Portuguese Results of the ETICC Study: Impact of the Pandemic COVID-19 in the Diagnosis and Management of Colorectal Cancer in 2020 in Portuguese Hospitals.

Introduction: The outbreak of coronavirus disease 2019 (COVID-19) had affected clinical practice in several ways, including the restriction of nonessential endoscopic procedures. Therefore, our aim was to evaluate how colorectal cancer (CRC) diagnosis and management was affected during the first year of pandemics in Portugal. Methods: This is a Portuguese substudy of the French retrospective multicentric study ETICC (Etude de l'Impact de la pandémie COVID-19 sur le diagnostic et la prise en charge du Cancer Colorectal). We compared patients' characteristics, clinical manifestations, CRC staging at diagnosis, delay to first medical appointment, histological diagnosis, surgical and medical treatments between the year previous to the pandemics (control) and the first year of pandemics. Results: We included 766 patients: 496 in the control group and 270 in the COVID group. There was no significant difference in CRC staging at diagnosis between both groups, with 21% being diagnosed as metastatic in the control group and 22% in the first year of pandemics (p = 0.770). Contrary to what happened in France, there was a significant decrease in CRC diagnosis in asymptomatic patients (25-8.4%; p < 0.001) and after a positive fecal immunochemical test (20.8-11.3%; p = 0.002) during the pandemics. Although the increase in the overall complication rate at diagnosis was nonsignificant, in Portugal, there was a significant increase in diagnosis of abdominal occlusion (12.1-18.1%; p = 0.033). In Portugal, time between the beginning of symptoms and the first medical appointment significantly increased from a median of 50 days to 64 days during COVID (p < 0.001). On the contrary, time between histological diagnosis and tumor resection had significantly decreased from a median of 65 to 39 days (p < 0.001). Time between histological diagnosis and neoadjuvant treatment was not statistically different (median of 64-67 days; p = 0.590), as was time between histological diagnosis and palliative chemotherapy (median of 50-51 days; p = 1.000). Time from CRC resection and adjuvant treatment has significantly decreased from a median of 54 to 43 days (p = 0.001). Discussion: We found a significant impact in CRC diagnosis in the first year of pandemics, more pronounced than what was found in France. These are likely related not only with the closing of endoscopy units but also with the difficulties patients had in finding an appointment with their general practitioners. On the other hand, both in France and Portugal, the first year of pandemics did not worsen CRC staging at diagnosis and did not significantly affect medical and surgical treatments once the diagnosis was made.

Introdução: A pandemia provocada pelo coronovírus (COVID-19) condicionou a prática clínica de múltiplas formas, incluindo a restrição a exames endoscópicos não urgentes. Por este motivo, decidimos avaliar o impacto do primeiro ano de pandemia no diagnóstico e tratamento do cancro colorretal (CCR) em Portugal. Métodos: Este é um subestudo do estudo Francês retrospetivo multicêntrico ETICC (Etude de l'Impact de la pandémie COVID-19 sur le diagnostic et la prise en charge du Cancer Colorectal). Foram comparadas as características dos doentes, manifestações clínicas, estadiamento do CCR ao diagnóstico, intervalos entre primeiro contacto médico neste contexto, diagnóstico histológico e tratamentos, entre o primeiro ano de pandemia e o ano precedente. Resultados: Foram incluídos 766 doentes, 496 no grupo controlo e 270 no grupo COVID. Em França e em Portugal não se verificou um agravamento no estadiamento do CCR à data do diagnóstico no primeiro ano de pandemia, com 21% dos casos metastáticos à data de diagnóstico no grupo controlo e 22% no primeiro ano da pandemia (p = 0.770). Contudo, apenas em Portugal se constatou uma redução significativa do número de CCR em doentes assintomáticos (25% para 8.4%; p < 0.001) ou após uma pesquisa de sangue oculto positiva (20.8% para 11.3%; p = 0.002) durante a pandemia. Apesar do aumento na taxa de complicações ao diagnóstico não ser significativa, em Portugal a taxa de diagnósticos em contexto de oclusão intestinal aumentou significativamente (12.1% para 18.1%; p = 0.033). Em Portugal, o tempo entre início dos sintomas e a primeira consulta médica aumentou significativamente, de uma mediana de 50 para 64 dias durante o COVID (p < 0.001). Por outro lado, o tempo entre diagnóstico histológico e resseção tumoral reduziu significativamente de 65 para 39 dias (p < 0.001). O tempo entre diagnóstico histológico e tratamento neoadjuvante (mediana de 64 para 67 dias; p = 0.590) ou quimioterapia paliativa (mediana de 50 para 51 dias; p = 1.000) não foi estatisticamente significativo, tendo decrescido significativamente o tempo entre resseção e adjuvância (mediana de 54 para 43 dias, p = 0.001). Discussão: Este estudo evidenciou um impacto significativo no diagnóstico de CCR durante o primeiro ano de pandemia, mais pronunciado que em França. Este achado dever-se-á não só à limitação do acesso aos exames endoscópicos, mas também à dificuldade da população portuguesa em aceder aos Cuidados de Saúde Primários. Por outro lado, tanto em França como em Portugal, no primeiro ano de pandemia não se verificou um agravamento no estadiamento ou atraso no tratamento médico e cirúrgico do CCR.

Autoimmune Liver Disease in Human Immunodeficiency Virus-Infected Patients: 3 Case Series.

We present 3 cases of autoimmune liver disease in human immunodeficiency virus (HIV)-infected patients and describe the different diagnostic and therapeutic approaches used in each case. The first patient was diagnosed with primary biliary cholangitis (PBC) with features of autoimmune hepatitis (AIH), requiring second-line therapy due to incomplete response to ursodeoxycholic acid. The second patient was diagnosed with AIH with features of PBC and had the particular challenges of presenting with advanced liver fibrosis and having a past history of disseminated cytomegalovirus infection. The last case concerns an AIH with acute liver injury, successfully treated with corticosteroids and azathioprine. Recently, the number of patients on antiretroviral therapy (ART) for HIV disease has increased significantly. Therefore, more patients with this chronic infection have been diagnosed with autoimmune diseases, leading to concerns regarding immunosuppressive therapies in this population. With these cases, we alert for these increasingly incident diseases and support the safety of immunosuppressive therapies, provided that HIV is suppressed with ART.

Apresentamos três casos distintos de doença hepática autoimune em doentes com infeção pelo vírus da imunodeficiência humana (VIH), descrevendo as diferentes abordagens diagnósticas e terapêuticas. O primeiro doente foi diagnosticado com colangite biliar primária (CBP) com caraterísticas de hepatite autoimune (HAI), necessitando de terapêutica de segunda linha por resposta incompleta ao ácido ursodesoxicólico (AUDC). O segundo doente foi diagnosticado com HAI com caraterísticas de CBP, com as particularidades de se apresentar com fibrose hepática avançada e de ter tido uma infeção disseminada pelo citomegalovírus. O terceiro caso apresentou-se como uma hepatite aguda grave, tratada com corticoterapia e azatioprina. Recentemente, o número de doentes sob terapêutica antirretroviral (TARV) para a infeção pelo VIH tem aumentado significativamente. Consequentemente, mais doentes com esta infeção crónica têm sido diagnosticados com doenças autoimunes, levando a receios na administração de terapêuticas imunossupressoras. Com esta série de casos pretendemos alertar para esta incidência crescente e para a segurança dos imunossupressores, desde que os doentes apresentem a sua infeção pelo VIH controlada com a TARV.

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease.

BACKGROUND: Immunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AIMS: This study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. METHODS: We conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. RESULTS: Our study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. CONCLUSIONS: Anti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.

Risk factors for the emergence of multidrug-resistant organisms in liver cirrhosis / Factores de riesgo para la aparición de organismos multirresistentes en la cirrosis hepática

Background: Multidrug-resistant organisms (MDROs) are a reality that can alter the paradigm of treatment and prevention of infection in patients with liver cirrhosis (LC).ObjectiveIdentify risk factors for the occurrence of MDROs in patients with LC.Patients and methods: Prospective study from October 2017 to March 2018 in consecutively hospitalized patients with decompensated LC with infection. Blood, urine and ascitic fluid cultures were analyzed. A p-value ≤0.05 was considered statistically significant. Results: MDROs isolated in 18 of 52 episodes of infection. MDROs were associated with the use of proton pump inhibitors (PPIs) (p=0.0312), antibiotic therapy in the last 90 days (p=0.0033) and discharge within preceding 30 days or current hospitalization above 48h (p=0.0082). There was higher 90-day mortality in patients with MDROs infection (71.4% versus 35.7%, p=0.0316).Conclusion: MDROs infections were prevalent in this cohort and associated with 90-day mortality. Use of PPIs and antibiotics increased the risk of MDROs infections, suggesting that its prescription should be restricted to formal indication. Hospitalization was associated with the onset of MDROs, so LC patients should stay at the hospital the least possible. It is relevant to investigate other factors predisposing to the emergence of these microorganisms, in order to prevent it. (AU)

Antecedentes: Los organismos multirresistentes (MDROs, por sus siglas en inglés) son una realidad que puede alterar el paradigma del tratamiento y la prevención de la infección en los pacientes con cirrosis hepática (LC, por sus siglas en inglés).Objetivo: Identificar los factores de riesgo para la aparición de MDROs en pacientes con LC.Pacientes y métodos: Estudio prospectivo de octubre de 2017 a marzo de 2018 en pacientes hospitalizados consecutivamente con LC descompensada con infección. Se analizaron los cultivos de sangre, orina y líquido ascítico. Se consideró estadísticamente significativo un valor de p≤0,05.Resultados: Se aislaron MDROs en 18 de los 52 episodios de infección. Los MDROs se asociaron con el uso de inhibidores de la bomba de protones (IBP) (p=0,0312), la terapia antibiótica en los últimos 90 días (p=0,0033) y el alta en los 30 días anteriores o la hospitalización actual superior a 48h (p=0,0082). Hubo una mayor mortalidad a los 90 días en los pacientes con infección por MDROs (71,4 frente al 35,7%; p=0,0316).Conclusión: Las infecciones por MDROs fueron prevalentes en esta cohorte, y se asociaron con la mortalidad a los 90 días. El uso de IBP y antibióticos aumentó el riesgo de infecciones por MDROs, lo que sugiere que su prescripción debe restringirse a la indicación formal. La hospitalización se asoció a la aparición de MDROs, por lo que los pacientes con LC deberían permanecer en el hospital el menor tiempo posible. Es relevante investigar otros factores que predisponen a la aparición de estos microorganismos para prevenirla. (AU)

Sclerotherapy using 2 % polidocanol foam in the treatment of hemorrhoidal disease - a single-center experience.

Elastic banding and sclerotherapy are the two most commonly performed instrumental therapies in the treatment of symptomatic internal hemorrhoids. Promising results have been shown with sclerotherapy using 2 % polidocanol foam. The present study aimed to evaluate the efficacy and safety of polidocanol foam in the treatment of symptomatic internal hemorrhoids.

Risk factors for the emergence of multidrug-resistant organisms in liver cirrhosis.

BACKGROUND: Multidrug-resistant organisms (MDROs) are a reality that can alter the paradigm of treatment and prevention of infection in patients with liver cirrhosis (LC). OBJECTIVE: Identify risk factors for the occurrence of MDROs in patients with LC. PATIENTS AND METHODS: Prospective study from October 2017 to March 2018 in consecutively hospitalized patients with decompensated LC with infection. Blood, urine and ascitic fluid cultures were analyzed. A p-value ≤0.05 was considered statistically significant. RESULTS: MDROs isolated in 18 of 52 episodes of infection. MDROs were associated with the use of proton pump inhibitors (PPIs) (p=0.0312), antibiotic therapy in the last 90 days (p=0.0033) and discharge within preceding 30 days or current hospitalization above 48h (p=0.0082). There was higher 90-day mortality in patients with MDROs infection (71.4% versus 35.7%, p=0.0316). CONCLUSION: MDROs infections were prevalent in this cohort and associated with 90-day mortality. Use of PPIs and antibiotics increased the risk of MDROs infections, suggesting that its prescription should be restricted to formal indication. Hospitalization was associated with the onset of MDROs, so LC patients should stay at the hospital the least possible. It is relevant to investigate other factors predisposing to the emergence of these microorganisms, in order to prevent it.

Gastrointestinal Tuberculosis Mimicking Crohn's Disease.

We present the case of a 24-year-old woman with complaints of abdominal pain, bloody diarrhea, and weight loss for 3 months. An outpatient colonoscopy revealed scattered ulcers, suggestive of Crohn's disease (CD). Histopathology also favored the diagnosis of CD. However, after admission to our hospital for further investigation, a chest radiograph revealed pulmonary cavitations. A computed tomography scan suggested the diagnosis of active pulmonary tuberculosis (TB). Therefore, a bronchofibroscopy, a total colonoscopy with ileoscopy, and an upper endoscopy were performed. Not only were acid-fast bacilli present in both bronchoalveolar lavage fluid and gastric juice, but also in colonic biopsies. A complete resolution of gastrointestinal symptoms was achieved 2 weeks after starting anti-TB drugs.

Apresentamos o caso de uma mulher de 24 anos com queixas de dor abdominal, diarreia sanguinolenta e perda ponderal com 3 meses de evolução. Uma colonoscopia de ambulatório revelou, de forma descontínua, úlceras sugestivas de doença de Crohn (DC). Também a histologia era sugestiva de DC. Contudo, após admissão no nosso hospital, uma radiografia de tórax evidenciou cavitações pulmonares. A tomografia computorizada sugeriu o diagnóstico de tuberculose (TB) pulmonar ativa. Por esse motivo, foram realizadas broncofibroscopia, endoscopia digestiva alta e colonoscopia total com ileoscopia. A pesquisa de bacilos ácido-álcool resistentes foi positiva não só no lavado broncoalveolar e no suco gástrico, mas também nas biópsias do cólon. Verificouse uma resolução completa das queixas gastrointestinais 2 semanas após iniciar antibacilares.

Successful treatment of severe perianal Crohn's disease with infliximab in an HIV-positive patient.

We present the case of a woman infected with the HIV type 1, controlled with highly active antiretroviral therapy. In the meantime, she developed a severe perianal disease, with complex fistulae and chronic anal fissures. After developing a severe chronic diarrhea, a total ileocolonoscopy with biopsies was performed, showing multiple ileal and segmental colonic erosions. Histology favoured a Crohn's disease diagnosis. Despite the limited experience of anti-tumour necrosis factor agents in the HIV-infected population, infliximab was started in this patient, due to her severe and symptomatic Crohn's disease, with a controlled HIV infection. No side effects were reported and her bowel movements and perianal disease improved right after induction regimen with infliximab. 1 year after starting this therapy she is in clinical and endoscopic remission. The CD4+ T-cell count remained stable, the HIV-RNA undetectable and no opportunistic infections were reported during follow-up period. Data concerning the use of anti-tumour necrosis factor drugs is limited in patients with both inflammatory bowel disease and HIV infection. Only three cases of Crohn's disease and concomitant HIV infection treated with infliximab were reported in the literature. This case report might help future decisions in patients with a similar clinical situation.