scholarly journals Terminal Ileum Thickness During Maintenance Therapy Is a Predictive Marker of the Outcome of Infliximab Therapy in Crohn Disease

2020 ◽  
Vol 26 (10) ◽  
pp. 1619-1625
Author(s):  
Ahmad Albshesh ◽  
Bella Ungar ◽  
Shomron Ben-Horin ◽  
Rami Eliakim ◽  
Uri Kopylov ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Crohn Disease ◽  
Terminal Ileum ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Maintenance Phase ◽  
Predictive Marker ◽  
Failure Criteria ◽  
Subsequent Treatment ◽  
Response To Therapy

Abstract Background Mucosal healing has been associated with long-term response to therapy for Crohn disease (CD). However, little is known about the significance of terminal ileum (TI) transmural thickness in predicting clinical outcomes. Methods In this retrospective observational cohort study, we examined the association of an index ultrasonographic assessment of TI thickness during the maintenance phase and the subsequent clinical outcome of CD in a cohort of patients treated with infliximab (IFX). Treatment failure was defined as treatment discontinuation because of lack of efficacy, a need for dose escalation, or surgery. Clinical response was defined as treatment continuation in the absence of any of the aforementioned failure criteria. Results Sixty patients with CD receiving IFX therapy were included in the study. The patients were followed for a median of 16 months (5-24 months) after an index intestinal ultrasound. Thirty-eight patients (63.3%) maintained response to the therapy and 22 patients (36.6%) failed the treatment, with a mean follow up of 10.5 months (6.5-17 months) vs 9.25 months (1-10.25 months), respectively. On univariate analysis, the only variables differing between treatment response and failure were a TI thickness of 2.8 vs 5 mm (P < 0.0001) and an IFX trough level of 6.6 vs 3.9 µg/mL (P = 0.008). On multivariable analysis, only a small bowel thickness of ≥4 mm was associated with the risk of treatment failure (odds ratio, 2.9; 95% CI, 1.49-5.55; P = 0.002). Conclusions Our findings suggest that transmural thickness of ≥4 mm can predict subsequent treatment failure in patients with CD treated using IFX, indicating transmural thickness <4 mm as a potential novel valuable therapeutic target.

Minimizing Carry-Over Effects After Treatment Failure and Maximizing Therapeutic Outcome

2014 ◽  
Vol 222 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Mareile Hofmann ◽  
Nathalie Wrobel ◽  
Simon Kessner ◽  
Ulrike Bingel
Keyword(s):  
Treatment Failure ◽  
Human Subjects ◽  
Subsequent Treatment ◽  
Clinical Samples ◽  
Administration Route ◽  
Healthy Human ◽  
Negative Experiences ◽  
Analgesic Treatment ◽  
Balanced Design ◽  
Carry Over

According to experimental and clinical evidence, the experiences of previous treatments are carried over to different therapeutic approaches and impair the outcome of subsequent treatments. In this behavioral pilot study we used a change in administration route to investigate whether the effect of prior treatment experience on a subsequent treatment depends on the similarity of both treatments. We experimentally induced positive or negative experiences with a topical analgesic treatment in two groups of healthy human subjects. Subsequently, we compared responses to a second, unrelated and systemic analgesic treatment between both the positive and negative group. We found that there was no difference in the analgesic response to the second treatment between the two groups. Our data indicate that a change in administration route might reduce the influence of treatment history and therefore be a way to reduce negative carry-over effects after treatment failure. Future studies will have to validate these findings in a fully balanced design including larger, clinical samples.

Neurophysiological seizure-onset predictors of epilepsy surgery outcome: a multivariable analysis

2020 ◽  
Vol 133 (6) ◽  
pp. 1863-1872 ◽  
Author(s):  
Hideaki Tanaka ◽  
Jean Gotman ◽  
Hui Ming Khoo ◽  
André Olivier ◽  
Jeffery Hall ◽  
...  
Keyword(s):  
Surgical Outcome ◽  
Focal Epilepsy ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Postoperative Outcome ◽  
Seizure Onset ◽  
Resective Surgery ◽  
Scalp Eeg ◽  
Surgery Outcome ◽  
Intracerebral Eeg

OBJECTIVEThe authors sought to determine which neurophysiological seizure-onset features seen during scalp electroencephalography (EEG) and intracerebral EEG (iEEG) monitoring are predictors of postoperative outcome in a large series of patients with drug-resistant focal epilepsy who underwent resective surgery.METHODSThe authors retrospectively analyzed the records of 75 consecutive patients with focal epilepsy, who first underwent scalp EEG and then iEEG (stereo-EEG) for presurgical assessment and who went on to undergo resective surgery between 2004 and 2015. To determine the independent prognostic factors from the neurophysiological scalp EEG and iEEG seizure-onset information, univariate and standard multivariable logistic regression analyses were used. Since scalp EEG and iEEG data were recorded at different times, the authors matched scalp seizures with intracerebral seizures for each patient using strict criteria.RESULTSA total of 3057 seizures were assessed. Forty-eight percent (36/75) of patients had a favorable outcome (Engel class I–II) after a minimum follow-up of at least 1 year. According to univariate analysis, a localized scalp EEG seizure onset (p < 0.001), a multilobar intracerebral seizure-onset zone (SOZ) (p < 0.001), and an extended SOZ (p = 0.001) were significantly associated with surgical outcome. According to multivariable analysis, the following two independent factors were found: 1) the ability of scalp EEG to localize the seizure onset was a predictor of a favorable postoperative outcome (OR 6.073, 95% CI 2.011–18.339, p = 0.001), and 2) a multilobar SOZ was a predictor of an unfavorable outcome (OR 0.076, 95% CI 0.009–0.663, p = 0.020).CONCLUSIONSThe study findings show that localization at scalp seizure onset and a multilobar SOZ were strong predictors of surgical outcome. These predictors can help to select the better candidates for resective surgery.

Carcinoid Tumour of the Terminal Ileum Simulating Crohn Disease

2003 ◽  
Vol 38 (9) ◽  
pp. 1004-1006 ◽  
Author(s):  
Bassi A. ◽  
Loughran C. ◽  
Foster P.
Keyword(s):  
Crohn Disease ◽  
Terminal Ileum ◽  
Carcinoid Tumour

scholarly journals Histologic Remission Is Associated With Lower Risk of Treatment Failure in Patients With Crohn Disease in Endoscopic Remission

2020 ◽  
Author(s):  
Hyuk Yoon ◽  
Sushrut Jangi ◽  
Parambir S Dulai ◽  
Brigid S Boland ◽  
Vipul Jairath ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Crohn Disease ◽  
Lower Risk ◽  
Hazard Analysis ◽  
Cumulative Risk ◽  
Treatment Optimization ◽  
Cox Proportional Hazard ◽  
Endoscopic Remission ◽  
Risk Of Treatment

Abstract Background Although achieving histologic remission in ulcerative colitis is established, the incremental benefit of achieving histologic remission in patients with Crohn disease (CD) treated to a target of endoscopic remission is unclear. We evaluated the risk of treatment failure in patients with CD in clinical and endoscopic remission by histologic activity status. Methods In a single-center retrospective cohort study, we identified adults with active CD who achieved clinical and endoscopic remission through treatment optimization. We evaluated the risk of treatment failure (composite of clinical flare requiring treatment modification, hospitalization, and/or surgery) in patients who achieved histologic remission vs persistent histologic activity through Cox proportional hazard analysis. Results Of 470 patients with active CD, 260 (55%) achieved clinical and endoscopic remission with treatment optimization; 215 patients with histology were included (median age, 33 years; 46% males). Overall, 132 patients (61%) achieved histologic remission. No baseline demographic, disease, or treatment factor was associated with achieving histologic remission. Over a 2-year follow-up, patients with CD in clinical and endoscopic remission who achieved histologic remission experienced a 43% lower risk of treatment failure (1-year cumulative risk: 12.9% vs 18.2%; adjusted hazard ratio, 0.57 [95% confidence interval, 0.35-0.94]) as compared with persistent histologic activity. Conclusions Approximately 61% of patients with active CD who achieved clinical and endoscopic remission with treatment optimization simultaneously achieved histologic remission, which was associated with a lower risk of treatment failure. Whether histologic remission should be a treatment target in CD requires evaluation in randomized trials.

scholarly journals Only peak thyroglobulin concentration on day 1 and 3 of rhTSH-aided RAI adjuvant treatment has prognostic implications in differentiated thyroid cancer

2021 ◽  
Author(s):  
Aleksandra Ledwon ◽  
Ewa Paliczka-Cieślik ◽  
Aleksandra Syguła ◽  
Tomasz Olczyk ◽  
Aleksandra Kropińska ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Treatment Failure ◽  
Adjuvant Treatment ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Distant Metastases ◽  
Thyroid Stimulating Hormone ◽  
Human Thyroid ◽  
Serum Thyroglobulin ◽  
Thyroid Hormone Withdrawal

Abstract Objective In patients with differentiated thyroid carcinoma (DTC), serum thyroglobulin levels measured at the time of remnant ablation after thyroid hormone withdrawal were shown to have prognostic value for disease-free status. We sought to evaluate serial thyroglobulin measurements at the time of recombinant human thyroid-stimulating hormone (rhTSH)-aided iodine 131 (131I) adjuvant treatment as prognostic markers of DTC. Methods Six hundred-fifty patients with DTC given total/near-total thyroidectomy and adjuvant radioiodine post-rhTSH stimulation were evaluated. Thyroglobulin was measured on day 1 (Tg1; at the time of the first rhTSH injection), day 3 (Tg3; 1 day after the second, final rhTSH injection), and day 6 (Tg6; 3 days post-radioiodine administration). Treatment failure was defined as histopathologically confirmed locoregional recurrence, or radiologically-evident distant metastases (signs of disease on computer tomography (CT) or magnetic resonance imaging (MRI), or abnormal foci of radioiodine or [18F] fluorodeoxyglucose ([18F]FDG) uptake. Results In univariate analysis, Tg1 (p < 0.001) and Tg3 (p < 0.001), but not Tg6, were significantly associated with structural recurrence. In multivariate analysis of the overall cohort, only Tg3 was independently associated with structural recurrence. In multivariate analysis of the subgroup (n = 561) with anti-Tg antibodies titers below the institutional cut-off, 115 IU/mL, Tg1 was an independent prognostic marker. Tg1 and Tg3 cutoffs to best predict structural recurrence were established at 0.7 ng/mL and 1.4 ng/mL, respectively. Conclusions Tg1 and Tg3, measurements made after rhTSH stimulation but before radioiodine treatment, independently predict a low risk of treatment failure in patients with DTC. Levels measured post-radioiodine application (e.g., Tg6) are highly variable, lack prognostic value, and hence can be omitted.

scholarly journals Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

2016 ◽  
Vol 397 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Nancy Ahmed ◽  
Julia Dorn ◽  
Rudolf Napieralski ◽  
Enken Drecoll ◽  
Matthias Kotzsch ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Residual Tumor ◽  
Mrna Levels ◽  
Serous Ovarian Cancer ◽  
Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

scholarly journals ATRT-26. META-ANALYSIS OF TREATMENT MODALITIES IN METASTATIC ATYPICAL TERATOID/RHABDOID TUMORS IN CHILDREN

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii281-iii281
Author(s):  
Reena M Underiner ◽  
Mostafa Eltobgy ◽  
Joseph R Stanek ◽  
Jonathan L Finlay ◽  
Mohamed S AbdelBaki
Keyword(s):  
Surgical Resection ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Substantial Effect ◽  
Treatment Modalities ◽  
Risk Of Death ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Abstract BACKGROUND Metastatic atypical teratoid/rhabdoid tumors (AT/RT) are aggressive central nervous system tumors that present during infancy and are associated with dismal outcomes. Patients receive multimodal treatment including surgical resection, systemic chemotherapy and one or more of intrathecal chemotherapy (IT), marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and radiation therapy (XRT). While data regarding treatment modalities for AT/RT patients exist, no comprehensive data have been published regarding the metastatic patient population. METHODS We performed a meta-analysis of 1,578 articles published through September 2018, including 44 studies with a total of 123 subjects. Additionally, seven patients were incorporated through chart review of patients treated at Nationwide Children’s Hospital. RESULTS Analysis of 130 patients revealed a 3-year overall survival (OS) of 25%. Age at diagnosis had a significant impact on survival (p=0.0355); 3-year OS for infants &lt; 18 months was 21%; 18–36 months was 26%; and &gt; 36 months was 36%. Location of the primary tumor, metastatic stage and extent of surgical resection did not have significant impact on OS. On univariate analysis, XRT (p&lt;0.0001), IT (p=0.01) and AuHCR (p&lt;0.0001) were found to significantly improve survival. The most substantial effect was noted in patients who received AuHCR (3-year OS of 60% versus 9% in those who did not). On multivariable analysis XRT (p=0.0006), IT (p=0.0124) and AuHCR (p&lt;0.0001) were independently associated with reduced risk of death.

Abstract WP7: Leukoaraiosis And Outcomes After Intra-arterial Therapy In Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Dan-Victor V Giurgiutiu ◽  
Albert J Yoo ◽  
Kaitlin Fitzpatrick ◽  
Zeshan Chaudhry ◽  
Lee H Schwamm ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Artery Occlusion ◽  
Post Stroke ◽  
Good Functional Outcome ◽  
Grade 3 ◽  
Risk Of Hemorrhage

Background: Selecting patients most likely to benefit (MLTB) from intra-arterial therapy (IAT) is essential to assure favorable outcomes after intervention for acute ischemic stroke (AIS). Leukoaraiosis (LA) has been linked to infarct growth, risk of hemorrhage after IV rt-PA, and poor post-stroke outcomes. We investigated whether LA severity is associated with AIS outcomes after IAT. Methods: We analyzed consecutive AIS subjects from our institutional GWTG-Stroke database enrolled between 01/01/2007-06/30/2009, who met our pre-specified criteria for MLTB: CTA and MRI within 6 hours from last known well, NIHSS score ≥8, baseline DWI volume (DWIv) ≤ 100 cc, and proximal artery occlusion and were treated with IAT. LA volume (LAv) was assessed on FLAIR using validated, semi-automated protocols. We analyzed CTA to assess collateral grade; post-IAT angiogram for recanalization status (TICI score ≥2B); and the 24-hour CT for symptomatic ICH (sICH). Logistic regression was used to determine independent predictors of good functional outcome (mRS≤ 2) and mortality at 90 days post-stroke. Results: There were 48 AIS subjects in this analysis (mean age 69.2, SD±13.8; 55% male; median LAv 4cc, IQR 2.2-8.8cc; median NIHSS 15, IQR 13-19; median DWIv 15.4cc, IQR 9.2-20.3cc). Of these, 34 (72%) received IV rt-PA; 3 (6%) had sICH; 21 (44.7%) recanalized; and 23 (50%) had collateral grade ≥3. At 90 days, 15/48 (36.6%) were deceased and 15/48 had mRS≤ 2. In univariate analysis, recanalization (OR 6.2, 95%CI 1.5-25.5), NIHSS (OR 0.8 per point, 95%CI 0.64-0.95), age (OR 0.95 per yr, 95%CI 0.89-0.99) were associated with good outcome, whereas age (OR 1.1, 95%CI 1.01-1.14) and HTN (OR 5.6, 95%CI 1.04-29.8) were associated with mortality. In multivariable analysis including age, NIHSS, recanalization, collateral grade, and LAv, only recanalization independently predicted good functional outcome (OR 21.3, 95%CI 2.3-199.9) and reduced mortality (OR 0.15, 95%CI 0.02-1.12) after IAT. Conclusions: LA severity is not associated with poor outcome in patients selected MLTB for IAT. Among AIS patients considered likely to benefit from IAT, only recanalization independently predicted good functional outcome and decreased mortality.

TERT promoter mutation as a prognostic marker in patients with advanced urothelial carcinoma treated with immune checkpoint inhibitors.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 476-476
Author(s):  
Ivan de Kouchkovsky ◽  
Li Zhang ◽  
Errol Philip ◽  
Francis Wright ◽  
Daniel Myung Kim ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Genomic Profiling ◽  
Clinical Variables ◽  
Tert Promoter ◽  
Visceral Metastases

476 Background: Reliable predictive markers are lacking in patients (pts) with locally advanced or metastatic urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICI). We sought to determine whether specific genomic alterations could be used to predict overall survival (OS) in this patient population. Methods: We undertook a retrospective cohort study of pts with aUC who received ICI and underwent genomic profiling by next-generation sequencing (NGS). All patients underwent NGS using commercially available platforms (e.g. Foundation Medicine, Strata, Invitae), or testing on the CLIA-certified institutional panel UCSF500. Associations between the 20 most frequently altered genes and OS were first examined by Cox regression. Genes with a p <0.1 on univariate analysis and relevant clinical variables were then included in a multivariable analysis. Results: We identified 78 pts treated with ICI for aUC with available genomic profiling results. Median age at ICI initiation was 71; the majority of patients had visceral metastases (70.5%), ECOG performance status ≤1 (62.8%) and received ICI in the post-platinum setting (52.6%). Objective response rate in this cohort was 35.9%, median progression free survival was 4.0 months (95% CI 2.6-10.5) and median OS was 17.5 months (95% CI 14.1-NR) from ICI start. The most commonly altered genes were the TERT promoter (TERTp) (61%), TP53 (52%), RB1 (31%), CDKN2A(29%) and CDKN2B (27%). On univariable analysis there was a trend towards longer OS in pts with TERTp mutations (HR 0.53, 95% CI 0.27-1.06, p = 0.07), and shorter OS in pts with CDKN2B mutations (HR 1.91, 95% CI 0.98-3.73, p = 0.06). Both mutations were included in a multivariable analysis. After adjusting for known prognostic variables (ECOG PS, visceral metastases, albumin, hemoglobin, body mass index [BMI], neutrophil to lymphocyte ratio [NLR], and histology), the presence of a TERTp mutation was significantly associated with improved OS (HR 0.30, 95% CI 0.10-0.93, p = 0.04; Table). Conclusions: The presence of a TERTp mutation was an independent predictor of improved OS in a cohort of aUC pts treated with ICI. Other common mutations and clinical variables were not associated with OS on a multivariable analysis. These findings are hypothesis-generating and prospective validation is needed. [Table: see text]

Primary Epstein-Barr Virus–Associated Hodgkin Disease of the Ileum Complicating Crohn Disease

2001 ◽  
Vol 125 (3) ◽  
pp. 424-427 ◽  
Author(s):  
Shiyong Li ◽  
Michael J. Borowitz
Keyword(s):  
Lymph Node ◽  
Crohn Disease ◽  
Terminal Ileum ◽  
Messenger Rna ◽  
Epstein Barr Virus ◽  
Hodgkin Disease ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection

Abstract We describe a case of primary Hodgkin disease of the terminal ileum in a 38-year-old man with Crohn disease of 24 years' duration. The infiltrate was located in an ulcerated fistula involving the terminal ileum and urinary bladder. Reed-Sternberg cells and their variants were characteristically positive for CD15, fascin, and CD30 and showed focal positivity for CD20. Epstein-Barr virus messenger RNA was also detected in the neoplastic cells. Staging revealed no evidence of other lymph node or organ involvement. Although rare, primary gastrointestinal Hodgkin disease arising in the setting of Crohn disease may have a stronger association with Epstein-Barr virus infection than conventional Hodgkin disease.

Sign in / Sign up

Export Citation Format

Share Document