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GI fellowships do not mandate curricula in career development. Often, fellows resort to peer mentorship for guidance. Fellows should recognize that the path to a successful career varies greatly based on how one defines and measures success. Keywords are preferr Through introspection, fellows will be able to craft their ideal post-fellowship position that balances wants versus needs. In this article, we cover four practical tips for trainees entering the job negotiation process.
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GI fellowships do not mandate curricula in career development. Often, fellows resort to peer mentorship for guidance. Fellows should recognize that the path to a successful career varies greatly based on how one defines and measures success. Through introspection, fellows will be able to craft their ideal post-fellowship position that balances wants versus needs. In this article, we cover the breadth of post-fellowship opportunities available with a focus on unique considerations for LGBTQ+ and IMG trainees.
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BACKGROUND: Inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. METHODS: A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. RESULTS: A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. CONCLUSIONS: This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.
This systematic review highlights the lack of an evidence-based approach to the diagnosis of inflammatory bowel diseaseassociated peripheral spondyloarthritis and the need to standardize evaluation and diagnosis via multidisciplinary collaboration with development of patient-reported outcomes and imaging indices.
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BACKGROUND & AIMS: Non-invasive cross-sectional imaging via magnetic resonance enterography (MRE) offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease (CD) but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathologic inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. METHODS: This single center, cross-sectional study, included 51 CD patients (n=34 for discovery; n=17 for validation) with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both evaluated against histopathology. RESULTS: Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both discovery (area under the curve (AUC)=0.69, 0.83) and validation (AUCs=0.67,0.78) cohorts. Radiologist visual scoring had an AUC=0.67 for identifying severe inflammation and AUC=0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation (AUC=0.79) and modestly improved assessment of severe fibrosis (AUC=0.79 for severe fibrosis) over individual approaches. CONCLUSIONS: Radiomic features of CD strictures on MRE can accurately identify severe histopathologic inflammation and severe histopathologic fibrosis, as well as augment performance of radiologist visual scoring in stricture characterization.
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BACKGROUND AND AIMS: No endoscopic scoring system has been established for immune-mediated colitis (IMC). This study aimed to establish such a system for IMC and explore its utility in guiding future selective immunosuppressive therapy (SIT) use compared to clinical symptoms. METHODS: This retrospective, international, 14-center study included 674 patients who developed IMC after immunotherapy and underwent endoscopic evaluation. Ten endoscopic features were selected by group consensus and assigned 1 point each to calculate an IMC endoscopic score (IMCES). IMCES cutoffs were chosen to maximize specificity for SIT use. This specificity was compared between IMCESs, and clinical symptoms were graded according to a standardized instrument. RESULTS: A total of 309 (45.8%) patients received SIT. IMCES specificity for SIT use was 82.8% with a cutoff of 4. The inclusion of ulceration as a mandatory criterion resulted in higher specificity (85.0% for a cutoff of 4). In comparison, the specificity of a Mayo endoscopic subscore of 3 was 74.6%, and the specificity of clinical symptom grading was much lower at 27.4% and 12.3%, respectively. Early endoscopy was associated with timely SIT use (P < .001; r = 0.4084). CONCLUSIONS: This is the largest multicenter study to devise an endoscopic scoring system to guide IMC management. An IMCES cutoff of 4 has a higher specificity for SIT use than clinical symptoms, supporting early endoscopic evaluation for IMC.
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Colitis , Colonoscopía , Índice de Severidad de la Enfermedad , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Colitis/patología , Colonoscopía/métodos , Inmunosupresores/uso terapéutico , Anciano , Inmunoterapia/métodos , Sensibilidad y Especificidad , Úlcera/patologíaRESUMEN
Knots are deeply entangled with every branch of science. One of the biggest open challenges in knot theory is to formalise a knot invariant that can unambiguously and efficiently distinguish any two knotted curves. Additionally, the conjecture that the geometrical embedding of a curve encodes information on its underlying topology is, albeit physically intuitive, far from proven. Here we attempt to tackle both these outstanding challenges by proposing a neural network (NN) approach that takes as input a geometric representation of a knotted curve and tries to make predictions of the curve's topology. Intriguingly, we discover that NNs trained with a so-called geometrical "local writhe" representation of a knot can distinguish curves that share one or many topological invariants and knot polynomials, such as mutant and composite knots, and can thus classify knotted curves more precisely than some knot polynomials. Additionally, we also show that our approach can be scaled up to classify all prime knots up to 10-crossings with more than 95% accuracy. Finally, we show that our NNs can also be trained to solve knot localisation problems on open and closed curves. Our main discovery is that the pattern of "local writhe" is a potentially unique geometric signature of the underlying topology of a curve. We hope that our results will suggest new methods for quantifying generic entanglements in soft matter and even inform new topological invariants.
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BACKGROUND: Cutaneous extra-intestinal manifestations (EIM) occur in up to 20% of patients with IBD. Information about Sweet syndrome (SS)'s clinical course as a rare cutaneous EIM in IBD is limited to case reports. We present the largest retrospective cohort on the occurrence and management of SS in IBD. STUDY: Electronic medical records and paper charts since 1980 were retrospectively reviewed at a large quaternary medical center to identify all adult IBD patients with histopathology-proven SS. Patient characteristics and clinical outcomes were evaluated. RESULTS: 25 IBD patients with SS were identified; 3 patients were assessed to have AZA-induced SS. The majority of SS patients were female. Median age at diagnosis was 47 years (IQR 33-54 years) and SS appeared at a median of 6.4 years after IBD diagnosis. IBD patients with SS had a high rate of complicated IBD phenotypes (75% extensive colitis in UC and 73% stricturing or penetrating disease in CD, with 100% colonic involvement), as well as frequent co-occurring EIMs (60%). SS correlated with global IBD disease activity. Corticosteroids were an effective therapy for SS in IBD. Recurrence rate of SS was 36%. CONCLUSION: Contrary to previous case reports, SS was a cutaneous EIM occurring late after diagnosis of IBD in our cohort, with occurrences paralleling global IBD disease activity. Although AZA-induced and IBD-associated SS were both effectively treated with corticosteroids, distinguishing them is relevant for future IBD treatment strategies.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Síndrome de Sweet , Femenino , Masculino , Humanos , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Estudios Retrospectivos , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamiento farmacológico , Síndrome de Sweet/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
Immune checkpoint inhibitors (ICI) have transformed the management of cancer, producing durable responses in a subset of treated patients across multiple malignancies. Immune-mediated diarrhea and colitis (imDC) occurs in up to 20% of ICI-treated patients. The risk of ICI imDC is dependent upon the agent and is commoner with anti-CTLA-4 compared to anti-PD-1 ICIs. Generally, imDC is treated with steroids and agents targeting TNFα or α4ß7 integrin. However, the management of steroids and/or biologic refractory imDC is unclear. We present a case of imDC in a 68-year-old female who failed to respond clinically, biochemically and immunohistochemically to corticosteroids, infliximab and vedolizumab. A trial of tofacitinib, a pan-JAK inhibitor, led to rapid clinical, biochemical and immunohistochemical control of imDC. ICIs result in a striking accumulation of cytotoxic and proliferative CD8 + T cells within tumor. However, the cellular and molecular mechanisms underlying imDC remain unclear. Herein, we observed significant T cell enrichment; and the successful treatment with tofacitinib highlights the potential of multiple convergent inflammatory pathways in imDC and inflammatory colitis.
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BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.
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Adenoma , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Neoplasias Endometriales , Femenino , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Incidencia , Prevalencia , Proteína 2 Homóloga a MutS/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico , Adenoma/diagnósticoRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) have increased our ability to treat an ever-expanding number of cancers. We describe a case series of 25 patients who were diagnosed with gastritis following ICI therapy. MATERIALS AND METHODS: This was a retrospective study involving 1712 patients treated for malignancy with immunotherapy at Cleveland Clinic from January 2011 to June 2019 (IRB 18-1225). We searched electronic medical records using ICD-10 codes for gastritis diagnosis confirmed on endoscopy and histology within 3 months of ICI therapy. Patients with upper gastrointestinal tract malignancy or documented Helicobacter pylori-associated gastritis were excluded. RESULTS: Twenty-five patients were found to meet the criteria for diagnosis of gastritis. Of these 25 patients, most common malignancies were non-small cell lung cancer (52%) and melanoma (24%). Median number of infusions preceding symptoms was 4 (1-30) and time to symptom onset 2 (0.5-12) weeks after last infusion. Symptoms experienced were nausea (80%), vomiting (52%), abdominal pain (72%), and melena (44%). Common endoscopic findings were erythema (88%), edema (52%), and friability (48%). The most common diagnosis of pathology was chronic active gastritis in 24% of patients. Ninety-six percent received acid suppression treatment and 36% of patients also received steroids with an initial median dose of prednisone 75 (20-80) mg. Within 2 months, 64% had documented complete resolution of symptoms and 52% were able to resume immunotherapy. CONCLUSION: Patients presenting with nausea, vomiting, abdominal pain, or melena following immunotherapy should be assessed for gastritis and if other causes are excluded, may require treatment as consideration for complication of immunotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Gastritis , Infecciones por Helicobacter , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Melena/complicaciones , Melena/tratamiento farmacológico , Centros de Atención Terciaria , Neoplasias Pulmonares/tratamiento farmacológico , Gastritis/inducido químicamente , Gastritis/complicaciones , Gastritis/tratamiento farmacológico , Dolor Abdominal/complicaciones , Dolor Abdominal/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Náusea/tratamiento farmacológicoRESUMEN
Strictures in Crohn's disease (CD) are a hallmark of long-standing intestinal damage, brought about by inflammatory and non-inflammatory pathways. Understanding the complex pathophysiology related to inflammatory infiltrates, extracellular matrix deposition, as well as muscular hyperplasia is crucial to produce high-quality scoring indices for assessing CD strictures. In addition, cross-sectional imaging modalities are the primary tool for diagnosis and follow-up of strictures, especially with the initiation of anti-fibrotic therapy clinical trials. This in turn requires such modalities to both diagnose strictures with high accuracy, as well as be able to delineate the impact of each histomorphologic component on the individual stricture. We discuss the current knowledge on cross-sectional imaging modalities used for stricturing CD, with an emphasis on histomorphologic correlates, novel imaging parameters which may improve segregation between inflammatory, muscular, and fibrotic stricture components, as well as a future outlook on the role of artificial intelligence in this field of gastroenterology.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Constricción Patológica/patología , Inteligencia Artificial , Intestinos/patología , FibrosisRESUMEN
Inspired by how certain proteins "sense" knots and entanglements in DNA molecules, here, we ask if local geometric features that may be used as a readout of the underlying topology of generic polymers exist. We perform molecular simulations of knotted and linked semiflexible polymers and study four geometric measures to predict topological entanglements: local curvature, local density, local 1D writhe, and nonlocal 3D writhe. We discover that local curvature is a poor predictor of entanglements. In contrast, segments with maximum local density or writhe correlate as much as 90% of the time with the shortest knotted and linked arcs. We find that this accuracy is preserved across different knot types and also under significant spherical confinement, which is known to delocalize essential crossings in knotted polymers. We further discover that nonlocal 3D writhe is the best geometric readout of the knot location. Finally, we discuss how these geometric features may be used to computationally analyze entanglements in generic polymer melts and gels.
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BACKGROUND: Immunotherapy has become one of the mainstays for metastatic urothelial carcinoma treatment. Whether immune checkpoint inhibitor therapy increases thromboembolism (TE) risk is unknown. OBJECTIVE: We investigated the incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) events and its associated outcomes in patients with metastatic urothelial cancer treated with immune checkpoint inhibitors. METHODS: Patients with urothelial cancer treated with immune checkpoint inhibitors at the Cleveland Clinic from 1/1/2015 to 12/31/2019 were identified. The Kaplan-Meier method estimated overall survival and Cox proportional hazards regression evaluated the impact of TE on overall survival. RESULTS: Of 279 patients, 72% were men with pure urothelial cancer (62%) who started atezolizumab (40%), nivolumab (3%), or pembrolizumab (57%). At a median follow-up of 5.6 months (range 0.3-51.6), 42 patients developed a TE (VTE n = 37, 13%, ATE n = 5, 2%). The cumulative incidence of TE after immune checkpoint inhibitor therapy was 9.1% (95% confidence interval 6.0-13.0) at 6 months and 13.6% (95% confidence interval 9.6-18.4) at 12 months. Most TE (VTE 62%, ATE 100%) occurred within 6 months of immune checkpoint inhibitor initiation (median doses 5, range 1-59), and the majority (VTE 81%, ATE 100%) resulted in hospitalization (median: 5 days, 4 days, respectively). Thromboembolism (hazard ratio 2.296, p = 0.0004), Bajorin score 1 or 2 (hazard ratio 1.490, p = 0.0315), and Bajorin score 2 (hazard ratio 3.50, p < 0.0001) were associated with worse overall survival. CONCLUSIONS: Immune checkpoint inhibitors are associated with a high TE risk. Thromboembolism is associated with worsened survival, among other poor outcomes. Further investigation into the mechanism behind immune checkpoint inhibitor-associated TE is needed.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Tromboembolia Venosa , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Masculino , Nivolumab/efectos adversos , Estudios Retrospectivos , Tromboembolia Venosa/etiologíaRESUMEN
The landscape of management of ulcerative colitis, a type of inflammatory bowel disease, continues to change with advancement in pharmaceutical options as well as clinical treatment targets. Ulcerative colitis primarily involves the superficial layers of the large bowel, and cause active inflammation that can affect the colon from the rectum to the cecum in a relapsing and a remitting course. In this review, we provide evidence-based guidance on the selection of appropriate medical therapies based on individual patient and disease characteristics, with a focus on biologics and small molecules. We also review the role of surgery and management of acute severe ulcerative colitis.
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BACKGROUND AND AIMS: Lynch syndrome (LS) predisposes patients to multiple cancers including of the gastric and small bowel. Data supporting EGD surveillance in LS are limited. Our aim is to describe upper GI (UGI) findings in asymptomatic LS patients undergoing EGD surveillance within a hereditary colorectal cancer registry. METHODS: Asymptomatic patients with LS who underwent ≥1 surveillance EGD were included. Demographics, genotype, and EGD findings were reviewed. The frequency of clinically actionable findings including neoplasia (cancer, adenomas), Barrett's esophagus (BE), Helicobacter pylori, and hyperplastic polyps >5 mm were assessed. RESULTS: Three hundred twenty-three patients underwent 717 EGDs starting at a median age of 49.5 years. On average, each patient had 2 EGDs with an interval of 2.3 years between examinations. Clinically actionable findings were identified in 57 patients (17.6%). On baseline EGD 27.7% of findings were identified, with the remainder on surveillance EGD over an average of 3.5 years. Five asymptomatic patients (1.5%) had an UGI cancer detected during surveillance, all at early stage, including 1 patient each with BE-related esophageal adenocarcinoma, gastric neuroendocrine tumor, and gastric adenocarcinoma and 2 patients with duodenal adenocarcinoma. Two cancers were found on baseline EGD and 3 on follow-up EGD. CONCLUSIONS: Clinically actionable findings were found in approximately 1 in 6 asymptomatic patients with LS undergoing EGD surveillance. Five patients (1.5%) were diagnosed with cancer, all detected at an early stage. These data suggest that both baseline and follow-up EGD surveillance are effective in detecting early-stage UGI cancers in asymptomatic patients with LS.
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Adenocarcinoma , Esófago de Barrett , Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Esofágicas , Esófago de Barrett/diagnóstico , Esófago de Barrett/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Endoscopía del Sistema Digestivo , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Metastatic renal cell carcinoma (mRCC) is associated with a high risk of thromboembolism (TE). OBJECTIVE: We investigated whether immunotherapy (IO) increases the hypercoagulable state in this high-risk population. PATIENTS AND METHODS: Patients with mRCC treated with IO between 1 January 2015 and 31 December 2019 at the Cleveland Clinic were identified. Cumulative incidence analysis calculated TE rates over time and Gray's test determined differences in TE rates among groups. The Kaplan-Meier method estimated survival, while Cox proportional hazard regression evaluated the impact of TE on OS. RESULTS: Of 351 patients, 75% were men with clear cell mRCC (81%) and International Metastatic Renal Cell Carcinoma (IMDC) intermediate- to poor-risk disease (77%). Patients received single-agent IO (52%), doublet IO (31%), or IO with non-IO therapy (17%). The median number of IO doses was 8 (range 1-81). At a median follow-up of 12.8 months, 12% of patients (n = 43) had a TE event (venous n = 37 [11%], arterial n = 6 [2%]). The cumulative TE incidence at 6 months was 4.4% (95% confidence interval [CI] 2.6-6.9) and 9.8% (95% CI 6.8-13.4) at 12 months. No factors, including IMDC or Khorana score, were identified to predict TE development. Seventy-two percent of TE resulted in hospitalization (9% TE-related mortality and 21% TE-related dose delay). TE (p < 0.0001), poor IMDC score (p < 0.0001), and Khorana score ≥ 2 (p < 0.0001) were associated with worse OS. CONCLUSIONS: Patients with mRCC treated with IO had a high incidence of TE. TE was associated with risk of treatment delay, hospitalization, and mortality, while TE, IMDC poor risk, and Khorana score ≥ 2 were associated with worse survival. Further investigations into IO-associated TE are needed to identify benefit from primary thromboprophylaxis.
Patients with advanced renal cell carcinoma carry an increased risk of clotting, both in their arteries and veins. Historically, risk scores such as the Khorana score were used to assess which patients with solid tumors would benefit from preventative blood thinning medications as they undergo chemotherapy. Whether the Khorana score can be applied to use with immunotherapy is not known. Currently, limited knowledge exists of the impact of immunotherapy on additional clotting in patients with renal cell carcinoma. This study shows an increased incidence of clotting under immunotherapy treatment in patients with advanced renal cancer compared with rates seen in the literature. This study highlights an associated risk of hospitalization, need to stop cancer therapy, as well as risk of death from clotting. Additionally, we determine that clotting, poor disease pathology (as assessed by the International Metastatic Renal Cell Carcinoma Database Consortium), and a Khorana score of ≥2 are predictors of a worse overall survival. This information will be useful in future studies that will address the usefulness of preventative blood thinner medications in this high-risk population.
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Carcinoma de Células Renales , Neoplasias Renales , Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Carcinoma de Células Renales/patología , Femenino , Humanos , Inmunoterapia , Neoplasias Renales/patología , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The most common genetic and molecular process leading to sporadic colorectal cancer is chromosomal instability. By contrast, mismatch repair deficiency, which results in high levels of microsatellite instability or lack of mismatch repair (MMR) protein expression on immunohistochemistry (IHC), is the predominant cancer pathway in patients with Lynch syndrome (LS). Importantly, patients with LS may still develop sporadic tumors through chromosomal instability. Testing tumors with IHC staining helps expand the spectrum of LS-related tumors. In this series, we describe 4 cancers in patients with LS that are not typical of the syndrome. Lack of MMR protein expression on IHC staining confirmed that 2 cancers are related to LS, expanding the spectrum of LS-related tumors, and the presence of MMR protein expression on IHC in the other 2 cases confirmed that they were sporadic and not related to mismatch repair deficiency and, thus, not related to LS.
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BACKGROUND AND AIMS: The risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD. METHODS: Patients with IBD from a tertiary center cancer registry who underwent immune checkpoint inhibitor (ICI) therapy from 2011 to 2019 were identified. A 1:5 matched cohort of patients with and without a history of IBD was created, based on age, ICI therapy, and cancer type. Demographic data, clinical history of IBD, cancer, ICI agent, imDC events after ICI therapy, and overall survival were analyzed. Overall survival and time-to-imDC (TTimDC) were estimated by Kaplan-Meier and multivariate Cox proportional-hazards models. RESULTS: From a retrospective cohort of 3900 patients who received ICI therapy, 30 patients with IBD were matched with 150 patients without a history of IBD. Most patients received PD-1/PD-L1 inhibitor monotherapy (154/180, 85.6%). Individuals with preexisting IBD showed significantly shorter TTimDC than those in the non-IBD group (1-year imDC-free rate 67% vs 93%; HR 7.59, 95% CI 3.00 to 19.15, p<0.0001). Eleven (36%) from the IBD cohort experienced imDC events; none led to life-threatening conditions needing surgical interventions or death. Corticosteroids or biologics were needed in 8/11 (73%) patients, and discontinuation of therapy improved imDC in the remaining three. Half of patients required hospitalization. In contrast, no significant difference in overall survival was observed between IBD and non-IBD cohorts (HR 0.89, 95% CI 0.54 to 1.48). Both groups had overall comparable rates of other non-imDC immune-related adverse events. CONCLUSION: Patients with preexisting IBD had worse time-to-imDC than non-IBD matched controls, yet did not exhibit worse overall survival. While close monitoring of patients with preexisting IBD is warranted while on immunotherapy, this comorbidity should not preclude ICI therapy if clinically required.
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Colitis/inducido químicamente , Diarrea/inducido químicamente , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Neoplasias/complicaciones , Femenino , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Neoplasias/tratamiento farmacológico , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Sweet syndrome [SS] is a dermatological condition associated with both inflammatory bowel disease [IBD] and azathioprine use. We performed a systematic review to better delineate clinical characteristics and outcomes of SS in IBD patients. METHODS: Peer-reviewed, full-text journal publications from inception to April 2020 in English language and adult subjects with IBD were included. Skin biopsy was required as SS gold-standard diagnosis. Azathioprine-associated SS required recent azathioprine introduction or recurrence of SS after azathioprine re-challenge. RESULTS: We included 89 publications with 95 patients [mean age of SS diagnosis: 44 years; 59% female; 20 with azathioprine-associated SS and 75 without]. SS was diagnosed prior to IBD in 5.3%, at time of IBD diagnosis in 29.5% and after diagnosis in 64.2%. In total, 91% of patients with SS had known colonic involvement and the majority [76%] had active IBD at diagnosis; 22% had additional extra-intestinal manifestations. Successful therapies for SS included corticosteroids [90.5%], anti-tumour necrosis factor [TNF]-α inhibitor therapy [14.8%] and azathioprine [11.6%]. Azathioprine-associated SS was distinct, with 85% male patients, mean age of SS diagnosis of 50 years and a lower likelihood to be prescribed corticosteroids for treatment [75% vs 94.7% of non-azathioprine-associated SS, p = 0.008]. All patients with azathioprine-associated SS improved with medication cessation and developed recurrence after re-challenge. CONCLUSIONS: SS may precede or occur with IBD diagnosis in almost one-third of cases. Azathioprine and IBD-associated SS present and behave distinctly, especially with regard to gender, age at diagnosis and recurrence risk. Corticosteroids and TNF-α inhibitors have demonstrated efficacy in treating SS in IBD.