Intraabdominal Urokinase for the Treatment of Secondary Bacterial Peritonitis in Cirrhosis.

Bacterial peritonitis with loculated ascites in patients with liver cirrhosis can be a therapeutic challenge. We present the case of a patient with liver cirrhosis undergoing pre-transplant evaluation, diagnosed with bacterial peritonitis secondary to urgent surgical intervention Imaging studies identified markedly loculated ascites, with a poor response despite broad-spectrum antibiotic therapy. The use of intraabdominal urokinase was a safe and effective adjuvant treatment for the resolution of this complication.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Bivalent Omicron BA.4/BA.5 BNT162b2 Vaccine in 6-Month- to <12-Year-Olds.

BACKGROUND: With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important. METHODS: We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. RESULTS: In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation. CONCLUSIONS: These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old.

Prematurity and congenital malformations differ according to the type of pregestational diabetes.

BACKGROUND: Diabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM. METHODS: Single-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected. RESULTS: As expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI. CONCLUSIONS: Newborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications.

[Initial experience with cardiac contractility modulation devices in Latin America for the treatment of heart failure]. / Experiencia inicial con dispositivos de modulación de contractilidad cardiaca en Latinoamérica para el tratamiento de la insuficiencia cardiaca.

Objective: To describe the initial experience of cardiac contractility modulation (CCM) implantation in Latin America. Method: We present the first two cases in Latin America of patients with heart failure with reduced left ventricular ejection fraction (LVEF) not candidates for cardiac resynchronization therapy in whom a CCM device was implanted. Results. Results: In both patients we described improvement of the 6-minute walk test, functional class according to the NYHA and LVEF. Conclusions: The modulation of cardiac contractility is currently a treatment option for patients with heart failure in functional class III-IV, with LVEF 25-45%, and a QRS < 130 ms who are not candidates for cardiac resynchronization therapy.

Objetivo: Describir la experiencia inicial de implante de modulación de la contractilidad cardiaca (CCM) en Latinoamérica. Método: Presentamos los dos primeros casos en Latinoamérica de pacientes con insuficiencia cardiaca y fracción de eyección del ventrículo izquierdo (FEVI) reducida no candidatos a terapia de resincronización en quienes se implantó un dispositivo de CCM. Resultados: En ambos pacientes se observó mejoría en la prueba de caminata de 6 minutos, de la clase funcional según la NYHA y de la FEVI. Conclusiones: La CCM actualmente es una opción de tratamiento en pacientes con insuficiencia cardiaca en clase funcional III-IV, con FEVI del 25-45% y QRS < 130 ms que no son candidatos a terapia de resincronización cardiaca. Palabras clave: Insuficiencia cardiaca.

Active microscopic colitis precipitated by fluoxetine.

Microscopic colitis is a form of chronic and recurrent inflammatory bowel disease characterized by non-bloody, watery diarrhea, macroscopically normal colonic mucosa, and characteristic histopathological findings. Some drugs have been described as triggers of colonic inflammation in predisposed individuals, while others may exacerbate microscopic colitis that evolves on its own. We present the case of a patient diagnosed with active microscopic colitis in relation to taking fluoxetine at high doses.

Prolapsed hyperplastic gastric polyp: an uncommon cause of acute pancreatitis.

A 68-year-old male presented to the Emergency Department with a one-month history of intermittent epigastrium pain. Laboratory tests revealed leukocytosis and elevated lipase (4129 UI/l), with normal liver function, so he was admitted for its first episode of acute pancreatitis. Abdominal ultrasound showed liver steatosis, without cholelithiasis or bile duct dilatation. A thoraco-abdominal computed tomography was performed, revealing a pedunculated gastric polyp in lesser curvature measuring 64x38mm with no evidence of metastatic disease. Gastroscopy was performed, showing a 7-cm pedunculated gastric polyp prolapsed through the pylorus into the duodenum. The polyp was moved into the stomach, and a fragmented resection of the polyp was carried out with a hot snare. Histopathologic evaluation was compatible with hyperplastic polyp with low-grade dysplasia. The patient had a favourable evolution with no complications after the procedure.

Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants.

BACKGROUND AND OBJECTIVES: Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS: Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS: Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS: Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.

Remdesivir for COVID-19 in Hospitalized Children: A Phase 2/3 Study.

OBJECTIVES: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. METHODS: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. RESULTS: Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. CONCLUSIONS: In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.

Thrombosis with thrombocytopenia syndrome (TTS) and vaccine-induced immune thrombocytopenia and thrombosis (VITT): Brighton Collaboration case definitions and guidelines for data collection, analysis, and presentation of immunisation safety data.

This is a revision of the online November 2021 Brighton thrombosis with thrombocytopenia syndrome (TTS) case definition and a new Brighton Collaboration case definition for vaccine-induced immune thrombocytopenia and thrombosis (VITT). These case definitions are intended for use in clinical trials and post-licensure pharmacovigilance activities to facilitate safety data comparability across multiple settings. They are not intended to guide clinical management. The case definitions were developed by a group of subject matter and Brighton Collaboration process experts as part of the Coalition for Epidemic Preparedness Innovations (CEPI)-funded Safety Platform for Evaluation of vACcines (SPEAC). The case definitions, each with defined levels of diagnostic certainty, are based on relevant published evidence and expert consensus and are accompanied by specific guidelines for TTS and VITT data collection and analysis. The document underwent peer review by a reference group of vaccine safety stakeholders and haematology experts to ensure case definition useability, applicability and scientific integrity.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

ABSTRACT: Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

Maternal Vaccine Effectiveness Against Influenza-Associated Hospitalizations and Emergency Department Visits in Infants.

Importance: Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited. Objective: To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months. Design, Setting, and Participants: This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to 2020 influenza seasons. Infants younger than 6 months with an ED visit or hospitalization for acute respiratory illness were included from 7 pediatric medical institutions in US cities. Control infants with an influenza-negative molecular test were included for comparison. Data were analyzed from June 2022 to September 2023. Exposure: Maternal influenza vaccination during pregnancy. Main Outcomes and Measures: We estimated maternal vaccine effectiveness against hospitalizations or ED visits in infants younger than 6 months, those younger than 3 months, and by trimester of vaccination. Maternal vaccination status was determined using immunization information systems, medical records, or self-report. Vaccine effectiveness was estimated by comparing the odds of maternal influenza vaccination 14 days or more before delivery in infants with influenza vs those without. Results: Of 3764 infants (223 with influenza and 3541 control infants), 2007 (53%) were born to mothers who were vaccinated during pregnancy. Overall vaccine effectiveness in infants was 34% (95% CI, 12 to 50), 39% (95% CI, 12 to 58) against influenza-associated hospitalizations, and 19% (95% CI, -24 to 48) against ED visits. Among infants younger than 3 months, effectiveness was 53% (95% CI, 30 to 68). Effectiveness was 52% (95% CI, 30 to 68) among infants with mothers who were vaccinated during the third trimester and 17% (95% CI, -15 to 40) among those with mothers who were vaccinated during the first or second trimesters. Conclusions and Relevance: Maternal vaccination was associated with reduced odds of influenza-associated hospitalizations and ED visits in infants younger than 6 months. Effectiveness was greatest among infants younger than 3 months, for those born to mothers vaccinated during the third trimester, and against influenza-associated hospitalizations.

Are the first 1,000 days of life a neglected vital period to prevent the impact on maternal and infant morbimortality of infectious diseases in Latin America? Proceedings of a workshop of experts from the Latin American Pediatric Infectious Diseases Society, SLIPE.

While the first 1,000 days of life are a critical period in child's development, limited information on the main determinants affecting this period in the Latin America and the Caribbean (LAC) region is available. Therefore, the Latin American Pediatric Infectious Diseases Society (SLIPE) held an ad hoc workshop in May 2022 with an expert panel designed to analyze the main factors impacting the development of childhood in the region during this period and the main causes of maternal infant morbimortality. The aim was to identify priorities, generate recommendations, and advise practical actions to improve this situation. Considerations were made about the challenges involved in bridging the gap that separates the region from more developed countries regarding an optimal early childhood and maternal care. Extensive discussion was conducted to reach consensus recommendations on general strategies intended to reduce maternal and infant mortality associated with infections and immune-preventable diseases during the first 1,000 days of life in LAC.

Persistently elevated alkaline phosphatase without hepatopathy?: literature review.

Elevated alkaline phosphatase (ALP) levels are found in multiple hepatobiliary diseases and in bone diseases. ALP can also originate in the intestine and placenta. Very few cases of persistent elevations of IALP or in the context of benign familial intestinal hyperphosphatasemia (BFIH) without underlying pathology have been reported in the literature. In the evaluation of elevated ALP, most patients will not require determination of its isoenzymes. However, it is important to be aware of this entity to avoid unnecessary additional studies and to establish the diagnosis of a persistent but benign biochemical abnormality.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Pediatric High-Grade Gliomas.

Pediatric high-grade gliomas (pHGGs) are diffuse and highly aggressive CNS tumors which remain incurable, with a 5-year overall survival of less than 20%. Within glioma, mutations in the genes encoding the histones H3.1 and H3.3 have been discovered to be age-restricted and specific of pHGGs. This work focuses on the study of pHGGs harboring the H3.3-G34R mutation. H3.3-G34R tumors represent the 9-15% of pHGGs, are restricted to the cerebral hemispheres, and are found predominantly in the adolescent population (median 15.0 years). We have utilized a genetically engineered immunocompetent mouse model for this subtype of pHGG generated via the Sleeping Beauty-transposon system. The analysis of H3.3-G34R genetically engineered brain tumors by RNA-Sequencing and ChIP-Sequencing revealed alterations in the molecular landscape associated to H3.3-G34R expression. In particular, the expression of H3.3-G34R modifies the histone marks deposited at the regulatory elements of genes belonging to the JAK/STAT pathway, leading to an increased activation of this pathway. This histone G34R-mediated epigenetic modifications lead to changes in the tumor immune microenvironment of these tumors, towards an immune-permissive phenotype, making these gliomas susceptible to TK/Flt3L immune-stimulatory gene therapy. The application of this therapeutic approach increased median survival of H3.3-G34R tumor bearing animals, while stimulating the development of anti-tumor immune response and immunological memory. Our data suggests that the proposed immune-mediated gene therapy has potential for clinical translation for the treatment of patients harboring H3.3-G34R high grade gliomas.

Association between Love Breakup and Suicidal Ideation in Peruvian Medical Students: A Cross-Sectional Study during the COVID-19 Pandemic.

Objective: We aimed to determine the association between a major romantic breakup and suicidal ideation in medical students from three universities in Peru. Methods: A cross-sectional study was conducted during the first pandemic wave in 2021 on medical students from three universities in northern Peru. The outcome was suicidal ideation, measured with question nine of the PHQ-9. The exposure was the experience of a major love breakup during the pandemic. In addition, its association with other covariates (age, sex, family members infected with COVID-19, deceased family members with COVID-19, insomnia, and anxiety, among others) was examined. Results and discussions: Out of 370 students, 19.5% reported a major love breakup during the pandemic (95%CI: 15.5-23.8), and 34.3% had suicidal ideation (95%CI: 29.4-39.4). Having a major love breakup was associated with a higher prevalence of suicidal ideation (PR: 1.49, 95%CI: 1.32-1.67). Moderate insomnia (PR: 2.56, 95%CI: 1.70-3.87) and anxiety symptoms (PR: 1.94, 1.10-3.44) were also associated with suicidal ideation. Conclusion: Our study provides evidence of a significant association between a major love breakup and suicidal ideation. This finding emphasizes the need for further research to better understand this association and inform the development of effective suicide prevention policies in medical education.

Body surface area compared to body weight dosing of valganciclovir is associated with increased toxicity in pediatric solid organ transplantation recipients.

Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.