[Natural history of mucopolysaccharidosis type III in a series of Colombian patients]. / Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.

INTRODUCTION: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. CASE REPORTS: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. CONCLUSIONS: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.

TITLE: Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos.Introducción. La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos. Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones. La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.

Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos / Natural history of mucopolysaccharidosis type III in a series of Colombian patients

Introducción: La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos: Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones: La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.(AU)

Introduction: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. Case reports: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. Conclusions: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.(AU)

CAR-T Cell Therapy: From the Shop to Cancer Therapy.

Cancer is a worldwide health problem. Nevertheless, new technologies in the immunotherapy field have emerged. Chimeric antigen receptor (CAR) technology is a novel biological form to treat cancer; CAR-T cell genetic engineering has positively revolutionized cancer immunotherapy. In this paper, we review the latest developments in CAR-T in cancer treatment. We present the structure of the different generations and variants of CAR-T cells including TRUCK (T cells redirected for universal cytokine killing. We explain the approaches of the CAR-T cells manufactured ex vivo and in vivo. Moreover, we describe the limitations and areas of opportunity for this immunotherapy and the current challenges of treating hematological and solid cancer using CAR-T technology as well as its constraints and engineering approaches. We summarize other immune cells that have been using CAR technology, such as natural killer (NK), macrophages (M), and dendritic cells (DC). We conclude that CAR-T cells have the potential to treat not only cancer but other chronic diseases.

Análisis de las fases del rescate acuático como elemento discriminativo del rendimiento / Analysis of the phases of lifesaving as a discriminative element of performance

Purpose: The aim of this study was to analyze the different phases of a water rescue, their influence in the whole lifesavingand if lifeguards could be differentiated according to their abilities during a water rescue.Methods: A cross-sectional study was carried out to analyze the different phases and lifeguard’sabilities of a simulated water rescue of 100 m. Thirty-fourprofessional lifeguards performed the test and the time was recorded for the first phase (swimming to the victim), the second phase (towing back the victim) and the third phase (extracting the victim). A discriminant analysis was conducted in order to classifylifeguards in two groups (high or medium level of abilities during the water rescue) and the times were compared on each phase.Results: The time during the second and the third phase classify correctly the lifeguards according to their level of abilities. Lifeguards with higher level of abilities performed the water rescue significantly faster, specifically during the second (p < 0.001, ES =1.38, large) and the third phase (p =0.002, ES = 1.09, medium), but no differences were found in the first part of the water rescue (p > 0.05). Conclusion: The time of a simulated water rescue seems to bea good method to classify lifeguards according to their abilities. These findings could allow rescue teams to know the skills of their lifeguards and design strategiesin order to decrease risks and enhance lifesaving (AU)

Objetivo: Analizar las diferentes fases del rescate para conocer su influencia sobre el resultado final y categorizar a los socorristas de acuerdo a su competencia acuática.Métodos: Se realizó un estudio cruzado simulando un rescate a 100 metros con 34 socorristas, analizando las tres fases del rescate: nado hacia la víctima, traslado a tierra y extracción. Se realizó un análisis discriminante para clasificar a los socorristas según el tiempo de rescate.Resultados: La segunda y la tercera fase clasificó correctamente a los socorristas de acuerdo al tiempo empleado. La mayor competencia fue determinada especialmente en la segunda fase del salvamento (p<0,001, TE=1,38, grande) y en menor medida de la tercera fase (p=0,002, TE=1,09, mediano).Conclusión: El tiempo empleado en la segunda fase parece ser un buen método para clasificar la competencia de los socorristas durante el rescate. Estos hallazgos proporcionan información relevante para el entrenamiento y organización de equipos de rescate (AU)

p16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC. METHODS: Tumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry. RESULTS: Of the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05). CONCLUSION: Our results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.

Maternal separation differentially modulates early pathology by sex in 5xFAD Alzheimer's disease-transgenic mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Most cases of AD are considered idiopathic and likely due to a combination of genetic, environmental, and lifestyle-related risk factors. Despite occurring decades before the typical age of an AD diagnosis, early-life stress (ELS) has been suggested to have long-lasting effects that may contribute to AD risk and pathogenesis. Still, the mechanisms that underlie the role of ELS on AD risk remain largely unknown. Here, we used 5xFAD transgenic mice to study relatively short-term alterations related to ELS in an AD-like susceptible mouse model at 6 weeks of age. To model ELS, we separated pups from their dams for 3 h per day from postnatal day 2-14. Around 6 weeks of age, we found that maternally separated (MS) 5xFAD mice, particularly female mice, displayed increased amyloid-ß-immunoreactivity in the anterior cingulate cortex (ACC) and basolateral amygdala (BLA). In anterior cingulate cortex, we also noted significantly increased intraneuronal amyloid-ß-immunoreactivity associated with MS but only in female mice. Moreover, IBA1-positive DAPI density was significantly increased in relation to MS in ACC and BLA, and microglia in BLA of MS mice had significantly different morphology compared to microglia in non-MS 5xFAD mice. Cytokine analysis showed that male MS mice, specifically, had increased levels of neuroinflammatory markers CXCL1 and IL-10 in hippocampal extracts compared to non-MS counterparts. Additionally, hippocampal extracts from both male and female MS 5xFAD mice had decreased levels of synapse- and activity-related markers Bdnf, 5htr6, Cox2, and Syp in hippocampus. Lastly, we performed behavioral tests to evaluate anxiety- and depressive-like behavior and working memory but could not detect any significant differences between groups. Overall, we detected several sex-specific molecular and cellular alterations in 6-week-old adolescent 5xFAD mice associated with MS that may help explain the connection between ELS and AD risk.

Psychological impact of COVID-19 containment on CADASIL patients.

INTRODUCTION: COVID-19 restrictive containment was responsible for major psychological distress and alteration of quality of life (QoL) in the general population. Their impact in a group of patients having cerebral small vessel disease (SVD) and at high risk of stroke and disability was unknown. OBJECTIVE: We aimed to determine the potential psychological impact of strict containment during the COVID-19 pandemic in a sample of CADASIL patients, a rare SVD caused by NOTCH3 gene mutations. METHODS: Interviews of 135 CADASIL patients were obtained just after the end of the strict containment in France. Depression, QoL and negative subjective experience of the containment were analysed, as well as predictors of posttraumatic and stressor-related manifestations, defined as an Impact Event Scale-Revised score ≥ 24, using multivariable logistic analysis. RESULTS: Only 9% of patients showed a depressive episode. A similar proportion had significant posttraumatic and stressor-related disorder manifestations independently associated only with socio-environment factors, rather than clinical ones: living alone outside a couple (OR 7.86 (1.87-38.32), unemployment (OR 4.73 (1.17-18.70)) and the presence of 2 or more children at home (OR 6.34 (1.35-38.34). CONCLUSION: Psychological impact of the containment was limited in CADASIL patients and did not appear related to the disease status. About 9% of patients presented with significant posttraumatic and stressor-related disorder manifestations which were predicted by living alone, unemployment, or exhaustion related to parental burden.

Perceptions of change in the environment caused by the COVID-19 pandemic: Implications for environmental policy.

COVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy.

Molecular epidemiology and drug resistance of Mycobacterium tuberculosis in a tertiary care hospital in northeastern Mexico.

INTRODUCTION: Tuberculosis (TB) is a re-emerging disease considered a public health concern. In the present study, we analyzed the epidemiology and drug resistance of Mycobacterium tuberculosis strains isolated from patients with pulmonary TB. METHODOLOGY: Mycobacterium tuberculosis isolates (n = 190) were obtained from patients with pulmonary TB admitted to Dr. José Eleuterio González University Hospital (UH). Each M. tuberculosis isolate was analyzed by spoligotyping (spacer oligonucleotide typing) and MIRU-VNTR (Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat). Drug resistance was evaluated using the Anyplex™ II MTB/MDR/XDR assay. RESULTS: The predominant spoligotypes observed were X1 (SIT 119, n = 46), T1 (SIT 53, n = 40), H3 (SIT 50, n = 13), Beijing (SIT 1, n = 11), and EAI2-Manila (SIT 19, n = 8). MIRU-VNTR analysis showed that the locus QUB-26 had the highest allelic variability. The observed drug resistance included monoresistance to rifampicin (2.6%; n = 5), isoniazid (3.2%; n = 6), and fluoroquinolones (1.6%; n = 3) as well as multidrug resistance (5.3%; n = 10). All of the Beijing strains were susceptible. Regarding comorbidities, 13.7% (26/190) of the patients were co-infected with TB and HIV (TB+HIV+), and 31.6% (55/190) had TB along with diabetes (TB + diabetes). CONCLUSIONS: The most prevalent lineages were X1 (SIT 119; 24.3%) and T1 (SIT 53; 21%). An alarming proportion (12.6%) of M. tuberculosis isolates presented drug resistance. To effectively manage TB, continuous surveillance of regional strain dissemination, drug resistance profiles, and TB-associated comorbidities is crucial.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

Changes in the natural killer cell repertoire and function induced by the cancer immune adjuvant candidate IMMUNEPOTENT-CRP.

Natural killer (NK) cells are CD3-, CD16+, CD56+ that play a crucial role in immune response by recognizing and eliminating a variety of virus-infected, malignant, and antibody-coated target cells. We examined activation; repertoire changes and effector functions of human NK cells normal donors treated with IMMUNEPOTENT-CRP (I-CRP), a bovine dialyzable leukocyte extract (DLE) containing a mixture of low molecular weight molecules. I-CRP induces human NK cells activation and increase CD56Dim CD16- subset, without inducing proliferation. Human NK cells showed an increase on NKp30, NKp44, NKp46, NKG2D, NKG2C and KIR receptors, whereas no significant differences on CD160, CD85j and CD226 where observed. I-CRP-treated human NK cells exhibited an increased degranulation activity against K562 target cells, as shown by CD107a assay, and this correlates with cytotoxicity against K562 cells observed in calcein release assay. These results indicate that I-CRP can modify human NK cells receptor repertoire leading to an increased cytotoxic activity, supporting evidence for its use to stimulate NK cells.

Síndrome de la boca ardiente: revisión de la literatura / Burning mouth syndrome: literature review

Resumen El síndrome de la boca ardiente (SBA) es una condición de dolor crónico en la cavidad oral, que se presenta mayoritariamente en mujeres de edad media. Diversas causas locales y sistémicas pueden producirlo en forma secundaria, o bien, puede representar un cuadro primario, sin etiología específica identificable. Su etiopatogenia y evolución clínica es poco comprendida. Las opciones terapéuticas son variadas y en general es necesario un tratamiento multidisciplinario. A continuación, se presenta una revisión de la literatura respecto a esta patología para difusión en nuestro medio.

Abstract Burning mouth syndrome (BMS) is a chronic pain condition of the oral cavity, which occurs more frequently in middle-aged women. It can be secondary to different local and systemic causes, or represent a primary condition, with no specific identifiable etiology. Its etiopathogenesis and clinical evolution are poorly understood. Therapeutic options are multiple and a multidisciplinary treatment is necessary. We present a review of the literature regarding BMS, to provide information relevant to our area of expertise.

A nonrandomized phase 2 trial of oral thymic peptides in hospitalized patients with Covid-19

BackgroundCoronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. MethodsWe conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparison based on standard care from registry data was performed after propensity score matching. The primary outcomes were survival, time to recovery and the number of participants with treatment-related adverse events or side effects by day 20. ResultsA total of 44 patients were analyzed in this study, 22 in the thymic peptides group and 22 in the standard care group. There were no deaths in the intervention group, compared to 24% mortality in standard care by day 20 (log-rank P=0.02). The Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptides group as compared with standard care (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ConclusionIn patients hospitalized with Covid-19, the use of thymic peptides reported no side effects, adverse events, or deaths by day 20. When compared with registry data, a significantly shorter time to recovery and mortality reduction was measured. The Catholic University of Honduras Medical Research Group (GIMUNICAH) is working on a more extensive phase 3 trial. Trial registrationClinicalTrials.gov NCT04771013. February 25, 2021.

Electroencefalograma cuantitativo en la predicción precoz de la isquemia cerebral tardía en hemorragia subaracnoidea aneurismática: reporte de un caso / Quantitative electroencephalogram for prediction of delayed ischemia in subarachnoid haemorrhage: report of one case

Subarachnoid hemorrhage (SAH) is a devastating disease, with a mortality rate of 35%. Among patients who survive the initial bleeding, the leading cause of morbidity and mortality is delayed cerebral ischemia (DCI). Electroencephalography (EEG) can detect cerebral ischemia in the early stages. We report a 66-year-old female patient who consulted for ictal headache and impaired consciousness. On admission, she was confused, dysarthric, and with meningeal signs. Brain angio-CT showed SAH FISHER IV and an aneurysm of the left posterior cerebral artery. After excluding the aneurysm (by coiling), the patient recovered the altered consciousness. Continuous EEG monitoring was initiated. On the sixth day of follow up, she had a transient headache and apathy. The brain MRI showed low cerebral blood flow in the left frontotemporal area, without ischemic lesions. On the seventh day, she presented expression aphasia and right facial-brachial paresis. Angiography confirmed severe vasospasm in M1 and M2 segments bilaterally. Pharmacological angioplasty with nimodipine was performed, with an excellent radiological response, although not clinical. A second MRI was carried out on the eighth day, which showed a left insular infarction and generalized vasospasm. A second therapeutic angiography was performed; the patient persisted with aphasia and left central facial paresis. The quantitative EEG analysis performed retrospectively showed a generalized reduction in the spectral edge frequency 95 (SEF95; meaning slowing in the EEG signal) at the fourth day of follow up, three days earlier than the clinical and imaging diagnosis of DCI was established.

[Tolerability and adverse effects of propofol in the Wada test]. / Tolerabilidad y efectos adversos del propofol en la prueba de Wada.

INTRODUCTION: The Wada test consists of the selective and reversible inhibition of a cerebral hemisphere by intracarotid injection of amobarbital in order to evaluate the laterality of language and memory. However, there are other anesthetic drugs such as propofol, as an alternative for the test. OBJECTIVE: The objective of the study was to describe the tolerability and adverse effects (AE) of the use of propofol for the Wada test, during the presurgical study of patients with drug-resistant epilepsy. METHODS: Consecutive patients with a diagnosis of drug-resistant structural epilepsy were selected who underwent the Wada test during the pre-surgical study in the period from June 2012 to May 2019. The patients were retrospectively evaluated. The AE were described according to the Mikuni classification, modified by Curot. The variables of sex, age, epileptic foci laterality, language laterality, lesional substrate, etiology and dose of administered Propofol were analyzed for any statistical significance. RESULTS: A total of 74 patients, 40 men (54%), were studied. Forty-seven patients (63.5%) had at least one AE. The mean dose of propofol was 9.23 mg. The most frequent AE were tearing, sweating and red eye, corresponding to group I (57%). One patient developed convulsive status epilepticus, an important AE not previously described during the Wada test. CONCLUSION: Performing the Wada test with propofol causes frequent mild adverse effects, which do not prevent its completion. We describe a case of convulsive status epilepticus as the only serious AE.

TITLE: Tolerabilidad y efectos adversos del propofol en la prueba de Wada.Introducción. La prueba de Wada consiste en la inhibición selectiva y reversible de un hemisferio cerebral mediante la inyección intracarotídea de amobarbital con el objetivo de evaluar la lateralidad del lenguaje y la memoria. Existen otros fármacos anestésicos, como el propofol, como alternativa para la prueba. Objetivo. El objetivo del estudio fue describir la tolerabilidad y los efectos adversos (EA) del uso de propofol para la prueba de Wada durante el estudio prequirúrgico de pacientes con epilepsia farmacorresistente. Pacientes y métodos. Se seleccionó a pacientes con diagnóstico de epilepsia estructural farmacorresistente consecutivos, quienes se sometieron a la prueba de Wada durante el estudio prequirúrgico en el período de junio de 2012 a mayo de 2019. Los pacientes fueron evaluados de manera retrospectiva. Los EA se describieron según la clasificación de Mikuni, modificada por Curot. Se analizaron las variables de sexo, edad, lateralidad del foco epiléptico, lateralidad del lenguaje, sustrato lesional, etiología y dosis de propofol administrada en busca de significación estadística. Resultados. Se estudió a un total de 74 pacientes, de los cuales 40 eran hombres (54%). Cuarenta y siete pacientes (63,5%) tuvieron al menos un EA. La dosis media de propofol fue de 9,23 mg. Los EA más frecuentes fueron lagrimeo, sudoración y ojo rojo, correspondientes al grupo I (57%). Un paciente desarrolló estado epiléptico convulsivo, EA importante no descrito anteriormente durante la prueba de Wada. Conclusión. La realización de la prueba de Wada con propofol ocasiona frecuentes efectos adversos leves, los cuales no impiden su finalización. Describimos un caso de estado epiléptico convulsivo como único EA grave.

Short-term neuropsychiatric outcomes and quality of life in COVID-19 survivors.

BACKGROUND: The general medical impacts of coronavirus (COVID-19) are increasingly appreciated. However, its impact on neurocognitive, psychiatric health and quality of life (QoL) in survivors after the acute phase is poorly understood. We aimed to evaluate neurocognitive function, psychiatric symptoms and QoL in COVID-19 survivors shortly after hospital discharge. METHODS: This was a cross-sectional analysis of a prospective study of hospitalized COVID-19 survivors followed up for 2 months after discharge. A battery of standardized instruments evaluating neurocognitive function, psychiatric morbidity and QoL (mental and physical components) was administered by telephone. RESULTS: Of the 229 screened patients, 179 were included in the final analysis. Amongst survivors, the prevalence of moderately impaired immediate verbal memory and learning was 38%, delayed verbal memory (11.8%), verbal fluency (34.6%) and working memory (executive function) (6.1%), respectively. Moreover, 58.7% of patients had neurocognitive impairment in at least one function. Rates of positive screening for anxiety, depression and post-traumatic stress disorder were 29.6%, 26.8% and 25.1%, respectively. In addition, 39.1% of the patients had psychiatric morbidity. Low QoL for physical and mental components was detected in 44.1% and 39.1% of patients respectively. Delirium and psychiatric morbidity were associated with neurocognitive impairment, and female gender was related with psychiatric morbidity. CONCLUSION: Hospitalized COVID-19 survivors showed a considerable prevalence of neurocognitive impairment, psychiatric morbidity and poor QoL in the short term. It is uncertain if these impacts persist over the long term.