Integrative single-cell expression and functional studies unravels a sensitization to cytarabine-based chemotherapy through HIF pathway inhibition in AML leukemia stem cells.

Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML) and is driven by rare therapy-resistant leukemia stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling maintains cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hypothesis that hypoxia contributes to the chemoresistance of AML-LSCs and may represent a therapeutic target to sensitize AML-LSCs to chemotherapy. Here, we identify HIFhigh and HIFlow specific AML subgroups (inv(16)/t(8;21) and MLLr, respectively) and provide a comprehensive single-cell expression atlas of 119,000 AML cells and AML-LSCs in paired diagnostic-relapse samples from these molecular subgroups. The HIF/hypoxia pathway signature is attenuated in AML-LSCs compared with more differentiated AML cells but is more expressed than in healthy hematopoietic cells. Importantly, chemical inhibition of HIF cooperates with standard-of-care chemotherapy to impair AML growth and to substantially eliminate AML-LSCs in vitro and in vivo. These findings support the HIF pathway in the stem cell-driven drug resistance of AML and unravel avenues for combinatorial targeted and chemotherapy-based approaches to specifically eliminate AML-LSCs.

Trigeminal neuralgia secondary to epidermoid cyst and neurovascular conflict: An illustrative case with literature review.

Background: Trigeminal neuralgia (TN) is a highly disabling facial pain syndrome, historically known as the suicide disease, in which most cases can be cured with appropriate surgical treatment. Case Description: We present the case of a 43-year-old male farmer with acute, self-limiting episodes of shock-like pain on the left side of the face that started in June of 2021. He was diagnosed with TN and was treated with carbamazepine. Magnetic resonance imaging was performed, which revealed an epidermoid cyst (EC) at the prepontine cistern with an extension to the left cerebellopontine angle. The neurosurgery department at our institution was consulted, which performed surgical tumor resection and Vth cranial nerve decompression. During the resection, a neurovascular conflict (NVC) was identified at the root entry zone. After the resection around the nerve and its whole tract was completed, a microvascular decompression (MVD) was performed. Conclusion: TN secondary to EC in association with a NVC is a rare phenomenon, due to the growth pattern of the EC. TN may remit if an appropriate treatment is carried out. In cases of NVC, an MVD is required apart from an appropriate resection to achieve pain relief.

Impact and evolution of risk factors associated with hospitalization and mortality due to COVID-19 during the six epidemic waves in Mexico.

Objectives: This study aims to analyze and compare the main risk factors for hospitalization and deaths due to COVID-19 during the six epidemic waves from February 2020 to June 2023 in Mexico. Methods: First, a descriptive analysis of the risk factors that led to hospitalization and mortality due to COVID-19 was performed. Next, the degree of relationship of each risk factor with hospitalization and death was determined using Cramer's V coefficient. Finally, logistic regression models were applied to estimate the odds ratios of the most statistically significant risk factors for hospitalization and mortality. Results: A direct relationship between age and the possibility of hospitalization and death due to COVID-19 was found. Moreover, the comorbidities most likely to lead to hospitalization and death were pneumonia, hypertension, diabetes, obesity and CKD. It is also remarkable that the second factor of death is endotracheal intubation. Conclusion: The COVID-19 pandemic in Mexico revealed the reality of an epidemiological scenario where infectious diseases and chronic degenerative diseases coexist and interrelate.

A Retrospective Analysis of High Resolution Ultrasound Evaluation of the "Split Fat Sign" in Peripheral Nerve Sheath Tumors.

Peripheral nerve sheath tumors (PNST) comprise schwannomas and neurofibromas. The finding of increased adipose tissue around benign PNSTs has been described as the "split fat sign" on magnetic resonance imaging exams, which is suggestive of an intramuscular or intermuscular location of the tumor. However, few studies have described this sign as a salient ultrasound feature of PNSTs. The main purpose of this study was to retrospectively evaluate the presence of increased fatty tissue deposition around benign PNSTs diagnosed by high-resolution ultrasound. In addition, we aimed to corroborate the presence of vascularization around the affected area. A retrospective analysis of ten cases of PNSTs and two cases of post-traumatic neuromas diagnosed by high-resolution ultrasound was performed with a Logiq® P8 ultrasound with a 2-11 MHz multifrequency linear probe L3-12-D (central frequency: 10 MHz). Localized types of neurofibromas and schwannomas in any location were seen as predominantly hypoechoic tumors with an oval or fusiform shape. Exiting and entering nerves (tail sign) were observed in six cases, showing localized lesions both in intermuscular and subcutaneous locations. The presence of increased hyperechoic tissue (the split fat sign) was noted in cases of solitary intermuscular and intramuscular peripheral nerve sheath tumors, mainly the schwannomas. Though small tumors did not demonstrate the tail sign, the increase in adipose tissue and vascularity on US was well demonstrated. In conclusion, the nerve in continuity forms the basis of the ultrasonographic diagnosis of PNSTs. However, high-resolution US can convincingly demonstrate the increased presence of fat in the upper and lower poles as well as circumferentially in intermuscular or intramuscular benign PNSTs.

Generation of glucocorticoid-producing cells derived from human pluripotent stem cells.

Adrenal insufficiency is a life-threatening condition resulting from the inability to produce adrenal hormones in a dose- and time-dependent manner. Establishing a cell-based therapy would provide a physiologically responsive approach for the treatment of this condition. We report the generation of large numbers of human-induced steroidogenic cells (hiSCs) from human pluripotent stem cells (hPSCs). Directed differentiation of hPSCs into hiSCs recapitulates the initial stages of human adrenal development. Following expression of steroidogenic factor 1, activation of protein kinase A signaling drives a steroidogenic gene expression profile most comparable to human fetal adrenal cells, and leads to dynamic secretion of steroid hormones, in vitro. Moreover, expression of the adrenocorticotrophic hormone (ACTH) receptor/co-receptor (MC2R/MRAP) results in dose-dependent ACTH responsiveness. This protocol recapitulates adrenal insufficiency resulting from loss-of-function mutations in AAAS, which cause the enigmatic triple A syndrome. Our differentiation protocol generates sufficient numbers of hiSCs for cell-based therapy and offers a platform to study disorders causing adrenal insufficiency.

Microvascular decompression for hemifacial spasm: Complications after 292 procedures without neurophysiological monitoring.

Background: Hemifacial spasm (HFS) is characterized by involuntary, progressive, and intermittent spasms in the upper and lower facial muscles. Due to the high success rate, microvascular decompression (MVD) is the treatment of choice, and intraoperative neuromonitoring (INM) is considered useful for achieving safe surgery. Still, most centers do not have this technology. Methods: We analyzed 294 patients with HFS treated with MVD without INM. We only included patients with a neurovascular etiology while excluding other causes, such as tumors. As part of the postoperative evaluation, we assessed preoperative magnetic resonance imaging and pure-tone audiometry. Results: The main complication was peripheral facial paralysis in 50 patients, followed by hypoacusis in 22 patients and deafness in 17 patients, associated with a failed surgical outcome (P = 0.0002). The anterior inferior cerebellar artery (AICA) was an offending vessel, and the involvement of more than one vessel was significantly associated with the development of facial nerve palsy (P = 0.01). AICA was also associated with hearing impairment (P = 0.04). Over 90% of immediate complications improve in the follow-up (6 months), and one patient did not show a cure for initial HFS. Conclusion: MVD is the method with the highest long-term cure rates for treating HFS; however, we must inquire into the multiple factors of the patient and the surgeon to predict surgical outcomes. INM is not a must during MVD for HFS. We recommend its use depending on the availability and mainly on the surgeon's skills, for surgeons.

Lung Function and Asthma Clinical Control in N-ERD Patients, Three-Year Follow-Up in the Context of Real-World Evidence.

Purpose: To describe the lung function and clinical control of asthma in patients with N-ERD during three years of medical follow-up using GINA guidelines. Methods: We evaluated 75 N-ERD and 68 asthma patients (AG). Clinical control, lung function, and asthma treatment were evaluated according to GINA-2014. We compared all variables at baseline and one, two, and three years after treatment. Results: At baseline, the N-ERD group had better basal lung function (LF) than the AG group (p<0.01), and the AG group used higher doses of inhaled corticosteroids than the N-ERD group (52.4% vs 30.5%, p=0.01) and short-term oral corticosteroid (OCS) use (52.4% vs 30.5%, p<0.01). Instead, N-ERD patients needed more use of leukotriene receptor antagonists (LTRA) (29.3% vs 5.9%, p<0.01). This group had better clinical control than the AG group (62.1% vs 34.1%, p<0.01). During the medical follow-up, the LF of the N-ERD group remained at normal values; however, these parameters improved in AG from one year (p<0.01). Likewise, there was a diminished use of high doses of ICS (52.4% vs 33%, p<0.05) and short-term OCS (67.6% vs 20.6%, p<0.01) in asthma patients. However, N-ERD patients still needed more use of LTRAs (p<0.02) during the study. In this context, one-third of N-ERD patients had to use a combination of two drugs to maintain this control. From the second year on, clinical control of asthma was similar in both groups (p>0.05). Conclusion: According to GINA guidelines, only one-third of patients with N-ERD can gradually achieve adequate lung function and good asthma control with a high ICS dosage. Only a very small portion of patients will require the continued use of a second medication as an LTRA to keep their asthma under control.

Glossopharyngeal and vagoglossopharyngeal neuralgia: Long-term surgical outcomes in a single institution.

Background: Glossopharyngeal neuralgia (GPN) and vagoglossopharyngeal neuralgia (VGPN) are infrequent syndromes that can have great negative impact on a patient's quality of life. The objective of this study is to describe the characteristics and long-term results of patients with GPN-VGPN who are treated surgically with microvascular decompression (MVD) in one institution. Methods: This is a retrospective series of 20 patients with the diagnosis of GPN-VGPN who underwent MVD. Demographic characteristics, surgical results, complications, and long-term follow-up were analyzed. Results: The mean age of symptom onset was 51.25 years and the majority of patients were women (60%). The posterior inferior cerebellar artery was the main offending vessel (75%). The immediate MVD success rate was 100%, but during follow-up, two patients (10%) were diagnosed with VGPN and both cases presented pain recurrence. The mean follow-up was 120.4 (25-333) months. VGPN (P = 0.005) and a ≥5 day hospital stay (P = 0.032) were associated with unsuccessful outcomes. Two complications were documented, which resolved without sequelae. There was no surgical mortality. Conclusion: MVD is an effective and safe treatment for long-term pain relief of GPN-VGPN. VGPN and a prolonged hospital stay were associated with poor outcomes. More studies are required to confirm these findings.

[DRESS syndrome induced by anti-TB drugs]. / Síndrome de DRESS inducido por fármacos antituberculosos.

OBJETIVE: To describe the phenotype of DRESS syndrome induced by antituberculosis drugs. METHODS: Descriptive study, withdrawn from the review of the records of patients with DRESS syndrome, identified in the interconsultation of the Department of Research in Immunogenetics and Allergy, of the Insti-tuto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, among 2014 and 2020. Frequency analysis was performed. The associations between biomarkers and latency are calculated with the χ2 test and log-rank, and the evaluation of the change in the biomarkers with the Wilcoxon test. The value of p < 0.05 is considered statistically significant. For data analysis, the SPSS v.21 program was obtained. RESULTS: 15 patients were identified; represented by 0.02% of total cases treated in the Department for so-meimmuno-allergic condition (15/7052); the main symptomatology were: rash (100%), eosinophilia (93%), fe-ver (80%), adenomegaly (60%), kidney damage (40%), liver damage (33%), and latency of 21 days. Liver damage was associated with prolonged latency (p = 0.02). After treatment, the total levels of eosinophils (p < 0.001) and liver and kidney biomarkers (p < 0.04) decreased. DRESS syndrome induced by antituberculosis drugs is not associated with the number of drugs prescribed or with the pattern of resistance of Mycobacterium tuberculosis. CONCLUSIONS: DRESS syndrome induced by antituberculosis drugs is an atypical clinical reaction, similar to other types of DRESS syndrome that respond favorably to systemic corticosteroids.

OBJETIVO: Describir el fenotipo del síndrome de DRESS inducido por fármacos antituberculosos. MÉTODOS: Estudio descriptivo efectuado a partir de la revisión de los expedientes de pacientes con síndrome de DRESS, identificados en la interconsulta del Departamento de Investigación en Inmunogénetica y Alergia, del Instituto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, entre 2014 y 2020. Se realizó análisis de frecuencias. Las asociaciones entre biomarcadores y latencia se calcularon con la prueba de χ2 y log-rank, y la evaluación del cambio en los biomarcadores con la prueba de Wilcoxon. Se consideró esta-dísticamente significativo el valor de p < 0.05. Para el análisis de los datos se utilizó el programa SPSS v.21. RESULTADOS: Se identificaron 15 pacientes, que representaron el 0.2% de los casos atendidos en el Departa-mento por algún padecimiento inmuno-alérgico (15/7052); las principales manifestaciones fueron: exantema (100%), eosinofilia (93%), fiebre (80%), adenomegalia (60%), daño renal (40%), daño hepático (33%) y latencia de 21 días. El daño hepático se asoció con latencia prolongada (p = 0.02). Posterior al tratamiento disminu-yeron las concentraciones totales de eosinófilos (p < 0.001) y biomarcadores hepáticos y renales (p < 0.04). El síndrome de DRESS inducido por fármacos antituberculosos no se asoció con la cantidad de fármacos prescritos ni con el patrón de resistencia de Mycobacterium tuberculosis. CONCLUSIONES: El síndrome de DRESS inducido por fármacos antituberculosos es una reacción clínica atípica, similar a otros tipos de síndrome de DRESS que responden favorablemente a corticosteroides sisté-micos.

Risk Factors Associated With Neurological and Extra-Neurological Complications and Mortality in Patients With Stroke.

Introduction Understanding when and how systemic complications can occur after an acute stroke is crucial. It is important to identify patients who are at higher risk for these complications. Early and effective treatment based on this knowledge can significantly improve patient outcomes. The objective of this study was to identify the risk factors associated with neurological and extra-neurological complications and mortality in stroke patients treated at a secondary care hospital. Methods Of a total of 170 patients diagnosed with hemorrhagic/ischemic stroke and transient cerebral ischemia at a secondary care hospital in Mexico, the records of 125 were reviewed and of these, 86 were included in the study. The study group comprised 86 adult patients (> 18 years of age) diagnosed with ischemic or hemorrhagic stroke or transient cerebral ischemia. Their demographics, clinical characteristics, in-hospital complications, and mortality were retrospectively analyzed.  Results Of the 86 patients examined, 34.9% experienced complications, regardless of the type of stroke. The most significant factor associated with mortality and complications during hospitalization in patients with stroke was previous diseases. Other factors that were linked to higher mortality were pre-existing medical conditions. The most common neurological complication among patients with stroke during hospitalization was intracranial hypertension (3.5%). As for extra-neurological complications, pressure ulcers and nosocomial pneumonia had an occurrence rate of 4.7%. Conclusions The main neurological complication during hospitalization of patients with stroke was intracranial hypertension, while the extra neurological complications were pressure ulcers and nosocomial pneumonia.

Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future.

The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and Tezepelumab have been approved. These biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they can improve the quality of life of many patients. Given the success in asthma, these drugs have been used in other diseases with type 2 inflammation, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and chronic urticaria. Like the Th2-type cytokines, chemokines have also been the target of novel monoclonal therapies. However, they have not proved successful to date. In this review, targeted therapy is addressed from its inception to future applications in allergic diseases.

Influencia del ciclo menstrual en el rendimiento físico y cognitivo en mujeres eumenorreicas / Influence of the menstrual cycle on physical and cognitive performance in eumenorrheic women

Introducción: Las hormonas sexuales femeninas propias del ciclo menstrual no solo tienen funciones reproductivas, tambiéninfluyen en otros sistemas fisiológicos pudiendo afectar al rendimiento deportivo y cognitivo. El propósito del presente estudioha sido evaluar distintos aspectos como la composición corporal, la resistencia, la fuerza muscular y algunas capacidadescognitivas en diferentes etapas del ciclo menstrual. Material y método: En el estudio participaron ocho mujeres jóvenes eumenorreicas (edad = 23,1 ± 4,4 años) con ciclosmenstruales regulares. Se realizó una prueba de densitometría y una bioimpedancia para estudiar la composición corporal, unaprueba de memoria visual a corto plazo y un test de tiempo de reacción para evaluar habilidades cognitivas y se analizaroncaracterísticas del músculo (grosor y rigidez del recto anterior y fuerza muscular) junto a una prueba de esfuerzo para evaluarel rendimiento durante las fases folicular media (FF) y lútea media (FL) del ciclo menstrual de las participantes. Resultados: Durante la fase folicular las participantes registraron un mayor tiempo total (FF = 488,5 ± 93,18 s vs. FL = 468,6± 81,29 s; p = 0,015) y una frecuencia cardiaca inicial menor (FF = 83,3 ± 10,23 PPM vs. FL = 92,9 ± 7,67 PPM; p = 0,034) en laprueba de esfuerzo. Además, Respecto a las habilidades cognitivas, en la fase folicular se obtuvieron mejores resultados enel tiempo de reacción tanto con la mano derecha (FF = 0,426 ± 0,082 s vs. FL = 0,453 ± 0,087 s; p = 0,036) como con la manoizquierda (FF = 0,435 ± 0,096 s vs. FL = 0,466 ± 0,077 s; p = 0,034). Por otro lado, se encontró un mayor porcentaje de grasa(FF = 27,3 ± 5,1% vs. FL = 27,9 ± 5,0%; p = 0,041) en la fase lútea. Conclusión: El rendimiento en resistencia y en aspectos cognitivos como es el tiempo de reacción fue mejor en la FaseFolicular mientras que se observó un mayor porcentaje de grasa en la Fase Lútea. Sin embargo, la memoria, la fuerza y lascaracterísticas...(AU)

Introduction: The female sexual hormones typical of the menstrual cycle not only have reproductive functions, they alsoinfluence other physiological systems and can affect sports and cognitive performance. The purpose of this study has beento evaluate different aspects such as body composition, endurance, muscle strength and some cognitive abilities at differentstages of the menstrual cycle. Material and method: Eight young eumenorrheic women (age = 23.1 ± 4.4 years) with regular menstrual cycles participatedin the study. A densitometry and bioimpedance test were performed to study body composition, a short-term visual memorytest and a reaction time test to assess cognitive abilities, and muscle characteristics (thickness and stiffness of the anteriorrectus and muscle strength) along with a progressive test to exhaustion were analyzed to assess performance during themid-follicular (FF) and mid-luteal (FL) phases of the participants’ menstrual cycle. Results: During the follicular phase, the participants registered a greater total time (FF = 488.5 ± 93.18 s vs. FL = 468.6 ± 81.29 s;P = 0.015) and a lower initial heart rate (FF = 83.3 ± 10.23 PPM vs. FL = 92.9 ± 7.67 PPM; P = 0.034) in the progressive test toexhaustion. Regarding cognitive abilities, in the follicular phase, better results were obtained in reaction time both with theright hand (FF = 0.426 ± 0.082 s vs. FL = 0.453 ± 0.087 s; P = 0.036) and with the left hand (FF = 0.435 ± 0.096 s vs. FL = 0.466 ±0.077 s; P = 0.034). On the other hand, a higher percentage of fat (FF = 27.3 ± 5.1% vs. FL = 27.9 ± 5.0%; P = 0.041) was foundin the luteal phase. Conclusion: Performance in endurance and in cognitive test, such as reaction time was better in the Follicular Phase, whilea higher percentage of fat was observed in the Luteal Phase. However, memory, strength and muscular characteristics werenot affected by the hormonal fluctuations of the menstrual cycle.(AU)

Surrogate-Assisted and Filter-Based Multiobjective Evolutionary Feature Selection for Deep Learning.

Feature selection (FS) for deep learning prediction models is a difficult topic for researchers to tackle. Most of the approaches proposed in the literature consist of embedded methods through the use of hidden layers added to the neural network architecture that modify the weights of the units associated with each input attribute so that the worst attributes have less weight in the learning process. Other approaches used for deep learning are filter methods, which are independent of the learning algorithm, which can limit the precision of the prediction model. Wrapper methods are impractical with deep learning due to their high computational cost. In this article, we propose new attribute subset evaluation FS methods for deep learning of the wrapper, filter and wrapper-filter hybrid types, where multiobjective and many-objective evolutionary algorithms are used as search strategies. A novel surrogate-assisted approach is used to reduce the high computational cost of the wrapper-type objective function, while the filter-type objective functions are based on correlation and an adaptation of the reliefF algorithm. The proposed techniques have been applied in a time series forecasting problem of air quality in the Spanish south-east and an indoor temperature forecasting problem in a domotic house, with promising results compared to other FS techniques used in the literature.

DRESS, una reacción alérgica no mediada por IgE / DRESS, a Non-IgE Mediated Allergic Reaction

Resumen El síndrome de reacción a medicamentos con eosinofilia y síntomas sistémicos (DRESS, por sus siglas en inglés) es una respuesta de hipersensibilidad multisistémica poco frecuente inducida por uno o varios medicamentos que puede inducir una reacción adversa cutánea grave, la cual es difícil de diagnosticar y pone en peligro la vida del paciente si no es identificada y no se recibe tratamiento. Frecuentemente, se manifiesta como una erupción cutánea amplia, linfadenopatía, signos de afectación de órganos viscerales y alteraciones hematológicas, como leucocitosis, eosinofilia y, en ocasiones, linfocitosis atípica que se presentan de 2 a 8 semanas posterior a la administración del fármaco responsable. Los medicamentos responsables con mayor número de reportes son la fenitoína, la carbamazepina, el alopurinol y el abacavir. Se han identificado algunos alelos específicos del antígeno leucocitario humano (HLA) que se asocian a la hipersensibilidad de estos fármacos. La fisiopatología del síndrome de DRESS aún no se conoce por completo, generalmente se trata de una respuesta de hipersensibilidad mediada por células T, al interactuar con el receptor del complejo principal de histocompatibilidad en individuos con factores de susceptibilidad genética, como ocurre en otros cuadros de reacciones graves secundarias a la ingesta de fármacos. Los criterios del European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) son los más utilizados para su diagnóstico. El síndrome de hipersensibilidad inducido por fármacos (DiHS), el síndrome de Stevens-Johnson (SSJ), la necrólisis epidérmica tóxica (NET), y la pustulosis exantemática generalizada aguda (PEGA) deben considerarse ante cualquier exantema que aparezca posterior a la administración de cualquier fármaco. La terapia incluye la eliminación del agente causal lo antes posible, así como los corticosteroides sistémicos, los cuales son los pilares del tratamiento.. Los agentes ahorradores de esteroides, como la ciclosporina, las inmunoglobulinas intravenosas (IVIGs) y otros agentes inmunosupresores, se han utilizado con éxito para contribuir al tratamiento.

Abstract DRESS (drug reaction syndrome with eosinophilia and systemic symptoms) is a rare drug-induced multisystemic hypersensitivity response that can induce a severe cutaneous adverse reaction that is difficult to diagnose and treat. It frequently manifests as an extensive skin rash, systemic symptoms, lymphadenopathy, visceral organ involvement, and hematological alterations, mainly leukocytosis, eosinophilia, and sometimes atypical lymphocytosis that manifest 2 to 8 weeks after continuous administration of the responsible drug. The most prevalent drugs related with this syndrome are phenytoin, carbamazepine, allopurinol, and abacavir. Some specific human leukocyte antigen (HLA) alleles have been identified that are associated with hypersensitivity to these drugs. The pathophysiology of DRESS syndrome is not yet fully understood; the main hypothesis is a T-cell mediated hypersensitivity response when interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. The criteria of the European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) are the most commonly used for the diagnosis of DRESS syndrome. Drug-induced hypersensitivity syndrome (DiHS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) should be considered for any rash that appears following the administration of any drug. Therapy of DRESS includes the elimination of the causative agent as soon as possible, as well as systemic corticosteroids which are the cornerstones of treatment. Steroid-sparing agents such as cyclosporine, intravenous immunoglobulins (IVIGs), and other immunosuppressive agents have been used successfully to contribute to treatment.

Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer.

Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.

Transanal Hemorrhoidal Dearterialization With Mucopexy Versus Vessel-Sealing Device Hemorrhoidectomy for Grade III to IV Hemorrhoids: Long-term Outcomes From the THDLIGA Randomized Controlled Trial.

BACKGROUND: Both transanal hemorrhoidal dearterialization and vessel-sealing device hemorrhoidectomy are safe for grade III to IV hemorrhoid treatment. Whether one of them is superior regarding long-term results remains unclear. OBJECTIVE: To compare long-term results after transanal hemorrhoidal dearterialization and vessel-sealing device hemorrhoidectomy. DESIGN: Multicenter randomized controlled trial. SETTINGS: This study was conducted at 6 centers. PATIENTS: Patients ≥18 years of age with grade III to IV hemorrhoids were included in the study. INTERVENTIONS: Patients were randomly assigned to transanal hemorrhoidal dearterialization (n = 39) or vessel-sealing device hemorrhoidectomy (n = 41). MAIN OUTCOME MEASURES: The primary outcome was hemorrhoid symptom recurrence assessed by a specific questionnaire 2 years postoperatively. Secondary outcomes included long-term complications, reoperations, fecal continence, and patient satisfaction and quality of life. RESULTS: Five of the 80 patients included in the study were lost to follow-up. Thirty-six patients randomly assigned to transanal hemorrhoidal dearterialization and 39 patients randomly assigned to vessel-sealing device hemorrhoidectomy were included in the long-term analysis. The differences between mean baseline and mean 2-year score in the 2 groups were similar (-11.0, SD 3.8 vs -12.5, SD 3.6; p = 0.080). Three patients in the transanal hemorrhoidal dearterialization group underwent supplementary procedures for hemorrhoid symptoms, compared with none in the vessel-sealing device hemorrhoidectomy group ( p = 0.106). Four patients in the vessel-sealing hemorrhoidectomy group and none in the transanal hemorrhoidal dearterialization group experienced chronic opened wound ( p = 0.116). LIMITATIONS: Lack of stratification for hemorrhoid grade and power calculation based on the main outcome trial but not on the end point of this long-term study. CONCLUSIONS: Transanal hemorrhoidal dearterialization with mucopexy is associated with hemorrhoid symptom recurrence similar to vessel-sealing device hemorrhoidectomy at 2 years. See Video Abstract at http://links.lww.com/DCR/B933 . REGISTRATION: Clinicaltrials.gov ; ID: NCT02654249. DESARTERIALIZACIN HEMORROIDAL TRANSANAL CON MUCOPEXIA VERSUS HEMORROIDECTOMA CON DISPOSITIVO DE SELLADO DE VASOS PARA HEMORROIDES DE GRADO IIIIV RESULTADOS A LARGO PLAZO DEL ENSAYO CLNICO ALEATORIZADO THDLIGARCT: ANTECEDENTES:Tanto la desarterialización hemorroidal transanal como la hemorroidectomía con dispositivo de sellado de vasos son seguras y bien toleradas para el tratamiento de las hemorroides de grado III-IV. La primera se asocia con una necesidad más breve de analgesia posoperatoria que la hemorroidectomía con dispositivo de sellado de vasos. No está claro si uno de ellos es superior con respecto a los resultados a largo plazo.OBJETIVO:El objetivo fue comparar los resultados a largo plazo después de la desarterialización hemorroidal transanal y la hemorroidectomía con dispositivo de sellado de vasos.DISEÑO:Se realizó un ensayo clínico aleatorizado multicéntrico.AJUSTE:Este estudio se realizó en 6 centros.PACIENTES:Se incluyeron en el estudio pacientes de ≥18 años con hemorroides de grado III-IV.INTERVENCIONES:Los pacientes fueron asignados al azar a desarterialización hemorroidal transanal (n = 39) o hemorroidectomía con dispositivo de sellado de vasos (n = 41).PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la recurrencia de los síntomas de hemorroides evaluada mediante un cuestionario específico 2 años después de la operación. Los resultados secundarios incluyeron complicaciones a largo plazo, reoperaciones, continencia fecal, satisfacción del paciente y calidad de vida.RESULTADOS:Cinco de los 80 pacientes incluidos en el estudio se perdieron durante el seguimiento. En el análisis a largo plazo se incluyeron 36 pacientes aleatorizados a desarterialización hemorroidal transanal y 39 aleatorizados a hemorroidectomía con dispositivo de sellado de vasos. Las diferencias entre la puntuación inicial media y la puntuación media a los 2 años en los dos grupos fueron similares (-11,0, DE 3,8 frente a -12,5, DE 3,6; p = 0,080). Tres pacientes en el grupo de desarterialización hemorroidal transanal se sometieron a procedimientos complementarios por síntomas de hemorroides, en comparación con ninguno en el grupo de hemorroidectomía con dispositivo de sellado de vasos (p = 0,106). Cuatro pacientes en el grupo de hemorroidectomía con sellado de vasos y ninguno en el grupo de desarterialización hemorroidal transanal experimentaron herida abierta crónica (p = 0,116). No se encontraron diferencias en cuanto a continencia fecal (p = 0,657), satisfacción del paciente (p = 0,483) y calidad de vida.LIMITACIONES:No hay estratificación para el grado de hemorroides ni el cálculo del poder basado en el resultado principal del ensayo, pero no en el criterio de valoración de este estudio a largo plazo.CONCLUSIONES:La desarterialización hemorroidal transanal con mucopexia se asocia con una recurrencia de síntomas de hemorroides similar a la hemorroidectomía con dispositivo de sellado de vasos a los dos años. See Video Abstract at http://links.lww.com/DCR/B933 . (Traducción- Dr. Francisco M. Abarca-Rendon )REGISTRO DE PRUEBA:Clinicaltrials.gov (NCT02654249).

Myxolipoma of hand in a child: case report of a rare tumor.

Lipomatous tumors account for less than 10% of tumors in the pediatric population. Myxolipomas (a subset of lipoma characterised by mature adipose tissue and abundant mucoid substance) are found to be even rarer. There are a few case reports in different body parts like heart, kidney, oral cavity, epiglottis, cervical and mediastinal regions. However, there are no case reports on the involvement of the hands in any age group. High resolution ultrasound is the imaging modality of choice for the initial evaluation of superficial soft tissue tumors, their site, nature and extent. In conjunction with clinical findings and age of presentation, it helps in narrowing down the differential diagnosis and planning the management. Hyperechoic fatty tumors in the pediatric hand are mostly benign and includes lipomas, lipoblastomas and fibrous hamartomas of infancy as the main differentials. A definitive diagnosis is based on a histo-pathological and molecular cytogenetic examination. This article presents a never before reported case of a rare, large, myxolipoma of the hand in a 22-month-old boy.

Five-Compressions Protocol as a Valid Myotonometric Method to Assess the Stiffness of the Lower Limbs: A Brief Report.

The objective of this study was to evaluate the validity of a short assessment MyotonPRO protocol to measure the stiffness of the superficial muscles and tendons of the lower limbs. The stiffness of the dominant lower limb vastus lateralis (VL), rectus femoris (RF) and patellar tendon (PT) was evaluated in 52 healthy participants (26.9 ± 3.4 years) with two MyotonPRO protocols: the standard protocol (10 mechanical taps) and the short protocol (five mechanical taps). The myotonometry was performed at the midpoint of the length from the upper pole of the patella to the greater trochanter for the VL, and to the anterior superior iliac spine for the RF. The PT was evaluated 1 cm caudal from the inferior pole of the patella. Pearson's correlation coefficients were calculated to determine the relationships between protocols. The validity of the short protocol was evaluated with Student's t-test. High positive correlations were observed between the short and standard protocols in the stiffness of the VL (r = 0.959; p < 0.001), the RF (r = 0.967; p < 0.001) and the PT (r = 0.953; p < 0.001) and no differences were found between both protocols in the stiffness assessment of the VL, RF and PT (p > 0.05). Therefore, the five-compressions protocol is a valid protocol for the assessment of lower limb mechanical properties.