Molecular mechanisms in trophoblastic cells after LIF-stimulation with special regard to microRNAs: microRNAs in trophoblast cells

Human beings are not very fertile and the main reason seems to be dysregulation during the blastocyst implantation. This process is controlled by several molecules and their dysregulation can result in miscarries, pre-eclampsia or choriocarcinoma. One of those molecules is LIF. In this thesis, two review articles summarized LIF production, LIF-induced effects in trophoblastic cells, and the information about the potential clinical applications of LIF. The second part includes original articles focused on the activation and cross-talk of the JAK/STAT and MAPK cascades. It was demonstrated that ERK1/2 plays an important role in the proliferation of trophoblast cells. Likewise, a cross-talk between ERK1/2 and STAT3 was defined: ERK1/2 is not responsible for the STAT3 ser727 phosphorylation, but it has a negative effect on the translocation of STAT3 into the nucleus, which results in a decrease of trophoblast invasiveness

Synergies of Extracellular Vesicles and Microchimerism in Promoting Immunotolerance During Pregnancy

The concept of biological identity has been traditionally a central issue in immunology. The assumption that entities foreign to a specific organism should be rejected by its immune system, while self-entities do not trigger an immune response is challenged by the expanded immunotolerance observed in pregnancy. To explain this “immunological paradox”, as it was first called by Sir Peter Medawar, several mechanisms have been described in the last decades. Among them, the intentional transfer and retention of small amounts of cells between a mother and her child have gained back attention. These microchimeric cells contribute to expanding allotolerance in both organisms and enhancing genetic fitness, but they could also provoke aberrant alloimmune activation. Understanding the mechanisms used by microchimeric cells to exert their function in pregnancy has proven to be challenging as per definition they are extremely rare. Profiting from studies in the field of transplantation and cancer research, a synergistic effect of microchimerism and cellular communication based on the secretion of extracellular vesicles (EVs) has begun to be unveiled. EVs are already known to play a pivotal role in feto-maternal tolerance by transferring cargo from fetal to maternal immune cells to reshape their function. A further aspect of EVs is their function in antigen presentation either directly or on the surface of recipient cells. Here, we review the current understanding of microchimerism in the feto-maternal tolerance during human pregnancy and the potential role of EVs in mediating the allorecognition and tropism of microchimeric cells

Placental damage in pregnancies with systemic lupus erythematosus: A narrative review

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause, which mainly affects women of childbearing age, especially between 15 and 55 years of age. During pregnancy, SLE is associated with a high risk of perinatal morbidity and mortality. Among the most frequent complications are spontaneous abortion, fetal death, prematurity, intrauterine Fetal growth restriction (FGR), and preeclampsia (PE). The pathophysiology underlying obstetric mortality and morbidity in SLE is still under investigation, but several studies in recent years have suggested that placental dysfunction may play a crucial role. Understanding this association will contribute to developing therapeutic options and improving patient management thus reducing the occurrence of adverse pregnancy outcomes in this group of women. In this review, we will focus on the relationship between SLE and placental insufficiency leading to adverse pregnancy outcomes

Molecular Principles of Intrauterine Growth Restriction in Plasmodium Falciparum Infection

Malaria in pregnancy still constitutes a particular medical challenge in tropical and subtropical regions. Of the five Plasmodium species that are pathogenic to humans, infection with Plasmodium falciparum leads to fulminant progression of the disease with massive impact on pregnancy. Severe anemia of the mother, miscarriage, stillbirth, preterm delivery and intrauterine growth restriction (IUGR) with reduced birth weight are frequent complications that lead to more than 10,000 maternal and 200,000 perinatal deaths annually in sub-Saharan Africa alone. P. falciparum can adhere to the placenta via the expression of the surface antigen VAR2CSA, which leads to sequestration of infected erythrocytes in the intervillous space. This process induces a placental inflammation with involvement of immune cells and humoral factors. Especially, monocytes get activated and change the release of soluble mediators, including a variety of cytokines. This proinflammatory environment contributes to disorders of angiogenesis, blood flow, autophagy, and nutrient transport in the placenta and erythropoiesis. Collectively, they impair placental functions and, consequently, fetal growth. The discovery that women in endemic regions develop a certain immunity against VAR2CSA-expressing parasites with increasing number of pregnancies has redefined the understanding of malaria in pregnancy and offers strategies for the development of vaccines. The following review gives an overview of molecular processes in P. falciparum infection in pregnancy which may be involved in the development of IUGR

Characteristics and outcomes of over 300,000 patients with COVID-19 and history of cancer in the United States and Spain

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin’s lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n ¼ 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.</p

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Competencias de los estudiantes del sexto año de medicina de la Universidad del Zulia (LUZ) para comunicar malas noticias.

En medicina, la comunicaci&oacute;n de la verdad, cuando se desea informar malas noticias, se convierte en una situaci&oacute;n estresante para los m&eacute;dicos, entendi&eacute;ndose como mala noticia cualquier informaci&oacute;n que afecte negativamente la visi&oacute;n de un individuo sobre s&iacute; mismo y su futuro. Actualmente en la Facultad de Medicina de la Universidad del Zulia (LUZ) se evidencia d&eacute;ficit en la formaci&oacute;n curricular de las destrezas de comunicar malas noticias, debido a que la educaci&oacute;n se basa en ense&ntilde;ar aspectos t&eacute;cnicos y se descuidan aspectos &eacute;ticos de la medicina. El prop&oacute;sito de esta investigaci&oacute;n consiste en determinar las competencias para comunicar malas noticias de los estudiantes del &uacute;ltimo a&ntilde;o de la Escuela de Medicina de LUZ. Se realiz&oacute; un estudio de campo, descriptivo, de tipo encuesta transversal, con una poblaci&oacute;n de 800 estudiantes del &uacute;ltimo a&ntilde;o de medicina, con una muestra de 146, a quienes les fue aplicada una encuesta online a trav&eacute;s de Google Forms, constituida por 38 &iacute;tems, evaluando diferentes dominios (cognoscitivo, actitudinal, metodol&oacute;gico, procedimental y &eacute;tico-legal), analizando las dos preguntas m&aacute;s polarizadas de cada dominio. Los resultados indican que los estudiantes actuar&iacute;an con acciones similares a las de los protocolos, aun cuando los desconocen, lo que indica que los conocimientos adquiridos son emp&iacute;ricos y no por educaci&oacute;n formal. Un gran porcentaje desea instrucci&oacute;n sobre comunicar malas noticias y as&iacute; abarcar al paciente integralmente. Finalmente, se determina que la mayor&iacute;a se siente incapaz de comunicar malas noticias, por lo que se sugiere incluir este t&oacute;pico en el dise&ntilde;o curricular de la carrera de medicinaCompetencies towards breaking bad news in sixth year medical students from the Zulia University (LUZ), VenezuelaIn medicine, conveying a truthful message when breaking bad news has come to be a very stressful situation for physicians; considering a bad news as any information that negatively affects a patient&rsquo;s perception about himself or his future. Currently, in the School of Medicine of the Zulia University (LUZ) there is a noted deficit in curricula for the developing of skills in breaking bad news, mostly because of a lack in teaching ethical aspects of medicine in favor of more technical aspects of it. The purpose of this research consists in the determination of competencies for breaking bad news among senior medical students at University of Zulia&rsquo;s School of Medicine. A descriptive, survey type, transversal field study was performed, recruiting a sample of 146 students, who responded an online form delivered through Google Forms, constituted by 38 questions, evaluating different domains of competency (cognitive, attitude, methodology, procedural, ethical and legal). We then analyzed the two more polarized items of each domain. The results indicate that students would act competently according to current guidelines, even in the absence of formal knowledge, which may indicate empirical competency in the context of lack of formal training. The majority of these students would like to be formally trained about breaking bad news in order to offer better care for their patients. Lastly, most of the students perceive their own competency on breaking bad news as poor, suggesting that this kind of training should be included formally into the curricular design of this career