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Avelumab and cetuximab as a therapeutic combination: An overview of scientific rationale and current clinical trials in cancer.

Cancer Treat Rev 2021 Mar 2;97:102172. Epub 2021 Mar 2.

Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Treatment outcomes have improved with the advent of immune checkpoint inhibitors and small molecule inhibitors. However, many patients do not respond with single agents. Consequently, ongoing research is focused on the use of combination therapies to increase clinical efficacy by potential synergistic effects. Read More

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Cell-autonomous role of EGFR in spontaneous duodenal tumors in LRIG1 null mice.

Cell Mol Gastroenterol Hepatol 2021 May 11. Epub 2021 May 11.

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. Electronic address:

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Efficacy and Safety of Intrathecal Pemetrexed Combined with Dexamethasone for Treating TKI-failed Leptomeningeal Metastases from EGFR-mutant NSCLC-A Prospective Open-label Single-arm Phase I/II Clinical Trial (unique identifier: ChiCTR1800016615).

J Thorac Oncol 2021 May 11. Epub 2021 May 11.

Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address:

Introduction: We aimed to examine the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LM) from EGFR-mutant non-small cell lung cancer (NSCLC).

Methods: EGFR-mutant NSCLC patients with LM who had failed tyrosine-kinase inhibitors (TKIs) were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a Phase I study. Read More

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Kidney Function and Outcomes in Patients Hospitalized with Heart Failure.

J Am Coll Cardiol 2021 May 4. Epub 2021 May 4.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Background: Few contemporary data exist evaluating care patterns and outcomes in HF across the spectrum of kidney function.

Objectives: To characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction.

Methods: We evaluated quality metrics among patients hospitalized with HF at 418 sites in the GWTG-HF registry from 2014-2019 by discharge CKD-EPI-derived eGFR. Read More

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SOX9 promotes epidermal growth factor receptor-tyrosine kinase inhibitor resistance via targeting β-catenin and epithelial to mesenchymal transition in lung cancer.

Life Sci 2021 May 11:119608. Epub 2021 May 11.

Cancer Drug Resistance Laboratory, Department of Life Science, National Institute of Technology Rourkela, Odisha 769008, India. Electronic address:

Aims: The first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), gefitinib, continues to be a primary treatment option for lung cancer patients. However, acquisition of resistance to gefitinib is a major obstacle in lung cancer treatment and its cause is poorly understood. The present study aimed to implicate the role of SOX9-β-catenin in developed resistance to gefitinib through epithelial to mesenchymal transition (EMT) in lung cancer in vitro and ex vitro. Read More

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Pesticide Use and Kidney Function Among Farmers in the Biomarkers of Exposure and Effect in Agriculture Study.

Environ Res 2021 May 11:111276. Epub 2021 May 11.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. Electronic address:

Background: Pesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction.

Objective: We evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study. Read More

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Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial.

Lancet Oncol 2021 May 11. Epub 2021 May 11.

Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Background: Pembrolizumab (PD-1 inhibitor) and cetuximab (EGFR inhibitor) are active as single agents and in combination with cytotoxic chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Given each drug's single agent activity and unique mechanism of action, we aimed to evaluate the anti-tumour activity of PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC.

Methods: This study is an open-label, non-randomised, multi-arm, phase 2 trial done at four academic centres in the USA. Read More

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Isolated autosomal recessive woolly hair/hypotrichosis: genetics, pathogenesis and therapies.

Authors:
Masashi Akiyama

J Eur Acad Dermatol Venereol 2021 May 14. Epub 2021 May 14.

Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Isolated autosomal recessive woolly hair/hypotrichosis (ARWH) is a rare hereditary hair disease characterized by tightly curled sparse hair at birth or in early infancy. Patients with ARWH consist of genetically heterogeneous groups. Woolly hair autosomal recessive 1 (ARWH1) (MIM #278150), woolly hair autosomal recessive 2 (ARWH2) (MIM #604379) and woolly hair autosomal recessive 3 (ARWH3) (MIM #616760) are caused by mutations in LPAR6, LIPH and KRT25, respectively. Read More

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Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology.

Neurochem Res 2021 May 14. Epub 2021 May 14.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, Liaoning, People's Republic of China.

Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs). Read More

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Quantitative evaluation of COVID-19 pneumonia severity by CT pneumonia analysis algorithm using deep learning technology and blood test results.

Jpn J Radiol 2021 May 14. Epub 2021 May 14.

Department of Diagnostic and Interventional Radiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Purpose: To evaluate whether early chest computed tomography (CT) lesions quantified by an artificial intelligence (AI)-based commercial software and blood test values at the initial presentation can differentiate the severity of COVID-19 pneumonia.

Materials And Methods: This retrospective study included 100 SARS-CoV-2-positive patients with mild (n = 23), moderate (n = 37) or severe (n = 40) pneumonia classified according to the Japanese guidelines. Univariate Kruskal-Wallis and multivariate ordinal logistic analyses were used to examine whether CT parameters (opacity score, volume of opacity, % opacity, volume of high opacity, % high opacity and mean HU total on CT) as well as blood test parameters [procalcitonin, estimated glomerular filtration rate (eGFR), C-reactive protein, % lymphocyte, ferritin, aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, creatine kinase, hemoglobin A1c, prothrombin time, activated partial prothrombin time (APTT), white blood cell count and creatinine] differed by disease severity. Read More

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Outcomes of Kidney Donors With Impaired Fasting Glucose.

Transplantation 2021 Feb 5. Epub 2021 Feb 5.

1Department of Medicine, Houston Methodist Hospital, Houston, TX 2Department of Pathology and Genomic Medicine, Institute for Academic Medicine, Houston Methodist Hospital, Houston, TX 3Department of Surgery, Houston Methodist Hospital, Houston, TX 4Department of Surgery, University of Minnesota, Minneapolis, MN.

Background: Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes mellitus (DM) are currently excluded from kidney donation fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney.

Methods: We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 -2007 according to donation fasting plasma glucose (FPG): <100 mg/dL (n = 6204), 100 - 125 mg/dL (n = 1826), ≥126 mg/dL (n = 250).

Results: Donors with IFG and those with FPG≥126 mg/dL were older, less likely to be non-Hispanic white, had a higher BMI and were more likely to be related to their recipient. Read More

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February 2021

Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus.

Transplantation 2021 Feb 22. Epub 2021 Feb 22.

1 Nephrology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil. 2 Infectious Diseases Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil. 3 Immunogenetics Institute, Associação Fundo de Incentivo à Pesquisa, São Paulo, Brazil. 4 Pathology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil. 5 Urology Division, Hospital do Rim, Universidade Federal de São Paulo, São Paulo, Brazil.

Background: The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus is lacking.

Methods: This is a 5-year follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3 mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus, and prednisone (r-ATG/EVR, n=85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n=102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n=101). Read More

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February 2021

Real-world data on treatment outcomes in mutant non-small-cell lung cancer patients receiving osimertinib in second or further lines.

Future Oncol 2021 May 14. Epub 2021 May 14.

Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, 35128, Italy.

This study describes real-world outcomes of pretreated T790M-positive (T790M) advanced non-small-cell lung cancer patients progressing after first- or second-generation tyrosine kinase inhibitors and receiving osimertinib, compared with T790M-negative (T790M) patients. We have also described progression patterns and treatment sequences. This is a retrospective multicenter Italian observational study including consecutive Caucasian patients referred between 2014 and 2018. Read More

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Plasma mutation abundance affects clinical response to first-line EGFR-TKIs in patients with advanced non-small cell lung cancer.

Ann Transl Med 2021 Apr;9(8):635

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Activated epidermal growth factor receptor () mutation is the main pathogenic cause of non-small cell lung cancer (NSCLC) in Asia. However, the impact of plasma mutation abundance, especially of the ultra-low abundance of mutation detected by highly sensitive techniques on clinical outcomes of first-line EGFR tyrosine kinase inhibitors (TKIs) for advanced NSCLC patients remains unclear.

Methods: We qualitatively detected baseline status of NSCLC tissues using amplification-refractory mutation system and quantified the plasma abundance of mutations through next-generation sequencing (NGS). Read More

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Postoperative adjuvant EGFR-TKIs for resected -mutant NSCLC-opportunities and obstacles.

Ann Transl Med 2021 Apr;9(7):586

University of Queensland Thoracic Research Centre at The Prince Charles Hospital, Brisbane, Australia.

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Association between renal function and retinal neurodegeneration in Chinese patients with type 2 diabetes mellitus.

Ann Transl Med 2021 Apr;9(7):560

Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China.

Background: Chronic kidney disease (CKD) and diabetic retinopathy (DR) are two serious complications of diabetes. However, the association between retinal neurodegeneration in DR and renal function decline is still unclear. Our objective was to evaluate the association by measure estimated glomerular filtration rate (eGFR), macular ganglion cell-inner plexiform layer (GC-IPL), and ganglion cell complex (GCC) thickness in patients with type 2 diabetes mellitus (T2DM). Read More

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A computed tomography (CT)-derived radiomics approach for predicting primary co-mutations involving and epidermal growth factor receptor () in patients with advanced lung adenocarcinomas (LUAD).

Ann Transl Med 2021 Apr;9(7):545

Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Epidermal growth factor receptor () co-mutated with could reduce responsiveness to tyrosine kinase inhibitors (TKIs) and worsen patients' prognosis compared to wild type patients in.

Egfr: mutated lung adenocarcinomas (LUAD). To identify this genetically unique subset prior to treatment through computed tomography (CT) images had not been reported yet. Read More

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Blood Omega-3 Fatty Acids Are Inversely Associated With Albumin-Creatinine Ratio in Young and Healthy Adults (The Omega-Kid Study).

Front Cardiovasc Med 2021 27;8:622619. Epub 2021 Apr 27.

Department of Internal Medicine, Cantonal Hospital of Baden, Baden, Switzerland.

Omega-3 fatty acids are associated with a lower risk of cardiovascular disease (CVD) and with beneficial effects on CV risk factors. The albumin-creatinine ratio (ACR) is a risk factor for CVD, all-cause mortality and accelerated glomerular filtration rate (GFR) decline in the general population. We aimed to investigate the association between n-3 PUFAS and ACR in heathy individuals with preserved GFR. Read More

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Cost-Effectiveness Analysis of Atezolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer With Different PD-L1 Expression Status.

Front Oncol 2021 27;11:669195. Epub 2021 Apr 27.

Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Atezolizumab could significantly improve clinical outcomes and was associated with less toxicity compared with chemotherapy as the first-line treatment of PD-L1-selected patients with EGFR and ALK wild-type metastatic non-small-cell lung cancer (NSCLC). However, the economic outcomes remain unclear yet in China. This study aimed to investigate the cost-effectiveness of atezolizumab versus chemotherapy as first-line therapy for metastatic NSCLC with different PD-L1 expression status from the Chinese health sector perspective. Read More

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In vitro and in silico anticancer potential analysis of sp. extract against human lung cancer cell line, A549.

3 Biotech 2021 Jun 7;11(6):254. Epub 2021 May 7.

Microbial Technology Lab, Acharya Narendra Dev College, University of Delhi, Govindpuri, Kalkaji, New Delhi, 110 019 India.

During our previous investigation, bioactive compounds present in the extract of sp. strain 196 were characterized using LC-MS/MS and H NMR studies. These compounds were K-252-C aglycone indolocarbazole alkaloid, decoyinine, and cycloheximide; the study of these natural drugs against lung carcinoma is still limited. Read More

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TUC338 Promotes Diffuse Large B Cell Lymphoma Growth via Regulating EGFR/PI3K/AKT Signaling Pathway.

J Oncol 2021 19;2021:5593720. Epub 2021 Apr 19.

Department of Hematology, Handan First Hospital, Handan, Hebei 056002, China.

TUC338 is emerging as a novel vital long noncoding RNA (lncRNA) in human cancer; however, its role in diffuse large B cell lymphoma (DLBCL) remains unknown. In this study, we found that TUC338 was remarkably upregulated in DLBCL tissues as compared to matched normal tissues. High TUC338 was closely related to advanced Ann Arbor stage, resistance to CHOP-like treatment, and high IPI (International Prognostic Index). Read More

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Recent Understanding and Future Directions of Recurrent Corticotroph Tumors.

Front Endocrinol (Lausanne) 2021 26;12:657382. Epub 2021 Apr 26.

Neuroendocrinology Clinic, Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. "Non-functioning" or silent CTs (SCT) and the Crooke's cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Read More

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SH-1028, An Irreversible Third-Generation EGFR TKI, Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer.

Front Pharmacol 2021 27;12:665253. Epub 2021 Apr 27.

Department of Pharmacy, China Pharmaceutical University, Nanjing, China.

SH-1028 is an irreversible third-generation EGFR TKI. Both SH-1028 and osimertinib have a pyrimidine structure (a typical mutant-selective EGFR TKI structure). Compared with osimertinib, SH-1028 is modified on the indole ring, thus resulting in a more stable 6,7,8,9-tetrahydro-pyrrolo [1, 2-a] indol structure. Read More

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Distribution of estimated glomerular filtration rate and determinants of its age dependent loss in a German population-based study.

Sci Rep 2021 May 13;11(1):10165. Epub 2021 May 13.

Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.

Glomerular filtration rate (GFR) declines with age by approx. 1 ml/min/m per year beginning in the third decade of life. At 70 years of age > 40 ml/min/m of GFR will be lost. Read More

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Ciliated muconodular papillary tumor/bronchiolar adenoma of the lung.

Semin Diagn Pathol 2021 Apr 19. Epub 2021 Apr 19.

Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Ciliated muconodular papillary tumor (CMPT) is an uncommon tumor of the lung, usually detected incidentally in the peripheral lung fields on computed tomography. It is most commonly diagnosed in patients between the sixth and last decades of life. The canonical microscopic feature is a tripartite mixture of ciliated columnar, mucous, and basal cells with papillary architecture. Read More

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Updates in the molecular pathology of non-small cell lung cancer.

Semin Diagn Pathol 2021 Apr 25. Epub 2021 Apr 25.

Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Sydney, NSW, Australia. Electronic address:

An understanding of the molecular pathology of non-small cell lung cancer (NSCLC) is important for pathologists as molecular characterization is now required for treatment decisions in advanced stage disease. While assessment for EGFR mutations, ALK and ROS1 fusions, and in some countries BRAF mutations, is now standard practice, other oncogenic mutations are also emerging that may impact routine clinical practice including alterations involving KRAS, NTRK, RET, MET and HER2. In addition, molecular pathology alterations of NSCLC are associated with responses to immune checkpoint therapy and are being increasingly investigated. Read More

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Long-term renal outcome in methylmalonic acidemia in adolescents and adults.

Orphanet J Rare Dis 2021 May 13;16(1):220. Epub 2021 May 13.

Adult Nephrology and Transplantation Department, Hôpital Necker Enfants Malades, APHP, 149 rue de Sèvres, 75015, Paris, France.

Background: Chronic kidney disease (CKD) is one of the main long-term prognosis factors in methylmalonic acidemia (MMA), a rare disease of propionate catabolism. Our objective was to precisely address the clinical and biological characteristics of long-term CKD in MMA adolescent and adult patients.

Patients And Methods: In this retrospective study, we included MMA patients older than 13 years who had not received kidney and/or liver transplantation. Read More

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miR-155 and miR-146a collectively regulate meningitic Escherichia coli infection-mediated neuroinflammatory responses.

J Neuroinflammation 2021 May 13;18(1):114. Epub 2021 May 13.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.

Background: Escherichia coli is the most common Gram-negative bacterium causing meningitis, and E. coli meningitis is associated with high mortality and morbidity throughout the world. Our previous study showed that E. Read More

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Association between Kidney Function, Proteinuria and the Risk of Kidney Cancer: a Nationwide Cohort Study involving 10 Million Participants.

Am J Epidemiol 2021 May 12. Epub 2021 May 12.

Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Chronic kidney disease in its later stages is associated with increased kidney cancer risk. We investigated whether chronic kidney disease at milder stages is associated with increased risk of kidney cancer, using a retrospective cohort of 9,809,317 adults in Republic of Korea who participated in a nationwide health screening (2009-2016). We examined the impact of estimated glomerular filtration rate (eGFR), dipstick proteinuria, and interactive associations of the two factors on the risk of incident kidney cancer. Read More

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Outcome Stratified Analysis of Biomarker Trajectories for Patients With SARS-CoV-2 Infection.

Am J Epidemiol 2021 May 12. Epub 2021 May 12.

Department of Biostatistics Johns Hopkins University Bloomberg School of Public Health, Baltimore Maryland.

Longitudinal trajectories of vital signs and biomarkers during admission remain poorly characterized for COVID-19 patients despite their potential to provide critical insights about disease progression. We studied 1884 patients with SARS-CoV2 infection from 3/4/2020-6/25/2020 within one Maryland hospital system and used a retrospective longitudinal framework with linear mixed-effects models to investigate relevant biomarker trajectories leading up to three critical outcomes: mechanical ventilation, discharge, and death. Trajectories of four vital signs (respiratory rate, SpO2/FiO2, pulse, and temperature) and four lab values (C-reactive protein (CRP), absolute lymphocyte count (ALC), estimated glomerular filtration rate (eGFR), and D-dimer) clearly distinguished the trajectories of COVID-19 patients. Read More

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