Inter-parental conflict and empathy in early adolescence as predictors of dating violence perpetration in adolescence and adulthood.

Witnessing inter-parental conflict is associated with dating violence perpetration in late adolescence and adulthood. This relationship may be moderated by adolescents' empathy, with more empathic youth viewing their parents' conflict behavior as less acceptable, and thus refraining from dating violence perpetration. This study sought to determine if empathy buffers the effects of inter-parental conflict in early adolescence on expected dating violence perpetration in early adolescence and actual dating violence perpetration in late adolescence and adulthood. Moreover, this study tested if expected dating violence perpetration in early adolescence and dating violence perpetration in late adolescence mediate the effects of inter-parental conflict and empathy on dating violence perpetration in adulthood. Sex differences in these relationships were also examined. The sample included 412 adolescents (52% male, 73% Black, 25% White, 2% Other) who participated at three time points between 2006 and 2022 (T1-T3, Mean age = 13, 18, 28 years). Results indicated that higher inter-parental conflict and lower empathy were associated with higher expected dating violence perpetration at T1 in both males and females. Inter-parental conflict at T1 predicted higher dating violence perpetration at T3 through expected dating violence perpetration at T1 and dating violence perpetration at T2. Empathy at T1 predicted lower dating violence perpetration at T3 directly and also indirectly through lower expected dating violence at T1 and lower dating violence perpetration at T2 in both sexes. There were no interaction effects of inter-parental conflict and empathy on expected or actual dating violence perpetration at any age.

Interpersonal school violence and mother-child communication about violence in relation to empathy in early adolescence.

INTRODUCTION: Exposure to interpersonal violence at school has been linked with lower empathy, but less is known about factors that may moderate this relationship. Positive parent-child communication has been associated with higher empathy during adolescence and children of parents that communicate their disapproval of violent behavior respond more peacefully in situations involving violence. Mother-child communication about violence may therefore reduce the risk of desensitization to violent behavior and promote empathy in youth that are frequently exposed to violence. Thus, this study examines whether mother-child communication about violence mitigates the association between exposure to interpersonal school violence and adolescents' empathy. METHODS: This study addressed this question using a diverse sample of early adolescents from the Southeastern United States in 2003 (N = 642; mean age 11.3 years; 52% male; 76% Black, 22% non-Hispanic White). Adolescents reported on how often they witness or experience interpersonal violence at school and how often they communicate with their mother about violence and how to avoid it. Adolescents also self-reported on their level of empathy. RESULTS: Results from a hierarchical regression model showed that exposure to interpersonal school violence and lower mother-child communication about violence were uniquely associated with lower empathy, but communication about violence did not moderate the link between interpersonal school violence exposure and empathy. There were no sex differences in these relationships. CONCLUSIONS: Contrary to the hypothesis, youth who experience and witness interpersonal violence at school show lower empathy independent of whether youth communicate with their mother about violence and responding to violent situations.

Using digital photographs as a tool to assess the clinical color stability of lithium disilicate veneers: A clinical trial.

STATEMENT OF PROBLEM: Clinical information regarding the color stability of lithium disilicate veneers by using different methods of evaluation is scarce. PURPOSE: This clinical trial aimed to evaluate whether digital photographs are a reliable method of clinically assessing the color stability of lithium disilicate veneers. Standardized digital photographs (ELAB) were compared with the VITA Easyshade spectrophotometer (ES) at baseline and at a 6-month follow-up. MATERIAL AND METHODS: A split-mouth model was used in this randomized clinical trial to assess the performance of ceramic veneers (N=162), which were produced by either the CAD (IPS e.max CAD; n=81) or PRESS technique by heat pressing (IPS e.max PRESS; n=81), including the color dimension assessment. The ELAB evaluation was performed by making digital photographs with polarized light and a white balance (WhiBal) card. These data were transferred to the Adobe Lightroom CC2015 software program in RAW extension. The Digital Color Meter App (Apple) was used to measure L∗, a∗, and b∗ coordinates in this method. The ES color evaluation was performed with a spectrophotometer (Easy Shade) (control group) in the CIELab system. Measurements were performed 1 week after cementation (baseline) and at a 6-month follow-up. Data collected by the ELAB and ES methods were analyzed by a blinded calibrated operator to calculate ΔE by using the Mann-Whitney-Wilcoxon test (α=.05). RESULTS: For all periods, the comparison among ELAB and ES methods (P=.331), CAD×PRESS by ELAB (P=.658), and CAD×PRESS by ES (P=.833) showed no statistically significant differences. CONCLUSIONS: Standardized digital photographs (ELAB) were shown to be a straightforward and available resource for evaluating the color stability of lithium disilicate veneers, manufactured by CAD or PRESS.

Understanding drivers of domestic public expenditure on reproductive, maternal, neonatal and child health in Peru at district level: an ecological study.

BACKGROUND: Peru has increased substantially its domestic public expenditure in maternal and child health. Peruvian departments are heterogeneous in contextual and geographic factors, underlining the importance of disaggregated expenditure analysis up to the district level. We aimed to assess possible district level factors influencing public expenditure on reproductive, maternal, neonatal and child health (RMNCH) in Peru. METHODS: We performed an ecological study in 24 departments, with specific RMNCH expenditure indicators as outcomes, and covariates of different hierarchical dimensions as predictors. To account for the influence of variables included in the different dimensions over time and across departments, we chose a stepwise multilevel mixed-effects regression model, with department-year as the unit of analysis. RESULTS: Public expenditure increased in all departments, particularly for maternal-neonatal and child health activities, with a different pace across departments. The multilevel analysis did not reveal consistently influential factors, except for previous year expenditure on reproductive and maternal-neonatal health. Our findings may be explained by a combination of inertial expenditure, a results-based budgeting approach to increase expenditure efficiency and effectiveness, and by a mixed-effects decentralization process. Sample size, interactions and collinearity cannot be ruled out completely. CONCLUSIONS: Public district-level RMNCH expenditure has increased remarkably in Peru. Evidence on underlying factors influencing such trends warrants further research, most likely through a combination of quantitative and qualitative approaches.

Meckel's diverticulitis: a laparoscopic approach.

Meckel's diverticulum is an infrequent malformation (2% of the population) and the most frequent complication is bleeding followed by diverticulitis. This usually occurs with clinical signs and symptoms of acute appendicitis in adults. The diagnosis requires a high index of suspicion and is based on complementary tests in most cases (mainly CT).

Endovascular Repair of Iatrogenic Iliocaval Fistula Causing High-Output Cardiac Failure after Spine Fusion.

The case being presented is a 35-year-old female with a 3-year history of progressive dyspnea and right-sided heart failure following spine surgery. Physical examination identified a continuous bruit in the lower abdomen radiating to her back which prompted further evaluation. Echocardiography showed normal left ventricle systolic function, enlarged right ventricle, functional tricuspid regurgitation, and moderate pulmonary hypertension. A computed tomography (CT) scan of the abdomen and pelvis demonstrated findings consistent with an arteriovenous fistula (AVF) between the right common iliac artery and the inferior vena cava. She underwent an uneventful endovascular repair without perioperative complication. The patient's symptoms resolved a few hours after the procedure and she continued to be symptom free at 3-month follow-up. This case illustrates an iatrogenic iliocaval fistula causing high-output cardiac failure which was successfully treated endovascularly with excellent clinical result.

Factors behind the success story of under-five stunting in Peru: a district ecological multilevel analysis.

BACKGROUND: Stunting prevalence in children less than 5 years has remained stagnated in Peru from 1992 to 2007, with a rapid reduction thereafter. We aimed to assess the role of different predictors on stunting reduction over time and across departments, from 2000 to 2012. METHODS: We used various secondary data sources to describe time trends of stunting and of possible predictors that included distal to proximal determinants. We determined a ranking of departments by annual change of stunting and of different predictors. To account for variation over time and across departments, we used an ecological hierarchical approach based on a multilevel mixed-effects regression model, considering stunting as the outcome. Our unit of analysis was one department-year. RESULTS: Stunting followed a decreasing trend in all departments, with differing slopes. The reduction pace was higher from 2007-2008 onwards. The departments with the highest annual stunting reduction were Cusco (-2.31%), Amazonas (-1.57%), Puno (-1.54%), Huanuco (-1.52%), and Ancash (-1.44). Those with the lowest reduction were Ica (-0.67%), Ucayali (-0.64%), Tumbes (-0.45%), Lima (-0.37%), and Tacna (-0.31%). Amazon and Andean departments, with the highest baseline poverty rates and concentrating the highest rural populations, showed the highest stunting reduction. In the multilevel analysis, when accounting for confounding, social determinants seemed to be the most important factors influencing annual stunting reduction, with significant variation between departments. CONCLUSIONS: Stunting reduction may be explained by the adoption of anti-poverty policies and sustained implementation of equitable crosscutting interventions, with focus on poorest areas. Inclusion of quality indicators for reproductive, maternal, neonatal and child health interventions may enable further analyses to show the influence of these factors. After a long stagnation period, Peru reduced dramatically its national and departmental stunting prevalence, thanks to a combination of social determinants and crosscutting factors. This experience offers useful lessons to other countries trying to improve their children's nutrition.

Parity and Overweight/Obesity in Peruvian Women.

INTRODUCTION: The rise in noncommunicable diseases and their risk factors in developing countries may have changed or intensified the effect of parity on obesity. We aimed to assess this association in Peruvian women using data from a nationally representative survey. METHODS: We used data from Peru's Demographic and Health Survey, 2012. Parity was defined as the number of children ever born to a woman. We defined overweight as having a body mass index (BMI, kg/m2) of 25.0 to 29.9 and obesity as a BMI ≥30.0. Generalized linear models were used to evaluate the association between parity and BMI and BMI categories, by area of residence and age, adjusting for confounders. RESULTS: Data from 16,082 women were analyzed. Mean parity was 2.25 (95% confidence interval [CI], 2.17-2.33) among rural women and 1.40 (95% CI, 1.36-1.43) among urban women. Mean BMI was 26.0 (standard deviation, 4.6). We found evidence of an association between parity and BMI, particularly in younger women; BMI was up to 4 units higher in rural areas and 2 units higher in urban areas. An association between parity and BMI categories was observed in rural areas as a gradient, being highest in younger women. CONCLUSION: We found a positive association between parity and overweight/obesity. This relationship was stronger in rural areas and among younger mothers.

Remaining missed opportunities of child survival in Peru: modelling mortality impact of universal and equitable coverage of proven interventions.

BACKGROUND: Peru has made great improvements in reducing stunting and child mortality in the past decade, and has reached the Millennium Development Goals 1 and 4. The remaining challenges or missed opportunities for child survival needs to be identified and quantified, in order to guide the next steps to further improve child survival in Peru. METHODS: We used the Lives Saved Tool (LiST) to project the mortality impact of proven interventions reaching every women and child in need, and the mortality impact of eliminating inequalities in coverage distribution between wealth quintiles and urban-rural residence. RESULTS: Our analyses quantified the remaining missed opportunities in Peru, where prioritizing scale-up of facility-based case management for all small and sick babies will be most effective in mortality reduction, compared to other evidenced-based interventions that prevent maternal and child deaths. Eliminating coverage disparities between the poorest quintiles and the richest will reduce under-five and neonatal mortality by 22.0 and 40.6 %, while eliminating coverage disparities between those living in rural and urban areas will reduce under-five and neonatal mortality by 29.3 and 45.2 %. This projected neonatal mortality reduction achieved by eliminating coverage disparities is almost comparable to that already achieved by Peru over the past decade. CONCLUSIONS: Although Peru has made great strides in improving child survival, further improvement in child health, especially in newborn health can be achieved if there is universal and equitable coverage of proven, quality health facility-based interventions. The magnitude of reduction in mortality will be similar to what has been achieved in the past decade. Strengthening health system to identify, understand, and direct resources to the poor and rural areas will ensure that Peru achieve the Sustainable Development Goals by 2030.

Examining national and district-level trends in neonatal health in Peru through an equity lens: a success story driven by political will and societal advocacy.

BACKGROUND: Peru has impressively reduced its neonatal mortality rate (NMR). We aimed, for the period 2000-2013, to: (a) describe national and district NMR variations over time; (b) assess NMR trends by wealth quintile and place of residence; (c) describe evolution of mortality causes; (d) assess completeness of registered mortality; (e) assess coverage and equity of NMR-related interventions; and (f) explore underlying driving factors. METHODS: We compared national NMR time trends from different sources. To describe NMR trends by wealth quintiles, place of residence and districts, we pooled data on births and deaths by calendar year for neonates born to women interviewed in multiple surveys. We disaggregated coverage of NMR-related interventions by wealth quintiles and place of residence. To identify success factors, we ran regression analyses and combined desk reviews with qualitative interviews and group discussions. RESULTS: NMR fell by 51 % from 2000 to 2013, second only to Brazil in Latin America. Reduction was higher in rural and poorest segments (52 and 58 %). District NMR change varied by source. Regarding cause-specific NMRs, prematurity decreased from 7.0 to 3.2 per 1,000 live births, intra-partum related events from 2.9 to 1.2, congenital abnormalities from 2.4 to 1.8, sepsis from 1.9 to 0.8, pneumonia from 0.9 to 0.4, and other conditions from 1.2 to 0.7. Under-registration of neonatal deaths decreased recently, more in districts with higher development index and lower rural population. Coverage of family planning, antenatal care and skilled birth attendance increased more in rural areas and in the poorest quintile. Regressions did not show consistent associations between mortality and predictors. During the study period social determinants improved substantially, and dramatic out-of-health-sector and health-sector changes occurred. Rural areas and the poorest quintile experienced greater NMR reduction. This progress was driven, within a context of economic growth and poverty reduction, by a combination of strong societal advocacy and political will, which translated into pro-poor implementation of evidence-based interventions with a rights-based approach. CONCLUSIONS: Although progress in Peru for reducing NMR has been remarkable, future challenges include closing remaining gaps for urban and rural populations and improving newborn health with qualified staff and intermediate- and intensive-level health facilities.

Factors behind job preferences of Peruvian medical, nursing and midwifery students: a qualitative study focused on rural deployment.

BACKGROUND: Deployment of health workforce in rural areas is critical to reach universal health coverage. Students' perceptions towards practice in rural areas likely influence their later choice of a rural post. We aimed at exploring perceptions of students from health professions about career choice, job expectations, motivations and potential incentives to work in a rural area. METHODS: In-depth interviews and focus groups were conducted among medical, nursing and midwifery students from universities of two Peruvian cities (Ica and Ayacucho). Themes for assessment and analysis included career choice, job expectations, motivations and incentives, according to a background theory a priori built for the study purpose. RESULTS: Preference for urban jobs was already established at this undergraduate level. Solidarity, better income expectations, professional and personal recognition, early life experience and family models influenced career choice. Students also expressed altruism, willingness to choose a rural job after graduation and potential responsiveness to incentives for practising in rural areas, which emerged more frequent from the discourse of nursing and midwifery students and from all students of rural origin. Medical students expressed expectations to work in large urban hospitals offering higher salaries. They showed higher personal, professional and family welfare expectations. Participants consistently favoured both financial and non-financial incentives. CONCLUSIONS: Nursing and midwifery students showed a higher disposition to work in rural areas than medical doctors, which was more evident in students of rural origin. Our results may be useful to improve targeting and selection of undergraduate students, to stimulate the inclination of students to choose a rural job upon graduation and to reorient school programmes towards the production of socially committed health professionals. Policymakers may also consider using our results when planning and implementing interventions to improve rural deployment of health professionals.

Disclosure of Exposure to Violence in Urban Adolescents.

Research has documented high rates of exposure to violence in urban African American adolescents together with their negative effects on psychosocial adjustment. Coping with violence exposure may be facilitated by disclosure of these experiences to others, but little is known about the extent to which youth disclose their various experiences with violence. This study examined the prevalence of disclosure of violence experienced as a witness or victim in different contexts or locations to parents, friends, siblings, teachers, counselors, and relatives. Urban African American adolescents from Southeastern U.S. were interviewed at three time points (N = 81; average ages 13.3, 16.1, and 17.8). Across the three time points, 90% to 91% witnessed violence and 64% to 81% were victimized in the last year. Of these youth, 40% to 53% disclosed experiences of witnessing violence and 29% to 52% disclosed experiences of victimization. The results showed that disclosure of violence most often involved parents and friends, with fewer youth disclosing to teachers and counselors. Disclosure of violence victimization increased from early to late adolescence. Experiences of dating violence victimization were less likely to be disclosed by adolescents, especially among males. These findings support the need for more research on adolescents' disclosure of violence exposure and its links to adjustment, with implications for interventions aimed at improving coping in youth exposed to violence.

Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. Patients with IPF have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated cancer. Understanding the molecular pathogenesis of IPF-associated lung cancer is imperative for identifying diagnostic biomarkers and targeted therapies that will facilitate prevention of IPF and progression to lung cancer. To understand how IPF-associated fibroblast activation, matrix remodeling, epithelial-to-mesenchymal transition (EMT), and immune modulation influences lung cancer predisposition, we developed a mouse model to recapitulate the molecular pathogenesis of pulmonary fibrosis-associated lung cancer using the bleomycin and Lewis lung carcinoma models. We demonstrate that development of pulmonary fibrosis-associated lung cancer is likely linked to increased abundance of tumor-associated macrophages and a unique gene signature that supports an immune-suppressive microenvironment through secreted factors. Not surprisingly, preexisting fibrosis provides a pre-metastatic niche and results in augmented tumor growth, and tumors associated with bleomycin-induced fibrosis are characterized by a dramatic loss of cytokeratin expression, indicative of EMT. IMPLICATIONS: This characterization of tumors associated with lung diseases provides new therapeutic targets that may aid in the development of treatment paradigms for lung cancer patients with preexisting pulmonary diseases.

Targeting DNA Repair and Survival Signaling in Diffuse Intrinsic Pontine Gliomas to Prevent Tumor Recurrence.

Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), a high-grade pediatric tumor of the brain stem. In nearly all patients, available therapies fail to prevent progression. Innovative combinatorial therapies that penetrate the blood-brain barrier and lead to long-term control of tumor growth are desperately needed. We identified mechanisms of resistance to radiotherapy, the standard of care for DIPG. On the basis of these findings, we rationally designed a brain-penetrant small molecule, MTX-241F, that is a highly selective inhibitor of EGFR and PI3 kinase family members, including the DNA repair protein DNA-PK. Preliminary studies demonstrated that micromolar levels of this inhibitor can be achieved in murine brain tissue and that MTX-241F exhibits promising single-agent efficacy and radiosensitizing activity in patient-derived DIPG neurospheres. Its physiochemical properties include high exposure in the brain, indicating excellent brain penetrance. Because radiotherapy results in double-strand breaks that are repaired by homologous recombination (HR) and non-homologous DNA end joining (NHEJ), we have tested the combination of MTX-241F with an inhibitor of Ataxia Telangiectasia Mutated to achieve blockade of HR and NHEJ, respectively, with or without radiotherapy. When HR blockers were combined with MTX-241F and radiotherapy, synthetic lethality was observed, providing impetus to explore this combination in clinically relevant models of DIPG. Our data provide proof-of-concept evidence to support advanced development of MTX-241F for the treatment of DIPG. Future studies will be designed to inform rapid clinical translation to ultimately impact patients diagnosed with this devastating disease.

Malic enzyme 1 knockout has no deleterious phenotype and is favored in the male germline under standard laboratory conditions.

Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH and pyruvate. As such, it has been identified as a gene of interest in obesity, type 2 diabetes, and an array of epithelial cancers, with most work being performed in vitro. The current standard model for ME1 loss in vivo is the spontaneous Mod-1 null allele, which produces a canonically inactive form of ME1. Herein, we describe two new genetically engineered mouse models exhibiting ME1 loss at dynamic timepoints. Using murine embryonic stem cells and Flp/FRT and Cre/loxP class switch recombination, we established a germline Me1 knockout model (Me1 KO) and an inducible conditional knockout model (Me1 cKO), activated upon tamoxifen treatment in adulthood. Collectively, neither the Me1 KO nor Me1 cKO models exhibited deleterious phenotype under standard laboratory conditions. Knockout of ME1 was validated by immunohistochemistry and genotype confirmed by PCR. Transmission patterns favor Me1 loss in Me1 KO mice when maternally transmitted to male progeny. Hematological examination of these models through complete blood count and serum chemistry panels revealed no discrepancy with their wild-type counterparts. Orthotopic pancreatic tumors in Me1 cKO mice grow similarly to Me1 expressing mice. Similarly, no behavioral phenotype was observed in Me1 cKO mice when aged for 52 weeks. Histological analysis of several tissues revealed no pathological phenotype. These models provide a more modern approach to ME1 knockout in vivo while opening the door for further study into the role of ME1 loss under more biologically relevant, stressful conditions.

WITHDRAWN: Oncogenic KRAS G12D extrinsically induces an immunosuppressive microenvironment in lung adenocarcinoma.

This manuscript has been withdrawn by the authors due to a dispute over co-first authorship that is currently being arbitrated by the medical school at our institution. Therefore, the authors do not wish this work to be cited as reference for the project. Upon completion of the arbitration process, we will take steps to revert the current withdrawn status. If you have any questions, please contact the corresponding author.

Oncogenic KRAS-dependent stromal interleukin-33 directs the pancreatic microenvironment to promote tumor growth.

Pancreatic cancer is characterized by an extensive fibroinflammatory microenvironment. During carcinogenesis, normal stromal cells are converted to cytokine-high cancer associated fibroblasts (CAFs). The mechanisms underlying this conversion, including regulation and function of fibroblast-derived cytokines, are poorly understood. Thus, efforts to target CAFs therapeutically have so far failed. Here, we show that signals from epithelial cells expressing oncogenic KRAS -a hallmark pancreatic cancer mutation- activate fibroblast autocrine signaling, which drives expression of the cytokine interleukin-33 (IL-33). Stromal IL-33 expression remains high and dependent on epithelial KRAS throughout carcinogenesis; in turn, environmental stress induces IL-33 secretion. Using compartment-specific IL-33 knockout mice, we observed that lack of stromal IL-33 leads to profound reprogramming of multiple components of the pancreatic tumor microenvironment, including CAFs, myeloid cells and lymphocytes. Notably, loss of stromal IL-33 leads to an increase in CD8+ T cell infiltration and activation, and, ultimately, reduced tumor growth.

[Pediatric cardiovascular surgical data base registry in México. First report]. / El Registro Mexicano de Cirurgía Cardiaca Pediátrica. Primer informe.

INTRODUCTION: Current world tendency is the detection of health problems in order to offer solution alternatives by means of the development of computarized data bases. OBJECTIVE: To present the results of a computerized data base developed for the registry of pediatric cardiac surgery with the support of Asociación Mexicana de Especialistas en Cardiopatías Congénitas (AMECC, A.C.). MATERIAL AND METHODS: A one-year analysis (from August 1, 2011 to July 31, 2012) of a computerized data base was performed with the support of AMECC and the participation of the most important Mexican institutions for pediatric surgical heart disease health care, particularly for the uninsured population. RESULTS: There were 7 health institutions voluntarily incorporated to the national data base registry, and in the first year of observation, 943 surgical procedures in 880 patients and 7% re-operations (n = 63), were reported. Patients up to one-year old accounted for 38%. The most frequent types of operated congenital heart diseases were: patent ductus arteriosus (n = 96), ventricular septal defect (n = 86), tetralogy of Fallot (n = 72), atrial septal defect (n = 68), and aortic coarctation (n = 54). Elective procedures were 90%, and 62% of them were performed with the use of cardiopulmonary bypass. Overall mortality was 7.5% with the following RACHS-1 score risk distribution: 1 (n = 4.2%), 2 (n = 19.6%), 3 (n = 22.8%), 4 (n = 12.19%), 5 (n = 1.25%), 6 (n = 6.44%) and not classifiable (n = 2.9%). CONCLUSIONS: Although this analysis gives a representative vision of the cardiovascular surgical health care for the uninsured national pediatric population, the incorporation of other health institutions to this data base may lead us to have a most realistic overview in relation to the surgical cardiovascular health care for the up to 18 year-old population.

Coumel tachycardia in children.

BACKGROUND: Coumel tachycardia is an infrequent form of supraventricular tachycardia (SVT) that usually occurs in infants and children. It is a tachycardia mediated by an accessory pathway with retrograde slow conduction that explains the classic ECG pattern with long RP' interval and negative P waves in leads II, III, and aVF. In this study, we describe the clinical course and management of Coumel tachycardia in children. CASE REPORT: We conducted a retrospective review of five consecutive pediatric patients, mean age 11 ± 3 years (range 6 to 14). The first episode of SVT was at a mean age of 10.4 ± 4.8 years (range 2 to 14) with a mean evolution of 7.4 ± 9.4 months (range 1 to 24). Pharmacological therapy was unsuccessful despite the combination of antiarrhythmic drugs. The tachycardia was incessant with a density > 85% by 24-hour Holter monitoring; one patient developed tachycardia-induced cardiomyopathy. All children underwent successful radiofrequency catheter ablation, mean 5 ± 3 applications (range 1 to 8) with a single session and with no complications. After a mean follow-up of 24 ± 16 months, all patients were asymptomatic and recurrence-free without antiarrhythmic treatment. CONCLUSIONS: Coumel tachycardia is clinically persistent and usually refractory to antiarrhythmic treatment with substantial risk of tachycardia-mediated cardiomyopathy. Catheter ablation is effective and safe in children; thus, it should be indicated promptly and based on individual selection.

INTRODUCCIÓN: La taquicardia de Coumel es una forma poco frecuente de taquicardia supraventricular que suele presentarse en lactantes. Es una taquicardia mediada por una vía accesoria de conducción lenta retrógrada que explica el patrón ECG clásico con intervalo RP' largo y ondas P negativas en las derivaciones II, III y aVF. En este trabajo se describe el curso clínico y el manejo de la taquicardia de Coumel en niños. CASO CLÍNICO: Se llevó a cabo una revisión retrospectiva de cinco pacientes pediátricos consecutivos, con una media de edad de 11 ± 3 años (intervalos 6 a 14). El primer episodio de taquicardia 10.4 ± 4.8 años con evolución de 7.4 ± 9.4 meses. El tratamiento farmacológico fue ineficaz a pesar de la combinación de antiarrítmicos. La taquicardia era incesante con una densidad > 85% por Holter-24h; un paciente desarrolló miocardiopatía inducida por taquicardia. Todos los niños fueron sometidos a ablación con catéter y radiofrecuencia con éxito, y un promedio de 5 ± 3 aplicaciones en una sola sesión y sin complicaciones. Después de un seguimiento de 24 ± 16 meses, todos los pacientes fueron asintomáticos y libres de recurrencia sin tratamiento antiarrítmico. CONCLUSIONES: La taquicardia de Coumel es clínicamente persistente y generalmente refractaria al tratamiento antiarrítmico con un riesgo sustancial de miocardiopatía mediada por taquicardia. La ablación con catéter es eficaz y segura en niños, por lo que debe indicarse de forma temprana y en lactantes de una selección individual.

Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early pre-neoplastic pancreatic lesions.

The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathological analysis of the samples revealed PanIN lesions in most individuals irrespective of age. Using a combination of multiplex immunohistochemistry, single cell RNA sequencing, and spatial transcriptomics, we provide the first ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts, and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis. Statement of significance: The causes underlying the onset of pancreatic cancer remain largely unknown, hampering early detection and prevention strategies. Here, we show that PanIN are abundant in healthy individuals and present at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell intrinsic factors that restrain, or, conversely, promote, malignant progression.