Background and Purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms. Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death. Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable. Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.
Alongside to respiratory cancers, exposure to asbestos has been associated with gastrointestinal cancers. An association between exposure to amphibole fibres and their presence in hepatic tissue has been reported. We conducted a case-control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma.
Methods
We used historical data from 155 consecutive patients referred to our centre for diagnosis and treatment of cholangiocarcinoma in 2007–2011 (69 affected by Intrahepatic Cholangiocarcinoma (ICC) and 86 by Extrahepatic Cholangiocarcinoma (ECC)). When feasible, cases were individually matched (ratio up to 1:4) by calendar period of birth (5-year interval), sex and provenience to historical population controls (originally sampled to study other occupational diseases, not related to asbestos). Occupational exposure to asbestos was assessed by industrial hygienists considering life-prevalent job titles. Separate conditional logistic regression models were conducted for ICC and ECC, adjusting for smoking status and socioeconomic class.
Results
We matched 149 controls to 49 cases of ICC and 212 controls to 59 cases of ECC (47 cases were not matched mainly due to provenience). We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.73, 95% CI 1.54 to 14.54); conversely, no clear evidence of increased risk was found for ECC (adjusted OR 1.84, 95% CI 0.66 to 5.08). Sensitivity analysis conducted using only patients from our city district (conducted to minimise referral bias) produced confirmatory figures.
Conclusions
Findings from our exploratory study support the hypothesis that intrahepatic cholangiocarcinoma could arise from chronic irritation and inflammation caused by deposition of asbestos fibres.
Sex-related differences in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) are poorly investigated so far. This study elucidates whether sex-related differences in ICH care in a neurocritical care setting exist, particularly regarding provided care, while also taking patient characteristics, and outcomes into account.This retrospective single center study includes all consecutive patients with spontaneous ICH admitted to the neurocritical care unit in a 10-year period. Patients' demographics, comorbidities, symptoms at presentation, radiological findings, surgical and medical provided care, intensive care unit mortality and 12 month-mortality, and functional outcome at discharge were compared among men and women.Overall, 398 patients were included (male = 198 and female = 200). No differences in demographics, Charlson Comorbidity Index (CCI), symptoms at presentation, radiological findings, intensive care unit mortality and 12-month mortality were observed among men and women. Men received an external ventricular drain (EVD) for hydrocephalus-therapy significantly more often than women, despite similar location of the ICH and radiographic parameters. In the multivariate analysis, EVD insertion was independently associated with male sex (odds ratio 2.82, 95% confidence interval 1.61-4.95, P < 0.001) irrespective of demographic or radiological features. Functional outcome after ICH as assessed by the modified Rankin scale, was more favorable for women (P = 0.044).Sex-related differences in patients with ICH regarding to provided neurosurgical care exist. We provide evidence that insertion of EVD is associated with male sex, disregarding clear reasoning. A sex-bias as well as social factors may play a significant role in decision-making for the insertion of an EVD.
Estimation of cardiac output (CO) and evaluation of change in CO as a result of therapeutic interventions are essential in critical care medicine. Whether noninvasive tools estimating CO, such as continuous cardiac output (esCCOTM) methods, are sufficiently accurate and precise to guide therapy needs further evaluation. We compared esCCOTM with an established method, namely, transpulmonary thermodilution (TPTD). Patients and Methods. In a single center mixed ICU, esCCOTM was compared with the TPTD method in 38 patients. The primary endpoint was accuracy and precision. The cardiac output was assessed by two investigators at baseline and after eight hours.In 38 critically ill patients, the two methods correlated significantly (r = 0.742). The Bland-Altman analysis showed a bias of 1.6 l/min with limits of agreement of -1.76 l/min and +4.98 l/min. The percentage error for COesCCO was 47%. The correlation of trends in cardiac output after eight hours was significant (r = 0.442), with a concordance of 74%. The performance of COesCCO could not be linked to the patient's condition.The accuracy and precision of the esCCOTM method were not clinically acceptable for our critical patients. EsCCOTM also failed to reliably detect changes in cardiac output.
Delirium is a common complication in patients at the intensive care unit (ICU) and is associated with prolonged ICU-stay and hospitalization and with increased morbidity. The impact of ICU-delirium on long-term survival is not clearly understood. This retrospective single center observational study was conducted at the Institute of Intensive Care Medicine at the University Hospital Zurich, Switzerland. All adult ICU-survivors over a four-year period were screened for eligibility. ICU-delirium was defined based on the Intensive Care Delirium Screening Checklist (ICDSC), together with the coded diagnosis F05 in the International Classification of Diseases (ICD-2019). ICU-survivors who developed delirium during their ICU stay (group D) were compared with ICU-survivors who did not (group ND). Survival was evaluated according to data from hospital electronic health records up to four years from ICU-discharge. The survival analysis was reported using Kaplan-Meier curves and absolute risk differences (ARD). A multivariable logistic regression model was fitted with long-term survival at four years after ICU-discharge as outcome of interest, including several clinical conditions and interventions associated with long-term survival for ICU patients. For subgroup analysis, ICU-survivors were grouped based on age at the time of admission (45–54, 55–64, ≥ 65 years), and on relevant clinical conditions. A total of 9'604 patients fulfilled the inclusion criteria, of them 22.6% (n = 2'171) developed ICU-delirium. Overall, patients in the group D had a significantly lower probability of survival than patients in the group ND (p < 0.0001, ARD = 11.8%). In the multivariable analysis, ICU-delirium was confirmed as independently associated with long-term survival. After grouping for age categories, patients between 55 and 64 years of age in the group D were less likely to survive than patients in the group ND at every time point analyzed, up to four years after ICU discharge (p < 0.001, ARD = 7.3%). This difference was even more significant in the comparison between patients over 65 years (p < 0.0001, ARD 11.1%). No significant difference was observed in the other age groups. In the study population, ICU-delirium was independently associated with a reduced long-term survival. Patients who developed ICU-delirium had a reduced survival up to four years after ICU discharge and this association was particularly evident in patients above 55 years of age.
Bleeding and thromboembolic (TE) complications in neurosurgical diseases have a detrimental impact on clinical outcomes. The aim of this study is to provide a scoping review of the available literature and address challenges and knowledge gaps in the management of coagulation disorders in neurosurgical diseases. Additionally, we introduce a novel research project that seeks to reduce coagulation disorder-associated complications in neurosurgical patients. The risk of bleeding after elective craniotomy is about 3%, and higher (14-33%) in other indications, such as trauma and intracranial hemorrhage. In spinal surgery, the incidence of postoperative clinically relevant bleeding is approximately 0.5-1.4%. The risk for TE complications in intracranial pathologies ranges from 3 to 20%, whereas in spinal surgery it is around 7%. These findings highlight a relevant problem in neurosurgical diseases and current guidelines do not adequately address individual circumstances. The multidisciplinary COagulation MAnagement in Neurosurgical Diseases (COMAND) project has been developed to tackle this challenge by devising an individualized coagulation management strategy for patients with neurosurgical diseases. Importantly, this project is designed to ensure that these management strategies can be readily implemented into healthcare practices of different types and with sustainable integration.
Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 μmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 μmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 μmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 μmol/ l; p < 0.05, ANOVA, post hoc Dunn's test). Plasma glutamate remained unchanged and cerebral glutamate was decreased without any signs of cerebral impairment. Urea and ammonia were significantly increased within normal limits without signs of organ dysfunction (urea: from 2.7 ± 1.6 to 5.5 ± 1.5 mmol/ l; ammonia: from 12 ± 6.3 to 26 ± 8.3 μmol/ l; p < 0.05, ANOVA, post hoc Dunn's test). High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. Clinicaltrials.gov NCT02130674 . Registered 5 April 2014
