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BACKGROUND: Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD. METHODS: In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m2 twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing. FINDINGS: Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment discontinuation), one due to Aspergillus infection, one due to septic shock, and one due to acute respiratory distress syndrome; none were considered to be related to study drug. INTERPRETATION: Pending final analysis, this study suggests that ruxolitinib is active and well tolerated in both treatment-naive and corticosteroid-refractory patients aged 2 years to younger than 18 years with chronic GVHD, thereby supporting its use in this patient population. The safety profile of ruxolitinib in this patient population is consistent with that of adults. Final analysis of this study will provide further information on the long-term benefits of ruxolitinib in children with chronic GVHD. FUNDING: Novartis.
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Corticoesteroides , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Nitrilos , Pirazoles , Pirimidinas , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Corticoesteroides/uso terapéutico , Enfermedad Crónica , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirimidinas/uso terapéutico , Resultado del TratamientoRESUMEN
Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre de Sangre Periférica , Humanos , Niño , Adulto Joven , Anemia Aplásica/terapia , Abatacept , Estudios Retrospectivos , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , TiotepaRESUMEN
Desmoid fibromatosis (DF) arising from musculoaponeurotic structures rarely affects the head and neck region with the abdomen being the most common site of origin. These are benign tumors with locally infiltrative nature usually presenting as painless swellings that are rapidly growing. The infratemporal fossa DF is an extremely rare location with few clinical reports. This article discusses the management of a 2-year-old child with DF of the infratemporal fossa (ITF) along with literature review.
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JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.
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Anemia Ferropénica , Anemia Macrocítica , Anemia , Deficiencia de Ácido Fólico , Hematología , Deficiencia de Vitamina B 12 , Lactante , Adolescente , Humanos , Niño , Preescolar , Deficiencia de Ácido Fólico/complicaciones , Deficiencia de Ácido Fólico/epidemiología , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/epidemiología , Anemia/diagnóstico , Anemia/epidemiología , Anemia/etiología , Vitamina B 12 , Anemia Ferropénica/complicaciones , Ácido Fólico/uso terapéutico , Hierro/uso terapéutico , Anemia Macrocítica/complicaciones , Hemoglobinas/análisis , FerritinasRESUMEN
JUSTIFICATION: In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT). PROCESS: Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts. Objective: To facilitate appropriate management of children with acquired aplastic anemia. RECOMMENDATIONS: Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophos-phamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3-6 months for the response assessment and consideration of next line therapy.
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Anemia Aplásica , Ciclosporinas , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Pediatría , Anemia Aplásica/diagnóstico , Anemia Aplásica/patología , Anemia Aplásica/terapia , Niño , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND: Children diagnosed with haematological and oncology conditions spend long periods of time undergoing treatments in hospital. Treatments are intensive and may include combinations of chemotherapy, radiation, surgery and bone marrow transplants. This often means that they have prolonged hospital stays away from family, friends and familiar environments. AIM: We aimed at starting an activity group and learning centre based in the hospital setting for children undergoing treatment for haematological and oncology conditions. METHODS: The activity group and learning centre was set up in a tertiary care hospital under the department of Paediatric Haematology, Oncology and Bone Marrow Transplantation with the support of a local NGO called 'Samiksha Foundation' in Bangalore, India. Children who participated in the programme engaged in learning through participation in the activity groups which engaged in academic and non-academic activities. The activity group and learning centre was piloted in April and May of 2019. During the pilot sessions, 156 children participated in the group. Children of all ages were welcome to attend and were given activities based on their age and learning levels. Until March 2020, the group has seen over 600 children in attendance. RESULTS: This methods report examines various aspects of the activity group such as setting up of the activity groups, how they are run, the activities conducted in the groups and the effects the group has had on children and their families as reported by them while undergoing treatment. CONCLUSION: The overall response to the activity groups was positive and widely accepted among our patient community. The intervention proved to be effective, easy to implement and relatively inexpensive. We hope that by sharing data from our centre, more paediatric units may be able to implement such groups for children.
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Oncología Médica , Niño , Humanos , India/epidemiologíaRESUMEN
Natural killer (NK) cell enteropathy is a newly described disease entity with benign behavior and an indolent clinical course, characterized by the atypical proliferation of NK cells throughout the gastrointestinal tract. The exact etiology is unknown. It closely mimics NK/T-cell lymphoma. We describe this atypical entity in a young adult man presenting with vague upper gastrointestinal symptoms and anemia requiring blood transfusion. The response to budesonide therapy points toward a possible low-grade autoimmune process. Considering the benign behavior and self-limiting course, recognizing this entity is essential to avoid over the investigation and aggressive, inappropriate therapy.
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Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.
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Anemia de Fanconi , ADN Helicasas , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Humanos , IndiaAsunto(s)
Gastritis/diagnóstico , Gastritis/microbiología , Infecciones por Helicobacter/diagnóstico , Helicobacter heilmannii/patogenicidad , Anciano , Endoscopía , Tracto Gastrointestinal/diagnóstico por imagen , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/patología , Infecciones por Helicobacter/microbiología , Humanos , MasculinoRESUMEN
Gastrointestinal basidiobolomycosis (GIB) is a rare fungal infection with limited geographic distribution. However, the incidence of GIB has shown an increasing trend because of globalization and frequent traveling. GIB is commonly seen to mimic gastrointestinal malignancy and other diseases such as intestinal tuberculosis and inflammatory bowel disease. Tissue diagnosis is considered to be the gold standard for differentiating these mycotic lesions from tuberculosis and malignancy with confirmation of species performed by culture or polymerase chain reaction. The diagnosis of GIB should be conjectured in patients with suspicion of malignancy, with an inconclusive biopsy. It seems prudent to proceed with radical excision of mass early because both colonic malignancy and GIB have high mortality if untreated.
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Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.
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Predisposición Genética a la Enfermedad/genética , Inmunidad Innata/genética , Mutación , Infecciones por Mycobacterium/genética , Infecciones por Mycobacterium/inmunología , Adolescente , Adulto , Vacuna BCG/inmunología , Niño , Preescolar , Coinfección/epidemiología , Coinfección/microbiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , India/epidemiología , Lactante , Recién Nacido , Masculino , Infecciones por Mycobacterium/epidemiología , Infecciones por Mycobacterium/microbiología , Fenotipo , Receptores de Interleucina-12/genética , Receptores de Interleucina-12/inmunología , Estudios Retrospectivos , Adulto JovenRESUMEN
IgG4-related disease (IgG4 RD) is a multisystem disorder characterized by tumefactive (mass forming) lesions, storiform fibrosis, and IgG4-positive plasma cell infiltration. IgG4 sclerosing cholangitis (IgG4 SC) is the biliary manifestation of IgG4 RD, often in association with autoimmune pancreatitis (AIP). Here, we report two patients with IgG4-related cholangitis mimicking primary sclerosing cholangitis.
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Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Pancreatitis Autoinmune , Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/inmunología , Colangitis Esclerosante/patología , Diagnóstico Diferencial , Femenino , Fibrosis , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/patología , MasculinoRESUMEN
Determination of the magnitude of body iron stores helps to identify individuals at risk of iron-induced organ damage in Thalassemia patients. The most direct clinical method of measuring liver iron concentration (LIC) is through chemical analysis of needle biopsy specimens. Here we present a noninvasive method for the measurement of LIC in vivo using magnetic resonance imaging (MRI). Twenty-three pediatric Thalassemia major patients undergoing bone marrow transplantation at our centre were studied. All 23 patients had MRI T2* and R2* decay time for evaluation of LIC on a 1.5 Tesla MRI system followed by liver tissue biopsy for the assessment of iron concentration using an atomic absorption spectrometry. Simultaneously, serum ferritin levels were measured by enzymatic assay. We have correlated biopsy LIC with liver T2* and serum ferritin values with liver R2*. Of the 23 patients 11 were males, the mean age was 8.3 ± 3.7 years. The study results showed a significant correlation between biopsy LIC and liver T2* MRI (r = 0.768; p < 0.001). Also, there was a significant correlation between serum ferritin levels and liver R2* MRI (r = 0.5647; p < 0.01). Two patients had high variance in serum ferritin levels (2100 and 4100 mg/g) while their LIC was around 24 mg/g, whereas the difference was not seen in T2* MRI. Hence, the liver T2* MRI is a better modality for assessing LIC. Serum ferritin is less reliable than quantitative MRI. The liver T2* MRI is a safe, reliable, feasible and cost-effective method compared to liver tissue biopsy for LIC assessment.
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The outbreak of rapidly spreading COVID-19 pandemic in December 2019 has witnessed a major transformation in the health care system worldwide. This has led to the re-organization of the specialty services for the effective utilization of available resources and ensuring the safety of patients and healthcare workers. Suspension of oncology services will have major implications on cancer care due to delayed diagnosis and treatment leading to irreversible adverse consequences. Therefore various oncology organizations have called for a continuation of cancer care during this crisis with diligence. The COVID-19 pandemic has forced the clinicians to transform the components of care from screening to outpatient care and primary management. The purpose of this article is to establish guidelines and recommendations for ocular oncology in the management of ocular tumors set by a multidisciplinary team of experts including ocular, medical and radiation oncologists, and pathologists. As the pandemic is evolving fast, it will require constant updates and reformation of health strategies and guidelines for safe and quality health care.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Transmisión de Enfermedad Infecciosa/prevención & control , Neoplasias del Ojo/terapia , Oncología Médica/normas , Oftalmología/normas , Pandemias , Neumonía Viral/epidemiología , COVID-19 , Consenso , Infecciones por Coronavirus/transmisión , Humanos , Neumonía Viral/transmisión , SARS-CoV-2RESUMEN
Background: Hematopoietic stem cell transplantation (HSCT) is the curative option for many primary immune deficiency disorders (PID). In the last 5 years, increased awareness, availability of diagnostics based on flow cytometry, genetic testing, improved supportive care, use of reduced toxicity conditioning, and success of haploidentical donor HSCT have improved access to HSCT for children with PID in India. We present results on children with PID who underwent HSCT across India and the factors that influenced outcome. Patients and Methods: We collected retrospective data on the outcome of HSCT for PID from seven centers. We analyzed the impact of the type of PID, conditioning regimen, time period of HSCT- before or after January 2016, graft versus host disease prophylaxis, cause of mortality and overall survival. Results: A total of 228 children underwent HSCT for PID at a median age of 12 months (range, 1 to 220 months) with a median follow up of 14.4 months. Infants accounted for 51.3% of the cohort and the male female ratio was 3:1. SCID (25%) and HLH (25%) were the more frequent diagnoses. Matched family donor was available in 36.4% and 44.3% children had a haploidentical HSCT. Reduced and myeloablative conditioning regimens were used with 64% children receiving a treosulfan based conditioning regimen. Peripheral blood stem cells were the predominant graft source at 69.3%. The survival in infants (60.2%) was inferior to children aged over 1 year (75.7% p value = 0.01). Children with Wiskott Aldrich syndrome (74.3%) and chronic granulomatous disease (82.6%) had the best outcomes. The survival was superior in children receiving HSCT from a matched sibling (78%) versus an alternate donor HSCT (61% p value = 0.04). In the cohort transplanted after January 2016 survival improved from 26.8% to 77.5% (p value = 0.00). Infection remains the main cause of mortality at in over 50% children. The 5-year overall survival rate was 68%. Conclusion: Survival of children with PID undergoing HSCT in India has improved dramatically in last 5 years. Alternate donor HSCT is now feasible and has made a therapeutic option accessible to all children with PID.
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Trasplante de Células Madre Hematopoyéticas , Enfermedades de Inmunodeficiencia Primaria/cirugía , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , India , Lactante , Donadores Vivos , Masculino , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/inmunología , Enfermedades de Inmunodeficiencia Primaria/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Donante no EmparentadoRESUMEN
Cardiac tumors presenting as mediastinal masses in childhood are rare. This report describes the case of a 6-year-old girl who presented to us after a failed attempt at resection of a mass arising from the left atrial appendage. Computed tomography-guided biopsy suggested a perivascular epithelioid cell tumor (PEComa). Sirolimus was started in order to reduce the mass size. She subsequently underwent resection of the mass by midline sternotomy approach and cardiopulmonary bypass. Recovery was uneventful and the child is doing well at two-year follow-up. Contemporary literature is reviewed. Only seven cases, including two children, with mediastinal PEComa have been reported. Pathology and treatment options are discussed.
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Procedimientos Quirúrgicos Cardíacos/métodos , Neoplasias Cardíacas/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Biopsia , Niño , Diagnóstico Diferencial , Ecocardiografía , Femenino , Neoplasias Cardíacas/cirugía , Humanos , Neoplasias de Células Epitelioides Perivasculares/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos XRESUMEN
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is one of the most common heritable cerebral arteriopathy. Responsible for stroke and dementia in young adults and can be diagnosed by skin biopsy. We report a case of a 42 year old man with recurrent transient ischemic attacks (TIA). A detailed neurologic examination revealed poor score in MMSE (20/30) defect mainly seen in recall, repetitions. Executive dysfunction, memory and language impairment were also found. Motor system examination revealed grade 3 power in right upper and lower limb with more severe weakness of distal muscles in form of grip weakness and slippage of chappals. Neuroimaging and genetic analysis for Notch-3 confirmed the diagnosis. Imaging studies suggested greater involvement in the temporal and frontal lobes along with deep areas of the brain.
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CADASIL , Adulto , Biopsia , Infarto Cerebral , Humanos , Masculino , Neuroimagen , Accidente CerebrovascularRESUMEN
Primary immunodeficiency (PID) refers to a group of heterogeneous genetic disorders with a weakened immune system. Mendelian susceptibility to mycobacterial disease (MSMD) is a subset of PID in which patients exhibit defects in intrinsic and innate immunity. It is a rare congenital disorder characterized by severe and recurrent infections caused by weakly virulent mycobacteria or other environmental mycobacteria. Any delay in definitive diagnosis poses a major concern due to the confounding nature of infections and immune deficiencies. Here, we report the clinical, immunological, and genetic characteristics of two siblings (infants) with recurrent infections. There was a history of death of two other siblings in the family after BCG vaccination. Whole exome sequencing of the two affected surviving infants along with their consanguineous parents identified a novel, homozygous single nucleotide splice acceptor site variant in intron 2 of the interferon gamma receptor 2 (IFNGR2) gene. Sanger sequencing of DNA obtained from blood and fibroblasts confirmed the variant. The patients underwent bone marrow transplantation from their father as a donor. RT-PCR and Sanger sequencing of the cDNA of patients from blood samples after transplantation showed the expression of both wild type and mutant transcript expression of IFNGR2. To assess partial or complete expression of IFNGR2 mutant transcripts, fibroblasts were cultured from skin biopsies. RT-PCR and Sanger sequencing of cDNA obtained from patient fibroblasts revealed complete expression of mutant allele and acquisition of a cryptic splice acceptor site in exon 3 that resulted in deletion of 9 nucleotides in exon 3. This led to an in-frame deletion of three amino acids p.(Thr70-Ser72) located in a fibronectin type III (FN3) domain in the extracellular region of IFNGR2. This illustrates individualized medicine enabled by next generation sequencing as identification of this mutation helped in the clinical diagnosis of MSMD in the infants as well as in choosing the most appropriate therapeutic option.
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Predisposición Genética a la Enfermedad , Síndromes de Inmunodeficiencia/genética , Infecciones por Mycobacterium/genética , Receptores de Interferón/genética , Humanos , Lactante , Masculino , Mutación , Sitios de Empalme de ARNRESUMEN
This article summarises the main highlights of the abstracts presented at the annual meeting of American Society of Transplantation and Cellular Therapy (ASTCT). The highlights of ASTCT meeting were organised by iNDUS BMT group in Chennai, India. The purpose of the highlight meeting was to educate the students about the latest research in the field of hematopoietic stem cell transplantation and its applicability for the developing country perspective.