Pathological and immunohistochemical assessment of the impact of three different strains of swine enteric coronaviruses in the intestinal barrier.

Swine enteric coronaviruses, such as porcine epidemic diarrhea virus (PEDV) or transmissible gastroenteritis virus (TGEV), have risen concern for the porcine industry and research community due to the increase in their virulence, their potential recombination capacity and the emergence of new variants. This in vivo study aims to compare the impact of three different strains of swine enteric coronaviruses [(two G1b (S-INDEL) PEDV strains and a recombinant TGEV-PEDV or Swine enteric coronavirus (SeCoV)] in the intestine of 3-weeks-old infected piglets, focusing on the pathology and main components of the intestinal barrier, including the number of goblet cells, and the expression of IgA as well as FoxP3, a regulatory T cell marker. Severity of lesions was evidenced in the three infected groups and was highly correlated with the viral load in feces and the frequency of viral antigen-positive cells. Furthermore, higher cellular death together with an increase in the expression of the FoxP3 marker was detected in the duodenum and jejunum of infected animals at 3 days post-infection. Our results highlight a recruitment of FoxP3+ cells in the small intestine of infected animals which may represent a response to the tissue damage caused by viral replication and cell death. Further studies should be addressed to determine the potential role of these cells during swine enteric coronavirus infections.

Estimulación cerebral profunda combinada del núcleo subtalámico y el globo pálido interno en la enfermedad de Parkinson / Combined subthalamic nucleus and globus pallidus internus deep brain stimulation in Parkinson’s disease

Introducción: La estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) y el globo pálido interno (GPi) son los principales abordajes quirúrgicos en la enfermedad de Parkinson avanzada. La estimulación suele aplicarse de forma bilateral en la misma estructura cerebral. Sin embargo, cuando diferentes síntomas motores se presentan concomitantemente en el mismo paciente, la modulación simultánea de diferentes estructuras cerebrales puede ser una alternativa eficaz. Caso clínico: Presentamos un paciente con enfermedad de Parkinson avanzada en el que se realizó ECP combinada en NST y el GPi. La ECP del NST izquierdo controló de manera óptima la sintomatología del hemicuerpo derecho, mientras que las discinesias problemáticas que presentaba en el hemicuerpo izquierdo se redujeron con éxito mediante la estimulación del GPi derecho. Discusión. La estimulación combinada del NST/GPi puede considerarse un enfoque neuroquirúrgico adecuado cuando surge una sintomatología motora desafiante en pacientes con enfermedad de Parkinson avanzada.(AU)

Introduction: Subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) are the main surgical approaches for advanced Parkinson’s disease. Stimulation is usually applied bilaterally in the same brain structure. However, when various motor symptoms concomitantly present in the same patient, simultaneous modulation of different brain structures may be a suitable alternative. Case report: We present a patient with advanced Parkinson’s disease with a combined DBS neurosurgery. Left STN DBS optimally controlled the off right hemibody symptomatology while left side troublesome dyskinesias were successfully relieved by right GPi stimulation. Discussion: Combined STN/GPi stimulation can be considered a suitable approach when challenging motor symptomatology arises in advanced Parkinson’s disease patients.(AU)

Person-centered strategies for delivering TB diagnostic services in Lima, Peru.

SETTING: Lima, Peru. OBJECTIVE: To close the gap in TB diagnosis, TB diagnostic services must match care-seeking preferences. We sought to identify preferred strategies for delivering TB diagnostic services and to determine whether preferences differ among demographic groups. DESIGN: During May 2022-January 2023, we recruited adults who recently initiated treatment for pulmonary TB. We used an object-case best-worst scaling instrument to assess the desirability of nine hypothetical strategies for delivering TB diagnostic services. A t-test was used to assess differences in preference scores between groups. RESULTS: Among 150 participants, the strategies with the highest preference scores were an integrated mobile unit offering screening for multiple conditions, expedited attention at the health center, and home-based screening. These were strongly preferred by 42%, 25%, and 27% of participants, respectively, and 80% of participants strongly preferred at least one of the three. Expedited attention at the health center scored more highly among people who experienced >2 months delay in TB diagnosis compared to those who experienced a more rapid diagnosis (0.37 ± 0.06 vs. 0.17 ± 0.06; P = 0.031). CONCLUSION: Providing person-centered TB diagnostic services at diverse access points could help reach different populations, which could promote early diagnosis and help close the diagnosis gap.

CONTEXTE: Lima, Pérou. OBJECTIF: Pour combler les lacunes dans le diagnostic de la TB, les services de diagnostic de la TB doivent correspondre aux préférences en matière de recherche de soins. Nous avons cherché à identifier les stratégies préférées pour la prestation de services de diagnostic de la TB et à déterminer si les préférences diffèrent entre les groupes démographiques. MÉTHODE: De mai 2022 à janvier 2023, nous avons recruté des adultes ayant récemment commencé un traitement contre la TB pulmonaire. Nous avons utilisé un instrument d'évaluation du meilleur et du pire pour évaluer la désirabilité de neuf stratégies hypothétiques de prestation de services de diagnostic de la TB. Un test-t a été utilisé pour évaluer les différences dans les scores de préférence entre les groupes. RÉSULTATS: Parmi les 150 participants, les stratégies ayant les scores de préférence les plus élevés étaient une unité mobile intégrée offrant un dépistage pour des conditions multiples, une attention accélérée au centre de santé et un dépistage à domicile. Ces stratégies ont été fortement préférées par 42%, 25% et 27% des participants, respectivement, et 80% des participants ont fortement préféré au moins l'une des trois. L'attention accélérée au centre de santé a obtenu un score plus élevé chez les personnes ayant subi un retard de diagnostic de la TB de plus de 2 mois que chez celles ayant subi un diagnostic plus rapide (0,37 ± 0,06 contre 0,17 ± 0,06 ; P = 0,031). CONCLUSION: La fourniture de services de diagnostic de la TB centrés sur la personne à divers points d'accès pourrait permettre d'atteindre différentes populations, ce qui pourrait favoriser un diagnostic précoce et contribuer à combler le fossé en matière de diagnostic.

Combined subthalamic nucleus and globus pallidus internus deep brain stimulation in Parkinson's disease. / Estimulación cerebral profunda combinada del núcleo subtalámico y el globo pálido interno en la enfermedad de Parkinson.

INTRODUCTION: Subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) are the main surgical approaches for advanced Parkinson's disease. Stimulation is usually applied bilaterally in the same brain structure. However, when various motor symptoms concomitantly present in the same patient, simultaneous modulation of different brain structures may be a suitable alternative. CASE REPORT: We present a patient with advanced Parkinson's disease with a combined DBS neurosurgery. Left STN DBS optimally controlled the off right hemibody symptomatology while left side troublesome dyskinesias were successfully relieved by right GPi stimulation. DISCUSSION: Combined STN/GPi stimulation can be considered a suitable approach when challenging motor symptomatology arises in advanced Parkinson's disease patients.

TITLE: Estimulación cerebral profunda combinada del núcleo subtalámico y el globo pálido interno en la enfermedad de Parkinson.Introducción. La estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) y el globo pálido interno (GPi) son los principales abordajes quirúrgicos en la enfermedad de Parkinson avanzada. La estimulación suele aplicarse de forma bilateral en la misma estructura cerebral. Sin embargo, cuando diferentes síntomas motores se presentan concomitantemente en el mismo paciente, la modulación simultánea de diferentes estructuras cerebrales puede ser una alternativa eficaz. Caso clínico. Presentamos un paciente con enfermedad de Parkinson avanzada en el que se realizó ECP combinada en NST y el GPi. La ECP del NST izquierdo controló de manera óptima la sintomatología del hemicuerpo derecho, mientras que las discinesias problemáticas que presentaba en el hemicuerpo izquierdo se redujeron con éxito mediante la estimulación del GPi derecho. Discusión. La estimulación combinada del NST/GPi puede considerarse un enfoque neuroquirúrgico adecuado cuando surge una sintomatología motora desafiante en pacientes con enfermedad de Parkinson avanzada.

Laparoscopic and robotic intracorporeal resection and end-to-end anastomosis in left colectomy: a prospective cohort study - stage 2a IDEAL framework for evaluating surgical innovation.

PURPOSE: To analyze the safety and feasibility of intracorporeal resection and anastomosis in upper rectum, sigmoid, and left colon surgery, via both laparoscopic and robotic approaches. The secondary aim was to assess possible short-term differences between laparoscopic versus robotic surgery. METHODS: A prospective observational cohort study according to IDEAL framework exploration and assessment stage (Development, stage 2a), evaluating and comparing the laparoscopic approach and the robotic approach in left colon, sigmoid, and upper rectum surgery with intracorporeal resection and end-to-end anastomosis. Demographic, preoperative, surgical, and postoperative variables of patients undergoing laparoscopic and robotic surgery are described and compared according to the surgical technique used. RESULTS: Between May 2020 and March 2022, seventy-nine patients were consecutively included in the study, 41 operated via laparoscopy (laparoscopic left colectomy: LLC) and 38 by robotic surgery (robotic left colectomy: RLC). There were no statistically significant differences between the two groups in terms of demographic variables. In surgical variables, the median surgical times differed significantly: 198 min (SD 48 min) for LLC vs. 246 min (SD 72 min) for RLC (p = 0.01, 95% CI: - 75.2 to - 20.5)). The only significant difference regarding postoperative complications was a higher degree of relevant morbidity in the LLC (Clavien-Dindo > II (14.6% vs. 0%, p = 0.03) and Comprehensive Complication Index (IQR 22 vs. IQR 0, p = 0.03). The pathological results were similar in both approaches. CONCLUSION: Laparoscopic and robotic intracorporeal resection and anastomosis are feasible and safe, and obtain similar surgical, postoperative, and pathological results than described in literature. However, morbidity seems to be higher in LLC group with fewer relevant postoperative complications. The results of this study enable us to proceed to stage 2b of the IDEAL framework. CLINICAL TRIAL REGISTRATIONS: The study is registered in Clinical trials with the registration code NCT0445693.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Evaluation of the degradation of the graphene-polypropylene composites of masks in harsh working conditions.

The recent COVID-19 outbreak has led health authorities to recommend at least the use of surgical masks, most preferably respirators (FFP2 or KN95), to prevent the spread of the virus. Non-woven fabrics have been chosen as the best option to manufacture the face masks, due to their filtration efficiency, low cost, and versatility. Modifying the mask filters with graphene has been of great interest due to its potential use as antibacterial and virucidal properties. Indeed, some companies have commercialized face masks in which graphene is coated and/or embedded. However, the Canadian sanitary authorities advised against using the Shandong Shengquan New Materials Co. graphene masks because of the possibility of pulmonary damage produced by graphene inhalation. Thus, we have analyzed the stability of the graphene filter of these masks and compared it with two other commercially available graphene mask filters, evaluating the morphological and spectroscopical change of the fibers, as well as the particles released during the endurance tests. Our work introduces the necessary tools and methodology to evaluate the potential degradation of face masks under extreme working conditions. These methods complement the present standard tests ensuring the security of the new filters based on composites or nanomaterials.

Synchronous enteroid adenocarcinoma at the ureteral implantation site after ureterosigmoidostomy.

Ureterosigmoidostomy is considered to be the oldest urinary diversion technique performed for the first time in the 19th Century in patients with urinary malformations. However, the high rate of complications as well as the significant risk of developing tumors in the colonic portion of the ureteral anastomosis have given rise to other new intestinal urinary diversion techniques. We present the case of a patient with two synchronous enteroid adenocarcinomas, with a latency period of 66 years, at the site of both ureterocolonic anastomoses after ureterosigmoidostomy performed during childhood owing to bladder exstrophy.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Efectos adversos y complicaciones de la infusión intestinal continua de levodopa-carbidopa en una cohorte de pacientes con enfermedad de Parkinson de un hospital terciario / Adverse effects and complications of continuous intestinal infusion of levodopa-carbidopa in a cohort of patients with Parkinsons disease in a tertiary hospital

Introducción: La infusión intestinal continua de levodopa/carbidopa (IICLC) es un tratamiento de segunda línea indicado en fases avanzadas de la enfermedad de Parkinson (EP). Para su implantación se debe realizar una gastrostomía endoscópica percutánea. Objetivos: El objetivo principal ha sido describir la frecuencia y las características de los efectos secundarios asociados a este tratamiento. Como objetivo secundario se han analizado las características epidemiológicas y clínicas de pacientes afectos de EP que han recibido o reciben tratamiento con IICLC. Pacientes y métodos: Estudio descriptivo, unicéntrico y retrospectivo para una muestra consecutiva de pacientes con EP tratados con IICLC desde principios de 2006 hasta finales de agosto de 2021. Resultados: Se han analizado 81 planificaciones. El éxito del tratamiento (duración mayor de 12 meses) se alcanzó en el 78,1% (n = 50) de los pacientes en los que se disponía de ese período de seguimiento. La duración media del tratamiento fue de 35 meses. El 58,6% de los pacientes presentó algún tipo de complicación. Se notificaron 43 complicaciones leves y 16 complicaciones graves. Conclusión: La constitución de un equipo multidisciplinar experimentado es fundamental para garantizar un manejo y seguimiento adecuado de estos pacientes.(AU)

Introduction: Continuous intestinal infusion of levodopa/carbidopa is a second-line treatment indicated in advanced stages of Parkinson’s disease (PD). For its implantation, a percutaneous endoscopic gastrostomy must be performed. Objectives: The main objective has been to describe the frequency and characteristics of the side effects associated with this treatment. As a secondary objective, we have analyzed the epidemiological and clinical characteristics of the PD patients who have received this treatment in our hospital. Patients and methods: Descriptive, single-center, retrospective study for a consecutive sample of PD patients treated with Continuous intestinal infusion of Levodopa/Carbidopa from the beginning of 2006 to the end of August 2021. Results: 81 treatment planifications have been analyzed. Treatment success (duration greater than 12 months) was achieved in 78.1% (n = 50) of the patients in whom this follow-up period was available. The median duration of treatment was 35 months. 58.6% of the patients presented some type of complication. A total of 43 minor complications and 16 serious adverse events were reported. Conclusion: The constitution of an experienced multidisciplinary team is essential to guarantee the adequate management and follow-up of these patients.(AU)

[Adverse effects and complications of continuous intestinal infusion of levodopa-carbidopa in a cohort of patients with Parkinson's disease in a tertiary hospital]. / Efectos adversos y complicaciones de la infusión intestinal continua de levodopa-carbidopa en una cohorte de pacientes con enfermedad de Parkinson de un hospital terciario.

INTRODUCTION: Continuous intestinal infusion of levodopa/carbidopa is a second-line treatment indicated in advanced stages of Parkinson's disease (PD). For its implantation, a percutaneous endoscopic gastrostomy must be performed. OBJECTIVES: The main objective has been to describe the frequency and characteristics of the side effects associated with this treatment. As a secondary objective, we have analyzed the epidemiological and clinical characteristics of the PD patients who have received this treatment in our hospital. PATIENTS AND METHODS: Descriptive, single-center, retrospective study for a consecutive sample of PD patients treated with Continuous intestinal infusion of Levodopa/Carbidopa from the beginning of 2006 to the end of August 2021. RESULTS: 81 treatment planifications have been analyzed. Treatment success (duration greater than 12 months) was achieved in 78.1% (n = 50) of the patients in whom this follow-up period was available. The median duration of treatment was 35 months. 58.6% of the patients presented some type of complication. A total of 43 minor complications and 16 serious adverse events were reported. CONCLUSION: The constitution of an experienced multidisciplinary team is essential to guarantee the adequate management and follow-up of these patients.

TITLE: Efectos adversos y complicaciones de la infusión intestinal continua de levodopa-carbidopa en una cohorte de pacientes con enfermedad de Parkinson de un hospital terciario.Introducción. La infusión intestinal continua de levodopa/carbidopa (IICLC) es un tratamiento de segunda línea indicado en fases avanzadas de la enfermedad de Parkinson (EP). Para su implantación se debe realizar una gastrostomía endoscópica percutánea. Objetivos. El objetivo principal ha sido describir la frecuencia y las características de los efectos secundarios asociados a este tratamiento. Como objetivo secundario se han analizado las características epidemiológicas y clínicas de pacientes afectos de EP que han recibido o reciben tratamiento con IICLC. Pacientes y métodos. Estudio descriptivo, unicéntrico y retrospectivo para una muestra consecutiva de pacientes con EP tratados con IICLC desde principios de 2006 hasta finales de agosto de 2021. Resultados. Se han analizado 81 planificaciones. El éxito del tratamiento (duración mayor de 12 meses) se alcanzó en el 78,1% (n = 50) de los pacientes en los que se disponía de ese período de seguimiento. La duración media del tratamiento fue de 35 meses. El 58,6% de los pacientes presentó algún tipo de complicación. Se notificaron 43 complicaciones leves y 16 complicaciones graves. Conclusión. La constitución de un equipo multidisciplinar experimentado es fundamental para garantizar un manejo y seguimiento adecuado de estos pacientes.

Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1.

Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host's immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low-virulent PRRSV-1 strains are comparable and how they are conserved during the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level, a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low-virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an upregulation of co-stimulatory and co-inhibitory immune checkpoints that were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked "negative regulation of immune system process" with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load, and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related pathways. These immune checkpoints, together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. However, further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.