic. The transition to virtual and/or hybrid trainee learning and AM rounds underscores the importance of digital AM resources. Further study of the effects of the pandemic and its impact on AM trainee education, as well as patient care is warranted.
Subject(s)
Blood Component Removal , COVID-19 , Education, Medical , Humans , United States , COVID-19/epidemiology , Pandemics , Blood Component Removal/methods , Surveys and QuestionnairesABSTRACT
BACKGROUND: Current guidelines recommend thrombophilia evaluation in childhood arterial ischemic stroke, but the impact of screening on management is unknown. The objective of the current study is to report the incidence of thrombophilia identified as part of routine clinical care in the context of available literature reports, and to describe the impact of a diagnosis of thrombophilia on patient management. METHODS: We conducted a single-institution retrospective chart review for all children with arterial ischemic stroke occurring between January 1, 2009 and January 1, 2021. We collected thrombophilia screening results, stroke etiology, and management. We also reviewed the literature of thrombophilia testing in childhood arterial ischemic stroke published prior to June 30, 2022. Meta-analysis methods were used to assess prevalence rates. RESULTS: Among children with thrombophilia testing performed, 5% (six of 122 patients) were factor V Leiden heterozygous, 1% (one of 102 patients) were prothrombin gene mutation heterozygous, 1% (one of 122) had protein S deficiency, 20% (23/116 patients) had elevated lipoprotein(a), 3% (three of 110 patients) had elevated homocysteine levels, and 9% (10/112) had elevated antiphospholipid antibodies, only two of whom had persistently elevated levels. There was no change in stroke therapy due to these results. Literature review revealed a wide range of prevalence for most thrombophilia traits, with high cross-study heterogeneity in most cases. CONCLUSIONS: The rates of thrombophilia in our cohort were consistent with that expected in the general population. The identification of thrombophilia did not alter stroke care. However, some of the results were actionable, prompting evaluation for lipid disorders and patient-specific counseling on cardiovascular risk and risk for venous thrombosis.
Subject(s)
Ischemic Stroke , Stroke , Thrombophilia , Humans , Child , Retrospective Studies , Risk Factors , Thrombophilia/diagnosis , Thrombophilia/etiology , Stroke/etiology , Stroke/complicationsABSTRACT
Heavy metal pollution in water bodies is a global concern. The prominent source of metal contamination in aqueous streams and groundwater is wastewater containing heavy metal ions. Elevated concentrations of heavy metals in water bodies can have a negative impact on water quality and public health. The most effective way to remove metal contaminants from drinking water is thought to be adsorption. A deacetylated derivative of chitin, chitosan, has a wide range of commercial uses since it is biocompatible, nontoxic, and biodegradable. Due to its exceptional adsorption behavior toward numerous hazardous heavy metals from aqueous solutions, chitosan and its modifications have drawn a lot of interest in recent years. Due to its remarkable adsorption behavior toward a range of dangerous heavy metals, chitosan is a possible agent for eliminating metals from aqueous solutions. The review has focused on the ideas of biosorption, its kinds, architectures, and characteristics, as well as using modified (physically and chemically modified) chitosan, blends, and composites to remove heavy metals from water. The main objective of the review is to describe the most important aspects of chitosan-based adsorbents that might be beneficial for enhancing the adsorption capabilities of modified chitosan and promoting the usage of this material in the removal of heavy metal pollutants.
Subject(s)
Chitosan , Metals, Heavy , Water Pollutants, Chemical , Water Purification , Environmental Monitoring , Chitin , Wastewater , AdsorptionABSTRACT
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for a global pandemic that can cause severe infections in children, especially those with comorbid conditions. Here, we report a case of a child with a newly diagnosed medulloblastoma, Fanconi Anemia, and SARS-CoV-2 infection. Through multidisciplinary care coordination and meticulous planning, we were able to safely initiate this patient's oncology care and implement a long-term model to address the patient's care. This approach could be replicated with any newly diagnosed pediatric patient that requires monitoring for signs of COVID-19 with concurrent oncology care.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/complications , Fanconi Anemia/drug therapy , Medulloblastoma/drug therapy , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Child, Preschool , Fanconi Anemia/diagnosis , Fanconi Anemia/virology , Female , Humans , Medulloblastoma/diagnosis , Medulloblastoma/virology , PrognosisABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a major pandemic. While vaccine development moves forward, optimal treatment continues to be explored. Efforts include an ever-expanding number of clinical trials along with newly proposed experimental and off-label investigational therapies; one of which is therapeutic plasma exchange (TPE). There have been a number of publications on TPE use as adjunctive therapy for coronavirus disease 2019 (COVID-19), but no prospective randomized controlled trials (RCTs) have been completed. This article critically appraises the current available evidence on TPE as a treatment modality for SARS-CoV-2 infection.
Subject(s)
COVID-19/therapy , Clinical Trials as Topic , Cytokines/metabolism , Hemadsorption , Humans , Immunization, Passive/methods , Inflammation , Plasma Exchange , Plasmapheresis , Research Design , Viral Load , COVID-19 SerotherapyABSTRACT
Therapeutic plasma exchange is used to treat neurological diseases in the pediatric population. Since its first use in pediatric patients with hepatic coma in the form of manual whole blood exchange, therapeutic plasma exchange has been increasingly used to treat these disorders of the nervous system. This expansion is a result of improved techniques and apheresis instruments suitable for small children, as well as the recognition of its applicability to many diseases in the pediatric population. This review provides a historical overview of the use of therapeutic apheresis in children and highlights the most common applications for therapeutic plasma exchange to treat neurological disorders in children.
Subject(s)
Nervous System Diseases/therapy , Plasma Exchange/methods , Child , Encephalomyelitis/therapy , Guillain-Barre Syndrome/therapy , Humans , Lambert-Eaton Myasthenic Syndrome/therapy , Myasthenia Gravis/therapy , Neuromyelitis Optica/therapy , Receptors, N-Methyl-D-Aspartate/immunology , Streptococcal Infections/complications , Thyroiditis, Autoimmune/complicationsABSTRACT
BACKGROUND: Entrustable professional activities (EPAs) are well-defined, executable, observable, and measurable activities that are performed by a trainee and can be performed independently as training progresses. The purpose of this study is to develop EPAs specific for the practice of apheresis medicine (AM). METHODS: Members of the American Society for Apheresis Graduate Medical Education subcommittee developed a list of 28 apheresis medical activities linked to Accreditation Council for Graduate Medical Education milestones and competencies in five areas: (a) consultation, (b) clinical care for therapeutic apheresis, (c) clinical care for donor collections, (d) test optimization, and (e) vascular access. Ten AM experts using a validated tool to measure the quality of the EPAs (QUEPA) evaluated these activities with use of a Likert scale. Per group consensus, an activity was considered acceptable for each domain if it had received an average score greater than 3.7, and it was rated 4 or 5 (agree or strongly agree) by at least 70% of experts. RESULTS: Of the 28 activities, 11 did not have acceptable QUEPA scores: 7 activities were rated as unobservable, 4 were rated unfocused, 2 were rated unrealistic and not generalizable, and 2 were rated as not addressing multiple competencies. Four activities had unacceptable scores in more than one domain. Subcommittee members edited these 11 activities over two review cycles to produce a final list of 26 activities. CONCLUSION: A set of practical, focused, and observable EPAs in AM were systematically developed. These EPAs can be used to assess and support trainee performance in AM.
Subject(s)
Accreditation , Blood Component Removal , Education, Medical, Graduate , HumansABSTRACT
Quality of response to immunosuppressive therapy and long-term outcomes for pediatric severe aplastic anemia remain incompletely characterized. Contemporary evidence to inform treatment of relapsed or refractory severe aplastic anemia for pediatric patients is also limited. The clinical features and outcomes for 314 children treated from 2002 to 2014 with immunosuppressive therapy for acquired severe aplastic anemia were analyzed retrospectively from 25 institutions in the North American Pediatric Aplastic Anemia Consortium. The majority of subjects (n=264) received horse anti-thymocyte globulin (hATG) plus cyclosporine (CyA) with a median 61 months follow up. Following hATG/CyA, 71.2% (95%CI: 65.3,76.6) achieved an objective response. In contrast to adult studies, the quality of response achieved in pediatric patients was high, with 59.8% (95%CI: 53.7,65.8) complete response and 68.2% (95%CI: 62.2,73.8) achieving at least a very good partial response with a platelet count ≥50×109L. At five years post-hATG/CyA, overall survival was 93% (95%CI: 89,96), but event-free survival without subsequent treatment was only 64% (95%CI: 57,69) without a plateau. Twelve of 171 evaluable patients (7%) acquired clonal abnormalities after diagnosis after a median 25.2 months (range: 4.3-71 months) post treatment. Myelodysplastic syndrome or leukemia developed in 6 of 314 (1.9%). For relapsed/refractory disease, treatment with a hematopoietic stem cell transplant had a superior event-free survival compared to second immunosuppressive therapy treatment in a multivariate analysis (HR=0.19, 95%CI: 0.08,0.47; P=0.0003). This study highlights the need for improved therapies to achieve sustained high-quality remission for children with severe aplastic anemia.
Subject(s)
Anemia, Aplastic/drug therapy , Antilymphocyte Serum/administration & dosage , Cyclosporine/administration & dosage , Immunosuppression Therapy , Anemia, Aplastic/epidemiology , Anemia, Aplastic/pathology , Antilymphocyte Serum/adverse effects , Child, Preschool , Cyclosporine/adverse effects , Female , Follow-Up Studies , Humans , Infant , Male , Retrospective Studies , United States/epidemiologyABSTRACT
Silica gel chitosan composite was prepared to perform adsorptive experiment of different heavy metal ion solutions. The characterization of chitosan + silica gel (Ch + Sg) composite was done by FTIR and SEM-EDS to understand the presence of active sites and to have an insight on the surface morphology. The adsorption study of heavy metal ions by Ch + Sg composite gives maximum removal percent for Cu, Pb and Ni which were obtained at pH 5 and for Hg at pH 6.The trend of removal by Ch + Sg signifies that maximum removal percent was attained at 120 min. The surface of Ch + Sg is heterogeneous for the adsorption of Hg, Ni and Cu and homogeneous for Pb adsorption. The values obtained for Pb signify that its adsorption best fitted to pseudo first order with the R2 value of 0.986, whereas pseudo second order best fitted to the experimental data of Cu, Ni and Hg as R2 values which are 0.983, 0.819 and 0.957 respectively. The values of change in entropy (â¿S) obtained for Pb, Cu, Ni and Hg are - 69.33, - 118, - 63.33 and - 98.52 J/mol K respectively. Negative values of change in enthalpy, â¿H in (kJ/mol) are in the range of - 18.2 to - 37.66 which indicates both physical and chemical adsorption involves in the process of adsorption.
Subject(s)
Chitosan/chemistry , Metals, Heavy/chemistry , Metals, Heavy/isolation & purification , Silica Gel/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Adsorption , Entropy , Ions/chemistry , Ions/isolation & purification , Kinetics , ThermodynamicsABSTRACT
OBJECTIVES: To characterise the clinical features, immune manifestations and molecular mechanisms in a recently described autoinflammatory disease caused by mutations in TRNT1, a tRNA processing enzyme, and to explore the use of cytokine inhibitors in suppressing the inflammatory phenotype. METHODS: We studied nine patients with biallelic mutations in TRNT1 and the syndrome of congenital sideroblastic anaemia with immunodeficiency, fevers and developmental delay (SIFD). Genetic studies included whole exome sequencing (WES) and candidate gene screening. Patients' primary cells were used for deep RNA and tRNA sequencing, cytokine profiling, immunophenotyping, immunoblotting and electron microscopy (EM). RESULTS: We identified eight mutations in these nine patients, three of which have not been previously associated with SIFD. Three patients died in early childhood. Inflammatory cytokines, mainly interleukin (IL)-6, interferon gamma (IFN-γ) and IFN-induced cytokines were elevated in the serum, whereas tumour necrosis factor (TNF) and IL-1ß were present in tissue biopsies of patients with active inflammatory disease. Deep tRNA sequencing of patients' fibroblasts showed significant deficiency of mature cytosolic tRNAs. EM of bone marrow and skin biopsy samples revealed striking abnormalities across all cell types and a mix of necrotic and normal-appearing cells. By immunoprecipitation, we found evidence for dysregulation in protein clearance pathways. In 4/4 patients, treatment with a TNF inhibitor suppressed inflammation, reduced the need for blood transfusions and improved growth. CONCLUSIONS: Mutations of TRNT1 lead to a severe and often fatal syndrome, linking protein homeostasis and autoinflammation. Molecular diagnosis in early life will be crucial for initiating anti-TNF therapy, which might prevent some of the severe disease consequences.
Subject(s)
Anemia, Sideroblastic/genetics , Anti-Inflammatory Agents/therapeutic use , Genetic Diseases, X-Linked/genetics , Immunologic Deficiency Syndromes/genetics , Mutation , Nucleotidyltransferases/genetics , RNA, Transfer/genetics , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Anemia, Sideroblastic/blood , Child , Child, Preschool , Cytokines/blood , Cytokines/genetics , Developmental Disabilities/genetics , Female , Genetic Diseases, X-Linked/blood , Humans , Immunophenotyping , Male , Pedigree , Phenotype , Tumor Necrosis Factor-alpha/analysis , Exome SequencingABSTRACT
The Choosing Wisely campaign has stimulated clinicians to think about the appropriateness of various tests and procedures, compelling physicians to make smarter, safer and more effective choices for high quality patient care and to reduce healthcare cost. The American Society for Apheresis (ASFA) strives to advance apheresis medicine through education, evidence-based practice, research and advocacy. To complement these shared missions, ASFA created a working group, consisting of representatives from the various ASFA committees, to produce recommendations for apheresis medicine that reflect the Choosing Wisely guiding principles. A diverse group of ASFA physician and allied health members reviewed, rated and ranked 9 original draft proposals. Additional revisions and refinements were made prior to external review and adoption of five final recommendations by the ASFA Board of Directors. The ASFA Choosing Wisely recommendations encourage apheresis practitioners, patients and donors to discuss and prioritize best clinical practices that avoid harm and waste while optimizing clinical benefit.
Subject(s)
Blood Component Removal/methods , Health Planning Guidelines , Humans , Practice Guidelines as Topic/standards , Societies, MedicalABSTRACT
Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029-$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time.
Subject(s)
Anemia, Sickle Cell/therapy , Hematopoietic Stem Cell Transplantation , Patient Acceptance of Health Care , Adolescent , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/methods , Child , Child, Preschool , Clinical Decision-Making , Comorbidity , Databases, Factual , Female , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Health Care Costs , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Incidence , Infant , Infant, Newborn , Male , Mortality , Risk Assessment , Severity of Illness Index , Tissue Donors , Transplantation, Homologous , Treatment Failure , Treatment Outcome , United States/epidemiology , Young AdultABSTRACT
Acquired hemophilia A (AHA) is a rare autoimmune disorder that leads to factor VIII (FVIII) deficiency via autoantibody formation. Standard treatment options include FVIII bypassing factors and immunosuppression. However, the role of therapeutic plasma exchange (TPE) is not clear in the treatment of AHA. We present a case of idiopathic AHA in a 66 year old female with severe bleeding and a FVIII inhibitor of 17.6 Bethesda units (BU). She failed to respond to standard treatment including maximum dose of recombinant FVIIa (rFVIIa), rituximab, and other immunosuppressive agents. Her FVIII inhibitor rapidly increased to 140 BU and FVIII was below 5%. TPE was initiated 3 weeks after admission and her bleeding stabilized after the first treatment and completely stopped after three treatments. Repeat testing revealed increased FVIII to 15% and FVIII inhibitor decreased to 2.0 BU. After an additional TPE treatment, her FVIII increased to 27% and FVIII inhibitor decreased to 0.6 BU and she was discharged without bleeding 40 days after admission. In this case, TPE played a critical role in reducing FVIII inhibitor, which resulted in a recovery of FVIII activity and hemostasis. Therefore, TPE should be initiated early in AHA patients with bleeding and high titer of FVIII inhibitor.
Subject(s)
Hemophilia A/therapy , Plasma Exchange/methods , Aged , Autoantibodies/blood , Autoantibodies/isolation & purification , Factor VIII/immunology , Female , Hemorrhage/therapy , Humans , Salvage TherapyABSTRACT
BACKGROUND: Keratoacanthoma (KA) is a common keratinocytic skin neoplasm that typically develops rapidly and undergoes complete spontaneous regression. As the pro-apoptotic p53 protein may be involved in the lifecycle of KA, we studied the p53 status throughout the main stages of KA that include proliferation, maturation and regression in a large series of lesions. METHODS: One-hundred and twenty-four KAs were characterized with respect to age of the lesions both clinically and histopathologically, in addition to phenotypic characteristics such as cellular atypia, infiltration, inflammation and fibrosis. Tp53 mutations were detected by capillary electrophoresis, and p53 protein levels were assessed by immunohistochemistry. RESULTS: Tp53 mutations were detected in 49 cases (39.5%) and were associated with high p53 protein levels (p = 0.007) and histopathologic age of the lesions (p = 0.044). Significant association was also seen between high p53 protein levels and atypia (p = 0.036), whereas the association with infiltration showed borderline significance (p = 0.057). High p53 protein levels were significantly associated with gene mutations in transplanted, but not in non-transplanted patients. CONCLUSION: We show a high frequency of Tp53 mutations in KAs that is associated with increased p53 levels. The results indicate a role for the p53 protein in KA development.
Subject(s)
Keratoacanthoma/pathology , Skin Neoplasms/pathology , Tumor Suppressor Protein p53/biosynthesis , Adult , Aged , DNA Mutational Analysis , Electrophoresis, Capillary , Female , Humans , Immunohistochemistry , Keratoacanthoma/genetics , Keratoacanthoma/metabolism , Male , Middle Aged , Mutation , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Tumor Suppressor Protein p53/analysis , Tumor Suppressor Protein p53/geneticsABSTRACT
AIM: The study was carried to find a relationship between the postextraction stable landmark, the incisive papilla, and the most labial position of the maxillary central incisor teeth, which occurred in Nepalese population. MATERIALS AND METHODS: Casts of the subjects selected by nonprobability random sampling meeting the inclusion criteria were obtained. Each casts were standardized with respect to the occlusal plane and a photographic technique was used to measure the distance from the tangent of the labial surface of the central incisors to the posterior border of the incisive papilla. The measurements were made using Adobe Photoshop and results were analyzed by using appropriate statistical methods. Most appropriate software (SPSS) for the purpose was used to generate all desired values. RESULTS: The data obtained suggested that the distance from the labial surface of maxillary central incisors to the posterior border of the incisive papilla ranged from 9 to 15.9 mm with a mean of 11.59 mm (SD 1.3). Various other results were also found after evaluation of the arch forms in relation to sex and race. CONCLUSION: Within the limitations of the study, these results suggested that there is a relationship between the maxillary central incisors and the incisive papilla aiding in the anteroposterior positioning of the anterior tooth. The clinical relevance of the study lies in application of the incisive papilla as a starting point in the preliminary location of maxillary incisors and canines during construction of the denture in absence of preextraction records.
Subject(s)
Incisor/anatomy & histology , Palate/anatomy & histology , Adolescent , Adult , Asian People , Female , Humans , Male , Maxilla , Nepal , Young AdultABSTRACT
Little information exists on the effect of race and ethnicity on collection of peripheral blood stem cells (PBSC) for allogeneic transplantation. We studied 10,776 donors from the National Marrow Donor Program who underwent PBSC collection from 2006 to 2012. Self-reported donor race/ethnic information included Caucasian, Hispanic, Black/African American (AA), Asian/Pacific Islander (API), and Native American (NA). All donors were mobilized with subcutaneous filgrastim at an approximate dose of 10 µg/kg/day for 5 days. Overall, AA donors had the highest median yields of mononuclear cells per liter and CD34(+) cells per liter of blood processed (3.1 × 10(9) and 44 × 10(6), respectively), whereas Caucasians had the lowest median yields at 2.8 × 10(9) and 33.7 × 10(6), respectively. Multivariate analysis of CD34(+) per liter mobilization yields using Caucasians as the comparator and controlling for age, gender, body mass index, and year of apheresis revealed increased yields in overweight and obese AA and API donors. In Hispanic donors, only male obese donors had higher CD34(+) per liter mobilization yields compared with Caucasian donors. No differences in CD34(+) per liter yields were seen between Caucasian and NA donors. Characterization of these differences may allow optimization of mobilization regimens to allow enhancement of mobilization yields without compromising donor safety.
Subject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Racial Groups , Unrelated Donors , Adolescent , Adult , Antigens, CD34/analysis , Body Mass Index , Cell Count , Female , Filgrastim , Humans , Injections, Subcutaneous , International Cooperation , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Recombinant Proteins/administration & dosageABSTRACT
BACKGROUND: Diamond-Blackfan anemia (DBA), an inherited marrow failure syndrome, has severe hypoplastic anemia in infancy and association with aplastic anemia, MDS/leukemia, and other malignancies. Short stature is present in most patients. Isolated cases have demonstrated improved growth on growth hormone (GH) therapy. PROCEDURES: GH treatment data were obtained from 19 children with DBA (6 at our site and 13 from Genentech). Control data from 44 non-GH treated children were provided by Diamond Blackfan Anemia Registry. Annual growth velocity (GV) and height-for-age Z-scores (HAZ) were compared between groups and for up to 4y of GH treatment. RESULTS: Constructed DBA-specific male and female height-for-age charts for non-GH treated patients revealed short stature compared to CDC norms. GH-treated patients had significantly lower HAZ prior to treatment initiation compared to non-GH-treated controls. Among GH-treated patients, GV significantly improved in the first two years relative to pre-treatment. HAZ significantly improved in each of 4y of GH therapy compared to baseline. After 2y of therapy, HAZ for GH-treated patients were not significantly different from controls, demonstrating successful catch-up growth. CONCLUSIONS: GH treatment in children with DBA improves both GV and HAZ during treatment sustained for up to 4y. Very short children with DBA can be treated successfully with GH to restore stature to levels comparable to less affected patients. DBA height charts are useful tools for assessing age-specific growth in this typically short population. Careful consideration of individualized benefit of GH therapy versus risk is important in view of long-term underlying â¼5% malignancy risk in DBA.
Subject(s)
Anemia, Diamond-Blackfan/drug therapy , Human Growth Hormone/administration & dosage , Registries , Adolescent , Adult , Anemia, Diamond-Blackfan/complications , Anemia, Diamond-Blackfan/physiopathology , Child , Child, Preschool , Female , Follow-Up Studies , Growth Disorders/etiology , Growth Disorders/physiopathology , Humans , MaleABSTRACT
Recent experience suggests that reduced-intensity conditioning (RIC) regimens can improve the outcomes of patients with hemophagocytic lymphohistiocytosis (HLH) undergoing allogeneic hematopoietic cell transplantation (HCT). However, studies directly comparing RIC to myeloablative conditioning (MAC) regimens are lacking. Forty patients with HLH underwent allogeneic HCT between 2003-2009 at Cincinnati Children's Hospital. Fourteen patients received MAC consisting of busulfan, cyclophosphamide, and antithymocyte globulin plus or minus etoposide. Twenty-six patients received RIC consisting of fludarabine, melphalan, and alemtuzumab. All patients engrafted. Acute graft-versus-host disease grades II to III occurred in 14% of MAC patients and 8% of RIC patients (P = .3171). Posttransplantation mixed donor/recipient chimerism developed in 18% of MAC patients and 65% of RIC patients (P = .0110). The majority of patients with mixed chimerism received intervention with reduction of immune suppression plus or minus donor lymphocyte infusion or stem cell boost, which stabilized or increased donor contribution to hematopoiesis and prevented relapse of HLH in all but 1 patient. Grade II to III graft-versus-host disease occurred in 5 of 14 RIC patients after donor lymphocyte infusion. The overall estimated 3-year survival after HCT was 43% (confidence interval = ± 26%) for MAC patients and 92% (confidence interval = ± 11%) for RIC patients (P = .0001). We conclude that RIC significantly improves the outcome of patients with HLH undergoing allogeneic HCT.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Graft vs Host Disease/mortality , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , Lymphohistiocytosis, Hemophagocytic/mortality , Lymphohistiocytosis, Hemophagocytic/therapy , Adolescent , Adult , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Infant, Newborn , Male , Remission Induction , Retrospective Studies , Survival Rate , Transplantation Conditioning , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Establishing the predictive utility of Non stress test could be helpful to improve perinatal outcome especially in countries like Nepal, with heavy workload and limited resources. The aim of the study was to assess association between Non stress test abnormalities and fetal outcome in terms of Apgar score and newborn intensive care unit admission rate for patient with decreased fetal movement. METHODS: The study included total 54 women with decreased fetal movement at term without any pregnancy complication not in labor admitted to paropakar maternity and women's hospital, Thapathali, Kathmandu from June 2020 to December 2020. Non stress test was done for 20 to 40 minutes and the readings were categorized in to three groups. The results were compared to see the relationship between normal, suspicious and abnormal Non stress test result in terms of mode of delivery, Apgar score, neonatal resuscitation and need for neonatal intensive care unit newborn intensive care unit admission. RESULTS: Total 54 cases remained under inclusion criteria were included in this study. Mode of delivery on the basis of Non stress test result shows that 31.48% with abnormal Non stress test had a Lower segment Caesarian section, 1.8% had instrumental vaginal delivery and 14.8% had spontaneous vaginal delivery. While in reassuring Non stress test group 20.4% had spontaneous vaginal, 0% had Lower segment Caesarian section and 1.85% had instrumental vaginal delivery. There is statistically significant relationship between Non stress test result and Apgar score. In reactive Non stress test result only5.4% required neonatal resuscitation. However, in persistently non-reassuring or abnormal Non stress test result, 62.1% require neonatal resuscitation. Similarly, in reactive Non stress test result none of the neonate required newborn intensive care unit admission. However, in persistently non-reassuring or abnormal Non stress test result 46.1% neonates require newborn intensive care unit admission. There were 9 neonatal mortalities from abnormal Non stress test result. CONCLUSIONS: We concluded that the Non stress test is a good predictor of maternal and fetal outcome detecting fetal hypoxia already present or likely to develop in patient presenting with reduced fetal movement in term pregnancies without complication.
Subject(s)
Fetal Movement , Labor, Obstetric , Delivery, Obstetric , Female , Humans , Infant, Newborn , Nepal , Pregnancy , Pregnancy Outcome , ResuscitationABSTRACT
Preservation of fertility after hematopoietic cell transplantation (HCT) can have a significant influence on the quality of life of transplant survivors. We describe 178 pregnancies in HCT recipients that were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 2002 and 2007. There were 83 pregnancies in female HCT recipients and 95 pregnancies in female partners of male HCT recipients. Indications for transplantation included hematologic and other malignancies (N = 99) and nonmalignant disorders (N = 79, of which 75 patients had severe aplastic anemia). The cohort included recipients of autologous HCT (20 women, 13 men), myeloablative (MA) allogeneic HCT (12 women, 50 men), and nonmyeloablative allogeneic HCT (2 women, 2 men). Age at HCT was <20 years for 50% of women and 19% of men. Conditioning regimens included total body irradiation (TBI) in 16% of women and 19% of men; doses were MA in 10% of women and in 16% of men. Live births were reported in 86% of pregnancies in partners of male transplant patients and 85% of pregnancies in female transplant patients, with most pregnancies occurring 5 to 10 years after HCT. We conclude that some HCT recipients can retain fertility, including patients who have received TBI and/or MA conditioning. Young patients undergoing HCT should be counseled both before and after HCT about potential loss of fertility, methods for preserving fertility, and planning for future pregnancy. Fertility and outcomes of pregnancy after HCT need prospective evaluation in large transplant cohorts.