SUMMARYGene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system, and avoids lifetime highly active antiretroviral therapy. This study, the first randomized, double-blind, placebo-controlled, phase II cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1 infected adults who received a tat/vpr specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistical difference in viral load between the OZ1 and placebo group at the primary end-point (average at weeks 47 and 48) but time weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study provides the first indication that cell-delivered gene transfer is safe and biologically active in HIV patients and can be developed as a conventional therapeutic product.

BackgroundSince the overall prognosis of very elderly patients is generally limited, admissions to intensive care in these patients are often restricted. Therefore, only very few information is available on the prognosis of nonagenarians after intensive care treatment. The aim of this study was to analyze the clinical characteristics and outcomes of very elderly patients (≥90 years) admitted to an intensive care unit (ICU).MethodsMonocentric, retrospective observational study of all patients aged ≥90 years admitted to the Department of Intensive Care Medicine with a total capacity of 132 ICU beds at the University Medical Center Hamburg in Germany between January 2008 and June 2013. A multivariate Cox regression analysis was used to identify risk factors for 28-day outcome.ResultsA total of 372 patients ≥90 years of age were admitted to one of the departments ICUs. The majority of patients (66.7 %) were admitted as an emergency admission, of which half underwent unscheduled surgery. 39.8 % of patients required support by mechanical ventilation and vasoactive drugs, and 1.9 % of patients received renal replacement. ICU and hospital mortality rates were 18.3 and 30.9 %, respectively. Overall survival at 1 year after hospital discharge was 34.9 %. Multivariate Cox regression analysis revealed creatinine, bilirubin, age, and necessity of catecholamines as independent risk factors and scheduled surgery as protective factor for 28-day outcome.ConclusionNearly 70 % of patients aged ≥90 years were discharged alive from hospital following treatment at the ICU, and more than half of them were still alive 1 year after their discharge. The results suggest that 1-year survival prognosis of very old ICU patients is not as poor as often perceived and that age per se should not be an exclusion criterion for ICU admission.Trial registration: WF-0561/13

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Background: ORIENT-16 is a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of sintilimab in combination with chemo (S+C) vs chemo (C) as the first-line treatment for patients (pts) with advanced G/GEJ adenocarcinoma. We report the first results from a pre-specified interim analysis.Methods: Eligible pts were adults (18 years) with untreated, unresectable locally advanced or metastatic G/GEJ adenocarcinoma, regardless of PD-L1 expression. Pts were randomized 1:1 to receive sintilimab (3mg/kg and 200 mg, respectively, for body weights <60kg and 60kg, IV Q3W) or placebo plus chemo (CapeOX: oxaliplatin 130 mg/m 2 IV Q3W, up to 6 cycles, capecitabine 1000 mg/m 2 PO Bid d1-14 Q3W) for up to 24 months. The primary endpoints were OS in the pts with CPS 5 and all randomized pts. Data cutoff date for interim analysis was June 20, 2021.Conclusions: Trast/nivo/FOLFOX showed increased efficacy compared to the ToGA regimen, whereas trast/nivo/ipi did not improve OS over trast/chemo. Subgroupanalyses are ongoing and will be presented.Clinical trial identification: NCT03409848.Legal entity responsible for the study: AIO Studien gGmbH.

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