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1.
Clin Gastroenterol Hepatol ; 21(10): 2639-2648.e6, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36336312

RESUMO

BACKGROUND & AIMS: In this nationwide study from the Israeli Inflammatory Bowel Disease Research Nucleus, we aimed to describe the incidence of very early onset inflammatory bowel diseases (VEOIBDs) with a focus on infantile-onset disease and to compare management and disease course with older children. METHODS: Data were retrieved from the 4 Israeli Health Maintenance Organizations covering 98% of the population. Pediatric-onset IBD was categorized as follows: adolescent onset (10 to <18 y), early onset (6 to <10 y), VEOIBD (0 to <6 y), toddler onset (2 to <6 y), and infantile onset (<2 y). RESULTS: A total of 5243 children with 35,469 person-years of follow-up evaluation, were diagnosed with IBD during 2005 to 2020: 4444 (85%) with adolescent onset, 548 (10%) with early onset, and 251 (4.8%) with VEOIBD, of whom 81 (1.5%) had infantile onset. The incidence of pediatric-onset IBD increased from 10.8 per 100,000 in 2005 to 15.3 per 100,000 in 2019 (average annual percentage change, 2.8%; 95% CI, 2.2%-3.4%), but that of VEOIBD remained stable (average annual percentage change, 0%; 95% CI, -2.5% to 2.6%). The infantile-onset and toddler-onset groups were treated less often with biologics (36% and 35%, respectively) vs the early onset (57%) and adolescent-onset groups (53%; P < .001). The time to steroid dependency was shorter in infantile-onset (hazard ratio [HR], 2.1; 95% CI, 1.5-2.9) and toddler-onset disease (HR, 1.6; 95% CI, 1.2-2.0) vs early onset and adolescent-onset disease, but time to hospitalizations, time to surgery, and growth delay were worse only in infantile-onset disease. In a multivariable model, infantile-onset patients had a higher risk for surgery (HR, 1.4; 95% CI, 1.1-1.9) and hospitalization (HR, 1.7; 95% CI, 1.2-2.4) than the toddler-onset group. CONCLUSIONS: The incidence of VEOIBD remained stable. Infantile-onset IBD had worse outcomes than older children, while toddler onset had mostly similar outcomes, despite less frequent use of biologics.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Humanos , Criança , Doença de Crohn/epidemiologia , Incidência , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Intestinos , Colite Ulcerativa/epidemiologia
2.
Endoscopy ; 55(4): 303-310, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36150646

RESUMO

BACKGROUND: Current surveillance for Barrett's esophagus (BE), consisting of four-quadrant random forceps biopsies (FBs), has an inherent risk of sampling error. Wide-area transepithelial sampling (WATS) may increase detection of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). In this multicenter randomized trial, we aimed to evaluate WATS as a substitute for FB. METHODS: Patients with known BE and a recent history of dysplasia, without visible lesions, at 17 hospitals were randomized to receive either WATS followed by FB or vice versa. All WATS samples were examined, with computer assistance, by at least two experienced pathologists at the CDx Diagnostics laboratory. Similarly, all FBs were examined by two expert pathologists. The primary end point was concordance/discordance for detection of HGD/EAC between the two techniques. RESULTS: 172 patients were included, of whom 21 had HGD/EAC detected by both modalities, 18 had HGD/EAC detected by WATS but missed by FB, and 12 were detected by FB but missed by WATS. The detection rate of HGD/EAC did not differ between WATS and FB (P = 0.36). Using WATS as an adjunct to FB significantly increased the detection of HGD/EAC vs. FB alone (absolute increase 10 % [95 %CI 6 % to 16 %]). Mean procedural times in minutes for FB alone, WATS alone, and the combination were 6.6 (95 %CI 5.9 to 7.1), 4.9 (95 %CI 4.1 to 5.4), and 11.2 (95 %CI 10.5 to 14.0), respectively. CONCLUSIONS: Although the combination of WATS and FB increases dysplasia detection in a population of BE patients enriched for dysplasia, we did not find a statistically significant difference between WATS and FB for the detection of HGD/EAC as single modality.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Humanos , Esôfago de Barrett/complicações , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma/epidemiologia , Hiperplasia , Lesões Pré-Cancerosas/patologia , Progressão da Doença
3.
Dis Colon Rectum ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37878460

RESUMO

BACKGROUND: Patients with familial adenomatous polyposis often require prophylactic colectomy with ileal pouch-anal anastomosis to treat and/or reduce to risk of colorectal neoplasia. However, after surgery, patients are still at some risk of developing pouch polyps and even cancer in both handsewn or stapled anastomoses. Management relies mainly on endoscopic or surgical interventions, while chemopreventive agents have a limited role in the management and prevention of pouch neoplasia. Novel endoscopic techniques are evolving and may gradually overtake surgical intervention in selected cases. Since familial adenomatous polyposis is relatively rare, there is scarcity of data regarding the natural history of pouch polyps and cancer in this population. OBJECTIVE: This systematic literature review aims to describe the evolution, characteristics, various treatment modalities and their outcomes as well as recommended surveillance strategies of pouch neoplasia. DATA SOURCES: PubMed and Cochrane databases, the international pouch consortium (for expert opinion). STUDY SELECTION: Studies between 1990 and 2023, in English were included. Studies reporting neoplastic outcomes of inflammatory bowel disease pouch patients only were excluded. MAIN OUTCOME MEASURES: Incidence of pouch neoplasia and its outcomes (successful resections, surgical complications, mortality). RESULTS: Thirty-five studies were included. LIMITATIONS: Most studies focus on inflammatory bowel diseases pouch patients, there is scarce data regarding polyposis patients only. Most cohorts are small and retrospective. Data on interventions is mainly descriptive and no randomized controlled trials are available. CONCLUSIONS: Pouch adenoma are common and well managed by endoscopic resections, as advanced-endoscopic techniques are becoming more available. Additional data are required for defining updated recommendations for either endoscopic or surgical intervention. Pouch cancer is a very rare event and may arise despite surveillance. Continued endoscopic surveillance is key in cancer prevention and early detection. Outcome of cancer cases is poor and management in a referral center should be advised with tumor board discussions.

4.
Health Qual Life Outcomes ; 21(1): 2, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639633

RESUMO

BACKGROUND: Patient-reported outcome measures (PROMs) are recommended for assessing patient-centered outcomes in inflammatory bowel disease (IBD). The main aims were to assess the level of participation in an electronic PROM (ePROM) data collection system among patients with IBD, and evaluate reliability and validity of the resulting scores. METHODS: Patients included in the IBD registry of Maccabi Healthcare Services, a state-mandated healthcare provider for over 2.6 million people in Israel, were invited to complete the IBD-Control measure and a general health item, with follow-up ePROMs at 3 and 6 months including a global rating of change item. Descriptive statistics were used to compare patient characteristics by participation rate, and assess survey completion time. Initial scores were assessed for internal consistency reliability using Cronbach's alpha. Test-retest reliability was assessed using the intraclass correlation coefficient from paired scores of patients identified as unchanged between the initial and first follow-up. Construct validity was assessed by the ability of IBD-control scores to discriminate between patient sub-groups in expected ways. Empirical validity was assessed using ePROM score correlations with laboratory markers of disease activity. Score coverage was also assessed. RESULTS: A total of 13,588 patients were invited to participate [Mean age = 49 years (SD = 17); females = 51%]. Participation rate was 31.5%. Participants compared to non-participants were slightly older, were more likely to be female, to have a history of biologic treatment, to have higher socio-economic status, and to be more experienced in the usage of the digital patient portal. Median survey completion time was approximately 1:30 min. Internal consistency and test-retest reliability were 0.86 and 0.98, respectively. Scores discriminated between patient sub-groups in clinically expected ways, with expected correlations to laboratory markers of disease activity. A notable ceiling effect was observed (> 15%) for IBD-Control scores. CONCLUSIONS: Feasibility, reliability, and validity of the ePROM system was supported for measuring the level of perceived disease control in patients diagnosed with IBD in Israel. Additional research is needed to identify ways to increase patient participation, assess clinical implications of the identified measurement ceiling of the IBD-control, and evaluate the added value of the derived scores in support of clinical decision making.


Assuntos
Doenças Inflamatórias Intestinais , Participação do Paciente , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Reprodutibilidade dos Testes , Qualidade de Vida , Doenças Inflamatórias Intestinais/terapia , Inquéritos e Questionários , Medidas de Resultados Relatados pelo Paciente
5.
Dig Dis Sci ; 68(2): 414-422, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36221010

RESUMO

BACKGROUND: Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis. METHODS: This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years. RESULTS: This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p < 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p < 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC. CONCLUSIONS: Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Estudos de Coortes , Estudos Retrospectivos , Sistemas Pré-Pagos de Saúde , Doenças Inflamatórias Intestinais/diagnóstico , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico
6.
Gut ; 71(2): 287-295, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34344783

RESUMO

OBJECTIVE: Anti-drug antibodies (ADA) to anti-tumour necrosis factor (anti-TNF) therapy drive treatment loss of response. An association between intestinal microbial composition and response to anti-TNF therapy was noted. We therefore aimed to assess the implications of antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD). DESIGN: We analysed data from the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all patients with IBD in Israel. We included all patients treated with anti-TNF who had available ADA levels. Survival analysis with drug use as time varying covariates were used to assess the association between antibiotic use and ADA development. Next, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days. RESULTS: Among 1946 eligible patients, with a median follow-up of 651 days from initiation of therapy, 363 had positive ADA. Cox proportional hazard model demonstrated an increased risk of ADA development in patients who used cephalosporins (HR=1.97, 95% CI 1.58 to 2.44), or penicillins with ß-lactamase inhibitors (penicillin-BLI, HR=1.4, 95% CI 1.13 to 1.74), whereas a reduced risk was noted in patients treated with macrolides (HR=0.38, 95% CI 0.16 to 0.86) or fluoroquinolones (HR=0.20, 95% CI 0.12 to 0.35). In mice exposed to infliximab, significantly increased ADA production was observed in cephalosporin as compared with macrolide pretreated mice. Germ-free mice produced no ADA. CONCLUSION: ADA production is associated with the microbial composition. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillin-BLIs, or by treatment with fluoroquinolones or macrolides.


Assuntos
Adalimumab/imunologia , Antibacterianos/uso terapêutico , Formação de Anticorpos/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/imunologia , Inibidores do Fator de Necrose Tumoral/imunologia , Adalimumab/uso terapêutico , Adulto , Animais , Feminino , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/mortalidade , Infliximab/uso terapêutico , Israel , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Sistema de Registros , Análise de Sobrevida , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto Jovem
7.
Clin Gastroenterol Hepatol ; 20(3): e484-e495, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33845216

RESUMO

BACKGROUND & AIMS: Limited population-based data have explored perianal involvement in Crohn's disease (CD) and compared the disease course between severe and non-severe perianal CD (PCD). We aimed to explore the disease course of these phenotypes in a population-based study of CD. METHODS: Cases were identified from the epi-IIRN cohort and included 2 Israeli health maintenance organizations covering 78% of the population. We validated specific algorithms to identify fistulizing PCD and to differentiate severe from non-severe disease by medication utilization, International Classification of Disease, 9th Revision codes, and perianal procedures. RESULTS: A total of 12,904 CD patients were included in an inception cohort from 2005 (2186 pediatric-onset, 17%) providing 86,119 person-years of follow-up. Fistulizing PCD was diagnosed in 1530 patients (12%) (574 with severe PCD, 4%). The prevalence of PCD was 7.9%, 9.4%, 10.3%, and 11.6% at 1, 3, 5, and 10 years from CD diagnosis, respectively. At 5 years, PCD patients were more likely to be hospitalized (36% in non-PCD vs 64% in PCD; P < .001), undergo inflammatory bowel disease-related surgeries (9% vs 38%, respectively; P < .001), and develop anorectal cancer (1.2/10,000 person-years for non-PCD vs 4.2/10,000 for PCD; P = .01). Severe PCD was associated with poorer outcomes compared with non-severe PCD, as shown for hospitalizations (61% in non-severe PCD vs 73% in severe; P = .004) and surgeries (35% vs 43%; P = .001). CONCLUSIONS: Despite higher utilization of immunomodulators and biologics, PCD is associated with poor disease outcomes, especially in severe PCD.


Assuntos
Neoplasias do Ânus , Doença de Crohn , Doenças Inflamatórias Intestinais , Fístula Retal , Neoplasias Retais , Estudos de Coortes , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Fístula Retal/diagnóstico , Fístula Retal/epidemiologia
8.
Clin Gastroenterol Hepatol ; 20(6): e1263-e1282, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34954338

RESUMO

BACKGROUND & AIMS: Studies have shown decreased response to coronavirus disease 2019 (COVID-19) vaccinations in some populations. In addition, it is possible that vaccine-triggered immune activation could trigger immune dysregulation and thus exacerbate inflammatory bowel diseases (IBD). In this population-based study we used the epi-Israeli IBD Research Nucleus validated cohort to explore the effectiveness of COVID-19 vaccination in IBD and to assess its effect on disease outcomes. METHODS: We included all IBD patients insured in 2 of the 4 Israeli health maintenance organizations, covering 35% of the population. Patients receiving 2 Pfizer-BioNTech BNT162b2 vaccine doses between December 2020 and June 2021 were individually matched to non-IBD controls. To assess IBD outcomes, we matched vaccinated to unvaccinated IBD patients, and response was analyzed per medical treatment. RESULTS: In total, 12,109 IBD patients received 2 vaccine doses, of whom 4946 were matched to non-IBD controls (mean age, 51 ± 16 years; median follow-up, 22 weeks; interquartile range, 4-24). Fifteen patients in each group (0.3%) developed COVID-19 after vaccination (odds ratio, 1; 95% confidence interval, 0.49-2.05; P = 1.0). Patients on tumor necrosis factor (TNF) inhibitors and/or corticosteroids did not have a higher incidence of infection. To explore IBD outcomes, 707 vaccinated IBD patients were compared with unvaccinated IBD patients by stringent matching (median follow-up, 14 weeks; interquartile range, 2.3-20.4). The risk of exacerbation was 29% in the vaccinated patients compared with 26% in unvaccinated patients (P = .3). CONCLUSIONS: COVID-19 vaccine effectiveness in IBD patients is comparable with that in non-IBD controls and is not influenced by treatment with TNF inhibitors or corticosteroids. The IBD exacerbation rate did not differ between vaccinated and unvaccinated patients.


Assuntos
Vacina BNT162 , COVID-19 , Doenças Inflamatórias Intestinais , Adulto , Idoso , Vacina BNT162/efeitos adversos , Vacina BNT162/uso terapêutico , COVID-19/prevenção & controle , Doença Crônica , Progressão da Doença , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pessoa de Meia-Idade , SARS-CoV-2 , Inibidores do Fator de Necrose Tumoral/uso terapêutico
9.
J Pediatr Gastroenterol Nutr ; 74(6): 788-793, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35192577

RESUMO

BACKGROUND AND OBJECTIVES: Both perianal and pediatric-onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult-onset perianal CD and their disease course. METHODS: We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD-9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease. RESULTS: A total of 12,905 patients were included (2186 [17%] pediatric-onset, 10,719 [83%] adults), with a median follow-up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P  < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6-4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1-3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid-dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age. CONCLUSION: PCD is more common in pediatric-onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.


Assuntos
Produtos Biológicos , Doença de Crohn , Fístula Retal , Adulto , Produtos Biológicos/uso terapêutico , Criança , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Humanos , Israel/epidemiologia , Fístula Retal/diagnóstico
10.
Genet Med ; 23(4): 705-712, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33257847

RESUMO

PURPOSE: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. RESULTS: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. CONCLUSION: Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/prevenção & controle , Reparo de Erro de Pareamento de DNA/genética , Feminino , Heterozigoto , Humanos , Histerectomia , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Estudos Prospectivos , Salpingo-Ooforectomia
11.
Liver Int ; 41(11): 2635-2645, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34174011

RESUMO

BACKGROUND & AIMS: High consumption of ultra-processed food (UPF) is associated with mortality and chronic morbidity but has not been studied concerning to non-alcoholic fatty liver disease (NAFLD). We aimed to test the association of UPF consumption with metabolic syndrome, NAFLD and related-liver damage. METHODS: A cross-sectional study among volunteers who underwent abdominal ultrasound (AUS), anthropometrics, blood pressure measurements, and fasting blood tests including FibroMax for non-invasive assessment of NASH and significant fibrosis. A food-frequency questionnaire was used to evaluate UPF consumption using the NOVA classification. RESULTS: A total of 789 subjects were included in the total sample (mean age 58.83 ± 6.58 years, 52.60% men), a reliable FibroMax test was obtained from 714 subjects, 305 subjects were diagnosed with NAFLD. High consumption of UPF was associated with higher odds for metabolic syndrome (OR = 1.88, 95% CI 1.31-2.71, P = .001) and its components; hypertension, hypertriglyceridemia, and low HDL, among the entire sample (OR = 1.53, 1.07-2.19, P = .026; OR = 1.51, 1.08-2.11, P = .017; OR = 1.55, 1.05-2.29, P = .028). In addition, it was associated with higher odds for NASH and hypertension (OR = 1.89, 1.07-3.38, P = .030; OR = 2.26, 1.20-4.26, P = .012 respectively) among subjects with NAFLD. Stratification by smoking status revealed an association between high UPF consumption and significant fibrosis among ever smokers in the entire sample and among subjects with NAFLD (OR = 1.89, 95% CI 1.03-3.45, P = .039; OR = 2.85, 1.14-7.14, P = .026 respectively). CONCLUSIONS: High UPF consumption is associated with metabolic syndrome in the general population, and among those with NAFLD it is associated with NASH marker. Ever-smoking may act synergistically with UPF to amplify the risk for fibrosis.


Assuntos
Hipertensão , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Ultrassonografia
12.
J Pediatr Gastroenterol Nutr ; 73(2): 223-230, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587410

RESUMO

OBJECTIVES: The impact of pediatric-onset inflammatory bowel disease (IBD) on growth is debated. We aimed to investigate the effect of IBD on anthropometric measures at young adulthood. METHODS: Children diagnosed with Crohn disease (CD) or ulcerative colitis (UC) (2005-2019) were identified in a national database along with matched non-IBD controls. RESULTS: Overall, 2229 IBD cases (68% CD) were matched to 4338 controls. Only females with CD differed in final height from controls (z scores: -0.37 ±â€Š1.09 vs -0.25 ±â€Š1.06, respectively; P = 0.01), corresponding to a mean difference of 0.7 ±â€Š0.2 cm (all females) and 1.2 ±â€Š0.3 cm in females diagnosed <14 years (P = 0.02). Final height was reduced in both sexes according to adjusted mean height difference analysis (-0.43 cm, 95% confidence interval -0.85 to -0.02; P = 0.04). This difference increased in patients with CD who underwent abdominal surgery (-0.91 cm, 95% confidence interval -1.39 to -0.42; P = 0.01). The proportion of patients with CD achieving final height z scores of -1 and zero differed significantly from controls for both males (71.1% and 34.8% vs 79.1% and 43.0%, respectively; P < 0.001) and females (67.7% and 30.4% vs 79.6%, and 43.3%, respectively; P < 0.001). Patients treated with anti-tumor necrosis factor agents during growth potential had similar height improvement to other regimens. Predominantly, patients with CD were leaner, with a greater proportion of subjects with underweight, compared with controls. CONCLUSIONS: In pediatric-onset IBD, absolute final height was modestly affected by females with CD. Nevertheless, greater proportions of both sexes with early diagnosis of CD failed to achieve normal final height, compared with controls.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Estatura , Criança , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Humanos , Masculino , Adulto Jovem
13.
Pharmacoepidemiol Drug Saf ; 30(11): 1576-1587, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34453456

RESUMO

BACKGROUND: Proton pump inhibitors (PPI) are used for a variety of indications. Despite reported associations with undesirable effects, their long-term use is on the rise, while appropriate indications, dose, and treatment duration may deviate from guideline recommendations. OBJECTIVES: Primary to examine the annual patterns of PPI use. Secondary- to assess indications for initiating PPI treatment, long-term use, and factors associated with long-term use in a large Israeli health maintenance organization. METHODS: A historical cohort study of 528 420 eligible PPI users during 2000-2015, analyzed PPI use using defined daily doses and the proportion of patients covered method. Data on indications for treatment initiation, clinical and socio-demographic parameters were captured as well. A multivariable logistic-regression model was used to identify factors associated with long-term use of PPI. RESULTS: The annual incidence rates of patients initiating PPI treatment were relatively constant, ranging between 2.4% and 3.1% of the adult population, with a monotonic increase in annual consumption and prevalence (reaching 12.7% in 2015). Reflux, functional symptoms, and Helicobacter pylori eradication were the most common indications for initiating PPI therapy. However, 27% of patients had no recorded indication for treatment. Fifteen percent of patients used PPI for over 6 months, especially in older age groups. CONCLUSIONS: Utilization of PPI increases steadily, mainly due to chronic use. Prolonged consumption is associated with specific clinical indications and older age. Health organizations should encourage awareness of appropriate use among physicians, specifically in the elderly, patients with reflux, and those with functional disorders.


Assuntos
Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Adulto , Idoso , Estudos de Coortes , Sistemas Pré-Pagos de Saúde , Humanos , Incidência
14.
Int J Cancer ; 146(4): 1064-1074, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31283021

RESUMO

As a large number of cancers are caused by nonsense mutations in key genes, read-through of these mutations to restore full-length protein expression is a potential therapeutic strategy. Mutations in the adenomatous polyposis coli (APC) gene initiate the majority of both sporadic and hereditary colorectal cancers (CRC) and around 30% of these mutations are nonsense mutations. Our goal was to test the feasibility and effectiveness of APC nonsense mutation read-through as a potential chemo-preventive therapy in Familial Adenomatous Polyposis (FAP), an inherited CRC syndrome patients. Ten FAP patients harboring APC nonsense mutations were treated with the read-through inducing antibiotic erythromycin for 4 months. Endoscopic assessment of the adenomas was performed at baseline, after 4 and after 12 months. Adenoma burden was documented in terms of adenoma number, maximal polyp size and cumulative polyp size per procedure. Tissue samples were collected and subjected to molecular and genetic analyses. Our results show that in the majority of patients the treatment led to a decrease in cumulative adenoma burden, median reduction in cumulative adenoma size and median reduction in adenoma number. Molecular and genetic analyses of the adenomas revealed that the treatment led to a reduced number of somatic APC mutations, reduced cellular proliferation and restoration of APC tumor-suppressing activity. Together, our findings show that induced read-through of APC nonsense mutations leads to promising clinical results and should be further investigated to establish its therapeutic potential in FAP and sporadic CRCs harboring nonsense APC mutations.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/tratamento farmacológico , Eritromicina/administração & dosagem , Transcrição Gênica/efeitos dos fármacos , Polipose Adenomatosa do Colo/diagnóstico por imagem , Polipose Adenomatosa do Colo/genética , Administração Oral , Adolescente , Adulto , Idoso , Criança , Códon sem Sentido , Códon de Terminação/genética , Colonoscopia , Eritromicina/efeitos adversos , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Int J Cancer ; 146(1): 115-122, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211411

RESUMO

Epigenetic transformations may provide early indicators for cancer and other disease. Specifically, the amount of genomic 5-hydroxymethylcytosine (5-hmC) was shown to be globally reduced in a wide range of cancers. The integration of this global biomarker into diagnostic workflows is hampered by the limitations of current 5-hmC quantification methods. Here we present and validate a fluorescence-based platform for high-throughput and cost-effective quantification of global genomic 5-hmC levels. We utilized the assay to characterize cancerous tissues based on their 5-hmC content, and observed a pronounced reduction in 5-hmC level in various cancer types. We present data for glioblastoma, colorectal cancer, multiple myeloma, chronic lymphocytic leukemia and pancreatic cancer, compared to corresponding controls. Potentially, the technique could also be used to follow response to treatment for personalized treatment selection. We present initial proof-of-concept data for treatment of familial adenomatous polyposis.


Assuntos
5-Metilcitosina/análogos & derivados , Biomarcadores Tumorais/metabolismo , Epigênese Genética , Ensaios de Triagem em Larga Escala/métodos , Neoplasias/genética , 5-Metilcitosina/metabolismo , Animais , Análise Custo-Benefício , Fluorescência , Ensaios de Triagem em Larga Escala/economia , Humanos , Camundongos , Neoplasias/classificação , Estudo de Prova de Conceito
16.
Isr Med Assoc J ; 22(1): 32-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927803

RESUMO

BACKGROUND: Evaluation of mismatch repair (MMR) deficiency is conducted via immunohistochemistry or by microsatellite instability (MSI) analysis. Heterogeneous immunohistochemistry staining for MMR proteins may show different patterns; however, according to current guidelines, all of those patterns should be interpreted as MMR proficient. This conclusion might lead to false negative results because although most cases of heterogeneity stem from technical factors and biological variability, other types of heterogeneity represent true MMR deficiency. OBJECTIVES: To identify a unique heterogeneity pattern that is associated with true MMR loss. METHODS: We analyzed 145 cases of colorectal carcinoma. Immunohistochemistry staining for MLH1, PMS2, MSH2, and MSH6 were performed. We defined geographic heterogeneity as areas of tumor nuclear staining adjacent to areas of loss of tumor nuclear staining with intact staining in the surrounding stroma. All cases were evaluated for the presence of geographic heterogeneity. In addition, 24 cases were also evaluated by MSI testing. RESULTS: Of the 145 cases, 24 (16.5%) were MMR deficient. Of the 24 cases for which MSI analysis was also available, 10 cases (41.7%) demonstrated biological heterogeneity, 5 (20.8%) demonstrated technical heterogeneity, and 2 (8.3%) demonstrated geographic heterogeneity. Only the two cases with geographic heterogeneity were MSI-high via MSI analysis. In addition, a germline mutation in MSH-6 was identified in one of these cases. CONCLUSIONS: Geographic heterogeneity may raise a suspicion for a MMR-deficient case, which should be further analyzed using additional methodologies such as MSI analysis.


Assuntos
Reparo de Erro de Pareamento de DNA/genética , Proteínas MutS/genética , Adenoma/genética , Adenoma/patologia , Adulto , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Corantes , Heterogeneidade Genética , Humanos , Masculino
17.
J Clin Gastroenterol ; 53(2): e54-e60, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29099467

RESUMO

BACKGROUND: Patients with familial adenomatous polyposis (FAP) may carry various adenomatous polyposis coli (APC) mutations. However, genotype-phenotype correlation for APC mutations is still debated and is yet to be evaluated with regard to pouch polyp formation. OBJECTIVE: To evaluate the association between APC mutation type and exon location and the outcome of pouch adenoma. DESIGN SETTING AND PATIENTS: Forty-five FAP patients with defined pathogenic APC mutations, who underwent total proctocolectomy and ileal pouch anal anastomosis were classified by mutation type and location. Analysis was conducted for clinical and endoscopic parameters. RESULTS: Twenty patients had either indel/deletion mutations and 25 had nonsense/missense mutations. The indel/deletion group was associated with higher prevalence of preoperative hundreds of colonic adenomas (66.7% vs. 30%; P=0.030), lower rates of stapled versus sewn anastomosis (46.7% vs. 76%; P=0.060), of single stage surgery (13.3% vs. 44%; P=0.045) and with higher pouch adenoma formation rate (50% vs. 8%; P=0.002). Twenty-seven were carriers of exons 1 to 14 mutations and 18 were carriers of exon 15 mutations. Carriers of exon 15 mutations had higher prevalence of preoperative hundreds of colonic adenomas (55.6% vs. 22.2%; P=0.003) and a higher tendency for pouch and cuff adenoma formation rate. Adjusted odds ratio for pouch adenoma formation was 8.32 (1.42-48.80; P=0.019) for the indel/deletion group versus nonsense/missense, but no significant independent association was noted with mutation location. The mean number of pouch and cuff adenoma formation (per endoscopy) was higher among carriers of exon 15 mutations, but no significant independent association was noted the with mutation type. CONCLUSIONS: Type and location of APC mutation are associated with colonic polyp burden, surgical outcome and likelihood of developing pouch adenomas. These findings may contribute to surgical and endoscopic surveillance decisions for FAP patients.


Assuntos
Adenoma/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Neoplasias do Colo/patologia , Adenoma/cirurgia , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/cirurgia , Adolescente , Adulto , Estudos de Coortes , Neoplasias do Colo/cirurgia , Bolsas Cólicas/patologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Mutação , Prevalência , Proctocolectomia Restauradora/métodos , Estudos Retrospectivos , Adulto Jovem
18.
J Hepatol ; 68(6): 1239-1246, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29571924

RESUMO

BACKGROUND & AIMS: High red and processed meat consumption is related to type 2 diabetes. In addition, cooking meat at high temperatures for a long duration forms heterocyclic amines (HCAs), which are related to oxidative stress. However, the association between meat consumption and non-alcoholic fatty liver disease (NAFLD) is yet to be thoroughly tested. Therefore, we aimed to test the association of meat type and cooking method with NAFLD and insulin resistance (IR). METHODS: This was a cross-sectional study in individuals who were 40-70 years old and underwent screening colonoscopy between 2013 and 2015 in a single center in Israel. NAFLD and IR were evaluated by ultrasonography and homeostasis model assessment. Meat type and cooking method were measured by a food frequency questionnaire (FFQ) and a detailed meat questionnaire. Unhealthy cooking methods were considered as frying and grilling to a level of well done and very well done. Dietary HCA intake was calculated. RESULTS: A total of 789 individuals had a valid FFQ and 357 had a valid meat questionnaire. High consumption of total meat (portions/day above the median) (odds ratio [OR] 1.49; 95% CI 1.05-2.13; p = 0.028; OR 1.63; 1.12-2.37; p = 0.011), red and/or processed meat (OR1.47; 95% CI 1.04-2.09; p = 0.031; OR1.55; 1.07-2.23; p = 0.020) was independently associated with higher odds of NAFLD and IR, respectively, when adjusted for: body mass index, physical activity, smoking, alcohol, energy, saturated fat and cholesterol intake. High intake of meat cooked using unhealthy methods (OR1.92; 95% CI 1.12-3.30; p = 0.018) and HCAs (OR2.22; 95% CI 1.28-3.86; p = 0.005) were independently associated with higher odds of IR. CONCLUSION: High consumption of red and/or processed meat is associated with both NAFLD and IR. High HCA intake is associated with IR. If confirmed in prospective studies, limiting the consumption of unhealthy meat types and improving preparation methods may be considered as part of NAFLD lifestyle treatment. LAY SUMMARY: High red and processed meat consumption is related to several diseases. In addition, cooking meat at high temperatures for a long duration forms heterocyclic amines, which have harmful health effects. Non-alcoholic fatty liver disease is a significant public health burden and its formation is strongly related to insulin resistance. In this study, both were found to be more frequent in people who consume relatively high quantities of red and processed meat. In addition, a high intake of heterocyclic amines was associated with insulin resistance.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/etiologia , Carne Vermelha/efeitos adversos , Adulto , Idoso , Aminas/administração & dosagem , Culinária/métodos , Estudos Transversais , Ingestão de Alimentos , Feminino , Compostos Heterocíclicos/administração & dosagem , Humanos , Israel/epidemiologia , Masculino , Produtos da Carne/efeitos adversos , Produtos da Carne/análise , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Carne Vermelha/análise , Fatores de Risco , Inquéritos e Questionários
19.
Dis Colon Rectum ; 61(9): 1073-1079, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30086056

RESUMO

BACKGROUND: Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carriers are still not fully characterized. OBJECTIVE: The purpose of this study was to assess the prevalence of germline mutations and to describe the genotype-phenotype correlation in POLD1 and POLE genes in Jewish subjects with multiple colorectal adenomas and/or early-onset mismatch repair proficient colorectal cancers. DESIGN: This study is a comparison of genetic and clinical data from affected and control groups. SETTINGS: The study was conducted at a high-volume tertiary referral center. PATIENTS: The study cohort included 132 subjects: 68 with multiple colorectal adenomas and 64 with early-onset mismatch repair proficient colorectal cancers. The control group included 5685 individuals having no colorectal cancer or colorectal adenomas. MAIN OUTCOME MEASURES: Study and control subjects were tested for POLD1 and POLE mutations and a clinical correlation was assessed. RESULTS: Eleven of the 132 study subjects (8.3%) carried either a POLD1 or a POLE mutation: 7 of 68 (10.3%) subjects with multiple colorectal adenomas and 4 of 64 (6.2%) subjects with early-onset mismatch repair proficient colorectal cancer. Three mutations were detected, showing statistical significance in frequency between study and control groups (p < 0.001). Eight of the 11 mutation carriers were Ashkenazi Jews carrying the same POLD1 mutation (V759I), implicating it as a possible low-to-moderate risk founder mutation. Phenotype of mutation carriers was notable for age under 50 at diagnosis, a propensity toward left-sided colorectal cancer, and extracolonic tumors (64%, 100%, and 27% of cases). LIMITATIONS: The study cohort was limited by its relatively small size. CONCLUSIONS: Germline mutations in POLD1 and POLE were found to be relatively frequent in our Jewish cohorts. Further studies are needed to clarify the importance of POLD1 and POLE mutations and to define the most suitable surveillance program for Jewish and other POLD1 and POLE mutation carriers. See Video Abstract at http://links.lww.com/DCR/A658.


Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , DNA Polimerase III/genética , DNA Polimerase II/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adenoma/etnologia , Adulto , Idoso , Neoplasias Colorretais/etnologia , Reparo de Erro de Pareamento de DNA , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Judeus , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Sistema de Registros
20.
J Clin Gastroenterol ; 52(9): 805-811, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29210901

RESUMO

GOALS: The goal of this study is to test the association between lifetime smoking habits and colorectal polyps of different classifications. BACKGROUND: Smoking is an established risk factor for several cancers, including colorectal cancer. However, the association between lifetime smoking habits including intensity, duration, and cessation, and premalignant colorectal polyps is yet to be established. STUDY: A case-control study among 828 consecutive subjects aged 40 to 70 years, undergoing screening or diagnostic colonoscopy. Exclusion criteria were: medically treated diabetes, colectomy, and belonging to colorectal cancer high risk group. Polyps were stratified according to histology (serrated or adenomatous polyp) and location. All participants underwent anthropometric measurements and a structured medical and lifestyle interview. RESULTS: Current-smoking was more strongly associated with increased odds for distal rather than proximal polyps [odds ratio (OR), 4.00; 95% confidence interval (CI), 2.40-6.68 and OR, 2.52; 95% CI, 1.46-4.36, respectively], with serrated-polyps rather than adenomas (OR, 6.36; 95% CI, 2.77-14.57 and OR, 3.01; 1.90-4.74, respectively). All levels of smoking intensity (daily cigarettes) were associated with colorectal polyps. A dose-response association was seen between smoking duration and colorectal polyps. Smoking duration of ≥20 years was strongly associated with distal polyps (OR, 4.01; 95% CI, 1.62-9.84), independently of potential confounders, smoking intensity and years since smoking cessation. All associations were stronger for distal serrated polyps. CONCLUSIONS: Smoking duration is associated with colorectal plyps, independently of other potential confounders, smoking intensity, and cessation. The association is stronger with distal rather than proximal polyps, and with serrated polyps rather than adenomas.


Assuntos
Pólipos Adenomatosos/epidemiologia , Fumar Cigarros/epidemiologia , Pólipos do Colo/epidemiologia , Colonoscopia/métodos , Pólipos Adenomatosos/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Fumar Cigarros/efeitos adversos , Pólipos do Colo/etiologia , Pólipos do Colo/patologia , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Fatores de Risco , Abandono do Hábito de Fumar/estatística & dados numéricos , Fatores de Tempo
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