Improvement of Thymopoiesis after Hematopoietic Stem Cell Transplantation by Cytokines: Translational studies in experimental animal models

Allogeneic hematopoietic stem cell transplantation (AlloHSCT) is a powerful treatment modality that is frequently applied as part of treatment of hematological malignancies, aplastic anemia and inborn errors of hematopoietic progenitor cells. A major drawback of alloHSCT is the treatment related morbidity and treatment related mortality (TRM), which are largely accounted for by opportunistic infections. Those infections occur during a prolonged period (1-2 years), characterized by an impaired reconstitution of the adaptive immune system. Especially, the recovery of naïve T cells and thymopoiesis are protracted after transplantation, but are considered pivotal for restoration of anti-infectious immunity. This thesis has experimentally addressed new strategies that may improve thymopoiesis, including the post-transplant administration of cytokines that are physiologically involved in the differentiation and proliferation of thymocytes

Racial Disparities in Pulse Oximetry, in COVID-19 and ICU Settings

OBJECTIVES (BACKGROUND): This study aimed to assess the impact of race on pulse oximetry reliability, taking into account Spo2 ranges, COVID-19 diagnosis, and ICU admission. DESIGN: Retrospective cohort study covering admissions from January 2020 to April 2024. SETTING: National COVID Cohort Collaborative (N3C) database, consisting of electronic health records from 80 U.S. institutions.PATIENTS/SUBJECTS: Patients were selected from the N3C database based on the availability of data on self-identified race and both pulse oximetry estimated Spo2 and Sao2. Subgroups included patients in ICU and non-ICU settings, with or without a diagnosis of COVID-19 disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The agreement between Spo2 and Sao2 was assessed across racial groups (American Indian or Alaska Native, Asian, Black, Hispanic or Latino, Pacific Islander, and White). Each patient’s initial Sao2 measurement was matched with the closest Spo2 values recorded within the preceding 10-minute time frame. The risk of hidden hypoxemia (Spo2 ≥ 88% but Sao2 &lt; 88%) was determined for various Spo2 ranges, races, and clinical scenarios. We used a generalized logistic mixed-effects model to evaluate the impact of relevant variables, such as COVID-19, ICU admission, age, sex, race, and Spo2, on the risk of hidden hypoxemia, while accounting for the random effects within each hospital. A total of 80,541 patients were included, consisting of 596 American Indian or Alaska Native, 2,729 Asian, 11,889 Black, 13,154 Hispanic or Latino, 221 Pacific Islander, and 51,952 White individuals. Discrepancies between Spo2 and Sao2 were observed across all racial groups, with the most pronounced bias in Black patients. Hidden hypoxemia rates were higher in Black patients across all Spo2 subgroups, for all clinical scenarios. The odds of hidden hypoxemia were higher for Black and Hispanic or Latino patients and for those with COVID-19 disease. CONCLUSIONS: Race significantly impacts pulse oximetry reliability. Not only Black and Hispanic or Latino patients were at higher risk for hidden hypoxemia, but also those admitted with a COVID-19 diagnosis. Future in-depth explorations into the underlying causes and potential solutions are needed.</p

Physiological Effects of High-Flow Tracheal Oxygen in Tracheostomized Patients Weaning From Mechanical Ventilation

BACKGROUND: High-flow tracheal oxygen (HFTO) is being used as supportive therapy during weaning in tracheostomized patients difficult to wean from invasive mechanical ventilation. There is, however, no clinical evidence for such a strategy. Therefore, we conducted a systematic review to summarize studies evaluating the physiologic effects of HFTO during tracheostomy-facilitated weaning and to identify potential areas for future research in this field. METHODS: Observational and interventional studies on critically ill subjects weaning from mechanical ventilation via tracheostomy published until December 22, 2022, were eligible. Studies on high-flow oxygen, only in children, non-human models or animals, on clinical outcome only, abstracts without full-text availability, case reports, and reviews were excluded. Main outcomes were end-expiratory lung volume (EELV) and tidal volume using electrical impedance tomography, respiratory effort assessed by esophageal manometry, work of breathing and neuroventilatory drive as assessed by electrical activity of the diaphragm (EAdi) signal, airway pressure (Paw), oxygenation (PaO2 /FIO2 or SpO2 /FIO2 ), breathing frequency, tidal volume, and PaCO2 .RESULTS: In total, 1,327 references were identified, of which 5 were included. In all studies, HFTO was administered with flow 50 L/min and compared to conventional O2 therapy in a crossover design. The total average duration of invasive ventilation at time of measurements ranged from 11-27 d. In two studies, PaO2 /FIO2 and mean Paw were higher with HFTO. EELV, tidal volumes, esophageal pressure swings, and EAdi were similar during high-flow tracheal oxygen and conventional O2 therapy. CONCLUSIONS: The main physiological effect of HFTO as compared to conventional O2 therapy in tracheostomized subjects weaning from mechanical ventilation was improved oxygenation that is probably flow-dependent. Respiratory effort, lung aeration, neuroventilatory drive, and ventilation were similar for HFTO and conventional O2 therapy. Future studies on HFTO should be performed early in the weaning process and should evaluate its effect on sputum clearance and patient-centered outcomes like dyspnea.</p

The Value of Ischemic Cardiac Biomarkers to Predict Spontaneous Breathing Trial or Extubation Failure:A Systematic Review

Background: It is unclear whether other cardiac biomarkers than NT-proBNP can be useful in the risk stratification of patients weaning from mechanical ventilation. The aim of this study is to summarize the role of ischemic cardiac biomarkers in predicting spontaneous breathing trial (SBT) or extubation failure. Methods: We systematically searched Embase, MEDLINE, Web of Science, and Cochrane Central for studies published before January 2024 that reported the association between ischemic cardiac biomarkers and SBT or extubation failure. Data were extracted using a standardized form and methodological assessment was performed using the QUIPS tool. Results: Seven observational studies investigating four ischemic cardiac biomarkers (Troponin-T, Troponin-I, CK-MB, Myoglobin) were included. One study reported a higher peak Troponin-I in patients with extubation failure compared to extubation success (50 ng/L [IQR, 20–215] versus 30 ng/L [IQR, 10–86], p = 0.01). A second study found that Troponin-I measured before the SBT was higher in patients with SBT failure in comparison to patients with SBT success (100 ± 80 ng/L versus 70 ± 130 ng/L, p = 0.03). A third study reported a higher CK-MB measured at the end of the SBT in patients with weaning failure (SBT or extubation failure) in comparison to weaning success (8.77 ± 20.5 ng/mL versus 1.52 ± 1.42 ng/mL, p = 0.047). Troponin-T and Myoglobin as well as Troponin-I and CK-MB measured at other time points were not found to be related to SBT or extubation failure. However, most studies were underpowered and with high risk of bias. Conclusions: The association with SBT or extubation failure is limited for Troponin-I and CK-MB and appears absent for Troponin-T and Myoglobin, but available studies are hampered by significant methodological drawbacks. To more definitively determine the role of ischemic cardiac biomarkers, future studies should prioritize larger sample sizes, including patients at risk of cardiac disease, using stringent SBTs and structured timing of laboratory measurements before and after SBT.</p

Liberation from invasive mechanical ventilation:A nationwide survey among intensive care units in the Netherlands

Background:Liberation from invasive mechanical ventilation is a milestone in critical care, but approaches vary. This survey aimed to describe current ventilator liberation practices, relate them to available evidence, and identify areas for improvement.Methods:A survey was performed among Dutch intensive care unit (ICU) sites. The survey evaluated practice in seven domains of ventilator liberation: protocol availability, transition from controlled to assisted ventilation, spontaneous breathing trials (SBT), cuff-leak test, postextubation support, weaning failure and tracheostomised weaning. Results: The survey response rate was 93% (132/142), representing 97% (69/71) of Dutch ICUs. Protocols for postextubation support and weaning failure were available in less than half of the ICUs (44% and 49%, respectively). The transition from controlled to assisted ventilation is regularly evaluated daily in 78% of ICUs. Assisted ventilation tolerance is mainly assessed by clinical signs, respiratory parameters and non-invasive manoeuvres that assess respiratory drive (P 0.1). SBTs are regularly performed in 58% of ICUs, using one or more of the following methods: T-piece (52%), pressure support+positive end expiratory pressure (32%) and continuous positive airway pressure (28%). Cuff-leak tests are seldom performed (1.4%), predominantly in cases of intubation for upper-airway obstruction (92%). Postextubation respiratory support with high-flow nasal oxygen or non-invasive ventilation is used at least as often with therapeutic (43%/13%) rather than preventive (35%/4%) of facilitative intent (29%/3%). Delirium screening (87%) and reconsidering sedation (84%) are frequently assessed in case of weaning failure. Regular use of closed-loop ventilation is reported in a minority of ICUs throughout the process of ventilator liberation (3-9%). Conclusions:Various aspects of ventilator liberation practices show only limited alignment with existing guidelines. The results of this survey pinpoint areas to prioritise in guideline and practice improvement.<p/

High-flow nasal oxygen vs. conventional oxygen therapy in patients with COVID-19 related acute hypoxemic respiratory failure and a do not intubate order:a multicentre cohort study

Background: High-flow nasal oxygen (HFNO) is frequently used to treat patients with acute hypoxemic respiratory failure (AHRF) due to viral pneumonia, including COVID-19. However, its clinical effect compared to conventional oxygen therapy (COT) remains largely unexplored in patients with a do not intubate (DNI) order. We aimed to assess whether HFNO compared to COT is associated with improved clinical outcomes in hospitalized patients with AHRF due to COVID-19 and a DNI order. Methods:This analysis included patients with a DNI order and SARS-CoV-2 infection, selected from three observational studies, who were treated with COT only or HFNO. The primary endpoint was in-hospital mortality, the secondary endpoint was hospital length of stay (LOS). The effect of HFNO vs. COT was assessed using multivariable regression, accounting for pre-selected confounders. Results: Between March 2020 and September 2021, 116 patients received HFNO and 110 patients received COT. Median age was 78 [72–83], and 78% of the patients had a Clinical Frailty Scale score of 4 to 9. In-hospital mortality was 64% for HFNO and 71% for COT (p = 0.29), with an adjusted odds ratio of 0.72 (95% confidence interval [0.34–1.54], p = 0.40). Hospital LOS was 11 [6–18] days for HFNO, and 7 [4–12] days for COT (p &lt; 0.001), with a remaining difference after adjusting for confounders (p &lt; 0.01). Conclusion: The lack of survival benefit and increased hospital LOS should be taken into account when considering HFNO for patients with a DNI order, suffering from AHRF due to viral pneumonia, like COVID-19. Clinical trial registration : HFNO-COVID-19 study: DTR, NL9067 (Dutch Trial Registry), registration date: 27-11-2020.<p/

Patients suffering from psychological impairments following critical illness are in need of information

Background: Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient's post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge. Methods: In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL. Results: A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01). Conclusions: In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention

Airborne virus shedding of the alpha, delta, omicron SARS-CoV-2 variants and influenza virus in hospitalized patients

Airborne transmission is an important transmission route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological data indicate that certain SARS-CoV-2 variants, like the omicron variant, are associated with higher transmissibility. We compared virus detection in air samples between hospitalized patients infected with different SARS-CoV-2 variants or influenza virus. The study was performed during three separate time periods in which subsequently the alpha, delta, and omicron SARS-CoV-2 variants were predominant. In total, 79 patients with coronavirus disease 2019 (COVID-19) and 22 patients with influenza A virus infection were included. Collected air samples were positive in 55% of patients infected with the omicron variant in comparison to 15% of those infected with the delta variant (p < 0.01). In multivariable analysis, the SARS-CoV-2 omicron BA.1/BA.2 variant (as compared to the delta variant) and the viral load in nasopharynx were both independently associated with air sample positivity, but the alpha variant and COVID-19 vaccination were not. The proportion of positive air samples patients infected with the influenza A virus was 18%. In conclusion, the higher air sample positivity rate of the omicron variant compared to previous SARS-CoV-2 variants may partially explain the higher transmission rates seen in epidemiological trends