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Background: Post-intensive care syndrome could be responsible for inability to receive proper cancer treatment after ICU stay in patients with solid tumors (ST). Our purpose was to determine the factors associated with cancer treatment resumption and the impact of cancer treatment on the outcome of patients with ST after ICU stay., Methods: We conducted a retrospective study including all patients with ST admitted to the ICU between 2014 and 2019 in a French University-affiliated Hospital., Results: A total of 219 patients were included. Median SAPS II at ICU admission was 44.0 [IQR 32.8, 66.3]. Among the 136 patients who survived the ICU stay, 81 (59.6%) received cancer treatment after ICU discharge. There was an important increase in patients with poor performance status (PS) of 3 or 4 after ICU stay (16.2% at admission vs. 44.5% of patients who survived), with significant PS decline following the ICU stay (median difference - 1.5, 95% confidence interval [-1.5-1.0], p < 0.001). The difference between the PS after and before ICU stay (delta PS) was independently associated with inability to receive cancer treatment (Odds ratio OR 0.34, 95%CI 0.18-0.56, p value < 0.001) and with 1-year mortality in patients who survived at ICU discharge (Hazard ratio HR 1.76, 95%CI 1.34-2.31, p value < 0.001). PS before ICU stay (OR 3.73, 95%IC 2.01-7.82, p value < 0.001) and length of stay (OR 1.23, 95%CI 1.06-1.49, p value 0.018) were independently associated with poor PS after ICU stay. Survival rates at ICU discharge, at 1 and 3 years were 62.3% (n = 136), 27.3% (n = 59) and 17.1% (n = 37), respectively. The median survival for patients who resumed cancer treatment after ICU stay was 771 days (95%CI 376-1058), compared to 29 days (95%CI 15-49) for those who did not resume treatment (p < 0.001)., Conclusion: Delta PS, before and after ICU stay, stands out as a critical determinant of cancer treatment resumption and survival after ICU stay. Multidisciplinary intervention to improve the general condition of these patients, in ICU and after ICU stay, may improve access to cancer treatment and long-term survival., (© 2024. The Author(s).)

Background: Acute distress respiratory syndrome (ARDS) patients with veno-venous extra corporeal membrane oxygenation (ECMO) support are particularly exposed to ECMO-associated infection (ECMO-AI). Unfortunately, data regarding AI prophylaxis in this setting are lacking. Selective decontamination regimens decrease AI incidence, including ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) in critically ill patients. We hypothesized that a multiple-site decontamination (MSD) regimen is associated with a reduction in the incidence of AI among VV-ECMO patients., Methods: We conducted a retrospective observational study in three French ECMO referral centers from January 2010 to December 2021. All adult patients (> 18 years old) who received VV-ECMO support for ARDS were eligible. In addition to standard care (SC), 2 ICUs used MSD, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, once daily chlorhexidine body-wash and a 5-day nasal mupirocin course. AIs were compared between the 2 ICUs using MSD (MSD group) and the last ICU using SC., Results: They were 241 patients available for the study. Sixty-nine were admitted in an ICU that applied MSD while the 172 others received standard care and constituted the SC group. There were 19 ECMO-AIs (12 VAP, 7 BSI) in the MSD group (1162 ECMO-days) compared to 143 AIs (104 VAP, 39 BSI) in the SC group (2376 ECMO-days), (p < 0.05 for all infection site). In a Poisson regression model, MSD was independently associated with a lower incidence of ECMO-AI (IRR = 0.42, 95% CI [0.23-0.60] p < 0.001). There were 30 multidrug resistant microorganisms (MDRO) acquisition in the SC group as compared with two in the MSD group (IRR = 0.13, 95% CI [0.03-0.56] p = 0.001). Mortality in ICU was similar in both groups (43% in the SC group vs 45% in the MSD group p = 0.90). Results were similar after propensity-score matching., Conclusion: In this cohort of patients from different hospitals, MSD appeared to be safe in ECMO patients and may be associated with improved outcomes including lower ECMO-AI and MDRO acquisition incidences. Since residual confounders may persist, these promising results deserve confirmation by randomized controlled trials., (© 2023. The Author(s).)

Background: Among strategies that aimed to prevent acquired infections (AIs), selective decontamination regimens have been poorly studied in the COVID-19 setting. We assessed the impact of a multiple-site decontamination (MSD) regimen on the incidence of bloodstream infections (BSI) and ventilator-associated pneumonia (VAP) in COVID-19 patients receiving mechanical ventilation., Methods: We performed an ancillary analysis of a multicenter retrospective observational study in 15 ICUs in western France. In addition to standard-care (SC), 3 ICUs used MSD, a variant of selective digestive decontamination, which consists of the administration of topical antibiotics four times daily in the oropharynx and the gastric tube, chlorhexidine body wash and a 5-day nasal mupirocin course. AIs were compared between the 3 ICUs using MSD (MSD group) and the 12 ICUs using SC., Results: During study period, 614 of 1158 COVID-19 patients admitted in our ICU were intubated for at least 48 h. Due to missing data in 153 patients, 461 patients were finally included of whom 89 received MSD. There were 34 AIs in the MSD group (2117 patient-days), as compared with 274 AIs in the SC group (8957 patient-days) (p < 0.001). MSD was independently associated with a lower risk of AI (IRR = 0.56 [0.38-0.83]; p = 0.004) (Table 2). When the same model was used for each site of infection, MSD remained independently associated with a lower risk of VAP (IRR = 0.52 [0.33-0.89]; p = 0.005) but not of BSI (IRR = 0.58, [0.25-1.34], p = 0.21). Hospital mortality was lower in the MSD group (16.9% vs 30.1%, p = 0.017)., Conclusions: In ventilated COVID-19 patients, MSD was independently associated with lower AI incidence., (© 2022. The Author(s).)

A new genotyping-based DNA assay (Digene LQ(®)) was developed recently. The primary aim was to assess the distribution of HPV types using this new assay in atypical squamous cells of undeterminate significance (ASCUS). The secondary aim was to correlate the HPV types with the severity of the disease. The study population comprised 376 ASCUS women. The women were all Hybrid Capture II (HCII) positive and were admitted in three European referral gynecology clinics between 2007 and 2010. A colposcopy with histological examination was performed in all these patients. HPV 16 was typed in 40 % of patients, HPV 18 in 7 %, and HPV 31 in 17 %, and 18 % of patients had mixed genotypes. Patients aged over 30 more often had the HPV 16 genotype than patients aged under 30 (29 % vs. 11 %, chi-square test p < 0.001). The risk of cervical intra-epithelial neoplasia of grade 2 or more (CIN2 +) when HPV 18 positive is lower than the probability associated with HPV 16 or HPV 31: 28 % vs. 58 % and 52 %, respectively (chi-square test, p = 0.005 and p = 0.05, respectively). The Digene LQ(®), a new sequence-specific hybrid capture sample preparation, is fast and efficient and allows high-throughput genotyping of 18 HR HPV types by PCR compared to traditional non-sequence-specific sample preparation methods.

Background: A history of prolonged and excessive consumption of alcohol increases the risk for infections. The goal of this study was to investigate circulating white blood cells (WBC) differentiated by flow cytometry and neutrophil CD64 expression in excessive alcohol drinkers versus abstinent or moderate drinkers, and in those with or without infection, in medical patients admitted to the intensive care unit (ICU)., Methods: All patients admitted between September 2009 and March 2010 with an ICU-stay of 3 days or more were eligible for inclusion. Upon admission, hematological exams were conducted by flow cytometry., Results: Overall, 281 adult were included, with 37% identified as at-risk drinkers. The only significant difference found in circulating WBC between at-risk and not-at-risk drinkers was a lower number of B lymphocytes in at-risk drinkers (P = 0.002). Four groups of patients were defined: not-at-risk drinkers with no infection (n = 66); not-at-risk drinkers with infection (n = 112); at-risk drinkers with no infection (n = 53); and at-risk drinkers with infection (n = 50). Whilst the presence of infection significantly reduced levels of noncytotoxic and cytotoxic T lymphocytes and significantly increased levels of CD16- monocytes in not-at-risk drinkers, with variation related to infection severity, infection had no effect on any of the variables assessed in at-risk drinkers. Post-hoc comparisons showed that B-lymphocyte, noncytotoxic, and cytotoxic T lymphocyte and CD16- counts in at-risk drinkers were similar to those in not-at-risk drinkers with infection and significantly lower than those in not-at-risk drinkers without infection. Neutrophil CD64 index varied significantly between groups, with variations related to infection, not previous alcohol consumption., Conclusions: These results show that chronic alcohol exposure has an impact on the immune response to infection in critically ill medical patients. The absence of significant variations in circulating WBC seen in at-risk drinkers according to the severity of infection is suggestive of altered immune response.

Guanine Exchange Factor (GEF) activity for Ras proteins has been associated with a conserved domain in Cdc25p, Sdc25p in Saccharomyces cerevisiae and several other proteins recently found in other eukaryotes. We have assessed the structure-function relationships between three different members of this family in S. cerevisiae, Cdc25p, Sdc25p and Bud5p. Cdc25p controls the Ras pathway, whereas Bud5p controls bud site localization. We demonstrate that the GEF domain of Sdc25p is closely related to that of Cdc25p. We first constructed a thermosensitive allele of SDC25 by specifically altering amino acid positions known to be changed in the cdc25-1 mutation. Secondly, we constructed three chimeric genes from CDC25 and SDC25, the products of which are as active in the Ras pathway as are the wild-type proteins. In contrast, similar chimeras made between CDC25 and BUD5 lead to proteins that are inactive both in the Ras and budding control pathways. This difference in the ability of chimeric proteins to retain activity allows us to define two subclasses of structurally different GEFs: Cdc25p and Sdc25p are Ras-specific GEFs, and Bud5p is a putative GEF for the Rsr1/Bud1 Rap-like protein.