Malignancy and mass-forming phenotypes of IgG4-related disease: a challenging diagnosis.

Mass-forming phenotypes of IgG4-related disease (IgG4-RD) mimic malignancy and histological confirmation can be challenging. A woman in her 70s with HIV infection presented with painless obstructive jaundice and weight loss. Magnetic resonance imaging was suggestive of unresectable cholangiocarcinoma. Tumour markers and serum IgG4 were normal. Percutaneous liver biopsy was consistent with IgG4-RD inflammatory pseudotumour, with complete response to glucocorticoid therapy. Two years later, a new episode of obstructive jaundice occurred, with CT showing a solid lesion in the head of the pancreas with double duct sign and encasement of the portal vein. Re-induction therapy was tried without response. Fine-needle biopsy was consistent with pancreatic cancer. Supportive care was offered and the patient died 8 months later, with no signs of disease progression on subsequent imaging. We discuss the challenges of IgG4-RD diagnosis and treatment and the differential diagnosis between mass-forming phenotypes and malignancy, highlighting the difficulties in managing such patients.

Outcomes of Extracorporeal Life Support in Children with Meningococcal Septicemia: A Retrospective Cohort Study.

Meningococcal disease is associated with high mortality despite aggressive antibiotic therapy and intensive care support. Patients may develop refractory hypotension and acute respiratory distress syndrome in which extracorporeal membrane oxygenation (ECMO) could serve as a life-saving rescue therapy. However, there is limited data regarding the outcomes of ECMO support in the setting of meningococcal disease. This retrospective analysis of prospectively collected data from Extracorporeal Life Support Organization registry (1989-2019) enrolled children (29 days-18 years old) with Neisseria meningitidis infection receiving ECMO for any support type and mode. A total of 122 patients underwent a single course of ECMO support, equating to 122 ECMO runs. The overall survival-to-discharge rate was 46.7%. Patients receiving pulmonary venovenous (VV) ECMO had the highest survival-to-discharge of 85.7%, while those receiving venoarterial (VA) ECMO for pulmonary indications had a survival of 32.4%. Patients receiving VA ECMO support for cardiac indications had a survival-to-discharge rate of 60.9%. Those needing extracorporeal cardiopulmonary resuscitation (ECPR) had a poor survival (14.3%). Hemorrhagic complications were common, occurring in 43.4% of patients, but not found to be associated with mortality (complication was present in 47.7% of deceased and 38.6% of survivors, p = 0.31). Multivariable logistic regression analysis revealed that neurologic complications were associated with increased odds of mortality (odds ratio: 44.11; 95% confidence interval: 4.95-393.08). ECMO can be utilized as rescue therapy in children with refractory cardiopulmonary failure in setting of meningococcemia. Patients who require pulmonary VV or cardiac ECMO have the best ECMO outcomes. However, the use of ECMO in those suffering cardiac arrest (ECPR) should be undertaken with caution.

Measurement of Clavicular Symmetry in Healthy Subjects Using Tomographic Database of Public Hospitals.

Objective This study aimed to perform an imaging evaluation to prove the existence or not of symmetry between the clavicles of healthy subjects from Curitiba, Paraná, Brazil, and identify potential factors influencing the clavicular length. Method The study analyzed chest computed tomography (CT) scans of 211 patients with no clavicular fracture or malformations (100 women and 111 men). We measured the greatest clavicular diagonal on both sides, and the software automatically generated the maximum distance in millimeters. Relative and absolute frequencies described qualitative variables and mean values; quantitative variables used a 95% confidence interval. Value comparisons employed the student's t-test, and correlations determinations used Pearson's correlation coefficient. The significance level adopted was 5%. Results There was a significant difference between the clavicular length (right clavicle, 143.58 mm; left clavicle, 145.72 mm; p = 0.037), indicating asymmetry. On average, the left clavicle was 3.71 mm larger. Asymmetry was significant for both men and women (p < 0.001). The average difference was 4.13 mm for men and 3.23 mm for women. Seventy-three percent of the sample had < 5 mm of asymmetry, 23.7% had 5 to 10 mm, and 3.3% had > 10 mm of asymmetry. Conclusion The studied population did not present clavicular symmetry. On average, the left clavicle was longer than the right clavicle, with differences of 3.71 mm in the general sample, 3.23 mm in women, and 4.13 mm in men. The only significant factor was gender since men presented longer clavicles and higher differences than women.

Measurement of Clavicular Symmetry in Healthy Subjects Using Tomographic Database of Public Hospitals / Mensuração de simetria clavicular em indivíduos saudáveis utilizando-se de banco de dados tomográficos de hospitais públicos

Abstract Objective This study aimed to perform an imaging evaluation to prove the existence or not of symmetry between the clavicles of healthy subjects from Curitiba, Paraná, Brazil, and identify potential factors influencing the clavicular length. Method The study analyzed chest computed tomography (CT) scans of 211 patients with no clavicular fracture or malformations (100 women and 111 men). We measured the greatest clavicular diagonal on both sides, and the software automatically generated the maximum distance in millimeters. Relative and absolute frequencies described qualitative variables and mean values; quantitative variables used a 95% confidence interval. Value comparisons employed the student's t-test, and correlations determinations used Pearson's correlation coefficient. The significance level adopted was 5%. Results There was a significant difference between the clavicular length (right clavicle, 143.58 mm; left clavicle, 145.72 mm; p = 0.037), indicating asymmetry. On average, the left clavicle was 3.71 mm larger. Asymmetry was significant for both men and women (p < 0.001). The average difference was 4.13 mm for men and 3.23 mm for women. Seventy-three percent of the sample had < 5 mm of asymmetry, 23.7% had 5 to 10 mm, and 3.3% had > 10 mm of asymmetry. Conclusion The studied population did not present clavicular symmetry. On average, the left clavicle was longer than the right clavicle, with differences of 3.71 mm in the general sample, 3.23 mm in women, and 4.13 mm in men. The only significant factor was gender since men presented longer clavicles and higher differences than women.

Resumo Objetivo Realizar avaliação imagiológica com intuito de comprovar a existência ou não de simetria entre as clavículas de indivíduos saudáveis da cidade de Curitiba/PR, aliada à identificação de possíveis fatores de influência no comprimento clavicular. Método Foram analisadas tomografias computadorizadas de tórax de 211 pacientes sem fratura ou malformações na clavícula (100 mulheres e 111 homens). A maior diagonal clavicular foi medida em ambos os lados e o software gerou automaticamente a máxima distância em milímetros. Foram utilizadas frequências relativas e absolutas para descrever variáveis qualitativas e a média e intervalo de 95% de confiança para as quantitativas. As comparações foram feitas com o teste t de Student e correlações calculadas pelo coeficiente de correlação de Pearson. O nível de significância adotado foi de 5%. Resultados Verificou-se diferença significativa entre o comprimento das clavículas (direita 143.58mm e esquerda 145.72mm, p = 0.037), indicando assimetria. Em média, o lado esquerdo é 3.71mm maior. A assimetria foi significativa tanto para homens quanto para mulheres (p < 0.001). A diferença média foi de 4.13mm para homens e 3.23mm para mulheres. 73% da amostra apresentou <5mm de diferença, enquanto 23.7% apresentou 5-10mm e 3.3% apresentou >10mm de assimetria. Conclusão Não foi possível encontrar simetria nas clavículas da população de Curitiba/PR. Em média, a clavícula esquerda é maior que a direita, com diferenças de 3.71mm na amostra geral, 3.23mm para mulheres e 4.13mm para homens. O único fator significativo foi o sexo, com homens tendo maiores comprimentos claviculares e maiores diferenças em comparação às mulheres.

Outcomes of extracorporeal life support for respiratory failure in children with primary immunodeficiencies.

OBJECTIVE: Extracorporeal Membrane Oxygenation (ECMO) may serve as a life-saving rescue therapy in critically ill children with respiratory failure. While survival rates of ECMO in children with secondary immunodeficiency is considered relatively poor, survival rates in children with primary immunodeficiencies (PID) has yet to be thoroughly investigated. DESIGN: Retrospective analysis of prospectively collected data from children (29 days-18 years old). PID patients were identified by using International Classification of Diseases (ICD) codes. SETTING: Data were retrieved from Extracorporeal Life Support Organization Registry (1989-2018). INTERVENTIONS: ECMO for a pulmonary support indication. The survival-to-discharge rate was calculated and factors influencing outcomes were compared between survivors and non-survivors. MEASUREMENTS AND MAIN RESULTS: A total of 73 eligible ECMO runs were included. The survival-to-discharge rate in pediatric PID patients was 45.2%. No differences were noted in survival based on type of immunodeficiency (p = 0.42) or decade of support (p = 0.98). There was no difference in the rate of pre-ECMO infection in survivors versus non-survivors (p = 0.69). The survival-to-discharge rate in patients with a culture positive infection during the ECMO run was 45.0% versus 45.3% in those with no infection (p = 0.98). In multivariate analysis, only cardiac complications (OR 5.09, 95% CI: 1.15-22.53), pulmonary complications (OR: 13.00, 95% CI: 1.20-141.25), and neurologic complications (OR: 9.86, 95% CI: 1.64-59.21) were independently associated with increased mortality. CONCLUSION: Children with a PID who require extracorporeal life support due to respiratory failure have a reasonable chance of survival and should be considered candidates for ECMO. The presence of a pre-ECMO infection should not be considered an ECMO contraindication.

Evaluation of CSF kappa free light chains for the diagnosis of multiple sclerosis (MS): a comparison with oligoclonal bands (OCB) detection via isoelectric focusing (IEF) coupled with immunoblotting.

This study was done to evaluate the diagnostic accuracy of cerebrospinal fluid kappa free light chain (KFLC) for diagnosis of multiple sclerosis, against isoelectrofocusing (IEF) to detect oligoclonal bands (OCB) as gold standard. 64 cases were divided into positive and negative based on the OCB results. Diagnostic accuracy was calculated for the 1 mg/L cut-off. The 1 mg/L cut-off yielded a percent agreement of 86.1% and Cohen's kappa value of 0.8. Youden's index, yielded a cut-off of 0.92 mg/L as optimal (90.3% specificity and 90.9% sensitivity). The analytical time was 3 hours and 55 min for IEF and 25 min for KFLC. The cost of a single OCB test was PKR12 000 (US$68.17) compared with PKR4150 (US$23.58) for KFLC. KFLC proved to be an accurate, cheaper and time-saving alternative and can be performed prior to the contemporary testing.

'Meninos vestem azul e meninas vestem rosa': Análise do Discurso Crítica sobre a 'ideologia de gênero' no Ministério da Mulher, Família e Direitos Humanos / 'Boys wear blue and girls wear pink': Critical Discourse Analysis on 'gender ideology' in the Ministry of Women, Family and Human Rights

RESUMO Este artigo investiga qual foi a principal ideologia norteadora das políticas públicas do Ministério da Mulher, Família e Direitos Humanos (MMFDH) no governo Jair Bolsonaro (2019-2022). Em seu discurso de posse, Bolsonaro afirmou que um dos objetivos de seu governo seria combater a 'ideologia de gênero' e defender 'os verdadeiros direitos humanos'. Assim, esta pesquisa parte da perspectiva de que, no Brasil, existe uma disputa em torno da noção de direitos humanos, e a utilização do sintagma 'ideologia de gênero' é um elemento-chave para compreender de que modo essa disputa ocorre no cenário político, especialmente no que diz respeito à criação de pânico moral a respeito das pessoas LGBTQA+. Com o objetivo de compreender qual é a ideologia norteadora das políticas públicas desenvolvidas pelo MMFDH, setor estatal no qual essa disputa parecia ser um elemento central, foi utilizada a Análise do Discurso Crítica como metodologia analítica. Para compor o corpus da pesquisa, foram analisados os discursos das principais representantes do MMFDH, Damares Alves e Angela Gandra, no período de 2 de janeiro de 2019 a 31 de março de 2022. Concluiu-se que, no período analisado, o MMFDH foi promotor de 'ideologia de gênero'.

ABSTRACT This article investigates what was the main ideology guiding the public policies of the Ministry of Women, Family and Human Rights (MMFDH) in the Jair Bolsonaro administration (2019-2022). In his inauguration speech, Bolsonaro stated that one of his government's objectives would be to combat 'gender ideology' and defend 'true human rights'. Thus, this research starts from the perspective that there is a dispute in Brazil around the notion of human rights, and the use of the phrase 'gender ideology' is a key element to understand how this dispute occurs in the political scenario, especially with regard to creating moral panic regarding LGBTIQIA+ people. With the aim of understanding the guiding ideology of public policies developed by the MMFDH, a state sector where this dispute seemed to be a central element, Critical Discourse Analysis was used as an analytical methodology. To compose the research corpus, the speeches of the main representatives of the MMFDH, Damares Alves and Angela Gandra, were analyzed from January 2, 2019 to March 31, 2022. We concluded that, in the period analyzed, the MMFDH was a promoter of 'gender ideology'.

Age, Sex and Previous Comorbidities as Risk Factors Not Associated with SARS-CoV-2 Infection for Long COVID-19: A Systematic Review and Meta-Analysis.

Identification of predictors of long COVID-19 is essential for managing healthcare plans of patients. This systematic literature review and meta-analysis aimed to identify risk factors not associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, but rather potentially predictive of the development of long COVID-19. MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers were screened through 15 September 2022. Peer-reviewed studies or preprints evaluating potential pre-SARS-CoV-2 infection risk factors for the development of long-lasting symptoms were included. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPSs) tool. Random-effects meta-analyses with calculation of odds ratio (OR) were performed in those risk factors where a homogenous long COVID-19 definition was used. From 1978 studies identified, 37 peer-reviewed studies and one preprint were included. Eighteen articles evaluated age, sixteen articles evaluated sex, and twelve evaluated medical comorbidities as risk factors of long COVID-19. Overall, single studies reported that old age seems to be associated with long COVID-19 symptoms (n = 18); however, the meta-analysis did not reveal an association between old age and long COVID-19 (n = 3; OR 0.86, 95% CI 0.73 to 1.03, p = 0.17). Similarly, single studies revealed that female sex was associated with long COVID-19 symptoms (n = 16); which was confirmed in the meta-analysis (n = 7; OR 1.48, 95% CI 1.17 to 1.86, p = 0.01). Finally, medical comorbidities such as pulmonary disease (n = 4), diabetes (n = 1), obesity (n = 6), and organ transplantation (n = 1) were also identified as potential risk factors for long COVID-19. The risk of bias of most studies (71%, n = 27/38) was moderate or high. In conclusion, pooled evidence did not support an association between advancing age and long COVID-19 but supported that female sex is a risk factor for long COVID-19. Long COVID-19 was also associated with some previous medical comorbidities.

Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19).

BACKGROUND During the current Coronavirus Disease 2019 (COVID-19) pandemic, falls have been identified as a potential presenting symptom in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, data on factors increasing fall risk in this patient population are limited. This study aimed to examine the factors that may predispose hospitalized COVID-19 disease patients to falls. MATERIAL AND METHODS In this retrospective observational study, hospitalized COVID-19 disease patients were examined for fall incidence, as well as demographics, comorbidities, and clinical and laboratory data. Patients were stratified according to their fall status and their characteristics were compared using Fisher's exact test or Mann-Whitney U test. A total of 312 hospitalized COVID-19 disease patients were enrolled (median age, 75 years; males, 51.3%), of whom 11 (3.5%) fell. RESULTS There was a greater prevalence of falls among patients who experienced arrhythmias than those that did not (28.6% vs 1.7%; P<0.001). Additionally, a significantly greater proportion of those that were discharged to the internal ward and to the intensive care unit fell (10.3% and 10.0%, respectively) compared to those that were discharged home (1.6%, P=0.008). Thyroid-stimulating hormone (TSH) was significantly elevated in patients who fell (5.3 vs 0.97 µIU/mL, P=0.013), while alanine aminotransferase (ALT) was significantly lower in those who fell (17.1 vs 33.5 IU/L, P=0.041). CONCLUSIONS Arrhythmias may be an important predisposing factor for falls in COVID-19 disease patients and fall prevention programs should prioritize interventions directed at this vulnerable patient population.

Complement Levels at Admission Reflecting Progression to Severe Acute Kidney Injury (AKI) in Coronavirus Disease 2019 (COVID-19): A Multicenter Prospective Cohort Study.

Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients. Materials and Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers. The primary endpoint was development of severe AKI defined by KDIGO stage 2+3 criteria, while the secondary endpoint was need for renal replacement therapy (RRT). Complement markers with significant associations with endpoints were then correlated with a panel of inflammatory and thrombotic biomarkers and assessed for independent association with outcome measures using logistic regression. Results: A total of 131 hospitalized COVID-19 patients (median age 66 [IQR, 54-75] years; 54.2% males) were enrolled, 33 from the US, and 98 from Hungary. There was a greater prevalence of complement over-activation and consumption in those who developed severe AKI and need for RRT during hospitalization. C3a/C3 ratio was increased in groups developing severe AKI (3.29 vs. 1.71; p < 0.001) and requiring RRT (3.42 vs. 1.79; p < 0.001) in each cohort. Decrease in alternative and classical pathway activity, and consumption of C4 below reference range, as well as elevation of complement activation marker C3a above the normal was more common in patients progressing to severe AKI. In the Hungarian cohort, each standard deviation increase in C3a (SD = 210.1) was independently associated with 89.7% increased odds of developing severe AKI (95% CI, 7.6-234.5%). Complement was extensively correlated with an array of inflammatory biomarkers and a prothrombotic state. Conclusion: Consumption and dysregulation of complement system is associated with development of severe AKI in COVID-19 patients and could represent a promising therapeutic target for reducing thrombotic microangiopathy in SARS-CoV-2 infection.

Cell-Free DNA, Neutrophil extracellular traps (NETs), and Endothelial Injury in Coronavirus Disease 2019- (COVID-19-) Associated Acute Kidney Injury.

Introduction: Neutrophil extracellular traps (NETs) release (i.e., NETosis) has been recently implicated in the pathomechanism underlying severe end-organ damage in Coronavirus Disease 2019 (COVID-19) and could present a novel therapeutic target. We aimed to determine whether circulating levels of cell-free DNA (cfDNA), a surrogate for NETosis, may be associated with the development of acute kidney injury (AKI), a major contributor to poor outcomes and mortality in COVID-19. Methods: Blood samples were collected prospectively from adult patients infected with SARS-CoV-2 presenting to the emergency department (ED). Circulating levels of cfDNA were quantified from patients' serum. Further assessment of correlations between cfDNA levels and markers of AKI (i.e., serum creatinine (SCr), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL)), biomarkers of thrombotic microangiopathy and of inflammation in patients' serum was performed. Results: Fifty-one COVID-19 patients were enrolled. cfDNA levels were found to be significantly higher in those who developed severe AKI (p < 0.001) and those needing renal replacement therapy (p = 0.020). cfDNA positively correlated with ED SCr, NGAL, cystatin C, neutrophil count, neutrophil-to-lymphocyte ratio, C3a, C5a, Scb5-9, IL-6, IL-8, IL-10, TNF-α, LDH, CRP, ferritin, and fibrinogen and negatively correlated with ADAMTS13/von-Willebrand factor ratio and lymphocyte count. In a multivariate logistic regression, a one-unit increase in cfDNA value was associated with 4.6% increased odds of severe AKI (OR = 1.046; p = 0.040). Finally, cfDNA significantly correlated with established NETs components, myeloperoxidase, and neutrophil elastase. Conclusion: Intravascular NETosis could be an important contributing factor in the development of microthrombosis and COVID-19-associated AKI. Further research is urgently needed to understand the role of NETosis in COVID-19 and evaluate therapeutic avenues for targeting this process.

The Predictive Value of Serum ACE2 and TMPRSS2 Concentrations in Patients with COVID-19-A Prospective Pilot Study.

One of the major challenges for healthcare systems during the Coronavirus-2019 (COVID-19) pandemic was the inability to successfully predict which patients would require mechanical ventilation (MV). Angiotensin-Converting Enzyme 2 (ACE2) and TransMembrane Protease Serine S1 member 2 (TMPRSS2) are enzymes that play crucial roles in SARS-CoV-2 entry into human host cells. However, their predictive value as biomarkers for risk stratification for respiratory deterioration requiring MV has not yet been evaluated. We aimed to evaluate whether serum ACE2 and TMPRSS2 levels are associated with adverse outcomes in COVID-19, and specifically the need for MV. COVID-19 patients admitted to an Israeli tertiary medical center between March--November 2020, were included. Serum samples were obtained shortly after admission (day 0) and again following one week of admission (day 7). ACE2 and TMPRSS2 concentrations were measured with ELISA. Of 72 patients included, 30 (41.6%) ultimately required MV. Serum ACE2 concentrations >7.8 ng/mL at admission were significantly associated with the need for MV (p = 0.036), inotropic support, and renal replacement therapy. In multivariate logistic regression analysis, elevated ACE2 at admission was associated with the need for MV (OR = 7.49; p = 0.014). To conclude, elevated serum ACE2 concentration early in COVID-19 illness correlates with respiratory failure necessitating mechanical ventilation. We suggest that measuring serum ACE2 at admission may be useful for predicting the risk of severe disease.

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review.

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90-180 days and 55%-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

Phenotype-Genotype Correlation in Colorectal Cancer: A Real-Life Study.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a heterogeneous disease with distinctive genetic pathways, such as chromosomal instability, microsatellite instability and methylator pathway. Our aim was to correlate clinical and genetic characteristics of CRC patients in order to understand clinical implications of tumour genotype. METHODS: Single-institution retrospective cohort of patients who underwent curative surgery for CRC, from 2012 to 2014. RAS and BRAF mutations were evaluated with the real-time PCR technique Idylla®. Mismatch repair deficiency (dMMR) was characterized by absence of MLH1, MSH6, MSH2 and/or PMS2 expression, evaluated by tissue microarrays. Overall survival (OS) and disease-free survival (DFS) were assessed using survival analysis. RESULTS: Overall, 242 patients were included (males 57.4%, age 69.3 ± 12.9 years; median follow-up 49 months). RAS-mutated tumours were associated with reduced DFS (p = 0.02) and OS (p = 0.045) in stage I-III CRC. BRAF-mutated tumours were more predominant in females and in the right colon, similarly to dMMR tumours. BRAF status did not influence OS (4 years)/DFS (3.5 years) in stage I-III disease. However, after relapse, length of survival was 3.5 months in BRAF-mutated tumours in contrast to 18.6 months in BRAF wild-type tumours (p = NS). No germline mutations in mismatch repair genes were so far identified in the patients with dMMR tumours. Molecular phenotype (RAS, BRAF and MMR) did not influence OS in metastatic patients. Our small sample size may be a limitation of the study. CONCLUSION: In our cohort, RAS-mutated tumours were associated with worse DFS and OS in early-stage CRC, whereas the remaining molecular variables had no prognostic influence.

INTRODUÇÃO: O cancro colo-rectal (CCR) é uma doença heterogénea, com vias genéticas distintas, nomeadamente instabilidade cromossómica, instabilidade de microssatélites e via metiladora. O nosso objetivo foi correlacionar as características clínicas e genéticas dos doentes com CCR e, deste modo, conhecer as implicações na prática clínica do genótipo tumoral. MÉTODOS: Estudo de coorte retrospectivo unicêntrico de doentes diagnosticados com CCR e submetidos a cirurgia com intuito curativo, entre 2012 e 2014. As mutações RAS e BRAF foram avaliadas pela técnica de real time PCR Idylla®. A deficiência de mismatch repair (MMR) foi avaliada pela técnica de tissue microarrays e definida pela ausência de expressão de MLH1, MSH6, MSH2 e/ou PMS2. A sobrevivência global (SG) e a sobrevivência livre de doença (SLD) foram avaliadas por análise de sobrevivência. RESULTADOS: No total, foram incluídos 242 doentes (homens 57.4%, idade 69.3 ± 12.9 anos, mediana de seguimento de 49 meses). Os tumores RAS-mutados associaram-se a menor SLD (p = 0.02) e SG (p = 0.045) em doentes com CCR estadio I­III. Os tumores BRAF-mutados foram mais frequentes em mulheres e nos tumores do cólon direito, assim como os tumores com deficiência para MMR. O status BRAF não influenciou a SG (4 anos)/SLD (3.5 anos) nos estadio I­III. Contudo, após a recidiva, o tempo de sobrevivência foi de 3.5 meses nos tumores BRAF-mutados, em comparação com 18.6 meses nos tumores sem esta mutação (p = NS). Não se identificaram mutações germinativas nos genes de mismatch repair nos doentes com tumores deficientes para estas proteinas (dMMR). O perfil molecular (RAS, BRAF e MMR) não influenciou a sobrevivência global dos doentes com metástases ao diagnóstico. O tamanho da amostra pode ser uma limitação do estudo. CONCLUSÃO: Na nossa coorte, os tumores RASmutados associaram-se a pior SLD e SG nos estádios precoces de CCR. Os restantes marcadores moleculares não influenciaram o prognóstico dos doentes.

Mindfulness-based treatment for smoking cessation: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of a mindfulness-based treatment (MBT) for smoking cessation or reduction and compare it with that of cognitive behavioral therapy (CBT). METHODS: This was a single-center randomized controlled clinical trial including 113 patients divided into two groups: MBT (n = 54) and CBT (n = 59). The interventions comprised eight 90-min sessions. The primary outcome was smoking cessation at 16 weeks after program initiation. Secondary outcomes included reduction in the mean number of cigarettes smoked/day at 16 weeks after treatment initiation, as well as smoking cessation and reduction in the number of cigarettes smoked/day at the last program session. Participants had to attend ≥ 50% of the sessions to be included in the primary outcome analysis. An intention-to-treat analysis was also performed. RESULTS: There was no difference between the groups regarding the primary outcome (30.4% in the MBT group vs. 31.6% in the CBT group, p = 0.68) or immediate abstinence rates (47.8% in the MBT group vs. 36.8% in the CBT group, p = 0.47). Both treatments were equally effective in reducing the number of cigarettes smoked/day at the last program session (a reduction of 93.33% [0-100%] in the MBT group and of 70% [33.3-100%] in the CBT group, p = 0.92) and at 16 weeks after program initiation (a reduction of 57.1% [0-100%] in the MBT group and of 70% [25-100%] in the CBT group, p = 0.49). CONCLUSIONS: MBT appears to be as effective as CBT for smoking cessation or reduction and can be an option for the treatment of tobacco use disorders in Brazil (Brazilian Registry of Clinical Trials identifier: RBR-3w2scz [http://www.ensaiosclinicos.gov.br]).

Early prediction of COVID-19-associated acute kidney injury: Are serum NGAL and serum Cystatin C levels better than serum creatinine?

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with a high risk of acute kidney injury (AKI), often requiring renal replacement therapy (RRT). Serum Cystatin C (sCysC) and serum Neutrophil Gelatinase-Associated Lipocalin (sNGAL) are emerging biomarkers for kidney injury, and were suggested to be superior to serum creatinine (sCr) in several clinical settings. Moreover, elevated sCysC is associated with disease severity and mortality in COVID-19. We aimed to assess the utility of sCysC and sNGAL for predicting COVID-19-associated AKI, need for RRT, and need for intensive care unit (ICU) admission, when measured at presentation to the emergency department (ED). METHODS: Patients presenting to the ED with laboratory-confirmed COVID-19 were included. The primary outcome was development of COVID-19-associated AKI, while the secondary outcomes were need for RRT and ICU admission. RESULTS: Among 52 COVID-19 patients, 22 (42.3%) developed AKI with 8/22 (36.4%) requiring RRT. Both sCr and sCysC demonstrated excellent performance for predicting AKI (AUC, 0.86 and 0.87, respectively) and need for RRT (AUC, 0.94 and 0.95, respectively). sNGAL displayed acceptable performance for predicting AKI (AUC, 0.81) and need for RRT (AUC, 0.87). CONCLUSIONS: SCr and sCysC measured at ED presentation are both highly accurate predictors of AKI and need for RRT, whereas sNGAL demonstrated adequate diagnostic performance. While sCyC was previously shown to be superior to sCr as a diagnostic biomarker of kidney injury in certain etiologies, our findings demonstrate that sCr is comparable to sCyC in the context of predicting COVID-19-associated AKI. Given the high sensitivity of these biomarkers for predicting the need for RRT, and as sCysC is associated with mortality in COVID-19 patients, we recommend their measurement for enabling risk stratification and early intervention.

The role of lipoprotein(a) in coronavirus disease 2019 (COVID-19) with relation to development of severe acute kidney injury.

Lipoprotein(a) (Lp(a)) is a prothrombotic and anti-fibrinolytic lipoprotein, whose role has not been clearly defined in the pathogenesis of coronavirus disease 2019 (COVID-19). In this prospective observational study, serum Lp(a) as well as outcomes were measured in 50 COVID-19 patients and 30 matched sick controls. Lp(a) was also assessed for correlation with a wide panel of biomarkers. Serum Lp(a) did not significantly differ between COVID-19 patients and sick controls, though its concentration was found to be significantly associated with severity of COVID-19 illness, including acute kidney failure stage (r = 0.380, p = 0.007), admission disease severity (r = 0.355, p = 0.013), and peak severity (r = 0.314; p = 0.03). Lp(a) was also positively correlated with interleukin (IL)-8 (r = 0.308; p = 0.037), fibrinogen (r = 0.344; p = 0.032) and creatinine (r = 0.327; p = 0.027), and negatively correlated with ADAMTS13 activity/VWF:Ag (r = - 0.335; p = 0.021); but not with IL-6 (r = 0.241; p = 0.106). These results would hence suggest that adverse outcomes in patients with COVID-19 may be aggravated by a genetically determined hyper-Lp(a) state rather than any inflammation induced elevations.

Os 75 Anos da RBC e o Desafio da Ciência Aberta / The 75 Years of RBC and the Challenge of Open Science / Los 75 Años de RBC y el Desafío de la Ciencia Abierta

A Revista Brasileira de Cancerologia (RBC) representa um marco na editoração científica nas áreas do controle do câncer no Brasil. Sua história teve início em 1941, quando o Decreto-Lei n.º 3.643, de 23 de setembro de 19411, instituiu, no então Departamento Nacional de Saúde do Ministério da Educação e Saúde, o Serviço Nacional de Câncer e criou uma revista científica de cancerologia. No entanto, somente em setembro de 1947, foi publicado o seu primeiro número na intenção de divulgar, à comunidade acadêmica, conhecimentos no campo da cancerologia. Nas publicações da época, a RBC apresentava não somente artigos científicos e relatos de casos clínicos, mas também notícias relacionadas ao tema, material de divulgação de congressos e seminários, sessão de "perguntas e respostas", discursos completos do ministro da Saúde em eventos da área de câncer e saúde pública, além de anúncios de auxílios financeiros em pesquisa. Com o tempo, a RBC teve a sua importância e manutenção ainda mais valorizadas, e, em agosto de 1968, foi criado o Corpo Editorial, visando ao direcionamento e à indicação de pautas das futuras publicações. Até então, a revista trabalhava somente com redatores permanentes. Em 1982, buscando mais visibilidade, a revista foi indexada na base de dados denominada Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). Apesar do aperfeiçoamento do seu projeto editorial, e de ter se tornado um grande veículo de comunicação científica na área da cancerologia no país, poucos avanços aconteceram em busca de uma maior internacionalização e indexação em outras bases de dados, até 2017

The Revista Brasileira de Cancerologia (RBC) is a milestone in scientific editing in the area of cancer control in Brazil. Its history started in 1941 after the issue of Decree-Law number 3,643, dated September 23, 19411 , which created the National Cancer Service and a cancerology scientific journal at the former National Department of Health of the Ministry of Education and Health. Nevertheless, only in 1947 the first edition came to light with the purpose of divulging knowledge in cancerology to the scholar community. Of the journals published at that time, RBC issued not only scientific articles and case reports but also theme-related news, press material for congresses and seminaries, Q&A (questions and answers) sections, complete addresses of the Ministry of Health in events on cancer and public health, further to notices about financial funding of researches2 . As time went by, RBC grew in importance and worth and the Editorial Board was created in August 1968 to put together guidelines and agenda of the upcoming editions. Until then, the journal counted only with permanent writers. In 1982, for more visibility, the journal was indexed at the database Latin American and Caribbean in Health Sciences (LILACS). Notwithstanding its editorial betterment and having stepped up to be a great vehicle of scientific communication in cancerology in the country, few advances in attempting a wider internationalization and indexation occurred at other databases until 2017

Mirabegron as effective as oxybutynin for ureteral stent symptoms.

OBJECTIVE: Ureteral stents usually cause pain and lower urinary tract discomfort. This study aimed to compare the effect of mirabegron with oxybutynin in relieving ureteral stent-related symptoms over time. METHODS: A prospective, longitudinal, randomized, single-blinded study was conducted. Patients who had a ureteral stent inserted after urolithiasis treatment were classified into two groups and received either oxybutynin 5 mg/day (Group O) or mirabegron 50 mg/day (Group M). The Ureteral Stent Symptoms Questionnaire (USSQ) was applied on the 3rd, 6th, and 15th postoperative days. Group domain scores were compared, and a mixed linear model was used to better assess score differences. RESULTS: Ureteral Stent Symptoms Questionnaire scores were similar in both groups during all three postoperative days (p>0.05). A longitudinal analysis showed that global quality of life and general health improved over time, independently of the use of any of the medications (p<0.05), while urinary symptoms and body pain scores were lower over time in participants receiving oxybutynin. CONCLUSION: Both mirabegron and oxybutynin are equivalent in relieving ureteral stent symptoms. Moreover, some stent symptoms seem to decrease over time despite the use of medication.