Significance of clinical-immunological patterns and diagnostic yield of biopsies in microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are the two major antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). OBJECTIVES: To characterize a homogenous AAV cohort and to assess the impact of clinicopathological profiles and ANCA serotypes on clinical presentation and prognosis. Clinical differences in GPA patients according to ANCA serotype and the diagnostic yield for vasculitis of biopsies in different territories were also investigated. RESULTS: This retrospective study (2000-2021) included 152 patients with AAV (77 MPA/75 GPA). MPA patients (96.1% myeloperoxidase [MPO]-ANCA and 2.6% proteinase 3 [PR3]-ANCA) presented more often with weight loss, myalgia, renal involvement, interstitial lung disease (ILD), cutaneous purpura, and peripheral nerve involvement. Patients with GPA (44% PR3-ANCA, 33.3% MPO, and 22.7% negative/atypical ANCA) presented more commonly with ear, nose, and throat and eye/orbital manifestations, more relapses, and higher survival than patients with MPA. GPA was the only independent risk factor for relapse. Poor survival predictors were older age at diagnosis and peripheral nerve involvement. ANCA serotypes differentiated clinical features in a lesser degree than clinical phenotypes. A mean of 1.5 biopsies were performed in 93.4% of patients in different territories. Overall, vasculitis was identified in 80.3% (97.3% in MPA and 61.8% in GPA) of patients. CONCLUSIONS: The identification of GPA presentations associated with MPO-ANCA and awareness of risk factors for relapse and mortality are important to guide proper therapeutic strategies in AAV patients. Biopsies of different affected territories should be pursued in difficult-to-diagnose patients based on their significant diagnostic yield.

Pathological autoantibody internalisation in myositis.

OBJECTIVES: Autoantibodies targeting intracellular proteins are common in various autoimmune diseases. In the context of myositis, the pathologic significance of these autoantibodies has been questioned due to the assumption that autoantibodies cannot enter living muscle cells. This study aims to investigate the validity of this assumption. METHODS: Confocal immunofluorescence microscopy was employed to localise antibodies and other proteins of interest in myositis muscle biopsies. Bulk RNA sequencing was used to examine the transcriptomic profiles of 669 samples, including those from patients with myositis, disease controls and healthy controls. Additionally, antibodies from myositis patients were introduced into cultured myoblasts through electroporation, and their transcriptomic profiles were analysed using RNA sequencing. RESULTS: In patients with myositis autoantibodies, antibodies accumulated inside myofibres in the same subcellular compartment as the autoantigen. Bulk RNA sequencing revealed that muscle biopsies from patients with autoantibodies targeting transcriptional regulators exhibited transcriptomic patterns consistent with dysfunction of the autoantigen. For instance, in muscle biopsies from patients with anti-PM/Scl autoantibodies recognising components of the nuclear RNA exosome complex, an accumulation of divergent transcripts and long non-coding RNAs was observed; these RNA forms are typically degraded by the nuclear RNA exosome complex. Introducing patient antibodies into cultured muscle cells recapitulated the transcriptomic effects observed in human disease. Further supporting evidence suggested that myositis autoantibodies recognising other autoantigens may also disrupt the function of their targets. CONCLUSIONS: This study demonstrates that, in myositis, autoantibodies are internalised into living cells, causing biological effects consistent with the disrupted function of their autoantigen.

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

Implementation of web-based respondent driven sampling in epidemiological studies.

BACKGROUND: Respondent-driven sampling (RDS) is a peer chain-recruitment method for populations without a sampling frame or that are hard-to-reach. Although RDS is usually done face-to-face, the online version (WebRDS) has drawn a lot of attention as it has many potential benefits, despite this, to date there is no clear framework for its implementation. This article aims to provide guidance for researchers who want to recruit through a WebRDS. METHODS: Description of the development phase: guidance is provided addressing aspects related to the formative research, the design of the questionnaire, the implementation of the coupon system using a free software and the diffusion plan, using as an example a web-based cross-sectional study conducted in Spain between April and June 2022 describing the working conditions and health status of homecare workers for dependent people. RESULTS: The application of the survey: we discuss about the monitoring strategies throughout the recruitment process and potential problems along with proposed solutions. CONCLUSIONS: Under certain conditions, it is possible to obtain a sample with recruitment performance similar to that of other RDS without the need for monetary incentives and using a free access software, considerably reducing costs and allowing its use to be extended to other research groups.

Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families.

Alazami syndrome is a rare disorder with an autosomal recessive inheritance caused by pathogenic biallelic variants in the LARP7 gene. Clinically, it is mainly characterized by short stature, intellectual disability, and dysmorphic facial features. However, the phenotype is not yet well-defined because less than 50 cases have been described to date. Here, we report three new patients from two unrelated Spanish families who, in addition to the defined features of Alazami syndrome, also exhibit unique features that broaden the phenotypic spectrum of the syndrome. Moreover, we describe the novel frameshift variant c.690_699delins27 in the LARP7 gene, in which loss of function is a known mechanism of Alazami syndrome.

Whole Exome Sequencing of 20 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Cataracts.

Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose LONP1, ACACA, TRPM1, CLIC5, HSPE1, ODF1, PIKFYVE, and CHMP4A as potential candidates to further investigate for their role in pediatric cataracts, and AQP5 and locus 2q37 as causal genes.

Whole-Exome Sequencing of 21 Families: Candidate Genes for Early-Onset High Myopia.

High myopia is the most severe and pathological form of myopia. It occurs when the spherical refractive error exceeds -6.00 spherical diopters (SDs) or the axial length (AL) of the eye is greater than 26 mm. This article focuses on early-onset high myopia, an increasingly common condition that affects children under 10 years of age and can lead to other serious ocular pathologies. Through the genetic analysis of 21 families with early-onset high myopia, this study seeks to contribute to a better understanding of the role of genetics in this disease and to propose candidate genes. Whole-exome sequencing studies with a panel of genes known to be involved in the pathology were performed in families with inconclusive results: 3% of the variants found were classified as pathogenic, 6% were likely pathogenic and the remaining 91% were variants of uncertain significance. Most of the families in this study were found to have alterations in several of the proposed genes. This suggests a polygenic inheritance of the pathology due to the cumulative effect of the alterations. Further studies are needed to validate and confirm the role of these alterations in the development of early-onset high myopia and its polygenic inheritance.

Exploring the Decision-Making Process of People Living with HIV Enrolled in Antiretroviral Clinical Trials: A Qualitative Study of Decisions Guided by Trust and Emotions.

The informed consent is an ethical and legal requirement for potential participants to enroll in a study. There is ample of evidence that understanding consent information and enrollment is challenging for participants in clinical trials. On the other hand, the reasoning process behind decision-making in HIV clinical trials remains mostly unexplored. This study aims to examine the decision-making process of people living with HIV currently participating in antiretroviral clinical trials and their understanding of informed consent. We conducted a qualitative socio-constructivist study using semi-structured interviews. Eleven participants were selected by purposive sampling in Argentina until data saturation was reached. A content analysis was performed. The findings highlight the fact that some participants decided to enroll on the spot, while others made the decision a few days later. In all cases, the decision was based on different aspects of trust (in doctors, in the clinical research site, in the clinical trials system) but also on emotions associated with HIV and/or treatment. Moreover, while people living with HIV felt truly informed after the consent dialogue with a researcher, consent forms were unintelligible and unfriendly. The immediacy of patient decision-making has rarely been described before. Enrollment in an HIV clinical trial is mainly a trust-based decision but this does not contradict the ethical values of autonomy, voluntariness, non-manipulation, and non-exploitation. Thus, trust is a key issue to be included in reshaping professional practices to ensure the integrity of the informed consent process.

Expert patients leading activities on social justice: towards patient-centered education.

BACKGROUND: Social justice is recognized by reputable international organizations as a professional nursing value. However, there are serious doubts as to whether it is embodied in Catalan nursing education. OBJECTIVES: To explore what nursing students take away from two teaching activities led by expert patients (one presentation and three expert patient illness narratives) on the topics of social justice, patient rights, and person-centered care. RESEARCH DESIGN: Qualitative study using a content analysis approach. The research plan included (1) think-pair-share activities (additional faculty-assisted presentation and three faculty-assisted, semi-structured scripted narratives); (2) paired reflections; (3) focus groups; and (4) content analysis of paired reflections and focus groups. PARTICIPANTS AND RESEARCH CONTEXT: Fourth-year nursing degree students at the Autonomous University of Barcelona (UAB), Spain. Convenience sampling was used. ETHICAL CONSIDERATIONS: The UAB Research Ethics Committee did not deem it necessary to apply any specific measures. We fully explained to patients that they could decide what medical information they would share with the students that was relevant to their learning, and we provided students with guidelines about patient confidentiality, dignity, and respect. FINDINGS/RESULTS: The students engaged in reflection about their education (recognizing that it had been centered on the professional and not the patient) and their relationship with the patient, in which they reproduced low-involvement patient care by modeling behaviors of their nurse educator. Moreover, they valued a person-centered care model with an emphasis on the emotional part but left out decision-making as an individual right of people. CONCLUSIONS: The think-pair-share activities were useful to spark self-reflection among students, who identified aspects to change in their own practice, and reflected about their own education process, both of which promote change.

Multiresponsive Cyclometalated Crown Ether Bearing a Platinum(II) Metal Center.

Multiresponsive materials can adapt to numerous changes in their local environment, which makes them highly valuable for various applications. Although nanostructured and polymeric multiresponsive materials are plentiful, small-molecule analogues are scarce. This work presents a compact cyclometalated platinum(II) complex that bears a crown ether cavity (18C6-PtII); the intimate ring/emitter connectivity is key to unlocking multiresponsiveness. Complex 18C6-PtII responds to (i) cationic guests, producing changes in luminescence in both solution and the solid state, (ii) solvent molecules, which perturb the packing of the complex in the solid state and cause reversible color changes, and (iii) solvent polarity, which leads to controlled aggregation. These responses may enable 18C6-PtII to function as a sensor for ions and solvents, or as a functional unit for the fabrication of hybrid supramolecular polymers and metallogels.

Impact of resident involvement on patient outcomes in laparoscopic cholecystectomy of different degrees of complexity: analysis of 2331 cases.

BACKGROUND: Resident involvement in the operating room is a vital component of their medical education. Laparoscopic cholecystectomy (LC) represents the paradigmatic minimally invasive training procedure, both due to its prevalence and its different forms of complexity. We aim to evaluate whether the supervised participation of residents as operative surgeons in LC of different degrees of complexity affects postoperative outcomes in a university hospital. METHODS: This is a retrospective, single-center study that included all consecutive adult (> 18 years old) patients operated for a LC between January 1, 2012 and December 31, 2017. Each surgical procedure was recorded according to the level of complexity that we established in three types of categorization (level 1: elective surgery; level 2: cholecystitis; level 3: biliary instrumentation). Patients were clinically monitored at an outpatient clinic 7 and 30-day postoperative. Postoperative outcomes of patients operated by supervised residents (SR) and trained surgeons (TS) were compared. Postoperative complications were graded according to the Clavien-Dindo classification of surgical complications. RESULTS: A total of 2331 patients underwent LC during the study period, of whom 1573 patients (67.5%) were operated by SR and 758 patients (32.5%) by TS. There were no significant differences among age, sex, and BMI between patients operated in both groups, with the exception of ASA (P = 0.0001). Intraoperative cholangiography was performed in 100% of the patients, without bile duct injuries. There were no deaths in the 30 postoperative days. The overall complication rate was 5.70% (133 patients), with no significant differences when comparing LC performed by SR and TS (5.09 vs. 6.99%; P = 0.063). The severity rates of complications were similar in both groups (P = 0.379). Patient readmission showed a statistical difference comparing SR vs TS (0.76% vs. 2.2%; P = 0.010). The postoperative complications rate according to the complexity level of LC was not significant in level 1 and 2 for both groups. However in complexity level 3 the TS group experienced a greater rate of complications compared to the SR group (18.12% vs. 9.38%; P = 0.058). In the multivariate analysis, the participation of the residents as operating surgeons was not independently associated with an increased risk of complications (OR 1.22, 95% CI 0.84-1.77; P = 0.275), neither other risk factors like age ≥ 65 years, BMI, complexity level 2-3, or ASA ≥ 3-4. The association of another surgical procedure with the LC was an independent factor of morbidity (OR 3.85, 95% CI 2.54-5.85; P = 0.000). CONCLUSION: Resident involvement in LC with different degrees of complexity did not affect postoperative outcomes. The participation of a resident as operating surgeon is not an independent risk factor and may be considered ethical, safe, and reliable whenever implemented in the background of a residency-training program with continuous supervision and national accreditation. The sum of other procedures not related to a LC should be taken as a risk factor of morbidity.

The HeartWare Ventricular Assist Device (HVAD): A Single Institutional 10-Year Experience.

OBJECTIVES: The aim of this study was to analyze our 10-year experience with the HVAD in a real-world scenario in a high-volume German heart center. METHODS: We retrospectively analyzed outcomes of adults (≥18 years) with terminal heart failure (HF), who underwent HVAD implantation for durable LVAD therapy in our center between October 2009 and March 2020. Primary and secondary end points were all-cause death after implantation and LVAD-associated complications, respectively. We focused the distinct analyses on risk profiles at the time of implantation and implant strategies, i.e., bridge-to-transplant (BTT) or destination therapy (DT). RESULTS: A total of 510 patients were included, with 229 and 281 individuals in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level 1 (45%) and 2 to 4, respectively. Median follow-up was 26 months (IQR: 5-54 months). Overall survival at 1, 3, and 5 years after HVAD implantation was 66% (95% CI; 61.7-70%), 49.4% (95% CI; 44.9-53.8%), and 37.4% (95% CI; 32.8-42%), not censored for LVAD exchange, LVAD explantation, or heart transplantation. INTERMACS level 1 and peri-operative temporary right heart assistance were independent risk factors for survival. Survival was best in BTT patients undergoing heart transplantation at any time during follow-up. The INTERMACS level at time of HVAD implantation did not affect survival after heart transplantation. Freedom from the combined end point of any device-associated severe complication and death was 44.5% (95% CI; 40-48.8%) at 1-year after implantation. CONCLUSION: The HVAD is a reliable pump for durable mechanical circulatory support even in high-risk patients. Still, heart transplantation outperforms durable MCS therapy for a superior long-term survival.

Burden of non-communicable disease studies in Europe: a systematic review of data sources and methodological choices.

BACKGROUND: Assessment of disability-adjusted life years (DALYs) resulting from non-communicable diseases (NCDs) requires specific calculation methods and input data. The aims of this study were to (i) identify existing NCD burden of disease (BoD) activities in Europe; (ii) collate information on data sources for mortality and morbidity; and (iii) provide an overview of NCD-specific methods for calculating NCD DALYs. METHODS: NCD BoD studies were systematically searched in international electronic literature databases and in grey literature. We included all BoD studies that used the DALY metric to quantify the health impact of one or more NCDs in countries belonging to the European Region. RESULTS: A total of 163 BoD studies were retained: 96 (59%) were single-country or sub-national studies and 67 (41%) considered more than one country. Of the single-country studies, 29 (30%) consisted of secondary analyses using existing Global Burden of Disease (GBD) results. Mortality data were mainly derived (49%) from vital statistics. Morbidity data were frequently (40%) drawn from routine administrative and survey datasets, including disease registries and hospital discharge databases. The majority (60%) of national BoD studies reported mortality corrections. Multimorbidity adjustments were performed in 18% of national BoD studies. CONCLUSION: The number of national NCD BoD assessments across Europe increased over time, driven by an increase in BoD studies that consisted of secondary data analysis of GBD study findings. Ambiguity in reporting the use of NCD-specific BoD methods underlines the need for reporting guidelines of BoD studies to enhance the transparency of NCD BoD estimates across Europe.

Transformative learning experience among nursing students with patients acting as teachers: Mixed methods, non-randomized, single-arm study.

AIM: To examine the effects of expert HIV patients acting as teachers to Spanish nursing students both on their HIV-related knowledge, attitudes and practices and on their approach to the care model as well as to explore their learning experience. DESIGN: Non-randomized, single-arm study with quantitative before and after measurements and qualitative data. METHODS: The intervention consisted of five 90-min workshops led by two women living with HIV. Thirty-four nursing students participated, and quantitative and qualitative data were gathered from February to June 2018. We used the Patient-Practitioner Orientation Scale (PPOS) and the KAP questionnaire on HIV/AIDS to collect quantitative data. RESULTS: Statistically significant differences were found in the global score for care orientation and its two dimensions, caring and sharing. About the changes resulting from the workshops, the quantitative results-more patient-centred care perception and better attitudes towards people living with HIV-match the qualitative findings in all the aspects studied, except in sharing. CONCLUSION: Incorporating expert patients as teachers in the nursing bachelor's degree resulted in more patient-centred care and improved knowledge, attitudes and practices. The workshops conducted by qualified expert patients showed transformative learning power, as the participants improved professional and personal aspects.

Incidence, Clinical Characteristics, Risk Factors and Outcomes of Acute Coronary Syndrome in Patients With COVID-19: Results of the UMC-19-S1010.

BACKGROUND: There is a lack of knowledge about the real incidence of acute coronary syndrome (ACS) in patients with COVID-19, their clinical characteristics, and their prognoses. OBJECTIVE: We investigated the incidence, clinical characteristics, risk factors, and outcomes of ACS in patients with COVID-19 in the emergency department. METHODS: We retrospectively reviewed all COVID-19 patients diagnosed with ACS in 62 Spanish emergency departments between March and April 2020 (the first wave of COVID-19). We formed 2 control groups: COVID-19 patients without ACS (control A) and non-COVID-19 patients with ACS (control B). Unadjusted comparisons between cases and control subjects were performed regarding 58 characteristics and outcomes. RESULTS: We identified 110 patients with ACS in 74,814 patients with COVID-19 attending the ED (1.48% [95% confidence interval {CI} 1.21-1.78%]). This incidence was lower than that observed in non-COVID-19 patients (3.64% [95% CI 3.54-3.74%]; odds ratio [OR] 0.40 [95% CI 0.33-0.49]). The clinical characteristics of patients with COVID-19 associated with a higher risk of presenting ACS were: previous coronary artery disease, age ≥60 years, hypertension, chest pain, raised troponin, and hypoxemia. The need for hospitalization and admission to intensive care and in-hospital mortality were higher in cases than in control group A (adjusted OR [aOR] 6.36 [95% CI 1.84-22.1], aOR 4.63 [95% CI 1.88-11.4], and aOR 2.46 [95% CI 1.15-5.25]). When comparing cases with control group B, the aOR of admission to intensive care was 0.41 (95% CI 0.21-0.80), while the aOR for in-hospital mortality was 5.94 (95% CI 2.84-12.4). CONCLUSIONS: The incidence of ACS in patients with COVID-19 attending the emergency department was low, around 1.48%, but could be increased in some circumstances. Patients with COVID-19 with ACS had a worse prognosis than control subjects with higher in-hospital mortality.

Core Synergies Measured with Ultrasound in Subjects with Chronic Non-Specific Low Back Pain and Healthy Subjects: A Systematic Review.

Low back pain represents the leading cause of disability since 1990. In 90% of cases, it is classified as non-specific low back pain, being chronic in 10% of subjects. Ultrasound has proven to be an effective measurement tool to observe changes in the activity and morphology of the abdominal muscles. This article reviews which core synergies are studied with ultrasound in healthy subjects and with chronic non-specific low back pain. A systematic review was conducted on studies analyzing synergies between two or more core muscles. Publications from 2005 until July 2021 were identified by performing structured searched in Pubmed/MEDLINE, PEDro and WOS. Fifteen studies were eligible for the final systematic review. A total of 56% of the studies established synergies between the core muscles and 44% between the homo and contralateral sides of the core muscles. The most studied core synergies were transversus abdominis, internal oblique and external oblique followed by the rectus abdominis and the lumbar multifidus. No studies establishing synergies with diaphragm and pelvic floor were found. Eight studies were conducted in healthy subjects, five studies in subjects with chronic non-specific low back pain compared to healthy subjects and two studies in subjects with chronic non-specific low back pain.

Understanding factors that influence the decision to be vaccinated against influenza and pertussis in pregnancy: A qualitative study.

AIMS AND OBJECTIVES: To identify how pregnant women perceive pertussis and influenza and the factors that influence their decision to be vaccinated. BACKGROUND: Suffering from influenza during pregnancy increases complications in the pregnant woman, foetus and newborn. Pertussis in children under six months of age causes severe complications. Maternal vaccination against influenza and pertussis is effective and safe. However, vaccination rates are insufficient. DESIGN: We conducted a qualitative descriptive study, using semi-structured interviews. This research adheres to the COREQ guidelines and checklist. METHODS: We carried out 18 semi-structured face-to-face interviews with pregnant women, using intentional sampling and thematic analysis. RESULTS: We identified an overarching theme, 'factors that influenced participants' decision to be vaccinated or not', which was composed of four subthemes that were in turn made up of 12 categories. The factors that influenced participants' decision to be vaccinated against influenza and pertussis were related to their knowledge of and their perception of risk for these diseases. Participants perceived the risk of pertussis to be greater, and they focused their concern on the newborn. The recommendations and convictions of nurse-midwives were the most important factors encouraging vaccination. Participants trusted their nurse-midwives and most reported that they would have been vaccinated if their midwife had recommended it. Other factors were linked to lack of information, fear and concerns about economic interests. CONCLUSIONS: The convictions and actions of the nurse-midwife in recommending vaccination to pregnant women are decisive. Strategies to improve vaccination rates should be directed to helping health professionals understand how their practice affects the final decision of pregnant women. RELEVANCE TO CLINICAL PRACTICE: Understanding the factors that limit vaccination rates among pregnant women provides valuable information to nurse-midwives that can help to improve vaccination strategies and practices. Increased maternal vaccination rates would reduce morbidity and mortality among pregnant women and newborns.

New Insights into Adipokines in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.

Severe hepatotoxicity secondary to nintedanib.

Nintedanib is a multikinase inhibitor used for the treatment of pulmonary idiopathic fibrosis. We present the first report published to date of severe hepatotoxicity and jaundice secondary to nintedanib.

Efficacy and safety of tofacitinib in the treatment of ulcerative colitis: real-life experience in Andalusia.

BACKGROUND: tofacitinib is a Janus kinase inhibitor approved for the treatment of moderate-severe ulcerative colitis (UC). This study aimed to evaluate its efficacy in a real-life setting. METHODS: a retrospective and multicenter observational study was performed with UC patients treated with tofacitinib. Short and long-term treatment effectiveness, treatment survival, need for dose escalation and safety were analyzed. Clinical response and remission were defined in accordance with the partial Mayo score. RESULTS: seventy-four patients were included, 98.3 % had received prior biological treatment, 55.4 % with three or more biologicals and up to 64.9% with two or three different mechanisms of action. Clinical remission and response rates were 37.8 % and 77 % at eight weeks, and 41.8 % and 70.1 % at 16 weeks. With regard to non-responders at eight weeks, 37.5 % achieved a delayed clinical response at 16 weeks. Mean treatment duration was 19 months (95 % CI: 16-22), with a treatment survival of 56 % at 28 months, and remission and response rates at 24 months of 53.8 % and 61.5 %. Twenty-three treatments were withdrawn, most of them (18) during the induction period. There were adverse events in a quarter of the patients; only four were severe and led to treatment discontinuation. CONCLUSION: tofacitinib has a demonstrated efficacy in clinical practice to induce and maintain clinical response in treatment-refractory UC patients, with an acceptable safety profile.