Sex-related differences in extracranial complications in patients with traumatic brain injury.

Background: Extracranial complications after traumatic brain injury (TBI) are common. Their influence on outcome is uncertain. Furthermore, the role of sex on the development of extracranial complications following TBI remains poorly investigated. We aimed to investigate the incidence of extracranial complications after TBI with particular focus on sex-related differences with regard to complications and their influence on outcome. Methods: This retrospective, observational study was conducted in a level I universitary swiss trauma center. Consecutive patients with TBI admitted to the intensive care unit (ICU) between 2018 and 2021 were included. Patients' and trauma characteristics, in-hospital complications (i.e., cardiovascular, respiratory, renal, metabolic, gastrointestinal, hematological, and infectious) as well as functional outcome 3 months after trauma were analyzed. Data was dichotomized by sex or by outcome. Univariate as well as multivariate logistic regression was performed to reveal possible associations between sex, outcome and complications. Results: Overall, 608 patients were included (male n = 447, 73.5%). Extracranial complications occurred most frequently in cardiovascular, renal, hematological and infectious systems. Men and women suffered similarly from extracranial complications. While men needed correction of coagulopathies more often (p = 0.029), women suffered more frequently from urogenital infections (p = 0.001). Similar results were found in a subgroup of patients (n = 193) with isolated TBI. A multivariate analysis did not show extracranial complications to be independent predictors of unfavorable outcome. Conclusion: Extracranial complications following TBI occur frequently during the ICU-stay, can affect almost all organ systems but are not independent predictors of unfavorable outcome. The results suggest that sex-specific strategies for early recognition of extracranial complications might not be needed in patients with TBI.

Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report.

BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. MAIN BODY: We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months. CONCLUSIONS: This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.

Renal Tubular Acidosis in Pregnant Critically Ill COVID-19 Patients: A Secondary Analysis of a Prospective Cohort.

BACKGROUND: Renal tubular acidosis (RTA) is an extremely rare cause of metabolic acidosis (10 in 100,000). RTA has been linked neither to pregnancy nor to severe coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the prevalence and clinical course of normal anion gap metabolic acidosis in critically ill pregnant COVID-19 patients and to compare them to an age-matched nonpregnant female patient cohort. METHODS: Secondary analysis was conducted on a prospective observational cohort of critically ill patients suffering from COVID-19 consecutively admitted to a tertiary intensive care unit (ICU) between February 2020 and April 2021. RESULTS: A total of 321 COVID-19 patients required admission to the ICU; 95 (30%) were female, and 18 (19%) were of childbearing age. Seven of eight (88%) pregnant women (all in the last trimester) required advanced respiratory support due to COVID-19. The estimated glomerular filtration rate was 135 (123-158) mL/min/m2 body surface area, and six pregnant women (86%) were diagnosed with a normal, respiratory compensated, anion gap metabolic acidosis (pHmin 7.3 (7.18-7.31), HCO3-min 14.8 (12.8-18.6) mmol/L, and paCO2 3.4 (3.3-4.5) kPa). Three (43%) acidotic pregnant women fulfilled diagnostic criteria for RTA. All women recovered spontaneously within less 7 days. CONCLUSIONS: Metabolic acidosis seems to be very common (85%) in pregnant critically ill COVID-19 patients, and the prevalence of RTA might be higher than normal. It remains to be demonstrated if this observation is an indirect epiphenomenon or due to a direct viral effect on the tubular epithelium.

Delayed prophylaxis with unfractionated heparin increases the risk of venous thromboembolic events in patients with moderate to severe traumatic brain injury: a retrospective analysis.

BACKGROUND: Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis - PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. METHODS: In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. RESULTS: In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. CONCLUSIONS: In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.

ICU, hospital and one year mortality of patients suffering from solid or haematological malignancies.

OBJECTIVE: To examine the demographics, evolution and outcome of patients suffering from malignancies admitted to a medical intensive care unit. PATIENTS AND METHODS: Single centre retrospective cohort study of patients with malignancies. Data on demographics, diagnosis laboratory tests, provided therapy and outcome were retrospectively collected. Data was analysed for differences between patients suffering from solid compared to haematological malignancies as well as for predictors of one year survival. RESULTS: A total of 74 consecutive patients with a median age of 62 years were enrolled. From these, 42 (57%) suffered from solid and 32 (43%) from haematological malignancies. In total, 64% of patients with solid malignancies presented with metastatic disease. The main reason for intensive care unit admission in patients with solid malignancies was acute cardiovascular failure (39%) and infections in patients with haematological malignancies (38%). Intensive care unit mortality, hospital mortality and one year mortality were 26%, 35% and 71% overall; 17%, 29% and 69% respectively in patients with solid and 38%, 44% and 73% respectively in patients with haematological malignancies. Survival was close to 40% in patients with no or one organ failure. Survival dropped to 20% with 2 and 13% with ≥3 organs in failure. The number of organs in failure predicted hospital fatality with an AUCRoc of 0.87. CONCLUSION: The number of failing organs rather than malignancy itself drives outcome even in patients with malignancies. Thus the number of organs in failure rather than diagnosis should guide intensive care unit management in patients with malignancies.