BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors.

The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C+CD57-FcεRIγ+ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.

Complications in Patients with Surgically Altered Gastrointestinal Anatomy Undergoing Endoscopic Retrograde Cholangiopancreatography: 15-Year Experience at a Tertiary Care Center in Latin America.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure, but it poses challenges in patients with surgically altered gastrointestinal anatomy (SAGA). Alternative techniques like single-balloon enteroscopy (SBE), double-balloon enteroscopy (DBE), or push enteroscopy (PE) have been used, albeit with potential complications. Limited Latin American data exists on ERCP complications in SAGA patients. Our goal is to describe complications of ERCP in SAGA at a national referral institution. METHODS: Retrospective, single-center cohort study. All SAGA ERCP procedures performed at the Gastrointestinal Endoscopy Department of the National Institute of Medical Sciences and Nutrition Salvador Zubirán from January 2008 to May 2023 were included. Extracted data from records included procedure specifics, endoscope type, success, and complications. Complications were evaluated during procedure and 28-day post-procedure and classified using the AGREE system. RESULTS: A total of 266 procedures in 174 patients were included, 74% were women, and the median age was 44 years. Predominant modified anatomy was Roux-en-Y biliary reconstruction (79%), followed by Whipple procedure (13%) and subtotal gastrectomy with Roux-en-Y reconstruction (6.0%). The main indications were cholangitis with stricture (31%), stricture (19%), and cholangitis (19%). DBE was used in 89%, PE in 7.5%, and SBE in 3.4%. Success rates were 77% endoscopic, 72% technical, and 69% therapeutic; in 30%, the procedure was unsuccessful. Complications happened in 18% of cases, most commonly cholangitis (7.5%), followed by perforation (2.6%) and hemorrhage (1.9%). According to the AGREE classification, 10.9% were grades 1 and 2, 6.4% were grade 3, and 0.4% were grade 4 complications. No significant differences emerged between groups with and without complications. Procedures increased over time, but complications and unsuccessful procedures remained stable. CONCLUSION: ERCP complications align with international data, often not requiring invasive treatment. Enhanced exposure to such cases correlates with fewer complications and failures. Prospective studies are essential to identify complication and failure predictors.

Periosteal Ewing Sarcoma with Distant Metastases: Report of Two Patients and Review of the Literature.

Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in the long tubular bone diaphysis. PES rarely develops distant metastases. We report two patients of this rare ES location that were found on the distal tibial shaft and proximal femoral diaphysis of a 21-year-old man and an 8-year-old boy, respectively. Both patients were treated with neoadjuvant chemotherapy, wide resection, and adjuvant chemotherapy. One of our patients had lung metastases at the time of diagnosis and died 5 years later. The other patient presented intramedullary humeral bone metastasis 19 years after diagnosis. There has been no evidence of disease in the 26 years of follow-up. Close follow-up of periosteal ES is recommended because distant metastases may exceptionally occur, even several years after diagnosis.

Severe Impairment of T-cell Immunity and Pulmonary GvHD Are Major Risk Factors for Nontuberculous Mycobacterial Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but literature in children is scarce. We report 6 episodes of disseminated or pulmonary nontuberculous mycobacteria infection among 5 pediatric hematopoietic stem cell transplant recipients. All but one were caused by Mycobacterium avium complex. Four patients died, 2 related to nontuberculous mycobacteria infection.

Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies.

BACKGROUND: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients. METHODS: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation. RESULTS: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027). CONCLUSIONS: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.

"Prevalence and Associated Factors of Perinatal Suicide Risk in Spanish Women".

Suicide is one of the leading causes of death worldwide, and in the perinatal period, the trend is increasing, even up to 100 times in the US. No studies have been carried out with validated instruments despite abundant recommendations to do so. This study aims to determine the prevalence of perinatal suicide risk in Spanish women, as well as the factors associated with it. A cross-sectional study was carried out with 908 women in the perinatal stage. Sociodemographic and obstetric variables, anxiety level (GAD-7), social support (DUKE-UNC), risk of intimate violence (WAST), and suicidal ideation (Paykel) were collected. Crude (OR) and adjusted odds ratios (aOR) were calculated using logistic regression for the main risk factors for suicidal ideation. The prevalence of suicidal ideation was 19.3% (175), and suicide attempt 2.4% (22). In the perinatal stage, the risk factors were anxiety [aOR of 1.08 (95% CI: 1.04-1.31)], experiencing a possible situation of intimate partner violence [aOR of 1.59 (95% CI: 1.04-2.43)], and a risk of PPD [aOR of 3.00 (95% CI: 1.86-4.81)]. Perceived social support appears as a protective factor [aOR of 0.97 (95% CI: 0.95-0.99)], along with skin-to-skin contact with the baby during childbirth [aOR 0.50 (95% CI: 0.28-0.88)]. Conclusions: Presenting anxiety or depression, little social support, and living in a possible situation of intimate partner violence are associated with a greater risk of suicidal ideation during the perinatal stage.

Chromosome analysis of 303 pregnancy losses in Mexico.

BACKGROUND: Chromosomal abnormalities are present in 50 to 60% of miscarriages and in 6 to 19% of stillbirths. Although microarrays are preferred for studying chromosomal abnormalities, many hospitals cannot offer this methodology. OBJECTIVE: To present the results of the cytogenetic analysis of 303 products of conception (POC), which included 184 miscarriages, 49 stillbirths and 17 cases of undefined age. MATERIAL AND METHODS: Karyotyping, fluorescence in situ hybridization, short tandem repeats and microarrays were used, depending on the type of loss and available sample. RESULTS: In 29 POCs we found maternal tissue and were eliminated from the analyses. Informative results were obtained in 250 (91.2 %)/274 cases; the karyotyping success rate was 80.7%; that of single nucleotide polymorphism microarrays, 94.5%; and that of fluorescence in situ hybridization and short tandem repeat, 100%. Cytogenetic abnormalities were observed in 57.6% of miscarriages and in 24.5% of stillbirths; 94% of total anomalies were numerical and 6% were submicroscopic. CONCLUSIONS: Karyotyping with simultaneous short tandem repeat study to rule out contamination of maternal cells is effective for studying miscarriages; in stillbirths, microarrays are recommended.

ANTECEDENTES: Las alteraciones cromosómicas están presentes en 50 a 60 % de los abortos espontáneos y en 6 a 19 % de los mortinatos. Aunque se prefieren los microarreglos para estudiarlos, numerosos hospitales no pueden ofrecerlos. OBJETIVO: Presentar los resultados del estudio citogenético de 303 productos de la concepción (POC), 184 se obtuvieron de abortos espontáneos, 49 fueron mortinatos y en 17 no se identificó la de edad gestacional. MATERIAL Y MÉTODOS: Se empleó cariotipo, hibridación in situ con fluorescencia, secuencias cortas repetidas en tándem y microarreglos, según el tipo de pérdida y la muestra disponible. RESULTADOS: En 29 POC se encontró tejido materno, por lo que fueron eliminados de los análisis. En 250 (91.2 %)/274 casos se obtuvieron resultados informativos; la tasa de éxito del cariotipo fue de 80.7 %; la de los microarreglos de SNP, de 94.5 %; y la de la hibridación fluorescente in situ y la repetición corta en tándem, de 100 %. Se observaron anomalías citogenéticas en 57.6 % de los abortos espontáneos y en 24.5 % de los mortinatos; 94 % de las anomalías fueron numéricas y 6 %, submicroscópicas. CONCLUSIONES: El cariotipo en conjunto con el estudio de secuencias cortas repetidas en tándem para descartar contaminación de células maternas es efectivo para estudiar abortos espontáneos; los microarreglos se recomiendan en los mortinatos.

Development of a Predictive Model for Skin-to-Skin Contact Immediately after Birth: A Cross-Sectional Study.

The aim of this study was to develop and validate a predictive model for the establishment of skin-to-skin contact immediately after birth. A descriptive cross-sectional study was conducted during the last trimester of 2022 and the first trimester of 2023 with women who had given birth in Spain. A questionnaire containing sociodemographic, psychosocial, and health variables referring to the mother and the newborn, as well as the Bond and Attachment questionnaire (VAMF, for its name in Spanish) for the analysis of the mother-child bond and attachment, were administered. A multivariate analysis was performed, and areas under the ROC curve (AUC) with their 95% confidence intervals (CI) and the predictive characteristics of these models were estimated. In total, 1077 women participated. The prevalence of early skin-to-skin contact after delivery was 50.2% (468) in the derivation cohort and 49.8% (464) in the validation cohort. Multivariate analysis showed that prematurity, type of delivery, and birth experience were statistically significant, so they were included in the model (p ≤ 0.05). The predictive ability (AUC ROC) was good in both the derivation cohort, yielding 0.92 (95% CI: 0.89-0.95), and in the validation cohort, yielding 0.89 (95% CI: 0.85-0.93). This study developed a predictive model identifying factors facilitating early skin-to-skin contact between a mother and her newborn immediately after birth.

Preparation and validation of a predictive model of breastfeeding initiation in the first hour of life.

OBJECTIVE: The objective was to develop and validate a predictive model of initiation of breastfeeding in the first hour after delivery. METHODS: Retrospective cohort study on women who gave birth between 2013 and 2018 in Spain. For data collection, an ad hoc questionnaire was designed to be filled in by the mothers, which was distributed to the different Spanish breastfeeding associations which, in turn, shared it with their associate partners. The development of the predictive model was made on a cohort of 3218 women (2/3) and was validated on a cohort of 1609 women (1/3). Mothers whose children were admitted to hospital at the time of birth were excluded. A multivariate analysis was performed by means of logistic regression, and predictive ability was determined by areas under the ROC curve (AUC). RESULTS: 81.0 % (2608) women started breastfeeding in the first hour in the derivation cohort, and 80.1 % (1289) in the validation cohort. The predictive factors in the final model were: the highest number of children and skin-to-skin contact at birth as flattering factors, while dystocic delivery reduced the likelihood of the onset of breastfeeding. The predictive ability (ROC AUC) in the derivation cohort was 0.89 (CI 95 %: 0.87-0.90), while in the validation cohort it was 0.89 (CI 95 %: 0.87-0.92). CONCLUSIONS: This three-variable predictive model has excellent predictive ability in both the derivation cohort and the validation cohort. This model can identify women who are at high risk of non-initiating breastfeeding within the first hour after delivery.

Outcomes of allogeneic haematopoietic cell transplantation for myelofibrosis in children and adolescents: the retrospective study of the EBMT Paediatric Diseases WP.

This retrospective study evaluated 35 children (median age 5.2 years; range 0.4-18) with myelofibrosis (MF), including 33 with primary myelofibrosis and 2 with secondary myelofibrosis transplanted from matched sibling donor (MSD) (n = 17) or non-MSD (n = 18) between 2000 and 2022. Conditioning was usually chemotherapy-based (n = 33) and myeloablative (n = 32). Fifteen patients received bone marrow (BM), 14 haematopoietic cells (HC) from peripheral blood (PB), and 6 from cord blood (CB). Day +100 acute GvHD II-IV incidence was significantly lower after MSD-haematopoietic cell transplantation (MSD-HCT) than after non-MSD-HCT [18.8% (4.3-41.1) vs 58.8% (31-78.6); p = 0.01]. Six-year non-relapse mortality (NRM) was 18% (7.1-32.8), relapse incidence was 15.9% (5.6-30.9), progression-free survival (PFS) was 66.1% (47-79.7), GvHD-free relapse-free survival was 50% (30.6-66.7), and overall survival (OS) was 71.1% (51.4-84). Six-year PFS and OS were significantly higher after BM transplantation compared to HCT from other sources [85.1% (52.3-96.1) vs 50.8% (26.3-71), p = 0.03, and 90.9% (50.8-98.7) vs 54% (28.1-74.2), p = 0.01, respectively], whereas NRM was significantly lower [0% vs 32% (12.3-53.9); p = 0.02]. This first multicentre study on outcomes of allogeneic HCT in children with myelofibrosis proves feasibility and curative effect of transplantation in these children, suggests that bone marrow transplantation is associated with better outcomes, and indicates the need for further studies.

A Qualitative Exploration of the Perceptions of Women Living with Pelvic Floor Disorders and Factors Related to Quality of Life.

Background: Pelvic floor dysfunction encompasses conditions like urinary and fecal incontinence, pelvic organ prolapse, and pelvic pain, significantly affecting women's quality of life. Despite its prevalence, few studies have adopted a qualitative approach to understanding women's perceptions and emotions regarding these issues. This study aims to delve into how women with pelvic floor disorders perceive their condition and its impact on their daily lives. Methods: We analyzed qualitative data from interviews with 160 women suffering from pelvic floor dysfunctions. Using inductive qualitative content analysis, we systematically examined the data to identify variations, differences, and similarities. Results: The analysis revealed four primary themes in the women's narratives: "Physical Impacts", "Emotional and Psychological Impacts", "Social and Relational Impacts", and "Sexual Health Impacts", along with 12 subthemes. The findings predominantly highlight how pelvic floor dysfunctions detrimentally affect women's quality of life and emotional well-being, instilling fear and insecurity in daily activities, compounded by sleep disturbances and sexual dysfunction. Conclusions: Women living with pelvic floor dysfunction face multifaceted challenges that adversely affect various aspects of their lives, diminishing their overall quality of life. This includes notable impacts on sleep, physical, and sexual activities. However, not all affected women report these issues, often due to fear of stigma, choosing instead to conceal their struggles in an effort to maintain an appearance of normalcy.

Professional approach to the care of women who have suffered a perinatal loss.

To understand the experience, training, and needs of midwives in their approach to perinatal grief. A descriptive cross-sectional study was carried out using an online questionnaire with 26 questions related to institutional management and individual clinical practices in the care of a perinatal loss was developed by a team of midwives from the Hospital "La Mancha-Centro" of Alcazar de San Juan (Ciudad Real). Strobe checklist was followed. A total of 267 midwives participated. A total of 92.1% (246) of the centers had specific protocols for action, but each professional applied their own criteria. The presence of a perinatal psychology team was nonexistent according to 88% (235) of those surveyed. Regarding their training and professional experience, 16.5% (44) of the midwives had never received training. Only 4.1% (11) of the midwives felt very prepared to care for women with a perinatal loss. Among the factors associated with greater application of recommended practices in the face of perinatal death by midwives were being a woman, having prior training on care during perinatal death, and a greater perception of preparation (p < 0.05). The perception of lack of preparation on the part of midwives in the accompaniment of these families was high.

Midwives' approach to the prevention and repair of obstetric perineal trauma in Spain.

AIM: Different clinical practice guidelines include recommendations on how to prevent and repair obstetric perineal trauma, as well as the use of episiotomy. To evaluate the variability in midwives' professional practices for preventing and repairing perineal trauma, as well as the professional factors that may be associated with the restrictive use of episiotomy. DESIGN: Observational cross-sectional study. METHODS: Three hundred five midwives completed an anonymous questionnaire developed by the authors and distributed across various midwifery scientific societies. The main outcomes measured were the frequencies of adopting specific practices related to perineal injury prevention and repair, episiotomy technique and restrictive episiotomy use (<10%). Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals were estimated. RESULTS: Intrapartum perineal massage was not normally used by 253 (83%) of midwives, and 186 (61%) applied compresses soaked in warm water to the perineum. Regarding episiotomy, there was a great deal of variability, noting that 129 (42.3%) adopted a restrictive use of this procedure, 125 (41%) performed it between 10% and 20%, while 51 midwives (16.7%) performed it in more than 20% of cases. In addition, 165 (54.1%) midwives followed an incision angle of 60º. Concerning tears, 155 (50.8%) usually sutured first-degree tears and 273 (89.5%) always sutured second-degree tears. Midwives attending home births (aOR = 6.5; 95% CI: 2.69-15.69), working at a teaching hospital (aOR = 3.69; 95% CI: 1.39-9.84), and the ones who recently completed their professional training (aOR = 3.58; 95% CI: 1.46-8.79) were significantly more likely to adopt a restrictive use of episiotomy. CONCLUSIONS: There is a significant variability in Spanish midwives' practices for preventing and repairing perineal tears. Moreover, the restrictive use of episiotomy is associated with midwives attending home births, working in teaching hospitals and having recent professional training. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Mismatched related donor allogeneic haematopoietic cell transplantation compared to other donor types for Ph+ chronic myeloid leukaemia: A retrospective analysis from the Chronic Malignancies Working Party of the EBMT.

Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse-free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non-relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft-versus-host disease (GvHD)-free/relapse-free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.

Osteocalcin associates with bone mineral density and VDR gene polymorphisms in type 1 and type 2 diabetes.

Objectives: Bone metabolism is impaired in diabetes mellitus (DM). Our objective is to evaluate the association of bone turnover markers (BTM) and vitamin D receptor (VDR) gene polymorphisms with bone mineral density (BMD) in DM type 1 (T1D) and DM type 2 (T2D). Methods: A total of 165 patients (53 T1D and 112 T2D) were enrolled. BMD was measured by dual-energy X-ray absorptiometry (DEXA). Plasma osteocalcin (OC), beta-CrossLaps (ß-CTX) and N-amino terminal propeptide of type I collagen (P1NP) and VDR gene polymorphisms were evaluated. Results: Participants were 53 T1D (41 years [31-48]) and 112 T2D (60 years [51-66]). BMD were not statistically different between the groups. OC (p<0.001) and P1NP levels (p<0.001) were higher in patients with T1D. The areas under the curve for the prediction of bone pathology were 0.732 (p=0.038) for OC in T1D and 0.697 (p=0.007) in T2D. A significant association was found between lower lumbar BMD and the A allele of BsmI (p=0.03), the A allele of ApaI (p=0.04) and the allele C of the Taql (p=0.046). Also, a significant correlation was found with higher OC levels and the G allele of BsmI (p=0.044), C allele of ApaI (p=0.011), T allele of Taql (p=0.006) and with C allele of FokI (p=0.004). Conclusions: The high negative predictive value of the cut-off point for OC suggests that could be useful in excluding the risk suffering bone loss, allowing offering a personalized clinical approach to prevent this pathology.

The impact of incorporating a simulation program into the undergraduate nursing curricula: A cross-sectional descriptive study.

AIM: To determine the degree of satisfaction for each academic year and according to the type of simulation performed (simulated patient actor/advanced simulator) among nursing students after the use of clinical simulation. INTRODUCTION: Clinical simulation is currently being incorporated in a cross-cutting manner throughout undergraduate nursing education. Its implementation requires a novel curricular design and educational changes throughout the academic subjects. DESIGN: A cross-sectional descriptive study was performed. METHODS: During the academic years 2018-2019 and 2019-2020, 425 students completed the High-Fidelity Simulation Satisfaction Reduced Scale for Students based on 25 questions and six factors, with a total score between 0 and 125. In total, 91 simulation sessions were performed among students who had different degrees of clinical and previous experience with simulation as well as standardized patient versus advanced simulator. A bivariate analysis was performed, comparing the total scores and the different subscales by sex, previous experience, academic year, and simulation methodology. Linear regression was used for both bivariate and multivariate analysis. RESULTS: The mean scale score was 116.8 (SD=7.44). The factor with the highest score was "F2: feedback or subsequent reflection", with a mean score of 14.71 (SD=0.73) out of 15. Fourth year students scored the highest (mean=119.17; SD=5.28). Students who underwent simulation training with a simulated patient actor presented a higher level of overall satisfaction (p<0.05) (Mean=120.31; SD=4.91), compared to students who used an advanced simulator (Mean=118.11; SD=5.75). CONCLUSIONS: Satisfaction with the simulation program was higher in fourth-year students compared to first-year students and was also higher when a simulated patient actor was used compared to an advanced simulator. The most highly valued aspect was the subsequent debriefing or reflective process.

Trends in epidemiology, surgical management, and prognosis of infective endocarditis during the XXI century in Spain: A population-based nationwide study.

BACKGROUND: Few population-based studies have evaluated the epidemiology of infective endocarditis (IE). Changes in population demographics and guidelines on IE may have affected both the incidence and outcomes of IE. Therefore, the aim of our study is to provide contemporary population-based epidemiological data of IE in Spain. METHODS: Retrospective nationwide observational study using data from the Spanish National Health System Discharge Database. We included all patients hospitalized with IE from January 2000 to December 2019. RESULTS: A total of 64,550 IE episodes were included. The incidence of IE rose from 5.25 cases/100,000 person-year in 2000 to 7.21 in 2019, with a 2% annual percentage change (95% CI 1.3-2.6). IE incidence was higher among those aged 85 or older (43.5 cases/100.000 person-years). Trends across the study period varied with sex and age. Patients with IE were progressively older (63.9 years in 2000-2004 to 70.0 in 2015-2019, p < 0.001) and had more frequent comorbidities and predispositions, including, previous valvular prosthesis (12.1% vs 20.9%, p < 0.001). After adjustment, a progressive reduction in mortality was noted including in 2015-2019 compared to 2010-2014 (adjusted odds ratio 0.93, 95% confident interval 0.88-0.99, p = 0.023)., which was associated with more frequent cardiac surgery in recent years (15.1% in 2010-2014 vs 19.9% in 2015-2019). CONCLUSIONS: In Spain, the incidence of IE has increased during the XXI century, with a more pronounced increase in elderly individuals. Adjusted-mortality decreased over the years, which could be related to a higher percentage of surgery. Our results highlight the changing epidemiology of IE.

The paradigm of total body irradiation in acute lymphoblastic leukaemia: Therapeutic effectiveness versus the challenges of toxicity.

INTRODUCTION: Total body irradiation (TBI) is part of the myeloablative conditioning for hematopoietic stem cell transplantation (HSCT) in malignant hematologic disorders. This therapy has recently shown improved survival in acute lymphoblastic leukemia (ALL) compared to chemotherapy-based regimens. However, side effects are a significant limitation, especially in the pediatric population. PATIENTS AND METHODS: We retrospectively analyzed the survival of patients with ALL who underwent an HSCT at a tertiary hospital between 1996 and 2009 (N = 69 HSCT in 57 patients). We differentiated a cohort that received TBI (N = 44) from another that did not (N = 25). Subsequently, we interviewed the survivors from the TBI group with a minimum of 10 years of follow-up (N = 18), asking about the presence of side effects. RESULTS: The overall survival (OS) at 2 and 5 years was 79.1% and 65.2% respectively for the TBI group and 66.2% and 55.8% for the non-TBI group, although this difference was not significant (P=.31). The event-free survival (EFS) at 2 and 5 years was 77.3% and 63.6% respectively for the TBI group and 56% and 32% for the non-TBI group (P=.02). The probability of relapse (PR) at 2 years for those who received TBI was 10% compared to 28.6% for those who did not receive TBI (P=.005). Survivors who received TBI developed secondary neoplasms (39%), dyslipidemia (67%), cognitive impairments affecting memory (44%), recurrent respiratory infections (39%), thyroid abnormalities (45%), premature ovarian failure (89%), cataracts (22%), and psychological problems (44%). However, the quality of life, as self-assessed by the patients, was considered good for 83% of the participants.. CONCLUSIONS: Patients who received TBI had significantly higher EFS and lower PR. However, adverse effects are frequent and significant, although they do not subjectively affect quality of life.

Impact of COVID-19 vaccination on liver transplant recipients. Experience in a reference center in Mexico.

BACKGROUND AND AIMS: COVID-19 vaccination has proved to be effective to prevent symptomatic infection and severe disease even in immunocompromised patients including liver transplant patients. We aim to assess the impact of COVID-19 vaccination on the mortality and development of severe and critical disease in our center. METHODS: A retrospective cohort study of LT patients in a reference center between March 2020 and February 2022. Demographic data, cirrhosis etiology, time on liver transplantation, immunosuppressive therapies, and vaccination status were recorded at the time of diagnosis. Primary outcome was death due to COVID-19, and secondary outcomes included the development of severe COVID-19 and intensive care unit (ICU) requirement. RESULTS: 153 of 324 LT recipients developed COVID-19, in whom the main causes of cirrhosis were HCV infection and metabolic-associated fatty liver disease. The vaccines used were BNT162b2 (48.6%), ChAdOx1 nCoV-19 (21.6%), mRNA-1273 vaccine (1.4%), Sputnik V (14.9%), Ad5-nCoV-S (4.1%) and CoronaVac (9.5%). Case fatality and ICU requirement risk were similar among vaccinated and unvaccinated LT patients (adjusted relative case fatality for vaccinated versus unvaccinated of 0.68, 95% CI 0.14-3.24, p = 0.62; adjusted relative risk [aRR] for ICU requirement of 0.45, 95% CI 0.11-1.88, p = 0.27). Nonetheless, vaccination was associated with a lower risk of severe disease (aRR for severe disease of 0.32, 95% CI 0.14-0.71, p = 0.005). CONCLUSIONS: Vaccination reduces the risk of severe COVID-19 in LT patients, regardless of the scheme used. Vaccination should be encouraged for all.