Anti-myeloma efficacy of CAR-iNKT is enhanced with a long-acting IL-7, rhIL-7-hyFc

Multiple myeloma (MM), a malignancy of mature plasma cells, remains incurable. B-cell maturation antigen (BCMA) is the lead protein target for chimeric antigen receptor (CAR) therapy because of its high expression in most MM, with limited expression in other cell types, resulting in favorable on-target, off tumor toxicity. The response rate to autologous BCMA CAR-T therapy is high; however, it is not curative and is associated with risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Outcomes in patients treated with BCMA CAR-T cells (CAR-Ts) may improve with allogeneic CAR T-cell therapy, which offer higher cell fitness and reduced time to treatment. However, to prevent the risk of graft-versus-host disease (GVHD), allogenic BCMA CAR-Ts require genetic deletion of the T-cell receptor (TCR), which has potential for unexpected functional or phenotype changes. Invariant natural killer T cells (iNKTs) have an invariant TCR that does not cause GVHD and, as a result, can be used in an allogeneic setting without the need for TCR gene editing. We demonstrate significant anti-myeloma activity of BCMA CAR-iNKTs in a xenograft mouse model of myeloma. We found that a long-acting interleukin-7 (IL-7), rhIL-7-hyFc, significantly prolonged survival and reduced tumor burden in BCMA CAR-iNKT-treated mice in both primary and re-challenge settings. Furthermore, in CRS in vitro assays, CAR-iNKTs induced less IL-6 than CAR-Ts, suggesting a reduced likelihood of CAR-iNKT therapy to induce CRS in patients. These data suggest that BCMA CAR-iNKTs are potentially a safer, effective alternative to BCMA CAR-Ts and that BCMA CAR-iNKT efficacy is further potentiated with rhIL-7-hyFc

The largest multicentre data collection on prepectoral breast reconstruction: The iBAG study

Background and Objectives: In the last years, prepectoral breast reconstruction has increased its popularity, becoming a standard reconstructive technique by preserving pectoralis major anatomy and functionality. Nevertheless, the lack of solid and extensive data negatively impacts on surgeons\u2019 correct information about postoperative complication rates and proper patient selection. This study aims to collect the largest evidence on this procedure. Methods: A multicentre retrospective audit, promoted by the Barcelona Hospital, collected the experience of 30 centers on prepectoral breast reconstruction with Braxon ADM. The study had the scientific support of INPECS and IIB societies which provided the online database Clinapsis. Results: A total of 1450 procedures were retrospectively collected in a 6-year period. Mean age 52.4 years, BMI 23.9, follow-up 22.7 months. Reconstruction was carried out after a tumor in 77.1% of the cases, 20.1% had prophylactic surgery, 2.8% had revisions. Diabetes, smoke, and immunosuppression had an influence on complications occurrence, as well as implant weight. Capsular contracture was associated with postoperative radiotherapy, but the overall rate was low (2.1%). Complications led to implant loss in 6.5% of the cases. Conclusions: The international Braxon Audit Group multicentre data collection represents a milestone in the field of breast reconstruction, extensively improving the knowledge of this procedure

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Not AvailableDiagnostic surveys were conducted during 2015 and 2016 for screening the susceptible mango germplasm. About five hundred mango germplasm were screened against burl throughout the country. It is a typically swelling of the trunk and branches. Significant variation was observed in shape, colour, site of burl formation, surface, side of burl formation, site of gummosis, branching pattern and canopy of burl-affected trees. The incidence of burl in twenty-three mango germplasm in different parts of India and its effect on yield was also observed. Highest incidence was observed in ‘Arka Aruna’, ‘Mahuvas’, ‘Seedling’, ‘Tree 253’, ‘Mehmud Vikarabad’, ‘Hybrid 10’, ‘Khaja Pasand’, ‘Gopalbhog’, ‘Malai’, ‘Seedling’ 68 and ‘Seedling’ 307 germplasm. Information was also collected on the relationship between the growth of the burl and the age of the trees in ‘Langra’, ‘Bathua’, ‘Sukul’, Banganpalli, ‘Mehmud Vikarabad’, ‘Khaja Pasand’ and ‘Rajapuri’ germplasm. The size of the burl coincides with age of the trees from 25 to 90 years. Orchards topography also play major role in disease incidence and intensity. Maximum fruit yield, minimum disease incidence and intensity recorded in bottom land. Maximum incompatibility, incidence percentage and disease severity were observed in grafted trees while no incidence was observed in non-grafted/’Seedling’ trees reported first time. Hence, the source of burl inoculum was scions taken from infected old mother trees for propagation. These findings may have implications in the understanding of this new woody disease in mango trees.Not Availabl

Drought impacts and adaptation strategies for agriculture and rural livelihood in Maharashtra State of India

Nearly one-sixth of India is defined as a Drought Prone Area, and as such recurring drought is one of the major challenges in the region. This article focuses on various drought impacts in an important state of India (i.e. Maharashtra State), which contributes about 15% of the country's gross domestic product (GDP). Drought impacts vary from region to region, but the overall issues are similar and Maharashtra State is indicative of the rest of the Drought Prone Area of the country. This article briefly reviews the major impacts of the 2012 drought on Maharashtra State¿s water resources, agriculture, food security, adopted adaptation and mitigation measures and also outlines scope for future research

Observational cohort study in older women with early breast cancer: use of radiation therapy and impact on health-related quality of life and mortality

Background Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL). Methods A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires. Results In 2013–2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months. Conclusion Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient