Early warning scores to assess the probability of critical illness in patients with COVID-19.

OBJECTIVE: Validated clinical risk scores are needed to identify patients with COVID-19 at risk of severe disease and to guide triage decision-making during the COVID-19 pandemic. The objective of the current study was to evaluate the performance of early warning scores (EWS) in the ED when identifying patients with COVID-19 who will require intensive care unit (ICU) admission for high-flow-oxygen usage or mechanical ventilation. METHODS: Patients with a proven SARS-CoV-2 infection with complete resuscitate orders treated in nine hospitals between 27 February and 30 July 2020 needing hospital admission were included. Primary outcome was the performance of EWS in identifying patients needing ICU admission within 24 hours after ED presentation. RESULTS: In total, 1501 patients were included. Median age was 71 (range 19-99) years and 60.3% were male. Of all patients, 86.9% were admitted to the general ward and 13.1% to the ICU within 24 hours after ED admission. ICU patients had lower peripheral oxygen saturation (86.7% vs 93.7, p≤0.001) and had a higher body mass index (29.2 vs 27.9 p=0.043) compared with non-ICU patients. National Early Warning Score 2 (NEWS2) ≥ 6 and q-COVID Score were superior to all other studied clinical risk scores in predicting ICU admission with a fair area under the receiver operating characteristics curve of 0.740 (95% CI 0.696 to 0.783) and 0.760 (95% CI 0.712 to 0.800), respectively. NEWS2 ≥6 and q-COVID Score ≥3 discriminated patients admitted to the ICU with a sensitivity of 78.1% and 75.9%, and specificity of 56.3% and 61.8%, respectively. CONCLUSION: In this multicentre study, the best performing models to predict ICU admittance were the NEWS2 and the Quick COVID-19 Severity Index Score, with fair diagnostic performance. However, due to the moderate performance, these models cannot be clinically used to adequately predict the need for ICU admission within 24 hours in patients with SARS-CoV-2 infection presenting at the ED.

Pheochromocytomas and Paragangliomas: New Developments with Regard to Classification, Genetics, and Cell of Origin.

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors that arise in the adrenal medulla and in extra-adrenal locations, such as the head, neck, thorax, abdomen, and pelvis. Classification of these tumors into those with or without metastatic potential on the basis of gross or microscopic features is challenging. Recent insights and scoring systems have attempted to develop solutions for this, as described in the latest World Health Organization (WHO) edition on endocrine tumor pathology. PCC and PGL are amongst the tumors most frequently accompanied by germline mutations. More than 20 genes are responsible for a hereditary background in up to 40% of these tumors; somatic mutations in the same and several additional genes form the basis for another 30%. However, this does not allow for a complete understanding of the pathogenesis or targeted treatment of PCC and PGL, for which surgery is the primary treatment and for which metastasis is associated with poor outcome. This review describes recent insights into the cell of origin of these tumors, the latest developments with regard to the genetic background, and the current status of tumor classification including proposed scoring systems.

An Update on the Histology of Pheochromocytomas: How Does it Relate to Genetics?

Pheochromocytomas are rare neuroendocrine tumors of the adrenal gland, whereas any extra-adrenal tumor with similar histology is designated as paraganglioma. These tumors have a very high rate of germline mutations in a large number of genes, up to 35% to 40%, frequently predisposing for other tumors as well. Therefore, they represent a phenomenal challenge for treating physicians. This review focuses on pheochromocytomas only, with special attention to gross and microscopic clues to the diagnosis of genetic syndromes, including the role of succinate dehydrogenase subunit A and subunit B immunohistochemistry as surrogate markers for genetic analysis in the field of succinate dehydrogenase subunit gene mutations.

Risk factors for cerebral venous thrombosis and deep venous thrombosis in patients aged between 15 and 50 years.

Cerebral venous thrombosis (CVT) and deep vein thrombosis or pulmonary embolism (DVT/PE) are associated with many risk factors. It is unclear why CVT occurs less often than DVT/PE. Age dependent risk factors may play a role. The aim of our study was to compare risk factors in a uniform age group of CVT and DVT/PE patients aged between 15 and 50 years. Thrombophilic markers and clinical risk factors of 79 CVT patients and 173 DVT/PE patients aged 15-50 years were compared. Multivariable logistic regression analysis was performed to investigate if risk factors were independently associated with CVT or DVT/PE. Cerebral venous thrombosis patients were younger (median age 30 years vs. 42 years; p<0.001) and more often female (82% vs. 52%; p<0.001). There were no differences in thrombophilic markers. Cerebral venous thrombosis was less often associated with trauma, immobilisation or surgery than DVT/PE (6% vs. 21%; adjusted OR 0.29; 95%CI 0.10-0.82). In women, CVT was more frequently associated with oral contraceptive use, pregnancy or puerperium (82% vs. 53%; adjusted OR 2.34; 95%CI 1.03-5.32). This study demonstrated no differences in thrombophilic markers between CVT patients and DVT/PE patients aged between 15 and 50 years, while the frequency of some transient risk factors was different. Cerebral venous thrombosis was relatively more common in women and hormonal factors may predispose to CVT compared to DVT/PE, while trauma, immobilisation and surgery may be less important in the pathophysiology of CVT.

Improved discrimination of autopsy-confirmed Alzheimer's disease (AD) from non-AD dementias using CSF P-tau(181P).

To establish diagnostic accuracy (acc) and optimal cut-off levels of CSF tau phosphorylated at threonine 181 (P-tau(181P)) for discriminating Alzheimer's disease (AD) from non-AD dementias in autopsy-confirmed dementia patients, CSF levels of beta-amyloid peptide (Abeta(1-42)), total tau protein (T-tau) and P-tau(181P) from patients with definite AD (n=95) and non-AD dementias (n=50) were determined with single-parameter ELISA kits. Optimal P-tau(181P) cut-off levels for differentiating AD from pooled non-AD dementias, dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) were 50.4pg/mL (acc=0.73), 52.8pg/mL (acc=0.73) and 35.3pg/mL (acc=0.90), respectively. The optimal CSF P-tau(181P) cut-off level for discriminating AD from non-AD dementias was 50.4pg/mL. Optimal CSF P-tau(181P) cut-off levels differed between non-AD diagnostic dementia categories.

Long-term sequelae after cerebral venous thrombosis in functionally independent patients.

BACKGROUND: The majority of survivors of cerebral venous thrombosis (CVT) regain functional independence, but it is unclear whether these patients experience long-term sequelae. The aim of this case-control study was to assess: (1) frequency of headache, fatigue, depression, and concentration impairment; and (2) impact of these sequelae on daily life and employment in patients with CVT who are functionally independent. METHODS: We included 44 patients with CVT older than 15 years diagnosed between January 1997 and July 2006 who were functionally independent (modified Rankin scale score

Thromboelastography in patients with cerebral venous thrombosis.

INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare presentation of venous thrombosis and has been associated with many conditions. In about 20% no risk factor is identified. The aim of this study was to assess the clot formation by thromboelastography (TEG) in patients with a history of CVT compared with healthy controls. MATERIALS AND METHODS: TEG analysis was performed on recalcified blood samples of 19 CVT patients from a single centre cohort and 1:1 sex/ age (+/-3 year) matched controls. Four TEG parameters were monitored: reaction time (r) to clot initiation, time to reach a 20 mm level of clot formation (K), slope angle alpha from r to K (alpha) and maximum vertical amplitude (MA). Patients were tested for thrombophilic defects, including deficiencies of antithrombin, protein C and protein S, factor V Leiden, prothrombin G20210A mutation, lupus anticoagulant, antiphospholipid antibodies, and high factor VIII levels. RESULTS: Thrombophilia testing identified a prothrombotic abnormality in 11 patients (58%). Sixteen patients (84%) had one or more transient risk factor. There were no significant differences in TEG parameters between CVT patients and controls, neither between the subgroup of patients with a thrombophilic defect and controls. Seven of all patients (37%), including 5 patients with abnormal thrombophilia testing, and 5 controls (26%) had one or more TEG hypercoagulable parameters. CONCLUSIONS: A persistent hypercoagulable state which could have predisposed to venous thrombosis in CVT patients and in the subgroup of patients with a thrombophilic defect could not be demonstrated by TEG.

Safety of antiplatelet therapy prior to intravenous thrombolysis in acute ischemic stroke.

BACKGROUND: There is some uncertainty whether prior use of antiplatelet (AP) drugs increases the risk of symptomatic intracerebral hemorrhage (SICH) and influences functional outcome in patients with ischemic stroke treated with intravenous thrombolysis. OBJECTIVE: To assess whether prior use of AP drugs is related to outcome following intravenous tissue plasminogen activator therapy in patients with ischemic stroke. DESIGN, SETTING, AND PATIENTS: A single-center prospective observational cohort study of the relation between prior AP therapy, occurrence of SICH, and functional outcome of consecutive patients with ischemic stroke undergoing intravenous thrombolysis with tissue plasminogen activator in a university hospital between April 1, 2002, and November 30, 2006. MAIN OUTCOME MEASURES: The occurrence of SICH and favorable outcome reflecting independence defined as a modified Rankin Scale score of 2 or lower at 3 months. RESULTS: Of the 301 patients who received intravenous tissue plasminogen activator, 89 used AP drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 12 patients (13.5%; 95% confidence interval, 7.8%-22.3%) who had received AP drugs and in 6 patients (2.8%; 95% confidence interval, 1.2%-6.2%) without prior AP therapy (P = .001). Multivariate analysis revealed that prior AP therapy was an independent predictor of SICH (odds ratio, 6.0; 95% confidence interval, 2.0-17.1). Nonetheless, prior AP therapy was independently associated with a favorable outcome (odds ratio, 2.0; 95% confidence interval, 1.0-4.3). CONCLUSION: Despite a higher incidence of SICH, the net benefit of intravenous tissue plasminogen activator therapy for acute ischemic stroke was greater in patients using AP drugs.