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1.
Endoscopy ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499197

RESUMO

BACKGROUND: Society guidelines on colorectal dysplasia screening, surveillance, and endoscopic management in inflammatory bowel disease (IBD) are complex, and physician adherence to them is suboptimal. We aimed to evaluate the use of ChatGPT, a large language model, in generating accurate guideline-based recommendations for colorectal dysplasia screening, surveillance, and endoscopic management in IBD in line with European Crohn's and Colitis Organization (ECCO) guidelines. METHODS: 30 clinical scenarios in the form of free text were prepared and presented to three separate sessions of ChatGPT and to eight gastroenterologists (four IBD specialists and four non-IBD gastroenterologists). Two additional IBD specialists subsequently assessed all responses provided by ChatGPT and the eight gastroenterologists, judging their accuracy according to ECCO guidelines. RESULTS: ChatGPT had a mean correct response rate of 87.8%. Among the eight gastroenterologists, the mean correct response rates were 85.8% for IBD experts and 89.2% for non-IBD experts. No statistically significant differences in accuracy were observed between ChatGPT and all gastroenterologists (P=0.95), or between ChatGPT and the IBD experts and non-IBD expert gastroenterologists, respectively (P=0.82). CONCLUSIONS: This study highlights the potential of language models in enhancing guideline adherence regarding colorectal dysplasia in IBD. Further investigation of additional resources and prospective evaluation in real-world settings are warranted.

2.
Gastrointest Endosc ; 98(4): 639-641.e4, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37385548

RESUMO

BACKGROUND AND AIMS: ChatGPT, an advanced language model, is increasingly used in diverse fields, including medicine. This study explores using ChatGPT to optimize postcolonoscopy management by providing guideline-based recommendations and addressing low compliance rates and timing issues. METHODS: In this proof-of-concept study, 20 clinical scenarios were prepared as structured reports and free-text notes, and ChatGPT's responses were evaluated by 2 senior gastroenterologists. Compliance with guidelines and accuracy were assessed, and inter-rater agreement was calculated using Fleiss' kappa coefficient. RESULTS: ChatGPT exhibited 90% compliance with guidelines and 85% accuracy, with a very good inter-rater agreement (Fleiss' kappa coefficient of .84, P < .01). ChatGPT handled multiple variations and descriptions and crafted concise patient letters. CONCLUSIONS: Results suggest that ChatGPT could aid healthcare providers in making informed decisions and improve compliance with postcolonoscopy surveillance guidelines. Future research should investigate integrating ChatGPT into electronic health record systems and evaluating its effectiveness in different healthcare settings and populations.


Assuntos
Colonoscopia , Gastroenterologistas , Humanos , Colonoscopia/métodos , Fidelidade a Diretrizes
3.
Gastrointest Endosc ; 97(3): 559-567, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36328207

RESUMO

BACKGROUND AND AIMS: Owing to its simplicity, effectiveness, and safety, EMR is the preferred treatment for the majority of large (≥20 mm) nonpedunculated colonic polyps (LNPCPs); however, residual and recurrent adenomas (RRAs) encountered during surveillance constitute a major limitation. Thermal ablation of the post-EMR mucosal defect margin has been shown to be highly efficacious in reducing RRA in a randomized trial setting, but data on effectiveness in clinical practice are scarce. We aimed to determine the effectiveness of this technique for reducing RRAs in routine clinical practice. METHODS: We analyzed data collected in 3 hospitals in Israel: Prospective data were available in 2 hospitals where margin thermal ablation with snare-tip soft coagulation (STSC) is routinely performed after EMR of LNPCP (TA-EMR). Only retrospective data were available from the third center, which exclusively did not perform STSC (standard EMR] [S-EMR]), during the study period. Surveillance was performed 4 to 6 months after resection. RRA was assessed endoscopically with high-definition white light and optical chromoendoscopy. The primary endpoint was RRA at first surveillance colonoscopy. RESULTS: Data from 764 patients with 824 LNPCPs were analyzed. The patient and lesion characteristics were similar between the groups. Four hundred sixty-four LNPCPs were treated by TA-EMR and 360 LNPCPs by S-EMR. RRA at first surveillance colonoscopy was detected in 14 (3.6%) of lesions in the TA-EMR group compared with 96 (31.6%) in the S-EMR group (P < .001; RR = .14; 95% CI, .07-.29). Adverse events were comparable between the 2 groups. CONCLUSION: TA-EMR leads to a significant reduction in post-EMR recurrence in routine clinical practice.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Pólipos do Colo/patologia , Estudos Prospectivos , Estudos Retrospectivos , Colonoscopia/métodos , Adenoma/patologia , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Colorretais/cirurgia
4.
Ren Fail ; 45(2): 2282707, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37975172

RESUMO

BACKGROUND: Concern exists regarding the renal safety of blocking the renin-angiotensin system (RAS) during acute illness, especially in the presence of volume depletion and hemodynamic instability. METHODS: We explored the impact of loop diuretics and RAS blockers on the likelihood of developing acute kidney injury (AKI) or acute kidney functional recovery (AKR) among inpatients. Adjusted odds ratio for AKI, AKR and mortality was calculated, using logistic regression models, with subgroup analysis for patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, corrected for blood pressure measurements. RESULTS: 53,289 patients were included. RAS blockade was associated with reduced adjusted odds ratio for both AKI (0.76, CI 0.70-0.83) AKR (0.55, 0.52-0.58), and mortality within 30 days (0.44, 0.41-0.48), whereas loop diuretics were associated with increased risk of AKI (3.75, 3.42-4.12) and mortality (1.71, 1.58-1.85) and reduced AKR (0.71, 0.66-0.75). Comparable impact of RAS blockers and loop diuretics on renal outcomes and death was found among 6,069 patients with eGFR < 30 ml/min/1.73m2. RAS inhibition and diuretics tended to increase the adjusted odds ratios for AKI and to reduce the likelihood of AKR in hypotensive patients. CONCLUSIONS: Reduced blood pressure, RAS blockers and diuretics affect the odds of developing AKI or AKR among inpatients, suggesting possible disruption in renal functional reserve (RFR). As long as blood pressure is maintained, RAS inhibition seems to be safe and renoprotective in this population, irrespective of kidney function upon admission, and is associated with reduced mortality.


Assuntos
Injúria Renal Aguda , Renina , Humanos , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Angiotensinas , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Estudos Retrospectivos , Rim , Sistema Renina-Angiotensina , Injúria Renal Aguda/etiologia , Diuréticos/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos
5.
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
6.
Am J Nephrol ; 52(1): 76-83, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657555

RESUMO

BACKGROUND: Large data analyses confirm the relative safety of contrast-enhanced computed tomography (CT), except for those with advanced renal failure. However, the prevalence of post-contrast acute kidney injury may be masked by acute kidney functional recovery (AKR) in unstable inpatients, irrespective of contrast-enhanced imaging. METHODS: In this work we aimed to assess AKI and AKR along with need for dialysis and mortality, among inpatients undergoing contrast-enhanced or non-enhanced CT. We performed a large-scale retrospective data analysis using propensity score matching (PSM) that compared patients undergoing contrast-enhanced and non-enhanced imaging. We also performed a subgroup analysis of subjects stratified by baseline renal function. RESULTS: A total of 41,456 patients were analyzed. PSM resulted in well-balanced groups. AKR occurred substantially more often than AKI among hospitalized patients following CT imaging, especially among those with low baseline renal function. Yet, in this population, whereas the rate of AKI significantly increased, the rate of AKR significantly decreased following contrast-enhanced studies as compared to patients that underwent non-enhanced CT. A significantly higher proportion of patients with baseline advanced renal failure that underwent contrast-enhanced imaging required dialysis. CONCLUSIONS: The increased incidence of AKI and AKR as seen in patients with lower pre-imaging kidney function possibly suggests that both entities reflect impaired renal functional reserve. Unstable kidney function in inpatients, as demonstrated by rates of AKR and AKI, is an important confounder which requires attention in similar observational studies on the renal effects of contrast media and of various other renal injurious events.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Meios de Contraste/efeitos adversos , Diálise Renal , Tomografia Computadorizada por Raios X/métodos , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Recuperação de Função Fisiológica , Estudos Retrospectivos
7.
Clin Exp Pharmacol Physiol ; 48(12): 1724-1727, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34545593

RESUMO

Renal functional reserve (RFR) reflects the ability of the kidney to enhance glomerular filtration rate (GFR) in response to a protein load. Chronic kidney disease (CKD) leads to diminished RFR, since the capacity for whole-body GFR to increase through hyperfiltration of remaining nephrons is limited. Evaluating 41,456 inpatients following computerised tomography we reported many exhibiting acute kidney injury (AKI) but more patients with recovering kidney function (AKR), presumably reflecting resolution of their critical conditions. The incidences of AKI and AKR were closely co-associated and were both inversely correlated with baseline kidney function. We discuss this phenomenon, arguing that AKR among inpatients with an acute illness, like AKI, may often reflect underlying subtle CKD with diminished RFR.


Assuntos
Pacientes Internados
8.
Harefuah ; 160(8): 537-540, 2021 Aug.
Artigo em Hebraico | MEDLINE | ID: mdl-34396731

RESUMO

INTRODUCTION: Reviewed are three studies we conducted, assessing the risk of contrast nephropathy in hospitalized patients undergoing computerized tomography. These were retrospective large data analyses at a single tertiary care facility, using meticulous and compound propensity score matching and inverse probability of treatment weighting. These studies indicate that overall, the risk of contrast nephropathy is likely negligible, with the exception of patients with grades 4-5 renal failure at baseline (eGFR<30 ml/min/1.73m2), with an odds ratio of 1.51 to develop AKI, associated with increased mortality as compared with patients undergoing non-enhanced imaging. We also assessed the incidence and magnitude of improved kidney function (acute kidney recovery) around imaging, underscoring its potential to mask subclinical AKI. These studies illustrate the strengths of large data analysis with advanced statistical tools.


Assuntos
Injúria Renal Aguda , Análise de Dados , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Meios de Contraste/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Estudos Retrospectivos , Fatores de Risco
9.
Nephrol Dial Transplant ; 35(2): 206-212, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768198

RESUMO

Concepts regarding hypoxic acute kidney injury (AKI) are derived from widely used warm ischemia-reflow (WIR) models, characterized by extensive proximal tubular injury and associated with profound inflammation. However, there is ample clinical and experimental data indicating that hypoxic AKI may develop without total cessation of renal blood flow, with a different injury pattern that principally affects medullary thick limbs in the outer medulla. This injury pattern likely reflects an imbalance between blood and oxygen supply and oxygen expenditure, principally for tubular transport. Experimental models of hypoxic AKI other than WIR are based on mismatched oxygen delivery and consumption, particularly within the physiologically hypoxic outer medulla. However, evidence for such circumstances in human AKI is lacking. Recent analysis of the clinical course and laboratory findings of patients following near-drowning (ND) provides a rare glimpse into such a scenario. This observation supports the role of renal hypoxia in the evolution of AKI, as renal impairment could be predicted by the degree of whole-body hypoxia (reflected by lactic acidosis). Furthermore, there was a close association of renal functional impairment with indices of reduced oxygen delivery (respiratory failure and features of intense sympathetic activity) and of enhanced oxygen consumption for active tubular transport (extrapolated from the calculated volume of consumed hypertonic seawater). This unique study in humans supports the concept of renal oxygenation imbalance in hypoxic AKI. The drowning scenario, particularly in seawater, may serve as an archetype of this disorder, resulting from reduced oxygen delivery, combined with intensified oxygen consumption for tubular transport.


Assuntos
Injúria Renal Aguda/etiologia , Hipóxia/complicações , Oxigênio/metabolismo , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Humanos , Consumo de Oxigênio , Circulação Renal
10.
Ren Fail ; 42(1): 836-844, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32787602

RESUMO

BACKGROUND: Inhibitors of sodium-glucose co-transporter-2 (SGLT2i) were found to improve renal outcome in diabetic patients in large prospective randomized trials. Yet, SGLT2i may acutely reduce kidney function through volume depletion, altered glomerular hemodynamics or intensified medullary hypoxia leading to acute tubular injury (ATI). The aim or this study was to prospectively assess the pathophysiology of acute kidney injury (AKI) in patients hospitalized while on SGLT2i, differing ATI from pre-renal causes using renal biomarkers. METHODS: Serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Ischemia Molecule (KIM)-1, markers of distal and proximal tubular injury, respectively, were determined in 46 diabetic patients who were on SGLT2i upon hospitalization with an acute illness. RESULTS: Serum and urine NGAL, but not KIM-1, were significantly increased in 21 of the patients who presented with AKI upon admission, as compared with 25 patients that maintained kidney function. Both serum and urinary NGAL correlated with the degree of impaired renal function, which in many cases was likely the result of additional acute renal perturbations, such as sepsis. CONCLUSIONS: Increased urinary and serum NGAL indicates that ATI, principally affecting distal tubular segments, may develop in some of the patients hospitalized with an acute illness and AKI while on SGLT2i. It is suggested that intensified medullary hypoxia by SGLT2i might be detrimental in this injury. By contrast, concomitantly unaltered KIM-1 might reflect improved cortical oxygenation by SGLT2i, and may explain an overall reduced risk of AKI with SGLT1i in large series. The independent potential of SGLT2i to inflict medullary hypoxic damage should be explored further.


Assuntos
Injúria Renal Aguda/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Receptor Celular 1 do Vírus da Hepatite A/análise , Lipocalina-2/análise , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Endosc Int Open ; 12(4): E600-E603, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38681146

RESUMO

Background and study aims Rising prevalence of pancreatic cysts and inconsistent management guidelines necessitate innovative approaches. New features of large language models (LLMs), namely custom GPT creation, provided by ChatGPT can be utilized to integrate multiple guidelines and settle inconsistencies. Methods A custom GPT was developed to provide guideline-based management advice for pancreatic cysts. Sixty clinical scenarios were evaluated by both the custom GPT and gastroenterology experts. A consensus was reached between experts and review of guidelines and the accuracy of recommendations provided by the custom GPT was evaluated and compared with experts. Results The custom GPT aligned with expert recommendations in 87% of scenarios. Initial expert recommendations were correct in 97% and 87% of cases, respectively. No significant difference was observed between the accuracy of custom GPT and the experts. Agreement analysis using Cohen's and Fleiss' Kappa coefficients indicated consistency among experts and the custom GPT. Conclusions This proof-of-concept study shows the custom GPT's potential to provide accurate, guideline-based recommendations for pancreatic cyst management, comparable to expert opinions. The study highlights the role of advanced features of LLMs in enhancing clinical decision-making in fields with significant practice variability.

13.
J Crohns Colitis ; 18(1): 38-46, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37465992

RESUMO

BACKGROUND: In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease [CD], stratified by monotherapy and combotherapy. METHODS: We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population [2005-2020]. Durability was defined as consistent treatment without surgery or added medications [except for combination therapy with thiopurines or methotrexate]. All comparisons were based on stringent propensity-score matching and paired time-to-event analyses. RESULTS: A total of 19 264 patients with CD were included, of whom 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [IQR] 3.6-10.7). Time to biologics decreased gradually from 6.7 years [IQR 2.7-10.4] in 2005 to 0.2 years [0.07-0.23] in 2020. The durability of the first biologic after 1 and 3 years was higher with adalimumab monotherapy [88%/61%] than vedolizumab monotherapy [81%/59%; n = 394 matched patients, p = 0.04] and similar between infliximab monotherapy and vedolizumab monotherapy [65%/43%; n = 182 matched patients, p = 0.1]. Durability was higher in adalimumab monotherapy vs infliximab monotherapy [83%/62% vs 71%/48% at 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <0.001]. CONCLUSION: Durability of the first biologic in CD was highest for adalimumab monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised.


Assuntos
Produtos Biológicos , Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Adalimumab/uso terapêutico , Infliximab , Resultado do Tratamento
14.
Inflamm Bowel Dis ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38190498

RESUMO

BACKGROUND: In a nationwide cohort, we aimed to compare the durability of infliximab and adalimumab as first biologic treatment in children with Crohn's disease (CD), stratified as combotherapy or monotherapy. METHODS: We used data from the epi-IIRN cohort that includes all patients with inflammatory bowel diseases in Israel. Durability was defined as consistent treatment without surgery or treatment escalation. All comparisons followed stringent propensity-score matching in Cox proportional hazard models. RESULTS: Of the 3487 children diagnosed with CD since 2005, 2157 (62%) received biologics (1127 [52%] infliximab, 964 [45%] adalimumab and 52 [2%] vedolizumab as first biologic), representing a higher proportion than that among adults diagnosed during the same time period (5295 of 15 776 [34%]; P < .001). Time from diagnosis to initiation of biologic was shorter in pediatric-onset compared with adult-onset disease (median time during the last 3 years was 2.7 months [interquartile range 1.2-5.4] vs 5.2 months [2.6-8.9]; P < .001). The durability of adalimumab monotherapy after 1 and 5 years from initiation of treatment was better than infliximab monotherapy (79%/54% vs 67%/37%, respectively; n = 452 matched children; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.3; P < .001), while in those treated with combotherapy, durability was similar (94%/66% with infliximab vs 90%/54% with adalimumab; n = 100; HR, 1.7; 95% CI, 0.9-3.3; P = .1). Durability was higher in children treated with infliximab combotherapy vs infliximab monotherapy (87%/45% vs 75%/39%; n = 440; HR, 1.4; 95% CI, 1.1-1.8; P = .01). The durability of adalimumab monotherapy was similar to infliximab combotherapy (83%/53% vs 89%/56%, respectively; n = 238; HR, 0.9; 95% CI, 0.7-1.2; P = .4). CONCLUSION: Our results support using adalimumab monotherapy as a first-line biologic in children with CD. When infliximab is used, combotherapy may be advantageous over monotherapy.

15.
Inflamm Bowel Dis ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578929

RESUMO

BACKGROUND: In this nationwide study, our objective was to compare the durability of first-line biologics in ulcerative colitis (UC), categorized into monotherapy and combotherapy with immunomodulators. METHODS: We utilized data from the nationwide epi-IIRN cohort from 2005 to 2020. Durability was defined as consistent treatment without surgery. Comparisons were based on stringent propensity score-matching. RESULTS: We included 15 111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years (interquartile range, 3.8-11.0). The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively; P = .8). Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively; n = 182 matched pairs, P = .3) or combotherapy (78%/56% vs 91%/58%, respectively; n = 46 matched pairs, P = .4). Durability of infliximab was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; n = 174 matched pairs, P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%; n = 53 matched pairs, P = .4). The durability rate was similar for vedolizumab monotherapy (77%/56%) compared with adalimumab monotherapy (69%/52%; n = 125 matched patients, P = .1), and infliximab monotherapy (73%/55% vs 62%/44%; n = 78 matched patients, P = .1). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%, respectively; n = 131 matched pairs, P = .02). CONCLUSION: After 5 years of treatment, 43% of the patients with UC sustained their first biologic, with similar durability in pediatric and adult-onset onset disease. Anti-TNFs had similar durability to vedolizumab and superior durability when prescribed as combotherapy.

16.
Cell Rep Med ; 5(1): 101300, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38118442

RESUMO

Personalized treatment of complex diseases has been mostly predicated on biomarker identification of one drug-disease combination at a time. Here, we use a computational approach termed Disruption Networks to generate a data type, contextualized by cell-centered individual-level networks, that captures biology otherwise overlooked when performing standard statistics. This data type extends beyond the "feature level space", to the "relations space", by quantifying individual-level breaking or rewiring of cross-feature relations. Applying Disruption Networks to dissect high-dimensional blood data, we discover and validate that the RAC1-PAK1 axis is predictive of anti-TNF response in inflammatory bowel disease. Intermediate monocytes, which correlate with the inflammatory state, play a key role in the RAC1-PAK1 responses, supporting their modulation as a therapeutic target. This axis also predicts response in rheumatoid arthritis, validated in three public cohorts. Our findings support blood-based drug response diagnostics across immune-mediated diseases, implicating common mechanisms of non-response.


Assuntos
Artrite Reumatoide , Doenças Inflamatórias Intestinais , Humanos , Infliximab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa , Artrite Reumatoide/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico
17.
J Crohns Colitis ; 17(9): 1410-1417, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37084088

RESUMO

BACKGROUND: Different antibiotic classes were reported to have variable effects on immunogenicity towards anti-tumour necrosis factor [TNF] agents. However, the impact of antibiotic administration on biologic treatment durability was not investigated. We aimed to assess the association between antibiotic treatment and persistence of different classes of biologic therapy in inflammatory bowel disease [IBD] patients. METHODS: Data from the epi-IIRN, a nationwide registry of all Israeli IBD patients were analysed. All patients who filled a prescription of either infliximab, adalimumab, vedolizumab, or ustekinumab, were included. Treatment cessation was defined as drug discontinuation of at least 6 months. Macrolides, cephalosporins, fluoroquinolones, and penicillins with beta-lactamase inhibitors were selected as primary exposure variables. Survival analysis was performed using marginal structural models for each drug separately. RESULTS: In all 13 513 IBD patients, with a total of 39 600 patient-years, were included. Significant differences of overall treatment persistence were demonstrated, with highest persistence rates for ustekinumab and the lowest for infliximab treatment. Macrolides were found to be significantly associated with reduced risk of infliximab cessation (adjusted hazard ratio [aHR] 0.72, 95% CI 0.62-0.89]. Fluoroquinolones and cephalosporins were associated with an elevated risk of adalimumab treatment cessation [aHR 1.33, 95% CI 1.22-1.46; and aHR 1.20, 95% CI 1.08-1.34, respectively]. No significant effects of the studied antibiotics were observed in ustekinumab and vedolizumab users. CONCLUSIONS: Specific antibiotic classes are associated with duration of anti-TNF treatment, but not with durability of vedolizumab or ustekinumab treatments. Further research is required to study the effect of specific antibiotics on response to biologics.

18.
Dig Liver Dis ; 55(7): 880-887, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36740502

RESUMO

BACKGROUND: Autosomal recessive conditions are common in consanguineous populations. Since consanguinity is common in the Israeli Arab population, we evaluated the rate of MUTYH polyposis (MAP) among polyposis patients in this population and studied Pathogenic Variants (PVs) spectrum. METHODS: We reviewed health records of all Arab and Druze polyposis patients referred for counseling during 2013-2020 who fulfilled the Israeli Genetic Society criteria for MUTYH/APC testing, in a tertiary center in Northern Israel and four additional gastro-genetic clinics in Israel. RESULTS: The Northern cohort included 37 patients from 30 unrelated families; 8(26.6%) carried bi-allelic MUTYH PVs. The major variant p.Glu452del was detected in 6/8 Druze and Muslim families who shared the same haplotype. Other PVs detected in both cohorts included p.Tyr56Ter, p.His57Arg, c.849+3A>C, p.Ala357fs, and p.Tyr151Cys. Among bi-allelic carriers, 88% reported consanguinity, and 100% had positive family history for polyposis or colorectal cancer (CRC). Generally, the age of CRC was 10 years younger than reported in the general MAP population. CONCLUSIONS: MAP accounted for 27% of polyposis cases in the Arab population of Northern Israel. PVs spectrum is unique, with high frequency of the founder variant p.Glu452del. Our results may inform the genetic testing strategy in the Israeli Arab population.


Assuntos
Neoplasias Colorretais , Predisposição Genética para Doença , Humanos , Criança , Israel/epidemiologia , Prevalência , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Minorias Desiguais em Saúde e Populações Vulneráveis , Mutação
19.
Pract Lab Med ; 30: e00276, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35509950

RESUMO

A rise in serum creatinine (SCr) is widely used for the detection and definition of evolving acute kidney injury (AKI). Yet, it takes time for SCr to re-adjust in response to changes in glomerular filtration rate (GFR), and subtle transient changes in GFR may remain concealed. Additionally, it cannot differentiate altered glomerular hemodynamics and pre-renal failure from true renal tissue injury, necessitating additional clinical and laboratory diagnostic tools. While these features limit the usefulness of SCr and subsequently estimated GFR (eGFR) at a single time point for the individual patient, their overall pattern of changes along time in a large cohort of hospitalized patients may provide a powerful perspective regarding the detection and assessment of shifting kidney function in this population. Herein we review our experience running large data analyses, evaluating patterns of day-to-day changes in SCr among inpatients, occurring around the exposure to iodinated radiocontrast agents. These large data evaluations helped substantiating the existence of contrast-induced nephropathy in patients with advanced renal failure, underscoring the impact of predisposing and confounding factors. It also provides novel insights regarding a phenomenon of "acute kidney functional recovery" (AKR), and illustrate that the incidence of AKI and AKR along the scale of baseline kidney function co-associates and is inversely proportional to kidney function. This can be attributed to renal functional reserve, which serves as a buffer for up-and-down changes in GFR, forming the physiologic explanation for concealed subclinical AKI.

20.
J Crohns Colitis ; 16(8): 1269-1280, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35143619

RESUMO

BACKGROUND AND AIMS: Ileocolonic resection is frequently needed in the course of Crohn's disease [CD] treatment and post-operative recurrence is extremely common. Our main objective was to analyse gene expression in the mucosa of CD patients at the time of surgery and at post-operative endoscopy, in order to identify predictors and mechanisms of early endoscopic recurrence. METHODS: We conducted transcriptome analyses on ileal mucosa samples collected from inflamed sections of the surgical specimens [n = 200], from ileal resection margins [n = 149] and in the neo-terminal ileum 6 months after surgery [n = 122]; these were compared with non-inflammatory bowel disease controls [n = 25]. The primary endpoint was post-operative endoscopic recurrence at 6 months. We applied regression models to identify gene signatures predicting endoscopic recurrence. RESULTS: Chronic inflammation was associated with strong expression of inflammatory genes [IL-6, IL-8, IL-1B] and decreased expression of genes involved in metabolic processes, but with a high inter-individual heterogeneity. Gene signatures associated with early endoscopic recurrence were mainly characterized by upregulation of TNFα, IFNγ, IL23A and IL17A. Pathway analyses showed that upregulation of mitochondrial dysfunction within the inflamed sections and JAK/STAT at the ileal margin were predictive of post-operative recurrence. A combined model integrating these top pathway signatures improved the prediction of endoscopic recurrence [area under the curve of 0.79]. STAT3 phosphorylation at the surgical ileal margin was associated with severe recurrence at 6 months. CONCLUSION: We identified several biological pathways in surgical ileal mucosa specimens associated with an increased risk of disease recurrence. Integration of the JAK/STAT and mitochondrial dysfunction pathways in the clinical model improved the prediction of post-operative recurrence.


Assuntos
Doença de Crohn , Anastomose Cirúrgica , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Doença de Crohn/cirurgia , Endoscopia Gastrointestinal , Humanos , Íleo/cirurgia , Recidiva , Transcriptoma
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