Ending preventable maternal mortality: phase II of a multi-step process to develop a monitoring framework, 2016-2030.

BACKGROUND: In February 2015, the World Health Organization (WHO) released "Strategies toward ending preventable maternal mortality (EPMM)" (EPMM Strategies), a direction-setting report outlining global targets and strategies for reducing maternal mortality in the Sustainable Development Goal (SDG) period. In May 2015, the EPMM Working Group outlined a plan to develop a comprehensive monitoring framework to track progress toward the achievement of these targets and priorities. This monitoring framework was developed in two phases. Phase I, which focused on identifying indicators related to the proximal causes of maternal mortality, was completed in October 2015. This paper describes the process and results of Phase II, which was completed in November 2016 and aimed to build consensus on a set of indicators that capture information on the social, political, and economic determinants of maternal health and mortality. FINDINGS: A total of 150 experts from more than 78 organizations worldwide participated in this second phase of the process to develop a comprehensive monitoring framework for EPMM. The experts considered a total of 118 indicators grouped into the 11 key themes outlined in the EPMM report, ultimately reaching consensus on a set of 25 indicators, five equity stratifiers, and one transparency stratifier. CONCLUSION: The indicators identified in Phase II will be used along with the Phase I indicators to monitor progress towards ending preventable maternal deaths. Together, they provide a means for monitoring not only the essential clinical interventions needed to save lives but also the equally important political, social, economic and health system determinants of maternal health and survival. These distal factors are essential to creating the enabling environment and high-performing health systems needed to ensure high-quality clinical care at the point of service for every woman, her fetus and newborn. They complement and support other monitoring efforts, in particular the "Survive, Thrive, and Transform" agenda laid out by the Global Strategy for Women's, Children's and Adolescents' Health (2016-2030) and the SDG3 global target on maternal mortality.

Elotuzumab as a novel anti-myeloma immunotherapy.

Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma. Although preclinical data looked very promising, elotuzumab monotherapy did not result in objective clinical responses in patients with relapsed/refractory multiple myeloma. However, combination treatment with immunomodulators and proteasome inhibitors resulted in substantial clinical activity in relapsed/refractory MM. Currently, there are several clinical trials ongoing investigating the role of elotuzumab in newly diagnosed myeloma patients and in patients receiving maintenance therapy.

Novel anti-myeloma immunotherapies targeting the SLAM family of receptors.

Treatment for multiple myeloma (MM) has significantly advanced in the last decade with the introduction of proteasome inhibitors and immunomodulatory therapies. Unfortunately, MM continues to cause significant morbidity and most patients eventually succumb to the disease. As in other areas of cancer, immunotherapy in MM has also evolved and holds promise to deliver long-lasting remissions or even cure. The signaling lymphocyte activation molecules (SLAM) family of surface proteins represents a group of potential targets for immunotherapy in MM as some of the family members are expressed consistently on plasma cells and also on myeloma propagating pre-plasma cells. Here, we review the SLAM family members in detail, describe their tissue distribution, biologic pathways, as well as relevant pre-clinical studies and clinical trials in MM. Our review demonstrates the value of SLAM family receptors as potential targets for anti-myeloma immunotherapies and outlines how immunotherapeutic approaches can be developed.

Chimeric Antigen Receptor (CAR) therapy for multiple myeloma.

The introduction of chimeric antigen receptor (CAR)-modified T cells has revolutionized immunotherapy and cancer treatment as a whole. However, so far, clinical efficacy has only been demonstrated for CD19-positive B cell lymphomas. For Multiple Myeloma (MM), the second most common haematological malignancy, there are currently no clinical results supporting the usefulness of the adoptive transfer of CAR-modified T cells. This might be related to the fact that an ideal surface target has not yet been identified or the presence of strong local immunosuppression in the tumour microenvironment, which is a hallmark of MM. In this review, we provide a comprehensive overview of promising target molecules for CAR T cell approaches in MM and we outline a number of ways in which the local immunosuppression in MM can be overcome. By providing a strategy for the design of CAR T cell treatments for MM we hope to transform this new therapeutic approach into a valuable tool within the therapeutic armamentarium for MM.

CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma.

Multiple Myeloma (MM) is a plasma cell (PC) malignancy, which despite significant therapeutic advances, is still considered incurable. This is due to the persistence of chemotherapy-resistant minimal residual disease in the patients' bone marrow (BM) after an effective induction therapy. Immunotherapies targeting surface molecules expressed on the bulk of tumor cells and the chemotherapy-resistant, myeloma-propagating cells could play a central role in this clinical setting. We recently described surface molecule CD229 as a potential therapeutic target for MM. In our current study we assessed the expression of CD229 on different PC subtypes and on cells with a myeloma-propagating phenotype in a total of 77 patients with PC dyscrasias independently at 2 different cancer centers. We found that CD229 was strongly and homogeneously overexpressed on the PC of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, MM, and PC leukemia. CD229 was particularly overexpressed on those PC showing an abnormal phenotype such as expression of CD56. Most importantly, CD229 was also highly expressed on those cells in the patients' BM displaying the phenotype of chemotherapy-resistant and myeloma-propagating cells. In conclusion, our combined findings suggest that immunotherapies targeting CD229 will not only be effective for the bulk of tumor cells but will also help to eradicate chemotherapy-resistant cells remaining in the patients' BM after induction treatment. Hopefully, the design of CD229-specific monoclonal antibodies or chimeric antigen receptor-transduced T cells will help to achieve prolonged remissions or even cures in MM patients.

Association of umbilical coiling index by colour Doppler ultrasonography at 18-22 weeks of gestation and perinatal outcome.

OBJECTIVE: To study the association between antenatal umbilical coiling index (aUCI) and perinatal outcome. METHODS: 600 primigravidas with uncomplicated singleton pregnancies had an ultrasonography between 18 and 22 weeks of gestation for aUCI by colour Doppler. The aUCI was calculated as the reciprocal of the distance between a pair of coils. It was then correlated with the following pregnancy outcomes: birth weight, mode of delivery, meconium staining of liquor, Apgar scores and gestational age. The results were statistically analysed by χ(2)-test. RESULTS: The mean aUCI was 0.41. Undercoiling was associated with spontaneous preterm delivery (47.87 %), low Apgar score (52.13 %), LBW (52.59 %), FGR (21.28 %) and NICU admission (76.34 %). Overcoiling was associated with preterm deliveries (65.38 %), increased caesarean sections (61.54 %), meconium staining of liquor (67.31 %), low Apgar score (63.46 %) and NICU admission (72.55 %). There was a positive strong correlation between aUCI and birth weight (r = +0.426). CONCLUSIONS: Abnormal coiling is strongly correlated with low birth weight.