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4. A New Approach to Estimate Semi-Parametric Gaussian Mixtures of Regressions with Varying Mixing Proportions

Author

Skhosana, Sphiwe B., Millard, Salomon M., Kanfer, Frans H. J., Chen, Ding-Geng, Editor-in-Chief, Bekker, Andriëtte, Editorial Board Member, Coelho, Carlos A., Editorial Board Member, Finkelstein, Maxim, Editorial Board Member, Wilson, Jeffrey R., Editorial Board Member, Ng, Hon Keung Tony, Series Editor, and Lio, Yuhlong, Editorial Board Member

Published
2024
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7. Longitudinal microbiome investigation throughout prion disease course reveals pre- and symptomatic compositional perturbations linked to short-chain fatty acid metabolism and cognitive impairment in mice

Author

Marco Losa, Yasser Morsy, Marc Emmenegger, Salomon M. Manz, Petra Schwarz, Adriano Aguzzi, and Michael Scharl

Subjects
gut–brain–microbiome axis, microbiome, fecal 16S rRNA seq, metabolism, short-chain fatty acids, prion disease, Microbiology, QR1-502
Abstract

Commensal intestinal bacteria shape our microbiome and have decisive roles in preserving host metabolic and immune homeostasis. They conspicuously impact disease development and progression, including amyloid-beta (Aβ) and alpha (α)-synuclein pathology in neurodegenerative diseases, conveying the importance of the brain–gut–microbiome axis in such conditions. However, little is known about the longitudinal microbiome landscape and its potential clinical implications in other protein misfolding disorders, such as prion disease. We investigated the microbiome architecture throughout prion disease course in mice. Fecal specimens were assessed by 16S ribosomal RNA sequencing. We report a temporal microbiome signature in prion disease and uncovered alterations in Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, and Muribaculaceae family members in this disease. Moreover, we determined the enrichment of Bilophila, a microorganism connected to cognitive impairment, long before the clinical manifestation of disease symptoms. Based on temporal microbial abundances, several associated metabolic pathways and resulting metabolites, including short-chain fatty acids, were linked to the disease. We propose that neuroinflammatory processes relate to perturbations of the intestinal microbiome and metabolic state by an interorgan brain–gut crosstalk. Furthermore, we describe biomarkers possibly suitable for early disease diagnostics and anti-prion therapy monitoring. While our study is confined to prion disease, our discoveries might be of equivalent relevance in other proteinopathies and central nervous system pathologies.

Published
2024
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8. Seeing the Trees From the Forest: Challenges in Subgroup Analysis-Based Guidelines in Oncology

Author

Ofer Rotem, Karyn Revital Geiger, Ekaterina Hanovich, Mor Moskovitz, Noga Kurman, Daniel Reinhorn, Idit Peretz, Rinat Yerushalmi, and Salomon M. Stemmer

Subjects
cancer, clinical outcomes, clinical trial, guidelines, reporting, subanalysis, Other systems of medicine, RZ201-999, Internal medicine, RC31-1245
Abstract

As clinical trials in oncology require substantial efforts, maximizing the insights gained from them by conducting subgroup analyses is often attempted. The goal of these analyses is to identify subgroups of patients who are likely to benefit, as well as the subgroups of patients who are unlikely to benefit from the studied intervention. International guidelines occasionally include or exclude novel medications and technologies for specific subpopulations based on such analyses of pivotal trials without requiring confirmatory trials. This Perspective discusses the importance of providing a complete dataset of clinical information when reporting subgroup analyses and explains why such transparency is key for better clinical interpretation of the results and the appropriate application to clinical care, by providing examples of transparent reporting of clinical studies and examples of incomplete reporting of clinical studies.

Published
2024
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10. Reducing Skin Toxicities from EGFR Inhibitors with Topical BRAF Inhibitor TherapyTopical BRAF Inhibitor for Anti-EGFR Toxicities

Author

Lacouture, Mario E, Wainberg, Zev A, Patel, Anisha B, Anadkat, Milan J, Stemmer, Salomon M, Shacham-Shmueli, Einat, Medina, Egmidio, Zelinger, Galit, Shelach, Noa, and Ribas, Antoni

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Digestive Diseases, Clinical Trials and Supportive Activities, Cancer, Clinical Research, Colo-Rectal Cancer, 6.1 Pharmaceuticals, Skin, Adult, Aged, Female, Humans, Male, Middle Aged, Acneiform Eruptions, Administration, Cutaneous, Antineoplastic Agents, Immunological, Cetuximab, Colorectal Neoplasms, Dermatologic Agents, ErbB Receptors, Panitumumab, Proto-Oncogene Proteins B-raf, Treatment Outcome, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Treatment of cancer with EGFR inhibitors is limited by on-target skin toxicities induced by inhibition of the MAPK pathway. BRAF inhibitors are known to paradoxically activate the MAPK downstream of EGFR, which we confirmed using human skin keratinocytes. We then conducted a phase I clinical trial testing the hypothesis that topical therapy with the BRAF inhibitor LUT014 could improve skin toxicities induced by EGFR inhibitors. Ten patients with metastatic colorectal cancer who had developed acneiform rash while being treated with cetuximab or panitumumab were enrolled in three cohorts. LUT014 was well tolerated, and there were no dose-limiting toxicities. The acneiform rash improved in the 6 patients who started with grade 2 rash in the low and intermediate cohorts. We conclude that topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation. SIGNIFICANCE: BRAF inhibitor topical therapy could avoid dose reductions of EGFR inhibitors, locally treating the main dose-limiting skin toxicity of this class of agents.This article is highlighted in the In This Issue feature, p. 2113.

Published
2021

11. Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes—exploratory analysis of the Clalit registry

Author

Shlomit S. Shachar, Michelle Leviov, Rinat Yerushalmi, Karen Drumea, Margarita Tokar, Lior Soussan-Gutman, Avital Bareket-Samish, Amir Sonnenblick, Noa Ben-Baruch, Ella Evron, Einav Nili Gal-Yam, Shani Paluch-Shimon, Gil Bar-Sela, Hadar Goldvaser, and Salomon M. Stemmer

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a ‘study-cohort’ (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a ‘general 21-gene-tested BC-cohort’ (2044 previously described N0/N1mi/N1 patients). The median time between the first and second BC was 5.2 (IQR, 3.1–7.1) years; the second BC was ipsilateral in 68%. Patient/tumor characteristics of the first- and second-BC in the ‘study-cohort’ were similar, except for the RS which was higher in the second BC (median [IQR]: 23 [17–30] vs 17 [14–22], p

Published
2023
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12. Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers

Author

Harding, James J., Piha-Paul, Sarina A., Shah, Ronak H., Murphy, Jessica J., Cleary, James M., Shapiro, Geoffrey I., Quinn, David I., Braña, Irene, Moreno, Victor, Borad, Mitesh, Loi, Sherene, Spanggaard, Iben, Park, Haeseong, Ford, James M., Arnedos, Mónica, Stemmer, Salomon M., de la Fouchardiere, Christelle, Fountzilas, Christos, Zhang, Jie, DiPrimeo, Daniel, Savin, Casey, Duygu Selcuklu, S., Berger, Michael F., Eli, Lisa D., Meric-Bernstam, Funda, Jhaveri, Komal, Solit, David B., and Abou-Alfa, Ghassan K.

Published
2023
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13. Clinical outcomes in estrogen receptor-positive early-stage breast cancer patients with Recurrence Score 26-30: observational real-world cohort study

Author

Ofer Rotem, Idit Peretz, Michelle Leviov, Iryna Kuchuk, Amit Itay, Margarita Tokar, Shani Paluch-Shimon, Ofra Maimon, Rinat Yerushalmi, Karen Drumea, Ella Evron, Amir Sonnenblick, Einav Gal-Yam, Hadar Goldvaser, Yosef Samih, Rotem Merose, Avital Bareket-Samish, Lior Soussan-Gutman, and Salomon M. Stemmer

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Data on adjuvant chemotherapy (CT) benefit in ER + HER2‒ early-stage breast cancer (EBC) patients with Recurrence Score (RS) 26-30 are limited. This real-world study evaluated the relationships between the RS, adjuvant treatments, and outcomes in 534 RS 26-30 patients tested through Clalit Health Services (N0: n = 394, 49% CT-treated; N1mi/N1: n = 140, 62% CT-treated). The CT-treated and untreated groups were imbalanced (more high-risk clinicopathologic characteristics in CT-treated patients). With median follow-up of 8 years, Kaplan–Meier estimates for overall survival (OS), distant recurrence-free survival (DRFS), and BC-specific mortality (BCSM) were not significantly different between CT-treated and untreated N0 patients. Seven-year rates (95% CI) in CT-treated vs untreated: OS, 97.9% (94.4–99.2%) vs 97.9% (94.6–99.2%); DRFS, 91.5% (86.6–94.7%) vs 91.2% (86.0–94.6%); BCSM, 0.5% (0.1–3.7%) vs 1.6% (0.5–4.7%). For N1mi/N1 patients, OS/DRFS did not differ significantly between treatment groups; whereas BCSM did (1.3% [0.2–8.6%] vs 6.2% [2.0–17.7%] for CT-treated and untreated patients, respectively, p = 0.024).

Published
2023
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14. High-Resolution Genomic Profiling of Liver Cancer Links Etiology With Mutation and Epigenetic SignaturesSummary

Author

Shira Perez, Anat Lavi-Itzkovitz, Moriah Gidoni, Tom Domovitz, Roba Dabour, Ishant Khurana, Ateret Davidovich, Ana Tobar, Alejandro Livoff, Evgeny Solomonov, Yaakov Maman, Assam El-Osta, Yishan Tsai, Ming-Lung Yu, Salomon M. Stemmer, Izhak Haviv, Gur Yaari, and Meital Gal-Tanamy

Subjects
Hepatocellular Carcinoma (HCC), Hepatitis C Virus (HCV), Cancer Epigenetics, Cancer Genomics, Regional Variation in Mutation Rates, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: Hepatocellular carcinoma (HCC) is a model of a diverse spectrum of cancers because it is induced by well-known etiologies, mainly hepatitis C virus (HCV) and hepatitis B virus. Here, we aimed to identify HCV-specific mutational signatures and explored the link between the HCV-related regional variation in mutations rates and HCV-induced alterations in genome-wide chromatin organization. Methods: To identify an HCV-specific mutational signature in HCC, we performed high-resolution targeted sequencing to detect passenger mutations on 64 HCC samples from 3 etiology groups: hepatitis B virus, HCV, or other. To explore the link between the genomic signature and genome-wide chromatin organization we performed chromatin immunoprecipitation sequencing for the transcriptionally permissive H3K4Me3, H3K9Ac, and suppressive H3K9Me3 modifications after HCV infection. Results: Regional variation in mutation rate analysis showed significant etiology-dependent regional mutation rates in 12 genes: LRP2, KRT84, TMEM132B, DOCK2, DMD, INADL, JAK2, DNAH6, MTMR9, ATM, SLX4, and ARSD. We found an enrichment of C->T transversion mutations in the HCV-associated HCC cases. Furthermore, these cases showed regional variation in mutation rates associated with genomic intervals in which HCV infection dictated epigenetic alterations. This signature may be related to the HCV-induced decreased expression of genes encoding key enzymes in the base excision repair pathway. Conclusions: We identified novel distinct HCV etiology-dependent mutation signatures in HCC associated with HCV-induced alterations in histone modification. This study presents a link between cancer-causing mutagenesis and the increased predisposition to liver cancer in chronic HCV-infected individuals, and unveils novel etiology-specific mechanisms leading to HCC and cancer in general.

Published
2023
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19. Efficient Estimation and Validation of Shrinkage Estimators in Big Data Analytics

Author

Salomi du Plessis, Mohammad Arashi, Gaonyalelwe Maribe, and Salomon M. Millard

Subjects
big data, efficient computation, Liu estimator, matrix of sufficient statistics, multicollinearity, ridge estimator, Mathematics, QA1-939
Abstract

Shrinkage estimators are often used to mitigate the consequences of multicollinearity in linear regression models. Despite the ease with which these techniques can be applied to small- or moderate-size datasets, they encounter significant challenges in the big data domain. Some of these challenges are that the volume of data often exceeds the storage capacity of a single computer and that the time required to obtain results becomes infeasible due to the computational burden of a high volume of data. We propose an algorithm for the efficient model estimation and validation of various well-known shrinkage estimators to be used in scenarios where the volume of the data is large. Our proposed algorithm utilises sufficient statistics that can be computed and updated at the row level, thus minimizing access to the entire dataset. A simulation study, as well as an application on a real-world dataset, illustrates the efficiency of the proposed approach.

Published
2023
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20. IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy

Author

Jacob Berger, Adi, Gigi, Elinor, Kupershmidt, Lana, Meir, Zohar, Gavert, Nancy, Zwang, Yaara, Prior, Amir, Gilad, Shlomit, Harush, Uzi, Haviv, Izhak, Stemmer, Salomon M., Blum, Galia, Merquiol, Emmanuelle, Mardamshina, Mariya, Kaminski Strauss, Sivan, Friedlander, Gilgi, Bar, Jair, Kamer, Iris, Reizel, Yitzhak, Geiger, Tamar, Pilpel, Yitzhak, Levin, Yishai, Tanay, Amos, Barzel, Baruch, Reuveni, Hadas, and Straussman, Ravid

Published
2021
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22. Three-month follow-up of durability of response to the third dose of the SARS-CoV-2 BNT162b2 vaccine in adults aged 60 years and older: a prospective cohort study

Author

Noa Eliakim-Raz, Haim Ben-Zvi, Erez Bar-Haim, Salomon M Stemmer, Amos Stemmer, Yaara Leibovici-Weisman, Asaf Ness, Muhammad Awwad, Nassem Ghantous, Noam Erez, Avital Bareket-Samish, Adva Levy-Barda, and Neta Moskovits

Subjects
Medicine
Abstract

Objective To evaluate the durability of response 3 months after the third BNT162b2 vaccine in adults aged 60 years and older.Design Prospective cohort study.Setting Single tertiary centre.Participants Healthcare workers/family members aged ≥60 years old who received the third BNT162b2 dose.Interventions Blood samples were drawn immediately before (T0), 10–19 days (T1) and 74–103 days (T2) after the third dose.Primary and secondary outcome measures Anti-spike IgG titres were determined using a commercial assay and seropositivity was defined as ≥50 arbitrary units (AU)/mL. Neutralising antibody titres were determined at T2. Adverse events, COVID-19 infections and Clinical Frailty Scale (CFS) levels were documented.Results The analysis included 97 participants (median age, 70 years (IQR, 66–74), 58% CFS level 2). IgG titres, which increased significantly from T0 to T1 (median, 440 AU/mL (IQR, 294–923) and median, 25 429 AU/mL (IQR, 14 203–36 114), respectively; p

Published
2022
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24. Interim analysis (IA) of the giredestrant (G) + everolimus (EVERO) arm in MORPHEUS Breast Cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC).

Author

Wander, Seth Andrew, primary, Stemmer, Salomon M., additional, Rugo, Hope S., additional, Im, Seock-Ah, additional, Lau, Peter Kar Han, additional, Paluch-Shimon, Shani, additional, Cahuzac, Clélia, additional, Collier, Annie, additional, Shah, Mona D., additional, Ngo, Huy X., additional, Schwab, Richard B., additional, Zhu, Jing, additional, and Oliveira, Mafalda, additional

Published
2024
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25. Development and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer.

Author

Pusztai, Lajos, primary, Hoag, Jess R, additional, Albain, Kathy S., additional, Barlow, William E., additional, Stemmer, Salomon M., additional, Meisner, Allison, additional, Hortobagyi, Gabriel N., additional, Shak, Steven, additional, Hayes, Daniel F., additional, Rae, James M., additional, Baehner, Frederick, additional, Sharma, Priyanka, additional, and Kalinsky, Kevin, additional

Published
2024
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27. Proteinoid Polymers and Nanocapsules for Cancer Diagnostics, Therapy and Theranostics: In Vitro and In Vivo Studies

Author

Ella Itzhaki, Yuval Elias, Neta Moskovits, Salomon M. Stemmer, and Shlomo Margel

Subjects
proteinoid polymers, proteinoid nanocapsules, fluorescent nanocarriers, cancer theranostics, RGD nanoparticles, Biotechnology, TP248.13-248.65, Medicine (General), R5-920
Abstract

Proteinoids—simple polymers composed of amino acids—were suggested decades ago by Fox and coworkers to form spontaneously by heat. These special polymers may self-assemble in micrometer structures called proteinoid microspheres, presented as the protocells of life on earth. Interest in proteinoids increased in recent years, in particular for nano-biomedicine. They were produced by stepwise polymerization of 3–4 amino acids. Proteinoids based on the RGD motif were prepared for targeting tumors. Nanocapsules form by heating proteinoids in an aqueous solution and slowly cooling to room temperature. Proteinoid polymers and nanocapsules suit many biomedical applications owing to their non-toxicity, biocompatibility and immune safety. Drugs and/or imaging reagents for cancer diagnostic, therapeutic and theranostic applications were encapsulated by dissolving them in aqueous proteinoid solutions. Here, recent in vitro and in vivo studies are reviewed.

Published
2023
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29. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial

Author

Bockorny, Bruno, Semenisty, Valerya, Macarulla, Teresa, Borazanci, Erkut, Wolpin, Brian M., Stemmer, Salomon M., and Golan, Talia

Subjects
Testing, Drug therapy, Health aspects, Pancreatic cancer -- Drug therapy, Combination drug therapy -- Testing -- Health aspects, Antagonists (Biochemistry) -- Testing -- Health aspects, Pembrolizumab -- Testing, Chemokine receptors -- Health aspects, Drug therapy, Combination -- Testing -- Health aspects
Abstract

Author(s): Bruno Bockorny [sup.1] [sup.2] , Valerya Semenisty [sup.3] , Teresa Macarulla [sup.4] , Erkut Borazanci [sup.5] [sup.6] , Brian M. Wolpin [sup.2] [sup.7] , Salomon M. Stemmer [sup.8] [sup.9] [...], Programmed cell death 1 (PD-1) inhibitors have limited effect in pancreatic ductal adenocarcinoma (PDAC), underscoring the need to co-target alternative pathways. CXC chemokine receptor 4 (CXCR4) blockade promotes T cell tumor infiltration and is synergistic with anti-PD-1 therapy in PDAC mouse models. We conducted a phase IIa, open-label, two-cohort study to assess the safety, efficacy and immunobiological effects of the CXCR4 antagonist BL-8040 (motixafortide) with pembrolizumab and chemotherapy in metastatic PDAC ((https://clinicaltrials.gov/ct2/show/NCT02826486?term=NCT02826486)). The primary outcome was objective response rate (ORR). Secondary outcomes were overall survival (OS), disease control rate (DCR) and safety. In cohort 1, 37 patients with chemotherapy-resistant disease received BL-8040 and pembrolizumab. The DCR was 34.5% in the evaluable population (modified intention to treat, mITT; N = 29), including nine patients (31%) with stable disease and one patient (3.4%) with partial response. Median OS (mOS) was 3.3 months in the ITT population. Notably, in patients receiving study drugs as second-line therapy, the mOS was 7.5 months. BL-8040 increased CD8.sup.+ effector T cell tumor infiltration, decreased myeloid-derived suppressor cells (MDSCs) and further decreased circulating regulatory T cells. In cohort 2, 22 patients received BL-8040 and pembrolizumab with chemotherapy, with an ORR, DCR and median duration of response of 32%, 77% and 7.8 months, respectively. These data suggest that combined CXCR4 and PD-1 blockade may expand the benefit of chemotherapy in PDAC and warrants confirmation in subsequent randomized trials. Results from the phase IIa COMBAT trial combining CXCR4 and PD-1 inhibition in patients with metastatic cancer show encouraging clinical responses in association with enhanced antitumor immune activation.

Published
2020
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30. Longitudinal microbiome investigation throughout prion disease course reveals pre- and symptomatic compositional perturbations linked to short-chain fatty acid metabolism and cognitive impairment in mice

Author

Losa, Marco; https://orcid.org/0000-0003-3428-418X, Morsy, Yasser; https://orcid.org/0000-0001-8234-1877, Emmenegger, Marc; https://orcid.org/0000-0002-6073-8811, Manz, Salomon M, Schwarz, Petra; https://orcid.org/0000-0003-1686-8624, Aguzzi, Adriano; https://orcid.org/0000-0002-0344-6708, Scharl, Michael; https://orcid.org/0000-0002-6729-1469, Losa, Marco; https://orcid.org/0000-0003-3428-418X, Morsy, Yasser; https://orcid.org/0000-0001-8234-1877, Emmenegger, Marc; https://orcid.org/0000-0002-6073-8811, Manz, Salomon M, Schwarz, Petra; https://orcid.org/0000-0003-1686-8624, Aguzzi, Adriano; https://orcid.org/0000-0002-0344-6708, and Scharl, Michael; https://orcid.org/0000-0002-6729-1469

Published
2024

31. A Novel EM-Type Algorithm to Estimate Semi-Parametric Mixtures of Partially Linear Models

Author

Sphiwe B. Skhosana, Salomon M. Millard, and Frans H. J. Kanfer

Subjects
mixture of regressions, EM algorithm, partial linear models, semi-parametric, local likelihood, label-switching, Mathematics, QA1-939
Abstract

Semi- and non-parametric mixture of normal regression models are a flexible class of mixture of regression models. These models assume that the component mixing proportions, regression functions and/or variances are non-parametric functions of the covariates. Among this class of models, the semi-parametric mixture of partially linear models (SPMPLMs) combine the desirable interpretability of a parametric model and the flexibility of a non-parametric model. However, local-likelihood estimation of the non-parametric term poses a computational challenge. Traditional EM optimisation of the local-likelihood functions is not appropriate due to the label-switching problem. Separately applying the EM algorithm on each local-likelihood function will likely result in non-smooth function estimates. This is because the local responsibilities calculated at the E-step of each local EM are not guaranteed to be aligned. To prevent this, the EM algorithm must be modified so that the same (global) responsibilities are used at each local M-step. In this paper, we propose a one-step backfitting EM-type algorithm to estimate the SPMPLMs and effectively address the label-switching problem. The proposed algorithm estimates the non-parametric term using each set of local responsibilities in turn and then incorporates a smoothing step to obtain the smoothest estimate. In addition, to reduce the computational burden imposed by the use of the partial-residuals estimator of the parametric term, we propose a plug-in estimator. The performance and practical usefulness of the proposed methods was tested using a simulated dataset and two real datasets, respectively. Our finite sample analysis revealed that the proposed methods are effective at solving the label-switching problem and producing reasonable and interpretable results in a reasonable amount of time.

Published
2023
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32. Nanohertz Frequency Determination for the Gravity Probe B HF SQUID Signal

Author

Salomon, M., Conklin, J. W., Kozaczuk, J., Berberian, J. E., Santiago, D. I., Keiser, G. M., Silbergleit, A. S., and Worden, P.

Subjects
Physics - Instrumentation and Detectors, Physics - Data Analysis, Statistics and Probability
Abstract

In this paper, we present a method to measure the frequency and the frequency change rate of a digital signal. This method consists of three consecutive algorithms: frequency interpolation, phase differencing, and a third algorithm specifically designed and tested by the authors. The succession of these three algorithms allowed a 5 parts in 10^10 resolution in frequency determination. The algorithm developed by the authors can be applied to a sampled scalar signal such that a model linking the harmonics of its main frequency to the underlying physical phenomenon is available. This method was developed in the framework of the Gravity Probe B (GP-B) mission. It was applied to the High Frequency (HF) component of GP-B's Superconducting QUantum Interference Device (SQUID) signal, whose main frequency fz is close to the spin frequency of the gyroscopes used in the experiment. A 30 nHz resolution in signal frequency and a 0.1 pHz/sec resolution in its decay rate were achieved out of a succession of 1.86 second-long stretches of signal sampled at 2200 Hz. This paper describes the underlying theory of the frequency measurement method as well as its application to GP-B's HF science signal., Comment: The following article has been submitted to Review of Scientific Instruments. After it is published, it will be found at (http://rsi.aip.org/)

Published
2011
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33. Factors Associated With Off-Label Oncology Prescriptions: The Role of Cost and Financing in a Universal Healthcare System

Author

Noa Gordon, Daniel A. Goldstein, Boaz Tadmor, Salomon M. Stemmer, and Dan Greenberg

Subjects
cancer, off-label, cost, reimbursement, universal healthcare system, Therapeutics. Pharmacology, RM1-950
Abstract

Purpose: Various solutions have been put forward for prescribing and reimbursing treatments outside their registered indications within universal healthcare systems. However, most off-label oncology prescriptions are not reimbursed by health funds. This study characterized the financing sources of off-label oncology use and the predictors of the decision to forego treatment.Materials and Methods: All 708 off-label oncology requests submitted for approval in a large tertiary cancer center in Israel between 2016 and 2018 were examined for disease and patient sociodemographic characteristics, costs and financing sources, and the factors predicting actual off-label drug administration using multivariate logistic regression analysis.Results: The mean monthly cost of a planned off-label treatment was ILS54,703 (SD = ILS61,487, median = ILS39,928) (approximately US$ 15,500). The main sources of funding were private health insurance (25%) and expanded access pharma company plans (30%). Approximately one third (31%) of the requests did not have a financing source at the time of approval. Of the 708 requests, 583 (or 82%) were filled and treatment was initiated. Predictors for forgoing treatment were the impossibility of out-of-pocket payments or the lack of a financing solution (OR = 0.407; p = 0.005 and OR = 0.400; p < 0.0005).Conclusion: Although off-label recommendations are widespread and institutional approval is often granted, a large proportion of these prescriptions are not filled. In a universal healthcare system, the financing sources for off-label treatments are likely to influence access.

Published
2021
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34. Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

Author

Greijdanus, N, Wienholts, K, Ubels, S, Talboom, K, Hannink, G, Wolthuis, A, de Lacy, F, Lefevre, J, Solomon, M, Frasson, M, Rotholtz, N, Denost, Q, Perez, R, Konishi, T, Panis, Y, Rutegard, M, Hompes, R, Rosman, C, van Workum, F, Tanis, P, de Wilt, J, Bremers, A, Ferenschild, F, de Vriendt, S, D'Hoore, A, Bislenghi, G, Farguell, J, Lacy, A, Atienza, P, van Kessel, C, Parc, Y, Voron, T, Collard, M, Muriel, J, Cholewa, H, Mattioni, L, Frontali, A, Polle, S, Polat, F, Obihara, N, Vailati, B, Kusters, M, Tuynmann, J, Hazen, S, Gruter, A, Amano, T, Fujiwara, H, Salomon, M, Ruiz, H, Gonzalez, R, Estefania, D, Avellaneda, N, Carrie, A, Santillan, M, Pachajoa, D, Parodi, M, Gielis, M, Binder, A, Gurtler, T, Riedl, P, Badiani, S, Berney, C, Morgan, M, Hollington, P, da Silva, N, Nair, G, Ho, Y, Lamparelli, M, Kapadia, R, Kroon, H, Dudi-Venkata, N, Liu, J, Sammour, T, Flamey, N, Pattyn, P, Chaoui, A, Vansteenbrugge, L, van den Broek, N, Vanclooster, P, de Gheldere, C, Pletinckx, P, Defoort, B, Dewulf, M, Slavchev, M, Belev, N, Atanasov, B, Krastev, P, Sokolov, M, Maslyankov, S, Gribnev, P, Pavlov, V, Ivanov, T, Karamanliev, M, Filipov, E, Tonchev, P, Aigner, F, Mitteregger, M, Allmer, C, Seitinger, G, Colucci, N, Buchs, N, Ris, F, Toso, C, Gialamas, E, Vuagniaux, A, Chautems, R, Sauvain, M, Daester, S, von Flue, M, Guenin, M, Taha-Mehlitz, S, Hess, G, Martinek, L, Skrovina, M, Machackova, M, Bencurik, V, Uluk, D, Pratschke, J, Dittrich, L, Guel-Klein, S, Perez, D, Grass, J, Melling, N, Mueller, S, Iversen, L, Eriksen, J, Baatrup, G, Al-Najami, I, Bjorsum-Meyer, T, Teras, J, Teras, R, Monib, F, Ahmed, N, Alkady, E, Ali, A, Khedr, G, Abdelaal, A, Ashoush, F, Ewedah, M, Elshennawy, E, Hussein, M, Fernandez-Martinez, D, Garcia-Florez, L, Fernandez-Hevia, M, Suarez-Sanchez, A, Aretxabala, I, Docampo, I, Zabala, J, Tejedor, P, Morales Bernaldo de Quiros, J, Quiroga, I, Navarro-Sanchez, A, Darias, I, Fernandez, C, de La Cruz Cuadrado, C, Sanchez-Guillen, L, Lopez-Rodriguez-Arias, 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Fioravanti, E, Rottoli, M, Romano, A, Tanzanu, M, Belvedere, A, Mariani, N, Ceretti, A, Opocher, E, Gallo, G, Sammarco, G, de Paola, G, Pucciarelli, S, Marchegiani, F, Spolverato, G, Buzzi, G, Di Saverio, S, Meroni, P, Parise, C, Bottazzoli, E, Lapolla, P, Brachini, G, Cirillo, B, Mingoli, A, Sica, G, Siragusa, L, Bellato, V, Cerbo, D, de Pasqual, C, de Manzoni, G, di Cosmo, M, Alrayes, B, Qandeel, M, Hani, M, Rabadi, A, el Muhtaseb, M, Abdeen, B, Karmi, F, Zilinskas, J, Latkauskas, T, Tamelis, A, Pikuniene, I, Slenfuktas, V, Poskus, T, Kryzauskas, M, Jakubauskas, M, Mikalauskas, S, Jakubauskiene, L, Hassan, S, Altrabulsi, A, Abdulwahed, E, Ghmagh, R, Deeknah, A, Alshareea, E, Elhadi, M, Abujamra, S, Msherghi, A, Tababa, O, Majbar, M, Souadka, A, Benkabbou, A, Mohsine, R, Echiguer, S, Moctezuma-Velazquez, P, Salgado-Nesme, N, Vergara-Fernandez, O, Sainz-Hernandez, J, Alvarez-Bautista, F, Zakaria, A, Zakaria, Z, Wong, M, Ismail, R, Ibrahim, A, Abdullah, N, Julaihi, R, Bhat, S, O'Grady, G, Bissett, I, Lamme, B, Musters, G, Dinaux, A, Grotenhuis, B, Steller, E, Aalbers, A, Leeuwenburgh, M, Rutten, H, Burger, J, Bloemen, J, Ketelaers, S, Waqar, U, Chawla, T, Rauf, H, Rani, P, Talsma, A, Scheurink, L, van Praagh, J, Segelman, J, Nygren, J, Anderin, K, Tiefenthal, M, de Andres, B, Beltran de Heredia, J, Vazquez, A, Gomez, T, Golshani, P, Kader, R, Mohamed, A, Westerterp, M, Marinelli, A, Niemer, Q, Doornebosch, P, Shapiro, J, Vermaas, M, de Graaf, E, van Westreenen, H, Zwakman, M, van Dalsen, A, Vles, W, Nonner, J, Toorenvliet, B, Janssen, P, Verdaasdonk, E, Amelung, F, Peeters, K, Bahadoer, R, Holman, F, Heemskerk, J, Vosbeek, N, Leijtens, J, Taverne, S, Heijnen, B, El-Massoudi, Y, de Groot-Van Veen, I, Hoff, C, Jou-Valencia, D, Consten, E, Burghgraef, T, Geitenbeek, R, Hulshof, L, Slooter, G, Reudink, M, Bouvy, N, Wildeboer, A, Verstappen, S, Pennings, A, van den Hengel, B, Wijma, A, de Haan, J, de Nes, L, Heesink, V, Karsten, T, Heidsma, C, Koemans, W, Dekker, J, van der Zijden, C, Roos, D, Demirkiran, A, van der Burg, S, Oosterling, S, Hoogteijling, T, Wiering, B, Smeeing, D, Havenga, K, Lutfi, H, Tsimogiannis, K, Skoldberg, F, Folkesson, J, den Boer, F, van Schaik, T, van Gerven, P, Sietses, C, Hol, J, Boerma, E, Creemers, D, Schultz, J, Frivold, T, Riis, R, Gregussen, H, Busund, S, Sjo, O, Gaard, M, Krohn, N, Ersryd, A, Leung, E, Sultan, H, Hajjaj, B, Alhisi, A, Khader, A, Mendes, A, Semiao, M, Faria, L, Azevedo, C, da Costa Devesa, H, Martins, S, Jarimba, A, Marques, S, Ferreira, R, Oliveira, A, Ferreira, C, Pereira, R, Surlin, V, Graure, G, Ramboiu, S, Negoi, I, Ciubotaru, C, Stoica, B, Tanase, I, Negoita, V, Florea, S, Macau, F, Vasile, M, Stefanescu, V, Dimofte, G, Lunca, S, Roata, C, Musina, A, Garmanova, T, Agapov, M, Markaryan, D, Eduard, G, Yanishev, A, Abelevich, A, Bazaev, A, Rodimov, S, Filimonov, V, Melnikov, A, Suchkov, I, Drozdov, E, Kostromitskiy, D, Sjostrom, O, Matthiessen, P, Baban, B, Gadan, S, Jadid, K, Staffan, M, Park, J, 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G., Wienholts K., Ubels S., Talboom K., Hannink G., Wolthuis A., de Lacy F. B., Lefevre J. H., Solomon M., Frasson M., Rotholtz N., Denost Q., Perez R. O., Konishi T., Panis Y., Rutegard M., Hompes R., Rosman C., van Workum F., Tanis P. J., de Wilt J. H. W., Bremers A. J. A., Ferenschild F. T., de Vriendt S., D'Hoore A., Bislenghi G., Farguell J., Lacy A. M., Atienza P. G., van Kessel C. S., Parc Y., Voron T., Collard M. K., Muriel J. S., Cholewa H., Mattioni L. A., Frontali A., Polle S. W., Polat F., Obihara N. J., Vailati B. B., Kusters M., Tuynmann J. B., Hazen S. J. A., Gruter A. A. J., Amano T., Fujiwara H., Salomon M., Ruiz H., Gonzalez R., Estefania D., Avellaneda N., Carrie A., Santillan M., Pachajoa D. A. P., Parodi M., Gielis M., Binder A. -D., Gurtler T., Riedl P., Badiani S., Berney C., Morgan M., Hollington P., da Silva N., Nair G., Ho Y. M., Lamparelli M., Kapadia R., Kroon H. M., Dudi-Venkata N. N., Liu J., Sammour T., Flamey N., Pattyn P., Chaoui A., Vansteenbrugge L., van den Broek N. E. J., Vanclooster P., de Gheldere C., Pletinckx P., Defoort B., Dewulf M., Slavchev M., Belev N., Atanasov B., Krastev P., Sokolov M., Maslyankov S., Gribnev P., Pavlov V., Ivanov T., Karamanliev M., Filipov E., Tonchev P., Aigner F., Mitteregger M., Allmer C., Seitinger G., Colucci N., Buchs N., Ris F., Toso C., Gialamas E., Vuagniaux A., Chautems R., Sauvain M. -O., Daester S., von Flue M., Guenin M. -O., Taha-Mehlitz S., Hess G. F., Martinek L., Skrovina M., Machackova M., Bencurik V., Uluk D., Pratschke J., Dittrich L. S., Guel-Klein S., Perez D., Grass J. -K., Melling N., Mueller S., Iversen L. H., Eriksen J. D., Baatrup G., Al-Najami I., Bjorsum-Meyer T., Teras J., Teras R. M., Monib F. A., Ahmed N. E. A. E., Alkady E., Ali A. K., Khedr G. A. E., Abdelaal A. S., Ashoush F. M. B., Ewedah M., Elshennawy E. M., Hussein M., Fernandez-Martinez D., Garcia-Florez L. 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G., Rodriguez-Infante A., Minguez-Ruiz G., Carreno-Villarreal G., Pire-Abaitua G., Dziakova J., Rodriguez C. S. -C., Aranda M. J. P., Huguet J. M. M., Borda-Arrizabalaga N., Enriquez-Navascues J. M., Echaniz G. E., Ansorena Y. S., Estaire-Gomez M., Martinez-Pinedo C., Barbero-Valenzuela A., Ruiz-Garcia P., Kraft M., Gomez-Jurado M. J., Pellino G., Espin-Basany E., Cotte E., Panel N., Goutard C. -A., de Angelis N., Lauka L., Shaikh S., Osborne L., Ramsay G., Nichita V. -I., Bhandari S., Sarmah P., Bethune R. M., Pringle H. C. M., Massey L., Fowler G. E., Hamid H. K. S., de Simone B. D., Kynaston J., Bradley N., Stienstra R. M., Gurjar S., Mukherjee T., Chandio A., Ahmed S., Singh B., Runau F., Chaudhri S., Siaw O., Sarveswaran J., Miu V., Ashmore D., Darwich H., Singh-Ranger D., Singh N., Shaban M., Gareb F., Petropolou T., Polydorou A., Dattani M., Afzal A., Bavikatte A., Sebastian B., Ward N., Mishra A., Manatakis D., Agalianos C., Tasis N., Antonopoulou M. -I., Karavokyros I., Charalabopoulos A., Schizas D., Baili E., Syllaios A., Karydakis L., Vailas M., Balalis D., Korkolis D., Plastiras A., Rompou A., Xenaki S., Xynos E., Chrysos E., Venianaki M., Christodoulidis G., Perivoliotis K., Tzovaras G., Baloyiannis I., Ho M. -F., Ng S. S., Mak T. W. -C., Futaba K., Santak G., Simlesa D., Cosic J., Zukanovic G., Kelly M. E., Larkin J. O., McCormick P. H., Mehigan B. J., Connelly T. M., Neary P., Ryan J., McCullough P., Al-Juaifari M. A., Hammoodi H., Abbood A. H., Calabro M., Muratore A., La Terra A., Farnesi F., Feo C. 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A., Zanus G., Iacomino A., Novello S., Passuello N., Zucchella M., Puca L., deGiuli M., Reddavid R., Scabini S., Aprile A., Soriero D., Fioravanti E., Rottoli M., Romano A., Tanzanu M., Belvedere A., Mariani N. M., Ceretti A. P., Opocher E., Gallo G., Sammarco G., de Paola G., Pucciarelli S., Marchegiani F., Spolverato G., Buzzi G., Di Saverio S., Meroni P., Parise C., Bottazzoli E. I., Lapolla P., Brachini G., Cirillo B., Mingoli A., Sica G., Siragusa L., Bellato V., Cerbo D., de Pasqual C. A., de Manzoni G., di Cosmo M. A., Alrayes B. M. H., Qandeel M. W. M., Hani M. B., Rabadi A., el Muhtaseb M. S., Abdeen B., Karmi F., Zilinskas J., Latkauskas T., Tamelis A., Pikuniene I., Slenfuktas V., Poskus T., Kryzauskas M., Jakubauskas M., Mikalauskas S., Jakubauskiene L., Hassan S. Y., Altrabulsi A., Abdulwahed E., Ghmagh R., Deeknah A., Alshareea E., Elhadi M., Abujamra S., Msherghi A. A., Tababa O. W. E., Majbar M. 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R., Holman F. A., Heemskerk J., Vosbeek N., Leijtens J. W. A., Taverne S. B. M., Heijnen B. H. M., El-Massoudi Y., de Groot-Van Veen I., Hoff C., Jou-Valencia D., Consten E. C. J., Burghgraef T. A., Geitenbeek R., Hulshof L. G. W. L., Slooter G. D., Reudink M., Bouvy N. D., Wildeboer A. C. L., Verstappen S., Pennings A. J., van den Hengel B., Wijma A. G., de Haan J., de Nes L. C. F., Heesink V., Karsten T., Heidsma C. M., Koemans W. J., Dekker J. -W. T., van der Zijden C. J., Roos D., Demirkiran A., van der Burg S., Oosterling S. J., Hoogteijling T. J., Wiering B., Smeeing D. P. J., Havenga K., Lutfi H., Tsimogiannis K., Skoldberg F., Folkesson J., den Boer F., van Schaik T. G., van Gerven P., Sietses C., Hol J. C., Boerma E. -J. G., Creemers D. M. J., Schultz J. K., Frivold T., Riis R., Gregussen H., Busund S., Sjo O. H., Gaard M., Krohn N., Ersryd A. L., Leung E., Sultan H., Hajjaj B. N., Alhisi A. J., Khader A. A. E., Mendes A. F. D., Semiao M., Faria L. Q., Azevedo C., da Costa Devesa H. M., Martins S. F., Jarimba A. M. R., Marques S. M. R., Ferreira R. M., Oliveira A., Ferreira C., Pereira R., Surlin V. M., Graure G. M., Ramboiu S. P. S. D., Negoi I., Ciubotaru C., Stoica B., Tanase I., Negoita V. M., Florea S., Macau F., Vasile M., Stefanescu V., Dimofte G. -M., Lunca S., Roata C. -E., Musina A. -M., Garmanova T., Agapov M. N., Markaryan D. G., Eduard G., Yanishev A., Abelevich A., Bazaev A., Rodimov S. V., Filimonov V. B., Melnikov A. A., Suchkov I. A., Drozdov E. S., Kostromitskiy D. N., Sjostrom O., Matthiessen P., Baban B., Gadan S., Jadid K. D., Staffan M., Park J. M., Rydbeck D., Lydrup M. -L., Buchwald P., Jutesten H., Darlin L., Lindqvist E., Nilsson K., Larsson P. -A., Jangmalm S., Kosir J. A., Tomazic A., Grosek J., Bozic T. K., Zazo A., Zazo R., Fares H., Ayoub K., Niazi A., Mansour A., Abbas A., Tantoura M., Hamdan A., Hassan N., Hasan B., Saad A., Sebai A., Haddad A., Maghrebi H., Kacem M., Yalkin O., Samsa M. V., Atak I., Balci B., Haberal E., Dogan L., Gecim I. E., Akyol C., Koc M. A., Sivrikoz E., Piyadeoglu D., Avanagh D. O., Sokmen S., Bisgin T., Gunenc E., Guzel M., Leventoglu S., Yuksel O., Kozan R., Gobut H., Cengiz F., Erdinc K., Acar N. C., Kamer E., Ozgur I., Aydin O., Keskin M., Bulut M. T., Kulle C. B., Kara Y., Sibic O., Ozata I. H., Bugra D., Balik E., Cakir M., Alhardan A., Colak E., Aybar A. B. C., Sari A. C., Atici S. D., Kaya T., Dursun A., Calik B., Ozkan O. F., Ulgur H. S., Duzgun O., Monson J., George S., Woods K., Al-Eryani F., Albakry R., Coetzee E., Boutall A., Herman A., Warden C., Mugla N., Forgan T., Mia I., Lambrechts A., Greijdanus, N, Wienholts, K, Ubels, S, Talboom, K, Hannink, G, Wolthuis, A, de Lacy, F, Lefevre, J, Solomon, M, Frasson, M, Rotholtz, N, Denost, Q, Perez, R, Konishi, T, Panis, Y, Rutegard, M, Hompes, R, Rosman, C, van Workum, F, Tanis, P, de Wilt, J, Bremers, A, Ferenschild, F, de Vriendt, S, D'Hoore, A, Bislenghi, G, Farguell, J, Lacy, A, Atienza, P, van Kessel, C, Parc, Y, Voron, T, Collard, M, Muriel, J, Cholewa, H, Mattioni, L, Frontali, A, Polle, S, Polat, F, Obihara, N, Vailati, B, Kusters, M, Tuynmann, J, Hazen, S, Gruter, A, Amano, T, Fujiwara, H, Salomon, M, Ruiz, H, Gonzalez, R, Estefania, D, Avellaneda, N, Carrie, A, Santillan, M, Pachajoa, D, Parodi, M, Gielis, M, Binder, A, Gurtler, T, Riedl, P, Badiani, S, Berney, C, Morgan, M, Hollington, P, da Silva, N, Nair, G, Ho, Y, Lamparelli, M, Kapadia, R, Kroon, H, Dudi-Venkata, N, Liu, J, Sammour, T, Flamey, N, Pattyn, P, Chaoui, A, Vansteenbrugge, L, van den Broek, N, Vanclooster, P, de Gheldere, C, Pletinckx, P, Defoort, B, Dewulf, M, Slavchev, M, Belev, N, Atanasov, B, Krastev, P, Sokolov, M, Maslyankov, S, Gribnev, P, Pavlov, V, Ivanov, T, Karamanliev, M, Filipov, E, Tonchev, P, Aigner, F, Mitteregger, M, Allmer, C, Seitinger, G, Colucci, N, Buchs, N, Ris, F, Toso, C, Gialamas, E, Vuagniaux, A, Chautems, R, Sauvain, M, Daester, S, von Flue, M, Guenin, M, Taha-Mehlitz, S, Hess, G, Martinek, L, Skrovina, M, Machackova, M, Bencurik, V, Uluk, D, Pratschke, J, Dittrich, L, Guel-Klein, S, Perez, D, Grass, J, Melling, N, Mueller, S, Iversen, L, Eriksen, J, Baatrup, G, Al-Najami, I, Bjorsum-Meyer, T, Teras, J, Teras, R, Monib, F, Ahmed, N, Alkady, E, Ali, A, Khedr, G, Abdelaal, A, Ashoush, F, Ewedah, M, Elshennawy, E, Hussein, M, Fernandez-Martinez, D, Garcia-Florez, L, Fernandez-Hevia, M, Suarez-Sanchez, A, Aretxabala, I, Docampo, I, Zabala, J, Tejedor, P, Morales Bernaldo de Quiros, J, Quiroga, I, Navarro-Sanchez, A, Darias, I, Fernandez, C, de La Cruz Cuadrado, C, Sanchez-Guillen, L, Lopez-Rodriguez-Arias, F, Soler-Silva, A, Arroyo, A, Bernal-Sprekelsen, J, Gomez-Abril, S, Gonzalvez, P, Torres, M, Sanchez, T, Antona, F, Lara, J, Montero, J, Mendoza-Moreno, F, Diez-Alonso, M, Matias-Garcia, B, Quiroga-Valcarcel, A, Colas-Ruiz, E, Tasende-Presedo, M, Fernandez-Hurtado, I, Cifuentes-Rodenas, J, Suarez, M, Losada, M, Hernandez, M, Alonso, A, Dieguez, B, Serralta, D, Quintana, R, Lopez, J, Pinto, F, Nieto-Moreno, E, Bonito, A, Santacruz, C, Marcos, E, Septiem, J, Calero-Lillo, A, Alanez-Saavedra, J, Munoz-Collado, S, Lopez-Lara, M, Martinez, M, Herrero, E, Borda, F, Villar, O, Escartin, J, Blas, J, Ferrer, R, Egea, J, Rodriguez-Infante, A, Minguez-Ruiz, G, Carreno-Villarreal, G, Pire-Abaitua, G, Dziakova, J, Rodriguez, C, Aranda, M, Huguet, J, Borda-Arrizabalaga, N, Enriquez-Navascues, J, Echaniz, G, Ansorena, Y, Estaire-Gomez, M, Martinez-Pinedo, C, Barbero-Valenzuela, A, Ruiz-Garcia, P, Kraft, M, Gomez-Jurado, M, Pellino, G, Espin-Basany, E, Cotte, E, Panel, N, Goutard, C, de Angelis, N, Lauka, L, Shaikh, S, Osborne, L, Ramsay, G, Nichita, V, Bhandari, S, Sarmah, P, Bethune, R, Pringle, H, Massey, L, Fowler, G, Hamid, H, de Simone, B, Kynaston, J, Bradley, N, Stienstra, R, Gurjar, S, Mukherjee, T, Chandio, A, Ahmed, S, Singh, B, Runau, F, Chaudhri, S, Siaw, O, Sarveswaran, J, Miu, V, Ashmore, D, Darwich, H, Singh-Ranger, D, Singh, N, Shaban, M, Gareb, F, Petropolou, T, Polydorou, A, Dattani, M, Afzal, A, Bavikatte, A, Sebastian, B, Ward, N, Mishra, A, Manatakis, D, Agalianos, C, Tasis, N, Antonopoulou, M, Karavokyros, I, Charalabopoulos, A, Schizas, D, Baili, E, Syllaios, A, Karydakis, L, Vailas, M, Balalis, D, Korkolis, D, Plastiras, A, Rompou, A, Xenaki, S, Xynos, E, Chrysos, E, Venianaki, M, Christodoulidis, G, Perivoliotis, K, Tzovaras, G, Baloyiannis, I, Ho, M, Ng, S, Mak, T, Futaba, K, Santak, G, Simlesa, D, Cosic, J, Zukanovic, G, Kelly, M, Larkin, J, Mccormick, P, Mehigan, B, Connelly, T, Neary, P, Ryan, J, Mccullough, P, Al-Juaifari, M, Hammoodi, H, Abbood, A, Calabro, M, Muratore, A, La Terra, A, Farnesi, F, Feo, C, Fabbri, N, Pesce, A, Fazzin, M, Roscio, F, Clerici, F, Lucchi, A, Vittori, L, Agostinelli, L, Ripoli, M, Sambucci, D, Porta, A, Sinibaldi, G, Crescentini, G, Larcinese, A, Picone, E, Persiani, R, Biondi, A, Pezzuto, R, Lorenzon, L, Rizzo, G, Coco, C, D'Agostino, L, Spinelli, A, Sacchi, M, Carvello, M, Foppa, C, Maroli, A, Palini, G, Garulli, G, Zanini, N, Delrio, P, Rega, D, Carbone, F, Aversano, A, Pirozzolo, G, Recordare, A, D'Alimonte, L, Vignotto, C, Corbellini, C, Sampietro, G, Lorusso, L, Manzo, C, Ghignone, F, Ugolini, G, Montroni, I, Pasini, F, Ballabio, M, Bisagni, P, Armao, F, Longhi, M, Ghazouani, O, Galleano, R, Tamini, N, Oldani, M, Nespoli, L, Picciariello, A, Altomare, D, Tomasicchio, G, Lantone, G, Catena, F, Giuffrida, M, Annicchiarico, A, Perrone, G, Grossi, U, Santoro, G, Zanus, G, Iacomino, A, Novello, S, Passuello, N, Zucchella, M, Puca, L, Degiuli, M, Reddavid, R, Scabini, S, Aprile, A, Soriero, D, Fioravanti, E, Rottoli, M, Romano, A, Tanzanu, M, Belvedere, A, Mariani, N, Ceretti, A, Opocher, E, Gallo, G, Sammarco, G, de Paola, G, Pucciarelli, S, Marchegiani, F, Spolverato, G, Buzzi, G, Di Saverio, S, Meroni, P, Parise, C, Bottazzoli, E, Lapolla, P, Brachini, G, Cirillo, B, Mingoli, A, Sica, G, Siragusa, L, Bellato, V, Cerbo, D, de Pasqual, C, de Manzoni, G, di Cosmo, M, Alrayes, B, Qandeel, M, Hani, M, Rabadi, A, el Muhtaseb, M, Abdeen, B, Karmi, F, Zilinskas, J, Latkauskas, T, Tamelis, A, Pikuniene, I, Slenfuktas, V, Poskus, T, Kryzauskas, M, Jakubauskas, M, Mikalauskas, S, Jakubauskiene, L, Hassan, S, Altrabulsi, A, Abdulwahed, E, Ghmagh, R, Deeknah, A, Alshareea, E, Elhadi, M, Abujamra, S, Msherghi, A, Tababa, O, Majbar, M, Souadka, A, Benkabbou, A, Mohsine, R, Echiguer, S, Moctezuma-Velazquez, P, Salgado-Nesme, N, Vergara-Fernandez, O, Sainz-Hernandez, J, Alvarez-Bautista, F, Zakaria, A, Zakaria, Z, Wong, M, Ismail, R, Ibrahim, A, Abdullah, N, Julaihi, R, Bhat, S, O'Grady, G, Bissett, I, Lamme, B, Musters, G, Dinaux, A, Grotenhuis, B, Steller, E, Aalbers, A, Leeuwenburgh, M, Rutten, H, Burger, J, Bloemen, J, Ketelaers, S, Waqar, U, Chawla, T, Rauf, H, Rani, P, Talsma, A, Scheurink, L, van Praagh, J, Segelman, J, Nygren, J, Anderin, K, Tiefenthal, M, de Andres, B, Beltran de Heredia, J, Vazquez, A, Gomez, T, Golshani, P, Kader, R, Mohamed, A, Westerterp, M, Marinelli, A, Niemer, Q, Doornebosch, P, Shapiro, J, Vermaas, M, de Graaf, E, van Westreenen, H, Zwakman, M, van Dalsen, A, Vles, W, Nonner, J, Toorenvliet, B, Janssen, P, Verdaasdonk, E, Amelung, F, Peeters, K, Bahadoer, R, Holman, F, Heemskerk, J, Vosbeek, N, Leijtens, J, Taverne, S, Heijnen, B, El-Massoudi, Y, de Groot-Van Veen, I, Hoff, C, Jou-Valencia, D, Consten, E, Burghgraef, T, Geitenbeek, R, Hulshof, L, Slooter, G, Reudink, M, Bouvy, N, Wildeboer, A, Verstappen, S, Pennings, A, van den Hengel, B, Wijma, A, de Haan, J, de Nes, L, Heesink, V, Karsten, T, Heidsma, C, Koemans, W, Dekker, J, van der Zijden, C, Roos, D, Demirkiran, A, van der Burg, S, Oosterling, S, Hoogteijling, T, Wiering, B, Smeeing, D, Havenga, K, Lutfi, H, Tsimogiannis, K, Skoldberg, F, Folkesson, J, den Boer, F, van Schaik, T, van Gerven, P, Sietses, C, Hol, J, Boerma, E, Creemers, D, Schultz, J, Frivold, T, Riis, R, Gregussen, H, Busund, S, Sjo, O, Gaard, M, Krohn, N, Ersryd, A, Leung, E, Sultan, H, Hajjaj, B, Alhisi, A, Khader, A, Mendes, A, Semiao, M, Faria, L, Azevedo, C, da Costa Devesa, H, Martins, S, Jarimba, A, Marques, S, Ferreira, R, Oliveira, A, Ferreira, C, Pereira, R, Surlin, V, Graure, G, Ramboiu, S, Negoi, I, Ciubotaru, C, Stoica, B, Tanase, I, Negoita, V, Florea, S, Macau, F, Vasile, M, Stefanescu, V, Dimofte, G, Lunca, S, Roata, C, Musina, A, Garmanova, T, Agapov, M, Markaryan, D, Eduard, G, Yanishev, A, Abelevich, A, Bazaev, A, Rodimov, S, Filimonov, V, Melnikov, A, Suchkov, I, Drozdov, E, Kostromitskiy, D, Sjostrom, O, Matthiessen, P, Baban, B, Gadan, S, Jadid, K, Staffan, M, Park, J, Rydbeck, D, Lydrup, M, Buchwald, P, Jutesten, H, Darlin, L, Lindqvist, E, Nilsson, K, Larsson, P, Jangmalm, S, Kosir, J, Tomazic, A, Grosek, J, Bozic, T, Zazo, A, Zazo, R, Fares, H, Ayoub, K, Niazi, A, Mansour, A, Abbas, A, Tantoura, M, Hamdan, A, Hassan, N, Hasan, B, Saad, A, Sebai, A, Haddad, A, Maghrebi, H, Kacem, M, Yalkin, O, Samsa, M, Atak, I, Balci, B, Haberal, E, Dogan, L, Gecim, I, Akyol, C, Koc, M, Sivrikoz, E, Piyadeoglu, D, Avanagh, D, Sokmen, S, Bisgin, T, Gunenc, E, Guzel, M, Leventoglu, S, Yuksel, O, Kozan, R, Gobut, H, Cengiz, F, Erdinc, K, Acar, N, Kamer, E, Ozgur, I, Aydin, O, Keskin, M, Bulut, M, Kulle, C, Kara, Y, Sibic, O, Ozata, I, Bugra, D, Balik, E, Cakir, M, Alhardan, A, Colak, E, Aybar, A, Sari, A, Atici, S, Kaya, T, Dursun, A, Calik, B, Ozkan, O, Ulgur, H, Duzgun, O, Monson, J, George, S, Woods, K, Al-Eryani, F, Albakry, R, Coetzee, E, Boutall, A, Herman, A, Warden, C, Mugla, N, Forgan, T, Mia, I, Lambrechts, A, Greijdanus N. G., Wienholts K., Ubels S., Talboom K., Hannink G., Wolthuis A., de Lacy F. B., Lefevre J. H., Solomon M., Frasson M., Rotholtz N., Denost Q., Perez R. O., Konishi T., Panis Y., Rutegard M., Hompes R., Rosman C., van Workum F., Tanis P. J., de Wilt J. H. W., Bremers A. J. A., Ferenschild F. T., de Vriendt S., D'Hoore A., Bislenghi G., Farguell J., Lacy A. M., Atienza P. G., van Kessel C. S., Parc Y., Voron T., Collard M. K., Muriel J. S., Cholewa H., Mattioni L. A., Frontali A., Polle S. W., Polat F., Obihara N. J., Vailati B. B., Kusters M., Tuynmann J. B., Hazen S. J. A., Gruter A. A. J., Amano T., Fujiwara H., Salomon M., Ruiz H., Gonzalez R., Estefania D., Avellaneda N., Carrie A., Santillan M., Pachajoa D. A. P., Parodi M., Gielis M., Binder A. -D., Gurtler T., Riedl P., Badiani S., Berney C., Morgan M., Hollington P., da Silva N., Nair G., Ho Y. M., Lamparelli M., Kapadia R., Kroon H. M., Dudi-Venkata N. N., Liu J., Sammour T., Flamey N., Pattyn P., Chaoui A., Vansteenbrugge L., van den Broek N. E. J., Vanclooster P., de Gheldere C., Pletinckx P., Defoort B., Dewulf M., Slavchev M., Belev N., Atanasov B., Krastev P., Sokolov M., Maslyankov S., Gribnev P., Pavlov V., Ivanov T., Karamanliev M., Filipov E., Tonchev P., Aigner F., Mitteregger M., Allmer C., Seitinger G., Colucci N., Buchs N., Ris F., Toso C., Gialamas E., Vuagniaux A., Chautems R., Sauvain M. -O., Daester S., von Flue M., Guenin M. -O., Taha-Mehlitz S., Hess G. F., Martinek L., Skrovina M., Machackova M., Bencurik V., Uluk D., Pratschke J., Dittrich L. S., Guel-Klein S., Perez D., Grass J. -K., Melling N., Mueller S., Iversen L. H., Eriksen J. D., Baatrup G., Al-Najami I., Bjorsum-Meyer T., Teras J., Teras R. M., Monib F. A., Ahmed N. E. A. E., Alkady E., Ali A. K., Khedr G. A. E., Abdelaal A. S., Ashoush F. M. B., Ewedah M., Elshennawy E. M., Hussein M., Fernandez-Martinez D., Garcia-Florez L. J., Fernandez-Hevia M., Suarez-Sanchez A., Aretxabala I. D. H., Docampo I. L., Zabala J. G., Tejedor P., Morales Bernaldo de Quiros J. T., Quiroga I. B., Navarro-Sanchez A., Darias I. S., Fernandez C. L., de La Cruz Cuadrado C., Sanchez-Guillen L., Lopez-Rodriguez-Arias F., Soler-Silva A., Arroyo A., Bernal-Sprekelsen J. C., Gomez-Abril S. A., Gonzalvez P., Torres M. T., Sanchez T. R., Antona F. B., Lara J. E. S., Montero J. A. A., Mendoza-Moreno F., Diez-Alonso M., Matias-Garcia B., Quiroga-Valcarcel A., Colas-Ruiz E., Tasende-Presedo M. M., Fernandez-Hurtado I., Cifuentes-Rodenas J. A., Suarez M. C., Losada M., Hernandez M., Alonso A., Dieguez B., Serralta D., Quintana R. E. M., Lopez J. M. G., Pinto F. L., Nieto-Moreno E., Bonito A. C., Santacruz C. C., Marcos E. B., Septiem J. G., Calero-Lillo A., Alanez-Saavedra J., Munoz-Collado S., Lopez-Lara M., Martinez M. L., Herrero E. F., Borda F. J. G., Villar O. G., Escartin J., Blas J. L., Ferrer R., Egea J. G., Rodriguez-Infante A., Minguez-Ruiz G., Carreno-Villarreal G., Pire-Abaitua G., Dziakova J., Rodriguez C. S. -C., Aranda M. J. P., Huguet J. M. M., Borda-Arrizabalaga N., Enriquez-Navascues J. M., Echaniz G. E., Ansorena Y. S., Estaire-Gomez M., Martinez-Pinedo C., Barbero-Valenzuela A., Ruiz-Garcia P., Kraft M., Gomez-Jurado M. J., Pellino G., Espin-Basany E., Cotte E., Panel N., Goutard C. -A., de Angelis N., Lauka L., Shaikh S., Osborne L., Ramsay G., Nichita V. -I., Bhandari S., Sarmah P., Bethune R. M., Pringle H. C. M., Massey L., Fowler G. E., Hamid H. K. S., de Simone B. D., Kynaston J., Bradley N., Stienstra R. M., Gurjar S., Mukherjee T., Chandio A., Ahmed S., Singh B., Runau F., Chaudhri S., Siaw O., Sarveswaran J., Miu V., Ashmore D., Darwich H., Singh-Ranger D., Singh N., Shaban M., Gareb F., Petropolou T., Polydorou A., Dattani M., Afzal A., Bavikatte A., Sebastian B., Ward N., Mishra A., Manatakis D., Agalianos C., Tasis N., Antonopoulou M. -I., Karavokyros I., Charalabopoulos A., Schizas D., Baili E., Syllaios A., Karydakis L., Vailas M., Balalis D., Korkolis D., Plastiras A., Rompou A., Xenaki S., Xynos E., Chrysos E., Venianaki M., Christodoulidis G., Perivoliotis K., Tzovaras G., Baloyiannis I., Ho M. -F., Ng S. S., Mak T. W. -C., Futaba K., Santak G., Simlesa D., Cosic J., Zukanovic G., Kelly M. E., Larkin J. O., McCormick P. H., Mehigan B. J., Connelly T. M., Neary P., Ryan J., McCullough P., Al-Juaifari M. A., Hammoodi H., Abbood A. H., Calabro M., Muratore A., La Terra A., Farnesi F., Feo C. V., Fabbri N., Pesce A., Fazzin M., Roscio F., Clerici F., Lucchi A., Vittori L., Agostinelli L., Ripoli M. C., Sambucci D., Porta A., Sinibaldi G., Crescentini G., Larcinese A., Picone E., Persiani R., Biondi A., Pezzuto R., Lorenzon L., Rizzo G., Coco C., D'Agostino L., Spinelli A., Sacchi M. M., Carvello M., Foppa C., Maroli A., Palini G. M., Garulli G., Zanini N., Delrio P., Rega D., Carbone F., Aversano A., Pirozzolo G., Recordare A., D'Alimonte L., Vignotto C., Corbellini C., Sampietro G. M., Lorusso L., Manzo C. A., Ghignone F., Ugolini G., Montroni I., Pasini F., Ballabio M., Bisagni P., Armao F. T., Longhi M., Ghazouani O., Galleano R., Tamini N., Oldani M., Nespoli L., Picciariello A., Altomare D. F., Tomasicchio G., Lantone G., Catena F., Giuffrida M., Annicchiarico A., Perrone G., Grossi U., Santoro G. A., Zanus G., Iacomino A., Novello S., Passuello N., Zucchella M., Puca L., deGiuli M., Reddavid R., Scabini S., Aprile A., Soriero D., Fioravanti E., Rottoli M., Romano A., Tanzanu M., Belvedere A., Mariani N. M., Ceretti A. P., Opocher E., Gallo G., Sammarco G., de Paola G., Pucciarelli S., Marchegiani F., Spolverato G., Buzzi G., Di Saverio S., Meroni P., Parise C., Bottazzoli E. I., Lapolla P., Brachini G., Cirillo B., Mingoli A., Sica G., Siragusa L., Bellato V., Cerbo D., de Pasqual C. A., de Manzoni G., di Cosmo M. A., Alrayes B. M. H., Qandeel M. W. M., Hani M. B., Rabadi A., el Muhtaseb M. S., Abdeen B., Karmi F., Zilinskas J., Latkauskas T., Tamelis A., Pikuniene I., Slenfuktas V., Poskus T., Kryzauskas M., Jakubauskas M., Mikalauskas S., Jakubauskiene L., Hassan S. Y., Altrabulsi A., Abdulwahed E., Ghmagh R., Deeknah A., Alshareea E., Elhadi M., Abujamra S., Msherghi A. A., Tababa O. W. E., Majbar M. A., Souadka A., Benkabbou A., Mohsine R., Echiguer S., Moctezuma-Velazquez P., Salgado-Nesme N., Vergara-Fernandez O., Sainz-Hernandez J. C., Alvarez-Bautista F. E., Zakaria A. D., Zakaria Z., Wong M. P. K., Ismail R., Ibrahim A. F., Abdullah N. A. N., Julaihi R., Bhat S., O'Grady G., Bissett I., Lamme B., Musters G. D., Dinaux A. M., Grotenhuis B. A., Steller E. J., Aalbers A. G. J., Leeuwenburgh M. M., Rutten H. J. T., Burger J. W. A., Bloemen J. G., Ketelaers S. H. J., Waqar U., Chawla T., Rauf H., Rani P., Talsma A. K., Scheurink L., van Praagh J. B., Segelman J., Nygren J., Anderin K., Tiefenthal M., de Andres B., Beltran de Heredia J. P., Vazquez A., Gomez T., Golshani P., Kader R., Mohamed A., Westerterp M., Marinelli A., Niemer Q., Doornebosch P. G., Shapiro J., Vermaas M., de Graaf E. J. R., van Westreenen H. L., Zwakman M., van Dalsen A. D., Vles W. J., Nonner J., Toorenvliet B. R., Janssen P. T. J., Verdaasdonk E. G. G., Amelung F. J., Peeters K. C. M. J., Bahadoer R. R., Holman F. A., Heemskerk J., Vosbeek N., Leijtens J. W. A., Taverne S. B. M., Heijnen B. H. M., El-Massoudi Y., de Groot-Van Veen I., Hoff C., Jou-Valencia D., Consten E. C. J., Burghgraef T. A., Geitenbeek R., Hulshof L. G. W. L., Slooter G. D., Reudink M., Bouvy N. D., Wildeboer A. C. L., Verstappen S., Pennings A. J., van den Hengel B., Wijma A. G., de Haan J., de Nes L. C. F., Heesink V., Karsten T., Heidsma C. M., Koemans W. J., Dekker J. -W. T., van der Zijden C. J., Roos D., Demirkiran A., van der Burg S., Oosterling S. J., Hoogteijling T. J., Wiering B., Smeeing D. P. J., Havenga K., Lutfi H., Tsimogiannis K., Skoldberg F., Folkesson J., den Boer F., van Schaik T. G., van Gerven P., Sietses C., Hol J. C., Boerma E. -J. G., Creemers D. M. J., Schultz J. K., Frivold T., Riis R., Gregussen H., Busund S., Sjo O. H., Gaard M., Krohn N., Ersryd A. L., Leung E., Sultan H., Hajjaj B. N., Alhisi A. J., Khader A. A. E., Mendes A. F. D., Semiao M., Faria L. Q., Azevedo C., da Costa Devesa H. M., Martins S. F., Jarimba A. M. R., Marques S. M. R., Ferreira R. M., Oliveira A., Ferreira C., Pereira R., Surlin V. M., Graure G. M., Ramboiu S. P. S. D., Negoi I., Ciubotaru C., Stoica B., Tanase I., Negoita V. M., Florea S., Macau F., Vasile M., Stefanescu V., Dimofte G. -M., Lunca S., Roata C. -E., Musina A. -M., Garmanova T., Agapov M. N., Markaryan D. G., Eduard G., Yanishev A., Abelevich A., Bazaev A., Rodimov S. V., Filimonov V. B., Melnikov A. A., Suchkov I. A., Drozdov E. S., Kostromitskiy D. N., Sjostrom O., Matthiessen P., Baban B., Gadan S., Jadid K. D., Staffan M., Park J. M., Rydbeck D., Lydrup M. -L., Buchwald P., Jutesten H., Darlin L., Lindqvist E., Nilsson K., Larsson P. -A., Jangmalm S., Kosir J. A., Tomazic A., Grosek J., Bozic T. K., Zazo A., Zazo R., Fares H., Ayoub K., Niazi A., Mansour A., Abbas A., Tantoura M., Hamdan A., Hassan N., Hasan B., Saad A., Sebai A., Haddad A., Maghrebi H., Kacem M., Yalkin O., Samsa M. V., Atak I., Balci B., Haberal E., Dogan L., Gecim I. E., Akyol C., Koc M. A., Sivrikoz E., Piyadeoglu D., Avanagh D. O., Sokmen S., Bisgin T., Gunenc E., Guzel M., Leventoglu S., Yuksel O., Kozan R., Gobut H., Cengiz F., Erdinc K., Acar N. C., Kamer E., Ozgur I., Aydin O., Keskin M., Bulut M. T., Kulle C. B., Kara Y., Sibic O., Ozata I. H., Bugra D., Balik E., Cakir M., Alhardan A., Colak E., Aybar A. B. C., Sari A. C., Atici S. D., Kaya T., Dursun A., Calik B., Ozkan O. F., Ulgur H. S., Duzgun O., Monson J., George S., Woods K., Al-Eryani F., Albakry R., Coetzee E., Boutall A., Herman A., Warden C., Mugla N., Forgan T., Mia I., and Lambrechts A.

Abstract

Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2: 1). Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.

Published
2023

35. Delimitation of the Final Pit in Open Pit Mines Using the Pseudoflow Maximum Flow Algorithm: A Comparative Analysis of 1×5 and 1×9 Arcs.

Author

Marquina-Araujo, Jairo J., Cotrina-Teatino, Marco A., Mamani-Quispe, José N., Ccatamayo-Barrios, Johnny H., Ortiz-Quintanilla, Salomon M., Antonio-Araujo, Eusebio, Castillo-Chung, Aldo R., and Portilla-Rodriguez, Hans R.

Subjects
NET present value, COPPER prices, COPPER, DATA analysis, SMELTING, ARCHES
Abstract

The primary aim of this research was to delimitate the final pit in an open pit mine using the 1×5 and 1×9 arch methods of the pseudoflow maximum flow algorithm. To achieve this, Exploratory Data Analysis (EDA), economic, and geomechanical parameters were utilized. Various final pit scenarios were generated by varying the revenue factor. The analysis was conducted using Python 3.11 (Jupyter Notebook) and SGeMS V.3.0 software. The block model comprised 480,000 blocks, each measuring 10×10×10 meters, with a copper grade range from 0 to 1.41%. Specific parameters were employed, including a slope angle of 45°, a base copper price of 3.90 US\$/lb, and smelting, extraction, and crushing-grinding costs of 0.40 US\$/lb, 2.30, and 11.00 US\$/ton, respectively. Twenty final pits were generated for each method, based on a revenue factor from 0.10 to 2.00. The results indicated that both methods are effective for final pit delineation, with the 1×5 method achieving an NPV of 17,855 MUS\$ and a REM of 0.27, and the 1×9 method attaining an NPV of 18,456 MUS$ and a REM of 0.35. It was concluded that the 1×9 arch method is preferable as it yields a higher NPV. This study underscores the importance of methodological selection in the planning of open-pit mines, demonstrating that despite a higher REM, the 1×9 method significantly enhances the NPV, implying substantial economic benefits for the industry. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Efficacy and side effects of immune checkpoint inhibitors in the treatment of colorectal cancer

Author

Salomon M. Manz, Marco Losa, Ralph Fritsch, and Michael Scharl

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Colorectal cancers (CRCs) remain one of the most common and challenging neoplasia in the Western world. The response rate of immunotherapeutic treatment approaches in a subset of advanced CRCs is remarkable and has sustainably changed treatment regimens. Unfortunately, currently available immunotherapeutics only displayed significant antitumoral activity – in terms of progression free survival (PFS) and objective response rate (ORR) – in microsatellite instability-high (MSI-H)/DNA mismatch repair deficient (dMMR) CRCs. Subsequently, these remarkable results had led to the US Food and Drug Administration’s approval of both immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab in the treatment of advanced MSI-H/dMMR CRCs. However, in microsatellite stable (MSS)/DNA mismatch repair proficient (pMMR) CRCs, ICIs have clearly failed to meet their expectations and are therefore not considered effective. As the vast majority of CRCs display a molecular MSS/pMMR profile, current treatment approaches endeavor to improve tumor immunogenicity that consecutively leads to increased proinflammatory cytokine levels as well as tumor infiltrating T-cells, which in turn may be targeted by various immunotherapeutic agents. Therefore, ongoing studies are investigating novel synergistic therapy modalities and approaches to overcome a “cold” to “hot” tumor conversion in MSS/pMMR CRCs. In this review, we summarize the efficacy and possible immune-related adverse events as well as novel therapeutic approaches of ICIs in the treatment of MSI-H/dMMR and MSS/pMMR CRCs.

Published
2021
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39. Why Is End-of-Life Spending So High? Evidence from Cancer Patients

Author

Dan Zeltzer, Liran Einav, Amy Finkelstein, Tzvi Shir, Salomon M. Stemmer, and Ran D. Balicer

Subjects
Economics and Econometrics, Social Sciences (miscellaneous)
Abstract

We study the sources of high end-of-life spending for cancer patients. Even among patients with similar initial prognoses, spending in the year postdiagnosis is over twice as high for those who die within the year than those who survive. Elevated spending on decedents is predominantly driven by higher inpatient spending, particularly low-intensity admissions. However, most such admissions do not result in death, making it difficult to target spending reductions. Furthermore, end-of-life spending is substantially more elevated for younger patients, compared to older patients with similar prognoses. Results highlight sources of high end-of-life spending without revealing any natural “remedies.”

Published
2023
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44. LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial

Author

Talia Golan, Ravit Geva, Donald Richards, Srinivasan Madhusudan, Boris Kin Lin, Haofei Tiffany Wang, Richard A. Walgren, and Salomon M. Stemmer

Subjects
Myostatin, Cachexia, Pancreatic cancer, Muscle mass, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract

Abstract Background Cachexia is a formidable clinical challenge in pancreatic cancer. We assessed LY2495655 (antimyostatin antibody) plus standard‐of‐care chemotherapy in pancreatic cancer using cachexia status as a stratifier. Methods In this randomized, phase 2 trial, patients with stage II–IV pancreatic cancer were randomized to 300 mg LY2495655, 100 mg LY2495655, or placebo, plus physician‐choice chemotherapy from a prespecified list of standard‐of‐care regimens for first and later lines of care. Investigational treatment was continued during second‐line treatment. The primary endpoint was overall survival. Results Overall, 125 patients were randomized. In August 2014, 300 mg LY2495655 was terminated due to imbalance in death rates between the treatment arms; in January 2015, 100 mg LY2495655 treatment was terminated due to futility. LY2495655 did not improve overall survival: the hazard ratio was 1.70 (90% confidence interval, 1.1–2.7) for 300 mg vs. placebo and 1.3 (0.82–2.1) for 100 mg vs. placebo (recommended doses). Progression‐free survival results were consistent with the overall survival results. A numerically higher hazard ratio was observed in patients with weight loss (WL) of ≥5% (cachexia) than with

Published
2018
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48. The Phototropin Family of Photoreceptors

Author

Briggs, W. R., Beck, C. F., Cashmore, A. R., Christie, J. M., Hughes, J., Jarillo, J. A., Kagawa, T., Kanegae, H., Liscum, E., Nagatani, A., Okada, K., Salomon, M., Rüdiger, W., Sakai, T., Takano, M., Wada, M., and Watson, J. C.

Published
2001
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49. Application of Multilayer Perceptron Neural Network in Geological Modeling of Categorical Variables: A Case Study in Peru.

Author

Marquina-Araujo, Jairo J., Cotrina-Teatino, Marco A., Mamani-Quispe, José N., Soto-Juscamayta, Luis M., Ccatamayo-Barrios, Johnny H., Ortiz-Quintanilla, Salomon M., and Cruz-Galvez, Juan A.

Subjects
ARTIFICIAL neural networks, GEOLOGICAL modeling, ARTIFICIAL intelligence, BORING & drilling (Earth & rocks), DATABASES
Abstract

The objective of this research was to use an Artificial Neural Network Multilayer Perceptron (ANN-MLP) for geological modeling of categorical variables, using a database of 5,654 samples obtained from a diamond drilling campaign in a mine in northern Peru. The ANN-PML architecture consisted of an input layer of 5 neurons, three hidden layers with 100, 50 and 20 neurons respectively, and an output layer with 5 neurons, optimized with the Adam algorithm. Variables analyzed included geographic coordinates (east, north and elevation), copper and molybdenum concentrations, and rock type classification. Five different geological models were generated within a 20×20×20 meter three-dimensional block model, where the estimated volumes for geological models 1 to 5 were 795.1, 4506.7, 1176.1, 333.3 and 24.7 million of tons, respectively. The results were validated by cross-validation, evidencing an efficiency of ANN-MLP with Recall metrics of 0.56, precision of 0.66 and an average F1-Score of 0.58, demonstrating the efficiency and precision of ANN-MLP in geological classification. This research highlights the integration of artificial intelligence in geology especially in geological modeling. [ABSTRACT FROM AUTHOR]

Published
2024
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50. An international assessment of the adoption of enhanced recovery after surgery (ERAS®) principles across colorectal units in 2019–2020

Author

Pinkney T., Taylor H., Tong C., Schmitz N. -D., Morton D. G., Pinkney T. D., Bhangu A., Blackwell S., Dardanov D., Dulskas A., Gallo G., Glasbey J., Keatley J., Knowles C., Li Y. E., McCourt V., Minaya-Bravo A., Neary P., Nepogodiev D., Pata F., Pellino G., Sivrikoz E., van Ramshorst G., Zmora O., Perry R., Magill E. L., Abdalkoddus M., Abelevich A., Abraham S., Abraham-Nordling M., Adamina M., Agalar C., Agresta F., Ahallat M., Ahmad N., Aiupov R., Akca O., Aleksic A., Aleotti F., Alias D., Alonso J., Alonso Goncalves S., Alonso Martin J., Alonso Poza A., Alonso-Hernandez N., Alos Company R., Al-Saeedi M., Alvarez-Laso C., Alvarez-Gallego M., Amanatidis T., Americano M., Amorim E., Anandan L., Anania G., Ancans G., Andreev P., Andrejevic P., Antonacci N., Anwer M., Aonzo P., Arencibia B., Argeny S., Arieli H., Arnold S., Ashraf M., Aslam M., Atanasov B., Atif M., Atladottir J., Avital S., Awny S., Aytac B., Azahr N., Aznar-Puig S., Bailey S., Balalis D., Baldi C., Baldonedo R., Balducci G., Balestra F., Balestri R., Balfour A., Baloyiannis I., Banky B., Baral J., Baranyai Z., Barbashinov N., Bargallo J., Barisic G., Barugola G., Batashki I., Battersby N., Belev N., Belli A., Beltran de Heredia J., Bemelman W., Benavides Buleje J., Benckert A., Bernal-Sprekelsen J., Bertocchi E., Beuran M., Bhan C., Bianco F., Bilali S., Bilali V., Bintintan V., Birindelli A., Birsan T., Blanco Antona F., Blas J., Blasco-Segura T., Blom R., Bocchetti T., Boerma E., Bogdan M., Boland M., Bomans B., Borda N., Bowen M., Bradulskis S., Branagan G., Brankovic B., Brenna M., Brewer H., Broadhurst J., Bronder C., Brouwer R., Buccianti P., Buchs N., Buchwald P., Bugatti A., Bui A., Burcos T., Buskens C., Bustamante C., Caceres N., Cagigas Fernandez C., Calero-Lillo A., Camps I., Canda A., Caravaca-Garcia I., Carballo F., Carcoforo P., Carlander J., Carlos S., Caro A., Carpelan A., Carrasco Prats M., Carrillo Lopez M., Carvello M., Casal E., Casoni Pattacini G., Castellvi Valls J., Castillo Diego J., Cavallesco G., Cavenaile V., Cayetano L., Ceccotti A., Cervera-Aldama J., Chabok A., Chafai N., Chandrasinghe P., Chandratreya N., Chaudhri S., Chaudhry Z., Cherdancev D., Chernov A., Chevallay M., Chirletti P., Chouillard E., Chouliaras C., Chowdri N., Cillo M., Cini C., Ciubotaru C., Ciuce C., Claeys D., Cocorullo G., Codina-Cazador A., Colak E., Coletta D., Colombo F., Copaescu C., Corte Real J., Corver M., Cosic J., Costa S., Costa Pereira J., Costa Pereira C., Costa-Navarro D., Cotte E., Cracco N., Cristian D., Cuadrado M., Cuk V., Cunha M., Cunha J., Curinga R., Curletti G., Curtis N., Dabic D., Dainius E., d'Alessandro A., Daniels I., Darvin V., Dauser B., David G., Davidova O., Davies E., de Andres Asenjo B., De franciscis S., de Graaf E., De la Portilla F., De Luca E., De Nisco C., De Toma G., Defoort B., Den Boer F., Di Candido F., Di Saverio S., Diaz Pavon J., Dieguez Fernandez B., Diez-Alonso M., Dimitrijevic I., Dindelegan G., Djuric M., Domingos H., Doornebosch P., Dos Santos M., Drami I., Dudarovaska H., Dusek T., Dzhumabaev H., Eden Y., Egenvall M., Eismiontas V., El Sorogy M., Elgeidie A., Elhemaly M., El-Hussuna A., Ellul S., Elmore U., ElNakeeb A., Elrefai M., Emile S., Enrriquez-Navascues J., Epstein J., Escartin J., Escola D., Escuder J., Espin E., Espina B., Estefania D., Etienne J., Fabbri S., Falato A., Fares R., Farina P., Farkasova M., Farres R., Fasolini F., Fatayer T., Febles G., Feliu F., Feo C., Feoktistov D., Fernandez F., Fernandez Isart M., Fernando J., Ferreira G., Ferrer R., Ferreras Garcia C., Ferri M., Figueiredo N., Finotti E., Fitzgerald J., Flateh Backe I., Flor-Lorente B., Forero-Torres A., Foschi D., Francart D., Francois Y., Frasson M., Freil-Lanter C., Frois Borges M., Fuzun M., Gala T., Galleano R., Galvez P., Galvez Saldana A., Gamundi Cuesta M., Garcia Cabrera A., Garcia Egea J., Garcia Olmo D., Garcia-Gonzalez J., Garcia-Granero A., Garcia-Granero E., Garcia-Septiem J., Gardea A., Garipov M., Gefen R., Geraghty A., Gerkis S., Germanos S., Ghaffari S., Ghilles E., Gianotti L., Gil Santos M., Gilsanz Martin C., Gingert C., Gklavas A., Glehen O., Golda T., Gomez N., Gomez R., Gomez Ruiz M., Gonzalez Santin V., Graham B., Grainger J., Grama F., Gregoir T., Gregori M., Grolich T., Grosek J., Guadalajara H., Guckenheimer S., Guevara J., Gulotta G., Gupta S., Gurevich N., Gurjar S., Haapaniemi S., Hahnloser D., Hamad Y., Hamid M., Hanly A., Harris G., Harsanyi L., Hartig N., Hawkin P., Henriques P., Herbst F., Hermann N., Hernandez Garcia M., Hoch J., Hrora A., Huhtinen H., Iarumov N., Ilkanich A., Insua C., Ioannidis P., Iqbal M., Iqbal A., Isik A., Ismaiel M., Ivlev D., Jadhav V., Jareno S., Jehaes C., Jimenez V., Jimenez-Toscano M., Jimenez-Miramon J., Jimenez-Rodriguez R., Jonsson T., Jotautas V., Julia D., Juloski J., Jung B., Kala Z., Kalayci M., Kara Y., Karachun A., Karagul S., Karvonen J., Katorkin S., Katsoulis I., Katsounis D., Kaubrys M., Kaul N., Kefalou E., Keijzers M., Kelly M., Kenic M., Kennelly R., Khan J., Khan M., Kho H., Kinas V., Knight J., Kocian P., Koeter T., Kokobelyan A., Konsten J., Koolen L., Kosir J., Kostic I., Krdzic I., Kreisler Moreno E., Krivokapic Z., Krstev P., Krsul D., Kumarasinghe N., La Torre F., Labarga F., Ladra M., Lage Laredo A., Lahodzich N., Lai C., Lakkis Z., Lal R., Lamas S., Lang T., Latkauskas T., Lawes D., Lazar G., Lebedev K., Lebedeva M., Lefevre J., Lekic Vitlov V., Lemma M., Leo C., Leon C., Leventoglu S., Levy B., Li L., Licari L., Lizdenis P., Loftas P., Longhi M., Longstaff L., Lopez Dominguez J., Lopez-Lara M., Lora P., Lorenzon L., Lorusso D., Lozev I., Lozoya Trujillo R., Lukic D., Lunins R., Luzan R., Luzzi A., Maderuelo V., Madsboll T., Mahotin D., Majbar M., Makhmudov A., Malik K., Maly O., Mamaloudis I., Mamedli Z., Manatakis D., Mandi D., Mangell P., Marharint T., Mariani N., Maric B., Marimuthu K., Marinello F., Marino F., Markiewicz S., Markovic V., Marom G., Maroni N., Maroulis I., Marsanic P., Marsman H., Martens M., Marti M., Martinek L., Martinez S., Martinez D., Martinez Manzano A., Martins R., Maslyankov S., McArdle K., McDermott F., Mege D., Mehraj A., Mehta A., Mendrila D., Menendez P., Mercantini P., Metwally I., Mikalauskas S., Millan M., Mingoli A., Mirshekar-Syahkal B., Moggia E., Mohan S., Moller P., Mompart Garcia S., Monami B., Moniz Pereira P., Montroni I., Morel P., Moshev B., Mostovoy E., Mothe S., Mukhtar H., Muller P., Munch S., Munoz Camarena J., Munoz-Collado S., Muratore A., Muscara F., Muysoms F., Myrelid P., N. Lah N., Nail S., Narayanan A., Nastos K., Negoi I., Nesbakken A., Nestler G., Nestorovic M., Nesytykh A., Newton K., Ng Y., Ngu J., Nguyen B., Nijs Y., Nikberg M., Nimmersgern T., Nogues E., Norcic G., Nutautiene V., Nygren J., O'Brien J., Ochogavia Segui A., O'Kelly J., Oliveira-Cunha M., Omar W., Omar G., Onishchenko S., Onody P., Opocher E., Orhalmi J., Oshowo A., Otero J., Ozgen U., Pace K., Padin H., Papaconstantinou I., Papadopoulos A., Papadopoulos G., Papandrea M., Paral J., Parc Y., Paredes J., Parmar M., Parra Banos P., Parray F., Pascual Damieta M., Pascual Miguelanez I., Passot G., Pastor C., Paszt A., Patel P., Paterson H., Patron Uriburu J., Paulos A., Pavlov V., Pcolkins A., Pecic V., Pena Ros E., Penkov R., Pera Roman M., Perunicic V., Pery R., Petrovic D., Pezzolla F., Photi E., Pikarsky A., Piramanayagam B., Pisani Ceretti A., Planellas P., Platt E., Pletinckx P., Podda M., Poskus T., Poskus E., Pozdnyakov A., Pravosudov I., Previsic A., Prieto D., Prochazka V., 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Cervera-Aldama J., Chabok A., Chafai N., Chandrasinghe P., Chandratreya N., Chaudhri S., Chaudhry Z., Cherdancev D., Chernov A., Chevallay M., Chirletti P., Chouillard E., Chouliaras C., Chowdri N., Cillo M., Cini C., Ciubotaru C., Ciuce C., Claeys D., Cocorullo G., Codina-Cazador A., Colak E., Coletta D., Colombo F., Copaescu C., Corte Real J., Corver M., Cosic J., Costa S., Costa Pereira J., Costa Pereira C., Costa-Navarro D., Cotte E., Cracco N., Cristian D., Cuadrado M., Cuk V., Cunha M., Cunha J., Curinga R., Curletti G., Curtis N., Dabic D., Dainius E., d'Alessandro A., Daniels I., Darvin V., Dauser B., David G., Davidova O., Davies E., de Andres Asenjo B., De franciscis S., de Graaf E., De la Portilla F., De Luca E., De Nisco C., De Toma G., Defoort B., Den Boer F., Di Candido F., Di Saverio S., Diaz Pavon J., Dieguez Fernandez B., Diez-Alonso M., Dimitrijevic I., Dindelegan G., Djuric M., Domingos H., Doornebosch P., Dos Santos M., Drami I., Dudarovaska H., Dusek T., Dzhumabaev H., Eden Y., Egenvall M., Eismiontas V., El Sorogy M., Elgeidie A., Elhemaly M., El-Hussuna A., Ellul S., Elmore U., ElNakeeb A., Elrefai M., Emile S., Enrriquez-Navascues J., Epstein J., Escartin J., Escola D., Escuder J., Espin E., Espina B., Estefania D., Etienne J., Fabbri S., Falato A., Fares R., Farina P., Farkasova M., Farres R., Fasolini F., Fatayer T., Febles G., Feliu F., Feo C., Feoktistov D., Fernandez F., Fernandez Isart M., Fernando J., Ferreira G., Ferrer R., Ferreras Garcia C., Ferri M., Figueiredo N., Finotti E., Fitzgerald J., Flateh Backe I., Flor-Lorente B., Forero-Torres A., Foschi D., Francart D., Francois Y., Frasson M., Freil-Lanter C., Frois Borges M., Fuzun M., Gala T., Galleano R., Galvez P., Galvez Saldana A., Gamundi Cuesta M., Garcia Cabrera A., Garcia Egea J., Garcia Olmo D., Garcia-Gonzalez J., Garcia-Granero A., Garcia-Granero E., Garcia-Septiem J., Gardea A., Garipov M., Gefen R., Geraghty A., Gerkis S., Germanos S., Ghaffari S., Ghilles E., Gianotti L., Gil Santos M., Gilsanz Martin C., Gingert C., Gklavas A., Glehen O., Golda T., Gomez N., Gomez R., Gomez Ruiz M., Gonzalez Santin V., Graham B., Grainger J., Grama F., Gregoir T., Gregori M., Grolich T., Grosek J., Guadalajara H., Guckenheimer S., Guevara J., Gulotta G., Gupta S., Gurevich N., Gurjar S., Haapaniemi S., Hahnloser D., Hamad Y., Hamid M., Hanly A., Harris G., Harsanyi L., Hartig N., Hawkin P., Henriques P., Herbst F., Hermann N., Hernandez Garcia M., Hoch J., Hrora A., Huhtinen H., Iarumov N., Ilkanich A., Insua C., Ioannidis P., Iqbal M., Iqbal A., Isik A., Ismaiel M., Ivlev D., Jadhav V., Jareno S., Jehaes C., Jimenez V., Jimenez-Toscano M., Jimenez-Miramon J., Jimenez-Rodriguez R., Jonsson T., Jotautas V., Julia D., Juloski J., Jung B., Kala Z., Kalayci M., Kara Y., Karachun A., Karagul S., Karvonen J., Katorkin S., Katsoulis I., Katsounis D., Kaubrys M., Kaul N., Kefalou E., Keijzers M., Kelly M., Kenic M., Kennelly R., Khan J., Khan M., Kho H., Kinas V., Knight J., Kocian P., Koeter T., Kokobelyan A., Konsten J., Koolen L., Kosir J., Kostic I., Krdzic I., Kreisler Moreno E., Krivokapic Z., Krstev P., Krsul D., Kumarasinghe N., La Torre F., Labarga F., Ladra M., Lage Laredo A., Lahodzich N., Lai C., Lakkis Z., Lal R., Lamas S., Lang T., Latkauskas T., Lawes D., Lazar G., Lebedev K., Lebedeva M., Lefevre J., Lekic Vitlov V., Lemma M., Leo C., Leon C., Leventoglu S., Levy B., Li L., Licari L., Lizdenis P., Loftas P., Longhi M., Longstaff L., Lopez Dominguez J., Lopez-Lara M., Lora P., Lorenzon L., Lorusso D., Lozev I., Lozoya Trujillo R., Lukic D., Lunins R., Luzan R., Luzzi A., Maderuelo V., Madsboll T., Mahotin D., Majbar M., Makhmudov A., Malik K., Maly O., Mamaloudis I., Mamedli Z., Manatakis D., Mandi D., Mangell P., Marharint T., Mariani N., Maric B., Marimuthu K., Marinello F., Marino F., Markiewicz S., Markovic V., Marom G., Maroni N., Maroulis I., Marsanic P., Marsman H., Martens M., Marti M., Martinek L., Martinez S., Martinez D., Martinez Manzano A., Martins R., Maslyankov S., McArdle K., McDermott F., Mege D., Mehraj A., Mehta A., Mendrila D., Menendez P., Mercantini P., Metwally I., Mikalauskas S., Millan M., Mingoli A., Mirshekar-Syahkal B., Moggia E., Mohan S., Moller P., Mompart Garcia S., Monami B., Moniz Pereira P., Montroni I., Morel P., Moshev B., Mostovoy E., Mothe S., Mukhtar H., Muller P., Munch S., Munoz Camarena J., Munoz-Collado S., Muratore A., Muscara F., Muysoms F., Myrelid P., N.Lah N., Nail S., Narayanan A., Nastos K., Negoi I., Nesbakken A., Nestler G., Nestorovic M., Nesytykh A., Newton K., Ng Y., Ngu J., Nguyen B., Nijs Y., Nikberg M., Nimmersgern T., Nogues E., Norcic G., Nutautiene V., Nygren J., O'Brien J., Ochogavia Segui A., O'Kelly J., Oliveira-Cunha M., Omar W., Omar G., Onishchenko S., Onody P., Opocher E., Orhalmi J., Oshowo A., Otero J., Ozgen U., Pace K., Padin H., Papaconstantinou I., Papadopoulos A., Papadopoulos G., Papandrea M., Paral J., Parc Y., Paredes J., Parmar M., Parra Banos P., Parray F., Pascual Damieta M., Pascual Miguelanez I., Passot G., Pastor C., Paszt A., Patel P., Paterson H., Patron Uriburu J., Paulos A., Pavlov V., Pcolkins A., Pecic V., Pena Ros E., Penkov R., Pera Roman M., Perunicic V., Pery R., Petrovic D., Pezzolla F., Photi E., Pikarsky A., Piramanayagam B., Pisani Ceretti A., Planellas P., Platt E., Pletinckx P., Podda M., Poskus T., Poskus E., Pozdnyakov A., Pravosudov I., Previsic A., Prieto D., Prochazka V., Prodan A., Proud D., Psaila J., Psaras G., Pulighe F., Pullig F., Qureshi M., Rachadell J., Radovanovic Z., Radovanovic D., Raguan B., Rahman M., Raiss M., Ramirez Faraco M., Ramos J., Ramos-Prada J., Rantala A., Rao M., Rasulov A., Ratnatunga K., Raymond T., Refky B., Reggiani L., Regusci L., Reyes Diaz M., Richardson J., Richiteanu G., Rios A., Ris F., Rodriguez Garcia P., Roffi N., Romairone E., Romano G., Romero I., Romero de Diego A., Romero-Simo M., Roque C., Rosati R., Rossi B., Rossi E., Rossini R., Ruano A., Rubbini M., Rubio-Perez I., Ruffo G., Ruiz H., Ruiz Carmona M., Ryska O., Sabia D., Sacchi M., Sacco R., Sakr A., Saladzinskas Z., Salamone G., Salomon M., Salvans Ruiz S., Sammarco G., Sampietro G., Samsonov D., Samsonyuk V., Sanchez J., Sanchez Romero A., Sanchez-Guillen L., Santak G., Santamaria-Olabarrieta M., Santos J., Saraceno F., Saralegui Y., Sarici I., Savino G., Scabini S., Schafli J., Schiltz B., Schofield A., Schon M., Scurtu R., Segalini E., Segelman J., Segura-Sampedro J., Seicean R., Sekulic A., Selniahina L., Seretis F., Serrano Paz P., Shaikh I., Shalaby M., Shams N., Sharma A., Sharma G., Shukla A., Shussman N., Shweejawee Z., Sielezneff I., Sigurdsson H., Sileri P., Silva M., Simcikas D., Simoes J., Simonka Z., Singh B., Sivins A., Skroubis G., Skull A., Slavchev M., Slavin M., Smart N., Smart C., Smart P., Smedh K., Smolarek S., Sokmen S., Sokolov M., Solana Bueno A., Solar L., Sorrentino L., Sotona O., Spacca D., Spinelli A., Stanojevic G., Stearns A., Stefan S., Stift A., Stijns J., Stoyanov V., Straarup D., Strupas K., Stubbs B., Subocius A., Sudlow A., Suero C., Sungurtekin U., Svagzdys S., Syk I., Tamelis A., Tamhane R., Tamini N., Tamosiunas A., Tanis P., Tarasov N., Tate S., Tennakoon A., Teo N., Terzi C., Tezas S., Thabet W., Tham J., Thavanesan N., Theodosopoulos T., Thomas W., Tiret E., Tiselius C., Todorov G., Tomazic A., Tomulescu V., Torkington J., Totis M., Trostchansky I., Truan N., Tulchinsky H., Tutino R., Tzivanakis A., Tzovaras G., Ugolini G., Unger L., Upanishad I., Urbani L., Uth Ovesen A., Vaizey C., Vallribera F., Valsdottir E., Valverde I., Valverde-Sintas J., Van Belle K., Van Cleven S., van Hagen P., van Loon Y., van Ruler O., Van Wijck K., Varabei A., Varcada M., Varpe P., Vartic M., Velchuru V., Vencius J., Venskutonis D., Vercher D., Vermaas M., Vertruyen M., Verza L., Vescio G., Vezakis A., Vieira P., Vignali A., Vigorita V., Vila Tura M., Vinson-Bonnet B., Viso Pons L., Voloshin S., Voronin Y., Vukusic L., Wang X., Wang J., Wani R., Warusavitarne J., Wasserberg N., Weerts J., Weiss D., Weizman A., Westerduin E., Wheat J., White I., Wik T., Wilson J., Winter D., Wolthuis A., Wong M., Yahia S., Yamamoto T., Yanishev A., Yao C., Yildiz A., Yuksel O., Zain Z., Zakaria A., Zakaria Z., Zampitis N., Zarand A., Zarco-Pleguezuelos A., Zattoni D., Zelic M., Zeromskas P., Zhuravlev A., Zimmerman D., Zuhdy M., Zukanovic G., Pinkney, T. D., Taylor, H., Tong, C., Schmitz, N. -D., Morton, D. G., Bhangu, A., Blackwell, S., Dardanov, D., Dulskas, A., Gallo, G., Glasbey, J., Keatley, J., Knowles, C., Li, Y. E., Mccourt, V., Minaya-Bravo, A., Neary, P., Nepogodiev, D., Pata, F., Pellino, G., Sivrikoz, E., van Ramshorst, G., Zmora, O., Perry, R., Magill, E. L., Abdalkoddus, M., Abelevich, A., Abraham, S., Abraham-Nordling, M., Adamina, M., Agalar, C., Agresta, F., Ahallat, M., Ahmad, N., Aiupov, R., Akca, O., Aleksic, A., Aleotti, F., Alias, D., Alonso, J., Alonso Goncalves, S., Alonso Martin, J., Alonso Poza, A., Alonso-Hernandez, N., Alos Company, R., Al-Saeedi, M., Alvarez-Laso, C., Alvarez-Gallego, M., Amanatidis, T., Americano, M., Amorim, E., Anandan, L., Anania, G., Ancans, G., Andreev, P., Andrejevic, P., Antonacci, N., Anwer, M., Aonzo, P., Arencibia, B., Argeny, S., Arieli, H., Arnold, S., Ashraf, M., Aslam, M., Atanasov, B., Atif, M., Atladottir, J., Avital, S., Awny, S., Aytac, B., Azahr, N., Aznar-Puig, S., Bailey, S., Balalis, D., Baldi, C., Baldonedo, R., Balducci, G., Balestra, F., Balestri, R., Balfour, A., Baloyiannis, I., Banky, B., Baral, J., Baranyai, Z., Barbashinov, N., Bargallo, J., Barisic, G., Barugola, G., Batashki, I., Battersby, N., Belev, N., Belli, A., Beltran de Heredia, J., Bemelman, W., Benavides Buleje, J., Benckert, A., Bernal-Sprekelsen, J., Bertocchi, E., Beuran, M., Bhan, C., Bianco, F., Bilali, S., Bilali, V., Bintintan, V., Birindelli, A., Birsan, T., Blanco Antona, F., Blas, J., Blasco-Segura, T., Blom, R., Bocchetti, T., Boerma, E., Bogdan, M., Boland, M., Bomans, B., Borda, N., Bowen, M., Bradulskis, S., Branagan, G., Brankovic, B., Brenna, M., Brewer, H., Broadhurst, J., Bronder, C., Brouwer, R., Buccianti, P., Buchs, N., Buchwald, P., Bugatti, A., Bui, A., Burcos, T., Buskens, C., Bustamante, C., Caceres, N., Cagigas Fernandez, C., Calero-Lillo, A., Camps, I., Canda, A., Caravaca-Garcia, I., Carballo, F., Carcoforo, P., Carlander, J., Carlos, S., Caro, A., Carpelan, A., Carrasco Prats, M., Carrillo Lopez, M., Carvello, M., Casal, E., Casoni Pattacini, G., Castellvi Valls, J., Castillo Diego, J., Cavallesco, G., Cavenaile, V., Cayetano, L., Ceccotti, A., Cervera-Aldama, J., Chabok, A., Chafai, N., Chandrasinghe, P., Chandratreya, N., Chaudhri, S., Chaudhry, Z., Cherdancev, D., Chernov, A., Chevallay, M., Chirletti, P., Chouillard, E., Chouliaras, C., Chowdri, N., Cillo, M., Cini, C., Ciubotaru, C., Ciuce, C., Claeys, D., Cocorullo, G., Codina-Cazador, A., Colak, E., Coletta, D., Colombo, F., Copaescu, C., Corte Real, J., Corver, M., Cosic, J., Costa, S., Costa Pereira, J., Costa Pereira, C., Costa-Navarro, D., Cotte, E., Cracco, N., Cristian, D., Cuadrado, M., Cuk, V., Cunha, M., Cunha, J., Curinga, R., Curletti, G., Curtis, N., Dabic, D., Dainius, E., D'Alessandro, A., Daniels, I., Darvin, V., Dauser, B., David, G., Davidova, O., Davies, E., de Andres Asenjo, B., De franciscis, S., de Graaf, E., De la Portilla, F., De Luca, E., De Nisco, C., De Toma, G., Defoort, B., Den Boer, F., Di Candido, F., Di Saverio, S., Diaz Pavon, J., Dieguez Fernandez, B., Diez-Alonso, M., Dimitrijevic, I., Dindelegan, G., Djuric, M., Domingos, H., Doornebosch, P., Dos Santos, M., Drami, I., Dudarovaska, H., Dusek, T., Dzhumabaev, H., Eden, Y., Egenvall, M., Eismiontas, V., El Sorogy, M., Elgeidie, A., Elhemaly, M., El-Hussuna, A., Ellul, S., Elmore, U., Elnakeeb, A., Elrefai, M., Emile, S., Enrriquez-Navascues, J., Epstein, J., Escartin, J., Escola, D., Escuder, J., Espin, E., Espina, B., Estefania, D., Etienne, J., Fabbri, S., Falato, A., Fares, R., Farina, P., Farkasova, M., Farres, R., Fasolini, F., Fatayer, T., Febles, G., Feliu, F., Feo, C., Feoktistov, D., Fernandez, F., Fernandez Isart, M., Fernando, J., Ferreira, G., Ferrer, R., Ferreras Garcia, C., Ferri, M., Figueiredo, N., Finotti, E., Fitzgerald, J., Flateh Backe, I., Flor-Lorente, B., Forero-Torres, A., Foschi, D., Francart, D., Francois, Y., Frasson, M., Freil-Lanter, C., Frois Borges, M., Fuzun, M., Gala, T., Galleano, R., Galvez, P., Galvez Saldana, A., Gamundi Cuesta, M., Garcia Cabrera, A., Garcia Egea, J., Garcia Olmo, D., Garcia-Gonzalez, J., Garcia-Granero, A., Garcia-Granero, E., Garcia-Septiem, J., Gardea, A., Garipov, M., Gefen, R., Geraghty, A., Gerkis, S., Germanos, S., Ghaffari, S., Ghilles, E., Gianotti, L., Gil Santos, M., Gilsanz Martin, C., Gingert, C., Gklavas, A., Glehen, O., Golda, T., Gomez, N., Gomez, R., Gomez Ruiz, M., Gonzalez Santin, V., Graham, B., Grainger, J., Grama, F., Gregoir, T., Gregori, M., Grolich, T., Grosek, J., Guadalajara, H., Guckenheimer, S., Guevara, J., Gulotta, G., Gupta, S., Gurevich, N., Gurjar, S., Haapaniemi, S., Hahnloser, D., Hamad, Y., Hamid, M., Hanly, A., Harris, G., Harsanyi, L., Hartig, N., Hawkin, P., Henriques, P., Herbst, F., Hermann, N., Hernandez Garcia, M., Hoch, J., Hrora, A., Huhtinen, H., Iarumov, N., Ilkanich, A., Insua, C., Ioannidis, P., Iqbal, M., Iqbal, A., Isik, A., Ismaiel, M., Ivlev, D., Jadhav, V., Jareno, S., Jehaes, C., Jimenez, V., Jimenez-Toscano, M., Jimenez-Miramon, J., Jimenez-Rodriguez, R., Jonsson, T., Jotautas, V., Julia, D., Juloski, J., Jung, B., Kala, Z., Kalayci, M., Kara, Y., Karachun, A., Karagul, S., Karvonen, J., Katorkin, S., Katsoulis, I., Katsounis, D., Kaubrys, M., Kaul, N., Kefalou, E., Keijzers, M., Kelly, M., Kenic, M., Kennelly, R., Khan, J., Khan, M., Kho, H., Kinas, V., Knight, J., Kocian, P., Koeter, T., Kokobelyan, A., Konsten, J., Koolen, L., Kosir, J., Kostic, I., Krdzic, I., Kreisler Moreno, E., Krivokapic, Z., Krstev, P., Krsul, D., Kumarasinghe, N., La Torre, F., Labarga, F., Ladra, M., Lage Laredo, A., Lahodzich, N., Lai, C., Lakkis, Z., Lal, R., Lamas, S., Lang, T., Latkauskas, T., Lawes, D., Lazar, G., Lebedev, K., Lebedeva, M., Lefevre, J., Lekic Vitlov, V., Lemma, M., Leo, C., Leon, C., Leventoglu, S., Levy, B., Li, L., Licari, L., Lizdenis, P., Loftas, P., Longhi, M., Longstaff, L., Lopez Dominguez, J., Lopez-Lara, M., Lora, P., Lorenzon, L., Lorusso, D., Lozev, I., Lozoya Trujillo, R., Lukic, D., Lunins, R., Luzan, R., Luzzi, A., Maderuelo, V., Madsboll, T., Mahotin, D., Majbar, M., Makhmudov, A., Malik, K., Maly, O., Mamaloudis, I., Mamedli, Z., Manatakis, D., Mandi, D., Mangell, P., Marharint, T., Mariani, N., Maric, B., Marimuthu, K., Marinello, F., Marino, F., Markiewicz, S., Markovic, V., Marom, G., Maroni, N., Maroulis, I., Marsanic, P., Marsman, H., Martens, M., Marti, M., Martinek, L., Martinez, S., Martinez, D., Martinez Manzano, A., Martins, R., Maslyankov, S., Mcardle, K., Mcdermott, F., Mege, D., Mehraj, A., Mehta, A., Mendrila, D., Menendez, P., Mercantini, P., Metwally, I., Mikalauskas, S., Millan, M., Mingoli, A., Mirshekar-Syahkal, B., Moggia, E., Mohan, S., Moller, P., Mompart Garcia, S., Monami, B., Moniz Pereira, P., Montroni, I., Morel, P., Moshev, B., Mostovoy, E., Mothe, S., Mukhtar, H., Muller, P., Munch, S., Munoz Camarena, J., Munoz-Collado, S., Muratore, A., Muscara, F., Muysoms, F., Myrelid, P., N. 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Subjects
medicine.medical_specialty, Prehabilitation, medicine.medical_treatment, MEDLINE, Colorectal Neoplasm, Perioperative Care, NO, medicine, Humans, 03.02. Klinikai orvostan, Perioperative Optimisation, Enhanced recovery after surgery, Digestive System Surgical Procedures, LS7_4, Enhanced Recovery After Surgery (ERAS), business.industry, Gastroenterology, Digestive System Surgical Procedure, Guideline, Colorectal surgery, Surgery, Family medicine, Perioperative care, Nasogastric intubation, Preoperative fasting, Colorectal Neoplasms, Enhanced Recovery After Surgery, business, Colorectal Surgery, Human
Abstract

Aim The Enhanced Recovery After Surgery (ERAS® ) Society guidelines aim to standardise perioperative care in colorectal surgery via 25 principles. We aimed to assess the variation in uptake of these principles across an international network of colorectal units. Method An online survey was circulated amongst European Society of Coloproctology members in 2019/20. For each ERAS® principle, respondents were asked to score how frequently the principle was implemented in their hospital, from 1 ('rarely') to 4 ('always'). Respondents were also asked to recall whether practice had changed since 2017. Subgroup analyses based on hospital characteristics were conducted. Results Of hospitals approached, 58% responded to the survey (195/335), with 296 individual responses (multiple responses were received from some hospitals). The majority were European (163/195 [83.6%]). Overall, respondents indicated they 'most often' or 'always' adhered to most individual ERAS® principles (18/25 [72%]). Variability in uptake of principles was reported, with universal uptake of some principles (e.g., prophylactic antibiotics; early mobilisation) and inconsistency from 'rarely' to 'always' in others (e.g., no nasogastric intubation; no preoperative fasting and carbohydrate drinks). In alignment with 2018 ERAS® guideline updates, adherence to principles for prehabilitation, managing anaemia, and postoperative nutrition appears to have increased since 2017. Conclusions Uptake of ERAS® principles varied across hospitals, and not all 25 principles were equally adhered to. Whilst some principles exhibited a high level of acceptance, others had a wide variability in uptake indicative of controversy or barriers to uptake. Further research into specific principles is required to improve ERAS® implementation.

Published
2021
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