Trends in Mortality after Intensive Care of Patients with Aneurysmal Subarachnoid Hemorrhage in Finland in 2003-2019: A Finnish Intensive Care Consortium study

Daniel Strbian konsortion jäsenenäPeer reviewe

Trends in Mortality after Intensive Care of Patients with Aneurysmal Subarachnoid Hemorrhage in Finland in 2003-2019: A Finnish Intensive Care Consortium study

Background: Previous studies suggest that case mortality of aneurysmal subarachnoid hemorrhage (aSAH) has decreased during the last decades, but most studies have been unable to assess case severities among individual patients. We aimed to assess changes in severity-adjusted aSAH mortality in patients admitted to intensive care units (ICUs).Methods: We conducted a retrospective, register-based study by using the prospectively collected Finnish Intensive Care Consortium database. Four out of five ICUs providing neurosurgical and neurointensive care in Finland participated in the Finnish Intensive Care Consortium. We extracted data on adult patients admitted to Finnish ICUs with aSAH between 2003 and 2019. The primary outcome was 12-month mortality during three periods: 2003-2008, 2009-2014, and 2015-2019. Using a multivariable logistic regression model-with variables including age, sex, World Federation of Neurological Surgeons grade, preadmission dependency, significant comorbidities, and modified Simplified Acute Physiology Score II-we analyzed whether admission period was independently associated with mortality.Results: A total of 1,847 patients were included in the study. For the periods 2003-2008 and 2015-2019, the mean number of patients with aSAH admitted per year increased from 81 to 123. At the same time, the patients' median age increased from 55 to 58 years (p = 0.001), and the proportion of patients with World Federation of Neurological Surgeons grades I-III increased from 42 to 58% (p Conclusions: Between 2003 and 2019, patients with aSAH admitted to ICUs became older and the proportion of less severe cases increased. Unadjusted mortality decreased but age and case severity adjusted-mortality remained unchanged.</p

Traumatic brain injury patient volume and mortality in neurosurgical intensive care units: a Finnish nationwide study

Background: Differences in outcomes after traumatic brain injury (TBI) between neurosurgical centers exist, although the reasons for this are not clear. Thus, our aim was to assess the association between the annual volume of TBI patients and mortality in neurosurgical intensive care units (NICUs).Methods: We collected data on all patients treated in the five Finnish university hospitals to examine all patients with TBI treated in NICUs in Finland from 2009 to 2012. We used a random effect logistic regression model to adjust for important prognostic factors to assess the independent effect of ICU volume on 6-month mortality. Subgroup analyses were performed for patients with severe TBI, moderate-to-severe TBI, and those who were undergoing mechanical ventilation or intracranial pressure monitoring.Results: Altogether 2,328 TBI patients were treated during the study period in five NICUs. The annual TBI patient volume ranged from 61 to 206 patients between the NICUs. Univariate analysis, showed no association between the NICUs' annual TBI patient volume and 6-month mortality (p = 0.063). The random effect model showed no independent association between the NICUs' annual TBI patient volume and 6-month mortality (OR = 1.000, 95% CI = 0.996-1.004, p = 0.876). None of the pre-defined subgroup analyses indicated any association between NICU volume and patient mortality (p > 0.05 for all).Discussion and Conclusion: We did not find any association between annual TBI patient volume and 6-month mortality in NICUs. These findings should be interpreted taking into account that we only included NICUs, which by international standards all treated high volumes of TBI patients, and that we were not able to study the effect of NICU volume on neurological outcome

Effect of antiplatelet and anticoagulant medication use on injury severity and mortality in patients with traumatic brain injury treated in the intensive care unit

Background: Antiplatelet and anticoagulant medication are increasingly common and can increase the risks of morbidity and mortality in traumatic brain injury (TBI) patients. Our study aimed to quantify the association of antiplatelet or anticoagulant use in intensive care unit (ICU)–treated TBI patients with 1-year mortality and head CT findings. Method: We conducted a retrospective, multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted to four university hospital ICUs during 2003–2013. The patients were followed up until the end of 2016. The national drug reimbursement database provided information on prescribed medication for our study. We used multivariable logistic regression models to assess the association between TBI severity, prescribed antiplatelet and anticoagulant medication, and their association with 1-year mortality. Results: Of 3031 patients, 128 (4%) had antiplatelet and 342 (11%) anticoagulant medication before their TBI. Clopidogrel (2%) and warfarin (9%) were the most common antiplatelets and anticoagulants. Three patients had direct oral anticoagulant (DOAC) medication. The median age was higher among antiplatelet/anticoagulant users than in non-users (70 years vs. 52 years, p < 0.001), and their head CT findings were more severe (median Helsinki CT score 3 vs. 2, p < 0.05). In multivariable analysis, antiplatelets (OR 1.62, 95% CI 1.02–2.58) and anticoagulants (OR 1.43, 95% CI 1.06–1.94) were independently associated with higher odds of 1-year mortality. In a sensitivity analysis including only patients over 70, antiplatelets (OR 2.28, 95% CI 1.16–4.22) and anticoagulants (1.50, 95% CI 0.97–2.32) were associated with an increased risk of 1-year mortality. Conclusions: Both antiplatelet and anticoagulant use before TBI were risk factors in our study for 1-year mortality. Antiplatelet and anticoagulation medication users had a higher radiological intracranial injury burden than non-users defined by the Helsinki CT score. Further investigation on the effect of DOACs on mortality should be done in ICU–treated TBI patients.Peer reviewe

Comparison of high versus low frequency cerebral physiology for cerebrovascular reactivity assessment in traumatic brain injury: a multi-center pilot study

Current accepted cerebrovascular reactivity indices suffer from the need of high frequency data capture and export for post-acquisition processing. The role for minute-by-minute data in cerebrovascular reactivity monitoring remains uncertain. The goal was to explore the statistical time-series relationships between intra-cranial pressure (ICP), mean arterial pressure (MAP) and pressure reactivity index (PRx) using both 10-s and minute data update frequency in TBI. Prospective data from 31 patients from 3 centers with moderate/severe TBI and high-frequency archived physiology were reviewed. Both 10-s by 10-s and minute-by-minute mean values were derived for ICP and MAP for each patient. Similarly, PRx was derived using 30 consecutive 10-s data points, updated every minute. While long-PRx (L-PRx) was derived via similar methodology using minute-by-minute data, with L-PRx derived using various window lengths (5, 10, 20, 30, 40, and 60 min; denoted L-PRx_5, etc.). Time-series autoregressive integrative moving average (ARIMA) and vector autoregressive integrative moving average (VARIMA) models were created to analyze the relationship of these parameters over time. ARIMA modelling, Granger causality testing and VARIMA impulse response function (IRF) plotting demonstrated that similar information is carried in minute mean ICP and MAP data, compared to 10-s mean slow-wave ICP and MAP data. Shorter window L-PRx variants, such as L-PRx_5, appear to have a similar ARIMA structure, have a linear association with PRx and display moderate-to-strong correlations (r ~ 0.700, p Peer reviewe

Copy Number Alteration and Uniparental Disomy Analysis Categorizes Japanese Papillary Thyroid Carcinomas into Distinct Groups

The aim of the present study was to investigate chromosomal aberrations in sporadic Japanese papillary thyroid carcinomas (PTCs), concomitant with the analysis of oncogene mutational status. Twenty-five PTCs (11 with BRAFV600E, 4 with RET/PTC1, and 10 without mutation in HRAS, KRAS, NRAS, BRAF, RET/PTC1, or RET/PTC3) were analyzed using Genome-Wide Human SNP Array 6.0 which allows us to detect copy number alteration (CNA) and uniparental disomy (UPD), also referred to as copy neutral loss of heterozygosity, in a single experiment. The Japanese PTCs showed relatively stable karyotypes. Seven cases (28%) showed CNA(s), and 6 (24%) showed UPD(s). Interestingly, CNA and UPD were rarely overlapped in the same tumor; the only one advanced case showed both CNA and UPD with a highly complex karyotype. Thirteen (52%) showed neither CNA nor UPD. Regarding CNA, deletions tended to be more frequent than amplifications. The most frequent and recurrent region was the deletion in chromosome 22; however, it was found in only 4 cases (16%). The degree of genomic instability did not depend on the oncogene status. However, in oncogene-positive cases (BRAFV600E and RET/PTC1), tumors with CNA/UPD were less frequent (5/15, 33%), whereas tumors with CNA/UPD were more frequent in oncogene-negative cases (7/10, 70%), suggesting that chromosomal aberrations may play a role in the development of PTC, especially in oncogene-negative tumors. These data suggest that Japanese PTCs may be classified into three distinct groups: CNA+, UPD+, and no chromosomal aberrations. BRAFV600E mutational status did not correlate with any parameters of chromosomal defects

Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage

Subarachnoid hemorrhage after the rupture of a cerebral aneurysm is the cause of 6% to 8% of all cerebrovascular accidents involving 10 of 100,000 people each year. Despite effective treatment of the aneurysm, delayed cerebral ischemia (DCI) is observed in 30% of patients, with a peak on the tenth day, resulting in significant infirmity and mortality. Cerebral vasospasm occurs in more than half of all patients and is recognized as the main cause of delayed cerebral ischemia after subarachnoid hemorrhage. Its treatment comprises hemodynamic management and endovascular procedures. To date, the only drug shown to be efficacious on both the incidence of vasospasm and poor outcome is nimodipine. Given its modest effects, new pharmacological treatments are being developed to prevent and treat DCI. We review the different drugs currently being tested

Low VHL mRNA Expression is Associated with More Aggressive Tumor Features of Papillary Thyroid Carcinoma

Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR55.78, 95% CI 3.17-10.53, P<0.0001), classical papillary morphology of the tumor (OR52.92, 95% CI 1.33-6.44, P=50.008) and multifocality (OR51.96, 95% CI 1.06-3.62, P=50.031). In disease-free survival analysis, low VHL expression had marginal significance (P=50.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated