Abstract Background Therapeutic drug monitoring (TDM) in patients receiving infliximab (IFX) has a role in assessing treatment and managing outcomes. Infliximab trough levels (ITL) have been suggested as useful markers for treatment optimization in Crohn’s disease (CD).Our goals were: to assess the relationship between ITL and transmural inflammation as assessed by intestinal ultrasound(IUS), following induction therapy with IFX; to assess which clinical, laboratorial or IUS parameters better predicted adequate levels by the end of induction therapy. Methods Prospective multicentric cohort study including patients with active CD starting IFX therapy. Clinical disease activity assessed using the Harvey-Bradshaw index (HBI), C-reactive protein (CRP), fecal calprotectin (FC) were measured at week 0 and after induction therapy (week 14). IUS was performed at week 0 and 14, bowel wall thickness (BWT) from the worst segment was selected for analysis. Ileocolonoscopy was performed at W0 and SES-CD was registered. ITL were measured at W14. Results We included 36 patients with CD (61% male; median age 30 years (range 16–73)). According to Montreal classification, most patients were A2 (69%), had ileocolonic disease (L3 56%) and an inflammatory phenotype (B1 58%).Perianal disease was present in 42%. Combination therapy was used in 61%. After induction therapy, 81% were in clinical remission (HBI <5) and 43% had laboratorial remission (normal CRP and FC). IUS response (decrease >25% in BWT) was observed in 24% of patients and remission (BWT normalization) in 11%. Median ITL were 4.3 (IQR 2.3–8.1) and 64% had ITL >3 ug/ml. There was a good negative correlation between ITL and SES-CD (r=-0.492, p=0.003). Adequate ITL were associated with lower HBI (1.5 vs 4.5, p=0.052), laboratory remission (61% vs 15%, p=0.014), lower BWT (4 vs 5.5 mm, p=0.009) and sonographic response (39% vs 0%, p=0.014) at W14. At the end of induction, we found a fair to good correlation between ITL and HBI (r=-0.430, p=0.009),CRP (r=-0,510, p=0.001), FC (r=-0.590, p=0.001) and BWT (R=-0.506, p=0.002). Receiver operating characteristic (ROC) curve analysis showed that FC at W14 had the largest area under the curve (AUC) in predicting adequate ITL (0.813 vs 0.716 vs 0.739 vs 0.772, p<0.05). Conclusion Patients with higher disease burden measured by ileocolonoscopy at baseline had lower ITL after induction. Adequate ITL were associated with laboratorial remission and sonographic response at the end of induction, with a good correlation with clinical, laboratorial and sonographic parameters. These findings suggest that adequate IFX levels after induction are associated with a better control of inflammation in IBD, so early proactive TDM during induction may be helpful in treatment management.
Introducao: Os acidentes rodoviarios sao a principal causa de morte e incapacidade infantil em Portugal. A utilizacao dos sistemas de retencao adequados no transporte automovel de recem-nascidos, lactentes e criancas contribui para a diminuicao de lesoes em caso de acidente. Objectivos: Determinar os conhecimentos e respectiva fonte de informacao das puerperas sobre transporte automovel de recem-nascidos e criancas e avaliar a intencao sobre a forma de transporte do recem-nascido a saida da maternidade. Metodos: Estudo transversal, realizado na Maternidade de um Hospital Universitario em 2003, com aplicacao de um inque rito a uma amostra de 475 puerperas entre as 24 e as 48 horas pos-parto. Foram estudadas as variaveis respeitantes a caracterizacao socio-demografica, gravidez, parto e recem-nascido e transporte automovel de recem-nascidos e criancas. Resultados: Verificou-se que 92% das maes nao considera seguro o transporte ao colo no automovel e 80,4% considera mais segura a utilizacao de cadeira apropriada. A alta hospitalar, 72,8% tenciona utilizar a cadeira apropriada, 18,5% a alcofa e 7,2% tenciona transportar o recem-nascido ao colo no percurso automovel ate ao domicilio. A intencao sobre o modo de transporte do recem-nascido no automovel relaciona- se com a idade (p=0,011), com a etnia (p<0,01), com a escolaridade (p<0,01) e com a paridade das maes (p=0,04). Apenas 52,6% das mulheres se encontram bem informadas sobre o transporte automovel seguro e 80,8% refere a comunicacao social como fonte de informacao. Conclusao: Considera-se necessario que os profissionais de saude se envolvam na informacao sobre transporte automovel de recem-nascidos e criancas durante a gravidez e puerperio, de forma a incentivar o transporte correcto e a diminuir a morbilidade e mortalidade infantis nos acidentes de viacao.
Tumor microenvironment has gained great relevance due to its ability to regulate distinct checkpoints mediators, orchestrating tumor progression. Serum programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) levels were compared with healthy controls and with serum cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and tumor necrosis factor-alpha (TNF-α) levels in order to understand the role of PD-1/PD-L1 axis in cats with mammary carcinoma. PD-1 and PD-L1 expression was evaluated in tumor-infiltrating lymphocytes (TILs) and cancer cells, as the presence of somatic mutations. Results showed that serum PD-1 and PD-L1 levels were significantly higher in cats with HER2-positive (p = 0.017; p = 0.032) and triple negative (TN) normal-like mammary carcinomas (p = 0.004; p = 0.015), showing a strong positive correlation between serum CTLA-4 and TNF-α levels. In tumors, PD-L1 expression in cancer cells was significantly higher in HER2-positive samples than in TN normal-like tumors (p = 0.010), as the percentage of PD-L1-positive TILs (p = 0.037). PD-L1 gene sequencing identified two heterozygous mutations in exon 4 (A245T; V252M) and one in exon 5 (T267S). In summary, results support the use of spontaneous feline mammary carcinoma as a model for human breast cancer and suggest that the development of monoclonal antibodies may be a therapeutic strategy.
Vascular endothelial growth factor (VEGF-A) plays an essential role in tumor-associated angiogenesis, exerting its biological activity by binding and activating membrane receptors, as vascular endothelial growth factor receptor 1 and 2 (VEGFR-1, VEGFR-2). In this study, serum VEGF-A, VEGFR-1, and VEGFR-2 levels were quantified in 50 cats with mammary carcinoma and 14 healthy controls. The expression of these molecules in tumor-infiltrating lymphocytes (TILs) and in cancer cells was evaluated and compared with its serum levels. Results obtained showed that serum VEGF-A levels were significantly higher in cats with HER2-positive and Triple Negative (TN) Normal-Like subtypes, when compared to control group (p = 0.001, p = 0.020). Additionally, serum VEGFR-1 levels were significantly elevated in cats presenting luminal A, HER2-positive and TN Normal-Like tumors (p = 0.011, p = 0.048, p = 0.006), as serum VEGFR-2 levels (p = 0.010, p = 0.046, p = 0.005). Moreover, a positive interaction was found between the expression of VEGF-A, VEGFR-1, and VEGFR-2 in TILs and their serum levels (p = 0.002, p = 0.003, p = 0.003). In summary, these findings point to the usefulness of VEGF-A and its serum receptors assessment in clinical evaluation of cats with HER2-positive and TN Normal-Like tumors, suggesting that targeted therapies against these molecules may be effective for the treatment of these animals, as described in human breast cancer.
Aims Colorectal cancer (CRC) incidence is rising in young adults and recent US guidelines recommend CRC screening in individuals between 45-49yo. We aim to assess the utility of CRC screening colonoscopy in a younger Portuguese population.
In recent years there has been a great increase of scientific research regarding physical exercise during pregnancy. Nevertheless, many doubts persist leading to a decrease of its practice. We aimed to evaluate the main factors that influence the practice of physical activity during pregnancy and mothers' knowledge regarding its effects. Physical activity has decreased significantly, although it was higher in nulliparous mothers, with higher educational level, employment and between 25 and 34 years old. Mothers who practiced exercise during pregnancy breastfed longer. No correlation was found concerning birth weight, gestational age or obstetric pathology. Although most mothers understand the benefits of physical activity in pregnancy, that doesn't seem to translate in an increasing practice. We believe there should be an increased awareness of health professionals in order to promote controlled physical exercise in pregnant woman.
The increased risk of bowel cancer in patients with inflammatory bowel disease can be related with the extent, duration and severity of inflammation or with the cancer immune surveillance interference of immunosuppressive drugs used in inflammatory bowel disease treatment. Therefore, the risk-benefit ratio associated with long-term therapeutic strategies should be based on the patient's age, sex, comorbidities and disease phenotype.We present the case of a 76-year-old man with a history of melanoma stage Clark III and steroid-dependent left-sided colitis, refractory to mesalamine and thiopurines, with a diagnosis of a multifocal colorectal adenocarcinoma shortly after clinical and endoscopic remission 1 year after starting vedolizumab.Vedolizumab is a gut-selective monoclonal anti-α4β7-integrin antibody that inhibits lymphocyte migration into the gastrointestinal submucosa. Its effectiveness for induction and maintenance of remission and its favorable safety profile make it an alternative in patients with chronic refractory colitis and contraindications to anti-TNF-α. However, there is the hypothesis that, by reducing the migration of activated leukocytes to the gastrointestinal tract, it may also reduce immunosurveillance, increasing the colorectal malignancy risk in the long term. More studies are necessary to address this issue.O aumento do risco de neoplasias intestinais em doentes com doença inflamatória intestinal correlacionase com a extensão, duração e gravidade de inflamação assim como com o potencial efeito na vigilância imunitária associado aos fármacos imunossupressores utilizados no seu tratamento. Por isso, a avaliação do risco-benefício da utilização de estratégias terapêuticas a longo prazo deve basear-se no género, idade, comorbilidades e fenótipo da doença.Os autores apresentam o caso de um homem de 76 anos com história pregressa de melanoma maligno estadio Clark III e colite ulcerosa esquerda cortico-dependente e refratária à terapêutica convencional, com o diagnóstico de um adenocarcinoma colo-rectal um ano após ter iniciado terapêutica com vedolizumab e ter atingido remissão clínica e endoscópica.O vedolizumab é um anticorpo anti-integrina α4β7 que inibe a migração dos linfócitos para a submucosa gastrointestinal. A sua eficácia na indução e manutenção da remissão e o seu perfil de segurança tornam-no uma boa alternativa em doentes com doença refratária e contraindicações para anti-TNF-α. Contudo, ao diminuir a migração dos leucócitos para o trato gastrointestinal, poderá reduzir a imunovigilância, aumentando o risco de neoplasia colo-rectal. No entanto, este é ainda um conceito teórico, sendo necessários mais estudos que o comprovem.
Feline mammary carcinoma (FMC) shares key molecular and clinicopathological features with human breast cancer. We have herein studied the inflammatory infiltrate of FMC in order to uncover potential therapeutic targets and prognostic markers. To this end, the expression of different markers (CD3, CD4, CD8, CD20, CD56, FoxP3, CD68 and CD163) was analyzed in total, stromal (s) and intratumoral (i) tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), in 73 feline mammary carcinomas. The results revealed that higher percentages of sCD8+ TILs were associated with longer disease-free survival (p = 0.05) and overall survival (p = 0.021). Additionally, higher percentages of iCD4+ TILs correlated with positive lymph node status (p = 0.003), whereas CD163+ TAMs were associated with undifferentiated tumors (p = 0.013). In addition, sCD3+ (p = 0.033), sCD8+ (p = 0.044) and sCD68+ (p = 0.023) immune cells were enriched in triple negative normal-like carcinomas compared to other subtypes. Altogether, our results suggest that specific subsets of immune cells may play a major role in clinical outcome of cats with mammary carcinoma, resembling what has been reported in human breast cancer. These data further support the relevance of the feline model in breast cancer studies.
Introduction: Patients with inflammatory bowel disease (IBD) do not seem to be at increased risk of infection by SARS-CoV-2, but there is a concern whether immunosuppressive therapy may be associated with more severe disease. Several clinical practice recommendations have been published to help guide IBD care during the COVID-19 pandemic. Nonetheless, few studies have addressed patients’ perspectives and fears. We aimed to evaluate Portuguese IBD patients’ perspectives on the clinical management of their disease during the SARS-CoV-2 pandemic as well as the impact on their professional life. Methods: An anonymous electronic survey was created using REDCap and was distributed by the Portuguese Association of Inflammatory Bowel Disease (APDI) between May and August 2020. Patients’ perspectives on immunosuppressive therapy, disease management, interaction with gastroenterology departments, and the impact of the pandemic in their professional life were assessed. Patients’ proposals to improve medical care were also evaluated. Descriptive analysis and logistic regression were performed. Results: A total of 137 participants answered the survey (79.6% females, mean age 41.7 ± 12.1 years). Although having IBD and receiving treatment with immunosuppressors (thiopurines, steroids, or biologics) were considered promotors of anxiety, most patients (85.4%) agreed that disease remission was a priority and only a minority of patients interrupted their treatment during the pandemic. In multivariate analysis, active disease, biologic treatment, and use of corticosteroids in the last 3 months were perceived by the patients as high-risk features for increased risk of SARS-Cov-2 infection and more severe disease. Fifty-nine patients (44%) believed that their follow-up was influenced by the pandemic and only 58.8% felt that they had the opportunity to discuss their therapeutic options with their doctor. Sixty-three patients (46.0%) were working from home during the pandemic, although this decision was related to IBD and immunosuppressive therapy in only 36.5 and 39.7% of the cases, respectively. Areas where care could have been improved during the pandemic were identified by patients, namely enhancement of the communication with IBD professionals, conciliation of telemedicine with face-to-face appointments, and facilitation of the interaction between patients and employers. Conclusion: Most patients agreed that maintaining IBD remission is crucial, and only a minority of the patients stopped their treatment as per their own initiative. IBD status only had a small influence on patients’ professional activity during the COVID-19 outbreak, with most changes being related to the pandemic itself.
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