A comprehensive and healthcare equity promoting response by a civil society-public partnership to COVID-19 in Chiapas, Mexico.

Following the first COVID-19 case in Chiapas, Mexico in March 2020, the non-governmental organisation Compañeros En Salud (CES) and the state's Ministry of Health (MOH) decided to join forces to respond to the global pandemic. The collaboration was built over 8 years of partnership to bring healthcare to underserved populations in the Sierra Madre region. The response consisted of a comprehensive SARS-CoV-2 infection prevention and control programme, which included prevention through communication campaigns to combat misinformation and stigma related to COVID-19, contact tracing of suspected and confirmed COVID-19 cases and their contacts, outpatient and inpatient care for patients with respiratory symptoms, and CES-MOH collaboration on anti-COVID-19 immunisation campaigns. In this article, we describe these interventions and their principal outcomes, as well as reflect on notable pitfalls identified during the collaboration, and we suggest a series of recommendations to prevent and mitigate their occurrence. As with many cities and towns across the globe, the poor preparedness of the local health system for a pandemic and pandemic response led to the collapse of the medical supply chain, the saturation of public medical facilities and the exhaustion of healthcare personnel, which had to be overcome through adaptation, collaboration and innovation. For our programme in particular, the lack of a formal definition of roles and clear lines of communication between CES and the MOH; thoughtful planning, monitoring and evaluation and active engagement of the communities served in the design and implementation of health interventions affected the outcomes of our efforts.

Combination high-dose interleukin-2 and nivolumab for programmed cell death-1 refractory metastatic melanoma: a case series.

BACKGROUND: Therapeutic options are needed for metastatic melanoma refractory to therapies directed against programmed cell death-1. High-dose interleukin-2 has the potential to overcome programmed cell death-1 resistance. CASE PRESENTATION: We report three consecutive Caucasian patients, two female (60 and 55 years old) and one male (56 years old), refractory to anti-programmed cell death-1 therapy who were treated with concurrent nivolumab and standard-dosing bolus high-dose interleukin-2. We did not see any unexpected toxicities with overlapping treatments as compared with either high-dose interleukin-2 or nivolumab alone. CONCLUSIONS: The tolerance and disease control observed among the three patients in this limited series support formal exploration of this combination.

Targeting ARID1A mutations in cancer.

Genes encoding SWI/SNF chromatin remodeling complex subunits are collectively mutated in approximately 20% of human cancers. ARID1A is a SWI/SNF subunit gene whose protein product binds DNA. ARID1A gene alterations result in loss of function. It is the most commonly mutated member of the SWI/SNF complex, being aberrant in ∼6% of cancers overall, including ovarian clear cell cancers (∼45% of patients) and uterine endometrioid cancers (∼37%). ARID1A has a crucial role in regulating gene expression that drives oncogenesis or tumor suppression. In particular, ARID1A participates in control of the PI3K/AKT/mTOR pathway, immune responsiveness to cancer, EZH2 methyltransferase activity, steroid receptor modulation, DNA damage checkpoints, and regulation of p53 targets and KRAS signaling. A variety of compounds may be of benefit in ARID1A-altered cancers: immune checkpoint blockade, and inhibitors of mTOR, EZH2, histone deacetylases, ATR and/or PARP. ARID1A alterations may also mediate resistance to platinum chemotherapy and estrogen receptor degraders/modulators.