Ionothermal Synthesis of Four New Nickel Thiophosphate Anions: [Ni(P₂S₈)₂]^2–, [Ni(P₃S₉)(P₂S₈)]^3–, [Ni(P₃S₉)₂]^4–, and [(NiP₃S₈)₄(PS₄)]^7–

Four new nickel thiophosphate anions have been isolated as 1-ethyl-3-methylimidazolium (EMIM) salts: [EMIM]₂[Ni­(P₂S₈)₂] (<b>1</b>), [EMIM]₃[Ni­(P₃S₉)­(P₂S₈)] (<b>2</b>), [EMIM]₄[Ni­(P₃S₉)₂] (<b>3</b>), and [EMIM]₇[(NiP₃S₈)₄(PS₄)] (<b>4</b>). Single crystals of each were prepared by ionothermal reaction of the elements in [EMIM]­[BF₄]. <b>1</b> can also be obtained from [EMIM]­[CF₃SO₃]. In all four anions, Ni atoms are octahedrally coordinated and P atoms are tetrahedrally coordinated. In the anion found in <b>1</b>, two tridentate 1,3-P₂S₈^2– ligands are cis to each other. The anion in <b>2</b> contains two different tridentate thiophosphate ligands, 1,3-P₂S₈^2– and P₃S₉^3–, whereas the anion in <b>3</b> consists of two P₃S₉^3– ligands coordinated to the central Ni atom. The anion in <b>4</b> is complex, consisting of four NiP₃S₈^– clusters surrounding a central PS₄ tetrahedron; within the NiP₃S₈^– groups, one P atom is directly bound to Ni. The discovery of these four new compounds demonstrates the versatility of ionothermal methods for the synthesis of novel thiophosphates

Phase 2 study of preoperative chemotherapy with nab‐paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node‐positive pancreatic ductal adenocarcinoma

Abstract Background Neoadjuvant treatment with nab‐paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down‐stage tumors to achieve negative surgical margins. Methods A single‐arm, open‐label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node‐positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m2 and nab‐paclitaxel 125 mg/m2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity‐modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab‐paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events. Results Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near‐complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12‐month progression‐free survival was 58%, and 12‐month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia. Conclusion Gemcitabine and nab‐paclitaxel followed by long‐course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node‐positive pancreatic cancer

Neoadjuvant Therapy Is Associated with Improved Chemotherapy Delivery and Overall Survival Compared to Upfront Resection in Pancreatic Cancer without Increasing Perioperative Complications.

The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection

Evolution of plastic transmission strategies in avian malaria

International audienceMalaria parasites have been shown to adjust their life history traits to changing environmental conditions. Parasite relapses and recrudescences—marked increases in blood parasite numbers following a period when the parasite was either absent or present at very low levels in the blood, respectively—are expected to be part of such adaptive plastic strategies. Here, we first present a theoretical model that analyses the evolution of transmission strategies in fluctuating seasonal environments and we show that relapses may be adaptive if they are concomitant with the presence of mosquitoes in the vicinity of the host. We then experimentally test the hypothesis that Plasmodium parasites can respond to the presence of vectors. For this purpose, we repeatedly exposed birds infected by the avian malaria parasite Plasmodium relictum to the bites of uninfected females of its natural vector, the mosquito Culex pipiens, at three different stages of the infection: acute (∼34 days post infection), early chronic (∼122 dpi) and late chronic (∼291 dpi). We show that: (i) mosquito-exposed birds have significantly higher blood parasitaemia than control unexposed birds during the chronic stages of the infection and that (ii) this translates into significantly higher infection prevalence in the mosquito. Our results demonstrate the ability of Plasmodium relictum to maximize their transmission by adopting plastic life history strategies in response to the availability of insect vectors

Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

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