Neoadjuvant Immunotherapy: A Promising New Standard of Care.

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various malignancies, with preclinical studies showing improved immune responses in the preoperative setting. FDA-approved neoadjuvant-immunotherapy-based approaches include triple-negative breast cancer and early non-small cell lung cancer on the basis of improvement in pathological response and event free survival. Nevertheless, current trials have only shown benefits in a fraction of patients. It is therefore crucial to identify predictive biomarkers to improve patient selection for such approaches. This review aims to provide an overview of potential biomarkers of neoadjuvant immunotherapy in early triple-negative breast cancer, bladder cancer, melanoma, non-small cell lung cancer, colorectal cancer and gastric cancer. By the extrapolation of the metastatic setting, we explore known predictive biomarkers, i.e., PD-L1, mismatch repair deficiency and tumour mutational burden, as well as potential early-disease-specific biomarkers. We also discuss the challenges of identifying reliable biomarkers and the need for standardized protocols and guidelines for their validation and clinical implementation.

Hospital Arrival and Functional Outcome after Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with an ominous outcome influenced by the time to hospital presentation. OBJECTIVE: This study aims to identify the factors that influence an early hospital arrival after ICH and the relationship with outcome. METHODS: In this multicenter registry, patients with confirmed ICH on CT scan and well-known time of symptoms onset were studied. Clinical data, arrival conditions, and prognostic scores were analyzed. Multivariate models were built to find independent predictors of < 6 h arrival (logistic regression) and in-hospital death (Cox proportional-hazards model). RESULTS: Among the 473 patients analyzed (51% women, median age 63 years), the median delay since onset to admission was 6.25 h (interquartile range: 2.5-24 h); 7.8% arrived in < 1 h, 26.3% in < 3 h, 45.3% in < 6 h, and 62.3% in < 12 h. The in-hospital, 30-day and 90-day case fatality rates were 28.8%, 30.0%, and 32.6%, respectively. Predictors of arrival in < 6 h were hypertension treatment (odds ratios [OR]: 1.675, 95% confidence intervals [CI]: 1.030-2.724), ≥ 3 years of schooling (OR: 1.804, 95% CI: 1.055-3.084), and seizures at ICH onset (OR: 2.416, 95% CI: 1.068-5.465). Predictors of death (56.9% neurological) were systolic blood pressure > 180 mmHg (hazards ratios [HR]: 1.839, 95% CI: 1.031-3.281), ICH score ≥ 3 (HR: 2.302, 95% CI: 1.300-4.074), and admission Glasgow Coma Scale < 8 (HR: 4.497, 95% CI: 2.466-8.199). Early arrival was not associated with outcome at discharge, 30 or 90 days. CONCLUSIONS: In this study, less than half of patients with ICH arrived to the hospital in < 6 h. However, early arrival was not associated with the short-term outcome in this data set.

Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution.

Human cancers, including breast cancers, comprise clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However, the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours have not been systematically examined at single-cell resolution. Here we show, using deep-genome and single-cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (<5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single-cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies using patient-derived breast cancer xenoengraftment.

SOX4 can redirect TGF-ß-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis.

Expression of the transcription factor SOX4 is often elevated in human cancers, where it generally correlates with tumor-progression and poor-disease outcome. Reduction of SOX4 expression results in both diminished tumor-incidence and metastasis. In breast cancer, TGF-ß-mediated induction of SOX4 has been shown to contribute to epithelial-to-mesenchymal transition (EMT), which controls pro-metastatic events. Here, we identify SMAD3 as a novel, functionally relevant SOX4 interaction partner. Genome-wide analysis showed that SOX4 and SMAD3 co-occupy a large number of genomic loci in a cell-type specific manner. Moreover, SOX4 expression was required for TGF-ß-mediated induction of a subset of SMAD3/SOX4-co-bound genes regulating migration and extracellular matrix-associated processes, and correlating with poor-prognosis. These findings identify SOX4 as an important SMAD3 co-factor controlling transcription of pro-metastatic genes and context-dependent shaping of the cellular response to TGF-ß. Targeted disruption of the interaction between these factors may have the potential to disrupt pro-oncogenic TGF-ß signaling, thereby impairing tumorigenesis.

Reliability of Bystander Recognition of Clinical Features in Pre-Hospital Classification of Acute Cerebrovascular Syndromes: Preliminary Findings.

BACKGROUND: The recognition of stroke symptoms by patients or bystanders directly affects the outcomes of patients with acute cerebrovascular disease. OBJECTIVE: The objective of the study was to assess the predictive value of the medical his- tory and clinical features recognized by the patients' bystanders to classify neurovascular syndromes in pre-hospital settings. METHODS: We included 150 stroke patients of two Mexican referral centers: 50 with acute ischemic stroke (AIS), 50 with intracerebral hemorrhage (ICH), and 50 with subarachnoid hemorrhage (SAH). The performance of clinical prediction rules (CPR) to identify the stroke types was evaluated with features recognized by the patients' bystanders before hospital arrival. The impact of CPRs on early arrival and in-hospital mortality was also analyzed. RESULTS: Overall, 72% of the patients had previous medical evaluations in other centers before final referral to our hospitals, and therefore, only 45% had a final onset- to-door time <6 h, even when the first medical assessment had occurred in ≤1 h in 75% of cases. Clinical features noticed by the patients' bystanders had low positive predictive values (PPV) for any stroke type. The CPR "language or speech disor- der + focal motor deficit" had 93% sensitivity and a negative predictive value (NPV) of 84% to distinguish AIS. In SAH, head- ache alone showed a sensitivity of 84% and NPV of 97%. No CPR had an adequate performance on ICH. CPRs were not as- sociated with final onset-to-door time. Altered consciousness, age ≥65 years, indirect arrival with stops before final referral, and atrial fibrillation increased in-hospital mortality. CONCLUSION: Clinical features referred by the witness of a neurovascular emergency have limited PPV, but adequate NPV in ruling-out AIS and SAH among stroke types. The use of CPRs had no impact on onset-to-door time or in-hospital mortality when the final arrival to a third-level center occurs with previous medical refer- rals.

Hypertensive thalamic hemorrhage: analysis of short-term outcome.

BACKGROUND: Hypertension is the main cause of intracerebral hemorrhage with a thalamic location frequency that varies from 6% to 26.5%. OBJECTIVE: We aimed to identify clinical and radiological features that could impact the short-term prognosis in patients with hypertensive thalamic hemorrhage (HTH). METHODS: Consecutive patients presenting to a tertiary referral hospital with HTH were analyzed from 2010 to 2014. Clinical features at emergency department and a 30-day outcome using the modified Rankin Scale (mRS) were obtained. RESULTS: A total of 104 patients were studied (53 women, mean age 68.2 years, range 27-91 years), 91 (87.5%) of them with hypertension history. Mean hemorrhage volume was 12.2 mL (range 2-45 mL), without significant differences according to gender or age group. Irruption into the ventricular system occurred in 79 (76%) cases. Thirty-day mortality was 38.5% and occurred with a higher frequency in men, in patients with GCS <8, intraventricular irruption, ventriculostomy, and intracerebral hemorrhage volumes >15 mL. CONCLUSIONS: Although HTH is associated with relatively small hemorrhage volume, it had a higher frequency of ventricular irruption and bad prognosis at short-term.

Arl13b regulates endocytic recycling traffic.

Intracellular recycling pathways play critical roles in internalizing membrane and fluid phase cargo and in balancing the inflow and outflow of membrane and cell surface molecules. To identify proteins involved in the regulation of endocytic recycling, we used an shRNA trafficking library and screened for changes in the surface expression of CD1a antigen-presenting molecules that follow an endocytic recycling route. We found that silencing of the ADP-ribosylation factor (Arf)-like small GTPase Arl13b led to a decrease in CD1a surface expression, diminished CD1a function, and delayed CD1a recycling, suggesting that Arl13b is involved in the regulation of endocytic recycling traffic. Arl13b appears to be required for the major route of endocytic trafficking, causing clustering of early endosomes and leading to the accumulation of endocytic cargo. Moreover, Arl13b colocalized with markers of the endocytic recycling pathway followed by CD1a, namely Arf6 and Rab22a. We also detected an interaction between Arl13b and the actin cytoskeleton. Arl13b was previously implicated in cilia formation and function. Our present results indicate a previously unidentified role for Arl13b in endocytic recycling traffic and suggest a link between Arl13b function and the actin cytoskeleton.

[Myasthenia gravis in adults of institutions pertaining to the Mexican public health system: an analysis of hospital discharges during 2010]. / Miastenia gravis (MG) en adultos de instituciones pertenecientes al sistema público sanitario mexicano: un análisis de egresos hospitalarios durante el año 2010.

INTRODUCTION: Epidemiological studies on myasthenia gravis (MG) in Mexico is mainly derived from experiences in referral centers. OBJECTIVE: To describe the epidemiological characteristics of hospital discharges during 2010 with the diagnosis of MG in adults hospitalized in the Mexican public health system. METHODS: We consulted the database of hospital discharges during 2010 of the National Health Information System (Ministry of Health, IMSS, IMSS oportunidades, ISSSTE, PEMEX, and the Ministry of Defense). The MG records were identified by the code G70.0 of the International Classification of Diseases 10th revision. RESULTS: During 2010 there were 5,314,132 hospital discharges (4,254,312 adults). Among them, 587 (0.01%) were adults with MG (median age: 47 years, 60% women). Women with MG were significantly younger than men (median age: 37 vs. 54 years, respectively; p < 0.001). The median hospital stay was six days. The case fatality rate was 3.4%, without gender differences. Age was associated with the probability of death. CONCLUSIONS: We confirmed the bimodal age-gender distribution in MG. The in-hospital case fatality rate in Mexico is consistent with recent reports around the world.

Roles of H-Bonding and Hydride Solvation in the Reaction of Hydrated (Di)electrons with Water to Create H2 and OH.

Even though single hydrated electrons (ehyd-'s) are stable in liquid water, two hydrated electrons can bimolecularly react with water to create H2 and hydroxide: ehyd- + ehyd- + 2H2O → H2 + 2OH-. The rate of this reaction has an unusual temperature and isotope dependence as well as no dependence on ionic strength, which suggests that cosolvation of two electrons as a single hydrated dielectron (e2,hyd2-) might be an important intermediate in the mechanism of this reaction. Here, we present an ab initio density functional theory study of this reaction to better understand the potential properties, reactivity, and experimental accessibility of hydrated dielectrons. Our simulations create hydrated dielectrons by first simulating single ehyd-'s and then injecting a second electron, providing a well-defined time zero for e2,hyd2- formation and offering insight into a potential experimental route to creating dielectrons and optically inducing the reaction. We find that e2,hyd2- immediately forms in every member of our ensemble of trajectories, allowing us to study the molecular mechanism of H2 and OH- formation. The subsequent reaction involves separate proton transfer steps with a generally well-defined hydride subintermediate. The time scales for both proton transfer steps are quite broad, with the first proton transfer step spanning times over a few ps, while the second proton transfer step varies over ∼150 fs. We find that the first proton transfer rate is dictated by whether or not the reacting water is part of an H-bond chain that allows the newly created OH- to rapidly move by Grotthuss-type proton hopping to minimize electrostatic repulsion with H-. The second proton transfer step depends significantly on the degree of solvation of H-, leading to a wide range of reactive geometries where the two waters involved can lie either across the dielectron cavity or more adjacent to each other. This also allows the two proton transfer events to take place either effectively concertedly or sequentially, explaining differing views that have been presented in the literature.

How to Probe Hydrated Dielectrons Experimentally: Ab Initio Simulations of the Absorption Spectra of Aqueous Dielectrons, Electron Pairs, and Hydride.

In the radiation chemistry of water, two hydrated electrons (ehyd-) can react to form H2 and OH-. Experiments and simulations suggest that this reaction occurs through a mechanism involving colocalization of two ehyd-'s into the same solvent cavity, forming a hydrated dielectron ((ehyd)22-) intermediate, with aqueous hydride (H-) as a subintermediate. However, there has been no direct experimental observation of either (ehyd)22- or H-. Here, we present TD-DFT-based predictions for the absorption spectrum of open-shell-singlet and triplet ehyd- pairs, (ehyd)22-, and H-. We find that relative to ehyd-, triplet and open-shell singlet electron pairs show spectral shifts to the blue and red, respectively. Additionally, we find that (ehyd)22- absorbs even further to the red, and that H- has a charge-transfer-to-solvent-like transition at wavelengths several eV to the blue, providing a direct experimental handle with which to probe these species. We propose a three-pulse transient absorption experiment that should allow detection of (ehyd)22- and H-.

Serum uric acid and outcome after acute ischemic stroke: PREMIER study.

BACKGROUND: Current evidence shows that uric acid is a potent antioxidant whose serum concentration increases rapidly after acute ischemic stroke (AIS). Nevertheless, the relationship between serum uric acid (SUA) levels and AIS outcome remains debatable. We aimed to describe the prognostic significance of SUA in AIS. METHODS: We studied 463 patients (52% men, mean age 68 years, 13% with glomerular filtration rate <60 ml/min at hospital arrival) with AIS pertaining to the multicenter registry PREMIER, who had SUA measurements at hospital presentation. Multivariate models were constructed to analyze the association of SUA with functional outcome as assessed by the modified Rankin scale (mRS) at 30-day, 3-, 6- and 12-month follow-up. A mRS 0-1 was regarded as a very good outcome. RESULTS: Mean SUA concentration at hospital arrival was 6.1 ± 3.7 mg/dl (362.8 ± 220.0 µmol/l). Compared with cases with higher SUA levels at hospital admission, patients with ≤4.5 mg/dl (≤267.7 µmol/l; the lowest tertile of the sample) had more cases of a very good 30-day outcome (30.5 vs. 18.9%, respectively; p = 0.004). SUA was not associated with mortality or functional dependence (mRS >2) at 30 days, or with any outcome measure at 3, 6 or 12 months poststroke. After adjustment for age, gender, stroke type and severity (NIHSS <9), time since event onset, serum creatinine, hypertension, diabetes and smoking, a SUA ≤4.5 mg/dl (≤267.7 µmol/l) was positively associated with a very good short-term outcome (odds ratio: 1.76, 95% confidence interval: 1.05-2.95; negative predictive value: 81.1%), but not at 3, 6 or 12 months of follow-up. When NIHSS was entered in the multivariate model as a continuous variable, the independent association of SUA with outcome was lost. Compared with cases with higher levels, patients with SUA ≤4.5 mg/dl (≤267.7 µmol/l) were more frequently younger than 55 years, women, with mild strokes, with normal serum creatinine and fewer had hypertension. The time since event onset to hospital arrival was not significantly associated with AIS severity or SUA levels; nevertheless, a nonsignificant tendency was observed for patients with severe strokes and high SUA levels arriving in <24 h. CONCLUSIONS: A low SUA concentration is modestly associated with a very good short-term outcome. Our findings support the hypothesis that SUA is more a marker of the magnitude of the cerebral infarction than an independent predictor of stroke outcome.

Central adiposity and mortality after first-ever acute ischemic stroke.

BACKGROUND: The waist-to-height ratio (WHtR) may be a better adiposity measure than the body mass index (BMI). We evaluated the prognostic performance of WHtR in patients with acute ischemic stroke (AIS). METHODS: First, we compared WHtR and BMI as adiposity measures in 712 healthy adults by tetrapolar bioimpedance analysis. Thereafter, baseline WHtR was analyzed as predictor of 12-month all-cause mortality in 821 Mexican mestizo adults with first-ever AIS by a Cox proportional hazards model adjusted for baseline predictors. RESULTS: In healthy individuals, WHtR correlated higher than BMI with total fat mass and showed a higher accuracy in identifying a high percentage of body fat (p < 0.01). In AIS patients a U-shaped relationship was observed between baseline WHtR and mortality (fatality rate 29.1%). On multivariate analysis, baseline WHtR ≤ 0.300 or >0.800 independently predicted 12-month all-cause mortality (hazard ratio 1.91, 95% confidence interval 1.04-3.51). BMI was not associated with mortality, tested either as continuous, binomial or stratified variable. CONCLUSION: WHtR is a modifiable risk factor that accurately demonstrates body fat excess. Extreme WHtR values were associated with increased 12-month all-cause mortality in Mexican mestizo patients with AIS. No survival advantage was found with high WHtR as the pragmatic indicator of obesity in this population.

Hematologic toxicities of chemotherapy in breast and ovarian cancer patients carrying BRCA1/BRCA2 germline pathogenic variants. A single center experience and review of the literature.

BRCA1 and BRCA2 play a central role in DNA repair and their germline pathogenic variants (gBRCA) confer a high risk for developing breast and ovarian cancer. Standard chemotherapy regimens for these cancers include DNA-damaging agents. We hypothesized that gBRCA carriers might be at higher risk of developing chemotherapy-related hematologic toxicity and therapy-related myeloid neoplasms (t-MN). We conducted a retrospective study of women newly diagnosed with invasive breast or ovarian cancer who were screened for gBRCA1/gBRCA2 at Geneva University Hospitals. All patients were treated with (neo-)adjuvant chemotherapy. We evaluated acute hematologic toxicities by analyzing the occurrence of febrile neutropenia and severe neutropenia (grade 4) at day 7-14 of the first cycle of chemotherapy and G-CSF use during the entire chemotherapy regimen. Characteristics of t-MN were collected. We reviewed medical records from 447 patients: 58 gBRCA1 and 40 gBRCA2 carriers and 349 non-carriers. gBRCA1 carriers were at higher risk of developing severe neutropenia (32% vs. 14.5%, p = 0.007; OR = 3.3, 95% CI [1.6-7], p = 0.001) and of requiring G-CSF for secondary prophylaxis (58.3% vs. 38.2%, p = 0.011; OR = 2.5, 95% CI [1.4-4.8], p = 0.004). gBRCA2 carriers did not show increased acute hematologic toxicities. t-MN were observed in 2 patients (1 gBRCA1 and one non-carrier). Our results suggested an increased acute hematologic toxicity upon exposure to chemotherapy for breast and ovarian cancer among gBRCA1 but not gBRCA2 carriers. A deeper characterization of t-MN is warranted with the recent development of PARP inhibitors in frontline therapy in gBRCA breast and ovarian cancer.

Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study.

BACKGROUND: Carriers of germline pathogenic variants of the BRCA1 gene (gBRCA1) tend to have a higher incidence of haematological toxicity upon exposure to chemotherapy. We hypothesised that the occurrence of agranulocytosis during the first cycle of (neo-)adjuvant chemotherapy (C1) in breast cancer (BC) patients could predict gBRCA1 pathogenic variants. PATIENTS AND METHODS: The study population included non-metastatic BC patients selected for genetic counselling at Hôpitaux Universitaires de Genève (Jan. 1998 to Dec. 2017) with available mid-cycle blood counts performed during C1. The BOADICEA and Manchester scoring system risk-prediction models were applied. The primary outcome was the predicted likelihood of harbouring gBRCA1 pathogenic variants among patients presenting agranulocytosis during C1. RESULTS: Three hundred seven BC patients were included: 32 (10.4%) gBRCA1, 27 (8.8%) gBRCA2, and 248 (81.1%) non-heterozygotes. Mean age at diagnosis was 40 years. Compared with non-heterozygotes, gBRCA1 heterozygotes more frequently had grade 3 BC (78.1%; p = 0.014), triple-negative subtype (68.8%; p <0.001), bilateral BC (25%; p = 0.004), and agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy (45.8%; p = 0.002). Agranulocytosis and febrile neutropenia that developed following the first cycle of chemotherapy were independently predictive for gBRCA1 pathogenic variants (odds ratio: 6.1; p = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value for agranulocytosis predicting gBRCA1 were 45.8% (25.6-67.2%), 82.8% (77.5-87.3%), 22.9% (6.1-37.3%), and 93.4% (88.9-96.4%), respectively. Agranulocytosis substantially improved the positive predictive value of the risk-prediction models used for gBRCA1 evaluation. CONCLUSION: Agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy is an independent predictive factor for gBRCA1 detection in non-metastatic BC patients.

Cerebral venous thrombosis in a Mexican multicenter registry of acute cerebrovascular disease: the RENAMEVASC study.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that is usually not mentioned in multicenter registries on all-type acute stroke. We aimed to describe the experience on hospitalized patients with CVT in a Mexican multicenter registry on acute cerebrovascular disease. METHODS: CVT patients were selected from the RENAMEVASC registry, which was conducted between 2002 and 2004 in 25 Mexican hospitals. Risk factors, neuroimaging, and 30-day outcome as assessed by the modified Rankin scale (mRS) were analyzed. RESULTS: Among 2000 all-type acute stroke patients, 59 (3%; 95% CI, 2.3-3.8%) had CVT (50 women; female:male ratio, 5:1; median age, 31 years). Puerperium (42%), contraceptive use (18%), and pregnancy (12%) were the main risk factors in women. In 67% of men, CVT was registered as idiopathic, but thrombophilia assessment was suboptimal. Longitudinal superior sinus was the most frequent thrombosis location (78%). Extensive (>5 cm) venous infarction occurred in 36% of patients. Only 81% of patients received anticoagulation since the acute phase, and 3% needed decompressive craniectomy. Mechanical ventilation (13.6%), pneumonia (10.2%) and systemic thromboembolism (8.5%) were the main in-hospital complications. The 30-day case fatality rate was 3% (2 patients; 95% CI, 0.23-12.2%). In a Cox proportional hazards model, only age <40 years was associated with a mRS score of 0 to 2 (functional independence; rate ratio, 3.46; 95% CI, 1.34-8.92). CONCLUSIONS: The relative frequency of CVT and the associated in-hospital complications were higher than in other registries. Thrombophilia assessment and acute treatment was suboptimal. Young age is the main determinant of a good short-term outcome.

Primary spontaneous intracerebral hemorrhage in COVID-19 patients: differences among presentation patterns - A systematic review.

OBJECTIVE: The objective of this study was to determine if there are differences between the presentation patterns of hemorrhagic stroke (HS) associated to COVID-19. METHODS: It was performed a systematic search based on PRISMA guidelines of the cases reported in PUBMED of HS associated to SARS-CoV-2 infection and we added to this sample cases from our own hospital cohort. Patients in the database were separated by groups according to presentation symptoms: if they debuted with neurological symptoms or debuted with pulmonary symptoms. RESULTS: Seventy cases were included in the study. Patients that debuted with pulmonary symptoms accounted for 68.6% of the cases with an interval between the development of symptoms and the presentation of HS of 15.6 days. We found that the use of anticoagulants during hospitalization, multifocal image pattern, and the elevation of D-dimer, Ferritin, and lactate dehydrogenase levels were significantly associated with the group of pulmonary presentation, whereas the presence of hypertension during hospitalization, and a lower hemoglobin level was associated with the group of neurologic symptoms. CONCLUSION: Although HS associated with COVID-19 is a clinical entity with increasing evidence, it is necessary to establish that there are two forms of presentation with their own characteristics.

OBJETIVO: determinar si existen diferencias entre los patrones de presentación de hemorragia intracraneal asociada a COVID-19. PACIENTES Y MÉTODOS: Se realizó una búsqueda sistemática basada en la guía PRISMA de los casos reportados en PUBMED de hemorragia intracraneal asociados a infección por SARS-CoV-2 y se agregaron a esta muestra casos de nuestra propia cohorte hospitalaria. RESULTADOS: se incluyeron 70 casos. Los pacientes que debutaron con síntomas pulmonares representaron el 68.6% de los casos con un intervalo entre el desarrollo de los síntomas y la presentación de la hemorragia intracraneal de 15.6 días. Encontramos que el uso de anticoagulantes durante la hospitalización, el patrón de imagen multifocal y la elevación de los niveles de dímero D, ferritina y deshidrogenasa láctica se asociaron significativamente con el grupo de presentación pulmonar, mientras que la presencia de hipertensión durante la hospitalización, y un nivel de hemoglobina más bajo se asoció con el grupo que debutó con síntomas neurológicos. CONCLUSIÓN: si bien la hemorragia intracraneal asociada a COVID-19 es una entidad clínica con evidencia creciente, es necesario establecer que existen dos formas de presentación con características propias.

Isolated vein thrombosis of the posterior fossa presenting as localized cerebellar venous infarctions or hemorrhages.

BACKGROUND AND PURPOSE: Cerebellar venous infarction or hemorrhage due to isolated venous thrombosis of the posterior fossa is a rare form of intracranial vein thrombosis that can be unsuspected in clinical practice. METHODS: We studied 230 patients with intracranial vein thrombosis, identifying 9 (3.9%: 7 women, mean age 34 years) with neuroimaging or histopathologic evidence of localized posterior fossa vein thrombosis causing parenchymal injury limited exclusively to the cerebellum. RESULTS: All patients had an insidious presentation suggesting other diagnoses. Intracranial hypertension (n=6) and cerebellar (n=4) syndromes were the main clinical presentations. Intracranial vein thrombosis was idiopathic in 3 patients; associated with puerperium in 3; and with contraceptives, protein C deficiency, and dehydration in 1 case each. CT was abnormal but not diagnostic in 5 patients, showing a cerebellar hypodensity with fourth ventricle compression and variable hydrocephalus in 5 patients, and cerebellar hemorrhage in 2. Conventional MRI provided diagnosis in 6 cases, showing the causal thrombosis and cerebellar involvement; angiography was practiced in 2 of them, confirming the findings identified by MRI. In the other 3 patients, diagnosis was reached by histopathology. Thromboses were localized at the straight sinus (n=4), lateral sinuses (n=3), and superior petrosal vein (n=2). The acute case fatality rate was 22.2% (n=2), 1 (11.1%) patient was discharged in a vegetative state, 1 (11.1%) was severely disabled, and 5 (55.6%) were moderately disabled. CONCLUSIONS: Isolated venous thrombosis of the posterior fossa is infrequent and implies a challenging diagnosis. Risk factors for intracranial vein thrombosis and atypical cerebellar findings on CT should lead to further MRI assessment.

Acute Disseminated Encephalomyelitis with Baló-like Lesion by Scorpion Sting: Case Report.

Acute disseminated encephalomyelitis (ADEM) has been linked to immunizations, viral infections, and occasionally to arthropods stings. Its association with scorpion stings has not been described. A 29-year-old man, who after being stung by a scorpion presented right hemiparesis and language impairment. Brain MRI showed subcortical bihemispheric lesion characteristics of ADEM and a bigger one compatible with Baló concentric sclerosis (BCS). Patient was managed with steroids, showing complete clinical improvement. Magnetic resonance imaging (MRI) after 6 months showed cavitation of the bigger lesion with no new findings. In 2 years of follow-up, there is no clinical relapse or new lesions in MRI. Although cases of ADEM have been reported due to venom of chilopoda and hymenoptera, the scorpion sting can be considered as another new cause; this case being even more relevant due to present a Baló-like lesion in MRI.

Aneurysmal subarachnoid hemorrhage in a Mexican multicenter registry of cerebrovascular disease: the RENAMEVASC study.

BACKGROUND: Information on risk factors and outcome of persons with aneurysmal subarachnoid hemorrhage (SAH) in Mexico is unknown. We sought to describe the clinical characteristics, risk factors, and outcome at discharge of Mexican patients with aneurysmal SAH. METHODS: A first-step surveillance system was conducted on consecutive cases confirmed by 4-vessel angiography from November 2002 to October 2004 in 25 tertiary referral centers. Age- and sex-matched control subjects were randomly selected by a 1:1 factor, for multivariate analysis on risk factors. RESULTS: We studied 231 patients (66% women; mean age 52 years, range 16-90 years). In 92%, the aneurysms were in the anterior circulation, and 15% had more than two aneurysms. After multivariate analysis, hypertension (odds ratio 2.46, 95% confidence interval 1.59-3.81) and diabetes mellitus (odds ratio 0.34, 95% confidence interval 0.17-0.68) were directly and inversely associated with aneurysmal SAH, respectively. Median hospital stay was 23 days (range 2-98 days). Invasive treatment was performed in 159 (69%) patients: aneurysm clipping in 126 (79%), endovascular coiling in 29 (18%), and aneurysm wrapping in 4 (2%). The in-hospital mortality was 20% (mostly due to neurologic causes), and 25% of patients were discharged with a modified Rankin score of 4 or 5. CONCLUSIONS: Hypertension is the main risk factor for aneurysmal SAH in hospitalized patients from Mexico. The female:male ratio is 2:1. A relatively low in-hospital mortality and a high frequency of invasive interventions are observed. However, a high proportion of patients are discharged with important neurologic impairment.