Darvadstrocel for complex perianal fistulas in Crohn's disease: A systematic review and meta-analysis.

BACKGROUND: Local injection of darvadstrocel, a suspension of expanded adipose-derived allogenic mesenchymal stem cells, has been used for treatment-refractory perianal fistulas in Crohn's disease (CD). OBJECTIVE: This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD. METHODS: A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random-effects meta-analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I2 value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted. RESULTS: Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4-72.7) and 77.2% (95% CI 70.1-83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow-up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow-up time (p = 0.85). For effectiveness outcomes, between-study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient-years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively. CONCLUSION: Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long-term in most patients, with negligible between-study heterogeneity, as well as a favorable safety profile.

Interpersonal Difficulties Arising from Child Sexual Abuse: Differences Between Intra-familial and Extra-familial Abuse Victims.

Child sexual abuse (CSA) often has serious implications for the victims. The scientific literature reflects a diversity of sequelae that may appear in the short and long term. Interpersonal difficulties have been shown to be one of the most common consequences. However, studies comparing these sequelae between victims of intra-familial (IF) and extra-familial (EF) CSA are scarce. The aim of this research was to analyze differences in dyadic satisfaction, sexual satisfaction, and attachment patterns in adulthood between Spanish IF victims, EF victims, and non-victims of CSA. The Sexual Victimization Subscale of the Juvenile Victimization Questionnaire, the Relationship Assessment Scale, the New Sexual Satisfaction Scale, and the Adult Attachment Questionnaire were administered to 140 adults (94 CSA victims and 46 non-victims) aged 18 to 54 years. CSA victims scored lower than the non-victims on the personal sexual satisfaction factor and attachment factors characterized by the need for approval, hostile resolution of conflicts, and emotional self-sufficiency. Statistically significant differences were also found between the victim groups in the factors characterized by the need for approval and communication of feelings and comfort with relationships showing the IF group to have more impairment in these areas than the EF group. In conclusion, CSA may have serious implications for the development of victims' interpersonal relationships. The context of sexual abuse and the relationship between victim and offender appears to play a role in the development of relational problems. These findings highlight the need to implement specific strategies in the psychological treatment of victims depending on their relationship with the offender and the environment in which the abuse occurred.

Familial intrahepatic cholestasis - An uncommon cause of jaundice in young patients.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders resulting from mutations in genes involved in bile secretion, characterized by chronic cholestasis. The onset is typically in early childhood, with main clinical manifestations including jaundice, pruritus, and symptoms related to malabsorption, which can rapidly progress to liver failure. We present a case of PFIC secondary to myosin 5B mutations.

Family reaction to coming out (FRCO): A Spanish adaptation and validation of perceived parental reactions scale.

Family reactions to coming out can affect the mental health of individuals who disclose their sexual orientation or gender identity. Therefore, it is important to have an appropriate tool to assess them. The Perceived Parental Reactions Scale (PPRS) assessed perceived parental reactions to the disclosure of gay, lesbian, or bisexual sexual orientation by their children. We adapted the PPRS so that it can be answered by any individual belonging to a sexual or gender minority, and can be answered regarding any member of the family, not just parents. A total of 2627 individuals from Spain participated in this study, with a mean age of 31.59 (SD = 11.26). Participants completed the adapted PPRS questionnaire, now named the Family Reaction to Coming Out (FRCO). The FRCO assessed family reactions when disclosing their sexual orientation or gender identity. The majority of participants identified as cisgender men (47.5%) or cisgender women (44.9%), and as gay/lesbian (51.9%). A one-factor model emerged through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The FRCO displayed excellent internal consistency and demonstrated good levels of invariance for participants' gender (male vs female vs nonbinary gender), family member's gender (male vs female), and type of family member (parents vs other family member). Supporting convergent validity, the FRCO has shown a positive correlation with fear of family reaction to coming out. These findings support the validity and reliability of the FRCO tool in assessing the reactions of any family member within the Spanish context.

Acquired chronic hepatocerebral degeneration (CAHD) - Simulation of parkinsonism, secondary to chronic liver disease.

Acquired chronic hepatocerebral degeneration (CAHD) is a rare and irreversible neurological disorder that can occur in patients with chronic liver disease. It is characterized by neurological symptoms similar to parkinsonism and the presence of brain damage secondary to manganese deposition. We present the case of a 60-year-old patient with episodes of recurrent hepatic encephalopathy and diagnosis of CAHD.

Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study.

INTRODUCTION: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. METHODS: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. REGISTRATION: https://www.comet-initiative.org/Studies/Details/1580. RESULTS: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. CONCLUSION: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020197293.

Approach to interstitial lung disease associated with systemic sclerosis-A survey to pulmonologists and rheumatologists in Colombia.

INTRODUCTION: Interstitial lung disease is a leading cause of mortality in patients with systemic sclerosis. Currently, there is a lack of consensus regarding screening, rescreening, diagnosis, and follow-up practices in interstitial lung disease associated with systemic sclerosis (SSc-ILD) in Colombia. METHODS: A structured survey focused on clinical practices in patients with SSc-ILD was conducted. Members of the Asociación Colombiana de Neumología y Cirugía de Tórax (Asoneumocito) and the Asociación Colombiana de Reumatología (Asoreuma) were invited to participate from March 2023 to May 2023. RESULTS: We surveyed 51 pulmonologists and 44 rheumatologists. Overall, 51.6% reported having access to multidisciplinary team discussion in ILD. Among the 95 participants, 78.9% would routinely perform a high-resolution computed tomography scan of the chest once a diagnosis of systemic sclerosis was established. This practice is more frequent among rheumatologists (84.1%) than among pulmonologists (74.5%). Approximately half of the participants would rescreen patients annually with computed tomography scan (56.8%) if baseline images were negative. Spirometry (81.1%), diffusing capacity of the lung for carbon monoxide (80.0%), and 6-min walk test (55.8%) were the most frequently performed tests upon diagnosis of systemic sclerosis. During follow-up, participants would consider repeating pulmonary function tests mostly every 6 months. CONCLUSIONS: Screening of SSc-ILD is high among pulmonologists and rheumatologists. Decision-making on diagnosis and follow-up is similar between specialties, but there are variations in their frequency and indications. Further research is needed to evaluate how to adapt recommendations for assessing SSc-ILD in different settings.

Intralesional Vessel Diameter Measured by Optical Coherence Tomography Angiography Could Improve the Differential Diagnosis of Small Melanocytic Choroidal Lesions.

In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our centre from 2016 to 2021. Clinical management involved active surveillance followed by brachytherapy if growth was detected. The lesions were classified into two groups according to whether they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to identify the possible predictors of growth. Significant between-group differences were observed in thickness (p = 0.00), greatest basal diameter (p = 0.00), number of risk factors (p = 0.00), symptoms (p = 0.001; relative risk [RR]: 4.3), orange pigment (p = 0.00; RR: 6.02), and ultrasonographic hollowness (Kappa sign); p = 0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm (p = 0.02; RR: 2.46). The time to growth in these lesions was significantly shorter (p = 0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors.

Psychological intervention in women victims of childhood sexual abuse: a randomized controlled clinical trial comparing EMDR psychotherapy and trauma-focused cognitive behavioral therapy.

Introduction: Childhood sexual abuse persists as a painful societal reality, necessitating responses from institutions and healthcare professionals to prevent and address its severe long-term consequences in victims. This study implements an intervention comprising two psychotherapeutic approaches recommended by the WHO and international clinical guidelines for addressing short-, medium-, and long-term posttraumatic symptomatology: Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and Eye Movement Desensitization and Reprocessing (EMDR). Both approaches are adapted from group formats for implementation in small online groups via Zoom. Methods: The impact of both therapeutic approaches on trauma improvement was assessed in a sample of 19 women who were victims of childhood sexual abuse through a Randomized Clinical Trial comparing EMDR Psychotherapy and Trauma-Focused Cognitive Behavioral Therapy after a baseline period. Intra and inter comparison were made using statistics appropriate to the sample. Results: Both therapeutic approaches significantly reduced symptomatology across various evaluated variables, suggesting their efficacy in improving the quality of life for these individuals. Following CBT-FT treatment, patients exhibited enhanced emotional regulation, reduced reexperiencing, and avoidance. The EMDR group, utilizing the G-TEP group protocol, significantly improved dissociation, along with other crucial clinical variables and the perception of quality of life. Discussion: Although the limitations of this study must be taken into account due to the size of the sample and the lack of long-term follow-up, the results align with existing scientific literature, underscoring the benefits of trauma-focused psychological treatments. The online group format appears promising for enhancing the accessibility of psychological treatment for these women. Furthermore, the differential outcomes of each treatment support recent research advocating for the inclusion of both approaches for individuals with trauma-related symptomatology. Ethics and dissemination: The study has been approved by the Ethics Committee of the Valencian International University (VIU) (Valencia, Spain) (Ref. CEID2021_07). The results will be submitted for publication in peer-reviewed journals and disseminated to the scientific community. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04813224, identifier NCT04813224.

Appendicular Muscle Mass Index as the Most Important Determinant of Bone Mineral Content and Density in Small for Gestational Age Children.

Preterm small for gestational age (SGA) children are at increased risk for low bone mineral content later in life; however, data on SGA children born at term are scarce. We included 44 SGA and 57 adequate for gestational age (AGA) children aged 6 to 11 years to compare bone mineral density (BMD) and bone mineral content (BMC) and to identify which anthropometric and biochemical values influence bone mineralization in these children. Fat mass, appendicular skeletal muscle mass index (ASMMI), BMC, and BMD were significantly lower in SGA children than in AGA (P ≤ .005). Appendicular muscle mass index correlated with BMC(TBLH,FN,L1-L4) and BMD(TBLH,FN,L1-L4) in both groups (r2 = 0.7, P < .05). In multivariate analysis, ASMMI was strongly associated with BMC and BMD in both groups. There were no differences in clinical biomarkers, calcium intake, and physical activity between the groups. Achieving adequate muscle mass contributes to adequate bone mineralization and a lower risk for low BMC and BMD in SGA children.

Dietary Energy Density Is Associated with Biomarkers of Chronic Diseases-A Cross-Sectional Study of School-Aged Children in Rural Mexico.

Background: Dietary energy density (DED) is associated with chronic disease markers in adults. However, results in children are still controversial. Objective: To evaluate the DED of children and its association with obesity and biomarkers of chronic disease. Methods: In this cross-sectional study, we recruited 284 children (6-10 y) from rural Mexico. Dietary intake was assessed using three 24-h recalls. DED was calculated for "foods only" (DEDfo) and for "foods and beverages" (DEDfb). Weight, height, and body fat percent (dual-energy X-ray absorptiometry) were measured. Inflammatory cytokines, lipid profile, leptin, and insulin resistance were determined from a fasting blood sample. Results: DEDfo was 1.91 ± 0.36 kcal/g and DEDfb was 1.36 ± 0.31 kcal/g. Higher DEDfo and DEDfb were associated with higher risk to have insulin resistance [odds ratio (OR) = 3.92, 95% confidence interval (CI): 1.66, 9.22, P < 0.01; OR = 3.51, 95% CI: 1.25, 9.87, P = 0.02, respectively]. Higher DEDfo was associated with higher risk of higher leptin levels (OR = 3.17, 95% CI: 1.01, 10.23). Also, DEDfo and DEDfb were associated with higher concentrations of cholesterol (ß = 11.67, 95% CI: 1.81, 19.53, P = 0.03; and ß = 11.74, 95% CI: 2.69, 20.74 P = 0.01, respectively) and higher odds of having high insulin concentrations (OR = 2.52, 95% CI: 1.26, 5.06, P = 0.01; and OR = 2.95, 95% CI: 1.30, 6.70, P = 0.01). DEDfo and DEDfb were not associated with any measure of obesity and inflammatory cytokines in the adjusted models. Conclusions: DED was associated with higher leptin and cholesterol concentrations, and having insulin resistance, but not with any measure of obesity or inflammation. Reducing DED may reduce risk of cardiovascular disease and improve insulin sensitivity in school-aged children.

Exploring Functional Polymers in the Synthesis of Luminescent ZnO Quantum Dots for the Detection of Cr6+, Fe2+, and Cu2.

The main aim of this work is to demonstrate that well-defined methacrylate-based copolymers with oligoethylene glycol side chains and functional groups such as thiol and glycidyl, obtained by photo-initiated reversible addition-fragmentation chain transfer (RAFT) in ethanol, are highly suitable as templates in the synthesis and protection of ZnO quantum dots (ZnO QDs) with remarkable photoluminescent properties. While the affinity of thiol groups to metallic surfaces is well established, their interaction with metal oxides has received less scrutiny. Furthermore, under basic conditions, glycidyl groups could react with hydroxyl groups on the surface of ZnO, representing another strategy for hybrid synthesis. The size and crystalline morphology of the resulting hybrids were assessed using DLS, TEM, and XRD, indicating that both polymers, even with a low proportion of functional groups (5% mol) are appropriate as templates and ligands for ZnO QDs synthesis. Notably, thiol-containing polymers yield hybrids with ZnO featuring excellent quantum yield (up to 52%), while polymers with glycidyl groups require combination with the organosilane aminopropyl triethoxysilane (APTES) to achieve optimal results. In both cases, these hybrids exhibited robust stability in both ethanol and aqueous environments. Beyond fundamental research, due to the remarkable photoluminescent properties and affordability, these hybrid ZnO QDs are expected to have potential applications in biotechnology and green science; in particular, in this study, we examined their use in the detection of environmental contaminants like Fe2+, Cr6+, and Cu2+. Specifically, the limit of detection achieved at 1.13 µM for the highly toxic Cr6+ underscores the significant sensing capabilities of the hybrids.

Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue.

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1 mg/L) than subjects with overweight (87.0 ± 12.8 mg/L) and obesity (83.1 ± 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r = - 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.

Markers of Inflammation, Tissue Damage, and Fibrosis in Individuals Diagnosed with Human Immunodeficiency Virus and Pneumonia: A Cohort Study.

Previous studies have noted that persons living with human immunodeficiency virus (HIV) experience persistent lung dysfunction after an episode of community-acquired pneumonia (CAP), although the underlying mechanisms remain unclear. We hypothesized that inflammation during pneumonia triggers increased tissue damage and accelerated pulmonary fibrosis, resulting in a gradual loss of lung function. We carried out a prospective cohort study of people diagnosed with CAP and/or HIV between 2016 and 2018 in three clinical institutions in Medellín, Colombia. Clinical data, blood samples, and pulmonary function tests (PFTs) were collected at baseline. Forty-one patients were included, divided into two groups: HIV and CAP (n = 17) and HIV alone (n = 24). We compared the concentrations of 17 molecules and PFT values between the groups. Patients with HIV and pneumonia presented elevated levels of cytokines and chemokines (IL-6, IL-8, IL-18, IL-1RA, IL-10, IP-10, MCP-1, and MIP-1ß) compared to those with only HIV. A marked pulmonary dysfunction was evidenced by significant reductions in FEF25, FEF25-75, and FEV1. The correlation between these immune mediators and lung function parameters supports the connection between pneumonia-associated inflammation and end organ lung dysfunction. A low CD4 cell count (<200 cells/µL) predicted inflammation and lung dysfunction. These results underscore the need for targeted clinical approaches to mitigate the adverse impacts of CAP on lung function in this population.

Analysis of the Effectiveness of an Affective-Sexual Education Program for Adults with Intellectual Disabilities.

In recent years, the number of programs to improve sex education for people with intellectual disabilities has increased. However, in most cases, these programs do not provide any evidence of their impact. In the present study we analyzed the effectiveness of the SALUDIVERSEX affective-sexual education program for people with intellectual disabilities using a controlled trial design. 246 individuals from eastern Spain completed a battery of questionnaires before and after the intervention. Multilevel statistical analyses showed that the risk of experiencing sexual abuse had significantly decreased and knowledge about sexuality significantly increased among those who received the intervention compared to those who did not. The evaluation of the professionals who worked daily with the participants agreed on how knowledge about sexuality and intimacy increased and concerns about sexuality decreased among those in the intervention group. The SALUDIVERSEX program is a powerful educational strategy to promote better sexual health and quality of life for people with intellectual disabilities.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.

Sexual Victimization of Adolescents in Residential Care: Self-Reported and Other-Reported Prevalence.

Adolescents in the child welfare system have been exposed to multiple forms of victimization, most notably sexual victimization, many times underreported and misreported. The main aim of this study was to explore the lifetime prevalence of sexual victimization among adolescents in residential care in Eastern Spain, contrasting self-reported information compared to the information reported by the professionals. Sexual abuse/assault characteristics and effects of gender and age were analyzed. Additionally, the association between sexual revictimization and the relationship with the aggressor as well as the age of the first episode of sexual abuse/assault was analyzed. The sample comprised 346 adolescents (34.1% females, 65.9% males) aged between 11 and 19 years old. The prevalence of sexual victimization reported by adolescents was 35.3%, more than double compared to the information reported by professionals (16.9%). Females experienced significantly more sexual victimization than males (OR = 0.23, 95% CI [0.14, 0.37]). The age of the victim at the first episode of sexual abuse/assault and the relationship with the aggressor were explanatory variables of revictimization. Research such as this is crucial to ascertain that these adolescents have very different needs that will influence the design of affective-sexual education initiatives, which are essential to ensure healthy sexual development.