A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions. / [Articulo traducido] Serie de 69 dermatosis relacionadas con la COVID-19 con biopsia, estudio inmunohistoquímico con anti-spike 3, hibridación in situ y PCR: Una revisión crítica de la afectación cutánea relacionada con la COVID-19.

BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. MATERIAL AND METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions.

BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. MATERIAL AND METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

The global burden of chronic urticaria for the patient and society.

Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.

Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma.

Among the numerous changes associated with the transformation to cancer, cellular metabolism is one of the first discovered and most prominent[1, 2]. However, despite the knowledge that nearly every cancer is associated with the strong upregulation of various metabolic pathways, there has yet to be much clinical progress on the treatment of cancer by targeting a single metabolic enzyme directly[3-6]. We previously showed that inhibition of glycolysis through lactate dehydrogenase (LDHA) deletion in cancer cells of origin had no effect on the initiation or progression of cutaneous squamous cell carcinoma[7], suggesting that these cancers are metabolically flexible enough to produce the necessary metabolites required for sustained growth in the absence of glycolysis. Here we focused on glutaminolysis, another metabolic pathway frequently implicated as important for tumorigenesis in correlative studies. We genetically blocked glutaminolysis through glutaminase (GLS) deletion in cancer cells of origin, and found that this had little effect on tumorigenesis, similar to what we previously showed for blocking glycolysis. Tumors with genetic deletion of glutaminolysis instead upregulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We also found that the metabolic flexibility observed upon inhibition of glycolysis or glutaminolysis is due to post-transcriptional changes in the levels of plasma membrane lactate and glutamine transporters. To define the limits of metabolic flexibility in cancer initiating hair follicle stem cells, we genetically blocked both glycolysis and glutaminolysis simultaneously and found that frank carcinoma was not compatible with abrogation of both of these carbon utilization pathways. These data point towards metabolic flexibility mediated by regulation of nutrient consumption, and suggest that treatment of cancer through metabolic manipulation will require multiple interventions on distinct pathways.

[Humeral anterograde nailing. Functional results. A 5 years experience]. / Enclavado centromedular anterógrado de húmero. Resultados funcionales. Experiencia de cinco años.

PURPOSE: The purpose of this study was to investigate the clinical impact on the global function of the shoulder of the use of the anterolateral approach for nailing. MATERIAL AND METHODS: A retrospective cohort at the public sector of Centenario Hospital Miguel Hidalgo in Aguascalientes, Mexico between 2011 and 2016 was analysed. Inclusion criteria were: patients with anterolateral humeral nailing approach. Clinical assessment using the Constant-Murley score, shoulder range of motion and quick DASH questionnaire. RESULTS: Seventeen patients, 16 treated for humeral shaft fracture and one for humeral fibrous dyslasia were obtained. Mean score on Constant-Murley scale was 84.05 with 76.4% of patients achieving excellent result ( 75 points). One patient had a poor functional outcome. The mean quickDASH score was 17.5 points. CONCLUSIONS: The anterolateral approach for humeral nailing has good functional outcome in our series.

OBJETIVO: El propósito de este estudio es investigar el impacto clínico en la función global en el hombro intervenido para el abordaje anterolateral de enclavado centromedular de húmero. MATERIAL Y MÉTODOS: Se trata de una cohorte retrospectiva de casos tratados entre 2011 y 2016. Como criterio de inclusión se revisó todo paciente con antecedente de enclavado de húmero con abordaje anterolateral. Se realizó una evaluación con la escala funcional de Constant-Murley, arquimetría comparativa de ambos hombros y la aplicación de cuestionario quick DASH. RESULTADOS: Se obtuvieron 17 pacientes, 16 tratados para fracturas diafisarias de húmero y uno para displasia fibrosa de húmero. El puntaje promedio de la escala de Constant-Murley obtenido fue de 84.05, 76.4% de los pacientes obtuvieron excelentes resultados ( 75 puntos). Un paciente tuvo un resultado funcional deficiente. El puntaje promedio de quick DASH obtenido fue de 17.5 puntos. CONCLUSIONES: El abordaje anterolateral para enclavado centromedular de húmero tiene buen pronóstico funcional en nuestra serie de casos.

Blockade of neuronal activity during hippocampal development produces a chronic focal epilepsy in the rat.

During brain development, neuronal activity can transform neurons characterized by widely ranging axonal projections to ones with more restricted patterns of synaptic connectivity. Previous studies have shown that an exuberant outgrowth of local recurrent excitatory axons occurs in hippocampal area CA3 during postnatal weeks 2 and 3. Axons are remodeled with maturation, and nearly half of the branches are eliminated. Postnatal weeks 2 and 3 also coincide with a "critical" period of development, when CA3 networks have a marked propensity to generate electrographic seizures. In an attempt to prevent axonal remodeling, local circuit activity was blocked unilaterally in dorsal hippocampus by continuous infusion of tetrodotoxin (TTX). Field potential recordings from behaving animals were dramatically altered when TTX infusion was initiated at the beginning of the critical period, week 2, but not later in life. Spontaneous, synchronized spikes and electrographic seizures with behavioral accompaniments were observed after 4 weeks of TTX infusion and persisted into adulthood. When recordings were made during TTX infusion, synchronized spiking was recorded in ventral hippocampus as early as 2 weeks after infusate introduction. At this same time, extracellular field recordings from in vitro slices demonstrated spontaneous network-driven "mini-bursts" arising from ventral hippocampal slices. These were abolished by glutamate receptor antagonists. Whole-cell recordings from CA3 neurons revealed bursts of excitatory synaptic potentials coincident with the network bursts recorded extracellularly. Thus, local assemblies of mutually excitatory CA3 pyramidal cells are hyperexcitable in these rats. Whether alterations in developmental axonal remodeling mediate these effects awaits further studies.

Evaluation of risk of deterministic effects in fluoroscopically guided procedures.

A methodology for the evaluation of skin dose distribution and possible skin injuries on patients undergoing interventional procedures has been developed as part of the European DIMOND programme. Relevant dosimetric data from the procedures are recorded and other specific measurements for skin dose evaluation (slow films for therapy, radiochromic films, thermoluminescence dosemeters and optically stimulated luminescence dosemeters) have been carried out. For non-cardiac and for some cardiac procedures, dose-area product values of 200 and 300 Gy cm2 were proposed, respectively, as a trigger level for further detailed skin dose investigation and possible clinical follow-up. Results from a survey of 191 selected complex procedures are reported. Out of all the patients included in the trial, 16% received skin doses > or =1.5 Gy. No skin injuries were found in any of the patients followed.

Direct ultrafiltration performance and membrane integrity monitoring by microbiological analysis.

The feasibility of substituting a conventional pre-treatment, consisting of dioxi-chlorination, coagulation/flocculation, settling and sand filtration, of a drinking water treatment plant (DWTP) by direct ultrafiltration (UF) has been assessed from a microbiological standpoint. Bacterial indicators, viral indicators and human viruses have been monitored in raw river, ultrafiltered and conventionally pre-treated water samples during two years. Direct UF has proven to remove bacterial indicators quite efficiently and to a greater extent than the conventional process does. Nevertheless, the removal of small viruses such as some small bacteriophages and human viruses (e.g. enteroviruses and noroviruses) is lower than the current conventional pre-treatment. Membrane integrity has been assessed during two years by means of tailored tests based on bacteriophages with different properties (MS-2, GA and PDR-1) and bacterial spores (Bacillus spores). Membrane integrity has not been compromised despite the challenging conditions faced by directly treating raw river water. Bacteriophage PDR-1 appears as a suitable microbe to test membrane integrity, as its size is slightly larger than the considered membrane pore size. However, its implementation at full scale plant is still challenging due to difficulties in obtaining enough phages for its seeding.

Distribution of thorny excrescences on CA3 pyramidal neurons in the rat hippocampus.

Thorny excrescences are the postsynaptic components of synapses between mossy fibers of granule cells and dendrites of CA3 pyramidal neurons in the hippocampal formation. Very little quantitative data on the number and distribution of excrescences in adult rats are available because, first, the vast majority are grouped into clusters and it is not possible to identify single excrescences within these clusters at the light microscope level. Second, clusters are of varying lengths and are distributed over hundreds of micrometers, making ultrastructural analysis prohibitively time-consuming. Here, by using three-dimensional analysis techniques at the light microscope level, we quantified the number, length, and distribution of excrescence clusters on proximal and midfield pyramidal neurons in the rat. Results indicated that proximal neurons had similar numbers of clusters on their apical and basal trees, and that cluster length was also similar. In contrast, midfield neurons had more apical than basal clusters, and apical clusters were longer. For neurons in both regions, basal clusters were located about 50% closer to somata. Overall, proximal neurons had more clusters than did midfield neurons, but the clusters were shorter; thus, proximal and midfield neurons had about the same total cluster length, and presumably the same number of single excrescences. Based on these data and on published ultrastructural measurements of single excrescences, we estimated an average of 41 excrescences/neuron, and suggest that a pyramidal neuron can be contacted by a maximum of 41 mossy fiber boutons, each from a different granule cell.

Skin dose and dose-area product values in patients undergoing intracoronary brachytherapy.

Entrance skin doses, dose-area product (DAP) values, fluoroscopy times and digital cine acquisition data were measured for 86 patients undergoing intracoronary brachytherapy procedures with beta sources, to estimate risk of skin injuries. Interventions were carried out in three dedicated X-ray interventional cardiology rooms equipped with X-ray systems operating in pulsed modes, with high filtration and edge filter options. Skin dose distribution was analysed in detail in 56 patients using slow films and thermoluminescent dosimetry. Digital recording of Digital Imaging and Communications in Medicine cine images also allowed analysis of the technical parameters used throughout the procedures. A protocol for clinical follow-up of these patients at the cardiology service is also presented, which prescribes special attention when a threshold dose is reached. Median values for DAP, fluoroscopy time and number of frames were 81.2 Gy cm(2), 17.5 min and 1569 frames, respectively, and maximum values were 323.3 Gy cm(2), 46.2 min and 3213 frames, respectively. In two cases, maximum skin doses in a procedure reached 3.5 Gy and 4.6 Gy. Comparing median values in this study, intracoronary brachytherapy involved approximately two-fold the DAP used in percutaneous transluminal coronary angioplasty procedures performed during the same period in the same catheterization laboratories, as a consequence of the need to monitor the radioactive source location used for the treatment of stenoses and the intravascular ultrasound. Special care must be paid in those cases of high dose in relation to potential patient skin injuries and late effects.

Skin radiation injuries in patients following repeated coronary angioplasty procedures.

This study investigates the incidence of skin injuries and retrospectively estimates skin doses in a sample of patients who had multiple coronary angiographies and who underwent more than four percutaneous transluminal coronary angioplasties (PTCAs), performed primarily by the same team of cardiologists in a university hospital. A database of 7824 PTCAs performed during the last 14 years was analysed. Patients were selected and reviewed by a cardiologist and two radiotherapists with experience in radiation-induced skin injuries. A retrospective analysis of skin doses was performed using data from the patients' files and from the quality assurance (QA) programme of the hospital, which includes periodic patient dose measurements. 14 patients were included in the study. Each patient had undergone between 4 and 14 coronary angiographies and between 5 and 10 PTCAs, performed over a period of 2-10 years. The estimated mean dose-area product per procedure was 46 Gy cm(2) for coronary angiography and 82 Gy cm(2) for PTCA. Mean values of maximum skin dose per procedure were 217 mGy for the diagnostic studies and 391 mGy for the PTCAs. Only a slight radiation skin injury was clinically demonstrated in one patient with a history of 10 coronary angiographies and 10 PTCAs (estimated maximum skin dose 9.5 Gy). Another patient who underwent 14 coronary angiographies and 10 PTCAs (estimated maximum skin dose 7.3 Gy) showed a slight telangiectasia and discrete pigmentation. Another patient with a cutaneous lupus erythematosus showed pigmentation in the area of the radiation field following seven coronary angiographies and six PTCAs (estimated maximum skin dose 5.6 Gy), as expected bearing in mind that skin tolerance to high doses may be altered for patients with this pathology. Each of the remaining 11 patients with no skin injuries had undergone between 5 and 7 PTCAs and between 5 and 14 additional angiographies. None of the 14 patients reported acute skin injuries and no necrosis or radiodermatitis was observed.

[The practical aspects of lipid management in secondary prevention]. / Aspectos prácticos del manejo de los lípidos en prevención secundaria.

Secondary prevention of ischaemic heart disease includes the important aim of reducing plasma lipids, as have been suggested by several recent trials focusing both on plaque regression-stabilization and on mortality (4S). The degree of acceptance of recommendations of the different panels of experts, however, has been low. Implementation of these secondary prevention measures in clinical practice requires the understanding of their pathophysiologic and epidemiologic basis, as well as an appropriate spread of experts recommendations and a good relationship of the different levels of health care to cardiac patients.

[Cholestatic jaundice and constitutional syndrome as early manifestations of primary systemic amyloidosis]. / Ictericia colestásica y síndrome constitucional como debut de una amiloidosis sistémica primaria.

We present the case of a 70-year-old woman who had been suffering from constitutional syndrome for several months, abdominal distension, and yellowish coloration of the skin for the previous few days with a rapidly fatal course. Examination revealed hepatomegaly and ascites. Laboratory investigations revealed hyperbilirubinemia with cholestasis. The remaining investigations (abdominal ultrasound, barium transit evaluation, bone marrow study, analysis of ascitic fluid and laparoscopy) did not establish the diagnosis. This was established by liver and subcutaneous fatty tissue biopsies, which revealed type AL amyloid deposits. Autopsy confirmed that the patient had primary systemic amyloidosis. This infrequent form of presentation of systemic amyloidosis and its poor prognosis are discussed.

[Severe accidental hypothermia: rewarming by total cardiopulmonary bypass]. / Hipotermia accidental grave: recalentamiento con derivación cardiopulmonar total.

We present a case of a 20-year-old male with a history of habitual drug use who suffered extreme hypothermia (26 degrees C) after several hours' accidental exposure to low ambient temperature. The patient presented in deep coma with recurring ventricular fibrillation that yielded to electrical defibrillation once a central temperature of 27.4 degrees C was reached through internal rewarming with intravenous liquids and gastric lavage with warm water. Because this method was slow, we decided to continue rewarming with extracorporeal circulation through cannulation of the femoral vein and artery. The patient recovered consciousness after three hours, with no neurological secuelae. Emergency room staff have available the means for recognizing hypothermia and a protocol for its management. Extracorporeal circulation is an effective method for internal rewarming and must be used when the patient requires cardiopulmonary resuscitation or presents signs of severe hemodynamic instability.

[Benefits of Decumanum Phlebodium intake on the muscle damage in the response to intense physical exercise in sedentary subjects]. / Beneficios de la ingesta del phlebodium decumanum sobre el daño muscular al efectuar ejercicio físico intenso en sujetos sedentarios.

INTRODUCTION: Intense physical exercise provoke muscle damage, that in sedentary people can increase cardiovascular risk. Phlebodium decumanum (PD) has shown to have immunomodulator effects in models of moderate intense physical activities in well conditioned groups. To evaluate the PD effects during eccentric exercise, as a model of muscle inflammation protocol, on a sedentary population with cardiovascular risk. METHODS: This is an experimental, double-blind, multigroup randomized study. Experimental Group 1 (n = 17)received PD, 9 doses of 400 mg (total amount 3.6 g) every 8 hours during 3 days, and Control Group 2 (n = 16)received a placebo. All the subjects performed two treadmill ergoespirometry tests: first, a modified Bruce protocol to discard ischemic responses during exercise and to evaluate VO2max before the experimental phase;and second, with an eccentric protocol (14% descending ramp test) during 10 minutes in stable state at 70-80%VO2max, as experimental inflammatory protocol.We compared intra and inter groups to evaluate differences in the pre and post-test differences results on blood muscle damage variables. RESULTS: The study shown statistically significant differences in all pre-post intra-groups results in muscle damage variables (CK, LDH and Myoglobin, but not in Cardiac Troponin), and in functional lower-limb test (SJand CMJ). The comparison of inter-group results shown less muscle damage and less functional lower-limb deterioration in Group 1 compared with Control group, with statistical significance in both cases. Differences in handgrip dynamometry were no statistically significant. CONCLUSIONS: The eccentric exercise protocol in that study has proven to be a good model to induce muscle and functional damage in sedentary people. Short PD treatment has shown to reduce muscle and functional acute damages compared with placebo control group in this specific population.

Introducción: El ejercicio intenso provoca un daño muscular inflamatorio que, en sujetos sedentarios provoca un aumento del riesgo cardiovascular. El Phlebodium decumanum (PD) ha evidenciado efectos inmunomoduladores protectores frente a ese daño en los deportistas. Para conocer los efectos del PD en una población sedentaria frente al ejercicio excéntrico, y como modelo del daño muscular inflamatorio. Metodología: Se llevó a cabo un estudio experimental, doble ciego, multigrupo, randomizado, con un grupo experimental (n = 17) al que se le administró una formulación de PD (3,6 g/sujeto distribuidos en 9 dosis de 400 mg desde el 3.er día pretest), y un grupo control (n = 16) que tomó sustancia placebo. Se realizaron dos ergoespirometrías en tapiz rodante a cada participante: una previa al estudio (protocolo de Bruce modificado) para descartar signos de isquemia durante el esfuerzo y valorar el VO2max; la segunda, aplicando un protocolo excéntrico (14% de desnivel descendente), durante 10 minutos en estado estable a una intensidad entre 70-80% del VO2max individual, como protocolo experimental. Se efectuaron comparaciones intragrupo e intergrupo del porcentaje de cambio pre-postesfuerzo en variables sanguíneas y de funcionalidad muscular. Resultados: El estudio evidencia aumentos significativos de enzimas musculares MG, CPK y LDH en los dos grupos de estudio, sin cambios para la TncI, siendo significativamente menores en el grupo al que se le administró PD. Se observaron reducciones significativas de los test funcionales SJ, CMJ en ambos grupos, lo que mostró un apreciable menor descenso en el grupo PD. Se apreció una reducción del índice elástico y de la dinamomentría manual solo en el grupo control, aunque las diferencias con el grupo PD no alcanzaron una significación estadística. Conclusiones: El protocolo del ejercicio excéntrico en el presente estudio ha inducido daños musculoesqueléticos y en la funcionalidad muscular, que han resultado significativamente menores en el grupo PD, al mostrar los efectos protectores del Phlebodium Decumanum en tratamientos cortos, frente al daño muscular también en el esfuerzo agudo.