From Liver to Brain: How MAFLD/MASLD Impacts Cognitive Function.

Metabolic dysfunction-associated fatty liver disease or metabolic dysfunction-associated steatotic liver disease (MAFLD/MASLD), is a common chronic liver condition affecting a substantial global population. Beyond its primary impact on liver function, MAFLD/MASLD is associated with a myriad of extrahepatic manifestations, including cognitive impairment. The scope of cognitive impairment within the realm of MAFLD/MASLD is a matter of escalating concern. Positioned as an intermediate stage between the normal aging process and the onset of dementia, cognitive impairment manifests as a substantial challenge associated with this liver condition. Insights from studies underscore the presence of compromised executive function and a global decline in cognitive capabilities among individuals identified as being at risk of progressing to liver fibrosis. Importantly, this cognitive impairment transcends mere association with metabolic factors, delving deep into the intricate pathophysiology characterizing MAFLD/MASLD. The multifaceted nature of cognitive impairment in the context of MAFLD/MASLD is underlined by a spectrum of factors, prominently featuring insulin resistance, lipotoxicity, and systemic inflammation as pivotal contributors. These factors interplay within the intricate landscape of MAFLD/MASLD, fostering a nuanced understanding of the links between hepatic health and cognitive function. By synthesizing the available evidence, exploring potential mechanisms, and assessing clinical implications, the overarching aim of this review is to contribute to a more complete understanding of the impact of MAFLD/MASLD on cognitive function.

Unveiling the Burden of Miscoding and Misclassification in Stroke Mortality: Analysis of Multiple Cause-of-Death Data in Mexico.

BACKGROUND: The prevalence of risk factors for cerebrovascular diseases in Mexico is increasing although stroke mortality declined from 1990 to 2010, without meaningful changes afterward. While improving access to adequate prevention and care could explain this trend, miscoding and misclassification in death certificates need to be assessed to unveil the true burden of stroke in Mexico. Practices in death certification along with the presence of multi-morbidity could contribute to this distortion. Analyses of multiple causes of death could reveal ill-defined stroke deaths, providing a glimpse of this bias. METHODS: Cause-of-death information from 4,262,666 death certificates in Mexico from 2009 to 2015, was examined to determine the extent of miscoding and misclassification on the true burden of stroke. Age-standardized mortality rates per 100,000 inhabitants (ASMR) were calculated for stroke as underlying and multiple causes of death, by sex and state. Deaths were classified following international standards as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and unspecified, which were kept as an independent category to measure miscoding. To approximate misclassification, we compared ASMR under three misclassification scenarios: (1) current (the status quo); (2) moderate, which includes deaths from selected causes mentioning stroke; and (3) high which includes all deaths mentioning stroke. National and subnational data were analyzed to search for geographical patterns. RESULTS: The burden of stroke in Mexico is underreported due to miscoding and misclassification. Miscoding is an important issue since almost 60% of all stroke deaths are registered as unspecified. Multiple cause analysis indicates that stroke ASMR could increase 39.9%-52.9% of the current ASMR under moderate and high misclassification scenarios, respectively. Both problems indicate the need to improve death codification procedures and cause-of-death classification. CONCLUSIONS: Miscoding and misclassification lead to underestimation of the burden of stroke in Mexico. Stroke deaths are underreported when other important causes coexist, being diabetes the most frequent.

Predictors of Mechanical Ventilation in Guillain-Barré Syndrome with Axonal Subtypes.

BACKGROUND: The early clinical predictors of respiratory failure in Latin Americans with Guillain-Barré syndrome (GBS) have scarcely been studied. This is of particular importance since Latin America has a high frequency of axonal GBS variants that may imply a worse prognosis. METHODS: We studied 86 Mexican patients with GBS admitted to the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a referral center of Mexico City, to describe predictors of invasive mechanical ventilation (IMV). RESULTS: The median age was 40 years (interquartile range: 26-53.5), with 60.5% men (male-to-female ratio: 1.53). Most patients (65%) had an infectious antecedent (40.6% gastrointestinal). At admission, 38% of patients had a Medical Research Council (MRC) sum score <30. Axonal subtypes predominated (60.5%), with acute motor axonal neuropathy being the most prevalent (34.9%), followed by acute inflammatory demyelinating polyneuropathy (32.6%), acute motor sensory axonal neuropathy (AMSAN) (25.6%), and Fisher syndrome (7%). Notably, 15.1% had onset in upper limbs, 75.6% dysautonomia, and 73.3% pain. In all, 86% received either IVIg (9.3%) or plasma exchange (74.4%). IMV was required in 39.5% patients (72.7% in AMSAN). A multivariate model without including published prognostic scores yielded the time since onset to admission <15 days, axonal variants, MRC sum score <30, and bulbar weakness as independent predictors of IMV. The model including grading scales yielded lower limbs onset, Erasmus GBS respiratory insufficiency score (EGRIS) >4, and dysautonomia as predictors. CONCLUSION: These results suggest that EGRIS is a good prognosticator of IMV in GBS patients with a predominance of axonal electrophysiological subtypes, but other early clinical data should also be considered.

Osmotic demyelination syndrome in patients with non-Hodgkin lymphoma: a case report and literature review.

INTRODUCTION: Osmotic demyelination syndrome (ODS) is a non-inflammatory process of the central nervous system caused by extracellular osmotic changes, which leads to oligodendrocyte apoptosis and disruption of myelin sheaths, usually affecting patients with underlying systemic conditions that impose susceptibility to osmotic stress. Description of ODS in patients with non-Hodgkin lymphoma (NHL) is limited to a few case reports. METHODS: Here, we report a 44-year-old man with NHL that had an incidental diagnosis of ODS. We conducted a literature review of the published cases of ODS in NHL patients from 1959 to 2020, aiming to describe the characteristics of these patients. RESULTS: A total of seven patients were summarized (four men and three women), including our case and six patients from published reports. Risk factors such as weight loss and alcoholism were reported in five (71.4%) patients. Hyponatremia was found in six (85.7%) of the cases, and none of them had overly rapid sodium correction. Four cases were asymptomatic, and diffuse large B-cell lymphoma was the most common subtype of NHL (85.7%). The outcome was favorable in most cases; only two deaths not directly related to ODS were reported. CONCLUSION: We wish to suggest that systemic and metabolic stress induced by NHL may be associated with the development of central osmotic demyelination, and therefore, NHL may be a novel risk factor for ODS. Clinicians should be aware of ODS in patients with hematological malignancies, even in the absence of traditional risk factors.

Posterior reversible encephalopathy syndrome during convalescence from COVID-19.

Background and aim: With an ever-increasing population of patients recovering form severe coronavirus disease 2019 (COVID-19), recognizing long-standing and delayed neurologic manifestations is crucial. Here, we present a patient developing posterior reversible encephalopathy syndrome (PRES) in the convalescence form severe coronavirus disease 2019 (COVID-19).Case presentation: A 61-year-old woman with severe (COVID-19) confirmed by nasopharyngeal real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) required invasive mechanical ventilation 24-hours after admission. During her intensive care unit stay, she developed transient acute kidney injury and septic shock. She was extubated after 22 days. On day 25, she developed generalized tonic-clonic seizures. Magnetic resonance imaging (MRI) of the brain showed bilateral subcortical lesions on the parietal and occipital lobes and multiple micro-and macro-bleeds, consistent with PRES. At this point, RT-PCR for SARS-CoV-2 in a respiratory specimen and cerebrospinal fluid was negative. She was discharged home 35 days after admission on oral levetiracetam. Control MRI five months after discharge showed bilateral focal gliosis. On follow-up, she remains seizure-free on levetiracetam.Conclusions: PRES has been observed before as a neurological manifestation of acute COVID-19; to our knowledge, this is the first PRES case occurring in a hospitalized patient already recovered from COVID-19. A persistent proinflammatory/prothrombotic state triggered by SARS-CoV-2 infection may lead to long-standing endothelial dysfunction, resulting in delayed PRES in patients recovering from COVID-19. With a rapid and exponential increase in survivors of acute COVID-19, clinicians should be aware of delayed (post-acute) neurological damage, including PRES.

Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction.

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Antiphospholipid syndrome-mediated acute cerebrovascular diseases and long-term outcomes.

OBJECTIVES: The antiphospholipid syndrome (APS) is an autoimmune disease associated with thrombotic and non-thrombotic neurologic manifestations. APS is classified as primary (PAPS) or secondary (SAPS) when it co-exists with another autoimmune disease. We aim to describe the spectrum of acute cerebrovascular disease among patients with APS, their differences between stroke subtypes, and long-term functional outcomes. METHODS: Retrospective cohort study including adult (≥18 years) patients with APS followed in the stroke clinic of a tertiary-care reference center for autoimmune diseases in Mexico from 2009 to 2019. RESULTS: We studied 120 cases; 99 (82.5%) women; median age 43 years (interquartile range 35-52); 63.3% with SAPS. Demographics, comorbidities, and antiphospholipid antibodies (aPL) positivity were similar between APS type and stroke subtypes. Amongst index events, we observed 84 (70%) acute ischemic strokes (AIS), 19 (15.8%) cerebral venous thromboses (CVT), 11 (9.2%) intracerebral hemorrhages (ICH), and six (5%) subarachnoid hemorrhages (SAH). Sixty-seven (55.8%) were known patients with APS; the median time from APS diagnosis to index stroke was 46 months (interquartile range 12-96); 64.7% of intracranial hemorrhages (ICH or SAH) occurred ≥4 years after APS was diagnosed (23.5% anticoagulation-related); 63.2% of CVT cases developed before APS was diagnosed or simultaneously. Recurrences occurred in 26 (22.8%) patients, AIS, in 18 (69.2%); intracranial hemorrhage, in eight (30.8%). Long-term functional outcomes were good (modified Rankin Scale ≤2) in 63.2% of cases, during follow-up, the all-cause mortality rate was 19.2%. CONCLUSION: We found no differences between stroke subtypes and APS types. aPL profiles were not associated with any of the acute cerebrovascular diseases described in this cohort. CVT may be an initial thrombotic manifestation of APS with low mortality and good long-term functional outcome.

Sugar- and artificially-sweetened soda consumption and subclinical atherosclerosis among Mexican women.

BACKGROUND AND AIMS: Sugar-sweetened soda consumption is associated with most cardiometabolic risk factors. The role of artificially-sweetened beverages in cardiovascular disease (CVD) is inconclusive, but their consumption correlates with health impairment. Little is known about the contribution of soda consumption in subclinical stages of atherosclerosis. Therefore, we evaluated the relation between sugar- and artificially-sweetened soda consumption and carotid intima-media thickness (IMT) among Mexican women. METHODS AND RESULTS: We cross-sectionally evaluated 1093 women enrolled in the Mexican Teachers' Cohort who were free of CVD, diabetes or cancer. Sugar- and artificially-sweetened soda consumption was estimated from a validated 140-item food frequency questionnaire in 2008 and all women underwent a carotid ultrasound assessment three years later. Participants were categorized into tertiles of soda consumption in servings/week. Subclinical atherosclerosis was defined as a mean left and/or right IMT ≥0.8 mm or the presence of plaque on either common carotid artery. In multivariable regression models, women in the highest tertile of sugar-sweetened soda consumption had 2.6% (95%CI: 0.8, 4.5) mean increased IMT, and had 2-fold the risk of carotid atherosclerosis (PR: 2.0, 95%CI: 1.3, 3.2) compared to those in the lowest tertile. In stratified analyses, older and postmenopausal women who consumed sugar-sweetened soda had an increased IMT and atherosclerosis risk. Artificially-sweetened soda consumption was not associated with IMT or carotid atherosclerosis. CONCLUSIONS: Sugar-sweetened soda consumption was associated with subclinical atherosclerosis among disease-free Mexican women. Public health strategies to decrease CVD should consider the impact of sugar-sweetened soda consumption, particularly in older women.

Paradoxical manifestations during tuberculous meningitis treatment among HIV-negative patients: a retrospective descriptive study and literature review.

BACKGROUND: Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. METHODS: Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. RESULTS: We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19-49 years old), developed a paradoxical manifestation within 4-14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. CONCLUSIONS: This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed.

Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis.

BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.

Headache related to personal protective equipment in healthcare workers during COVID-19 pandemic in Mexico: baseline and 6-month follow-up.

BACKGROUND AND AIM: Headaches related to the use of personal protective equipment (PPE) could affect performance at work in healthcare personnel. Our aim was to describe the prevalence and risk factors for headaches related to PPE, in the personnel of a specialized coronavirus disease 2019 (COVID-19) tertiary hospital. METHODS: In this cross-sectional survey study, we invited healthcare workers from COVID-19 referral center in Mexico (May 22-June 19, 2020) to answer a standardized structure questionnaire on characteristics of new-onset PPE-related headache or exacerbation of primary headache disorder. Participants were invited regardless of whether they had a current headache to avoid selection bias. This is the primary analysis of these data. RESULTS: Two hundred and sixty-eight subjects were analyzed, 181/268 (67.5%) women, 177/268 (66%) nurses, mean age 28 years. The prevalence of PPE-related headache was 210/268 (78.4%). Independent risk factors were occupation other than physician (OR 1.59, 95% CI 1.20-2.10), age > 30 years (OR 2.54, 95% CI 1.25-5.14), and female sex (OR 3.58, 95% CI 1.86-6.87). In the 6-month follow-up, 13.1% of subjects evolve to chronic headache, with stress as predictive risk factor. CONCLUSION: The frequency of PPE-associated headache is high, and a subgroup could evolve to chronic headache. More studies are necessary to improve the knowledge about this condition.

COVID-19-related diffuse posthypoxic leukoencephalopathy and microbleeds masquerades as acute necrotizing encephalopathy.

BACKGROUND: The complications of coronavirus disease 2019 (COVID-19), the clinical entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are not limited to the respiratory system. Leukoencephalopathy with microbleeds is increasingly seen in patients with COVID-19. New information is needed to delineate better the clinical implications of this infectious disease. CASE REPORT: A 46-year-old man with confirmed SARS-CoV-2 infection was admitted to the intensive care unit (ICU) with severe COVID-19. After transfer to the general wards, the patient was noted drowsy, disorientated, with slow thinking and speech. A brain MRI showed bilateral symmetrical hyperintense lesions in the deep and subcortical whiter matter, involving the splenium of the corpus callosum, as well as multiple microhemorrhages implicating the splenium and subcortical white matter. No contrast-enhanced lesions were observed in brain CT or MRI. CSF analysis showed no abnormalities, including a negative rtRT-PCR for SARS-CoV-2. An outpatient follow-up visit showed near-complete clinical recovery and resolution of the hyperintense lesions on MRI, without microbleeds change. CONCLUSION: We present the case of a survivor of severe COVID-19 who presented diffuse posthypoxic leukoencephalopathy, and microbleeds masquerading as acute necrotizing encephalopathy. We postulate that this kind of cerebral vasogenic edema with microbleeds could be the consequence of hypoxia, inflammation, the prothrombotic state and medical interventions such as mechanical ventilation and anticoagulation.

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.

Dairy consumption and subclinical atherosclerosis: A cross-sectional study among middle-aged Mexican women.

BACKGROUND AND AIMS: Many dietary guidelines encourage low-fat dairy products; however, recent studies have found null and inverse associations between high-fat dairy intake and cardiovascular disease (CVD) risk. We examined the association between the intake of total dairy and different types of dairy and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in Mexican women. METHODS AND RESULTS: Dairy consumption was assessed using a validated food-frequency questionnaire (FFQ) in 1759 women in the Mexican Teachers' Cohort (MTC) study who were free of CVD or cancer. We categorized participants according to total dairy intake and consumption of four mutually exclusive dairy groups: high-fat, low-fat, yogurt, and dairy with added sugars. IMT and atherosclerotic plaque were measured by B-mode ultrasonography. Subclinical atherosclerosis was defined as an IMT ≥0.8 mm and/or the presence of plaque. Multivariable linear regression and logistic regression models were used to respectively assess the mean percentage difference of mean IMT and odds ratios (OR) for subclinical atherosclerosis across quantiles of dairy consumption. Mean (±SD) age was 45.4 ± 5.0 years and the median (interquartile range: IQR) total dairy consumption was 11.0 (6.6, 17.1) servings/week. After adjusting for lifestyle, clinical, and dietary factors, comparing the highest category of consumption, to the lowest, total dairy was associated with increased IMT (2.6%, 95% confidence interval (CI): 0.6, 4.3; p-trend<0.01). Moreover, yogurt consumption was associated with lower odds of subclinical atherosclerosis (OR = 0.65, 95% CI: 0.47, 0.91; p-trend = 0.01). CONCLUSIONS: While total dairy consumption was associated with carotid wall thickening, yogurt consumption was related to lower subclinical atherosclerosis.

Prediction of acute neurovascular syndromes with prehospital clinical features witnessed by bystanders.

BACKGROUND: The prompt recognition of an acute neurovascular syndrome by the patient or a bystander witnessing the event can directly influence outcome. We aimed to study the predictive value of the medical history and clinical features recognized by the patients' bystanders to preclassify acute stroke syndromes in prehospital settings. METHODS: We analyzed 369 patients: 209 (56.6%) with acute ischemic stroke (AIS), 107 (29.0%) with intracerebral hemorrhage (ICH), and 53 (14.4%) with subarachnoid hemorrhage (SAH). All patients had neuroimaging as diagnostic gold standard. We constructed clinical prediction rules (CPRs) with features recognized by the bystanders witnessing the stroke onset to classify the acute neurovascular syndromes before final arrival to the emergency room (ER). RESULTS: In all, 83.2% cases were referred from other centers, and only 16.8% (17.2% in AIS, 15% in ICH, and 18.9% in SAH) had direct ER arrival. The time to first assessment in ≤ 3 h occurred in 72.4% (73.7%, 73.8%, and 64.2%, respectively), and final ER arrival in ≤ 3 h occurred in 26.8% (32.1%, 15.9%, and 28.3%, respectively). Clinical features referred by witnesses had low positive predictive values (PPVs) for stroke type prediction. Language or speech disorder + focal motor deficit showed 63.3% PPV, and 77.0% negative predictive value (NPV) for predicting AIS. Focal motor deficit + history of hypertension had 35.9% PPV and 78.8% NPV for ICH. Headache alone had 27.9% PPV and 95.3% NPV for SAH. In multivariate analyses, seizures, focal motor deficit, and hypertension increased the probability of a time to first assessment in ≤ 3 h, while obesity was inversely associated. Final ER arrival was determined by age and a direct ER arrival without previous referrals. CONCLUSION: CPRs constructed with the witnesses' narrative had only adequate NPVs in the prehospital classification of acute neurovascular syndromes, before neuroimaging confirmation.

Peripheral artery disease in outpatients with a recent history of acute coronary syndrome or at high atherothrombotic risk.

OBJECTIVES: The frequency and implications of peripheral artery disease (PAD) in some risk groups are not entirely characterized in Latin America. We studied PAD prevalence, risk factors, and six-month outcomes in stable outpatients with a history of a recent acute coronary syndrome (ACS), or at high coronary risk. METHODS: We recruited 830 outpatients in 43 Mexican sites (median age: 64.8 years; 57.8% men). Inclusion criteria were age >18 years, and ACS within 30 days, or age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors. Patients received standardized assessments at baseline and six-month follow-up for medical history, ankle-brachial index (ABI), and the Edinburgh Claudication Questionnaire (ECQ). RESULTS: ABI <0.8 was found in 10.5%, <0.9 in 22.5%, >1.3 in 4.8%, and >1.4 in 3.6%, without differences according to sex or selection criteria. Positive ECQ was found in 7.6%. ABI <0.9 was directly associated with age, diabetes, ACS, and chronic kidney disease, but inversely associated with BMI >27. The six-month case-fatality and atherothrombotic events rates were 1.6% and 3.6%, respectively. In patients with ABI <0.9 and ABI <0.8, the six-month case-fatality rates were 2.5% (p = 0.27) and 5.4% (p = 0.03), respectively. In a Cox proportional-hazards model, baseline factors associated with death were age ≥65, ABI <0.8, and ACS. CONCLUSIONS: Subclinical PAD is more common than symptomatic claudication in high-risk coronary outpatients. Low ABI is associated with reduced short-term survival in patients with recent ACS or at high coronary risk.

Detection of Pulmonary Shunts by Transcranial Doppler in Hospitalized Non-mechanically Ventilated Coronavirus Disease-19 Patients.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated disease coronavirus disease 2019 (COVID-19), hypoxemia mechanisms differ from those observed in acute respiratory distress syndrome. Hypoxemia and respiratory failure in COVID- 19 are attributed to pulmonary angiopathy, increasing physiological pulmonary shunting1-3.

Spasticity in practice (SPACE): an international non-interventional study of botulinum neurotoxin type A in treatment-naïve subjects with spasticity.

AIM OF THE STUDY: SPACE, a prospective, non-interventional, open-label, multinational study, investigated physicians' and subjects' assessment of safety, efficacy, and health-related quality of life (HRQoL) following botulinum neurotoxin type A (BoNT-A) treatment to understand real-world clinical usage for the management of focal and multifocal spasticity. CLINICAL RATIONALE FOR THE STUDY: Treatment guidelines recommend the use of BoNT-A for the management of spasticity in adults. This study assessed how physicians use BoNT-A therapy in real-world clinical practice, and provided evidence on long-term safety and efficacy over a period of up to 2 years. MATERIALS AND METHODS: BoNT treatment-naïve adults with spasticity of any aetiology received any BoNT-A formulation at their physician's discretion, and were observed for ≤ 8 treatment cycles (≤ 2 years). Daily practice information, physician's global assessments of tolerability and efficacy, and HRQoL were documented. Incidences of adverse drug reactions or all adverse events were documented for non-Mexican subjects and for Mexican subjects, respectively, due to protocol differences based on local regulatory requirements. RESULTS: A total of 701 subjects were enrolled (safety population; nine countries). Physicians rated the tolerability of BoNT-A as 'very good' or 'good' for 88.2-97.4% of subjects throughout the study (subject numbers declined throughout this non-interventional study). Adverse drug reactions were reported for 16/600 (2.7%) of the non-Mexican subjects, with two considered to be 'definitely related' to treatment (injection-site haematoma, n = 1; botulism, n = 1). For 687 subjects, efficacy was rated 'very good' or 'good' by most physicians and subjects. Improvements in HRQoL were observed. CONCLUSIONS AND CLINICAL IMPLICATIONS: Throughout this 2-year study, BoNT-A treatment was generally well-tolerated, effective, and associated with an improved HRQoL. This study makes a valuable contribution to the broader understanding of how physicians use BoNT-A therapy to manage spasticity in real-world clinical practice.

Clinical and neurophysiological description of patients with POEMS syndrome.

INTRODUCTION: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a monoclonal gammopathy with polyneuropathy as a mandatory criterion. OBJECTIVE: To describe potential associations between clinical expression and electrodiagnostic patterns in POEMS syndrome. METHOD: Observational, retrospective, cross-sectional study of cases cared for in a referral center, diagnosed with POEMS syndrome from 2009 to 2019. RESULTS: Eleven patients (8 men) were analyzed. Median age at diagnosis was 40 years (range: 31-51; mean: 37.19 ± 15.67 years). Mean latency at diagnosis was 9.7 ± 8.37 months. In all subjects, initial clinical manifestation was polyneuropathy. Most patients had an axonal pattern (n = 5), followed by demyelinating (n = 4) and mixed patterns (n = 2). Monoclonal gammopathy was observed in all (6 l and 5 k cases; immunoglobulin [Ig] G: 72 %; IgA: 18 %; IgM: 9 %). Medical Research Council sum score was lower in the axonal pattern (median: 37.00 vs. 45.5; p = 0.024). There were no differences in systemic involvement between electrophysiological patterns. CONCLUSION: Electrophysiological patterns are unlikely to have a clear extra-neurological clinical correspondence; however, this will have to be definitively proven with a larger sample size.

INTRODUCCIÓN: El síndrome POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) es una gammapatía monoclonal con polineuropatía como criterio obligatorio. OBJETIVO: Describir las potenciales asociaciones entre la expresión clínica y los patrones de electrodiagnóstico en el síndrome POEMS. MÉTODO: Estudio observacional, retrospectivo y transversal de los casos atendidos en un centro de referencia con diagnóstico de síndrome de POEMS de 2009 a 2019. RESULTADOS: Se analizó a 11 pacientes (8 hombres). La mediana de la edad al diagnóstico fue de 40 años (rango: 31-51, media: 37.19 ± 15.67 años). La latencia media al diagnóstico fue de 9.7 ± 8.37 meses. En todos la manifestación clínica inicial fue la polineuropatía. La mayoría de los pacientes presentaron un patrón axonal (n = 5), seguido del desmielinizante (n = 4) y mixto (n = 2). La gammapatía monoclonal se observó en todos (6 casos l y 5 k, inmunoglobulina [Ig] G: 72%, IgA: 18%, IgM: 9%). El Medical Research Council sum score fue menor en el patrón axonal (medianas: 37.00 vs. 45.5, p = 0.024). No se presentaron diferencias en la afección sistémica entre patrones electrofisiológicos. CONCLUSIÓN: Es poco probable que los patrones electrofisiológicos tengan una correspondencia clínica extraneurológica clara, sin embargo, esto deberá probarse de forma definitiva con un mayor tamaño de muestra.

Family Member Incarceration, Psychological Stress, and Subclinical Cardiovascular Disease in Mexican Women (2012-2016).

Objectives. To examine the association between family member incarceration, psychological stress, and subclinical cardiovascular disease (CVD).Methods. Between 2012 and 2016, 1849 CVD-free women from the Mexican Teachers' Cohort responded to questions on family incarceration from the Life Stressor Checklist. Perceived stress and hair cortisol levels were measured in a subset of participants. Carotid intima-media thickness was measured, and carotid atherosclerosis was determined in all participants. We used multivariable quantile, linear, and logistic regression models to evaluate the association between family member incarceration, stress, and subclinical CVD.Results. Among women with a mean age of 49.7 years (SD ±5.2), 15.3% reported family member incarceration. We found that both perceived stress and hair cortisol levels were significantly higher in women with an incarcerated family member relative to women without one. After multivariable adjustment, women who reported family member incarceration had 41% (95% confidence interval = 1.04, 2.00) higher odds of carotid atherosclerosis compared with those who did not.Conclusions. Family member incarceration was associated with robust markers of stress and cardiovascular risk. Mass incarceration may have a long-lasting impact on physical health of affected families.