Tracheostomy in critically ill patients with SARS 2 COVID-19 infection: a prospective observational multi-center study of short- and long-term outcomes

Background: We report the characteristics, timing, and factors related to the decision to perform a tracheostomy in patients with confirmed COVID-19 infection admitted to eight Italian intensive care units (ICUs). Materials and methods: Prospective observational cohort study of patients with COVID-19 disease on mechanical ventilation. Long-term functional impairment (up to 180 days' post-hospital discharge) was assessed using the Karnofsky scale. Kaplan-Meier analysis assessed differences in survival and freedom from tracheostomy in relation to ICU stay. Cox regression model was used to assess which variables impacted on tracheostomy as a categorical outcome. Results: A total of 248 patients were recruited in the eight participating ICUs. Patients undergoing tracheostomy (n = 128) had longer ICU (25 (18-36) vs. 10 (7-16), P = 0.001) and hospital (37 (26.5-50) vs. 19 (8.5-34.5) P = 0.02) stays. ICU and hospital mortality of patients tracheostomized was 34% and 37%, respectively. Cumulative survival Kaplan-Meier analysis documented improved survival rates in patients undergoing tracheostomy (Log-Rank, Mantel-Cox = 4.8, P = 0.028). Median Karnofsky scale values improved over time but were similar between survivors receiving or not receiving tracheostomy. No healthcare worker involved in the tracheostomy procedure developed COVID-19 infection during the study period. Conclusions: Patients with COVID-19 infection who underwent tracheostomy had a better cumulative survival but similar long-term functional outcomes at 30, 60, and 180 days after hospital discharge

Antiphospholipid Syndrome During Septic Shock: Hyper- or Hypocoagulability?: A Case Report

We report the clinical case of a septic patient with antiphospholipid syndrome who developed ischemia in all 4 limbs, despite a normal systemic blood pressure. Prolonged coagulation times suggested a hemorrhagic diathesis, requiring transfusion of fresh-frozen plasma and discontinuation of heparin infusion. In contrast, the study of the viscoelastic properties of the clot by thromboelastography suggested an uncontrolled activation of the coagulation cascade. This observation led to the reintroduction of heparin with improvement in the patient's laboratory findings. Anesthesiologists should consider thromboelastography to correct coagulopathies in patients with septic shock in the presence of antiphospholipid antibodies

Candida Infective Endocarditis Report of 15 Cases From a Prospective Multicenter Study

Candida species are an uncommon cause of infective endocarditis (IE). Given the rarity of this infection, the epidemiology, prognosis, and optimal therapy of Candida IE are poorly defined. We conducted a prospective, observational study at 18 medical centers in Italy, including all consecutive patients with a definite diagnosis of IE admitted front January 2004 through December 2007. A Candida species was the causative organism in 8 cases of prosthetic valve endocarditis (PVE), 5 cases of native valve endocarditis (NVE), I case of pacemaker endocarditis, and I case of left ventricular patch infection. Candida species accounted for 1.8% of total cases, and for 3.4% of PVE cases. Most patients (86.6%) had a health care-associated infection. PVE associated with a health care contact occurred after a median of 225 days from valve implantation. Ten patients (66.6%) were treated with caspofungin alone or in combination with other antifungal drugs. The overall mortality rate was 46.6%. Mortality was higher in patients with PVE (5 of 8 cases, 62.5%) than in patients with NVE (2 of 5 patients, 40%). A better outcome was observed in patients treated with a combined medical and surgical therapy. Candida IE should be classified as an emerging infectious disease, usually involving patients with intravascular prosthetic devices, and associated with substantial related morbidity and mortality. Candida PVE usually is a late-onset disease, which becomes clinically evident even several months after an initial episode of transient candidemia. (Medicine 2009;88: 160-168

Single cell-derived spheroids capture the self-renewing subpopulations of metastatic ovarian cancer

: High Grade Serous Ovarian cancer (HGSOC) is a major unmet need in oncology, due to its precocious dissemination and the lack of meaningful human models for the investigation of disease pathogenesis in a patient-specific manner. To overcome this roadblock, we present a new method to isolate and grow single cells directly from patients' metastatic ascites, establishing the conditions for propagating them as 3D cultures that we refer to as single cell-derived metastatic ovarian cancer spheroids (sMOCS). By single cell RNA sequencing (scRNAseq) we define the cellular composition of metastatic ascites and trace its propagation in 2D and 3D culture paradigms, finding that sMOCS retain and amplify key subpopulations from the original patients' samples and recapitulate features of the original metastasis that do not emerge from classical 2D culture, including retention of individual patients' specificities. By enabling the enrichment of uniquely informative cell subpopulations from HGSOC metastasis and the clonal interrogation of their diversity at the functional and molecular level, this method provides a powerful instrument for precision oncology in ovarian cancer

In vivo tracking of T cells in humans unveils decade-long survival and activity of genetically modified T memory stem cells

A definitive understanding of survival and differentiation potential in humans of T cell subpopulations is of paramount importance for the development of effective T cell therapies. In particular, uncovering the dynamics in vivo in humans of the recently described T memory stem cells (TSCM) would be crucial for therapeutic approaches that aim at taking advantage of a stable cellular vehicle with precursor potential. We exploited data derived from two gene therapy clinical trials for an inherited immunodeficiency, using either retrovirally engineered hematopoietic stem cells or mature lymphocytes to trace individual T cell clones directly in vivo in humans. We compared healthy donors and bone marrow-transplanted patients, studied long-term in vivo T cell composition under different clinical conditions, and specifically examined TSCMcontribution according to age, conditioning regimen, disease background, cell source, long-term reconstitution, and ex vivo gene correction processing. High-throughput sequencing of retroviral vector integration sites (ISs) allowed tracing the fate of more than 1700 individual T cell clones in gene therapy patients after infusion of gene-corrected hematopoietic stem cells or mature lymphocytes. We shed light on long-term in vivo clonal relationships among different T cell subtypes, and we unveiled that TSCMare able to persist and to preserve their precursor potential in humans for up to 12 years after infusion of gene-corrected lymphocytes. Overall, this work provides high-resolution tracking of T cell fate and activity and validates, in humans, the safe and functional decade-long survival of engineered TSCM, paving the way for their future application in clinical settings

Systemic allergic reactions induced by labile plant‐food allergens: Seeking potential cofactors. A multicenter study

Background: Heat-and-pepsin-sensitive plant food allergens (PR-10 and profilin) sometimes cause systemic reaction.Objective: To detect the risk factors for systemic reactions induced by labile food allergens.Methods: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age-matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti-inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered.Results: We studied 89 patients and 81 controls. Sensitization to PR-10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P < .025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P < .025). Soy milk-induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases.Conclusion: PR-10- and profilin-induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR-10 hypersensitive patients and should be avoided

The Burden of Carbapenem-Resistant Acinetobacter baumannii in ICU COVID-19 Patients: A Regional Experience

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028–1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572–18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team

Early extubation with immediate non-invasive ventilation versus standard weaning in intubated patients for coronavirus disease 2019: a retrospective multicenter study

In patients intubated for hypoxemic acute respiratory failure (ARF) related to novel coronavirus disease (COVID-19), we retrospectively compared two weaning strategies, early extubation with immediate non-invasive ventilation (NIV) versus standard weaning encompassing spontaneous breathing trial (SBT), with respect to IMV duration (primary endpoint), extubation failures and reintubations, rate of tracheostomy, intensive care unit (ICU) length of stay and mortality (additional endpoints). All COVID-19 adult patients, intubated for hypoxemic ARF and subsequently extubated, were enrolled. Patients were included in two groups, early extubation followed by immediate NIV application, and conventionally weaning after passing SBT. 121 patients were enrolled and analyzed, 66 early extubated and 55 conventionally weaned after passing an SBT. IMV duration was 9 [6-11] days in early extubated patients versus 11 [6-15] days in standard weaning group (p\u2009=\u20090.034). Extubation failures [12 (18.2%) vs. 25 (45.5%), p\u2009=\u20090.002] and reintubations [12 (18.2%) vs. 22 (40.0%) p\u2009=\u20090.009] were fewer in early extubation compared to the standard weaning groups, respectively. Rate of tracheostomy, ICU mortality, and ICU length of stay were no different between groups. Compared to standard weaning, early extubation followed by immediate NIV shortened IMV duration and reduced the rate of extubation failure and reintubation