Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

Clinical Evaluation of a New Spectral-Domain Optical Coherence Tomography-Based Biometer.

The VEMoS-AXL system is a new optical biometer based on spectral domain optical coherence tomography (SD-OCT) that has been tested in terms of intrasession repeatability and compared with a swept-source optical coherence tomography biometer (SS-OCT), which is recognized as the gold standard for the performance of an agreement analysis. A biometric analysis was performed three consecutive times in 120 healthy eyes of 120 patients aged between 18 and 40 years with the SD-OCT system, and afterwards, a single measurement was obtained with the SS-OCT system. Within-subject standard deviations were 0.004 mm, 4.394 µm, and 0.017 mm for axial length (AL), central corneal thickness (CCT), and anterior chamber depth (ACD) measures obtained with the SD-OCT biometer, respectively. The agreement between devices was good for AL (limits of agreement, LoA: -0.04 to 0.03 mm) and CCT (LoA: -4.36 to 14.38 µm), whereas differences between devices were clinically relevant for ACD (LoA: 0.03 to 0.21 mm). In conclusion, the VEMoS-AXL system provides consistent measures of anatomical parameters, being most of them interchangeable with those provided by the SS-OCT-based gold standard.

A Cross-Sectional Analysis of Parental Behavior and Adolescent Mental Health in Mexico: Insights into Excessive Alcohol Intake, Tobacco Use, Suicidal Behavior, and Depressive Symptomatology.

Depression, suicidal behavior, excessive alcohol intake, and tobacco use are the main mental health problems in adolescents. To address these problems, it is necessary to understand the many factors associated with them, including parental factors. The aim of this study was to assess the associations between parental behavior and mental health problems in adolescents in Mexico. Data from the National Health and Nutrition Survey (ENSANUT) 2018-2019, representative for Mexico, were used. Households in which a parent-adolescent child pairing was identified (regardless of family type) were selected; n = 8758 households. The four outcomes of interest that were measured in the adolescents were: excessive alcohol intake, tobacco use, suicidal behavior, and depressive symptomatology. Logistic regression models using the adjusted odds ratio (AOR) and 95% confidence interval (95% CI) were estimated. Adolescents whose parents used alcohol or tobacco and reported depressive symptoms and suicidal behavior were more likely to present these behaviors themselves (AOR = 1.47, 95% CI: 1.17-1.85; AOR = 2.26, 95% CI: 1.51-3.39; AOR = 2.61, 95% CI: 1.88-3.61; AOR = 1.74, 95% CI: 1.16-2.61, respectively). Child sexual abuse was also strongly associated with the four outcomes of interest in adolescents (AOR = 1.89, 95% CI: 1.06-3.36 for excessive alcohol intake; AOR = 2.97, 95% CI: 1.49-5.91 for tobacco use; AOR = 5.15, 95% CI: 3.27-8.09 for depressive symptoms; AOR = 6.71, 95% CI: 4.25-10.59 for suicidal behavior). The family constitutes the central nucleus of care for children and adolescents; therefore, any effort to promote adolescent mental health must necessarily involve their parents and family.

Sensitization to textile dyes in Spain: Epidemiological situation (2019-2022).

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.

Incorporación del dietista-nutricionista en un hospital universitario: declaración de postura de la Comisión de Nutrición del Hospital Universitario La Paz / Dietitian-nutritionist incorporation in a university hospital: position statement of the Commission on Nutrition, Hospital Universitario La Paz

El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares deatención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estadonutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid.El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que,actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva,habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes,los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedadrenal crónica, entre otras.(AU)

The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized carethat provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid.The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians usenutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hyper-tension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.(AU)

The state of transience, and its influence on the wish to die of advanced disease patients: insights from a qualitative phenomenological study.

BACKGROUND: The experience of Wish to Die is common in patients living with Advanced Disease. It has been studied worldwide and qualitative studies have contributed to the understanding of the complexity of the phenomenon of the WTD but a deeper understanding on the individual's views is still needed. The objective of this study was to identify common characteristics of the experience of wish to die in advanced disease. METHODS: A phenomenological study was carried out with multicenter participation of patients with advanced disease who had expressed their wish to die to health professionals. Semi-structured interviews were employed to obtain an in-depth perspective of each patient's lived experience. A phenomenological analysis of the data collected was performed to describe and explore the characteristic aspects of the phenomenon under study. RESULTS: Fourteen patients with advanced disease were interviewed. Most of them had cancer. In the analysis of the patients' accounts of their experiences, three common characteristics were identified: a) experiencing a state of transience; b) the attempt to reconnect with oneself; and c) additional disease-related aspects that influence the wish to die. Patients expressed the need for a safe space to address the wish to die and the importance of receiving care that considers both 'being' and 'doing'. CONCLUSIONS: Patients with advanced disease and wish to die experience a state of transience where the patient lives and ephemeral state of existence. Interventions focused on reinforcing the intrinsic value of the individual emerge as essential components of a compassionate accompaniment of those facing the wish to die.

Where does Hispanic Latin America stand in biomedical and life sciences literature production compared with other countries?

Objectives: to provide objective quantitative data about medical-related scientific production in Hispanic Latin America compared to different regions and identify demographic and political variables that could improve research. Study design: This is an analytical, observational, cross-section bibliometric study about all fields of medical-related scientific production over five years in different regions and its relationship with demographic and political variables that could impact research and the health system quality. Methods: Data on the total scientific production of all Hispanic Latin American countries and other countries representing almost 90% of mundial publications between 2017 and 2021 were retrieved from the PubMed database. Demographic and political data were obtained from open online databases. Counts of publications were rationed to population and analyzed with all other demographic, region, and language variables, using univariate Poisson regression and negative binomial regression (for over-disperse variables) analysis. Multivariate negative binomial regression was used to analyze the combined effect of variables related to the healthcare and research Sectors. Results: Hispanic Latin America increased yearly from 29,445 publications in 2017 to 47,053 in 2021. This cumulative growth of almost 60% exceeded the 36% increment in all countries' publications and was only below that of Russia and China, which grew 92% and 87%, respectively. Negative binomial regression showed that the percentage of gross income dedicated to research (IRR 2.036, 95% CI: 1.624, 2.553, p< .001), life expectancy at birth (IRR 1.444, 95% CI: 1.338, 1.558, p< .001), and the number of medical doctors per inhabitant (IRR 1.581, 95% CI: 1.17, 2.13, p = .003) positively impacted scientific production. A higher mortality associated with chronic diseases between ages 30 and 70 (IRR 0.782, 95% CI: 0.743 0.822, p< .001) and a lower population with access to medicine (IRR 0.960, 95% CI: 0.933, 0.967, p< .001) were found to impact scientific production negatively. Hispanic Latin American countries published less than 20% of those with English as their native language (p< .001). Conclusion: Hispanic Latin America has increased the gross number of publications by almost 60 % from 2017 to 2021. However, the number of publications per 100,000 inhabitants is still low compared to other countries. Our analysis highlights that this may be related to lower GDP, research investment, and less healthcare system quality.

Integrating Oral Health Within Kenyan HIV Research & Policy Structure: Stakeholder Analysis.

Background: Kenya has a remarkably high burden of oral diseases, especially in vulnerable communities like persons with HIV (PWH). In the last few decades, the National AIDS & STI Control Programme has efficiently and successfully provided care and prevention against HIV for people living in Kenya. Objective: To assess the feasibility of integrating oral health into HIV research and policy structures in Kenya. Methods: The study took place between November 2021 and April 2022 in the cities of Nairobi, Kisumu, Mombasa, and Eldoret town. Using a semi-structured interview, three remote and 14 in-person sessions were conducted. Participants included individuals with professional experience in HIV and/or oral health such as researchers, potential mentors, institutional administrators, and other grant-funded experts. A qualitative analysis of recordings was performed by nine pretested independent reviewers, all with qualitative data analysis experience. Areas of interest included research, motivation, obstacles, and support. The free coding phase as well as an iterative grouping analysis (MIRO) was used. Findings: Of the 22 stakeholders interviewed in the study, researchers accounted for the majority (48%) of stakeholders, with the rest composed of practitioners (29%), university administrators (19%), and one public health administrator. University administrators were identified as having the most ability for resource mobilization followed by researchers and practitioners. All participants desired improved health outcomes using an evidence-based approach. The primary motivators were increased networks, collaborations, publications, and bridging the gap between oral health and HIV. While the obstacles to their desires included time and lack of funding, Institutional support through recruitment of qualified personnel, mentors, and mentees was their major desirable support. Conclusion: Stakeholders were unanimous in supporting integrating oral health within the current research and policy environment to address the gap between oral health and HIV, and to improve health outcomes through evidence-based interventions.

Dietitian-nutritionist incorporation in a university hospital: position statement of the Commission on Nutrition, Hospital Universitario La Paz.

Introduction: The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized care that provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid. The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians use nutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hypertension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.

Introducción: El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares de atención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estado nutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid. El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que, actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva, habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes, los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedad renal crónica, entre otras.

Eventos de vida estresantes y su efecto en la conducta suicida en mujeres durante la pandemia por Covid-19 en México.

OBJETIVO: Analizar la estructura factorial, la validez convergente y divergente de la Escala Columbia de Severidad Suicida (CSSRS) y el Cuestionario de Eventos de Vida Estresantes (EVE) y medir la asociación entre EVE y conducta suicida (CS) en mujeres mexicanas durante la pandemia por Covid-19. Material y métodos. Se usaron datos de 2 398 mujeres que participaron en un estudio multicéntrico, realizado en México entre mayo y octubre de 2021. La información se recolectó mediante un cuestionario en línea que incluyó la CSSRS y el EVE. Se hizo un análisis factorial confirmatorio para valorar el ajuste de los modelos. RESULTADOS: El modelo final mostró asociación entre los EVE y la CS, y tuvo a la violencia como variable central. Dicho modelo presentó un ajuste adecuado (CFI = 0.950, IFI = 0.950, MFI = 0.975, RMSEA = 0.031, CI RMSEA = 0.026-0.036). CONCLUSIONES: La pandemia por Covid-19 evidenció la necesidad de crear e implementar estrategias que promuevan el cuidado de la salud mental, reduzcan la exposición a la violencia y faciliten los procesos de duelo para prevenir la CS en mujeres mexicanas.

Core Palliative Care Research Competencies Framework for Palliative Care Clinicians.

Background: Understanding the principles and practice of research by health care professionals helps to improve the evidence base for palliative care practice and service delivery. Research is a core competency in palliative care that enables the identification and addressing of problems for patients and their families, establishes best practice and improves ways to manage pain, other symptoms, and concerns. This work was undertaken in the research for all palliative care clinicians (RESPACC) Erasmus+ project. Aim: To identify and develop a set of core research competencies within a structured framework for all members of the multidisciplinary palliative team. Design: A multi-method approach was used including rapid review of literature, Nominal Group Technique, and expert consultation. A quiz to self-assess research competencies outlined within the Framework was produced. Results: The Framework includes 17 competencies organized in 7 domains: The clinical context, Scientific thinking and research design, Ethics and regulatory framework for research, Study and site management, Data management and informatics, Communication and relationships, and Research leadership. In the consultation process 6 of the 17 competencies were considered as required by each individual team member, and 3 to be present within the palliative care team. Conclusion: Using a multi-method approach, the first Palliative Care Research Framework identifying core research competencies for palliative care clinicians has been developed. The aim of the framework was not to transform palliative care clinicians into researchers, but to ensure that clinicians understand the important role of research and its integration into clinical practice.

Characterization of Sleep, Emotional, and Cognitive Functions in a New Rat Model of Concomitant Spinal Cord and Traumatic Brain Injuries.

Traumatic injuries to the spinal cord or the brain have serious medical consequences and lead to long-term disability. The epidemiology, medical complications, and prognosis of isolated spinal cord injury (SCI) and traumatic brain injury (TBI) have been well described. However, there are limited data on patients suffering from concurrent SCI and TBI, even if a large proportion of SCI patients have concomitant TBI. The complications associated with this "dual-diagnosis" such as cognitive or behavioral dysfunction are well known in the rehabilitation setting, but evidence-based and standardized approaches for diagnosis and treatment are lacking. Our goal was to develop and characterize a pre-clinical animal model of concurrent SCI and TBI to help identifying "dual-diagnosis" tools. Female rats received a unilateral contusive SCI at the thoracic level alone (SCI group) or combined with a TBI centered on the contralateral sensorimotor cortex (SCI-TBI group). We first validated that the SCI extent was comparable between SCI-TBI and SCI groups, and that hindlimb function was impaired. We characterized various neurological outcomes, including locomotion, sleep architecture, brain activity during sleep, depressive- and anxiety-like behaviors, and working memory. We report that SCI-TBI and SCI groups show similar impairments in global locomotor function. While wake/sleep amount and distribution and anxiety- and depression-like symptoms were not affected in SCI-TBI and SCI groups in comparison to the control group (laminectomy and craniotomy only), working memory was impaired only in SCI-TBI rats. This pre-clinical model of concomitant SCI and TBI, including more severe variations of it, shows a translational value for the identification of biomarkers to refine the "dual-diagnosis" of neurotrauma in humans.

Enfermedad de Still del adulto: serie de casos / Adult Still's disease: case series

Resumen La enfermedad de Still del adulto (ESA) es una enfermedad reumática e inflamatoria, infrecuente, de etiología desconocida. Su presentación clínica es variada y sus síntomas más frecuentes son fiebre, artralgias, exantema asalmonado evanescente, odinofagia, adenopatías, hepatoesplenomegalia, serositis y presencia en laboratorio de leucocitosis (neutrofilia), hiperferritinemia asociado a ausencia de anticuerpos. El diagnóstico es clínico y por exclusión. Existen criterios clasificatorios como son los de Yamaguchi1, Cush y Fautrel2,3 que ayudan a la orientación diagnóstica. El tratamiento se define según la presentación y la evolución clínica1. Se describen las características clínicas, diagnósticas, tratamiento y evolución de siete pacientes con ESA.

Abstract Adult Still's disease (ASD) is an uncommon rheumatic and inflammatory disorder of unknown etiology. The major clinical features include fever, arthralgia, transient salmon-pink rash, odynophagia, lymphadenopathy, hepatosplenomegaly, serositis, and laboratory findings such as leukocytosis with neutrophilia, hyperferritinemia, and negative immunologic laboratory testing. ASD diagnosis is reached by exclusion. Different classification criteria such as Yamaguchi, Cush and Fautrel have been developed for the identification of ASD. Treatment is based on the degree of disease activity and clinical response1. We describe clinical manifestations, diagnosis, treatment, and prognosis of seven patients with adult's Still disease.

Robust expression of the TRPC1 channel associated with photoreceptor loss in the rat retina.

Baseline intracellular calcium levels are significantly higher in neuronal and glial cells of rat retinas with retinitis pigmentosa (RP). Although this situation could initiate multiple detrimental pathways that lead to cell death, we considered the possibility of TRPC1 being involved in maintaining calcium homeostasis in the retina by acting as a component of store-operated calcium (SOC) channels with special relevance during photoreceptor degeneration. In this study, we examined by Western blot the expression of TRPC1 in healthy control rat retinas (Sprague-Dawley, SD) and retinas with RP (P23H-1 rats). We also analyzed its specific cellular distribution by immunofluorescence to recognize changes during neurodegeneration and to determine whether its presence is consistent with high basal calcium levels and cellular survival in degenerating retinas. We found that TRPC1 immunostaining was widely distributed across the retina in both rat strains, SD and P23H, and its expression levels significantly increased in the retinas with advanced degeneration compared to the age-control SD rats. In the outer retina, TRPC1 immunoreactivity was distributed in pigment epithelium cells, the photoreceptor inner segments of older animals, and the outer plexiform layer. In the inner retina, TRPC1 labeling was detected in horizontal cells, specific somata of bipolar and amacrine cells, and cellular processes in all the strata of the inner plexiform layer. Somata and processes were also highly immunoreactive in the ganglion cell layer and astrocytes in the nerve fiber layer in all animals. In the P23H rat retinas, the TRPC1 distribution pattern changed according to advancing photoreceptor degeneration and the gliosis reaction, with TRPC1 immunoreactive Müller cells mainly in advanced stages of disease. The cellular TRPC1 immunoreactivity found in this work suggests different mechanisms of activation of these channels depending on the cell type. Furthermore, the results support the idea that photoreceptor loss due to RP is associated with robust TRPC1 protein expression in the rat inner retina and raise the possibility of TRPC1 channels contributing to maintain high basal calcium levels during neurodegeneration and/or maintenance processes of the inner retina.

Measured GFR in murine animal models: review on methods, techniques, and procedures.

Chronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with increasing rates of morbidity and mortality. Thus, early detection is essential to prevent severe adverse events and the progression of kidney disease to an end stage. Glomerular filtration rate (GFR) is the most appropriate index to evaluate renal function in both clinical practice and basic medical research. Several animal models have been developed to understand renal disease induction and progression. Specifically, murine models are useful to study the pathogenesis of renal damage, so a reliable determination of GFR is essential to evaluate the progression of CKD. However, as in clinical practise, the estimation of GFR in murine by levels of serum/urine creatinine or cystatin-C could not be accurate and needed other more reliable methods. As an alternative, the measurement of GFR by the clearance of exogenous markers like inulin, sinistrin, 51Cr-EDTA, 99mTc-DTPA, 125I-iothalamate, or iohexol could be performed. Nevertheless, both approaches-estimation or measurement of GFR-have their limitations and a standard method for the GFR determination has not been defined. Altogether, in this review, we aim to give an overview of the current methods for GFR assessment in murine models, describing each methodology and focusing on their advantages and limitations.

Chimeric HLA antibody receptor T cells for targeted therapy of antibody-mediated rejection in transplantation.

The presence of donor-specific antibodies (DSA), mainly against HLA, increases the risk of allograft rejection. Moreover, antibody-mediated rejection (ABMR) remains an important barrier to optimal long-term outcomes after solid organ transplantation. The development of chimeric autoantibody receptor T lymphocytes has been postulated for targeted therapy of autoimmune diseases. We aimed to develop a targeted therapy for DSA desensitization and ABMR, generating T cells with a chimeric HLA antibody receptor (CHAR) that specifically eliminates DSA-producing B cells. We have genetically engineered an HLA-A2-specific CHAR (A2-CHAR) and transduced it into human T cells. Then, we have performed in vitro experiments such as cytokine measurement, effector cell activation, and cytotoxicity against anti-HLA-A2 antibody-expressing target cells. In addition, we have performed A2-CHAR-Tc cytotoxic assays in an immunodeficient mouse model. A2-CHAR expressing T cells could selectively eliminate HLA-A2 antibody-producing B cells in vitro. The cytotoxic capacity of A2-CHAR expressing T cells mainly depended on Granzyme B release. In the NSG mouse model, A2-CHAR-T cells could identify and eradicate HLA-A2 antibody-producing B cells even when those cells are localized in the bone marrow. This ability is effector:target ratio dependent. CHAR technology generates potent and functional human cytotoxic T cells to target alloreactive HLA class I antibody-producing B cells. Thus, we consider that CHAR technology may be used as a selective desensitization protocol or an ABMR therapy in transplantation.

KRAS(G12D) drives lepidic adenocarcinoma through stem-cell reprogramming.

Many cancers originate from stem or progenitor cells hijacked by somatic mutations that drive replication, exemplified by adenomatous transformation of pulmonary alveolar epithelial type II (AT2) cells1. Here we demonstrate a different scenario: expression of KRAS(G12D) in differentiated AT1 cells reprograms them slowly and asynchronously back into AT2 stem cells that go on to generate indolent tumours. Like human lepidic adenocarcinoma, the tumour cells slowly spread along alveolar walls in a non-destructive manner and have low ERK activity. We find that AT1 and AT2 cells act as distinct cells of origin and manifest divergent responses to concomitant WNT activation and KRAS(G12D) induction, which accelerates AT2-derived but inhibits AT1-derived adenoma proliferation. Augmentation of ERK activity in KRAS(G12D)-induced AT1 cells increases transformation efficiency, proliferation and progression from lepidic to mixed tumour histology. Overall, we have identified a new cell of origin for lung adenocarcinoma, the AT1 cell, which recapitulates features of human lepidic cancer. In so doing, we also uncover a capacity for oncogenic KRAS to reprogram a differentiated and quiescent cell back into its parent stem cell en route to adenomatous transformation. Our work further reveals that irrespective of a given cancer's current molecular profile and driver oncogene, the cell of origin exerts a pervasive and perduring influence on its subsequent behaviour.