Synthesis and evaluation of antibacterial and antibiofilm agents based on phenylamino-substituted 1,4-benzoquinones.

Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128 µg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 µg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.

[Box: see text].

Faecal Volatile Organic Compounds to Detect Colorectal Neoplasia in Lynch Syndrome-A Prospective Longitudinal Multicentre Study.

BACKGROUND: Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia. AIM: The aim of this study was to evaluate the potential of faecal VOCs-separately and with FIT-to guide optimal colonoscopy intervals in Lynch syndrome. METHODS: Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 µg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance. RESULTS: Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide. CONCLUSIONS: In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies. TRIAL REGISTRATION: NL8749.

Obesity as an aggravating factor of systemic lupus erythematosus disease: What we already know and what we must explore? - A rapid scoping review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect various organs and systems. Symptoms of SLE can vary widely from person to person and over time, including fatigue, joint pain, skin rashes, fever, and inflammation of multiple organs. The association between SLE and excess body weight has been the subject of study, with evidence suggesting that overweight and obesity can worsen the disease´s clinical presentation. Obesity is linked to a state of low-grade chronic inflammation, which can exacerbate the inflammation present in SLE. Additionally, obesity may negatively impact treatment response, disease progression, and patient prognosis. Patients with SLE and obesity may face additional challenges in managing the disease, such as increased symptom severity, higher risk of cardiovascular and renal complications, and a reduced response to conventional treatments. Obesity can also influence the quality of life of patients with SLE, making a holistic approach that considers the individual's nutritional status essential. Therefore, understanding the relationship between obesity and SLE is crucial for optimizing treatment, improving clinical outcomes, and enhancing patients' quality of life. Further research is needed to elucidate the underlying pathophysiological mechanisms, develop more precise and personalized management strategies, and identify biomarkers that can predict disease prognosis and treatment response.

Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The Molecular Stool Testing for Colorectal Cancer Surveillance Study.

BACKGROUND & AIMS: Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. METHODS: This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. RESULTS: There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. CONCLUSIONS: This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. CLINICALTRIALS: gov, Number: NCT02715141.

Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers.

Ovarian cancer is a leading cause of death for women worldwide in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I-IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I-IV. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC=0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.

Fitting a progressive three-state colorectal cancer model to interval-censored surveillance data under outcome-dependent sampling using a weighted likelihood approach.

To optimize colorectal cancer (CRC) surveillance, accurate information on the risk of developing CRC from premalignant lesions is essential. However, directly observing this risk is challenging since precursor lesions, i.e., advanced adenomas (AAs), are removed upon detection. Statistical methods for multistate models can estimate risks, but estimation is challenging due to low CRC incidence. We propose an outcome-dependent sampling (ODS) design for this problem in which we oversample CRCs. More specifically, we propose a three-state model for jointly estimating the time distributions from baseline colonoscopy to AA and from AA onset to CRC accounting for the ODS design using a weighted likelihood approach. We applied the methodology to a sample from a Norwegian adenoma cohort (1993-2007), comprising 1, 495 individuals (median follow-up 6.8 years [IQR: 1.1 - 12.8 years]) of whom 648 did and 847 did not develop CRC. We observed a 5-year AA risk of 13% and 34% for individuals having non-advanced adenoma (NAA) and AA removed at baseline colonoscopy, respectively. Upon AA development, the subsequent risk to develop CRC in 5 years was 17% and age-dependent. These estimates provide a basis for optimizing surveillance intensity and determining the optimal trade-off between CRC prevention, costs, and use of colonoscopy resources.

Fecal Immunochemical Test to Detect Colorectal Neoplasia in Lynch Syndrome: A Prospective Multicenter Study.

INTRODUCTION: Colonoscopy surveillance for Lynch syndrome is burdensome and postcolonoscopy colorectal cancers (CRCs) still occur. The noninvasive fecal immunochemical test (FIT) might guide optimal colonoscopy intervals. METHODS: Prospective, multicenter observational study in which individuals with Lynch syndrome performed a quantitative FIT before high-quality surveillance colonoscopy. Diagnostic performance of FIT at various thresholds ≤20 µg Hb/g feces was assessed for relevant neoplasia, including advanced neoplasia (CRC, advanced adenomas [AAs] and advanced serrated lesions [ASLs]) and non-advanced adenomas (NAAs). RESULTS: Of the 217 included individuals (59% female, median age 51 years), 4 had CRC, 5 AA, 4 ASL, and 57 NAA as most relevant neoplasia. The lowest FIT positivity threshold (2.5 µg Hb/g feces, 14% positivity rate) maximized detection: 4/4 CRCs, 4/5 AA, 1/4 ASL, and 9/57 NAA were detected, resulting in a sensitivity and negative predictive value of, respectively, 89% and 99% for CRC plus AA, 69% and 97% for advanced neoplasia, and 26% and 72% for all relevant neoplasia (91% specificity for all groups). At equal sensitivity and negative predictive value, specificity for advanced neoplasia optimized to 94% at threshold 4.1 µg/g. Per 100 FITs at threshold 4.1 µg/g, 11 individuals would test positive and thus proceed to colonoscopy, 2 individuals with advanced neoplasia would be missed and 3 individuals would need colonoscopy to detect 1 advanced neoplasia. DISCUSSION: FIT at thresholds ≤4.1 µg Hb/g feces may be a promising strategy to postpone colonoscopy in approximately 9 of 10 individuals with Lynch syndrome. Large validation studies that also provide gene variant-specific outcomes should be prioritized.

Association between Depressive Symptoms and Social Support in a Nationally Representative Sample Of Older Adults (ELSI-Brazil).

OBJECTIVE: To investigate the association between depressive symptoms and social support among a representative sample of the Brazilian population aged 50 years or older. METHODOLOGY: Cross-sectional study, based on 8,074 participants of the second wave of the Brazilian Longitudinal Study on Aging - ELSI-Brasil. Depressive symptoms were screened based on the CES-D8 instrument, and social support was investigated in its structural and functional dimensions. Sociodemographic variables and health conditions were considered for adjustment in investigating the association between social support and depressive symptoms using the Poisson regression model. RESULTS: The prevalence of depressive symptoms was estimated at 19.1% (95% CI:16.7;21.7). In the analysis adjusted for possible confounding factors, depressive symptoms were independently associated with negative social support in the items "not married" (RP=1.24; 95% CI: 1.07-1.44), "not having someone to trust" (RP=1.31; 95% CI: 1.10-1.56) and "not having someone to borrow money or an object from, in case of need" (RP=1.46; 95% CI: 1.21-1.75). CONCLUSION: The present results highlight the importance of social relations in determining the presence of depressive symptoms and reinforce the need to implement public policies aimed at strengthening social networks to minimize this public health problem.

Hypocoagulability in severe yellow fever infection is associated with bleeding: results from a cohort study.

Background: Severe yellow fever infection (YFI) may be complicated by a hemorrhagic diathesis. However, the hemostasis profile of YFI has rarely been reported. Objectives: The aim of this study was to characterize the hemostatic features of YFI by using a rotational thromboelastometry (ROTEM). Methods: We evaluated clinical, laboratory, and ROTEM parameters in adults with severe YFI and their correlation with hemostatic variables according to bleeding and death. Results: A total of 35 patients were included (median age, 49 years). ROTEM was performed in 22 patients, of whom 21 (96%) presented bleeding and 4 (18%) died. All patients who died had major bleeding. Patients who died presented prolonged clotting time (CT; median, 2326 seconds; IQR, 1898-2986 seconds) and reduced alpha angle (median, 12°; IQR, 12°-15°) in comparison with patients who had minor (median CT, 644 seconds; IQR, 552-845 seconds and alpha angle, 47°; IQR, 28°-65°) and major (median CT, 719 seconds; IQR, 368-1114 seconds and alpha angle, 43°; IQR, 32°-64°) bleeding who survived. In patients who had bleeding, CT showed a strong negative correlation with factor (F)V (r = -.68), FIX (r = -.84), and FX (r = -.63) as well as alpha angle showed a strong negative correlation with FIX (r = -.92). In patients who died, the correlations were even stronger. A total of 19/21 (90%) patients presented hypocoagulability assessed by ROTEM. Conclusion: Hypocoagulabitity is the hallmark of the bleeding diathesis of severe YFI. Abnormal CT and alpha angle associated with death and could be used as potential predictors of adverse outcome in severe YFI.

Baby Date: a mobile application for teaching nursing care to newborns in primary care.

OBJECTIVE: to develop and validate a mobile application for teaching undergraduates about the first nursing visit to a newborn in primary care. METHOD: methodological study with an Instructional Design framework; content drawn up from scientific documents on caring for newborns and their families, supported by the results of an integrative review on the subject. The Integrated Development Environment Android Studio 4.0.1 tool and the IntelliJ IDEA platform were used to build the digital technology. Experts validated content and students evaluated navigability. RESULTS: the final version of the mobile application contains 67 screens grouped into 12 sections with random access. The device is presented on the introductory screen; this is followed by content on the physical examination, neonatal screening, nutrition, oral health, the vaccination calendar, growth, development, danger signs, and accident prevention; at the end, there is a fact sheet and references. Audiovisual resources (texts, images, and videos) complement the application; experts presented a Content Validity Index (CVI) = 1.00; for nursing students all the items had a CVI = 1.00; only the item "layout and presentation" had a CVI = 0.95. CONCLUSION: the digital technology received a satisfactory evaluation from experts and students. It is innovative in child health care, with the potential to be used in the teaching-learning process of nursing students. BACKGROUND: (1) The mobile application provides content for newborn care in primary care. (2) The mobile application directs the nurse's consultation through evidence of care. (3) The mobile application can be used offline, offering knowledge at any time and place. (4) Navigation does not require a specific order, which gives the user freedom. (5) The mobile application promotes quality care in the first consultation with the newborn in primary care.

Polyketide synthase positive Escherichia coli one-time measurement in stool is not informative of colorectal cancer risk in a screening setting.

Environmental factors like the pathogenicity island polyketide synthase positive (pks+) Escherichia coli (E. coli) could have potential for risk stratification in colorectal cancer (CRC) screening. The association between pks+ E. coli measured in fecal immunochemical test (FIT) samples and the detection of advanced neoplasia (AN) at colonoscopy was investigated. Biobanked FIT samples were analyzed for both presence of E. coli and pks+ E. coli and correlated with colonoscopy findings; 5020 CRC screening participants were included. Controls were participants in which no relevant lesion was detected because of FIT-negative results (cut-off ≥15 µg Hb/g feces), a negative colonoscopy, or a colonoscopy during which only a nonadvanced polyp was detected. Cases were participants with AN [CRC, advanced adenoma (AA), or advanced serrated polyp (ASP)]. Existing DNA isolation and quantitative polymerase chain reaction (qPCR) procedures were used for the detection of E. coli and pks+ E. coli in stool. A total of 4542 (90.2%) individuals were E. coli positive, and 1322 (26.2%) were pks+ E. coli positive. The prevalence of E. coli in FIT samples from individuals with AN was 92.9% compared to 89.7% in FIT samples of controls (p = 0.010). The prevalence of pks+ E. coli in FIT samples from individuals with AN (28.6%) and controls (25.9%) was not significantly different (p = 0.13). The prevalences of pks+ E. coli in FIT samples from individuals with CRC, AA, or ASP were 29.6%, 28.3%, and 32.1%, respectively. In conclusion, the prevalence of pks+ E. coli in a screening population was 26.2% and did not differ significantly between individuals with AN and controls. These findings disqualify the straightforward option of using a snapshot measurement of pks+ E. coli in FIT samples as a stratification biomarker for CRC risk. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The multitarget faecal immunochemical test for improving stool-based colorectal cancer screening programmes: a Dutch population-based, paired-design, intervention study.

BACKGROUND: The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. METHODS: Individuals aged 55-75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 µg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov, NCT05314309, and is complete. FINDINGS: Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62-9·61) positivity rate and 2·27% (95% CI 2·02-2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75-4·43) and a detection rate of 1·21% (1·03-1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13-0·29) versus 0·17% (0·11-0·27) for colorectal cancer; 1·64% (1·43-1·87) versus 0·86% (0·72-1·04) for advanced adenoma, and 0·43% (0·33-0·56) versus 0·17% (0·11-0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. INTERPRETATION: The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. FUNDING: Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland.

Índice de massa corporal e desfechos clínicos: um estudo retrospectivo durante a pandemia de Covid-19 / Body mass index and clinical outcomes: a retrospective study in Covid-19 / Índice de masa corporal y resultado clínico: un estudio retrospectivo durante la pandemia de Covid-19

A COVID-19 é uma doença respiratória aguda provocada pela infecção do vírus SARS-CoV-2, que pode causar uma grave insuficiência respiratória hipoxêmica, complicações e mortes, principalmente na população com condições crônicas de saúde. Os mecanismos pelos quais a obesidade pode aumentar a gravidade da COVID-19 incluem mecanismos físicos, inflamação crônica e uma função imunológica prejudicada. Além disso, o índice de massa corporal elevado é um fator de risco para várias condições médicas que têm sido sugeridas para aumentar o risco de gravidade da COVID-19. Objetivo: analisar a associação entre o índice de massa corporal e desfechos clínicos dos casos confirmados de COVID-19. Metodologia: Estudo transversal, com coleta de dados de prontuários, conduzido de março de 2020 a dezembro 2021. Foram analisados os registros de prontuários, exames bioquímicos e de imagem de pacientes internados com COVID-19 em três hospitais da cidade de Francisco Beltrão (PR). As variáveis analisadas foram o diagnóstico nutricional, idade, sexo, necessidade de internação em UTI, comorbidades, dias de hospitalização, complicações, exames laboratoriais e desfecho. Os critérios para inclusão no estudo foram, pacientes hospitalizados com diagnóstico para COVID-19, com presença de diagnóstico nutricional relatado. Resultados: No ano de 2020 foram analisados 292 prontuários e no ano de 2021 foram 860 prontuários. Destes, somente 413 possuíam diagnóstico nutricional, sendo assim incluídos no presente estudo. Foram classificados como peso normal 78 (18,9%), com sobrepeso 153 (37%)e como obeso 182 (44,1%) participantes. A maior prevalência de obesidade foi encontrada no sexo feminino (52,5%), portadores de diabetes (27,6%), pacientes com estado geral comprometido (67,9%), que apresentaram complicações pulmonares (54,5%) e arritmias (23%). A média de idade encontrada em pacientes com obesidade foi mais jovem (55,54) em comparação com os classificados com sobrepeso (59,08) e normal (62,51). Observou-se que quanto maior o IMC menor foram os valores encontrados para idade (rho = -0,190), leucócitos (rho = -0,109), ureia (rho = -0,145) e D-dímero (rho = -0,155). Conclusão: Este estudo fornece evidências de que o sobrepeso e/ou obesidade então associadas a um pior quadro clínico durante a internação dos pacientes com COVID-19. Em relação a frequência de óbito, não houve diferença estatística em relação ao diagnóstico nutricional.

COVID-19 is an acute respiratory disease caused by SARS-CoV-2 virus infection, which can cause severe hypoxemic respiratory failure, complications, and deaths, especially in the population with chronic health conditions. The mechanisms by which obesity may increase the severity of COVID-19 include physical mechanisms, chronic inflammation, and impaired immune function. In addition, high body mass index is a risk factor for several medical conditions that have been suggested to increase the risk of COVID-19 severity. Objective: to analyze the association between body mass index and clinical outcomes of confirmed cases of COVID-19. Methodology: Cross-sectional study, with data collection from medical records, conducted from March 2020 to December 2021. The records of medical records, biochemical and imaging tests of patients hospitalized with COVID-19 in three hospitals in the city of Francisco Beltrão (PR) were analyzed. The variables analyzed were nutritional diagnosis, age, gender, need for ICU admission, comorbidities, days of hospitalization, complications, laboratory tests and outcome. The inclusion criteria for the study were, hospitalized patients with diagnosis for COVID-19, with presence of nutritional diagnosis reported. Results: In the year 2020, 292 medical records were analyzed and in the year 2021 there were 860 medical records. Of these, only 413 had nutritional diagnosis, thus being included in this study. Were classified as normal weight 78 (18.9%), overweight 153 (37%), and obese 182 (44.1%) participants. The highest prevalence of obesity was found in females (52.5%), patients with diabetes (27.6%), patients with impaired general condition (67.9%), who presented pulmonary complications (54.5%) and arrhythmias (23%). The mean age found in obese patients was younger (55.54) compared to those classified as overweight (59.08) and normal (62.51). It was observed that the higher the BMI the lower were the values found for age (rho = -0.190), leukocytes (rho = -0.109), urea (rho = -0.145) and D-dimer (rho = -0.155). Conclusion: This study provides evidence that overweight and/or obesity then associated with a worse clinical picture during hospitalization of patients with COVID-19. Regarding the frequency of death, there was no statistical difference in relation to nutritional diagnosis.

COVID-19 es una enfermedad respiratoria aguda causada por la infección por el virus SARS-CoV-2, que puede provocar insuficiencia respiratoria hipoxémica grave, complicaciones y muertes, especialmente en poblaciones con enfermedades crónicas. Los mecanismos por los cuales la obesidad puede aumentar la gravedad de la COVID-19 incluyen mecanismos físicos, inflamación crónica y función inmune deteriorada. Además, un índice de masa corporal alto es un factor de riesgo para varias afecciones médicas que, según se ha sugerido, aumentan el riesgo de gravedad del COVID-19. Objetivo: analizar la asociación entre el índice de masa corporal y los resultados clínicos de casos confirmados de COVID-19. Metodología: Estudio transversal, con recolección de datos de historias clínicas, realizado de marzo de 2020 a diciembre de 2021. Se analizaron historias clínicas, exámenes bioquímicos y de imagen de pacientes hospitalizados con COVID-19 en tres hospitales de la ciudad de Francisco Beltrão (PR). Las variables analizadas fueron diagnóstico nutricional, edad, sexo, necesidad de ingreso a UCI, comorbilidades, días de internación, complicaciones, exámenes de laboratorio y evolución. Los criterios de inclusión en el estudio fueron pacientes hospitalizados con diagnóstico de COVID-19, con presencia de diagnóstico nutricional informado. Resultados: En 2020 se analizaron 292 historias clínicas y en 2021 se analizaron 860 historias clínicas. De ellos, sólo 413 tenían diagnóstico nutricional, por lo que fueron incluidos en el presente estudio. 78 (18,9%) participantes fueron clasificados como normopeso, 153 (37%) como sobrepeso y 182 (44,1%) como obesidad. La mayor prevalencia de obesidad se encontró en el sexo femenino (52,5%), pacientes con diabetes (27,6%), pacientes con estado general comprometido (67,9%), quienes presentaron complicaciones pulmonares (54,5%) y arritmias (23%). La edad promedio encontrada en los pacientes con obesidad fue menor (55,54) en comparación con los clasificados como con sobrepeso (59,08) y normales (62,51). Se observó que a mayor IMC, menores son los valores encontrados para edad (rho = -0,190), leucocitos (rho = -0,109), urea (rho = -0,145) y dímero D (rho = -0,155). Conclusión: Este estudio proporciona evidencia de que el sobrepeso y/u obesidad se asocia con una peor condición clínica durante la hospitalización de pacientes con COVID-19. En cuanto a la frecuencia de muerte, no hubo diferencia estadística en relación al diagnóstico nutricional.

Baby Date: a mobile application for teaching nursing care to newborns in primary care / Baby Date: aplicación móvil instructora de consulta de enfermería al recién nacido en atención básica / Baby Date: aplicación móvil instructora de consulta de enfermería al recién nacido en atención básica

Objective: to develop and validate a mobile application for teaching undergraduates about the first nursing visit to a newborn in primary care. Method: methodological study with an Instructional Design framework; content drawn up from scientific documents on caring for newborns and their families, supported by the results of an integrative review on the subject. The Integrated Development Environment Android Studio 4.0.1 tool and the IntelliJ IDEA platform were used to build the digital technology. Experts validated content and students evaluated navigability. Results: the final version of the mobile application contains 67 screens grouped into 12 sections with random access. The device is presented on the introductory screen; this is followed by content on the physical examination, neonatal screening, nutrition, oral health, the vaccination calendar, growth, development, danger signs, and accident prevention; at the end, there is a fact sheet and references. Audiovisual resources (texts, images, and videos) complement the application; experts presented a Content Validity Index (CVI) = 1.00; for nursing students all the items had a CVI = 1.00; only the item "layout and presentation" had a CVI = 0.95. Conclusion: the digital technology received a satisfactory evaluation from experts and students. It is innovative in child health care, with the potential to be used in the teaching-learning process of nursing students.

Objetivo: desarrollar y validar aplicación móvil para instrucción de estudiantes sobre la primera consulta de Enfermería al recién nacido en atención básica. Método: estudio metodológico con referencial Diseño Instruccional; contenido elaborado partiendo de documentos científicos sobre atención al recién nacido y su familia, respaldado en resultados de revisión integrativa del tema. Fueron utilizadas la herramienta Integrated Development Environment Android Studio 4.0.1 y la plataforma IntelliJ IDEA para construir la tecnología digital. Expertos validaron contenido, y estudiantes evaluaron navegabilidad. Resultados: la versión final de la aplicación móvil incluye 67 pantallas agrupadas en 12 secciones de acceso aleatorio. El dispositivo es presentado en la pantalla introductora, a continuación, se muestra contenido referente al examen físico, cribado neonatal, alimentación, salud bucal, calendario de vacunación, crecimiento, desarrollo, señales de riesgo, prevención de accidentes; al final, ficha técnica y referencias. Recursos audiovisuales (textos, imágenes y videos) complementan la aplicación; para expertos, Índice de Validez de Contenido (IVC)=1,00; y para estudiantes de Enfermería, todos los ítems presentaron IVC=1,00; solo el ítem " layout y presentación" obtuvo IVC=0,95. Conclusión: la tecnología digital fue evaluada satisfactoriamente por expertos y estudiantes; es innovadora en el área de salud del niño, con potencial uso en el proceso de enseñanza-aprendizaje de los estudiantes de Enfermería.

Objetivo: desenvolver e validar aplicativo móvel para o ensino de graduandos sobre a primeira consulta de Enfermagem ao recém-nascido na atenção básica. Método: estudo metodológico com referencial Design Instrucional; conteúdo elaborado a partir de documentos científicos acerca do cuidado ao recém-nascido e sua família, apoiado em resultados de revisão integrativa sobre o tema. A ferramenta Integrated Development Environment Android Studio 4.0.1 e a plataforma IntelliJ IDEA foram utilizadas para a construção da tecnologia digital. Experts validaram conteúdo e alunos avaliaram navegabilidade. Resultados: a versão final do aplicativo móvel contém 67 telas agrupadas em 12 seções com acesso aleatório. O dispositivo é apresentado na tela introdutória; na sequência, tem-se conteúdo referente ao exame físico, triagem neonatal, alimentação, saúde bucal, calendário vacinal, crescimento, desenvolvimento, sinais de perigo, prevenção de acidentes; ao final, ficha técnica e referências. Recursos audiovisuais (textos, imagens e vídeos) complementam o aplicativo; para experts Índice de Validade de Conteúdo (IVC)=1,00; para estudantes de Enfermagem, todos os itens apresentaram IVC=1,00; somente o item " layout e apresentação" obteve IVC=0,95. Conclusão: a tecnologia digital obteve avaliação satisfatória entre experts e estudantes; é inovadora para a área da saúde da criança, com potencial para uso no processo de ensino-aprendizagem dos estudantes de Enfermagem.

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy.

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43-57) vs 55 years (IQR 51-62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P = .0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P < .0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P < .0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.

Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case-Control Study.

Current morphologic features defining advanced adenomas (size ≥10 mm, high-grade dysplasia or ≥25% villous component) cannot optimally distinguish individuals at high risk or low risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy-number alterations (CNAs) are associated with adenoma-to-carcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features.In this nested case-control study, 529 individuals with a single adenoma at first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy-number profiles were determined, by low-coverage whole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (with me-CRC) were matched to controls (without me-CRC) on follow-up, age and sex.CNAs associated with adenoma-to-carcinoma progression were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. me-CRC was statistically significantly associated, also after adjustment for other variables, with age at baseline [OR, 1.14; 95% confidence interval CI), 1.03-1.26; P = 0.012], advanced adenomas (OR, 2.46; 95% CI, 1.50-4.01; P < 0.001) and with the presence of ≥3 DNA copy-number losses (OR, 1.90; 95% CI. 1.02-3.54; P = 0.043).Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger. SIGNIFICANCE: Identifying new biomarkers may improve prediction of me-CRC for individuals with adenomas and optimize surveillance intervals to reduce risk of colorectal cancer and reduce oversurveillance of patients with low risk of colorectal cancer. Use of DNA CNAs alone does not improve prediction of me-CRC. Further research to improve risk classification is required.

Excess weight increases the risk of sarcopenia in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease. Nutritional status influences the course of the disease, however, its relationship with sarcopenia needs further investigation. The aim of the study was to identify patients with sarcopenia and assess its association with nutritional status and the clinical course of the disease. METHODS: The study assessed 110 patients submitted to evaluation of sociodemographic characteristics, level of physical activity, nutritional status, and presence of sarcopenia. The clinical course of the disease, age at onset, disease duration, disease-modifying therapy, and expanded scale of disability status (EDSS) were investigated. RESULTS: Mean age was 37.17 (SD = 10.60) years, disease duration was 6.29 years (SD = 4.65), with a predominance of female gender (80.90 %), relapsing-remitting clinical form (RRMS) (89.10 %) and mild level of disability (EDSS median = 1.92). The group had excess weight (53.6 %) according to body mass index (BMI) and abdominal fat accumulation measured by waist circumference (WC) (53.6 %). High percentage of fat mass ( % FM) was observed in 54.5 % and 38.2 % of the patients according to bioimpedance (BIA) and ultrasound (US), respectively. It was observed that 15.5 % were at risk for sarcopenia, which was associated with excess weight, and high % FM (p<0.05). CONCLUSION: These findings highlight the importance of including nutritional status indicators, and sarcopenia assessment in the care of patients with MS.

Gestational hypertension as a factor associated with chronic kidney disease: the importance of obstetric history of women undergoing hemodialysis / Hipertensão gestacional como fator associado à doença renal crônica: a importância do histórico obstétrico de mulheres submetidas à hemodiálise

ABSTRACT Introduction: Pregnancy-related complications may impact women's reproductive cycle and health through their lives. The objective of this study was to evaluate the sociodemographic, clinical, and obstetric history of women undergoing hemodialysis. Methods: We performed a cross-sectional study in a specialized health facility with four hemodialysis units. Sociodemographic characteristics, clinical and personal history, obstetric and perinatal results of women with pregnancies before hemodialysis were evaluated. Prevalence, bivariate, and logistic regression analyses were performed. Results: We included 208 (87.76%) women. Hypertension was the main cause of chronic kidney disease (CKD) (128 women). Rates of adverse perinatal outcomes, including prematurity, low birth weight, miscarriage, fetal death, and neonatal death, were 19.3%, 14.5%, 25.5%, 12.1%, and 5.3%, respectively. Hypertensive syndromes during pregnancy occurred in 37.0% of women, with 12.5% reporting preeclampsia and 1.4% reporting eclampsia. Up to 1 year after birth, 45.2% of women reported hypertension. Hemodialysis due to hypertension was associated with a history of hypertension during pregnancy (OR 2.33, CI 1.27 - 4.24), gestational hypertension (2.41, CI 3.30 - 4.45), and hypertension up to one year after birth (OR 1.98, CI 1.11 - 3.51). Logistic regression showed that gestational hypertension was independently associated with CKD due to hypertension (aOR 2.76, CI 1.45 - 5.24). Conclusion: Women undergoing hemodialysis due to hypertension were more likely to have gestational hypertension or hypertension up to one year after birth. To delay end-stage renal disease, it is necessary to identify women at risk of kidney failure according to their reproductive history.

RESUMO Introdução: Complicações relacionadas à gestação podem afetar o ciclo reprodutivo e a saúde das mulheres ao longo de suas vidas. Este estudo visou avaliar histórico sociodemográfico, clínico e obstétrico de mulheres em hemodiálise. Métodos: Realizamos estudo transversal em unidade de saúde especializada com quatro unidades de hemodiálise. Avaliou-se características sociodemográficas, histórico clínico e pessoal, resultados obstétricos e perinatais de mulheres com gestações anteriores à hemodiálise. Foram realizadas análises de prevalência, bivariadas e regressão logística. Resultados: Incluímos 208 (87,76%) mulheres. Hipertensão foi a principal causa de doença renal crônica (DRC) (128 mulheres). Taxas de desfechos perinatais adversos, incluindo prematuridade, baixo peso ao nascer, aborto espontâneo, óbito fetal e neonatal, foram de 19,3%, 14,5%, 25,5%, 12,1% e 5,3%, respectivamente. Síndromes hipertensivas durante a gestação ocorreram em 37,0% das mulheres, com 12,5% relatando pré-eclâmpsia e 1,4% relatando eclampsia. Até 1 ano após o parto, 45,2% das mulheres relataram hipertensão. Hemodiálise devido à hipertensão foi associada ao histórico de hipertensão na gestação (OR 2,33; IC 1,27 - 4,24), hipertensão gestacional (2,41; IC 3,30 - 4,45), e hipertensão até um ano após o parto (OR 1,98; IC 1,11 - 3,51). A regressão logística mostrou que hipertensão gestacional foi independentemente associada à DRC devido à hipertensão (ORa 2,76; IC 1,45 - 5,24). Conclusão: Mulheres submetidas à hemodiálise por hipertensão foram mais propensas a apresentar hipertensão gestacional ou hipertensão até um ano após o parto. Para retardar a doença renal em estágio terminal, deve-se identificar mulheres em risco de insuficiência renal de acordo com sua história reprodutiva.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.