IMPORTANCE Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).OBJECTIVE To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. DESIGN, SETTING, AND PARTICIPANTSThe CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018.INTERVENTIONS Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. MAIN OUTCOMES AND MEASURESThe primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. RESULTS Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, −0.10; 95% CI, −1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, −8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, −2.8 to 4.2; P = .70) at 168 hours. CONCLUSIONS AND RELEVANCEIn this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.

PURPOSE To describe the establishment of an oncology unit at the National Referral Hospital (NRH) in the Solomon Islands, a low-income nation in the South Pacific. METHODS A scoping visit was carried out in 2016 to assist in the development of coordinated cancer services and to establish a medical oncology unit at the NRH at the request of the Medical Superintendent. This was followed by an observership visit to Canberra by an NRH doctor training in oncology in 2017. After a request from the Solomon Islands Ministry of Health, the Australian Government Department of Foreign Affairs and Trade (DFAT) arranged an in-country multidisciplinary mission under the Royal Australasian College of Surgeons/Royal Australasian College of Physicians Pacific Islands Program to help in the commissioning of the NRH Medical Oncology Unit in September 2018. Staff training and education sessions were held. The team, with the assistance of an Australian Volunteers International Pharmacist, has helped the NRH staff to develop localized Solomon Islands Oncology Guidelines. Donated equipment and supplies have helped with the initial establishment of the service. A second DFAT Oncology mission visit was made in 2019 followed by two NRH oncology nurses visiting Canberra on observership later that year and support of the Solomon's doctor to pursue postgraduate education in cancer sciences. Ongoing mentorship and support has been maintained. RESULTS The island nation now has a sustainable oncology unit delivering chemotherapy treatments and management of patients with cancer. CONCLUSION A collaborative multidisciplinary team approach by professionals from the high-income country working with colleagues from the low-income nation with coordination of different stakeholders was the key to this successful initiative in improving cancer care.

The connection between indigenous peoples and Country (a multidimensional concept including land and water) enabled communities to thrive and survive over millennia. This has been eroded by colonisation, dispossession and increasing food and water insecurity due to climate change and supply constraints. Globally, indigenous peoples experience a disproportionate burden of chronic disease and poor nutrition is a major risk factor. Indigenous leaders have been advocating for community-led solutions. The primary aim of this systematic review is to determine what community-led programs have been undertaken to address food and/or water security globally. A comprehensive search of peer-reviewed literature will be performed in EMBASE, CINAHL, PsycINFO, PubMed, Scopus, LILACs, Informit and Business Source Premier. The grey literature search will include grey literature databases, customised Google search engines, targeted websites, and consultation with experts. The search strategy will consist of four concepts, combined as follows: (1) indigenous peoples AND (2) community program AND (3) food security OR (4) water security. Covidence will be used for study screening and data extraction by two authors. A deductive thematic analysis using indigenous-informed methodologies will be used to synthesise data. This review seeks to provide insight on models and mechanisms to encourage action and metrics for quantifying success of indigenous community-led programs to improve food and water security.

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Lung cancer is the second most common cancer in both men and women. Despite several treatment options, chemotherapy remains a major standard-of-care treatment modality. Over time cancer cells acquire drug resistance and evade its effects for survival. The combination of chemotherapeutic drugs with the non-overlapping mechanism of actions are one alternative approach to treat drug-resistant cancers. Paclitaxel (PAC) and cisplatin (CisPt) are widely used to treat non-small cell-lung cancer (NSCLC). However, dose-limiting toxicity, metastasis and chemoresistance have restricted its use. Our recent findings suggested that PAC, when loaded onto folic acid (FA)-functionalized colostrum exosomes (FA-ExoPAC) and administered orally, exceeded the efficacy of i.v. PAC but matched efficacy of i.v. albumin-bound PAC nanoformulation (Abraxane [Abx]) against A549 orthotopic lung tumors. Furthermore, unlike i.v. PAC and i.v. Abx, oral FA-ExoPAC lacked immune toxicity. In order to advance the FA-ExoPAC to clinical studies, we determined if the exosomal formulation will interfere in CisPt therapy. MTT assay showed similar antiproliferative activity of ExoPAC and PAC (IC50 6.25 nM) against drug-sensitive A549 lung cancer cells. However, the antiproliferative activity of ExoPAC (IC50 38 nM) was much greater than for PAC (IC50 >>100 nM) against drug-resistant A549TR lung cancer cells. The activity was further enhanced with FA-functionalized ExoPAC. The enhanced efficacy of the drug presumably resulted from higher cell uptake of ExoPAC and FA-ExoPAC by both drug-sensitive and drug-resistant cells. To determine the effect of the combination of ExoPAC and CisPt, A549 and A549TR cells were treated with increasing concentrations of both the drugs, alone and in combination, for 72 h. MTT assay showed that CisPt (20 µM) and ExoPAC (80 nM) inhibited the growth of A549 cells by 47% and 75%, respectively, the effect was significantly increased with the combination (>95% inhibition). The combination effect was likewise enhanced against the A549TR, except the respective concentration of CisPt (40 µM) and ExoPAC (200 nM) was increased to achieve >95% growth inhibition; the inhibition was lower (50–60%) when treated individually. Together, these data suggest that targeted oral therapy with FA-ExoPAC can potentially eliminate drug resistance and inhibit metastasis with minimal or no side effects and warrants testing in the clinical settings (Supported from the NIH grant R44-CA-221487 and Agnes Brown Duggan Endowment). Citation Format: Raghuram Kandimalla, Disha N. Moholkar, Jayaprakash Jeyabalan, Wendy Spencer, Ramesh C. Gupta, Farrukh Aqil. Exosomal paclitaxel formulation, alone and in combination with cisplatin, enhances drug’s efficacy against lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 371.