Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Efectos de un área de veda a la pesca de arrastre sobre la dieta y el nivel trófico de la merluza, Merluccius merluccius, en el sur del Mar Tirreno

14 pages, 5 figures, 5 tables, 1 appendix[En] This study assesses the effects of a trawling ban on the diet and trophodynamics of the hake Merluccius merluccius by comparing stomach contents and stable isotopes (δ15N and δ13C) in two trawled gulfs and one untrawled gulf in northern Sicily (western Mediterranean). Comparisons were made for three size classes of hake encompassing 60 to 410 mm total length. Fish were collected from 50 to 200 m depth on muddy bottoms. The diets of hake of small and medium size were similar overall but more selective in the untrawled gulf. Greater differences were detected between the diets of larger specimens from trawled and untrawled areas. In the untrawled gulf large hake mainly preyed on clupeoid fish, while in the trawled gulfs other fish prey were found in the stomach contents. δ15N values of hake did not vary significantly between trawled and untrawled areas, while there was a clear effect of size, with larger individuals being significantly more enriched than juveniles. Conversely, δ13C values were generally more depleted for individuals collected in the untrawled area, suggesting a more pelagic source of carbon. The results from the mixing model agree fairly well with the known feeding habits found for each size class in each area[Es] Este estudio evaluó los efectos de la pesca de arrastre comercial en la dieta y la trofodinámica de la merluza mediterránea, Merluccius merluccius, mediante la comparación de sus contenidos estomacales y de la composición isotópica (δ15N y δ13C) en dos golfos donde está permitida la pesca de arrastre y en uno donde está prohibida, en el norte de Sicilia (Mediterráneo Occidental). Las comparaciones se hicieron para tres clases de talla que abarca la merluza entre 60 y 410 mm de longitud total. Los peces fueron recolectados en los fondos fangosos de la plataforma continental de 50 a 200 m de profundidad. Los hábitos alimenticios de las merluzas pequeñas y medianas eran similares, pero más selectivo en el golfo donde la pesca está prohibida. Las mayores diferencias se produjeron en la dieta de los especímenes más grandes comparando los golfos arrastrados con el golfo protegido. En el área protegida las merluzas grandes cazaban sobre todo en clupeidos y engráulidos, mientras que otros peces se encuentran en el contenido estomacal de M. merluccius de las áreas de pesca. Los valores de δ15N de la merluza no variaron significativamente entre las áreas protegidas y no protegidas, mientras que hubo un efecto claro de la talla: valores más alto, se han observado en los animales más grandes. Por el contrario los valores de δ13C fueron en general más empobrecidos (más negativos) en los ejemplares recolectados en el área protegida, esto indica una fuente más planctónica de carbono. Los resultados de los mixing models concuerdan bastante bien con los hábitos de alimentación observados para cada clase de talla y en cada áreaSamples were collected under Project No. 6A84/2003 funded by the Italian Ministry of Agriculture and ForestsPeer reviewe

The importance of quantifying inherent variability when interpreting stable isotope field data

Stable isotope data are often used to assess diet, trophic level, trophic niche width and the extent of omnivory. Notwithstanding ongoing discussions about the value of these approaches, variations in isotopic signatures among individuals depend on inherent variability as well as differences in feeding habitats. Remarkably, the relative contributions of diet variation and inherent variability to differences in d15N and d13C among individuals have not been quantified for the same species at the same life history stages, and inherent variability has been ignored or assumed. We quantified inherent variability in d13C and d15N among individuals of a marine fish (the European sea bass, Dicentrarchus labrax) reared in a controlled environment on a diet of constant isotopic composition and compared it with variability in d13C and d15N among individuals from wild bass populations. The analysis showed that inherent variability among reared individuals on a controlled diet was equivalent to a large proportion of the observed variability among wild individuals and, therefore, that inherent variability should be measured to establish baseline variability in wild populations before any assumptions are made about the influence of diet. Given that inherent variability is known to be dependent on species, life history stage and the environment, our results show that it should be quantified on a case-by-case basis if diet studies are intended to provide absolute assessments of dietary habits

Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial

Contains fulltext : 118365.pdf (publisher's version ) (Closed access)BACKGROUND: Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. METHODS: We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were randomised in a 2:1 ratio (by computer-generated randomisation list and interactive voice response system; preallocated block design (block size 12); stratified by treatment line and geographical region) to receive either oral regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was progression-free survival (PFS). At disease progression, patients assigned placebo could crossover to open-label regorafenib. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01271712. RESULTS: From Jan 4, to Aug 18, 2011, 240 patients were screened and 199 were randomised to receive regorafenib (n=133) or matching placebo (n=66). Data cutoff was Jan 26, 2012. Median PFS per independent blinded central review was 4.8 months (IQR 1.4-9.2) for regorafenib and 0.9 months (0.9-1.8) for placebo (hazard ratio [HR] 0.27, 95% CI 0.19-0.39; p<0.0001). After progression, 56 patients (85%) assigned placebo crossed over to regorafenib. Drug-related adverse events were reported in 130 (98%) patients assigned regorafenib and 45 (68%) patients assigned placebo. The most common regorafenib-related adverse events of grade 3 or higher were hypertension (31 of 132, 23%), hand-foot skin reaction (26 of 132, 20%), and diarrhoea (seven of 132, 5%). INTERPRETATION: The results of this study show that oral regorafenib can provide a significant improvement in progression-free survival compared with placebo in patients with metastatic GIST after progression on standard treatments. As far as we are aware, this is the first clinical trial to show benefit from a kinase inhibitor in this highly refractory population of patients. FUNDING: Bayer HealthCare Pharmaceuticals