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Impact of the COVID-19 Pandemic on Oncology Clinical Research in Latin America (LACOG 0420).

JCO Glob Oncol 2021 04;7:649-658

Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.

Purpose: COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments.

Methods: This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group. Read More

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Predictive Factors of Chemotherapy Initiation after Biliary Drainage for Advanced Biliary Tract Cancer: A Retrospective Multicenter Study.

J Gastrointestin Liver Dis 2021 May 3. Epub 2021 May 3.

IMAD, Department of Gastroenterology and Digestive Oncology, University Hospital, Nantes, France.

Background And Aims: In unresectable biliary tract cancers, the management of biliary obstruction is often the first step before introduction of chemotherapy. Our aim was to study the predictive factors of chemotherapy initiation after biliary drainage in a series of patients presenting with advanced biliary tract cancer and obstructive jaundice.

Methods: Data of all patients treated for unresectable biliary tract cancer with initial biliary obstruction requiring a drainage in six institutions, from January 2009 to January 2019, were retrospectively collected. Read More

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Baseline total metabolic tumour volume on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography as a promising biomarker in patients with advanced non-small cell lung cancer treated with first-line pembrolizumab.

Eur J Cancer 2021 Apr 20;150:99-107. Epub 2021 Apr 20.

Medical Oncology, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Italy.

Introduction: Immune checkpoint inhibitors (ICIs) have become the standard of care in the management of advanced non-small cell lung cancer (NSCLC). Nevertheless, only a small proportion of patients benefit from ICIs. The aim of the present study is to assess whether 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography-computed tomography ([18F]FDG-PET/CT)-derived parameters may be used as biomarkers in patients with advanced NSCLC receiving first-line pembrolizumab. Read More

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Olefin oligomerization by main group Ga and Zn single site catalysts on SiO.

Nat Commun 2021 Apr 19;12(1):2322. Epub 2021 Apr 19.

Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA.

In heterogeneous catalysis, olefin oligomerization is typically performed on immobilized transition metal ions, such as Ni and Cr. Here we report that silica-supported, single site catalysts containing immobilized, main group Zn and Ga ion sites catalyze ethylene and propylene oligomerization to an equilibrium distribution of linear olefins with rates similar to that of Ni. The molecular weight distribution of products formed on Zn is similar to Ni, while Ga forms higher molecular weight olefins. Read More

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Neutrophil-to-Lymphocyte Ratio Is a Predictive Biomarker in Patients with Epidermal Growth Factor Receptor (EGFR) Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) Treated with Tyrosine Kinase Inhibitor (TKI) Therapy.

Cancers (Basel) 2021 Mar 20;13(6). Epub 2021 Mar 20.

Hematology, Oncology and Cell Therapy, Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA.

Background: First-line treatment for patients with non-small cell lung cancer (NSCLC) with a sensitizing epidermal growth factor receptor () mutation is a tyrosine kinase inhibitor (TKI). Despite higher response rates and prolonged progression free survival (PFS) compared with platinum doublet chemotherapy, a subset of these patients do not receive prolonged benefit from these agents. We investigate if the neutrophil-to-lymphocyte ratio (NLR) and other markers of cachexia and chronic inflammation correlate with worse outcomes in these patients. Read More

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Mid-Term Audit of a National Peritoneal Surface Malignancy Program Implementation in a Low Middle Income Country: The Moroccan Experience.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Department of Surgical Oncology, Gustave Roussy, Cancer Campus, 114 Rue Edouard Vaillant, 94805 Villejuif, France.

Implementing a multimodal management of peritoneal surface malignancies is a steep and complex process, especially as complete cytoreductive surgery (CRS) is the backbone and the major prognostic factor for hyperthermic intraperitoneal chemotherapy (HIPEC) procedures. The implementation of such a program is a challenging process, particularly in low-middle income (LMIC) countries where ressource restrictions may represent a major hurdle to HIPEC appliances acquisition. Herein is the first audit of the implementation of a national peritoneal malignancy program in a north African country. Read More

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Zebrafish as a Neuroblastoma Model: Progress Made, Promise for the Future.

Cells 2021 Mar 6;10(3). Epub 2021 Mar 6.

Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.

For nearly a decade, researchers in the field of pediatric oncology have been using zebrafish as a model for understanding the contributions of genetic alternations to the pathogenesis of neuroblastoma (NB), and exploring the molecular and cellular mechanisms that underlie neuroblastoma initiation and metastasis. In this review, we will enumerate and illustrate the key advantages of using the zebrafish model in NB research, which allows researchers to: monitor tumor development in real-time; robustly manipulate gene expression (either transiently or stably); rapidly evaluate the cooperative interactions of multiple genetic alterations to disease pathogenesis; and provide a highly efficient and low-cost methodology to screen for effective pharmaceutical interventions (both alone and in combination with one another). This review will then list some of the common challenges of using the zebrafish model and provide strategies for overcoming these difficulties. Read More

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Living with and beyond metastatic non-small cell lung cancer: the survivorship experience for people treated with immunotherapy or targeted therapy.

J Cancer Surviv 2021 Mar 31. Epub 2021 Mar 31.

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.

Purpose: Immunotherapy (IT) and targeted therapy (TT) have improved survival for some patients with metastatic non-small cell lung cancer (NSCLC). Their lived experience is under-studied. We conducted a single centre, qualitative study to understand concerns and unmet needs amongst this novel survivor population. Read More

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Novel Nutrition-Based Nomograms to Assess the Outcomes of Lung Cancer Patients Treated With Anlotinib or Apatinib.

Front Oncol 2021 8;11:628693. Epub 2021 Mar 8.

Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Background: Previous studies have indicated that the changes in body composition during treatment are prognostic in lung cancer. The question which follows is it may be too late to identify vulnerable patients after treatment and to improve outcomes for these patients. In our study, we sought to explore the alterations of body composition and weight before the outset of the antiangiogenic treatment and its role in predicting clinical response and outcomes. Read More

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Management of nonbacterial thrombotic endocarditis (NBTE) in advanced non-small cell lung cancer (NSCLC) patients with driver mutation: two case reports.

Ann Palliat Med 2021 Mar 10;10(3):3475-3482. Epub 2021 Mar 10.

Respiratory Medicine Department, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute for Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Nonbacterial thrombotic endocarditis (NBTE) is a rare disease that most often found post mortem. Malignant neoplasms, particularly adenocarcinomas, are the common underlying diseases associated with NBTE. In recent years, remarkable advances in targeted therapy have been made, but the effectiveness in treating NBTE in patients with severe lung cancer is poorly reported. Read More

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Modeling and Parameter Subset Selection for Fibrin Polymerization Kinetics with Applications to Wound Healing.

Bull Math Biol 2021 Mar 22;83(5):47. Epub 2021 Mar 22.

Department of Mathematics, North Carolina State University, Box 8205, Raleigh, NC, 27695-8205, USA.

During the hemostatic phase of wound healing, vascular injury leads to endothelial cell damage, initiation of a coagulation cascade involving platelets, and formation of a fibrin-rich clot. As this cascade culminates, activation of the protease thrombin occurs and soluble fibrinogen is converted into an insoluble polymerized fibrin network. Fibrin polymerization is critical for bleeding cessation and subsequent stages of wound healing. Read More

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Patient characteristics, treatment patterns, and clinical outcomes among patients with previously treated recurrent or metastatic cervical cancer: A community oncology-based analysis.

Gynecol Oncol 2021 May 17;161(2):422-428. Epub 2021 Mar 17.

Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.

Objective: There is no standard systemic treatment for recurrent or metastatic cervical cancer (r/mCC) after failure of first-line (1L) therapy. This study characterizes the patient experience, treatment patterns, and clinical outcomes of patients who initiated second-line (2L) therapy for r/mCC in a US community oncology setting.

Methods: This is an observational study of cervical cancer patients who failed 1L systemic treatment for r/mCC and initiated 2L systemic therapy between 2014 and 2019 within the US Oncology Network (USON). Read More

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Fast progression in non-small cell lung cancer: results from the randomized phase III OAK study evaluating second-line atezolizumab versus docetaxel.

J Immunother Cancer 2021 Mar;9(3)

Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland.

Background: Treatment-induced accelerated tumor growth is a progression pattern reported with immune checkpoint inhibitors that has never been evaluated in randomized phase III studies because it requires two pretreatment scans. This study aimed to develop clinically relevant and applicable criteria for fast progression (FP), incorporating tumor growth kinetics and early death from disease progression to analyze data from the randomized phase III OAK study.

Methods: The OAK study evaluated the efficacy and safety of atezolizumab versus docetaxel as second-line or third-line treatment for stage IIIb/IV non-small cell lung cancer. Read More

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Emergency management collaboration: A review and new collaboration cycle.

J Emerg Manag 2021 Jan-Feb;19(1):57-68

Associate Professor, Department of Emergency Management and Disaster Science, University of North Texas, Denton, Texas.

Objective: The purpose of this article is to review the nature of collaborations in the field of emergency management and to propose a new cyclical framework that better reflects how collaborations form, function, and evolve throughout the collaboration process.

Design: An extensive review of previous literature pertaining to the collaborative process was carried out in order to identify stages through which these collaborative relationships progress in the emergency management arena.

Setting: This article focuses on the nature of emergency management collaborations at the local, state, and federal levels in the United States. Read More

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Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage.

Virulence 2021 12;12(1):968-980

Department of Preventive Veterinary Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, P. R. China.

Thousands of human deaths occur annually due to Japanese encephalitis (JE), caused by Japanese encephalitis virus. During the virus infection of the central nervous system, reactive gliosis, uncontrolled inflammatory response, and neuronal cell death are considered as the characteristic features of JE. To date, no specific treatment has been approved to overcome JE, indicating a need for the development of novel therapies. Read More

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December 2021

Co-condensation between transcription factor and coactivator p300 modulates transcriptional bursting kinetics.

Mol Cell 2021 04 1;81(8):1682-1697.e7. Epub 2021 Mar 1.

Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China. Electronic address:

The coactivator p300/CREB-binding protein (CBP) regulates genes by facilitating the assembly of transcriptional machinery and by acetylating histones and other factors. However, it remains mostly unclear how both functions of p300 are dynamically coordinated during gene control. Here, we showed that p300 can orchestrate two functions through the formation of dynamic clusters with certain transcription factors (TFs), which is mediated by the interactions between a TF's transactivation domain (TAD) and the intrinsically disordered regions of p300. Read More

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Functioning of PPR Proteins in Organelle RNA Metabolism and Chloroplast Biogenesis.

Front Plant Sci 2021 9;12:627501. Epub 2021 Feb 9.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, China.

The pentatricopeptide repeat (PPR) proteins constitute one of the largest nuclear-encoded protein families in higher plants, with over 400 members in most sequenced plant species. The molecular functions of these proteins and their physiological roles during plant growth and development have been widely studied. Generally, there is mounting evidence that PPR proteins are involved in the post-transcriptional regulation of chloroplast and/or mitochondrial genes, including RNA maturation, editing, intron splicing, transcripts' stabilization, and translation initiation. Read More

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February 2021

Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)? A feasibility randomised trial.

BMJ Open 2021 02 22;11(2):e046791. Epub 2021 Feb 22.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Objectives: To determine the feasibility of conducting a randomised trial of the effectiveness of cranberry extract in reducing antibiotic use by women with symptoms of acute, uncomplicated urinary tract infection (UTI).

Design: Open-label feasibility randomised parallel group trial.

Setting: Four general practices in Oxfordshire. Read More

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February 2021

Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung.

J Immunother Cancer 2021 Feb;9(2)

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Little is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC).

Methods: 125 consecutive patients with aLCNEC were identified in the electronic databases of 4 participating cancer centers. The patients were divided into group A (patients who received ICI, n=41) and group B (patients who did not receive ICI, n=84). Read More

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February 2021

Dynamics of Ku and bacterial non-homologous end-joining characterized using single DNA molecule analysis.

Nucleic Acids Res 2021 03;49(5):2629-2641

Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg SE 41296, Sweden.

We use single-molecule techniques to characterize the dynamics of prokaryotic DNA repair by non-homologous end-joining (NHEJ), a system comprised only of the dimeric Ku and Ligase D (LigD). The Ku homodimer alone forms a ∼2 s synapsis between blunt DNA ends that is increased to ∼18 s upon addition of LigD, in a manner dependent on the C-terminal arms of Ku. The synapsis lifetime increases drastically for 4 nt complementary DNA overhangs, independently of the C-terminal arms of Ku. Read More

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Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer.

Cancers (Basel) 2021 Jan 30;13(3). Epub 2021 Jan 30.

Department of Urology, Osaka Medical College, Osaka 569-8686, Japan.

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Read More

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January 2021

Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy.

JAMA Netw Open 2021 02 1;4(2):e2037120. Epub 2021 Feb 1.

Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Importance: Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group.

Objective: To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy.

Design, Setting, And Participants: This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020. Read More

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February 2021

Impact of Baseline Corticosteroids on Immunotherapy Efficacy in Patients With Advanced Melanoma.

J Immunother 2021 May;44(4):167-174

Cancer Centre of Southeastern Ontario.

This is a 2-center, retrospective study which aimed to evaluate the effect of baseline corticosteroid use on immunotherapy efficacy in patients with advanced melanoma. We included all patients with advanced unresectable and metastatic melanoma on single-agent programmed cell death protein 1 (PD-1) inhibitors at the Cancer Centre of Southeastern Ontario and London Regional Cancer Program. We defined baseline corticosteroid use as prednisone-equivalent of ≥10 mg within 30 days of immunotherapy initiation. Read More

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Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

Int J Radiat Oncol Biol Phys 2021 Feb 3. Epub 2021 Feb 3.

Department of Neurologic Surgery, University of Virginia Health System, Charlottesville, Virginia.

Purpose: This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial.

Methods And Materials: From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Read More

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February 2021

MicroRNA: a novel implication for damage and protection against ionizing radiation.

Environ Sci Pollut Res Int 2021 Apr 3;28(13):15584-15596. Epub 2021 Feb 3.

Hengyang Medical College, Institute of Cytology and Genetics, The Hengyang Key Laboratory of Cellular Stress Biology, University of South China, Hengyang, 421001, Hunan Province, People's Republic of China.

Ionizing radiation (IR) is a form of high energy. It poses a serious threat to organisms, but radiotherapy is a key therapeutic strategy for various cancers. It is significant to reduce radiation injury but maximize the effect of radiotherapy. Read More

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Association of Secure Messaging with Primary Care In-Person and Telephone Visits Among Veterans: a Matched Difference-in-Difference Analysis.

J Gen Intern Med 2021 Apr 2;36(4):946-951. Epub 2021 Feb 2.

Veterans Rural Health Resource Center-Iowa City, VA Office of Rural Health, and Center for Access and Delivery Research and Evaluation (CADRE) at the Iowa City VA Healthcare System, Iowa City, IA, USA.

Background: Secure messaging (SM) between patients and primary care teams has expanded care access but may impact other clinical encounters.

Objective: To study associations between SM use and primary care in-person and telephone visits in the Veterans Health Administration (VHA).

Design: The SM feature of VHA's patient portal, MyHealtheVet, supports asynchronous communication between patients and primary care teams. Read More

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Cooperative Heterometallic Catalysts for Lactide Ring-Opening Polymerization: Combining Aluminum with Divalent Metals.

Inorg Chem 2021 Feb 29;60(4):2294-2303. Epub 2021 Jan 29.

EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, U.K.

While homometallic (salen)Al catalysts display excellent performance in lactide ring-opening polymerization (ROP), heterometallic (salen)Al complexes have yet to be reported. Herein, we describe four heterobimetallic (salen)Al catalysts and show that the choice of the heterometal is key. Cooperative Al/Mg and Al/Zn combinations improved the catalyst activity by a factor of up to 11 compared to the mono-Al analogue, whereas the mono-Mg and mono-Zn analogues were completely inactive. Read More

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February 2021

Evaluation of General Practice Pharmacists: Study Protocol to Assess Interprofessional Collaboration and Team Effectiveness.

Int J Environ Res Public Health 2021 01 22;18(3). Epub 2021 Jan 22.

Discipline of Pharmacy, Faculty of Health, University of Canberra, Bruce ACT 2617, Australia.

The inclusion of pharmacists into general practices has expanded in Australia. However, there is a paucity of research examining interprofessional collaboration and team effectiveness after including a pharmacist into the general practice team in primary or community care. This is a protocol for a cross-national comparative mixed-methods study to (i) investigate interprofessional collaboration and team effectiveness within the general practice team after employing pharmacists in general practices in the Australian Capital Territory (ACT) and (ii) to compare interprofessional collaboration and team effectiveness of pharmacists in general practice across Australia with international sites. Read More

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January 2021

Potential involvement of environmental triggers in protein aggregation with mercuric chloride as a model.

Int J Biol Macromol 2021 Mar 21;174:153-161. Epub 2021 Jan 21.

School of Environmental Studies, Cochin University of Science and Technology, Kochi 682022, India. Electronic address:

Heavy metal based toxicity has a direct relation with the perturbation of protein structure. We have investigated the progressive unfolding of ovalbumin, in the presence of increasing concentration mercury (0-6.25 μM) using different spectroscopic techniques. Read More

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The Association between Serum Hemoglobin and Renal Prognosis of IgA Nephropathy.

J Clin Med 2021 Jan 19;10(2). Epub 2021 Jan 19.

Department of Internal Medicine, Chonnan National University Medical School & Hospital, Gwangju 61469, Korea.

Immunoglobin A (IgA) nephropathy causes chronic kidney disease worldwide. Therefore, identifying risk factors associated with the progression of IgA nephropathy is crucial. Anemia is a common complication of chronic kidney disease; however, few studies have investigated the effect of serum hemoglobin on the renal prognosis of IgA nephropathy. Read More

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January 2021