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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.

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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.

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INTRODUCCIÓN: Las disecciones de arterias cervicales (DAC) son la primera causa de accidente cerebrovascular isquémico (ACVi) en personas jóvenes. Los factores asociados (FA) de ACVi y la relación temporal con la DAC no están bien caracterizados. Tampoco disponemos de una clasificación clínico-radio-lógica que permita conocer el riesgo de ACVi. OBJETIVO: Describir frecuencia y FA y temporalidad de los ACVi en pacientes con DAC. MÉTODOS: Estudio prospectivo de pacientes mayores de 18 años hospitalizados por una DAC carotidea y/o vertebral entre agosto de 2009 y junio de 2017. Las DAC se diagnosticaron clínico-radiológicamente y los ACVi con imagen con infarto. Se utilizo la Clasificación de Borgess para caracterizar radiológicamente las DAC. Se utilizaron análisis de regresión logística uni y multivariable para evaluar las características clínico-radiológicas y los FA. RESULTADOS: 163 pacientes con 182 DAC (60% vertebrales y 40% carotídeas). 73 pacientes (44,8%) tuvieron un ACVi 28 de 68 pacientes (41,2%) tuvieron simultáneamente síntomas de disección y de isquemia. 60 de 68 pacientes (88%) presentan síntomas de isquemia durante la primera semana. FR significativamente asociados a ACVi: Borgess tipo IB (p = 0,001; OR: 4,1; IC: 1,8-9,3), sexo masculino (p < 0,001; OR: 0,2; IC: 0,06-0,8) y anticonceptivos orales (p = 0,02; OR: 0,2; IC: 0,06-0,8). CONCLUSIÓN: Ocurre aproximadamente en la mitad de los pacientes, en su mayoría dentro de la primera semana, no es la forma habitual de presentación inicial y no se relaciona con el tipo de arteria disecada. El principal FA para desarrollar un ACVi fue la oclusión arterial (Borgess tipo IB).

INTRODUCTION: Cervical artery dissections (CAD) are the leading cause of ischemic stroke (CVA) in young people. The risk factors for stroke and the temporal relationship with CAD are not well characterized. Nor do we have a clinical-radiological classification that allows knowing the risk of stroke. OBJECTIVE: To describe the associated factors and temporality of ACVi in patients with CAD. METHODS: We performed a prospective study that included patients over 18 years of age, hospitalized for carotid and/or vertebral CAD between August 2009 and June 2017. CAD cases were diagnosed clinically and radiologically; ACVi was diagnosed when the imaging study demonstrated infarction. The Borgess Classification was used to characterize the CAD radiologically. For correlation studies, we used univariate and multivariate logistic regression analyses. RESULTS: We analyzed 163 patients with 182 CAD (60% vertebral and 40% carotid). 28 of 68 patients (41.2%) simultaneously had symptoms of dissection and ischemia. 60 of 68 patients (88%) presented symptoms of ischemia during the first week. CAD: Borgess type IB (p = 0.001; OR: 4.1; CI: 1.8-9.3), male (p < 0.001; OR: 0.2; CI: 0.06- 0.8) were significantly associated with ischemic strokes and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8). CONCLUSION: Stroke associated with CAD has a relatively low frequency. It is not related to the type of dissected artery. It mainly occurs not simultaneously with CAD and within the first week. The main associated factor for developing a stroke is arterial occlusion (Borgess type IB).1,8-9,3), male sex (p < 0.001; OR: 0.2; CI: 0.06-0.8) and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8).

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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.

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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.

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INTRODUCTION: Cervical artery dissections (CAD) are the leading cause of ischemic stroke (CVA) in young people. The risk factors for stroke and the temporal relationship with CAD are not well characterized. Nor do we have a clinical-radiological classification that allows knowing the risk of stroke. OBJECTIVE: To describe the associated factors and temporality of ACVi in patients with CAD. METHODS: We performed a prospective study that included patients over 18 years of age, hospitalized for carotid and/or vertebral CAD between August 2009 and June 2017. CAD cases were diagnosed clinically and radiologically; ACVi was diagnosed when the imaging study demonstrated infarction. The Borgess Classification was used to characterize the CAD radiologically. For correlation studies, we used univariate and multivariate logistic regression analyses. RESULTS: We analyzed 163 patients with 182 CAD (60% vertebral and 40% carotid). 28 of 68 patients (41.2%) simultaneously had symptoms of dissection and ischemia. 60 of 68 patients (88%) presented symptoms of ischemia during the first week. CAD: Borgess type IB (p = 0.001; OR: 4.1; CI: 1.8-9.3), male (p < 0.001; OR: 0.2; CI: 0.06- 0.8) were significantly associated with ischemic strokes and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8). CONCLUSION: Stroke associated with CAD has a relatively low frequency. It is not related to the type of dissected artery. It mainly occurs not simultaneously with CAD and within the first week. The main associated factor for developing a stroke is arterial occlusion (Borgess type IB).1,8-9,3), male sex (p < 0.001; OR: 0.2; CI: 0.06-0.8) and oral contraceptives (p = 0.02; OR: 0.2; CI: 0.06-0.8).

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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.

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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.

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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.

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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.

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