[Use of clinical ultrasound in primary care: Multicenter prospective study]. / Uso de la ecografía clínica en Atención Primaria. Estudio prospectivo multicéntrico.

OBJECTIVE: The objective was to describe the characteristics of the use of clinical ultrasound in two health centers (SC) of Health Area VII of the Region of Murcia (CS Murcia-Sur and CS Floridablanca). DESIGN: Observational, descriptive, longitudinal, prospective and multicenter study. SITE: CS Murcia-Sur and CS Floridablanca (Health Area VII of the Region of Murcia). PARTICIPANTS: One hundred and thirty-five patients were included. INTERVENTIONS: Performance of clinical ultrasound in the primary care (PC) consultation. MAIN MEASUREMENTS: Demographic variables (age, sex), as well as clinical variables (reason for consultation, type of ultrasound, results, referrals to the second hospital level, degree of diagnostic agreement) were collected. RESULTS: One hundred and thirty-five patients were included, more than 50% were female. The main reason for consultation was musculoskeletal and soft tissue symptoms (44.4%), followed by digestive symptoms (21.5%). 44.4% of the ultrasounds were classified as normal, while pathological findings were found in 55.6%. Confirmatory tests were requested in 43.7% and the findings were confirmed in 67% of the patients. CONCLUSIONS: The use of ultrasound in PC allows to show the high prevalence of pathological findings in the examination of patients. In a technique that helps the clinician in his diagnostic-therapeutic process. The integration of clinical ultrasound in the PC consultation can save complementary studies and referrals to a second level of care. Its implementation in PC requires proper training of professionals.

Plasma-induced nanoparticle aggregation for stratifying COVID-19 patients according to disease severity.

Stratifying patients according to disease severity has been a major hurdle during the COVID-19 pandemic. This usually requires evaluating the levels of several biomarkers, which may be cumbersome when rapid decisions are required. In this manuscript we show that a single nanoparticle aggregation test can be used to distinguish patients that require intensive care from those that have already been discharged from the intensive care unit (ICU). It consists of diluting a platelet-free plasma sample and then adding gold nanoparticles. The nanoparticles aggregate to a larger extent when the samples are obtained from a patient in the ICU. This changes the color of the colloidal suspension, which can be evaluated by measuring the pixel intensity of a photograph. Although the exact factor or combination of factors behind the different aggregation behavior is unknown, control experiments demonstrate that the presence of proteins in the samples is crucial for the test to work. Principal component analysis demonstrates that the test result is highly correlated to biomarkers of prognosis and inflammation that are commonly used to evaluate the severity of COVID-19 patients. The results shown here pave the way to develop nanoparticle aggregation assays that classify COVID-19 patients according to disease severity, which could be useful to de-escalate care safely and make a better use of hospital resources.

Immunodetection of Lung IgG and IgM Antibodies against SARS-CoV-2 via Enzymatic Liquefaction of Respiratory Samples from COVID-19 Patients.

Lung-secreted IgG and IgM antibodies are valuable biomarkers for monitoring the local immune response against respiratory infections. These biomarkers are found in lower airway secretions that need to be liquefied prior to analysis. Traditional methods for sample liquefaction rely on reducing disulfide bonds, which may damage the structure of the biomarkers and hamper their immunodetection. Here, we propose an alternative enzymatic method that uses O2 bubbles generated by endogenous catalase enzymes in order to liquefy respiratory samples. The proposed method is more efficient for liquefying medium- and high-viscosity samples and does not fragment the antibodies. This prevents damage to antigen recognition domains and recognition sites for secondary antibodies that can decrease the signal of immunodetection techniques. The suitability of the enzymatic method for detecting antibodies in respiratory samples is demonstrated by detecting anti-SARS-CoV-2 IgG and IgM to viral N-protein with gold standard ELISA in bronchial aspirate specimens from a multicenter cohort of 44 COVID-19 patients. The enzymatic detection sharply increases the sensitivity toward IgG and IgM detection compared to the traditional approach based on liquefying samples with dithiothreitol. This improved performance could reveal new mechanisms of the early local immune response against respiratory infections that may have gone unnoticed with current sample treatment methods.

Optimized detection of lung IL-6 via enzymatic liquefaction of low respiratory tract samples: application for managing ventilated patients.

Lung IL-6 is a promising biomarker for predicting respiratory failure during pulmonary infections. This biomarker is found in respiratory samples which need to be liquefied prior to analysis. Traditional liquefying methods use reducing agents such as dithiothreitol (DTT). However, DTT impairs immunodetection and does not liquefy highly viscous samples. We propose an enzymatic method that liquefies samples by means of generating O2 bubbles with endogenous catalase. Low respiratory tract specimens from 48 mechanically ventilated patients (38 with SARS-CoV-2 infection) were treated with DTT or with the enzymatic method. We used turbidimetry to compare the liquefaction degree and IL-6 was quantified with ELISA. Finally, we used AUC-ROC, time-to-event and principal component analysis to evaluate the association between respiratory compromise or local inflammation and IL-6 determined with both methods. Enzymatically treated samples were better liquefied than those reduced by DTT, which resulted in higher ELISA signals. Lung IL-6 levels obtained with the enzymatic procedure were negatively correlated with the oxygenation index (PaO2/FiO2) and the time of mechanical ventilation. The proposed enzymatic liquefaction method improves the sensitivity for lung IL-6 detection in respiratory samples, which increases its predictive power as a biomarker for evaluating respiratory compliance.

Nanoparticle transfer biosensors for the non-invasive detection of SARS-CoV-2 antigens trapped in surgical face masks.

Detecting SARS-CoV-2 antigens in respiratory tract samples has become a widespread method for screening new SARS-CoV-2 infections. This requires a nasopharyngeal swab performed by a trained healthcare worker, which puts strain on saturated healthcare services. In this manuscript we describe a new approach for non-invasive COVID-19 diagnosis. It consists of using mobile biosensors for detecting viral antigens trapped in surgical face masks worn by patients. The biosensors are made of filter paper containing a nanoparticle reservoir. The nanoparticles transfer from the biosensor to the mask on contact, where they generate colorimetric signals that are quantified with a smartphone app. Sample collection requires wearing a surgical mask for 30 min, and the total assay time is shorter than 10 min. When tested in a cohort of 27 patients with mild or no symptoms, an area under the receiving operating curve (AUROC) of 0.99 was obtained (96.2 % sensitivity and 100 % specificity). Serial measurements revealed a high sensitivity and specificity when masks were worn up to 6 days after diagnosis. Surgical face masks are inexpensive and widely available, which makes this approach easy to implement anywhere. The excellent sensitivity, even when tested with asymptomatic patient samples, along with the mobile detection scheme and non-invasive sampling procedure, makes this biosensor design ideal for mass screening.

Depression is associated with efavirenz-containing treatments in newly antiretroviral therapy initiated HIV patients in Ecuador.

BACKGROUND: It is well known that people living with HIV (PLWH) is in higher risk for the development of depression and it has also been suggested that the use of efavirenz into the antiretroviral regimens increases even that risk. OBJECTIVE: To evaluate the effect of efavirenz-containing antiretroviral regimens on the development of depression in newly ART initiated HIV patients in Ecuador. METHODS: In a prospective cohort study from June 2016 to May 2017, all newly HIV diagnosed patients at the HIV/AIDS Unit of the Hospital Eugenio Espejo in Quito, Ecuador were evaluated using the Hamilton Rating Scale for Depression followed by a second assessment 8-12 weeks after antiretroviral therapy containing efavirenz was initiated. RESULTS: A total of 79 patients, mainly males younger than 35 years were studied. Majority of them were on TDF/FTC/EFV. Initial score in Hamilton Rating Scale revealed that less than 30% had no depression symptoms while almost 40% had mild depression. However, in the second assessment, 22.6% of the subjects had a score in the Hamilton Rating Scale compatible with severe or very severe depression (RR 1.58, 95% CI 1.09 to 2.28; p = 0.05). CONCLUSION: In our cohort study, depression was much higher in patients on Efavirenz-containing treatments. Therefore, assessment for depression must be essential as part of follow-up in these patients.

Structured light enables biomimetic swimming and versatile locomotion of photoresponsive soft microrobots.

Microorganisms move in challenging environments by periodic changes in body shape. In contrast, current artificial microrobots cannot actively deform, exhibiting at best passive bending under external fields. Here, by taking advantage of the wireless, scalable and spatiotemporally selective capabilities that light allows, we show that soft microrobots consisting of photoactive liquid-crystal elastomers can be driven by structured monochromatic light to perform sophisticated biomimetic motions. We realize continuum yet selectively addressable artificial microswimmers that generate travelling-wave motions to self-propel without external forces or torques, as well as microrobots capable of versatile locomotion behaviours on demand. Both theoretical predictions and experimental results confirm that multiple gaits, mimicking either symplectic or antiplectic metachrony of ciliate protozoa, can be achieved with single microswimmers. The principle of using structured light can be extended to other applications that require microscale actuation with sophisticated spatiotemporal coordination for advanced microrobotic technologies.

Neural-Net Artificial Pancreas: A Randomized Crossover Trial of a First-in-Class Automated Insulin Delivery Algorithm.

Background: Automated insulin delivery (AID) is now integral to the clinical practice of type 1 diabetes (T1D). The objective of this pilot-feasibility study was to introduce a new regulatory and clinical paradigm-a Neural-Net Artificial Pancreas (NAP)-an encoding of an AID algorithm into a neural network that approximates its action and assess NAP versus the original AID algorithm. Methods: The University of Virginia Model-Predictive Control (UMPC) algorithm was encoded into a neural network, creating its NAP approximation. Seventeen AID users with T1D were recruited and 15 participated in two consecutive 20-h hotel sessions, receiving in random order either NAP or UMPC. Their demographic characteristics were ages 22-68 years old, duration of diabetes 7-58 years, gender 10/5 female/male, White Non-Hispanic/Black 13/2, and baseline glycated hemoglobin 5.4%-8.1%. Results: The time-in-range (TIR) difference between NAP and UMPC, adjusted for entry glucose level, was 1 percentage point, with absolute TIR values of 86% (NAP) and 87% (UMPC). The two algorithms achieved similar times <70 mg/dL of 2.0% versus 1.8% and coefficients of variation of 29.3% (NAP) versus 29.1 (UMPC)%. Under identical inputs, the average absolute insulin-recommendation difference was 0.031 U/h. There were no serious adverse events on either controller. NAP had sixfold lower computational demands than UMPC. Conclusion: In a randomized crossover study, a neural-network encoding of a complex model-predictive control algorithm demonstrated similar performance, at a fraction of the computational demands. Regulatory and clinical doors are therefore open for contemporary machine-learning methods to enter the AID field. Clinical Trial Registration number: NCT05876273.

Chitin and L(+)-lactic acid production from crab (Callinectes bellicosus) wastes by fermentation of Lactobacillus sp. B2 using sugar cane molasses as carbon source.

Crab wastes are employed for simultaneous production of chitin and L(+)-lactic acid by submerged fermentation of Lactobacillus sp. B2 using sugar cane molasses as carbon source. Response surface methodology was applied to design the culture media considering demineralization. Fermentations in stirred tank reactor (2L) using selected conditions produced 88% demineralization and 56% deproteinization with 34% yield of chitin and 19.5 gL(-1) of lactic acid (77% yield). The chitin purified from fermentation displayed 95% degree of acetylation and 0.81 and 1 ± 0.125% of residual ash and protein contents, respectively.

Predictive ESO-based control with guaranteed stability for uncertain MIMO constrained systems.

In this paper, a novel predictive Extended State Observer (ESO)-based discrete controller with guaranteed input-to-state stability is developed. Predictive controllers based on ESOs are gaining acceptance for regulating MIMO systems with disturbances, uncertainties or actuator constrains. However, there is an important concern about this control structure regarding its closed-loop stability; a key property that is not strictly guaranteed with the most part of the previous formulations. This paper shows that -under the same assumptions that are normally taken in the ESO literature- a predictive ESO-based controller that is proved to be input-to-state stable can be easily constructed by adding two fixed terms in the cost-index definition. A simulation case study of the glucose control in patients with type-1 diabetes is additionally given in order to illustrate the main advantages of this control structure.

Colorimetric Detection of Sepsis-Derived Hyperdegranulation with Plasmonic Nanosensors.

Hyperdegranulation of neutrophilic granulocytes is a common finding in sepsis that directly contributes to the heightened immune response leading to organ dysfunction. Currently, cell degranulation is detected by flow cytometry, which requires large infrastructure that is not always available at the point of care. Here, we propose a plasmonic assay for detecting the degranulation status of septic cells colorimetrically. It is based on triggering the aggregation of gold nanoparticles with cationic granule proteins. Cells from septic patients contain fewer granules and therefore release less cationic proteins than healthy cells. This results in red-colored assays than can be easily detected by eye. The assay can selectively detect cationic granule proteins even in the presence of an excess of unrelated proteins, which is key to detect degranulation with high specificity. Coupling this signal generation mechanism with a magnetic purification step enabled the identification of septic cells with the same performance as flow cytometry. This makes the proposed method a promising alternative for diagnosing sepsis in decentralized healthcare schemes.

Atypical Obstructive Pseudotumors in AIDS as the Initial Manifestation of Gastrointestinal Histoplasmosis.

Histoplasma capsulatum is a dysmorphic fungus distributed worldwide commonly associated with pulmonary histoplasmosis. We report the case of an unusual presentation of gastrointestinal histoplasmosis leading to the obstruction of the intestinal lumen in a 30-year-old female, HIV positive, admitted to the hospital due to chronic abdominal pain and constipation. An initial abdominal CT revealed a mass in the sigmoid colon. A further colonoscopy showed an infiltrating, friable mass obstructing 80% of the lumen staining positive for H. capsulatum. The unspecific nature of the patient's symptoms along with the unusual presentation of the infection raises awareness about the importance of including new pathologies to differential diagnoses when treating AIDS patients.

Low Albumin Levels Are Associated with Poorer Outcomes in a Case Series of COVID-19 Patients in Spain: A Retrospective Cohort Study.

There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for coronavirus disease 2019 (COVID-19). In this observational study, we aimed to describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior to hospitalization. Forty-eight patients (27 non-ICU and 21 ICU) with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were analyzed (mean age, 66 years, [range, 33-88 years]; 67% males). There were no differences in age or sex among groups. Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs. 61%, p = 0.022). ICU-patients had lymphopenia as well as hypoalbuminemia. Lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < 0.001). Lower albumin levels were associated with poor prognosis measured as longer hospital length (r = -0.472, p < 0.001) and mortality (r = -0.424, p = 0.003). As of 28 April 2020, 10 patients (8 ICU and 2 non-ICU) have died (21% mortality), and while 100% of the non-ICU patients have been discharged, 33% of the ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward). Critically ill patients with COVID-19 present lymphopenia, hypoalbuminemia and high levels of inflammation.

Quantifying alcohol use among Ecuadorian human immunodeficiency virus positive individuals and assessing alcohol as an independent risk factor for human immunodeficiency virus: A case control study STROBE.

Alcohol abuse has been identified as a risk factor for contracting human immunodeficiency virus (HIV) and accelerating disease progression. Our study aims to determine alcohol consumption rates among Ecuadorian HIV positive (HIV+) patients prior to diagnosis to evaluate its impact as an independent risk factor for contracting HIV. Additionally, we will examine post-diagnosis consumption rates among the HIV+ population.We provided anonymous questionnaires to 300 HIV+ patients and 600 internal medicine patients at 3 hospitals in Quito, Ecuador. Questionnaires quantified alcohol usage prior to HIV diagnosis, at time of diagnosis, and post-diagnosis while accounting for other potential HIV risk factors. We then determined frequencies of alcohol consumption and confounding variables. Finally, we performed a multivariable logistic regression controlling for confounders to determine the statistical significance of alcohol consumption as an independent risk factor for HIV.Our results showed increased odds for contracting HIV among those who drank daily (OR 5.3, CI 2.0-14.0) and those who consumed 6 or more alcoholic beverages on days they drank (OR 5.0, CI 3.1-8.2). Through multivariable analysis, we found that abstaining from binge drinking was a protective factor with an OR 0.5 (0.3-0.96). The percentage of HIV+ patients abstaining from alcohol increased from 30% twelve months prior to diagnosis to 57% after diagnosis.Our results show that alcohol abuse significantly increases the risk of contracting HIV. We found that prior to diagnosis, HIV patients consistently drank more frequently and a greater amount than the control group. Alcohol use significantly decreased among HIV+ patients after diagnosis.

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.

INTRODUCTION: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

Increased incidences of noninfectious comorbidities among aging populations living with human immunodeficiency virus in Ecuador: a multicenter retrospective analysis.

Introduction: Besides the well-known increased risk of developing HIV-related infectious comorbidities; compared with the general population, people living with HIV (PLHIV) may also have an increased risk of developing noninfectious comorbidities (NICMs). This is the first study intended to determine the NICMs rates affecting PLHIV who were under cART regimen in Ecuador. Methods: A total of 503 HIV-positive patients were evaluated during the period June 2015-November 2016 and included in a multicenter retrospective, cross-sectional study conducted in seven main government and nongovernment community-based hospitals in Ecuador. Results: The average age of the participants was 39.2±11.9 years old and the majority of them were male (67.2%). The average age at HIV diagnosis was 34.1 years old and cART in average was started 15.9 months after HIV-diagnosis. Recruited patients were receiving cART for an average of 59.2±40.2 months. Only 9.9% (n=50) of the patients did not show any NICMs. Diabetes and pre-diabetes was found in 6% (n=30) and 16.3% (n=82) patients, respectively; however, dyslipidemia and overweight/obesity was frequent, as they affected 41.4% (n=208) and 36.4% (n=183) patients, respectively. Sixty patients (11.9%) were diagnosed with depression and 28.2% (n=142) of the studied subjects were found to have other NICMs. Conclusion: Prevalence of NICMs among subjects under cART was greater than that reported among the Ecuadorian general population, therefore specific public health actions are required to make patients aware of and prevent NICMs among PLHIV in Ecuador.

A comparison of the isometric force fatigue-recovery profile in two posterior chain lower limb tests following simulated soccer competition.

AIM: To evaluate the reliability of isometric peak force (IPF) in a novel "long-length" 90°Hip:20°Knee (90:20) strength test and to compare the simulated soccer match induced fatigue-recovery profile of IPF in this test with that of an isometric 90°Hip:90°Knee (90:90) position test. METHODS: Twenty semi-professional soccer players volunteered for the study of which 14 participated in the first part of the study which assessed 90:20 reliability (age = 21.3 ± 2.5 years, height = 1.79 ± 0.07 m, body mass = 73.2 ± 8.8 kg), while 17 completed the second part of the study evaluating fatigue-recovery (age 21.2±2.4 yrs., height = 180 ± 0.09 m, body mass 73.8 ± 8.9 kg). We evaluated the inter-session reliability of IPF in two 90:20 test protocols (hands on the wall (HW); and hands on chest (HC)) both performed on two occasions, 7 days apart. We then assessed 90:20 (HC) and 90:90 IPF immediately before (PRE) and after (POST) after a simulated soccer match protocol (BEAST90mod) and 48 (+48 h) and 72 hours (+72 h) later. RESULTS: Part one: the 90:20 showed moderate to high overall reliability (CV's of 7.3% to 11.0%) across test positions and limbs. CV's were lower in the HW than HC in the dominant (7.3% vs 11.0%) but the opposite happened in the non-dominant limb where CV's were higher in the HW than HC (9.7% vs 7.3%). Based on these results, the HC position was used in part two of the study. Part two: 90:20 and 90:90 IPF was significantly lower POST compared to PRE BEAST90mod across all testing positions (p<0.001). IPF was significantly lower at +48 h compared to PRE in the 90:20 in both limbs (Dominant: p<0.01,Non-dominant: p≤0.05), but not in the 90:90. At +72 h, IPF was not significantly different from PRE in either test. CONCLUSIONS: Simple to implement posterior IPF tests can help to define recovery from competition and training load in football and, potentially, in other multiple sprint athletes. Testing posterior chain IPF in a more knee extended 90:20 position may provide greater sensitivity to fatigue at 48 h post simulated competition than testing in the 90:90 position, but also may require greater degree of familiarization due to more functional testing position.

Heterotopic neuroglial tissue associated with bilateral palatine cleft.

Isolated heterotopic lesions of neuroglial tissue may rarely present in the head and neck, or they may be associated with other congenital deviations. In this article we present the case of a 7-month-old patient with a central lesion that emerged through the anterior part of a bilateral palatine fissure.

Computerised sepsis protocol management. Description of an early warning system. / Protocolo informático de manejo integral de la sepsis. Descripción de un sistema de identificación precoz.

INTRODUCTION: New strategies need to be developed for the early recognition and rapid response for the management of sepsis. To achieve this purpose, the Multidisciplinary Sepsis Team (MST) developed the Computerised Sepsis Protocol Management (PIMIS). The aim of this study was to evaluate the convenience of using PIMIS, as well as the activity of the MST. METHODS: An analysis was performed on the data collected from solicited MST consultations (direct activation of PIMIS by attending physician or telephone request) and unsolicited ones (by referral from the microbiology laboratory or an automatic referral via the hospital vital signs recording software [SIDCV]), as well as the hospital department, source of infection, treatment recommendation, and acceptance of this. RESULTS: Of the 1,581 first consultations, 65.1% were solicited consultations (84.1% activation of PIMIS and 15.9% by telephone). The majority of unsolicited consultations were generated by the microbiology laboratory (95.2%), and 4.8% from the SIDCV. Referral from solicited consultations were generated sooner (5.63days vs 8.47days; P<.001) and came from clinical specialties rather than from the surgical ward (73.0% vs 39.1%; P<.001). A recommendation was made for antimicrobial prescription change in 32% of first consultations. The treating physician accepted 78.1% of recommendations. CONCLUSIONS: The high rate of solicited consultations and acceptance of recommended prescription changes suggest that a MST is seen as a helpful resource, and that PIMIS software is perceived to be useful and convenient to use, as it is the main source of referral.

[Clinical and pathological definition of temporal medium epilepsy subtypes with hypocampic sclerosis]. / Definición clínico-patológica de los subtipos de epilepsia temporal medial con esclerosis del hipocampo.

BACKGROUND AND OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy. PATIENTS AND METHOD: Clinical histories and anatomopathological specimens of 228 patients with temporal epilepsy surgically obtained at our hospital between 1993 and 2014 were retrospectively analysed. All patients underwent a standard preoperative evaluation and anterior temporal resection (modified from Spencer). The anatomopathological study included the standard hematoxylin-eosin and immunohistochemical protocol, with special interest in the assessment of neuronal loss with NeuN. Seizure control was assessed according to the scale of results of the ILAE and Engel. The mean follow-up was 8.6 years (2-19). RESULTS: At 10 years after the intervention, 67.9% of patients were seizure-free (ILAE 1) and as many as 77.5% of the patients were seizure-free (Engel 1) at the end of the follow-up. The probability of not having a seizure (ILAE 1) after surgery at 2 (p=.042), 5 (p=.001) and 7 years (p=.22) was higher in classic and severe forms compared to isolated sclerosis CA1 and CA4 forms. Higher neuronal loss measured with the NeuN immunostain in CA1 was associated with better outcome in seizure management (multivariate analysis, p=.08). The presence of a personal history of epilepsy was associated with greater neuronal loss in CA1 (p=.028) and CA3 (p=.034), and the presence of psychic auras was related with greater neuronal loss in CA3 (p=.025). In our case, the probability of medication withdrawal was related to the presence of personal history (p=.003) and, inversely, to neuronal loss in CA1 (p=.036) and CA3 (p=.038). The greatest impairment of verbal memory occurred in those patients with a lower neuronal loss in CA1 (p=.023), CA2 (p=.049) and CA3 (p=.035). CONCLUSIONS: The results indicate that the classical and severe subtypes have a better prognosis in the control of seizures against the atypical forms, validating the clinical and prognostic utility of the classification of histological subtypes of hippocampal sclerosis from the ILAE. The value of the immunohistochemistry in the mesial temporal lobe epilepsy with hippocampal sclerosis has been demonstrated as a key element to determine the neuropsychological prognosis and seizure management of the patients after surgery.