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1.
Inflamm Bowel Dis ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953641

RESUMO

BACKGROUND: Almost half of patients with Crohn's disease (CD) require bowel surgeries in their lifetime. Due to the high risk of postoperative disease recurrence and high rate of previous antitumor necrosis factor (anti-TNF) failure, often alternative therapy options such as ustekinumab (UST) and vedolizumab (VDZ) are used. We aimed to evaluate the efficacy of UST and VDZ among postoperative CD patients as postoperative prophylaxis and rescue therapy. METHODS: Consented CD patients who underwent initial ileocecal resection and were treated with UST and VDZ were included in this study. Demographics, clinical characteristics, health care utilization, endoscopy scores, and surgery outcomes were collected. Postoperative early CD recurrence was defined as a Rutgeerts endoscopic score ≥i2 within the first 2 years. The rescue therapy group was defined as patients who received either UST or VDZ after having Rutgeerts endoscopic score ≥i2 postoperatively. RESULTS: During 2009 to 2019, 98 CD patients were treated with UST or VDZ postoperatively. Postoperative early recurrence rates were 5% (n = 1 out of 20) and 6% (1 out of 15) for the UST and VDZ groups, respectively. Two patients from the UST group and 1 patient from the VDZ group required bowel surgery during follow-up with median drug exposure of 51 (95% confidence interval [CI], 29-61) and 30 (95% CI, 14-63) months, respectively; 55% and 69% of patients had at least 1 point of improvement on postoperative endoscopic Rutgeerts score, respectively, for UST and VDZ. Only 3 out of 40 and 1 out of 23 patients required bowel surgery during follow-up while receiving UST and VDZ as rescue therapy. CONCLUSIONS: Both UST and VDZ were effective as postoperative therapies either as prophylaxis or rescue therapy.


This retrospective 11-year data examines the efficacy of ustekinumab and vedolizumab among postoperative Crohn's disease patients. When utilizing postoperative Rutgeerts score, this study confirms that both ustekinumab and vedolizumab were effective as postoperative therapies either as prophylaxis or rescue therapy.

2.
Crohns Colitis 360 ; 6(2): otae022, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38720935

RESUMO

Background: Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications. Methods: Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results: Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions: The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

3.
Inflamm Bowel Dis ; 29(12): 1895-1900, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36721326

RESUMO

BACKGROUND: Approximately half of Crohn's disease (CD) patients experience recurrence and need for repeat resections, highlighting need for prognostic biomarkers. Presence of epithelioid granuloma on surgical tissue and high Rutgeerts endoscopic score are associated with postoperative CD clinical recurrence. We sought to evaluate presence of epithelioid granuloma at first surgery and Rutgeerts score as a combined risk assessment for CD surgical recurrence. METHODS: Our study included consented CD patients who underwent initial ileocecal resection and were prospectively followed postoperatively. From 2009 to 2019, 418 CD patients underwent initial ileocecal resection with >4 years of follow-up, including postoperative endoscopic assessment (Rutgeerts score). RESULTS: Postoperative CD patients were grouped based on granuloma presence (30.6%; n = 128) or absence (69.4%; n = 290). Endoscopic recurrence (defined as Rutgeerts score ≥i2) was similar between the granuloma (26%) and no granuloma (25%) groups, respectively (P = .82). Patients with granuloma and CD endoscopic recurrence at first postoperative endoscopy had higher number of bowel surgeries compared with all other groups (no granuloma or CD endoscopic recurrence, P = .007; no granuloma but CD endoscopic recurrence present, P = .04; granuloma present and no CD endoscopic recurrence, P = .04). Epithelioid granuloma presence was associated with 1.65 times higher risk of subsequent surgery independently from first postoperative endoscopic recurrence Rutgeerts score. CONCLUSIONS: Granuloma presence on initial surgical histology is immediately available and identifies high-risk CD patients who may benefit from early postoperative treatment, and these precision intervention trials are warranted.


This study shows the presence of epithelioid granuloma as a risk factor for repeat Crohn's disease­related surgery, which is independent of first postoperative Rugteerts score. These 11-year observational data provide a risk factor that is immediately available after surgery and identifies high-risk CD patients who may benefit from early postoperative treatment.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Colo/cirurgia , Colo/patologia , Colonoscopia , Reoperação , Íleo/cirurgia , Íleo/patologia , Granuloma/etiologia , Granuloma/cirurgia , Granuloma/patologia , Recidiva , Estudos Retrospectivos
4.
Clin Gastroenterol Hepatol ; 21(6): 1598-1606.e5, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36642291

RESUMO

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Neoplasias , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Fator de Necrose Tumoral alfa , Fatores Biológicos , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Neoplasias/epidemiologia , Neoplasias/induzido quimicamente , Inibidores do Fator de Necrose Tumoral , Produtos Biológicos/efeitos adversos
5.
Endosc Int Open ; 10(9): E1188-E1192, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36118627

RESUMO

Background and study aims N95-filtering facepiece respirators (FFR) use is associated with physiological changes and symptoms due to impaired nasal airflow and increased breathing resistance. We prospectively studied the effect of using an external nasal dilator (END) in gastroenterology laboratory (gastrointestinal lab) staff using N95FFR. Patients and methods N95FFR qualitative saccharine fit testing was performed on study participants with and without an END. Prospective data collection and comparisons included: 1) survey of perceived symptoms and difficulty of performing one day of gastrointestinal procedures with N95FFR and 1 day of gastrointestinal procedures with END plus N95FFR in random sequence; and 2) vitals and respiratory belt plethysmography in ten gastroenterologists performing simulated colonoscopy while wearing a surgical mask (SM), N95FFR plus SM, END plus N95FFR plus SM for 20 minutes each in random sequence and rapid succession. Results Twenty-nine of 31 participants passed the N95FFR and the END plus N95FFR fit test. Twenty-two participants (12 physicians; 11 males; mean age 44.1 years, range 31-61) performed 1 day of gastrointestinal procedures with an N95FFR and 1 day of gastrointestinal procedures with an END plus N95FFR. Significantly less difficulty with nasal breathing and severity of symptoms including breathing difficulty, headache, fatigue and frustration, occurred while using an END plus N95FFR. Respiratory plethysmography peak-to-trough measurement showed an increase during the N95FFR stage compared to the END plus N95FFR stage and the SM stage. Conclusions N95FFR related respiratory changes and symptom development may be mitigated by END use.

7.
Clin Infect Dis ; 75(1): e630-e644, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35179197

RESUMO

BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.


Assuntos
COVID-19 , Infecções por HIV , Adulto , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Infecções por HIV/complicações , Humanos , Hospedeiro Imunocomprometido , Estudos Prospectivos , SARS-CoV-2 , Vacinação
8.
Inflamm Bowel Dis ; 28(1): 70-78, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33693659

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization. METHODS: We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type. RESULTS: A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P < 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P < 0.001) and an increased likelihood of hospitalization (adjusted odds ratio [AOR], 4.5; P < 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P < 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P < 0.05). CONCLUSIONS: Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Biomarcadores , Colite Ulcerativa/complicações , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Sistema de Registros
9.
Fed Pract ; 38(6): 270-275, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34733074

RESUMO

INTRODUCTION: Colonoscopies and fecal immunochemical tests (FITs) are the preferred modalities for colorectal cancer (CRC) screening. In addition to proper patient selection, appropriate fecal immunochemical testing requires that negative tests be repeated annually, positive tests lead to a diagnostic colonoscopy, and FIT not be performed within 5 years of a colonoscopy with adequate bowel preparation. We sought to study the frequency of inappropriate FITs at the Veterans Affairs Pittsburgh Health Care System in Pennsylvania. METHODS: A retrospective quality assurance study was undertaken of veterans undergoing FIT in a 3-year period (2015-2017). We calculated the rate of a negative initial FIT in 2015/2016 followed by a second FIT in 2016/2017 in a random selection of veterans (3% SE, 95% CI). Demographics were compared in an equal random number of veterans that did and did not have a follow-up FIT (5% SE, 95% CI of all negative FIT). We also calculated the rate of completing colonoscopy following a positive FIT in a random selection of veterans (3% SE, 95% CI). Finally, we investigated use of FIT following a colonoscopy for all veterans in the study period. RESULTS: A total of 6,766 FITs were performed; 4,391 unique veterans had at least 1 negative FIT, and 709 unique veterans had a positive FIT. Of 1,742 veterans with at least 1 negative FIT, 870 were eligible for repeat testing during the study period, and only 543 (62.4%) underwent at least 2 FITs. There was no significant demographic difference in veterans that had only 1 or at least 2 FITs. Of 410 veterans with a positive FIT, 113 (27.5%) did not undergo a subsequent colonoscopy within 1 year due to patient refusal, or failure to schedule or keep a colonoscopy appointment. Of 832 veterans who had both a FIT and colonoscopy in the interval, 108 veterans underwent colonoscopy with a subsequent FIT (1.6% of total FITs performed). Of these, 95 (88%) were judged to be inappropriate. Thirteen instances of FIT following colonoscopy were appropriate based on patient preference to undergo fecal immunochemical testing for CRC screening modality after undergoing colonoscopy with an inadequate bowel preparation. CONCLUSIONS: Veterans underwent inappropriate testing due to failure to undergo serial FIT after a negative result (37.6%), failure to complete colonoscopy following a positive FIT (27.5%), and undergoing inappropriate FIT following a recent colonoscopy (88%). Efforts are still required to improve both patient and provider education and adherence to appropriate fecal immunochemical testing and CRC screening guidelines.

11.
Hum Pathol ; 112: 9-19, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33727167

RESUMO

Serrated epithelial change (SEC) manifests in patients with long-standing inflammatory bowel disease (IBD) and is characterized by disorganized crypt architecture, irregular serrations, and goblet cell-rich epithelium. The serrated nature of SEC is reminiscent of serrated colorectal polyps, which frequently harbor KRAS/BRAF mutations. SEC is, however, not only histologically distinct from sporadic serrated polyps but also associated with colorectal neoplasia. Whether SEC is a precursor to IBD-associated neoplasia remains unclear. To further define the relationship of SEC with serrated colorectal polyps and IBD-associated neoplasia, we performed targeted next-generation sequencing on colorectal specimens to include the following: SEC without dysplasia/neoplasia (n = 10), SEC with separate foci of associated dysplasia/adenocarcinoma from the same patients (n = 17), and uninvolved mucosa (n = 10) from 14 patients. In addition, we molecularly profiled sessile serrated lesion (SSL)-like or serrated lesion, not otherwise specified (SL-NOS), specimens, from 11 patients who also had IBD. This control cohort included SSL-like/SL-NOS without dysplasia/neoplasia (n = 11), SSL-like/SL-NOS with associated low-grade dysplasia (n = 2), and uninvolved mucosa (n = 8). By next-generation sequencing, the most frequently mutated gene in SEC without neoplasia and associated dysplasia/adenocarcinoma from separate foci in the same patients was TP53. Recurrent TP53 mutations were present in 50% of SEC specimens without dysplasia/neoplasia. In addition, alterations in TP53 were detected at a prevalence of 71% in low-grade dysplasia, 83% in high-grade dysplasia, and 100% in adenocarcinoma. Paired sequencing of SEC and associated neoplasia revealed identical TP53 missense mutations for 3 patients. In contrast, 91% of SSL-like/SL-NOS specimens without dysplasia/neoplasia harbored KRAS/BRAF mutations, which were conserved in associated low-grade dysplasia. No genomic alterations were found in uninvolved mucosa from either patients with SEC or patients with SSL-like/SL-NOS. Based on our findings, we conclude SEC is distinct from SSL-like serrated colorectal lesions in patients with IBD and an early precursor to IBD-associated neoplasia that warrants colonoscopic surveillance.


Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Mucosa Intestinal/patologia , Lesões Pré-Cancerosas/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Lesões Pré-Cancerosas/genética , Análise de Sequência de DNA
12.
Gastrointest Endosc ; 94(1): 160-168.e3, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33497642

RESUMO

BACKGROUND AND AIMS: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. METHODS: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. RESULTS: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). CONCLUSIONS: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.


Assuntos
COVID-19 , Gastroenterologistas , Respiradores N95 , Exposição Ocupacional , Colonoscopia , Eletrocardiografia , Frequência Cardíaca , Humanos , Exposição Ocupacional/prevenção & controle
13.
Inflamm Bowel Dis ; 27(6): 855-863, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-32879976

RESUMO

BACKGROUND: Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity. METHODS: We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels. RESULTS: We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals. CONCLUSIONS: An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.


Assuntos
Colangite Esclerosante , Imunoglobulina G/sangue , Doenças Inflamatórias Intestinais , Biomarcadores , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/imunologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/imunologia
14.
Mod Pathol ; 33(9): 1832-1843, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32376853

RESUMO

Mutations in RAS occur in 30-50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF, and PIK3CA. Molecular testing was performed on 1286 consecutive mCRC from 1271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS, and HRAS for 15, 5, and 2 cases, respectively (6-21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology, and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggest the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.


Assuntos
Adenocarcinoma/complicações , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias do Colo/complicações , Resistencia a Medicamentos Antineoplásicos/genética , Doenças Inflamatórias Intestinais/complicações , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Receptores ErbB/antagonistas & inibidores , Feminino , Amplificação de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Panitumumabe/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
15.
Fed Pract ; 37(5): 224-228, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32454576

RESUMO

INTRODUCTION: The Veterans Choice Program (VCP) was designed to provide a pathway for veterans to access health care in the community if wait times at the US Department of Veterans Affairs (VA) were > 30 days. However, the performance of this program, in terms of timeliness, quality assurance, and overall utilization by veterans for colonoscopy is not well studied. METHODS: We reviewed records of veterans at VA Pittsburgh Healthcare System (VAPHS) who underwent VCP colonoscopy from June 2015 through March 2017. We compared the number of days from the scheduling encounter to the first available colonoscopy at VAPHS to the actual colonoscopy through the VCP. Additionally, we examined the availability of procedure and pathology results, documentation of quality metrics, and if clear follow-up recommendations were present in community care records. We then separately examined VCP utilization in a representative sample (5% margin of error, 95% CI) of all colonoscopy referrals through the VCP. RESULTS: During the study period 3,855 veterans were eligible for colonoscopy via the VCP, and 190 colonoscopies were performed through VCP. Records were absent for 29 exams (15.3%). There was no statistically significant difference for the number of days from a veteran's initially scheduled first-available colonoscopy at VAPHS when compared with the actual VCP colonoscopy (median 2 days earlier, P = .62). Pathology results were absent in 14 of 118 (11.9%) patient records, and follow-up recommendations were absent in 29 of 161 (18%) cases. Documentation of colonoscopy quality metrics were deficient in 27% to 70% of procedure reports. In a utilization sample of 350 veterans, only 26 (7.4%) veterans referred for colonoscopy had documented VCP colonoscopies, and 231 (66%) had a VAPHS colonoscopy. The median actual wait time for colonoscopy was 61 days for VAPHS and 66 days through VCP (P = .15). CONCLUSIONS: Colonoscopies referred through the VCP were not performed sooner in aggregate compared with the first available colonoscopy at VAPHS, although there was wide variability in wait times. We recommend additional mechanisms be put into place when outsourcing to community care: Ensure seamless and require prompt transfer of records back to the VA, require reporting of quality metrics standard at the VA for community care colonoscopies, and establish clinically meaningful wait-time thresholds for referral into the community, rather than static ones.

16.
Crohns Colitis 360 ; 2(2): otaa028, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36777292
17.
Clin Case Rep ; 7(11): 2174-2176, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31788273

RESUMO

A subset of patients with alcoholic hepatitis present with atypical imaging resembling hepatic tumor infiltration. Our case involves a patient who was initially thought to have multiple large hepatic metastases, ultimately found to have alcoholic hepatitis. It is essential to ask about alcohol use when clinical suspicion is high.

18.
J Grad Med Educ ; 11(3): 295-300, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31210860

RESUMO

BACKGROUND: Identification of surrogate decision makers (SDMs) is an important part of advance care planning for hospitalized patients. Despite its importance, the best methods for engaging residents to sustainably improve SDM documentation have not been identified. OBJECTIVE: We implemented a hospital-wide quality improvement initiative to increase identification and documentation of SDMs in the electronic health record (EHR) for hospitalized patients, utilizing a Housestaff Quality and Safety Council (HQSC). METHODS: EHR documentation of SDMs for all adult patients admitted to a tertiary academic hospital, excluding psychiatry, were tracked and grouped by specialty in a weekly run chart during the intervention period (July 2015 through April 2016). This also continued postintervention. Interventions included educational outreach for residents, monthly plan-do-study-act cycles based on performance feedback, and a financial incentive of a one-time payment of 0.75% of a resident's salary put into the retirement account of each resident, contingent on meeting an SDM documentation target. Comparisons were made using statistical process control and chi-square tests. RESULTS: At baseline, SDMs were documented for 11.1% of hospitalized adults. The intervention period included 9146 eligible admissions. Hospital-wide SDM documentation increased significantly and peaked near the financial incentive deadline at 48% (196 of 407 admissions, P < 001). Postintervention, hospital-wide SDM documentation declined to 30% (134 of 446 admissions, P < .001), but remained stable. CONCLUSIONS: This resident-led intervention sustainably increased documentation of SDMs, despite a decline from peak rates after the financial incentive period and notable differences in performance patterns by specialty admitting service.


Assuntos
Planejamento Antecipado de Cuidados/organização & administração , Documentação/métodos , Internato e Residência/normas , Centros Médicos Acadêmicos/métodos , Centros Médicos Acadêmicos/organização & administração , Adulto , Tomada de Decisões , Registros Eletrônicos de Saúde , Planos para Motivação de Pessoal , Humanos , Oregon , Melhoria de Qualidade/organização & administração
19.
Gastrointest Endosc ; 89(4): 818-824, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30391253

RESUMO

BACKGROUND AND AIMS: Nonuniversal use of facial protection during endoscopy may place endoscopists at risk of exposure to blood and body fluids; however, the frequency of exposure is unknown. METHODS: A prospective 6-month study of 4 gastroenterologists using a face shield during endoscopy was undertaken. The face shield was swabbed in a standardized fashion before and at the end of the session. Controls included pre- and post-swabs of face shields placed on the (1) endoscopy suite wall, (2) remote patient intake bay wall, and (3) after deliberate contamination with a colonoscope immediately after colonoscopy. The swabs were cultured for 48 hours, and growth was reported as no growth or by number of colony-forming units (CFUs). The groups were compared for +CFU rate and CFU number. RESULTS: A total of 1100 procedures were performed in 239 endoscopy sessions. The +CFU rate in the pre-endoscopy groups (2%-4.8%, not significant) was significantly lower than the postendoscopist face shield (45.8%, P < .001) and endoscopy suite wall groups (21.4%, P < .001), respectively. Using a cut-off of >15 CFUs as an indicator of definite exposure, the occurrence rate was 5.6 per 100 half days of endoscopy to the endoscopist's face and 3.4 per 100 half days of endoscopy 6 feet away. CONCLUSIONS: This is the first study to quantify the rate of unrecognized exposure to the endoscopist's face to potentially infectious biologic samples during endoscopy (5.6/100 days of endoscopy). This exposure may result in transmission of infectious diseases. As such, we recommend the use of universal facial protection during GI endoscopy.


Assuntos
Bactérias/isolamento & purificação , Endoscopia do Sistema Digestório , Gastroenterologistas , Máscaras/microbiologia , Exposição Ocupacional/estatística & dados numéricos , Atitude do Pessoal de Saúde , Colonoscopia , Contagem de Colônia Microbiana , Técnicas de Cultura , Endossonografia , Humanos , Incidência , Estudos Prospectivos
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