Fundacion Favaloro Hospital Universitario

In November 2021, the Surviving Sepsis Campaign (SSC) published an update to its 2016 guidelines and recommendations. Subsequently, during the CIMU 2022 (33rd World Congress on Emergency Medicine, held in March 2022 in Guadalajara, Mexico), the 2021 SSC Guidelines were reviewed and analyzed from the perspective of emergency physicians (EPs). The experts involved in this task also reached consensus and published several key points of greatest interest and concern to EPs regarding the management of patients with severe infection or sepsis in hospital emergency departments (EDs). These points included several improvement proposals developed by GTLATINFURG (Latin American Working Group for Improving Infection Care in Emergency Departments) and formally presented in what became known as the "Guadalajara Declaration." That document outlined complementary or alternative considerations to the 2021 SSC Guidelines. The first proposal was to "develop guidelines aimed at detecting, preventing progression, and managing patients with severe infection and sepsis in EDs." Since then-and owing to numerous original research studies and review articles published by the GT-LATINFURG and INFURG-SEMES groups (Infection Study Group of the Spanish Society of Emergency Medicine)-we can now claim that there is scientific evidence generated in EDs themselves, or at least that existing evidence has been reviewed while considering the specific role of EPs. The main aim of this consensus document, as the initial presentation of the first proposal of the Guadalajara Declaration, is to analyze-based on routine clinical practice, experience, available evidence, and the perspective of ED physicians-several key issues and controversies in order to establish recommendations through expert consensus grounded in current scientific evidence.

ABSTRACTThe role of perioperative immunotherapy as a chemotherapy-free option for patients with resectable mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colon cancer is evolving, with early-phase neoadjuvant studies reporting favorable long-term outcomes. AZUR-2 is an ongoing global, Phase III, open-label, randomized study evaluating the efficacy of perioperative dostarlimab monotherapy compared with standard of care (SoC) (adjuvant chemotherapy or surveillance) in adult patients with previously untreated, pathologically confirmed, radiologically evaluable T4N0 or Stage III resectable dMMR/MSIH colon adenocarcinoma. Patients will be randomized 2:1 to receive neoadjuvant dostarlimab 500 mg every 3 weeks (4 cycles), followed by surgery, then adjuvant dostarlimab 1000 mg every 6 weeks (6 cycles), or to receive immediate surgery followed by SoC. The primary endpoint is event-free survival assessed by blinded independent central review. The key secondary endpoint is overall survival; additional secondary endpoints include pathological response assessed by residual viable tumor determined by local assessment, safety, and tolerability.Clinical trial registration: NCT05855200 (www.clinicaltrials.gov).

Stent failure (SF) is a complication of percutaneous coronary intervention (PCI). This study aimed to assess the relationship of the optical coherence tomography (OCT) determined cause of SF with time since stent implantation, treatment, and outcome. This retrospective study included patients who underwent an OCT evaluation for SF from January 2013 to July 2023. In-stent findings were evaluated on OCT including tissue proliferation, tissue type, underexpansion, thrombus, and multiple stent layers. The relationship between time to presentation, treatment, and outcome was assessed. Of the 309 patients who underwent an OCT-guided PCI for SF, tissue proliferation was present in 228 (74%) and absent in 81 (26%). Among patients with tissue proliferation, OCT commonly showed lipidic neointima (n = 122, 54%), thrombus (n = 81, 36%), and underexpansion (n = 71, 31%). In patients without tissue proliferation, OCT commonly identified underexpansion (n = 58, 72%), thrombus (n = 55, 68%), and uncovered struts (n = 37, 46%). The mean time to SF was 6.89 ± 5.88 years with tissue proliferation and 2.98 ± 3.75 years without (p < 0.001). Patients with tissue proliferation were more likely to be treated with repeat stenting (78% vs. 60%, p < 0.001). Lipidic neointimal tissue and >1 layer of stent were predictors of target SF recurrence during a median 3 years of follow-up. In a large series of OCT-guided treatments of SF, tissue proliferation was more common, occurred later after stent implantation, and was more likely to be treated with repeat stenting than no-tissue proliferation. Lipidic neointimal tissue and >1 layer of stent were significant predictors of target SF during follow-up.

There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed. Multivariate regression analysis showed anti-cd20 (β= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (β=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Findings regarding humoral and cellular response are consistent with previous reports.