Outcomes of HLA-mismatched HSCT with TCRαß/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity.

HLA-mismatched transplants with either in vitro depletion of CD3+TCRαß/CD19 (TCRαß) cells or in vivo T-cell depletion using post-transplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEI). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEI undergoing first transplant between 2010-2019 from an HLA-mismatched donor using TCRαß (n=167) or PTCY (n=139). Median age at HSCT was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84%) after TCRαß and 66% (57-74%) after PTCY (p=0.013). Pre-HSCT morbidity score (hazard ratio (HR) 2.27, 1.07-4.80, p=0.032) and non-Busulfan/Treosulfan conditioning (HR 3.12, 1.98-4.92, p<0.001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50-66%) after TCRαß and 57% (48-66%) after PTCY (p=0.804). Cumulative incidence of severe acute GvHD was higher after PTCY (15%, 9-21%) than TCRαß (6%, 2-9%, p=0.007), with no difference in chronic GvHD (PTCY, 11%, 6-17%; TCRαß, 7%, 3-11%, p=0.173). The 3-year GvHD-free EFS was 53% (44-61%) after TCRαß and 41% (32-50%) after PTCY (p=0.080). PTCY had significantly higher rates of veno-occlusive disease (14.4% versus TCRαß 4.9%, p=0.009), acute kidney injury (12.7% versus 4.6%, p=0.032) and pulmonary complications (38.2% versus 24.1%, p=0.017). Adenoviraemia (18.3% versus PTCY 8.0%, p=0.015), primary graft failure (10%, versus 5%, p=0.048), and second HSCT (17.4% versus 7.9%, p=0.023) were significantly higher in TCRαß. In conclusion, this study demonstrates that both approaches are suitable options in IEI patients, although characterized by different advantages and outcomes.

Physicochemical and bioactive constituents, microbial counts, and color components of spray-dried Syzygium cumini L. pulp powder stored in different packaging materials under two controlled environmental conditions.

Currently, the demand for functional food items that impart health benefits has been rising. Blackberry (Syzygium cumini L.) fruit has high anthocyanin content and other functional attributes. However, this seasonal fruit is highly perishable, and a large proportion of it goes unharvested and wasted worldwide. Spray drying of the fruit pulp can impart improved shelf life, ensuring long-term availability for consumers to exploit its health benefits. The storage quality varies according to the type of packaging material and the storage environment. Therefore, in this study, the shelf life span of the spray-dried Syzygium cumini L. pulp powder (SSCPP) was investigated during 6 months of storage under three types of packaging materials (i.e., polystyrene, metalized polyester, and 4-ply laminates) in a low-temperature environmental (LTE) and at ambient environmental conditions. The physicochemical stability of bioactive principles (TPC and TAC), microbial counts, and color components were analyzed at 0, 2, 4, and 6 months of storage. There was a significant gradual loss of dispersibility and solubility with an increase in flowability, bulk density, and wettability during the entire storage period for all three packaging materials. The TSS, pH, TPC, TAC, and microbial counts decreased in the SSCPP both at ambient and LTE conditions during the study. Among all the packaging materials, the 4-ply laminate was found to be the most appropriate and safe for storage of spray-dried SCPP at LTE conditions.

A comprehensive review on infant formula: nutritional and functional constituents, recent trends in processing and its impact on infants' gut microbiota.

Human milk is considered the most valuable form of nutrition for infants for their growth, development and function. So far, there are still some cases where feeding human milk is not feasible. As a result, the market for infant formula is widely increasing, and formula feeding become an alternative or substitute for breastfeeding. The nutritional value of the formula can be improved by adding functional bioactive compounds like probiotics, prebiotics, human milk oligosaccharides, vitamins, minerals, taurine, inositol, osteopontin, lactoferrin, gangliosides, carnitine etc. For processing of infant formula, diverse thermal and non-thermal technologies have been employed. Infant formula can be either in powdered form, which requires reconstitution with water or in ready-to-feed liquid form, among which powder form is readily available, shelf-stable and vastly marketed. Infants' gut microbiota is a complex ecosystem and the nutrient composition of infant formula is recognized to have a lasting effect on it. Likewise, the gut microbiota establishment closely parallels with host immune development and growth. Therefore, it must be contemplated as an important factor for consideration while developing formulas. In this review, we have focused on the formulation and manufacturing of safe and nutritious infant formula equivalent to human milk or aligning with the infant's needs and its ultimate impact on infants' gut microbiota.

Effect of Astaxanthin and Copper Supplementation on Growth, Immunity, Antioxidant, and Blood Biochemical Status of Growing Murrah Buffalo Heifers.

This study was aimed to explore the effect of astaxanthin (ASTX) and copper (Cu) supplementation on the growth, immunity, antioxidant, and blood biochemical status of growing Murrah buffalo heifers. Twenty-eight Murrah buffalo heifers were selected and randomly divided into 4 groups (n = 7) after blocking by body weight (BW) (129.86 ± 5.37 kg) and age (9.05 ± 1.02 months). The heifers were fed basal total mixed ration diet without supplementation (CON) or with ASTX (0.20 mg/kg BW; AX), Cu (10 mg/kg DM; CU), or ASTX + Cu (0.20 mg/kg BW + 10 mg/kg DM; AX + CU) for 90 days of study period. The result showed that BW and dry matter intake (DMI) were significantly higher (P < 0.05) in AX + CU than that in other groups. The average daily gain (ADG) and feed conversion efficiency (FCE) were statistically higher (P < 0.05) in treatments than the values observed in CON. The feed conversion ratio (FCR) was reported significantly lower (P < 0.05) in the AX + CU group followed by AX, CU, and CON groups. The total leukocytes count (TLC), lymphocytes, and total immunoglobulin (TIG) were statistically higher (P < 0.05) in AX + CU groups than that found in other groups. However, neutrophil % decreased (P < 0.05) in the AX + CU group than its level in other groups. Superoxide dismutase (SOD), catalase (CAT), and total antioxidant (TAA) levels were observed higher (P < 0.05) in treatments supplemented with ASTX, Cu, or both than CON group. Thiobarbituric acid reactive substance (TBARS) concentration was lower (P < 0.05) in treatments than its level found in the CON group. Glucose level was higher (P < 0.05); however, non-esterifies fatty acid (NEFA) was lower (P < 0.05) in AX + CU than that in others groups. The level of cholesterol (CH), HDL cholesterol (HDL-CH), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were reported lower (P < 0.05) in the AX + CU group followed by CU, AX, and CON groups. The copper (Cu) level was higher (P < 0.05) in CU and AX + CU than AX and CON groups. The result of the present study indicated that the supplementation of ASTX, Cu alone, or their combination improved the growth, immunity, antioxidant status, and liver function of growing heifers.

Wilms tumor with Mulibrey Nanism: A case report and review of literature.

BACKGROUND: Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT). The published literature lacks data regarding the best treatment protocol and outcome of this cohort of children with WT and MUL. We report here a 2-year-old boy with WT and MUL and present a review of literature on WT in MUL. CASE: Our patient had associated cardiac problems of atrial septal defect, atrial flutter and an episode of sudden cardiac arrest. We managed him successfully with chemotherapy, surgery and multi-speciality care. He is alive and in remission at follow-up of 6 months. CONCLUSION: A total of 14 cases (including present case) of WT have been reported in MUL and treatment details were available for six cases. They were managed primarily with surgery, chemotherapy with/without radiotherapy, and all achieved remission. The outcome data is available only for two cases, one has been followed up till 15 years post treatment for WT and other is our patient.

Bacillus cereus infection in pediatric oncology patients: A case report and review of literature.

INTRODUCTION: Bacillus Cereus infection can be life-threatening in immunocompromised patients. We report here a case of Bacillus Cereus septicemia in a child with relapsed acute lymphoblastic leukemia (ALL) and present review of literature. METHODS: We collected clinical, laboratory and outcome data of our patient with relapsed ALL and Bacillus Cereus infection. We reviewed literature for Bacillus Cereus infection in pediatric oncology patients by searching MED-LINE/PubMed/Google/Google Scholar/Cochrane and summarized the data obtained. Various risk factors like presence of gastrointestinal or central nervous system (CNS) symptoms, neutropenia, central venous catheter in-situ, corticosteroids use, intrathecal chemotherapy and outcomes were analyzed using Fisher Exact Chi Square test. RESULTS: A 15-years-old boy with relapsed ALL on induction chemotherapy presented with giddiness and difficulty in breathing. He had an episode of hematemesis followed by fainting at home. He had refractory shock which did not respond to fluid boluses, inotropes and hydrocortisone. He had severe metabolic acidosis with high lactate and ammonia and died within 36-hours of onset of symptoms. His blood culture was positive for Bacillus Cereus. We came across 36 published cases of Bacillus Cereus in children with cancer including present case. Of these, 28 had acute leukemia and rest 8 had other cancers. CNS symptoms were present in 13 patients. Overall mortality was 25%. Patients with multisystem involvement had significantly higher mortality compared to those having localized disease (p-value 0.033). CONCLUSION: In pediatric oncology patients on chemotherapy, cultures positive for Bacillus Cereus should be considered significant. Mortality is higher in those with multisystem involvement.

Soluble Interleukin-2 Receptor Level as a Marker of Hemophagocytic Lymphohistiocytosis in Children With Severe Dengue.

Dengue induced-hemophagocytic lymphohistiocytosis (HLH) is increasingly recognized as an important cause of secondary HLH. Early identification of dengue HLH and directed therapy for HLH may help to alter the outcomes in critically ill patients. Soluble interleukin-2 receptor (IL2R) is a useful inflammatory marker and is seen to correlate with HLH disease activity. There is scarcity of data on IL2R in pediatric dengue patients with HLH. All patients (age < 18 years) with severe dengue confirmed by positive dengue IgM ELISA admitted to PICU were retrospectively enrolled. Patientswere screened for presence of HLH according to HLH 2004 criteria. Hemogram, ferritin, fibrinogen, liver, and renal function tests were noted. Patients who met four or more HLH criteria were treated with steroids and IL2R levels were sent to confirm the diagnosis of HLH. Out of 15 patients, nine patients met the criteria of HLH. IL2R levels were high in all HLH patients (mean 51,711, range 18,000-98,715 pg/mL). Mean ferritin levels were high in the HLH group as compared to non-HLH group (mean ferritin 34,593 vs. 3,206 ng/mL; p-value 0.004). Liver dysfunction was notably higher in the HLH group compared to non-HLH group (mean alanine aminotransferase 6,621 U/L vs. 165.6 U/L; p-value 0.04, mean aspartate aminotransferase 2,145 U/L vs. 104.2 U/L; 0.04, bilirubin level 4.2 mg/dL vs. 0.7 mg/dL; p-value 0.03). Four patients in the HLH group had acute kidney injury (AKI) and two required renal replacement therapy in the form of sustained low efficiency dialysis (SLED). Requirement for invasive ventilation was exclusively seen in HLH group and three patients developed ARDS. Two patients each in HLH and non-HLH group had shock requiring vasoactive therapy in addition to fluids. Mean days of ICU and hospital stay were higher in HLH group vs. non-HLH group but not statistically significant (6.4 vs. 4.4; p-value 0.32 and 8.44 vs. 5.6; p-value 0.18 days, respectively). All children in HLH group received steroids as per HLH protocol. In the HLH group, seven survived while two died. In the non-HLH group, all five patients survived. We concluded that IL2R levels are high in dengue HLH and useful for definitive diagnosis. Early recognition of this condition in severe dengue and prompt steroid therapy improves chances of better outcome.

Dengue virus transmission from donor to recipient during haploidentical stem cell transplantation.

Dengue fever is endemic in tropical and subtropical countries. Dengue virus transmission through hematopoietic stem cells is very rare and just two such cases have been reported previously. We report here only third case of dengue virus transmission in a 2-year-old child with thalassemia major who underwent hematopoietic stem cell transplant (HSCT) from a haploidentical related donor. One week after HSCT, the recipient developed fever, pancytopenia and signs of capillary leak. On day 10, his dengue NS1 antigen test was positive which confirmed diagnosis of dengue fever. Donor also had fever few days prior to stem cell donation which was later diagnosed to be due to dengue fever. Child had a severe clinical course of dengue leading to primary graft failure. However, he had autologous recovery of his own bone marrow and is alive and well on day+200 post HSCT. Our report highlights the transmission of dengue virus from donor to recipient through hematopoietic stem cell graft although rare but possible. We suggest that in tropical and subtropical countries where dengue is endemic, hematopoietic stem cell donors should be screened for it.

Peripheral blood stem cell mobilization with pegylated granulocyte colony stimulating factor in children.

BACKGROUND AND AIM: We report here our experience of using pegylated granulocyte colony stimulating factor (peg-GCSF) for peripheral blood stem cell (PBSC) mobilization in children. METHODS AND RESULTS: A total of nine children suffering from high-risk/relapsed solid tumors were mobilized with chemotherapy and peg-GCSF (100 microgram/kg single dose). Mean age was 7.7 years (range 2-15 years).The mean time from peg-GCSF administration to PBSC harvest was 9.7 days. Adequate stem cells (median dose 26.9 million/kg) could be harvested in all children by a single apheresis procedure. No major adverse events observed. CONCLUSION: It is feasible and safe to mobilize PBSC with peg-GCSF in children with cancer.

High serum ferritin alone as a predictor of mortality and hemophagocytic lymphohistiocytosis.

We report here utility of high serum ferritin alone as a predictor of mortality and diagnosis of hemophagocytic lymphohistiocytosis (HLH). We compared mortality in patients with high serum ferritin >5000 ng/mL versus <5000 ng/mL and looked for presence of HLH. Mortality was significantly higher (P-value .0048) in patients with serum ferritin levels >5000 ug/dL. Of 21 patients with high serum ferritin, a median of three criteria were fulfilled to diagnose HLH. All patients had features of immune-activation, and 76.2% patients had features of immune-pathology favoring diagnosis of HLH. Serum ferritin can aid in prediction of mortality and help in the early diagnosis of HLH.

Image fusion using hybrid methods in multimodality medical images.

An image fusion based on multimodal medical images renders a considerable enhancement in the quality of fused images. An effective image fusion technique produces output images by preserving all the viable and prominent information gathered from the source images without any introduction of flaws or unnecessary distortions. This review paper intends to bring out the process of image fusion, its utilization in the medical domain, merits, and demerits and reviews the perspective of multimodal medical image fusion. It also discusses the involvement of various medical entities like medical resonance imaging (MRI), positron emission tomography (PET), and computed tomography (CT). The usefulness of such modalities is presented, suggesting plausible hybrid modality combinations which could greatly enhance image fusion. This review also discusses innovative dispositions in the medical image fusion techniques for the achievement of incisively desired, quality images focused on fusion with wavelet transform and use of independent component analysis (ICA) and principal component analysis (PCA) techniques for the purpose denoising and data dimension reductions. Additionally, the future-prospects of an ideal technique for medical image fusion through the utilization of various medical modalities have been also discussed in this review paper. Graphical abstract.

Multicenter Outcome of Hematopoietic Stem Cell Transplantation for Primary Immune Deficiency Disorders in India.

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.

Portal vein thrombosis in a child with essential thrombocythemia seven years after diagnosis.

Portal vein thrombosis in children with essential thrombocythemia (ET) is a rarity. Here, we describe the long-term follow up of our previously reported case that since has developed portal vein thrombosis (PVT) 7-years after diagnosis. Our patient had presented with PVT with normal platelet counts and massive asymptomatic splenomegaly. Ultrasound and Computerized tomography confirmed presence of PVT. Our case highlights the importance of long-term follow up of children with ET for thrombosis, especially PVT, as it can happen without symptoms and normal platelet counts.

Summary of the Highlights of 2019 ASTCT Meeting by iNDUS BMT Group at Chennai, India.

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.