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* Context.--The US Food and Drug Administration (FDA) approved immune checkpoint inhibitor therapy for patients with advanced solid tumors that have DNA mismatch repair defects or high levels of microsatellite instability; however, the FDA provided no guidance on which specific clinical assays should be used to determine mismatch repair status. Objective.--To develop an evidence-based guideline to identify the optimal clinical laboratory test to identify defects in DNA mismatch repair in patients with solid tumor malignancies who are being considered for immune checkpoint inhibitor therapy. Design.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Using the National Academy of Medicine-endorsed Grading of Recommendations Assessment, Development and Evaluation approach, the recommendations were derived from available evidence, strength of that evidence, open comment feedback, and expert panel consensus. Mismatch repair immunohistochemistry, microsatellite instability derived from both polymerase chain reaction and next-generation sequencing, and tumor mutation burden derived from large panel next-generation sequencing were within scope. Results.--Six recommendations and 3 good practice statements were developed. More evidence and evidence of higher quality were identified for colorectal cancer and other cancers of the gastrointestinal (GI) tract than for cancers arising outside the GI tract. Conclusions.--An optimal assay depends on cancer type. For most cancer types outside of the GI tract and the endometrium, there was insufficient published evidence to recommend a specific clinical assay. Absent published evidence, immunohistochemistry is an acceptable approach readily available in most clinical laboratories. doi: 10.5858/arpa.2021-0632-CP, Clinical laboratory assays for detection of high levels of tumor microsatellite instability (MSI-High) or loss of DNA mismatch repair (MMR) protein expression by immunohistochemistry (IHC) are familiar to many pathologists [...]

The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected.

Why you should read this article: • To increase your understanding of acupuncture • To enhance your knowledge of the evidence on the use of acupuncture as an additional pain management strategy for people with cancer • To recognise the potential beneficial effects of acupuncture on cancer pain and symptoms associated with cancer treatments. Pain is a common symptom experienced by people with cancer and inadequate pain management can adversely affect their quality of life. Acupuncture can be used as an additional supportive pain management strategy in people with cancer. This article reports the findings of a literature review that explored the role of acupuncture as an adjunct pain relief option for people with cancer. The findings suggest that acupuncture is effective in relieving pain when used in addition to pharmacological options and can reduce some of the side effects associated with cancer treatments; it also has minimal side effects. Further research into the optimal ‘dose’ of acupuncture in each treatment session and the optimal number and frequency of treatment sessions is required to facilitate incorporation of this therapy into routine cancer care. [ABSTRACT FROM AUTHOR]

Aims: NTRK‐rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma‐like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan‐TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan‐TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan‐TRK immunohistochemistry to distinguish NTRK‐rearranged sarcoma from its mimics. Methods and results: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK‐rearranged sarcomas) were selected. Pan‐TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan‐TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK‐rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan‐TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan‐TRK immunohistochemical expression: three low‐grade endometrial stromal sarcomas, seven high‐grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan‐TRK cytoplasmic staining with weak/moderate intensity. Conclusion: Even though pan‐TRK immunohistochemical expression is not entirely sensitive or specific for NTRK‐rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan‐TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation. [ABSTRACT FROM AUTHOR]