Back to the future: the novel art of digital auscultation applied in a prospective observational study of critically ill Covid-19 patients.

BACKGROUND: The Covid-19 pandemic has caused immense pressure on Intensive Care Units (ICU). In patients with severe ARDS due to Covid-19, respiratory mechanics are important for determining the severity of lung damage. Lung auscultation could not be used during the pandemic despite its merit. The main objective of this study was to investigate associations between lung auscultatory sound features and lung mechanical properties, length of stay (LOS) and survival, in adults with severe Covid-19 ARDS. METHODS: Consecutive patients admitted to a large ICU between 2020 and 2021 (n = 173) were included. Digital stethoscopes obtained auscultatory sounds and stored them in an on-line database for replay and further processing using advanced AI techniques. Correlation and regression analysis explored relationships between digital auscultation findings and lung mechanics or the ICU outcome. The resulting annotated lung sounds database is also publicly available as supplementary material. RESULTS: The presence of squawks was associated with the ICU LOS, outcome and 90-day mortality. Other features (age, SOFA score & oxygenation index upon admission, minimum crackle entropy) had significant impact on outcome. Additional features affecting the 90-d survival were age and mean crackle entropy. Multivariate logistic regression showed that survival was affected by age, baseline SOFA, baseline oxygenation index and minimum crackle entropy. CONCLUSIONS: Respiratory mechanics were associated with various adventitious sounds, whereas the lung sound analytics and the presence of certain adventitious sounds correlated with the ICU outcome and the 90-d survival. Spectral features of crackles sounds can serve as prognostic factors for survival, highlighting the importance of digital auscultation.

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

An observational study on factors associated with ICU mortality in Covid-19 patients and critical review of the literature.

The novel pandemic caused by SARS-CoV-2 has been associated with increased burden on healthcare system. Recognizing the variables that independently predict death in COVID-19 is of great importance. The study was carried out prospectively in a single ICU in northern Greece. It was based on the collection of data during clinical practice in 375 adult patients who were tested positive for SARS-CoV-2 between April 2020 and February 2022. All patients were intubated due to acute respiratory insufficiency and received Invasive Mechanical Ventilation. The primary outcome was ICU mortality. Secondary outcomes were 28-day mortality and independent predictors of mortality at 28 days and during ICU hospitalization. For continuous variables with normal distribution, t-test was used for means comparison between two groups and one-way ANOVA for multiple comparisons. When the distribution was not normal, comparisons were performed using the Mann-Whitney test. Comparisons between discrete variables were made using the x2 test, whereas the binary logistic regression was employed for the definition of factors affecting survival inside the ICU and after 28 days. Of the total number of patients intubated due to COVID-19 during the study period, 239 (63.7%) were male. Overall, the ICU survival was 49.6%, whereas the 28-day survival reached 46.9%. The survival rates inside the ICU for the four main viral variants were 54.9%, 50.3%, 39.7% and 50% for the Alpha, Beta, Delta and Omicron variants, respectively. Logistic regressions for outcome revealed that the following parameters were independently associated with ICU survival: wave, SOFA @day1, Remdesivir use, AKI, Sepsis, Enteral Insufficiency, Duration of ICU stay and WBC. Similarly, the parameters affecting the 28-days survival were: duration of stay in ICU, SOFA @day1, WBC, Wave, AKI and Enteral Insufficiency. In this observational cohort study of critically ill COVID-19 patients we report an association between mortality and the wave sequence, SOFA score on admission, the use of Remdesivir, presence of AKI, presence of gastrointestinal failure, sepsis and WBC levels. Strengths of this study are the large number of critically ill COVID-19 patients included, and the comparison of the adjusted mortality rates between pandemic waves within a two year-study period.

CoCross: An ICT Platform Enabling Monitoring Recording and Fusion of Clinical Information Chest Sounds and Imaging of COVID-19 ICU Patients.

Monitoring and treatment of severely ill COVID-19 patients in the ICU poses many challenges. The effort to understand the pathophysiology and progress of the disease requires high-quality annotated multi-parameter databases. We present CoCross, a platform that enables the monitoring and fusion of clinical information from in-ICU COVID-19 patients into an annotated database. CoCross consists of three components: (1) The CoCross4Pros native android application, a modular application, managing the interaction with portable medical devices, (2) the cloud-based data management services built-upon HL7 FHIR and ontologies, (3) the web-based application for intensivists, providing real-time review and analytics of the acquired measurements and auscultations. The platform has been successfully deployed since June 2020 in two ICUs in Greece resulting in a dynamic unified annotated database integrating clinical information with chest sounds and diagnostic imaging. Until today multisource data from 176 ICU patients were acquired and imported in the CoCross database, corresponding to a five-day average monitoring period including a dataset with 3477 distinct auscultations. The platform is well accepted and positively rated by the users regarding the overall experience.

Vaccinated and Convalescent Donor-Derived Severe Acute Respiratory Syndrome Coronavirus 2-Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19-infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients.

Determinants of Outcome in Burn ICU Patients with Septic Shock.

Infectious complications remain one of the most challenging concerns for the burn team. The goal of this study was to evaluate the diagnostic and therapeutic approaches and prognosis in burn patients with septic shock. This retrospective study included patients with severe burn injury who were admitted to a burn intensive care unit (ICU). Demographic and clinical data were recorded for each patient. The diagnostic and prognostic value of a number of clinical and laboratory parameters and various treatment options were evaluated. Sixty-four of the 378 patients (16.9%) were identified as having experienced a septic shock during ICU stay. The mortality rate of patients with septic shock was 46.9%. The main bacterial strains responsible for infection were Gram-negative bacteria (78.1%). Factors associated with outcome of septic shock on logistic regression analysis were presence of stage III of acute kidney injury (odds ratio [95% confidence interval] 2.03 [1.06-3.84]; P = 0.019), and lactate levels > 4 mmol/L during the first 48 hours of shock (odds ratio 1.92; 95% confidence interval: 1.02-3.62; P = 0.043). Prognosis of septic shock remains poor in burn patients with septic shock. The main causative pathogens of septic shock identified in our burn ICU were Gram-negative species. The main prognostic factors identified in this study were the presence of AKI, stage III, and high lactate levels early after the onset of septic shock.

Resting Energy Expenditure in Critically Ill Patients With Spontaneous Intracranial Hemorrhage.

BACKGROUND: Data on energy requirements of patients with spontaneous intracranial hemorrhage (SICH) are scarce. The objective of this study was to determine the resting energy expenditure (REE) in critically ill patients with SICH and to compare it with the predicted basal metabolic rate (BMR). METHODS: In 30 nonseptic patients with SICH, the REE was measured during the 10 first posthemorrhage days with the use of indirect calorimetry (IC). Predicted BMR was also evaluated by the Harris-Benedict (HB) equation. Bland-Altman analysis was used to evaluate the agreement between measured and predicted values. The possible effect of confounding factors (demographics, disease, and severity of illness score) on the evolution of continuous variables was also tested. RESULTS: mean predicted BMR, calculated by the HB equation, was 1580.3 ± 262 kcal/d, while measured REE was 1878.9 ± 478 kcal/d (117.5% BMR). Compared with BMR, measured REE values showed a statistically significant increase at all studied points (P < .005). Measured and predicted values showed a good correlation (r = 0.73, P < .001), but the test of agreement between the 2 methods with the Bland-Altman analysis showed a mean bias (294.6 ± 265.6 kcal/d) and limits of agreement (-226 to 815.29 kcal/d) that were beyond the clinically acceptable range. REE values presented a trend toward increase over time (P = .077), reaching significance (P < .005) after the seventh day. Significant correlation was found between REE and temperature (P = .002, r = 0.63), as well as between REE and cortisol level (P = .017, r = 0.62) on the 10th day. No correlation was identified between REE and depth of sedation, as well as Acute Physiology and Chronic Health Evaluation II, Glasgow Coma Scale, and Hunt and Hess scores. CONCLUSIONS: During the early posthemorrhagic stage, energy requirements of critically ill patients with SICH are increased, presenting a trend toward increase over time. Compared with IC, the HB equation underestimates energy requirements and is inefficient in detecting individual variability of REE in this group of patients.

Enteral nutrition intolerance in critically ill septic burn patients.

The purpose of this study was to investigate the frequency of enteral feeding intolerance in critically ill septic burn patients, the effect of enteral feeding intolerance on the efficacy of feeding, the correlation between the infection marker (procalcitonin [PCT]) and the nutrition status marker (prealbumin) and the impact of feeding intolerance on the outcome of septic burn patients. From January 2009 to December 2012 the data of all burn patients with the diagnosis of sepsis who were placed on enteral nutrition were analyzed. Septic patients were divided into two groups: group A, septic patients who developed feeding intolerance; group B, septic patients who did not develop feeding intolerance. Demographic and clinical characteristics of patients were analyzed and compared. The diagnosis of sepsis was applied to 29% of all patients. Of these patients 35% developed intolerance to enteral feeding throughout the septic period. A statistically significant increase in mean PCT level and a decrease in prealbumin level was observed during the sepsis period. Group A patients had statistically significant lower mean caloric intake, higher PCT:prealbumin ratio, higher pneumonia incidence, higher Sequential Organ Failure Assessment Maximum Score, a longer duration of mechanical ventilation, and a higher mortality rate in comparison with the septic patients without gastric feeding intolerance. The authors concluded that a high percentage of septic burn patients developed enteral feeding intolerance. Enteral feeding intolerance seems to have a negative impact on the patients' nutritional status, morbidity, and mortality.

The efficacy of antithrombin administration in the acute phase of burn injury.

Severe burn injury is characterized by the activation of coagulation, decreased fibrinolytic activity and decreased natural anticoagulant activity. The aim of our study was to investigate the effect of antithrombin (AT) administration on coagulation status and on organ function in the early post-burn period. Thirty-one patients were admitted to the burn intensive care unit and were then randomised into two groups (AT-treated and non-AT-treated) for four consecutive days after thermal injury. The clinical data, coagulation and fibrinolysis parameters were compared and the adverse effects were monitored. Significant differences in the time course of coagulation markers (thrombin/AT complexes, tissue plasminogen activator, D-dimer) were observed between AT-treated and non-AT treated groups. According to the International Society on Thrombosis and Haemostasis criteria, disseminated intravascular coagulation (DIC) diagnosis was made in 28 of 31 patients. The presence of overt DIC was associated with mortality (p < 0.001). The Sequential Organ Failure Assessment (SOFA) score time trend differed significantly between the two investigation groups (decreased in the treated group and did not change in the non-AT-treated group). AT-treated patients had an absolute reduction in a 28-day mortality of 25% as compared to the non-AT-treated group (p = 0.004). No treatment related side effects were observed. Treatment with AT seems to affect the coagulation status and reduce multiple organ failure incidence and mortality in the early post-burn period.

Early coagulation disorders after severe burn injury: impact on mortality.

OBJECTIVE: To evaluate the time course of coagulation markers in the early postburn period and clarify the role of coagulation alterations in organ failure and in mortality prognosis. DESIGN AND SETTING: This prospective study was conducted in the burn ICU of a tertiary hospital. PATIENTS: 45 patients with severe thermal burn injury. MEASUREMENTS AND RESULTS: Clinical data and coagulation and fibrinolysis parameters were measured during the first postburn week. The ICU 28-day mortality rate was 33%. Significant differences in the time course of coagulation markers were observed between survivors and nonsurvivors. SOFA score distinguished between patients with overt and nonovert disseminated intravascular coagulation (DIC) during the overall investigation period. Presence of overt DIC was related to mortality (OR=0.1). Antithrombin, protein S, plasminogen activator inhibitor 1, and SOFA score on day 3, protein C on day 5, and thrombin/antithrombin complexes on day 7 revealed a good prognostic value for ICU mortality, according to the area under ROC curves. CONCLUSIONS: Severe thermal injury is associated with the early activation of coagulation cascade, presence of DIC, organ failure, and increased mortality.

Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis?

OBJECTIVE: To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients. DESIGN AND SETTING: Prospective, observational study in a four bed Burn Intensive Care Unit. PATIENTS: Forty-three patients admitted in a Burn ICU were included in our study. MEASUREMENTS AND RESULTS: Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT. CONCLUSIONS: Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.

Reliability of selective surveillance colonoscopy in the early diagnosis of colonic ischemia after successful ruptured abdominal aortic aneurysm repair.

PURPOSE: To evaluate the reliability of selective surveillance colonoscopy based on 6 specific perioperative risk factors in the early diagnosis of colonic ischemia (CI) after successful ruptured abdominal aortic aneurysm (rAAA) repair. PATIENTS AND METHODS: From 1999 to 2005, 62 consecutive patients underwent rAAA repair. In 59 of them, routine aggressive surveillance colonoscopy was offered every 12 hours within the first 48 hours, and CI was graded consistently. Patients with stage I or stage II CI were treated conservatively and were followed up with repeat colonoscopy, whereas patients with stage III CI underwent immediate laparotomy and colectomy. In parallel, 6 specific perioperative risk factors (PRFs) were retrospectively analyzed. RESULTS: Overall mortality was 33.9%. Nineteen patients (32.2%) developed CI and 12 (63.2%) of them survived. Thirteen (22%) had grade III CI and among these 6 survived. In patients with CI the mortality rate was 36.2%. Patients with less than 3 PRFs had no CI whereas all instances of CI could be diagnosed if colonoscopy was offered selectively in patients with more than 3 PRFs. The positive predictive value of CI increased with the number of PRFs. Patients with 5 or 6 PRFs were about 101 times more likely to develop CI compared with patients with 0 to 4 PRFs (P<.001). CONCLUSION: Our study showed that CI is a frequent complication after successful rAAA repair and could reliably be early diagnosed if surveillance colonoscopy was offered selectively in patients with more than three PRFs.