External validation of the CHEDDAR score for suspected pulmonary embolism in patients with SARS-CoV-2 infection in an independent cohort.

The accuracy of the classic scores that help stratify the pretest clinical probability of pulmonary embolism (PE) in SARS-CoV-2 infection (COVID-19) is low. Therefore, to estimate the risk of PE in these patients, a new set of guidelines must be established. The recently published CHEDDAR score proposes a new diagnostic strategy to reduce the use of computed tomography pulmonary angiography (CTPA) in non-critically ill SARS-COV-2 patients with suspected PE. According to the nomogram, patients are segregated into low-risk (< 182 points) or high-risk (≥ 182 points) based on the best cut-off value to discard PE in the original cohort. We aimed to externally validate this diagnostic strategy in an independent cohort. We analyzed data from two retrospective cohorts of hospitalized non-critically ill COVID-19 patients who underwent a CTPA due to suspicion for PE. CHEDDAR score was applied. As per the CHEDDAR nomogram, patients were classified as having a low or high clinical pre-test probability. Of the 270 patients included, 69 (25.5%) had PE. Applying the CHEDDAR score, 182 (67.4%) patients could have had PE excluded without imaging. Among 58 patients classified as having high clinical pre-test probability, 39 (67.2%) had PE. Sensitivity, specificity, positive and negative predictive values, and AUC were 56%, 90%, 67%, 85%, and 0.783 (95% CI 0.71-0.85), respectively. We provide external validation of the CHEDDAR score in an independent cohort. Even though the CHEDDAR score showed good discrimination capacity, caution is required in patients classified as having low clinical pre-test probability with a D-dimer value > 3000 ng/mL, and a RALE score ≥ 4.

Prognostic factors and combined use of tocilizumab and corticosteroids in a Spanish cohort of elderly COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection in elderly patients is more aggressive and treatments have shown limited efficacy. Our objective is to describe the clinical course and to analyze the prognostic factors associated with a higher risk of mortality of a cohort of patients older than 80 years. In addition, we assess the efficacy of immunosuppressive treatments in this population. We analyzed the data from 163 patients older than 80 years admitted to our institution for COVID-19, during March and April 2020. A Lasso regression model and subsequent multivariate Cox regression were performed to select variables predictive of death. We evaluated the efficacy of immunomodulatory therapy in three cohorts using adjusted survival analysis. The mortality rate was 43%. The mean age was 85.2 years. The disease was considered severe in 76.1% of the cases. Lasso regression and multivariate Cox regression indicated that factors correlated with hospital mortality were: age (hazard ratio [HR] 1.12, 95% confidence interval [CI]: 1.03-1.22), alcohol consumption (HR 3.15, 95% CI: 1.27-7.84), CRP > 10 mg/dL (HR 2.67, 95% CI: 1.36-5.24), and oxygen support with Venturi Mask (HR 6.37, 95% CI: 2.18-18.62) or reservoir (HR 7.87, 95% CI: 3.37-18.38). Previous treatment with antiplatelets was the only protective factor (HR 0.47, 95% CI: 0.23-0.96). In the adjusted treatment efficacy analysis, we found benefit in the combined use of tocilizumab (TCZ) and corticosteroids (CS) (HR 0.09, 95% CI: 0.01-0.74) compared to standard treatment, with no benefit of CS alone (HR 0.95, 95% CI: 0.53-1.71). Hospitalized elderly patients suffer from a severe and often fatal form of COVID-19 disease. In this regard, several parameters might identify high-risk patients upon admission. Combined use of TCZ and CS could improve survival.

A Practical Approach to Imaging of the Supplementary Motor Area and Its Subcortical Connections.

PURPOSE OF REVIEW: First, an anatomical and functional review of these cortical areas and subcortical connections with T-fMRI and tractography techniques; second, to demonstrate the value of this approach in neurosurgical planning in a series of patients with tumors close to the SMA. RECENT FINDINGS: Implications in language and cognitive networks with a clear hemispheric lateralization of these SMA/pre-SMA. The recommendation of the use of the advanced neuroimaging studies for surgical planning and preservation of these areas. The SMA/pre-SMA and their subcortical connections are functional areas to be taken into consideration in neurosurgical planning. These areas would be involved in the control/inhibition of movement, in verbal expression and fluency and in tasks of cognitive control capacity. Its preservation is key to the patient's postsurgical cognitive and functional evolution.

Rethinking the use of direct oral anticoagulants for secondary thromboprophylaxis in patients with thrombotic antiphospholipid syndrome.

Patients with thrombotic antiphospholipid syndrome (APS) are at high risk for recurrent thrombosis, and indefinite anticoagulation is recommended. Patients with APS merit indefinite anticoagulation, and vitamin K antagonists (VKAs) have historically been the standard treatment. Direct oral anticoagulants (DOACs) present an appealing alternative to VKAs. Due to their pharmacokinetic and pharmacodynamic characteristics, DOACs offer advantages over VKAs, namely the lack of need for laboratory monitoring, the usage of a fixed dosage, and the absence of significant interaction with dietary components and drugs. The efficacy and safety of DOACs in patients with APS have been studied in four phase II/III clinical trials (three with rivaroxaban and one with apixaban). These studies showed DOACs' inferiority compared to VKAs in preventing recurrent thrombosis. Recurrence was significantly greater in patients with arterial thrombotic events and a triple positivity for antiphospholipid antibodies. No differences were observed in the incidence of venous thromboembolism between both groups. Major bleeding was similar in patients treated with DOACs or VKAs. Several observational studies have reported similar results. This review aims to analyse the existing evidence on the efficacy and safety of DOACs for secondary prevention in patients with APS.

External validation of the RIETE and SOME scores for occult cancer in patients with venous thromboembolism: a multicentre cohort study.

INTRODUCTION: Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. The RIETE and SOME scores aim to identify patients with acute VTE at high risk of occult cancer. In the present study, we evaluated the performance of both scores. METHODS: The scores were evaluated in a retrospective cohort from two centers. The area under the receiver-operating characteristics curve (AUC) evaluated the discriminatory performance. RESULTS: The RIETE score was applied to 815 patients with provoked and unprovoked VTE, of whom 56 (6.9%) were diagnosed with cancer. Of the 203 patients classified as high-risk, 18 were diagnosed with cancer, representing 32.1% (18/56) of the total cancer diagnoses. In the group of 612 low-risk patients, 67.9% of the cancer cases were diagnosed (38/56). Sensitivity, specificity, negative and positive predictive values, and AUC were 32%, 76%, 94%, 9%, and 0.430 (95% confidence interval [CI], 0.38‒0.47), respectively. The SOME score could be calculated in 418 patients with unprovoked VTE, of whom 33 (7.9%) were diagnosed with cancer. Of the 45 patients classified as high-risk, three were diagnosed with cancer, representing 9.1% (3/33) of the total cancer diagnoses. In the group of 373 low-risk patients, 90.9% of the cancer cases were diagnosed (30/33). Sensitivity, specificity, negative and positive predictive values, and AUC were 33%, 88%, 94%, 20%, and 0.351 (95% CI, 0.27‒0.43), respectively. CONCLUSIONS: The performance of both scores was poor. Our results highlight the need to develop new models to identify high-risk patients who may benefit from an extensive cancer screening strategy.

Prediction of Venous Thromboembolism in Patients With Cancer Using Machine Learning Approaches: A Systematic Review and Meta-Analysis.

PURPOSE: Recent studies have suggested that machine learning (ML) could be used to predict venous thromboembolism (VTE) in cancer patients with high accuracy. METHODS: We aimed to evaluate the performance of ML in predicting VTE events in patients with cancer. PubMed, Web of Science, and EMBASE to identify studies were searched. RESULTS: Seven studies involving 12,249 patients with cancer were included. The combined results of the different ML models demonstrated good accuracy in the prediction of VTE. In the training set, the global pooled sensitivity was 0.87, the global pooled specificity was 0.87, and the AUC was 0.91, and in the test set 0.65, 0.84, and 0.80, respectively. CONCLUSION: The prediction ML models showed good performance to predict VTE. External validation to determine the result's reproducibility is necessary.

Implementation of waste-to-energy options in landfill-dominated countries: Economic evaluation and GHG impact.

The economic and environmental impact of several waste-to-energy (WtE) schemes to produce electricity from municipal solid waste (MSW) refuse is evaluated and compared with landfill disposal. Both incineration and gasification alternatives are considered. The gasification option includes three different configurations: (1) a fluidized bed gasifier (FBG) with internal combustion engine (ICE), (2) a FBG with organic Rankine cycle (ORC) and (3) a grate gasifier with steam Rankine cycle (SRC). The study is primarily applied to regions where the management system is based on Mechanical Biological Treatment (MBT) plants, generating a large share of refuse (>70%), which is currently landfilled. The specific case of Andalusia, a region in the south of Spain with 23 MBT plants distributed over a region of 87.000 km2, where about 80% of municipal solid waste (MSW) is currently landfilled, is taken as main reference; thereafter, the study is further extended to preliminary assess other regions of some European landfill-dominated countries with similar characteristics. The results show that both incineration and gasification improve landfill disposal, contributing favorably to greenhouse gas (GHG) reduction and fulfilling EU environmental regulations, although the three gasification options analyzed yield lower GHG emissions than incineration. In addition, gasification enables better integration of WtE into existing MBT plants, especially in the particular case of Andalusia, where MBT plants are widespread on the region, making it a more promising option than incineration, which is mainly based on large centralized plants, and less socially accepted. From the options analyzed, the WtE scheme based on FBG with ICE gives the highest profitability for a given gate fee, due to much higher electrical efficiency. However, FBG with ORC seems to be a better option in the short-term for landfill-dominated countries, due to its higher technical reliability and the low gate fee currently available in these countries.

Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the time of diagnosis. They have very poor prognosis.

[Relation between intermediate troponin T values and diagnosis of cardiac disease]. / Relación de los valores intermedios de troponina T con el diagnóstico de enfermedad cardíaca.

BACKGROUND AND OBJECTIVE: Troponins are useful tools in management of patients with acute coronary syndrome (ACS). Small increases do not guarantee a desirable precision (CV < 10%) and there is a "grey zone" between 99 percentile and clinical cut off. Our objective was to evaluate if "grey zone" troponin values reflect heart damage or they are only "analyzer noise". PATIENTS AND METHOD: Final diagnoses of patients with "grey zone" values attended during 2001 and 2002 were reviewed (group Tn). Control group (Cn): patients with negative values (four months randomly chosen during the same period). Admitted patients were classified in: A, ACS; B, non ischemic heart disease, and C, non heart disease. RESULTS: Tn group (n = 521): admitted, 330 (63.3%); A (53.9%), B (30.9%), C (15.2%). Cn group (n = 652): admitted, 156 (23.9%); A (41%), B (24.4%), C (34.6%). Odds ratio for admittance (Tn vs Cn) was 4.82 (95% CI, 3.68-6.31); OR for diagnosis A, B and C (Tn vs Cn) were: A (1.56) (95% CI, 1.04-2.34), B (1.43) (95% CI, 0.90-2.25), C (0.38) (95% CI, 0.24-0.6). CONCLUSIONS: Intermediate troponin values are associated with diagnosis of heart disease, especially ACS.

Glossopharyngeal neuralgia in the context of a Chiari type I malformation.

A 34-year-old woman presented with disabling right-sided glossopharyngeal neuralgia. MRI revealed a Chiari I malformation with an asymmetric herniation of the right tonsil. Surgical inspection of the lower cranial nerves through a suboccipital approach showed no vascular compromise. The patient was pain free for three months before the same symptoms recurred. MRI showed a persisting crowding at the level of the foramen magnum. A second intervention with extension of the suboccipital craniectomy and resection of the right tonsil achieved definitive pain relief. To our knowledge this is the fourth report of a glossopharyngeal neuralgia caused by a Chiari I malformation. Recurrence of the pain after incomplete decompression of the posterior fossa underlines the importance of tonsillectomy in these patients.

Effects of enriched physical and social environments on motor performance, associative learning, and hippocampal neurogenesis in mice.

We have studied the motor abilities and associative learning capabilities of adult mice placed in different enriched environments. Three-month-old animals were maintained for a month alone (AL), alone in a physically enriched environment (PHY), and, finally, in groups in the absence (SO) or presence (SOPHY) of an enriched environment. The animals' capabilities were subsequently checked in the rotarod test, and for classical and instrumental learning. The PHY and SOPHY groups presented better performances in the rotarod test and in the acquisition of the instrumental learning task. In contrast, no significant differences between groups were observed for classical eyeblink conditioning. The four groups presented similar increases in the strength of field EPSPs (fEPSPs) evoked at the hippocampal CA3-CA1 synapse across classical conditioning sessions, with no significant differences between groups. These trained animals were pulse-injected with bromodeoxyuridine (BrdU) to determine hippocampal neurogenesis. No significant differences were found in the number of NeuN/BrdU double-labeled neurons. We repeated the same BrdU study in one-month-old mice raised for an additional month in the above-mentioned four different environments. These animals were not submitted to rotarod or conditioned tests. Non-trained PHY and SOPHY groups presented more neurogenesis than the other two groups. Thus, neurogenesis seems to be related to physical enrichment at early ages, but not to learning acquisition in adult mice.