| 1. |
- van de Munckhof, A., et al.
(author)
-
Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase
- 2022
-
In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
-
Journal article (peer-reviewed)abstract
- Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
|
|
| 2. |
- van de Munckhof, A., et al.
(author)
-
Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries
- 2023
-
In: International Journal of Stroke. - 1747-4930 .- 1747-4949. ; 18:9, s. 1112-1120
-
Journal article (peer-reviewed)abstract
- Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20-37) versus 47 (IQR 32-58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11-40]) than in HICs (44/102 [43%, 95% CI 34-53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.
|
|
| 3. |
- Scutelnic, A., et al.
(author)
-
Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19
- 2023
-
In: European Stroke Journal. - 2396-9873 .- 2396-9881. ; 8:4, s. 1001-1010
-
Journal article (peer-reviewed)abstract
- Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x10(9)/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.
|
|
| 4. |
- Van De Munckhof, Anita, et al.
(author)
-
Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase
- 2022
-
In: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
-
Journal article (peer-reviewed)abstract
- Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization.Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization).Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed).Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
|
|
| 5. |
- Bastien, G., et al.
(author)
-
Spin-glass state and reversed magnetic anisotropy induced by Cr doping in the Kitaev magnet alpha-RuCl3
- 2019
-
In: Physical Review B. - 2469-9950 .- 2469-9969. ; 99:21
-
Journal article (peer-reviewed)abstract
- Magnetic properties of the substitution series Ru1-xCrxCl3 were investigated to determine the evolution from the anisotropic Kitaev magnet alpha-RuCl3 with J(eff) = 1/2 magnetic Ru(3+ )ions to the isotropic Heisenberg magnet CrCl3 with S = 3/2 magnetic Cr3+ ions. Magnetization measurements on single crystals revealed a reversal of the magnetic anisotropy under doping, which we argue to arise from the competition between anisotropic Kitaev and off-diagonal interactions on the Ru-Ru links and approximately isotropic Cr-Ru and isotropic Cr-Cr interactions. In addition, combined magnetization, ac susceptibility, and specific-heat measurements clearly show the destabilization of the long-range magnetic order of alpha-RuCl3 in favor of a spin-glass state of Ru1-xCrxCl3 for a low doping of x similar or equal to 0.1. The corresponding freezing temperature as a function of Cr content shows a broad maximum around x similar or equal to 0.45.
|
|
| 6. |
- Haghighi, Mona, et al.
(author)
-
A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
|
|
| 7. |
- Insulander, J., et al.
(author)
-
Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma
- 2016
-
In: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:9, s. 1200-1208
-
Journal article (peer-reviewed)abstract
- Background: Resection with curative intent has been shown to prolong survival of patients with locoregional pancreatic ductal adenocarcinoma (PDAC). However, up to 33 per cent of patients are deemed unresectable at exploratory laparotomy owing to unanticipated locally advanced or metastatic disease. In these patients, prophylactic double bypass (PDB) procedures have been considered the standard of care. The aim of this study was to compare PDB with exploratory laparotomy alone in terms of impact on postoperative course, chemotherapy and overall survival.Methods: This retrospective observational cohort study (2004-2013) was conducted using a prospective institutional database. Patients with histologically confirmed, unresectable PDAC were included. Relationships between PDB procedures, exploratory laparotomy alone, postoperative chemotherapy and best supportive care were investigated by means of Cox regression. Overall survival was compared using Kaplan-Meier estimations and log rank test.Results: Of 503 patients with PDAC scheduled for resection with curative intent, 104 were deemed unresectable at laparotomy (resection rate 79·3 per cent). Seventy-four patients underwent PDB procedures and 30 had exploratory laparotomy alone. PDB and exploratory laparotomy were similar in terms of perioperative mortality, initiation of chemotherapy and overall survival. Compared with best supportive care, postoperative chemotherapy prolonged survival (8·0 versus 14·4 months in locally advanced PDAC, P = 0·007; 2·3 versus 8·0 months in metastatic PDAC, P < 0·001). Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival than patients undergoing chemotherapy following PDB procedures (16·3 versus 10·3 months; P = 0·040).Conclusion: Patients with pancreatic cancer deemed unresectable at laparotomy may derive survival benefit from subsequent chemotherapy as opposed to supportive care alone. At laparotomy, proceeding with a bypass procedure for prophylactic symptom control may be prognostically unfavourable.
|
|
| 8. |
- Johansson, Per, et al.
(author)
-
Convergence of chromogranin and amyloid metabolism in the brain.
- 2010
-
In: Alzheimer's & Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 6:4, s. 511-511
-
Conference paper (peer-reviewed)abstract
- Background: Much is unknown regarding the regulation of amyloid precursor protein (APP) processing in the human central nervous system. It has been hypothesized that amyloidogenic APP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of APP-derived molecules in CSF with chromogranin (Cg) derived peptides, representing the regulated secretion. Methods: Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50) and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides Aβ1-42, Aβx-42, Aβx-40, Aβx-38, α-cleaved soluble APP (α-sAPP), β-cleaved soluble APP (β-sAPP), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes APP into Aβ, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. Results: CSF Cg levels correlated to sAPP and Aβ peptides in AD, MS and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. Conclusions: These results suggest that a large part of APP in the human central nervous system is processed in the regulated secretory pathway of neurons.
|
|
| 9. |
- Krzywicka, Katarzyna, et al.
(author)
-
Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.
- 2023
-
In: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 30:5, s. 1335-1345
-
Journal article (peer-reviewed)abstract
- Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored.Data from an ongoing international registry of patients who developed CVST within 28days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included.Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p<0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p<0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p=0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6months, 8/10 of surgical CVST-VITT who survived admission were functionally independent.Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.
|
|
| 10. |
|
|
