Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Beyond conventional physical examination in hepatology: POCUS.

Point-of-care ultrasound (POCUS) refers to the use of ultrasound imaging through pocket-sized sonographic devices at the patient's bedside, to make a diagnosis or direct a procedure and immediately answer a clinical question. Its goal is to broaden the physical examination, not to replace conventional ultrasound studies. POCUS has evolved as a complement to physical examination and has been adopted by different medical specialties, including hepatology. A narrative synthesis of the evidence on the applications of POCUS in hepatology was carried out, describing its usefulness in the diagnosis of cirrhosis of the liver, metabolic dysfunction-associated steatotic liver disease (MASLD), decompensated cirrhosis, and portal hypertension. The review also encompasses more recent applications in the hemodynamic evaluation of the critically ill patient with cirrhosis of the liver, patients with other liver diseases, as well as in the ultrasound guidance of procedures. POCUS could make up part of the daily clinical practice of gastroenterologists and hepatologists, simplifying the initial evaluation of patients and optimizing clinical management. Its accessibility, ease of use, and low adverse event profile make POCUS a useful tool for the properly trained physician in the adequate clinical setting. The aim of this review was to describe the available evidence on the usefulness of POCUS in the daily clinical practice of gastroenterologists and hepatologists.

Evaluation and management of emergencies in the patient with cirrhosis.

The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.

Extrahepatic complications of non-alcoholic fatty liver disease: Its impact beyond the liver. / Complicaciones extrahepáticas de la enfermedad por hígado graso no alcohólico: impacto más allá del hígado.

Non-alcoholic fatty liver disease (NAFLD) is currently one of the main causes of chronic liver disease in Western countries, with a 25% prevalence reported in the general population worldwide. Visceral adiposity and liver fat promote a state of systemic inflammation, predisposing individuals with NAFLD to the extrahepatic pathologies of cardiovascular disease (the most common cause of death in patients with NAFLD), diabetes mellitus, chronic kidney disease, hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, and an increased risk for presenting with gastrointestinal and extraintestinal neoplasias. Different mechanisms between NAFLD and its association with extrahepatic diseases have been reported, and lipotoxicity is the main cause of inflammatory pathway activation that results in extrahepatic tissue damage.

Activating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents.

Multiple areas within the reticular activating system (RAS) can hasten awakening from sleep or light planes of anesthesia. However, stimulation in individual sites has shown limited recovery from deep global suppression of brain activity, such as coma. Here we identify a subset of RAS neurons within the anterior portion of nucleus gigantocellularis (aNGC) capable of producing a high degree of awakening represented by a broad high frequency cortical reactivation associated with organized movements and behavioral reactivity to the environment from two different models of deep pharmacologically-induced coma (PIC): isoflurane (1.25%-1.5%) and induced hypoglycemic coma. Activating aNGC neurons triggered awakening by recruiting cholinergic, noradrenergic, and glutamatergic arousal pathways. In summary, we identify an evolutionarily conserved population of RAS neurons, which broadly restore cerebral cortical activation and motor behavior in rodents through the coordinated activation of multiple arousal-promoting circuits.

Evaluación de la influencia del estrés térmico en el absentismo laboral de los trabajadores de una factoría de acero inoxidable / Evaluation of the influence of heat stress in the absenteeism of the employees of an stainless steel factory

Objetivo: Evaluar la influencia del Estrés Térmico en el Absentismo Laboral de los trabajadores de una empresa dedicada a la fabricación de acero inoxidable, conocer la situación actual de la factoría respecto a número de incapacidades temporales tanto por contingencias comunes como profesionales y su distribución por edad del trabajador y por su experiencia en el puesto de trabajo y medir la diferencia de riesgos de presentar una incapacidad temporal ya sea por contingencias comunes, por contingencias profesionales o por la suma de ambas entre expuestos y no expuestos a riesgo de estrés térmico en su puesto de trabajo. Material y método: Estudio analítico observacional de tipo cohorte histórica desde el año 1974 hasta 2016, sobre una muestra de 1609 trabajadores de una empresa dedicada a la fabricación de acero inoxidable. Resultados: Nos encontramos con una plantilla joven en cuanto a la antigüedad ya que más del 56% lleva menos de 15 años trabajando (grupo más numeroso), lo que contrasta con la edad de los trabajadores, en la que casi un 35% es mayor de 50 años. Los resultados apuntan a la existencia de una relación estadística entre el riesgo de estrés térmico y el número de incapacidades temporales por contingencias profesionales. Conclusiones: La Incidencia acumulada por cada 100 trabajadores de Incapacidades temporales debidas a contingencias comunes en el periodo comprendido entre 1974 y 2016 no es superior en el grupo de trabajadores expuestos a estrés térmico que en aquellos que no lo están. En el caso de las contingencias profesionales sí es superior en el grupo de trabajadores expuestos a estrés térmico. El Riesgo relativo de sufrir una Incapacidad Temporal de origen no laboral no es mayor en aquellos trabajadores sometidos a estrés térmico, pero sí cuando la contingencia es profesional. El Riesgo atribuible al estrés térmico en el grupo de trabajadores expuestos es del 32% en las incapacidades temporales por contingencias profesionales y del 44% en el total de la población para este mismo tipo de incapacidades temporales (AU)

Objective: To evaluate the influence of Thermal Stress on Occupational Absenteeism of the workers of a company dedicated to the manufacture of stainless steel, to know the current situation of the factory regarding the number of temporary incapacities for both common and professional contingencies and their distribution by age of the worker and his / her experience in the workplace and to measure the difference in risks of presenting a temporary incapacity either by common contingencies, by professional contingencies or by the sum of both exposed and not exposed to risk of thermal stress in their position of work. Material and method: An observational, historical ohort-type analytical study from 1974 to 2016 on a sample of 1609 workers from a company dedicated to the manufacture of stainless steel. Results: We have a young workforce in terms of seniority, since more than 56% work less than 15 years (larger group), which contrasts with the age of the workers, in which almost 35% is greater of 50 years. The results point to the existence of a statistical relationship between the risk of thermal stress and the number of temporary incapacities due to professional contingencies. Conclusions: The cumulative incidence for each 100 temporary incapacity workers due to common contingencies in the period between 1974 and 2016 is not higher in the group of workers exposed to thermal stress than in those who are not. In the case of professional contingencies, it is higher in the group of workers exposed to thermal stress. The relative risk of suffering a Temporary Incapacity of non-labor origin is not greater in those workers subjected to thermal stress, but when the contingency is professional. The risk attributable to thermal stress in the group of exposed workers is 32% in temporary incapacities due to professional contingencies and 44% in the total population for this same type of temporary incapacities (AU)

Generalized CNS arousal: An elementary force within the vertebrate nervous system.

Why do animals and humans do anything at all? Arousal is the most powerful and essential function of the brain, a continuous function that accounts for the ability of animals and humans to respond to stimuli in the environment by producing muscular responses. Following decades of psychological, neurophysiological and molecular investigations, generalized CNS arousal can now be analyzed using approaches usually applied to physical systems. The concept of "criticality" is a state that illustrates an advantage for arousal systems poised near a phase transition. This property provides speed and sensitivity and facilitates the transition of the system into different brain states, especially as the brain crosses a phase transition from less aroused to more aroused states. In summary, concepts derived from applied mathematics of physical systems will now find their application in this area of neuroscience, the neurobiology of CNS arousal.

[Changes associated with aging in angular kinematic parameters during a controlled speed walk]. / Cambios asociados al envejecimiento normal en los parámetros angulares de la marcha a una velocidad controlada.

BACKGROUND: During normal aging, a reduction in walking speed and changes in stability are observed. AIM: To characterize and compare gait kinematic parameters of young (YA) and older adults (OA) at a controlled speed. MATERIAL AND METHODS: Gait angular kinematic parameters were analyzed in OA aged over 60 years and YA aged between 20 and 30 years. For data capture, six VICON Bonita cameras were used. Recording were made at a gait speed of 1.2 m/s. Kinematic data were normalized to 100% of the gait cycle using the Polygon 4.1 software. Time windows representing the phases of gait were created for analysis. RESULTS: At the hip-pelvis level, OA reduce their pelvic obliquity motion and increase hip abduction. At the knee level OA reduce movements in the frontal plane during the plantar support and half swing phases. At the ankle level OA reduce their maximum ranges of plantar flexion, during the toe-off and final swing phases. CONCLUSIONS: At a controlled speed, kinematic changes observed in OA allow an increase in body support base to maintain gait stability.

Cambios asociados al envejecimiento normal en los parámetros angulares de la marcha a una velocidad controlada / Changes associated with aging in angular kinematic parameters during a controlled speed walk

Background: During normal aging, a reduction in walking speed and changes in stability are observed. Aim: To characterize and compare gait kinematic parameters of young (YA) and older adults (OA) at a controlled speed. Material and Methods: Gait angular kinematic parameters were analyzed in OA aged over 60 years and YA aged between 20 and 30 years. For data capture, six VICON Bonita cameras were used. Recording were made at a gait speed of 1.2 m/s. Kinematic data were normalized to 100% of the gait cycle using the Polygon 4.1 software. Time windows representing the phases of gait were created for analysis. Results: At the hip-pelvis level, OA reduce their pelvic obliquity motion and increase hip abduction. At the knee level OA reduce movements in the frontal plane during the plantar support and half swing phases. At the ankle level OA reduce their maximum ranges of plantar flexion, during the toe-off and final swing phases. Conclusions: At a controlled speed, kinematic changes observed in OA allow an increase in body support base to maintain gait stability.

Control of Immune Response to Allogeneic Embryonic Stem Cells by CD3 Antibody-Mediated Operational Tolerance Induction.

Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts. Recipients of either mouse ESC-derived embryoid bodies (EBs) or cardiac progenitors received a single short tolerogenic regimen of CD3 antibody. In immunocompetent mice, allogeneic EBs and cardiac progenitors were rejected within 20-25 days. Recipients treated with CD3 antibody showed long-term survival of implanted cardiac progenitors or EBs. In due course, EBs became teratomas, the growth of which was self-limited. Regulatory CD4(+)FoxP3(+) T cells and signaling through the PD1/PDL1 pathway played key roles in the CD3 antibody therapeutic effect. Gene profiling emphasized the importance of TGF-ß and the inhibitory T cell coreceptor Tim3 to the observed effect. These results demonstrate that CD3 antibody administered alone promotes prolonged survival of allogeneic ESC derivatives and thus could prove useful for enhancing cell engraftment in the absence of chronic immunosuppression.

Aplicaciones clínicas del colgajo en cono / Clinical applications of the cone shaped flap

Presentamos nuestra experiencia con el uso de un colgajo previamente descrito, el colgajo denominado en cono por la forma final que obtiene, como la de un barquillo de helado con su bocado. Consta de 2 colgajos acoplados: uno de rotación local y otro un avance en V-Y, ambos fasciocutáneos. Realizamos un análisis retrospectivo de 108 pacientes intervenidos entre 2000 y 2013 por lesiones en diferentes partes del organismo, con edades comprendidas entre los 20 y los 52 años, de los cuales 99 fueron varones, y en los que empleamos este tipo de colgajo. Los defectos cubiertos afectaban a las piernas en el 27% de los casos, tobillos en el 10%, planta del pie en el 9%, al talón en el 8% y a otras localizaciones en el resto de los pacientes. Del total, 80 colgajos tuvieron buena evolución (74%), 11 sufrieron dehiscencia mayor (10,2 %), 13 dehiscencia menor (12%) y 4 necrosis (3,7 %). Los resultados confirman que el colgajo en cono es versátil, reproducible, sencillo y seguro de realizar, y permite al cirujano plástico resolver problemas quirúrgicos complejos de forma muy segura y a bajo costo (AU)

We present our experience with a previously described flap, the shaped cone flap, to cover skin defects. This flap due its name to the shape, similar to an ice cream cone, that is formed by locally rotated and V-Y advance flaps joined together, being both fasciocutaneous flaps. We perform a retrospective analysis of 108 patients operated on between 2000 and 2013, aged 20 to 52 years, 99 males, treated with a cone shaped flap. The defects covered were located in the leg in 27%, in the ankle in 10%, in the sole of the foot in 9%, in the heel in 8% and in other locations in the rest of patients. Eighty flaps (74%) had a good evolution, 11 (10,2%) had a major dehiscence, 13 (12%) had a minor dehiscence and 4 flaps (3,7 %) had necrosis. We confirm the cone shaped flap as an easy and safe alternative for reconstruction that avoid complications in most of the cases and with a low surgical cost (AU)

Abnormal high-frequency burst firing of cerebellar neurons in rapid-onset dystonia-parkinsonism.

Loss-of-function mutations in the α3 isoform of the Na(+)/K(+) ATPase (sodium pump) are responsible for rapid-onset dystonia parkinsonism (DYT12). Recently, a pharmacological model of DYT12 was generated implicating both the cerebellum and basal ganglia in the disorder. Notably, partially blocking sodium pumps in the cerebellum was necessary and sufficient for induction of dystonia. Thus, a key question that remains is how partially blocking sodium pumps in the cerebellum induces dystonia. In vivo recordings from dystonic mice revealed abnormal high-frequency bursting activity in neurons of the deep cerebellar nuclei (DCN), which comprise the bulk of cerebellar output. In the same mice, Purkinje cells, which provide strong inhibitory drive to DCN cells, also fired in a similarly erratic manner. In vitro studies demonstrated that Purkinje cells are highly sensitive to sodium pump dysfunction that alters the intrinsic pacemaking of these neurons, resulting in erratic burst firing similar to that identified in vivo. This abnormal firing abates when sodium pump function is restored and dystonia caused by partial block of sodium pumps can be similarly alleviated. These findings suggest that persistent high-frequency burst firing of cerebellar neurons caused by sodium pump dysfunction underlies dystonia in this model of DYT12.

Unusual bilateral dentigerous cysts in a nonsyndromic patient assessed by cone beam computed tomography.

In the absence of syndromes, bilateral dentigerous cysts (DC) located on the jaws are unusual. In English based language literature review, we only found eight reports of nonsyndromic bilateral dentigerous cyst associated with mandibular third molars. Therefore, we report the unusual occurrence of sizable nonsyndromic bilateral DC associated with mandibular impacted third molars in a 42-year-old Caucasian woman. The lesions were assessed by cone beam computed tomography (CBCT) the right lesion showed approximately 23.64 mm and the left one, 16.57 mm diameter, both located intimately next to the mandibular canal. Bilateral surgical enucleation, related teeth excision of both third molars and plate for fixation placement on the right and bigger lesion, under general anesthesia was the final treatment choice. Clinical, radiographic and histopathological features confirmed diagnose of bilateral dentigerous cyst. Now-a-days, the patient is on 18 months radiograph follow-up with favorable osseous formation with no evidence of recurrence of the cysts.

The effect of lameness on the resting behavior and metabolic status of dairy cattle during the transition period in a freestall-housed dairy herd.

The objective of this observational study was to examine the effect of lameness on the resting behavior of dairy cattle through the transition period in a mattress-bedded commercial freestall facility, and explore the relationships between lameness, behavior, and metabolic indicators of disease. A convenience sample was used, comprised of 40 multiparous and 17 primiparous Holstein cows that were recruited as they entered the close-up pen and tracked through the maternity, hospital, and fresh pens. At recruitment, 87.5% of multiparous cows and 23.5% of primiparous cows showed evidence of abnormal gait. Lying time decreased from 16 d before calving from a least squares means ± standard error of 13.5 ± 0.6 h/d to a nadir of 10.6 ± 0.38 h/d on the day of calving. After a period of increased rest after calving, lying time stabilized by d 6 to between 9.8 and 10.8h/d. This change was accompanied by an increase in the number of lying bouts per day from least squares means (95% confidence limits) of 11.2 (10.0 to 12.4) bouts per day to a peak of 17.7 (16.5 to 18.8) bouts per day on the day before calving, and a decrease in the duration of each lying bout. Resting behavior was influenced by calving month, temperature humidity index, body condition, parity, and lameness. Moderate and severely lame cows had significantly longer lying times throughout the transition period before and after calving, but most notable was a dramatic increase in the number of lying bouts observed 3 d before and after calving. In the straw-bedded, loose-housed maternity pen, moderate and severely lame cows had 20.3 (19.1 to 21.5) bouts per day, compared with 15.6 (14.3 to 16.8) bouts per day for nonlame cows. We hypothesized that this alteration in behavior may be associated with hypersensitivity to pain due to lameness. A total of 26.3% of cows tested above a threshold of 1,400 µM ß-hydroxybutyrate. Moderate and severely lame cows had a least squares means (95% confidence limits) ß-hydroxybutyrate concentration of 1,165 (1,037 to 1,291) µM that was significantly greater than 697 (560 to 834) µM for slightly lame cows and 687 (551 to 824) µM for nonlame cows. In summary, lameness significantly altered the resting behavior of cows during the transition period and was associated with elevated risk for ketosis in the study herd.