Introduction: Long-term outcomes of elderly patients after medical ICU care are little known. The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU. Methods: We prospectively studied 112/230 healthy elderly patients (≥65 years surviving at least 12 months after ICU discharge) with full functional autonomy without cognitive impairment prior to ICU entry. The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III (APACHE III) classification diagnosis and length of ICU stay and ICU scores (APACHE II, Sepsis-related Organ Failure Assessment (SOFA) and OMEGA) at admission and discharge were collected. Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton, Barthel, and Charlson Indexes and Informant Questionnaire on Cognitive Decline to evaluate functionality, comorbidity and cognitive status, respectively. The EuroQol-5D assessed quality of life. Data were collected at baseline, during ICU and ward stay and 3, 6 and 12 months after hospital discharge. Paired or unpaired T-tests compared differences between groups (continuous variables), whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables. For variables significant (P ≤ 0.1) on univariate analysis, a forward multiple regression analysis was performed. Results: Only 48.9% of patients (mean age: 73.4 ± 5.5 years) were alive 12 months after discharge showing a significant decrease in functional autonomy (Lawton and Barthel Indexes) and quality of life (EuroQol-5D) compared to baseline status (P < 0.001, all). Multivariate analysis showed a higher Barthel Index and EQ-5D _vas at hospital discharge to be associated factors of full functional recovery (P < 0.01, both). Thus, in patients with a Barthel Index ≥ 60 or EQ-5D _vas ≥40 at discharge the hazard ratio for full functional recovery was 4.04 (95% CI: 1.58 to 10.33; P = 0.005) and 6.1 (95% CI: 1.9 to 19.9; P < 0.01), respectively. Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up (P < 0.001). Conclusions: The survival rate of elderly medical patients 12 months after discharge from the ICU is low (49%), although functional status and quality of life remained similar to baseline in most of the survivors. However, there was a two-fold increase in the prevalence of geriatric syndromes.

Purpose Thrombocytopenia (platelet count < 150 × 10⁹/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression.

We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020–February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57–3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69–4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11–2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19. Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values 94%.