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PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) have become a pillar of cancer therapy for many people around the world. However, up to two-thirds of all patients undergoing ICI therapy will have immune-related adverse events (irAEs), including immune-checkpoint inhibitor colitis (ICIC). This review summarizes the most valuable and currently available information about the mechanism, diagnosis, and management of ICIC. RECENT FINDINGS: Recent findings include several developments on the leading theories for the mechanisms of ICIC such as the role of the gut microbiome. New emerging therapy strategies include tocilizumab, ustekinumab, mycophenolate mofetil, and calcineurin inhibitors. SUMMARY: The occurrence of irAEs remains a limiting factor for the use of immunotherapy in cancer treatment. Prompt diagnosis of ICIC with endoscopy and histologic confirmation can lead to early utilization of known effective treatments such as corticosteroids, infliximab, vedolizumab, and other emerging therapy strategies. We summarize the key points of this review article in our abstract video, Supplemental Digital Content 1, http://links.lww.com/COG/A44.
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Colite , Microbioma Gastrointestinal , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Imunoterapia/efeitos adversos , Ácido MicofenólicoRESUMO
Partial anomalous pulmonary venous connection is defined by one or more of the pulmonary veins draining to the heart into a location other than the left atrium. Depending on the location of the anomalous venous connection, they can be categorized as supracardiac, infracardiac, cardiac, and mixed types. In some cases, there is no hemodynamic consequence; in others, it can result in tricuspid regurgitation, right heart dilation, and pulmonary hypertension. Frequently, the reason for referral can be asymptomatic right heart dilation of unknown significance. Diagnosis is often difficult by transthoracic echocardiogram unless there is a high index of suspicion, and the appropriate views are obtained. Cardiac CT (computed tomography) or cardiac MRI (magnetic resonance imaging) can provide more precise anatomic detail as needed. The current article reviews the etiology and pathophysiology of partial anomalous pulmonary venous connection, and also reviews the current knowledge on their treatment.
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Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Veias Pulmonares/anormalidades , Síndrome de Cimitarra/diagnóstico por imagem , Síndrome de Cimitarra/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Veias Pulmonares/diagnóstico por imagem , Adulto JovemRESUMO
Background: Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. Methods: We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. Results: The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. Conclusions: The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia.
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Mapeamento Encefálico , Condutos Olfatórios/patologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico por imagem , Transtornos do Olfato/etiologia , Transtornos do Olfato/patologia , Bulbo Olfatório/diagnóstico por imagem , Bulbo Olfatório/patologia , Condutos Olfatórios/diagnóstico por imagem , Oxigênio/sangue , Descanso , Esquizofrenia/patologia , Adulto JovemRESUMO
Graft-vs-host disease (GVHD) after liver transplant is a rare complication with high mortality outcomes. Because of the rarity of occurrence, there is no standardized consensus for treatment. Early recognition of symptoms and a multidisciplinary approach with input from transplant hepatology and hematology is important to determine a treatment plan and improve outcomes. We present a unique case of a 49-year-old woman who developed GVHD during a coronavirus disease 2019 (COVID-19) infection 3 months after receiving a liver transplant. More data are needed to determine whether COVID-19 infection itself correlates with a risk of developing GVHD.
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We present a rare case in which malignant catatonia led to acute liver failure (ALF). A 19-year-old male was admitted for psychosis and developed ALF with a peak aspartate aminotransferase and alanine aminotransferase of 5,728 U/L and 7,735 U/L, respectively, and a peak international normalized ratio of 7.1. Liver biopsy showed significant confluent necrosis involving >70% of the liver tissue. He was listed for a liver transplant but was ultimately taken off of because of significant improvement with treatment by N-acetylcysteine infusion. Through our research, we found that symptoms of hepatitis can be seen with psychotic disorders, but ALF is rare.
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Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating PALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.
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Tratamento Farmacológico da COVID-19 , Doença Hepática Induzida por Substâncias e Drogas , Causalidade , Humanos , Fatores de Risco , SARS-CoV-2 , Estados UnidosRESUMO
Herbal-induced liver injury (HILI) is an important and increasingly concerning cause of liver toxicity, and this study presents recent updates to the literature. An extensive literature review was conducted encompassing September 2019 through March 2021. Studies with clinically significant findings were analyzed and included in this review. We emphasized those studies that provided a causality assessment methodology, such as Roussel Uclaf Causality Assessment Method scores. Our review includes reports of individual herbals, including Garcinia cambogia, green tea extract, kratom as well as classes such as performance enhancing supplements, Traditional Chinese medicine, Ayurvedic medicine and herbal contamination. Newly described herbals include ashwagandha, boldo, skyfruit, and 'Thermo gun'. Several studies discussing data from national registries, including the United States Drug-Induced Liver Injury (DILI) Network, Spanish DILI Registry, and Latin American DILI Network were incorporated. There has also been a continued interest in hepatoprotection, with promising use of herbals to counter hepatotoxicity from anti-tubercular medications. We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration. The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.