Understanding of the role of serum creatinine in a subset of the Brazilian population / Conhecimento de uma amostragem da população brasileira sobre a função da creatinina sérica

Abstract Introduction: Chronic kidney disease is usually asymptomatic, and its diagnosis depends on laboratory tests, with emphasis on serum creatinine and proteinuria. Objective: To assess knowledge on the role of serum creatinine as a biomarker of kidney function in a sample of the Brazilian population. Method: Cross-sectional observational study conducted in São Paulo (SP, Brazil), in which a random adult population was interviewed. Results: A total of 1138 subjects were interviewed, with a median age of 36 years old (27-52); 55.1% were female. Regarding the "creatinine" biomarker, 40.6% stated they had never performed such a test. When asked about their knowledge on the usefulness of this exam, only 19.6% knew its function. The other responses were "I don't know" (71.6%), evaluating heart function (0.9%) and liver function (7.8%). Of those who reported they had already taken a creatinine test, only 29.4% correctly identified the role of creatinine. When dividing the groups into "knows" and "does not know" the function of creatinine, a statistically significant difference (p < 0.05) was observed regarding level of education, female sex, being a healthcare student/worker, having ever measured creatinine, knowing someone with kidney disease and older age. In the multivariate analysis, the main variable related to knowing the creatinine role was having previously taken the test (OR 5.16; 95% CI 3.16-8.43, p < 0.001). Conclusion: There is a significant lack of knowledge about creatinine and its use in checkups. The results indicate that greater efforts are needed from healthcare professionals to raise awareness on the role of serum creatinine.

Resumo Introdução: A doença renal crônica costuma ser assintomática e seu diagnóstico depende da realização de exames laboratoriais, com destaque para a creatinina sérica e pesquisa de proteinúria. Objetivo: Avaliar em uma amostra da população brasileira o conhecimento sobre o papel da creatinina sérica como marcador de função renal. Método: Estudo observacional transversal realizado na cidade de São Paulo (SP, Brasil), em que foi entrevistada uma população adulta aleatória. Resultados: Foram entrevistados 1138 indivíduos, com idade mediana de 36 anos (27-52); 55,1% do sexo feminino. Com relação ao marcador "creatinina", 40,6% afirmaram que nunca realizaram tal dosagem. Quando questionados quanto ao conhecimento sobre a utilidade desse exame, somente 19,6% sabiam a sua função. As outras respostas foram "não sei" (71,6%), avaliar o funcionamento do coração (0,9%) e fígado (7,8%). Dos que afirmaram já terem realizado o exame de creatinina, somente 29,4% acertaram a função da creatinina. Ao dividir os grupos em "sabe" e "não sabe" a função da creatinina, percebeu-se diferença estatisticamente significante (p < 0,05) em relação ao grau de escolaridade, sexo feminino, ser aluno/trabalhador da saúde, ter dosado creatinina alguma vez, conhecer alguém com doença renal e maior idade. Na análise multivariada, a principal variável relacionada com conhecer a função da creatinina foi ter realizado o exame anteriormente (OR 5,16; IC 95% 3,16-8,43, p < 0,001). Conclusão: Há grande desconhecimento sobre a creatinina e seu uso em check-ups. Os resultados indicam que é necessário maior esforço por parte dos profissionais de saúde para divulgar o papel da creatinina sérica.

PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation.

The regulated formation and resolution of R-loops is a natural process in physiological gene expression. Defects in R-loop metabolism can lead to DNA replication stress, which is associated with a variety of diseases and, ultimately, with cancer. The proteins PARP1, DIDO3, and DHX9 are important players in R-loop regulation. We previously described the interaction between DIDO3 and DHX9. Here, we show that, in mouse embryonic fibroblasts, the three proteins are physically linked and dependent on PARP1 activity. The C-terminal truncation of DIDO3 leads to the impairment of this interaction; concomitantly, the cells show increased replication stress and senescence. DIDO3 truncation also renders the cells partially resistant to in vitro oncogenic transformation, an effect that can be reversed by immortalization. We propose that PARP1, DIDO3, and DHX9 proteins form a ternary complex that regulates R-loop metabolism, preventing DNA replication stress and subsequent senescence.

miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication.

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Bruton's tyrosine kinase inhibitor ibrutinib. Combination therapy with miR-28 plus ibrutinib potentiated the anti-tumor effects of monotherapy with either agent by inducing a specific transcriptional cell-cycle arrest program that impairs DNA replication. The molecular actions of miR-28 and ibrutinib synergistically impair DNA replication by simultaneous inhibition of origin activation and fork progression. Moreover, we found that downregulation of the miR-28-plus-ibrutinib gene signature correlates with better survival of ABC-DLBCL patients. These results provide evidence for the effectiveness of a new miRNA-based ibrutinib combination therapy for DLBCL and unveil the miR-28-plus-ibrutinib gene signature as a new predictor of outcome in ABC-DLBCL patients.

Hemorragia digestiva como forma de presentación poco usual de amiloidosis intestinal primaria: reporte de caso

La amiloidosis intestinal es una enfermedad sistémica rara y subdiagnosticada, la cual se caracteriza por el depósito extracelular de proteínas que se agrupan en fibras amiloides. Esta entidad es infrecuente y suele ser una forma de presentación en el contexto de una amiloidosis sistémica, cuyo diagnóstico se basa en la presencia a amiloide en la histología. La clínica suele ser inespecífica; diarrea crónica, pérdida de peso, dolor y distensión abdominal; siendo la hemorragia digestiva una manifestación muy poco frecuente. Se presenta el caso de una mujer de 61 años con clínica de baja de peso, distención abdominal, náuseas, vómitos y melena. En la tomografía se evidenció un engrosamiento mural de asas yeyunales con captación de contraste, hallazgo que se corroboró con enteroscopia anterógrada a doble balón en el cual se evidenciaron múltiples úlceras en yeyuno, signos de atrofia, friabilidad y dilatación de luz yeyunal. En la anatomía patológica se aprecia arquitectura vellositaria distorsionada y ulcerada con histoquímica positiva a Rojo Congo e inmunohistoquímica lambda (+++). Además, se realizó aspirado de médula ósea y biopsia de hueso compatible con infiltración de mieloma múltiple monoclonal a cadena Lambda. Durante la estancia hospitalaria la paciente cursó con complicaciones como la desnutrición crónica, infección recurrente y varios episodios de suboclusión intestinal; caracterizada por neumatosis intestinal; debido a múltiples episodios de estas complicaciones la paciente fallece. Dentro de la práctica clínica en gastroenterología la amiloidosis intestinal como parte del diagnóstico diferencial de la hemorragia digestiva alta es infrecuente, por lo que los antecedentes de diagnóstico de mieloma múltiple u otras gammapatías monoclonales asociadas a cadenas ligeras es crucial para un diagnóstico precoz y tratamiento adecuado.

Intestinal amyloidosis is a rare and underdiagnosed systemic disease, which is characterized by the extracellular deposition of proteins that are grouped into amyloid fibers. This entity is rare and is usually a form of presentation in the context of systemic amyloidosis, the diagnosis of which is based on the presence of amyloid in histology. The clinic is usually non-specific; chronic diarrhea, weight loss, abdominal pain and bloating; Gastrointestinal bleeding is a very rare manifestation. The case of a 61-year-old woman with symptoms of weight loss, abdominal distension, nausea, vomiting and long hair is presented. Tomographically, a wall thickening of jejunal loops with contrast uptake was evidenced, a finding that was corroborated by a double-balloon anterograde stereoscopy in which multiple were evidenced. The pathology shows distorted and ulcerated villous architecture with positive histochemistry for Congo Red and LAMBDA (+++) immunohistochemistry. In addition, bone marrow aspirate and bone biopsy compatible with infiltration of Lambda chain monoclonal multiple myeloma were performed. During the hospital stay, the patient developed complications such as chronic malnutrition, recurrent infection and several episodes of intestinal subocclusion; characterized by intestinal pneumatosis; due to multiple episodes of these complications, the patient died. Within clinical practice in gastroenterology, intestinal amyloidosis as part of the differential diagnosis of upper gastrointestinal bleeding is infrequent, so a history of diagnosis of multiple myeloma or other monoclonal gammopathy associated with light chains is crucial for early diagnosis and adequate treatment.

Usefulness of artificial intelligence-assisted digital single-operator cholangioscopy as a second-opinion consultation tool during interhospital assessment of an indeterminate biliary stricture: a case report.

Video 1Application of a novel digital single-operator cholangioscopy-based convolutional neuronal network to detect neoplastic lesions as a second-opinion consultation tool between 2 hospitals and biopsy sampling.

[Inflammatory Bowel Disease in elderly patients: Clinical characteristics and management in a tertiary hospital]. / Enfermedad Inflamatoria Intestinal en el adulto mayor: Características clínicas y manejo en un hospital de referencia.

Inflammatory bowel disease (IBD) in elderly patients is characterized by its clinical variability, different differential diagnoses and therapeutic management. The objective of our investigation is to evaluate the clinical characteristics and management of elderly patients with IBD. We developed an observational, descriptive, retrospective study from January 2011 to December 2019 in patients with IBD at the Gastroenterology Service of Guillermo Almenara Irigoyen National Hospital, Lima-Peru. 55 patients with CD and 107 with UC were evaluated; 45.6% of patients with IBD are older adults. Of these, 28 had CD and 46 UC. Older adults with CD presented predominantly an inflammatory phenotype and colonic location, while extensive and left-sided colitis were the most frequent in UC. Elderly patients had a lower CDAI score (279.8 vs 323.2) and a lower Mayo index (7.1 vs 9.2) in relation to the younger, without significant differences. Regarding treatment, a lower use of azathioprine (2 vs 8, p <0.03) and Anti-TNF (9 vs 18, p <0.01) was observed in the elderly with CD. The need for surgery and the frequency of post-surgical complications were similar between both groups. In conclusion, nearly half of IBD patients are older adults. The colonic location was the most frequent in CD, and in UC extensive and left colitis. We observed a lower use of azathioprine and biological therapy in elderly patients, without significant differences in the use of corticosteroids and aminosalicylates compared to younger people.

Mortalidad perioperatoria en Tolima, perspectivas del cuarto indicador de The Lancet Commission on Global Surgery: Un análisis preliminar de la cohorte prospectiva del estudio Colombian Surgical Outcomes Study (ColSOS) / Perioperative mortality in Tolima and perspectives of the fourth indicator of The Lancet Commission on Global Surgery: A preliminary analysis of the prospective cohort of the Colombian Surgical Outcomes Study (ColSOS)

Introducción. La mortalidad perioperatoria en el mundo representa 4,2 millones de muertes anuales. El cuarto indicador de The Lancet Commission on Global Surgery permite estandarizar la mortalidad perioperatoria. En Colombia, existen aproximaciones por datos secundarios, limitando el análisis y las intervenciones aplicables a nuestra población. El objetivo de este estudio fue describir la mortalidad perioperatoria a través de datos primarios que permitan sustentar políticas públicas. Métodos. Se hizo el análisis preliminar de un estudio observacional, de cohorte prospectiva, multicéntrico en 6 instituciones del departamento de Tolima. Se incluyeron los pacientes llevados a procedimientos quirúrgicos por una semana, con posterior seguimiento hasta el egreso, fallecimiento o 30 días de hospitalización. La mortalidad perioperatoria fue el desenlace primario. Resultados. Fueron incluidos 378 pacientes, con mediana de 49 años (RIC 32-66), buen estado funcional (ASA I-II 80 %) y baja complejidad quirúrgica (42 %). Las cirugías más comunes fueron por Ortopedia (25,4 %) y Cirugía plástica (23,3 %). El 29,7 % presentaron complicaciones postoperatorias, las más comunes fueron síndrome de dificultad respiratoria agudo e íleo postoperatorio. La mortalidad perioperatoria fue de 1,3 %. Discusión. La mortalidad perioperatoria discrepó de la reportada en otros estudios nacionales, aun cuando los pacientes tenían un bajo perfil de riesgo y baja complejidad de los procedimientos. Sin embargo, coincide con la reportada internacionalmente y nos acerca a la realidad del país. Conclusión. La determinación del cuarto indicador es de vital importancia para mejorar la atención quirúrgica en Colombia. Este es el primer acercamiento con datos primarios que nos permite tener información aplicable a nuestra población

Introduction. Perioperative mortality accounts for 4.2 million deaths annually. The fourth indicator of The Lancet Commission on Global Surgery allows standardizing perioperative mortality. In Colombia, there are approximations based on secondary data, limiting the analysis and interventions applicable to our population. The objective of this study is to describe perioperative mortality through primary data that allow supporting public policies. Methods. A preliminary analysis of an observational, prospective cohort, multicenter study was carried out at six institutions in the District of Tolima. Patients undergoing surgical procedures were included for one week, for subsequent follow-up until discharge, death, or 30 days of hospitalization. Perioperative mortality was the primary outcome and was presented as a proportion. Results. A total of 378 patients were included, with a median age of 49 years (RIC 32-66), low-risk profile (ASA I-II 80%), and low surgical complexity (42%). The most common surgeries were Orthopedic (25.4%) and Plastic Surgery (23.3%). Postoperative complications occurred in 29.7%, the most common were ARDS and postoperative ileus. Perioperative mortality was 1.3%. Discussion. Perioperative mortality differed from that reported in national studies, even when the patients had a low-risk profile and low complexity of the procedures. However, it coincides with that reported internationally and brings us closer to the reality of the country. Conclusion. The determination of the fourth indicator is of vital importance to improving surgical care in Colombia. This is the first approach with primary data that allows us to have applicable information for our population

RHOJ controls EMT-associated resistance to chemotherapy.

The resistance of cancer cells to therapy is responsible for the death of most patients with cancer1. Epithelial-to-mesenchymal transition (EMT) has been associated with resistance to therapy in different cancer cells2,3. However, the mechanisms by which EMT mediates resistance to therapy remain poorly understood. Here, using a mouse model of skin squamous cell carcinoma undergoing spontaneous EMT during tumorigenesis, we found that EMT tumour cells are highly resistant to a wide range of anti-cancer therapies both in vivo and in vitro. Using gain and loss of function studies in vitro and in vivo, we found that RHOJ-a small GTPase that is preferentially expressed in EMT cancer cells-controls resistance to therapy. Using genome-wide transcriptomic and proteomic profiling, we found that RHOJ regulates EMT-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA-damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy. RHOJ interacts with proteins that regulate nuclear actin, and inhibition of actin polymerization sensitizes EMT tumour cells to chemotherapy-induced cell death in a RHOJ-dependent manner. Together, our study uncovers the role and the mechanisms through which RHOJ acts as a key regulator of EMT-associated resistance to chemotherapy.

Artificial intelligence for diagnosing neoplasia on digital cholangioscopy: development and multicenter validation of a convolutional neural network model.

BACKGROUND: We aimed to develop a convolutional neural network (CNN) model for detecting neoplastic lesions during real-time digital single-operator cholangioscopy (DSOC) and to clinically validate the model through comparisons with DSOC expert and nonexpert endoscopists. METHODS: In this two-stage study, we first developed and validated CNN1. Then, we performed a multicenter diagnostic trial to compare four DSOC experts and nonexperts against an improved model (CNN2). Lesions were classified into neoplastic and non-neoplastic in accordance with Carlos Robles-Medranda (CRM) and Mendoza disaggregated criteria. The final diagnosis of neoplasia was based on histopathology and 12-month follow-up outcomes. RESULTS: In stage I, CNN2 achieved a mean average precision of 0.88, an intersection over the union value of 83.24 %, and a total loss of 0.0975. For clinical validation, a total of 170 videos from newly included patients were analyzed with the CNN2. Half of cases (50 %) had neoplastic lesions. This model achieved significant accuracy values for neoplastic diagnosis, with a 90.5 % sensitivity, 68.2 % specificity, and 74.0 % and 87.8 % positive and negative predictive values, respectively. The CNN2 model outperformed nonexpert #2 (area under the receiver operating characteristic curve [AUC]-CRM 0.657 vs. AUC-CNN2 0.794, P < 0.05; AUC-Mendoza 0.582 vs. AUC-CNN2 0.794, P < 0.05), nonexpert #4 (AUC-CRM 0.683 vs. AUC-CNN2 0.791, P < 0.05), and expert #4 (AUC-CRM 0.755 vs. AUC-CNN2 0.848, P < 0.05; AUC-Mendoza 0.753 vs. AUC-CNN2 0.848, P < 0.05). CONCLUSIONS: The proposed CNN model distinguished neoplastic bile duct lesions with good accuracy and outperformed two nonexpert and one expert endoscopist.

Enfermedad Inflamatoria Intestinal en el adulto mayor: Características clínicas y manejo en un hospital de referencia

La enfermedad inflamatoria intestinal (EII) en adultos mayores se caracteriza por su variabilidad clínica, distintos diagnósticos diferenciales y manejo terapéutico. El objetivo de la presente investigación es evaluar las características clínicas y manejo de los pacientes adultos mayores con EII. Se realizó un estudio observacional, descriptivo, retrospectivo de enero del 2011 a diciembre del 2019 en pacientes con EII en el Servicio de Gastroenterología del Hospital Nacional Guillermo Almenara Irigoyen, Lima-Perú. Fueron evaluados 55 pacientes con EC y 107 con CU; 45,6% de pacientes con EII eran adultos mayores. De ellos, 28 tenían EC y 46 CU. Los adultos mayores con EC presentaron fenotipo inflamatorio y localización colónica predominantemente, mientras en CU, la colitis extensa e izquierda fueron las más frecuentes. Asimismo, los ancianos tuvieron menor puntaje CDAI (279,8 vs 323,2) y menor índice de Mayo (7,1 vs 9,2) con relación a los pacientes jóvenes, sin diferencias significativas. Respecto al tratamiento, se observó un menor uso de azatioprina (2 vs 8, p<0,03) y Anti-TNF (9 vs 18, p<0,01) en los adultos mayores con EC. La necesidad de cirugía y la frecuencia de complicaciones post quirúrgicas fueron similares entre ambos grupos. En conclusión, casi la mitad de los pacientes con EII son adultos mayores. La localización colónica fue la más frecuente en EC, y en CU la colitis extensa e izquierda. Observamos un menor uso de azatioprina y terapia biológica en adultos mayores, sin diferencias significativas en el uso de corticoides y aminosalicilatos respecto a los jóvenes.

Inflammatory bowel disease (IBD) in elderly patients is characterized by its clinical variability, different differential diagnoses and therapeutic management. The objective of our investigation is to evaluate the clinical characteristics and management of elderly patients with IBD. We developed an observational, descriptive, retrospective study from January 2011 to December 2019 in patients with IBD at the Gastroenterology Service of Guillermo Almenara Irigoyen National Hospital, Lima-Peru. 55 patients with CD and 107 with UC were evaluated; 45.6% of patients with IBD are older adults. Of these, 28 had CD and 46 UC. Older adults with CD presented predominantly an inflammatory phenotype and colonic location, while extensive and left-sided colitis were the most frequent in UC. Elderly patients had a lower CDAI score (279.8 vs 323.2) and a lower Mayo index (7.1 vs 9.2) in relation to the younger, without significant differences. Regarding treatment, a lower use of azathioprine (2 vs 8, p <0.03) and Anti-TNF (9 vs 18, p <0.01) was observed in the elderly with CD. The need for surgery and the frequency of post-surgical complications were similar between both groups. In conclusion, nearly half of IBD patients are older adults. The colonic location was the most frequent in CD, and in UC extensive and left colitis. We observed a lower use of azathioprine and biological therapy in elderly patients, without significant differences in the use of corticosteroids and aminosalicylates compared to younger people.

[Gastrointestinal hemorrhage as an uncommon form of presentation of primary intestinal amyloidosis: case report]. / Hemorragia digestiva como forma de presentación poco usual de amiloidosis intestinal primaria: reporte de caso.

Intestinal amyloidosis is a rare and underdiagnosed systemic disease, which is characterized by the extracellular deposition of proteins that are grouped into amyloid fibers. This entity is rare and is usually a form of presentation in the context of systemic amyloidosis, the diagnosis of which is based on the presence of amyloid in histology. The clinic is usually non-specific; chronic diarrhea, weight loss, abdominal pain and bloating; Gastrointestinal bleeding is a very rare manifestation. The case of a 61-year-old woman with symptoms of weight loss, abdominal distension, nausea, vomiting and long hair is presented. Tomographically, a wall thickening of jejunal loops with contrast uptake was evidenced, a finding that was corroborated by a double-balloon anterograde stereoscopy in which multiple were evidenced. The pathology shows distorted and ulcerated villous architecture with positive histochemistry for Congo Red and LAMBDA (+++) immunohistochemistry. In addition, bone marrow aspirate and bone biopsy compatible with infiltration of Lambda chain monoclonal multiple myeloma were performed. During the hospital stay, the patient developed complications such as chronic malnutrition, recurrent infection and several episodes of intestinal subocclusion; characterized by intestinal pneumatosis; due to multiple episodes of these complications, the patient died. Within clinical practice in gastroenterology, intestinal amyloidosis as part of the differential diagnosis of upper gastrointestinal bleeding is infrequent, so a history of diagnosis of multiple myeloma or other monoclonal gammopathy associated with light chains is crucial for early diagnosis and adequate treatment.

Perioperative mortality in Colombia: perspectives of the fourth indicator in The Lancet Commission on Global Surgery - Colombian Surgical Outcomes Study (ColSOS) - a protocol for a multicentre prospective cohort study.

INTRODUCTION: Death following surgical procedures is a global health problem, accounting for 4.2 million deaths annually within the first 30 postoperative days. The fourth indicator of The Lancet Commission on Global Surgery is essential as it seeks to standardise postoperative mortality. Consequently, it helps identify the strengths and weaknesses of each country's healthcare system. Accurate information on this indicator is not available in Colombia, limiting the possibility of interventions applied to our population. We aim to describe the in-hospital perioperative mortality of the surgical procedures performed in Colombia. The data obtained will help formulate public policies, improving the quality of the surgical departments. METHODS AND ANALYSIS: An observational, analytical, multicentre prospective cohort study will be conducted throughout Colombia. Patients over 18 years of age who have undergone a surgical procedure, excluding radiological/endoscopic procedures, will be included. A sample size of 1353 patients has been projected to achieve significance in our primary objective; however, convenience sampling will be used, as we aim to include all possible patients. Data collection will be carried out prospectively for 1 week. Follow-up will continue until hospital discharge, death or a maximum of 30 inpatient days. The primary outcome is perioperative mortality. A descriptive analysis of the data will be performed, along with a case mix analysis of mortality by procedure-related, patient-related and hospital-related conditions ETHICS AND DISSEMINATION: The Fundación Cardioinfantil-Instituto de Cardiología Ethics Committee approved this study (No. 41-2021). The results are planned to be disseminated in three scenarios: the submission of an article for publication in a high-impact scientific journal and presentations at the Colombian Surgical Forum and the Congress of the American College of Surgeons. TRIAL REGISTRATION NUMBER: NCT05147623.

Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming.

Stem cell division is linked to tumorigenesis by yet-elusive mechanisms. The hematopoietic system reacts to stress by triggering hematopoietic stem and progenitor cell (HSPC) proliferation, which can be accompanied by chromosomal breakage in activated hematopoietic stem cells (HSCs). However, whether these lesions persist in their downstream progeny and induce a canonical DNA damage response (DDR) remains unclear. Inducing HSPC proliferation by simulated viral infection, we report that the associated DNA damage is restricted to HSCs and that proliferating HSCs rewire their DDR upon endogenous and clastogen-induced damage. Combining transcriptomics, single-cell and single-molecule assays on murine bone marrow cells, we found accelerated fork progression in stimulated HSPCs, reflecting engagement of PrimPol-dependent repriming, at the expense of replication fork reversal. Ultimately, competitive bone marrow transplantation revealed the requirement of PrimPol for efficient HSC amplification and bone marrow reconstitution. Hence, fine-tuning replication fork plasticity is essential to support stem cell functionality upon proliferation stimuli.

A Screening Tool for Self-Evaluation of Risk for Age-Related Macular Degeneration: Validation in a Spanish Population.

Purpose: The objectives of this study were the creation and validation of a screening tool for age-related macular degeneration (AMD) for routine assessment by primary care physicians, ophthalmologists, other healthcare professionals, and the general population. Methods: A simple, self-administered questionnaire (Simplified Théa AMD Risk-Assessment Scale [STARS] version 4.0) which included well-established risk factors for AMD, such as family history, smoking, and dietary factors, was administered to patients during ophthalmology visits. A fundus examination was performed to determine presence of large soft drusen, pigmentary abnormalities, or late AMD. Based on data from the questionnaire and the clinical examination, predictive models were developed to estimate probability of the Age-Related Eye Disease Study (AREDS) score (categorized as low risk/high risk). The models were evaluated by area under the receiving operating characteristic curve analysis. Results: A total of 3854 subjects completed the questionnaire and underwent a fundus examination. Early/intermediate and late AMD were detected in 15.9% and 23.8% of the patients, respectively. A predictive model was developed with training, validation, and test datasets. The model in the test set had an area under the curve of 0.745 (95% confidence interval [CI] = 0.705-0.784), a positive predictive value of 0.500 (95% CI = 0.449-0.557), and a negative predictive value of 0.810 (95% CI = 0.770-0.844). Conclusions: The STARS questionnaire version 4.0 and the model identify patients at high risk of developing late AMD. Translational Relevance: The screening instrument described could be useful to evaluate the risk of late AMD in patients >55 years without having an eye examination, which could lead to more timely referrals and encourage lifestyle changes.

Early preoperative progressive pneumoperitoneum for a symptomatic giant abdominal incisional hernia.

INTRODUCTION AND IMPORTANCE: Early preoperative progressive pneumoperitoneum (PPP) is a technique that helps large eventrations with loss of domain to reintroduce protruded organs. However, a standardized technique has not been developed. This technique has been proved in elective patients, but the evidence is scarce in patients with a high risk of incarceration/strangulation. CLINICAL FINDINGS AND INVESTIGATIONS: We present a 61-year-old patient with history of a thoracoabdominal aneurysm repair, developed a massive incisional hernia with loss of domain. At admission, he presented with abdominal pain and inability to reduce the hernia by himself, however it reduced after clinical examination. Aortic syndromes were excluded. INTERVENTIONS AND OUTCOME: After a multidisciplinary meeting, early PPP was initially performed. Later he was taken to surgery and admitted in the ICU to prevent abdominal hypertension. Medical complications resolved within 14 days. The patient did not report long-term complications. RELEVANCE AND IMPACT: PPP is a technique that pursues the prevention of abdominal hypertension syndrome in patients with large hernias with loss of domain electively. For patients with high risk of hernia complications, the evidence is limited regarding the applicability of early PPP. A multidisciplinary team can improve decision making and therefore reduce the risk of long-term complications. We show a case where PPP was performed in an acute painful, reducible hernia with a high risk of incarceration, showing that this approach can be an option for acutely ill patients.

Sera from women with different metabolic and menopause states differentially regulate cell viability and Akt activation in a breast cancer in-vitro model.

Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-ß/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-ß and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.

Leptin and its receptor are overexpressed in breast cancer tissue of postmenopausal Mexican-Mestizo women with obesity.

The aim of this study was to investigate the expression of leptin (LEP) and its receptor (LEPR) in breast cancer tissue of postmenopausal women with different body mass indexes (BMI), as well as the relationship of this expression with the rate of recurrence free survival (RFS). Leptin and LEPR expression, determined by immunohistochemistry, were studied in breast cancer tissues of 154 patients. Qualitative and semi-quantitative analysis of protein expression was performed by the H-Score method, through the ImageJ's IHC Profiler software. Kaplan-Meier survival analysis and log-rank statistic were used to estimate RFS differences. Protein expression of LEP, was significantly higher in women with overweight or with obesity, when compared to women with normal BMI (P = 0.032 and P = 0.013, respectively). We also observed a significantly higher expression of LEPR in breast tumor cells of women with obesity (58.8%), when compared to women with normal BMI (32.7%) (P = 0.007). Five-year survival rate, regarding LEPR expression, was 82.4% when positive and 94% when negative (P = 0.024). In the Cox proportional-hazards regression model, LEPR expression represented a risk factor for disease recurrence after adjustment for confounding factors (HR = 4.67; 95% CI: 1.13-19.31; P = 0.033). In conclusion, postmenopausal women with obesity and breast cancer present higher LEP and LEPR expression in breast tumors, when compared to women with normal BMI. Independently from BMI, women with tumors LEPR positive have worst RFS, when compared to women with tumors LEPR negative.

[Medical and surgical management of moderate-to-severe inflamatory bowel disease]. / Manejo médico quirúrgico de la enfermedad inflamatoria intestinal moderada-severa.

The management of inflammatory bowel disease (IBD) is mainly medical, however, more than 70% of patients with Crohn's disease (CD) and 25% with ulcerative colitis (UC) will require surgery during their lifetime. OBJECTIVE: To evaluate medical, surgical management and evolution in patients with moderate-to-severe IBD. MATERIALS AND METHODS: Observational, descriptive, retrospective study from January 2011 to December 2019 in the Gastroenterology Service of the Guillermo Almenara Irigoyen National Hospital, Lima-Peru. RESULTS: Twenty two patients with IBD, 17 with CD and 5 with UC were included. Male predominance (59%). Emergency surgery was performed in 35.2% and 60% of patients with CD and UC, respectively. Stenosis and toxic megacolon were the most frequent indications. According to the type of surgery, hemicolectomy (41%) and intestinalresection (41%) were the most frequently performed in CD, while in UC it was total colectomy (60%). Among the postoperative complications, dehiscence/fistula and intra-abdominal collections were the most frequently reported in CD; whereas in UC it was surgical site infection and adynamic ileus. After surgery, biologics and 5-ASA associated with immunomodulator were the most used treatment in CD and UC, respectively. Mortality was 17.6% in CD and 60% in UC. CONCLUSIONS: Surgical treatment is an option in the management of moderate-to-severe IBD. Emergency surgery in IBD continues to have a high morbidity and mortality rate.