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Therapeutic aspects of bile acid signalling in the gut-liver axis.

Aliment Pharmacol Ther 2021 Sep 23. Epub 2021 Sep 23.

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Background: Bile acids are important endocrine modulators of intestinal and hepatic signalling cascades orchestrating critical pathophysiological processes in various liver diseases. Increasing knowledge on bile acid signalling has stimulated the development of synthetic ligands of nuclear bile acid receptors and other bile acid analogues.

Aim: This review summarises important aspects of bile acid-mediated crosstalk between the gut and the liver ("gut-liver axis") as well as recent findings from experimental and clinical studies. Read More

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September 2021

Accelerating drug access from advanced to early breast cancer: the special case of oral selective estrogen receptor degraders.

Curr Opin Oncol 2021 Sep 22. Epub 2021 Sep 22.

Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada University of New South Wales, Kensington, New South Wales, Australia.

Purpose Of Review: For hormone receptor positive breast cancer, the development of endocrine resistance commonly occurs, presenting as either disease progression in the metastatic setting or recurrence during or following adjuvant endocrine therapy. Various mechanisms of resistance have been described. In order to reduce or overcome endocrine resistance, there has been substantial interest in developing potent and orally bioavailable selective estrogen receptor degraders (SERDs) for metastatic disease and select patients with early-stage estrogen receptor positive breast cancer. Read More

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September 2021

Clinicopathological and Prognostic Features of 67 Cases with Pulmonary Sarcomatoid Carcinoma: An 18-Year Single-Centre Experience.

Oncol Res Treat 2021 Sep 23:1-10. Epub 2021 Sep 23.

Department of Medical Oncology, Istanbul University Institute of Oncology, Istanbul, Turkey.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a very rare subtype of non-small-cell lung cancer (NSCLC). It is frequently diagnosed in the advanced stage and is resistant to conventional chemotherapeutics. Due to the unique nature and rarity, we evaluated the epidemiological, clinicopathological, and survival data of PSC patients treated at our centre. Read More

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September 2021

High Inter- and Intratumoral Variability of Ki67 Labeling Index in Newly Diagnosed Prostate Cancer with High Gleason Scores.

Pathobiology 2021 Sep 23:1-7. Epub 2021 Sep 23.

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: The majority of studies investigating the role of Ki67 labeling index (LI) in prostate carcinoma (PC) focused on localized PC treated radically, where Ki67 LI is regarded as a prognostic marker. The relevance of Ki67 in advanced PC remains largely unexplored. While Gleason score is still one of the best indicators of clinical outcomes in PC, differences in progression-free survival and overall survival in patients with high Gleason scores suggest that additional factors are involved in tumor progression. Read More

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September 2021

Neurology consultations in the intensive care units.

Clin Neurol Neurosurg 2021 Sep 2;209:106930. Epub 2021 Sep 2.

Dokuz Eylül University, Faculty of Medicine, Department of Neurology, İzmir, Turkey. Electronic address:

Objective: Critical treatment and management have advanced over the recent decades, bringing many benefits but also causing increasing complication rates. Among these complications, neurological complications have an important place and may increase in mortality rates. The aim of our study was to find the causes of neurological consultations in the level 3 adult intensive care units (ICU). Read More

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September 2021

Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab.

Mult Scler Relat Disord 2021 Sep 15;56:103266. Epub 2021 Sep 15.

Neuroimmunology Unit, National Institute of Neurology and Neurosurgery, Mexico City, Mexico. Electronic address:

Background: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. Read More

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September 2021

Oncoplastic Mammoplasty with disguised geometric compensation.

Surg Oncol 2021 Sep 20;39:101660. Epub 2021 Sep 20.

Gynaecology and Breast Unit, Araujo Jorge Cancer Hospital, ACCG, Goiania, Goias, Brazil; Program of Mastology, Department of Gynaecology and Obstetrics, Federal University of Goiás, Goiania, Goias, Brazil.

Objective: To evaluate the results of a cohort of patients submitted to a new technique of oncoplastic mammoplasty, referred to as Disguised Geometric Compensation Mammoplasty (GCM), which is suitable for tumours involving the glandular tissue in the pillars of the mammoplasty.

Materials And Methods: Twenty-five breast tumours involving the pillars of the mammoplasty were included, 20 (80.0%) invasive ductal carcinomas, 3 (12. Read More

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September 2021

Individual patient data meta-analysis of neoadjuvant chemotherapy followed by surgery versus upfront surgery for carcinoma of the oesophagus or the gastro-oesophageal junction.

Eur J Cancer 2021 Sep 20;157:278-290. Epub 2021 Sep 20.

Oncostat U1018, Inserm, Université Paris-Saclay, Équipe Labellisée Ligue Contre le Cancer, Villejuif, France; Bureau de Biostatistiques et Epidémiologie, Gustave Roussy Cancer Campus, Villejuif, France.

Introduction: Which neoadjuvant treatment for locally advanced thoracic oesophagus (TE) or gastro-oesophageal junction carcinoma is best remains an open question. Randomised controlled trials variously accrued patients with adenocarcinoma and squamous cell carcinoma, making strong conclusions hard to obtain. The primary objective of this individual participant data meta-analysis was to investigate the effect of neoadjuvant chemotherapy on overall survival (OS). Read More

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September 2021

Lightweight deep neural networks for cholelithiasis and cholecystitis detection by point-of-care ultrasound.

Comput Methods Programs Biomed 2021 Aug 30;211:106382. Epub 2021 Aug 30.

Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan. Electronic address:

Background And Objective: Emergency physicians (EPs) frequently deal with abdominal pain, including that is caused by either gallstones or acute cholecystitis. Easy access and low cost justify point-of-care ultrasound (POCUS) use as a first-line test to detect these diseases; yet, the detection performance of POCUS by EPs is unreliable, causing misdiagnoses with serious impacts. This study aimed to develop a machine learning system to detect and localize gallstones and to detect acute cholecystitis by ultrasound (US) still images taken by physicians or technicians for preliminary diagnoses. Read More

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NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options.

J Hepatol 2021 Sep 20. Epub 2021 Sep 20.

Department of Medicine I, University Medical Center of the Johannes-Gutenberg University Mainz, Germany. Electronic address:

In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying etiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation due to excessive accumulation of neutral lipids in the liver are characterized by several unique features: In contrast to viral-driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis, and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and diagnosis occurs more frequently at an advanced stage. Read More

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September 2021

Morphological Changes in Nasal Mucosa in Patients with Sarcoidosis.

Clin Otolaryngol 2021 Sep 23. Epub 2021 Sep 23.

Pulmonary Department of Aristotle University of Thessaloniki, Thessaloniki, Greece.

•Changes in the microvascular network of the nasal mucosa may be accompanied by changes in olfaction. •Contact endoscopic changes in the microvascular network of the nasal mucosa may be used as a marker of sinonasal sarcoidosis. •A modified version of the Negoro's classification, in use for the tongue mucosa, may be used for the classification of contact endoscopic microvascular patterns of the nasal mucosa in patients with sarcoidosis •The validation of the use of the vascular patterns of nasal mucosa on contact endoscopy as a marker of nasal disease activity is a major future research challenge •Contact endoscopy emerges as a promising technique for on-site diagnosis of early, advanced or late inflammatory mucosal spots or generalized mucosal affection in sarcoidosis. Read More

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September 2021

Advanced radiotherapy technique in hepatocellular carcinoma with portal vein thrombosis: Feasibility and clinical outcomes.

PLoS One 2021 23;16(9):e0257556. Epub 2021 Sep 23.

Faculty of Medicine, Division of Radiation Oncology, Department of Radiology, Chulalongkorn University, Bangkok, Thailand.

Background: In Thailand, individuals with hepatocellular carcinoma (HCC) who develop portal vein tumor thrombosis (PVTT) have a restricted treatment option because to the extent of the disease, poor underlying liver function, and non-coverage of immuno/targeted therapy. Radiotherapy (RT) plays an increasingly important function in these patients. To investigate the feasibility, efficacy, and adverse event rates, we performed a retrospective analysis of patients with HCC with PVTT who underwent 3-dimensional conformal radiation (3DCRT), intensity-modulated radiation (IMRT), volumetric-modulated radiotherapy (VMAT), and stereotactic body radiotherapy (SBRT) in a single-institution. Read More

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September 2021

Effect of advanced periodontal self-care in patients with early-stage periodontal diseases on endothelial function: An open-label, randomized controlled trial.

PLoS One 2021 23;16(9):e0257247. Epub 2021 Sep 23.

Department of Translational Research, Tsurumi University School of Dental Medicine, Yokohama, Japan.

Although a significant association between periodontal disease and atherosclerotic cardiovascular disease has been reported, their cause-to-effect relationship remains controversial. This randomized controlled clinical trial aimed to investigate the effect of advanced self-care on atherosclerotic cardiovascular disease-related vascular function markers flow-mediated brachial artery dilatation (FMD) and serum asymmetric dimethylarginine (ADMA) level in patients with early-stage periodontal disease. The study was designed as a parallel group, 3-month follow-up, open-label, randomized controlled trial. Read More

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September 2021

Epigenetic-based targeted therapies for well-differentiated pancreatic neuroendocrine tumors: recent advances and future perspectives.

Expert Rev Endocrinol Metab 2021 Sep 23:1-13. Epub 2021 Sep 23.

F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy.

Introduction: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of primary tumors of the endocrine pancreas. Dysregulation of chromatin remodeling, gene expression alteration, global DNA hypomethylation of non-coding regions, DNA hypermethylation and silencing of tumor suppressor gene promoters are frequent epigenetic changes in PanNETs. These changes exert a role in neoplastic transformation and progression. Read More

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September 2021

An advanced self-care delivery model for leg ulcer management: a service evaluation.

J Wound Care 2021 Sep;30(9):751-762

L&R Medical UK Ltd.

Background: Lower limb ulceration is a common cause of suffering in patients and its management poses a significant burden on the NHS, with venous leg ulcers (VLUs) being the most common hard-to-heal wound in the UK. It is estimated that over one million patients in the UK have lower limb ulceration, of which 560,000 were categorised as VLUs, with a cost burden of over £3 billion each year.

Objective: The aim of this service evaluation was to assess the effects of implementing a self-care delivery model on clinical outcomes with the intention of limiting face-to-face health professional contact to one appointment every 6 weeks. Read More

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September 2021

My Cancer Genome: Coevolution of Precision Oncology and a Molecular Oncology Knowledgebase.

JCO Clin Cancer Inform 2021 Sep;5:995-1004

Rush University Medical Center, Chicago, IL.

Purpose: The My Cancer Genome (MCG) knowledgebase and resulting website were launched in 2011 with the purpose of guiding clinicians in the application of genomic testing results for treatment of patients with cancer. Both knowledgebase and website were originally developed using a wiki-style approach that relied on manual evidence curation and synthesis of that evidence into cancer-related biomarker, disease, and pathway pages on the website that summarized the literature for a clinical audience. This approach required significant time investment for each page, which limited website scalability as the field advanced. Read More

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September 2021

Clinical, advanced imaging data and outcome of inflammatory and neoplastic orbital disease in 81 dogs and 16 cats in Australia (2010-2019).

Vet Ophthalmol 2021 Sep 23. Epub 2021 Sep 23.

Department of Ophthalmology, Small Animal Specialist Hospital, Sydney, New South Wales, Australia.

Objective: To characterize the clinical presentation, advanced imaging features, and outcome of orbital disease in a referral population of dogs and cats that underwent computed tomography (CT) or magnetic resonance imaging (MRI).

Animals Studied: Client-owned animals.

Procedures: Animals referred for orbital disease undergoing ophthalmic examination and either head MRI or CT were included. Read More

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September 2021

Evaluation of a Novel Cardiac Signal Processing System for Electrophysiology Procedures: The PURE EP 2.0 Study.

J Cardiovasc Electrophysiol 2021 Sep 23. Epub 2021 Sep 23.

Texas Cardiac Arrhythmia Institute, Austin, Texas.

Background: Intracardiac electrogram data remain one of the primary diagnostic inputs guiding complex ablation procedures. However, the technology to collect, process, and display intracardiac signals has known shortcomings and has not advanced in several decades.

Objective: The purpose of this study was to evaluate a new signal processing platform, the PURE EP™ system (PURE), in a multi-center, prospective study. Read More

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September 2021

Liver stiffness measurement as a quantitative method for liver fibrosis in children with non-alcoholic fatty liver disease: A meta-analysis.

J Paediatr Child Health 2021 Sep 23. Epub 2021 Sep 23.

Department of Ultrasound, The Chenggong Hospital, Xiamen University, Xiamen, China.

Aim: This study assessed the diagnostic performance of liver stiffness measurement (LSM) in detecting liver fibrosis in paediatric patients with non-alcoholic fatty liver disease (NAFLD) through meta-analysis.

Methods: Online database searches of PubMed, EMBASE, the Cochrane Library and the Web of Science were conducted for studies that evaluated the performance of LSM for diagnosing liver fibrosis in paediatric patients with NAFLD until 1 January 2021. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. Read More

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September 2021

Pharmacodynamic Modeling of CDK4/6 Inhibition Related Biomarkers and the Characterization of the Relationship between Biomarker Response and Progression Free Survival in Patients with Advanced Breast Cancer.

J Clin Pharmacol 2021 Sep 23. Epub 2021 Sep 23.

Clinical pharmacology, Pfizer, San Diego, CA, USA.

Identification of a pharmacodynamic (PD) biomarker which is predictive of the efficacy outcome is of ultimate interest in drug development. The objectives of the current analyses are to develop the PKPD model for biomarkers (thymidine kinase 1 (TK1) in serum and phosphor-Rb (pRb) and Ki67 in skin tissues) related to CDK4/6 inhibition by palbociclib and to explore the relationship of the biomarker response with the efficacy endpoint (PFS). The data used for analysis consisted of extensive sampling of palbociclib PK and longitudinal rich sampling for the PD biomarkers TK1, pRb, and Ki67 in 26 patients. Read More

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September 2021

Lack of cross-resistance between non-steroidal and steroidal aromatase inhibitors in breast cancer patients: the potential role of the adipokine leptin.

Breast Cancer Res Treat 2021 Sep 23. Epub 2021 Sep 23.

Department of Oncology, Akershus University Hospital, Lørenskog, Norway.

Purpose: The aromatase inactivator exemestane may cause clinical disease stabilization following progression on non-steroidal aromatase inhibitors like letrozole in patients with metastatic breast cancer, indicating that additional therapeutic effects, not necessarily related to estrogen-suppression, may be involved in this well-known "lack of cross-resistance".

Methods: Postmenopausal women with ER positive, HER-2 negative, locally advanced breast cancer were enrolled in the NEOLETEXE-trial and randomized to sequential treatment starting with either letrozole (2.5 mg o. Read More

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September 2021

A phase II study of sequential treatment with anthracycline and taxane followed by eribulin in patients with HER2-negative, locally advanced breast cancer (JBCRG-17).

Breast Cancer Res Treat 2021 Sep 23. Epub 2021 Sep 23.

Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, Japan.

Purpose: The sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.

Methods: In this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. Read More

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September 2021

Impact of preoperative comorbidities on postoperative complication rate and outcome in surgically resected non-small cell lung cancer patients.

Gen Thorac Cardiovasc Surg 2021 Sep 23. Epub 2021 Sep 23.

Department of Thoracic Surgery, Zurich University Hospital, Raemistrasse 100, 8091, Zurich, Switzerland.

Objective: This study aimed to analyze whether comorbidities impact postoperative complication rate or survival after anatomical lung resection for non-small cell lung cancer (NSCLC).

Methods: A retrospective analysis of 1219 patients who underwent NSCLC resection between 2000 and 2015 was performed. Analyzed comorbidities included chronic obstructive lung disease (COPD), hypertension, coronary artery disease (CAD), peripheral artery disease, myocardial infarction history, diabetes mellitus, renal insufficiency and other malignancies. Read More

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September 2021

Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review.

Clin Rheumatol 2021 Sep 23. Epub 2021 Sep 23.

Divsion of Cardiology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan.

Janus kinase (JAK) inhibitors have been developed as disease-modifying antirheumatic drugs. Despite the positive therapeutic impacts of JAK inhibitors, concerns have been raised regarding the risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE). A recent post hoc safety analysis of placebo-controlled trials of JAK inhibitors in rheumatoid arthritis (RA) reported an imbalance in the incidence of VTE for a 4-mg daily dose of baricitinib versus placebo. Read More

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September 2021

Pharmacokinetics and Efficacy of Human Hyperimmune Intravenous Immunoglobulin Treatment of SARS-CoV-2 Infection in Adult Syrian Hamsters.

Clin Infect Dis 2021 Sep 23. Epub 2021 Sep 23.

Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, Maryland, USA.

Background: Following the failure of antibody therapies in treating COVID-19 hospitalized patients we investigated the impact of viral replication on the pharmacokinetics (PK) and efficacy of a hyperimmune SARS-CoV-2 Immune Globulin (CoVIG) product in treatment of SARS-CoV-2 infection using the adult Syrian hamster model.

Methods: The CoVIG was manufactured from plasma donors who had recovered from COVID-19. The dose used (400 mg/kg) was based on the dose given in clinical trials to hospitalized COVID-19 patients. Read More

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September 2021

timeOmics: an R package for longitudinal multi-omics data integration.

Bioinformatics 2021 Sep 23. Epub 2021 Sep 23.

Molecular Medicine Department, CHU de Québec Research Center, Université Laval, Québec, QC, Canada.

Motivation: Multi-omics data integration enables the global analysis of biological systems and discovery of new biological insights. Multi-omics experimental designs have been further extended with a longitudinal dimension to study dynamic relationships between molecules. However, methods that integrate longitudinal multi-omics data are still in their infancy. Read More

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September 2021

Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial.

JAMA Oncol 2021 Sep 23. Epub 2021 Sep 23.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Isocitrate dehydrogenase 1 (IDH1) variations occur in up to approximately 20% of patients with intrahepatic cholangiocarcinoma. In the ClarIDHy trial, progression-free survival as determined by central review was significantly improved with ivosidenib vs placebo.

Objective: To report the final overall survival (OS) results from the ClarIDHy trial, which aimed to demonstrate the efficacy of ivosidenib (AG-120)-a first-in-class, oral, small-molecule inhibitor of mutant IDH1-vs placebo for patients with unresectable or metastatic cholangiocarcinoma with IDH1 mutation. Read More

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September 2021

Analysis of Population Differences in Digital Conversations About Cancer Clinical Trials: Advanced Data Mining and Extraction Study.

JMIR Cancer 2021 Sep 23;7(3):e25621. Epub 2021 Sep 23.

Stand Up To Cancer, Los Angeles, CA, United States.

Background: Racial and ethnic diversity in clinical trials for cancer treatment is essential for the development of treatments that are effective for all patients and for identifying potential differences in toxicity between different demographics. Mining of social media discussions about clinical trials has been used previously to identify patient barriers to enrollment in clinical trials; however, a comprehensive breakdown of sentiments and barriers by various racial and ethnic groups is lacking.

Objective: The aim of this study is to use an innovative methodology to analyze web-based conversations about cancer clinical trials and to identify and compare conversation topics, barriers, and sentiments between different racial and ethnic populations. Read More

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September 2021

Systemic immune-inflammation index (SII) and neutrophil to lymphocyte ratio (NLR) are useful markers for assessing effects of anti-inflammatory diet in patients before coronary artery bypass grafting.

Rocz Panstw Zakl Hig 2021 ;72(3):327-335

Department of Haemostasis and Haemostatic Disorders, Faculty of Biomedical Sciences, Medical University of Lodz, Lodz, Poland.

Background: One of the risk factors responsible for coronary artery disease (CAD) is an inadequate diet that is frequently deficient in anti-inflammatory components, such as polyphenols and omega-3 fatty acids. The neutrophil to lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII) are inflammatory markers that may reflect a diet's antiinflammatory potential.

Objective: The aim of this study was to evaluate the effects that CAD patients' nutrition patterns have on NLR and SII. Read More

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January 2021