Correlation of platelet crossmatch results by Solid Phase Red Cell Adherence Assay (SPRCA) with post-transfusion platelet count increment in adult hemato-oncology patients of a tertiary care oncology centre in India.

AIMS: To assess platelet crossmatch result by SPRCA and find its correlation with post-transfusion platelet count increment among adult hemato-oncology patients. METHODS: A prospective observational pilot study of 50 adult hematologic malignancy patients previously transfused, but not already known to be transfusion-refractory and without any nonimmune causes for inadequate response to platelet transfusion were included after obtaining informed consent. They were transfused one unit of ABO identical single donor platelet. Ten minutes to 1 -h post-transfusion CCI was calculated. CCI ≥ 7500 was considered as adequate response. Post-transfusion crossmatching by SPRCA was performed by using preserved platelet samples from donor units with the serum of the respective patient. Statistical analysis of the correlation between platelet crossmatch results and CCI was done. RESULTS: Out of 50 crossmatches, 78% (39/50) showed compatible and 22% (11/50) showed incompatible results. Among 39 compatible results, 87.2% (34/39) showed adequate CCI and 12.8% (5/39) showed inadequate CCI. Among 11 incompatible results, 18.2% had adequate CCI and 81.8% had inadequate CCI. The difference between the response in terms of CCI to compatible and incompatible crossmatches was found to be statistically significant (p < 0.05). Other variables like age, sex, number of previous transfusions and underlying clinical condition of the patient were not found to have any effect on the compatibility of crossmatch. CONCLUSIONS: Transfusion of crossmatched platelets to non-refractory, multiply transfused hematological malignancy patients without serious illness might provide a small benefit over transfusing randomly selected platelets, though these data must be confirmed with a larger sample size.

Development of High Yielding Fusarium Wilt Resistant Cultivar by Pyramiding of "Genes" Through Marker-Assisted Backcrossing in Chickpea (Cicer arietinum L.).

Pusa 391, a mega desi chickpea variety with medium maturity duration is extensively cultivated in the Central Zone of India. Of late, this variety has become susceptible to Fusarium wilt (FW), which has drastic impact on its yield. Presence of variability in the wilt causing pathogen, Fusarium oxysporum f.sp. ciceri (foc) across geographical locations necessitates the role of pyramiding for FW resistance for different races (foc 1,2,3,4 and 5). Subsequently, the introgression lines developed in Pusa 391 genetic background were subjected to foreground selection using three SSR markers (GA16, TA 27 and TA 96) while 48 SSR markers uniformly distributed on all chromosomes, were used for background selection to observe the recovery of recurrent parent genome (RPG). BC1F1 lines with 75-85% RPG recovery were used to generate BC2F1. The plants that showed more than 90% RPG recovery in BC2F1 were used for generating BC3F1. The plants that showed more than 96% RPG recovery were selected and selfed to generate BC3F3. Multi-location evaluation of advanced introgression lines (BC2F3) in six locations for grain yield (kg/ha), days to fifty percent flowering, days to maturity, 100 seed weight and disease incidence was done. In case of disease incidence, the genotype IL1 (BGM 20211) was highly resistant to FW in Junagarh, Indore, New Delhi, Badnapur and moderately resistant at Sehore and Nandyal. GGE biplot analysis revealed that IL1(BGM20211) was the most stable genotype at Junagadh, Sehore and Nandyal. GGE biplot analysis revealed that IL1(BGM 20211) and IL4(BGM 20212) were the top performers in yield and highly stable across six environments and were nominated for Advanced Varietal Trials (AVT) of AICRP (All India Coordinated Research Project on Chickpea) in 2018-19. BGM20211 and BGM 20212 recorded 29 and 28.5% average yield gain over the recurrent parent Pusa 391, in the AVT-1 and AVT-2 over five environments. Thus, BGM20211 was identified for release and notified as Pusa Manav/Pusa Chickpea 20211 for Madhya Pradesh, Gujarat and Maharashtra, Southern Rajasthan, Bundhelkhand region of Uttar Pradesh states by the Central Sub-Committees on Crop Standards, Notification and Release of Varieties of Agricultural Crops, Ministry of Agriculture and Farmers Welfare, Government of India, for commercial cultivation in India (Gazette notification number S.O.500 (E) dt. 29-1-2021).Such pyramided lines give resilience to multiple races of fusarium wilt with added yield advantage.

Modeling BCR-ABL and MLL-AF9 leukemia in a human bone marrow-like scaffold-based xenograft model.

Although NOD-SCID IL2Rγ-/- (NSG) xenograft mice are currently the most frequently used model to study human leukemia in vivo, the absence of a human niche severely hampers faithful recapitulation of the disease. We used NSG mice in which ceramic scaffolds seeded with human mesenchymal stromal cells were implanted to generate a human bone marrow (huBM-sc)-like niche. We observed that, in contrast to the murine bone marrow (mBM) niche, the expression of BCR-ABL or MLL-AF9 was sufficient to induce both primary acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Stemness was preserved within the human niches as demonstrated by serial transplantation assays. Efficient engraftment of AML MLL-AF9 and blast-crisis chronic myeloid leukemia patient cells was also observed, whereby the immature blast-like phenotype was maintained in the huBM-sc niche but to a much lesser extent in mBM niches. We compared transcriptomes of leukemias derived from mBM niches versus leukemias from huBM-like scaffold-based niches, which revealed striking differences in the expression of genes associated with hypoxia, mitochondria and metabolism. Finally, we utilized the huBM-sc MLL-AF9 B-ALL model to evaluate the efficacy of the I-BET151 inhibitor in vivo. In conclusion, we have established human niche models in which the myeloid and lymphoid features of BCR-ABL+ and MLL-AF9+ leukemias can be studied in detail.

Management of childhood pneumonia by traditional birth attendants. The SEARCH Team.

In a field trial in Gadchiroli, India, we trained 30 paramedical workers (PMWs), 25 village health workers (VHWs) and 86 traditional birth attendants (TBAs) from 58 villages to diagnose childhood pneumonia and treat it with sulfamethoxazole+trimethoprim. Continued training, the development of a breath counter, and educative supervision progressively reduced errors in case management made by the TBAs. Over the 3.5-year period 1988-91, 2568 attacks of childhood pneumonia were managed and the case fatality rate was 0.9%, compared with a rate of 13.5% in the control area. The case fatality rates for the three types of worker were similar. The TBAs were superior to the other workers in terms of their availability, outreach, access to neonates, and cost. Satisfaction with the VHWs, and PMWs was expressed by 85%, 69% and 18% of users, respectively. In the intervention area the mortality rate attributable to pneumonia among neonates declined by 44% (P < 0.01) while the total neonatal mortality fell by 20%, presumably because of the involvement of TBAs in the control of acute respiratory infections (ARI). If adequately supported by the health system, TBAs can successfully manage childhood pneumonia in villages at the lowest possible cost and with a high degree of community acceptance. TBAs and VHWs are the most suitable community-based health workers for ARI control programmes in developing countries.

Reduction in pneumonia mortality and total childhood mortality by means of community-based intervention trial in Gadchiroli, India.

In a community-based intervention trial to reduce childhood mortality from pneumonia the intervention area included 58 villages (6176 children aged 0-4 years) and the control area 44 villages (3947 children) in Gadchiroli, India. The interventions included mass education about childhood pneumonia and case-management of pneumonia by paramedics, village health workers, and traditional birth attendants (TBAs) who were trained to recognise childhood pneumonia and treat it with co-trimoxazole. Parents sought treatment, and coverage was 76% without active case-detection efforts. The case-fatality rate among the 612 cases treated by health workers was 0.8%, compared with 13.5% in the control area. After a year of intervention pneumonia-specific childhood mortality was significantly lower in the intervention than in the control area (8.1 vs 17.5 deaths per 1000 children under 5 years); the difference between the areas was greatest in children under 1 year. The differences in infant mortality (89 vs 121 per 1000) and total under-5 mortality (28.5 vs 40.7 per 1000) were highly significant. Mortality from other causes remained similar in the two areas but neonatal mortality due to birth injury and prematurity was significantly lower in the intervention area, presumably owing to the combination of better maternal and neonatal care by the TBAs trained in the project and the availability of treatment for pneumonia. The cost of co-trimoxazole was US $0.025 per child per year ($2.64 per child saved).

Pneumonia in neonates: can it be managed in the community?

Neonatal pneumonia kills about two million children a year worldwide. The World Health Organisation recommends hospitalisation of all cases of pneumonia in the first two months of infancy. In a field trial of community based management of childhood pneumonia in Gadchiroli, India, neonatal pneumonia contributed more than half of the pneumonia deaths. Parents refused referral even when advised therefore community based health workers and traditional birth attendants managed cases of neonatal pneumonia with co-trimoxazole. Case fatality was 15% (10/65) in all cases and 6% (3/52) in cases without high risk or referral indications. Case fatality in 56 babies aged 30-59 days treated for pneumonia was zero. During the two years of the trial, pneumonia specific mortality rate in the intervention area was 40% less in the neonates and about 80% less in the second month and rest of infancy compared with the control area. Pneumonia in the second month of infancy and uncomplicated cases of neonatal pneumonia can be safely and effectively managed in the community using co-trimoxazole.