20,073 results match your criteria Investigational new drugs[Journal]


Therapeutic Trends in Pancreatic ductal adenocarcinoma (PDAC).

Expert Opin Investig Drugs 2018 Dec 12. Epub 2018 Dec 12.

d Early Phase Therapeutics Program , University of Arizona Cancer Center , Tucson AZ , USA .

Introduction: Prognosis remains dismal for pancreatic ductal adenocarcinoma (PDAC). Genomics and proteomics has depicted heterogeneity in PDAC. Collectively, this information could be useful in improving diagnosis, prognosis, modalities of therapy, treatment responses, deciphering drug resistance and new drug development. Read More

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December 2018

A Binding Potency Assay for Pritumumab and Ecto-Domain Vimentin.

Methods Mol Biol 2019 ;1904:401-415

Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, CA, USA.

Pritumumab, a natural human IgG1kappa mAb, was isolated from the regional lymph node of a patient with cervical cancer. This antibody has been reported to bind the cytoskeletal protein vimentin, and to cell surface expressed vimentin referred to as ecto-domain vimentin (EDV). Here, we report details of the development of a potency of binding assay for pritumumab as a prerequisite before pursuing clinical trials. Read More

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January 2019

Decontamination of Biobank Facilities.

Methods Mol Biol 2019 ;1897:227-241

Biospecimen Laboratory, Loma Linda University Cancer Center, Loma Linda, CA, USA.

Biobanks are facilities that collect, process, store, annotate, and distribute high-quality and well-maintained human biological specimens (biospecimens) for investigational use. They play a crucial role in biomarker research and contribute to our understanding about preventing, diagnosing, and treating diseases. Majority of the biospecimens are from patients volunteering to provide biospecimens that would normally be discarded after diagnostic or therapeutic procedures. Read More

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January 2019

Current and Emerging Therapeutic Options for Gastroparesis.

Gastroenterol Hepatol (N Y) 2018 Nov;14(11):639-645

Dr Myint, Dr Rieders, and Dr Tashkandi are gastroenterology fellows in the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center and are affiliated with Medical Faculty Associates, both in Washington, DC. Dr Borum is a professor of medicine at George Washington University School of Medicine in Washington, DC; director of the Division of Gastroenterology and Liver Diseases at George Washington University Medical Center; and is affiliated with Medical Faculty Associates. Dr Koh and Dr Stephen are in private practice in Silver Spring, Maryland. Dr Doman is a clinical professor of medicine at George Washington University School of Medicine and is in private practice in Silver Spring, Maryland.

Gastroparesis is a complex, debilitating dysmotility disorder with challenging symptom management. A diagnosis of gastroparesis is based on objectively delayed gastric emptying in the absence of mechanical obstruction. Given the limited efficacy of treatment options and serious side effects, significant research continues for therapeutic options for gastroparesis. Read More

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November 2018

Medication dosing for heart failure with reduced ejection fraction - opportunities and challenges.

Eur J Heart Fail 2018 Dec 10. Epub 2018 Dec 10.

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Multiple drug classes have shown incremental benefits in heart failure with reduced ejection fraction. Most of these trials were designed to achieve specific doses of the investigational agent. Clinical practice guidelines recommend using the same target dosing of therapies, as tolerated. Read More

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December 2018
2 Reads

Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management.

Am J Hematol 2018 Dec 8. Epub 2018 Dec 8.

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Overview: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs.

Diagnosis: The major criterion is presence of multifocal clusters of abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. Read More

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December 2018
8 Reads

Ethics codes and use of new and innovative drugs.

Br J Clin Pharmacol 2018 Dec 9. Epub 2018 Dec 9.

Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka Str. 59, 02-006, Warsaw, Poland.

Treatment with new and/or innovative drugs with uncertain safety and efficacy profile is associated with substantial ethical concerns. The main objective of this paper is to present guidance on the use of such drugs contained in: 1) major international codes and guidelines pertaining to medical ethics and biomedical research; 2) national codes of medical ethics and professional conduct of the US, Canada, Australia, New Zealand, the UK, Ireland, France and Germany. Out of the four international codes and guidelines analyzed, only the Declaration of Helsinki addresses the question of the use of unproven drugs. Read More

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December 2018

Correction to: An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis.

Pediatr Nephrol 2018 Dec 7. Epub 2018 Dec 7.

Children's Mercy Hospital, Kansas City, MO, USA.

The original version of this article unfortunately contained three mistakes. In Table 1, the last line under "Key Inclusion Criteria" should read "Normal or clinically acceptable ECGs at screening and at day - 1." In addition, the abbreviation "IP" in the legend to Table 1 stands for "investigational product. Read More

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December 2018
1 Read

Facilitators and Barriers to Contraceptive Use Among U.S. Servicewomen Who Had an Abortion.

Mil Med 2018 Dec 7. Epub 2018 Dec 7.

Ibis Reproductive Health, 2067 Massachusetts Avenue, Cambridge, MA.

Introduction: Despite evidence that the unintended pregnancy rate is higher among U.S. servicewomen than the general population and that servicewomen may face barriers to contraceptive use, there is little research about contraceptive access and use experiences of non-deployed active duty servicewomen. Read More

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December 2018
1 Read

Translational approaches in treatment-resistant depression based on animal model.

Rom J Morphol Embryol 2018 ;59(3):955-964

Department of Psychiatry, "Dr. Carol Davila" Central Military Emergency University Hospital, Bucharest, Romania;

An intensively researched and yet poorly understood phenomenon, both at clinical and neurobiological level, is the determinism of treatment-resistant depression. Even more controversial are the stages of approaching therapeutically this pathology because there are no evidence-based recommendations stating that a pharmacological agent is superior to another, on medium and long-term. Due to the lack of "golden standard" approaches, physician's experience, therapeutic alliance and a close monitoring stand as the most useful good practices in the treatment of resistant depression. Read More

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January 2018
1 Read

Activating Mutations in Contribute to Anal Carcinogenesis in the Presence or Absence of HPV-16 Oncogenes.

Clin Cancer Res 2018 Dec 7. Epub 2018 Dec 7.

McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health

Purpose: Over 95% of human anal cancers are etiologically associated with high-risk HPVs, with HPV type 16 (HPV16) the genotype most commonly found. Activating mutations in the catalytic subunit of Phosphatidylinositol (3,4,5)-trisphosphatekinase (PI3K), encoded by the gene, are detected in approximately 20% of human anal cancers.

Experimental Design: We asked if common activating mutations in contribute to anal carcinogenesis using an established mouse model for anal carcinogenesis in which mice are topically treated with the chemical carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA). Read More

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December 2018

Identification of swine protein biomarkers of inflammation-associated pain.

Res Vet Sci 2018 Dec 1;122:186-188. Epub 2018 Dec 1.

Center for Veterinary Medicine, Office of Research, Division of Applied Veterinary Research, 8401 Muirkirk Road, Laurel, MD 20708, United States.

This study sought to determine if proteins associated with pain in humans could be measured using a swine in vitro model of inflammation. This would constitute the first step towards using them as surrogate endpoints to help support effectiveness indications for investigational new animal drugs to control pain in swine. Swine whole blood samples were cultured in vitro with E. Read More

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December 2018

New developments in investigational HDAC inhibitors for the potential multimodal treatment of cachexia.

Expert Opin Investig Drugs 2018 Dec 10. Epub 2018 Dec 10.

b Interuniversity Institute of Myology , Italy.

Introduction: Cachexia is a frequent feature of chronic diseases. This syndrome includes loss of body weight, depletion of skeletal muscle mass and altered metabolic homeostasis. Acceleration of protein and energy metabolism, impaired myogenesis and systemic inflammation contribute to cachexia. Read More

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December 2018

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028.

Gynecol Oncol 2018 Dec 3. Epub 2018 Dec 3.

Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Objective: To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)-expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.

Methods: Key inclusion criteria were age ≥18 years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10 mg/kg every 2 weeks) for ≤24 months or until disease progression/intolerable toxicity. Read More

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December 2018

Single-Dose Pharmacokinetics and Pharmacodynamics of IPX203 in Patients With Advanced Parkinson Disease: A Comparison With Immediate-Release Carbidopa-Levodopa and With Extended-Release Carbidopa-Levodopa Capsules.

Clin Neuropharmacol 2018 Dec 4. Epub 2018 Dec 4.

Impax Laboratories, LLC, Hayward, CA.

Objective: IPX203 is an investigational oral extended-release capsule formulation of carbidopa-levodopa (CD-LD). The aim of this study was to characterize the single-dose pharmacodynamics, pharmacokinetics, and safety of IPX203 in subjects with advanced Parkinson disease compared with immediate-release (IR) CD-LD and extended-release CD-LD (Rytary).

Methods: This was a randomized, open-label, rater-blinded, multicenter, single-dose crossover study. Read More

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December 2018

Advanced Non Small Cell Lung Cancer with activating Epidermal Growth Factor Receptor mutation: First line treatment and beyond.

Rev Recent Clin Trials 2018 Dec 5. Epub 2018 Dec 5.

Division of Medical Oncology, AORN Giuseppe Moscati, Avellino. Italy.

Background: Lung cancer is the leading cause of cancer mortality, being responsible for more than 1.6 million deaths each year worldwide and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers; moreover, 10 to 15% of all NSCLCs harbors EGFR (epidermal growth factor receptor) activating mutations, being suitable for EGFR-Tyrosine Kinase Inhibitors (TKI) molecular targeted therapy. However, EGFR+ NSCLCs gain acquired resistance to these agents, representing one of the key challenges for modern precision oncology. Read More

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December 2018
1 Read

Preoperative Administration of Olive Oil Reduces Chylothorax after Minimally Invasive Esophagectomy.

Ann Thorac Surg 2018 Nov 30. Epub 2018 Nov 30.

Department of Surgical Oncology, Shantou Central Hospital, China. Electronic address:

Background: Chylothorax after esophagectomy is uncommon but potentially fatal. We performed a retrospective study to assess the effect of olive oil administered orally before surgery on reducing chylothorax in patients who underwent minimal invasive esophagectomy.

Methods: Between May 2013 and December 2016, patients with esophageal squamous cell cancer who underwent minimal invasive esophagectomy were screened. Read More

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November 2018
1 Read

Role of a high throughput biodosimetry test in treatment prioritization after a nuclear incident.

Int J Radiat Biol 2018 Dec 3:1-9. Epub 2018 Dec 3.

a DxTerity Diagnostics , Los Angeles , CA , USA.

Purpose: We introduce and evaluate a high throughput biodosimetry test system (REDI-Dx) suitable for testing of thousands of potential radiation victims following a mass scale nuclear event caused by detonation of a nuclear device or a nuclear accident, as part of an overall strategy for effective medical management of the crisis.

Materials And Methods: The performance of a high throughput biodosimetry test was evaluated by collecting samples of both non-irradiated presumed healthy donors as well as irradiated subjects collected as part of either cancer treatment regimens or banked from previous studies. The test measures the gene expression of a set of radiation responsive genes based on the DxDirect genomic platform. Read More

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December 2018

Stem cell-based cell therapy for neuroprotection in stroke: A review.

J Cell Biochem 2018 Dec 2. Epub 2018 Dec 2.

Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Neurological disorders, such as stroke, are triggered by a loss of neurons and glial cells. Ischemic stroke remains a substantial problem for industrialized countries. Over the previous few decades our understanding about the pathophysiology of stroke has enhanced, nevertheless, more awareness is required to advance the field of stroke recovery. Read More

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December 2018

A Videogame-Based Digital Therapeutic to Improve Processing Speed in People with Multiple Sclerosis: A Feasibility Study.

Neurol Ther 2018 Nov 30. Epub 2018 Nov 30.

Department of Neurology, Weill Institute for the Neurosciences, University of California, San Francisco, USA.

Introduction: Self-administered in-home digital therapeutics could expand access to cognitive rehabilitation for individuals with multiple sclerosis (MS), over half of whom experience cognitive impairment (CI). However, feasibility in an MS population must be clarified. This study was conducted to assess the feasibility of deploying a videogame-like digital treatment for CI in MS, including initial efficacy and barriers to adherence. Read More

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November 2018

Finite Element Analysis of the Mouse Distal Femur with Tumor Burden in Response to Knee Loading.

Int J Orthop (Hong Kong) 2018 28;5(1):863-871. Epub 2018 Feb 28.

Department of Mechanical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.

Breast cancer-associated bone metastasis induces bone loss, followed by an increased risk of bone fracture. To develop a strategy for preventing tumor growth and protecting bone, an understanding of the mechanical properties of bone under tumor burden is indispensable. Using a mouse model of mammary tumor, we conducted finite element analysis (FEA) of two bone samples from the distal femur. Read More

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February 2018
2 Reads

Immune-mediated neurological manifestations of dengue virus- a study of clinico-investigational variability, predictors of neuraxial involvement, and outcome with the role of immunomodulation.

Neurol India 2018 Nov-Dec;66(6):1634-1643

Department of Neurology, Government Medical College Kota, Rajasthan, India.

Introduction: Our aim was to study dengue-related immune-mediated neurological complications (IMNC) during the recent epidemic.

Materials And Methods: This was a cross-sectional observational study of 79 IMNC cases from 1627 laboratory confirmed dengue cases from January 2015 to January 2016 and their follow-up for 3 months. According to the World Health Organization, cases were categorized into those having dengue fever (DF), and those having a severe syndrome that includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Read More

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December 2018
4 Reads

Altered Transcranial Magnetic Stimulation-Electroencephalographic Markers of Inhibition and Excitation in the Dorsolateral Prefrontal Cortex in Major Depressive Disorder.

Biol Psychiatry 2018 Oct 18. Epub 2018 Oct 18.

Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: The neurophysiology of major depressive disorder (MDD) has become a particular focus of transcranial magnetic stimulation (TMS) investigational studies. TMS combined with electroencephalography (TMS-EEG) affords a window to directly measure evoked activity from the dorsolateral prefrontal cortex (DLPFC), which is of considerable interest in MDD. Our study examined TMS-EEG responses from the DLPFC in persons with MDD compared with those in healthy participants. Read More

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October 2018
1 Read

Audit of toxic effects of body paint in the Tiger dancers (Hulivesha) of Mangalore, India: an investigational study.

Cutan Ocul Toxicol 2018 Dec 2:1-26. Epub 2018 Dec 2.

h Father Muller Research Centre, Kankanady , Mangalore , India 575002.

Introduction: Tiger dancing or Hulivesha, where the volunteers paint their bare body like a tiger and dance is a ritual during the Navaratri festival in Mangalore, India. There are no scientific studies done with the hulivesha dancers at all and therefore we investigated the adverse effects of painting body like a tiger and dancing in the volunteers.

Objective/aim: In this study we investigated the clinicohematological effects of topical application of lead containing paint and dancing for three consecutive days in these dancers to ascertain the toxic effects of whole body painting and dancing. Read More

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December 2018

The Molecular Profiling Lottery: More Accuracy, Less Precision, and No Cost.

Authors:
Mark J Ratain

Clin Cancer Res 2018 Dec 4. Epub 2018 Dec 4.

Department of Medicine, Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, University of Chicago

The concept of complete molecular profiling to select investigational treatment options is appealing; theoretically allowing the matching of patients to investigational drugs specifically targeted to molecular features of each patient's cancer. While some patients do benefit from such a strategy, the vast majority do not. Read More

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December 2018
1 Read

Imaging Biomarkers for Precision Medicine in Locally Advanced Breast Cancer.

J Med Imaging Radiat Sci 2018 Dec 1;49(4):342-351. Epub 2018 Apr 1.

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada; Physical Sciences, Sunnybrook Research Institute, Toronto, Canada.

Guidelines from the American National Comprehensive Cancer Network recommend neoadjuvant chemotherapy to patients with locally advanced breast cancer (LABC) to downstage tumours before surgery. However, only a small fraction (15%-17%) of LABC patients achieve pathological complete response (pCR); that is, no residual tumour in the breast, after treatment. Measuring tumour response during neoadjuvant chemotherapy can potentially help physicians adapt treatment, thus potentially improving the pCR rate. Read More

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December 2018

Investigational therapies in phase II clinical trials for the treatment of soft tissue sarcoma.

Expert Opin Investig Drugs 2019 Jan 5;28(1):39-50. Epub 2018 Dec 5.

a Sarcoma, Melanoma and Genitourinary Tumors Unit , Institut Català d'Oncologia (ICO) L'Hospitalet , Barcelona , Spain.

Introduction: Soft-tissue sarcomas (STS) are a heterogeneous group of diseases that are characterized by a historic lack of active treatment options. However, several new drugs and indications have become available in recent years. Areas covered: This article reviews the most relevant phase II studies that utilize chemotherapy agents (aldoxorubicin, amrubicin, trabectedin alone or in combination with doxorubicin, and gemcitabine plus docetaxel), targeted therapies (Imatinib, dasatinib, regorafenib, tivozanib, palbociclib and selinexor), a combination of chemotherapy plus targeted therapies (fucusing on doxorubicin plus olaratumab) and immunotherapies (pembrolizumab, combination of nivolumab plus ipilimumab and adaptive cell therapy) in STS (other than gastrointestinal stromal tumors) (GIST) published from 2015. Read More

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January 2019

Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes.

Arch Toxicol 2018 Dec 3;92(12):3517-3533. Epub 2018 Dec 3.

Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.

Transcriptomics is developing into an invaluable tool in toxicology. The aim of this study was, using a transcriptomics approach, to identify genes that respond similar to many different chemicals (including drugs and industrial compounds) in both rat liver in vivo and in cultivated hepatocytes. For this purpose, we analyzed Affymetrix microarray expression data from 162 compounds that were previously tested in a concentration-dependent manner in rat livers in vivo and in rat hepatocytes cultivated in sandwich culture. Read More

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December 2018

Is One Sample Enough? β-lactam Target Attainment and Penetration into Epithelial Lining Fluid based on Multiple Bronchoalveolar Lavage Sampling Time Points in a Swine Pneumonia Model.

Antimicrob Agents Chemother 2018 Dec 3. Epub 2018 Dec 3.

Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA

Describing the disposition of antimicrobials agents at the site of infection is crucial to guide optimal dosing for investigational agents. For antibiotics in development for nosocomial pneumonia, concentrations are frequently determined in the epithelial lining fluid (ELF) of the lung from a bronchoscopy at a single time point. The influence of profiles constructed from a single ELF concentration point for each subject has never been reported. Read More

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December 2018
1 Read

Uveitis and spondyloarthropathies.

Best Pract Res Clin Rheumatol 2017 12 25;31(6):846-862. Epub 2018 Oct 25.

Oxford Eye Hospital, John Radcliffe Hospital, Headley Way, Oxford, United Kingdom. Electronic address:

Uveitis is a frequently occurring extra-articular manifestation of spondyloarthropathies (SpAs), ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA) and inflammatory bowel disease (IBD), occurring in both adults and children with SpA. Uveitis occurs with varying frequency according to the SpA subtype (33% in AS, 6-9% in PsA, 25% in ReA, 13% in undifferentiated SpA and 2-5% in IBD), the presence of HLA-B27 and with increasing duration of disease. The majority of cases of uveitis in SpA are attributed to acute anterior uveitis but a minority of uveitis cases occur in the posterior segment of the eye. Read More

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December 2017
1 Read

Reviewing the role of healthy volunteer studies in drug development.

J Transl Med 2018 Dec 4;16(1):336. Epub 2018 Dec 4.

Stanford Cancer Institute, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA.

Background: With the exception of genotoxic oncology drugs, first-in-human, Phase 1 clinical studies of investigational drugs have traditionally been conducted in healthy volunteers (HVs). The primary goal of these studies is to investigate the pharmacokinetics and pharmacodynamics of a novel drug candidate, determine appropriate dosing, and document safety and tolerability.

Main Body: When tailored to specific study objectives, HV studies are beneficial to manufacturers and patients alike and can be applied to both non-oncology and oncology drug development. Read More

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December 2018
1 Read

Hydatidiform Moles: Ancillary Techniques to Refine Diagnosis.

Arch Pathol Lab Med 2018 Dec;142(12):1485-1502

From the Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland.

Context.—: Distinction of hydatidiform moles from nonmolar specimens and subclassification of hydatidiform moles as complete hydatidiform mole versus partial hydatidiform mole are important for clinical practice and investigational studies. Risk of persistent gestational trophoblastic disease and clinical management differ for these entities. Read More

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December 2018
2 Reads

Stem Cells and Platelet-rich Plasma for Knee Osteoarthritis: Prevalence and Cost in South Florida.

J Am Acad Orthop Surg 2018 Nov 28. Epub 2018 Nov 28.

From the Department of Orthopaedic Surgery, Arthritis Surgery Research Foundation, Coral Gables, FL (Dr. Alcerro), the Department of Orthopedics & Rehabilitation, University of Miami, Coral Gables, FL (Dr. Lavernia), the Department of Mechanical and Materials Engineering (Dr. Lavernia), Florida International University, and the Department of Physical Therapy (Dr. Lavernia), Florida International University, University Park, FL.

Introduction: The use of stem cell therapy (SCT) and platelet-rich plasma (PRP) injection for knee osteoarthritis (OA) is extremely controversial and at best experimental stage. These treatments are being offered across the nation for "cash-only payments." Our objectives were to determine (1) what proportion of board-certified orthopedic surgeons in Miami-Dade County offer SCT or PRP and (2) how much do practices charge for these services. Read More

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November 2018
3 Reads

Development of PARP and Immune-Checkpoint Inhibitor Combinations.

Cancer Res 2018 Nov 29. Epub 2018 Nov 29.

Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine; Khalifa Institute for Personalized Cancer Therapy; Department of Thoracic/Head and Neck Medical Oncology; The Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas.

PARP inhibitors drive increased DNA damage, particularly in tumors with existing defects in DNA repair. This damage not only promotes immune priming through a range of molecular mechanisms, but also leads to adaptive upregulation of programmed death ligand 1 (PD-L1) expression. In this context, PARP inhibition and programmed cell death 1(PD-1)/PD-L1-targeting antibodies represent a rationale combination. Read More

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November 2018
3 Reads

The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase.

EBioMedicine 2018 Nov 27. Epub 2018 Nov 27.

Orphazyme A/S, Ole Maaloes vej 3, DK-2200 Copenhagen, Denmark. Electronic address:

Background: Gaucher Disease is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase function by perturbing its protein homeostasis rather than its catalytic activity. Heat shock proteins are well known cytoprotective molecules with functions in protein homeostasis and lysosomal function and their manipulation has been suggested as a potential therapeutic strategy for GD. Read More

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November 2018

Endocarditis After Transcatheter Pulmonary Valve Replacement.

J Am Coll Cardiol 2018 Dec;72(22):2717-2728

German Heart Center Munich, Munich, Germany.

Background: Endocarditis has emerged as one of the most concerning adverse outcomes in patients with congenital anomalies involving the right ventricular outflow tract (RVOT) and prosthetic valves.

Objectives: The aim of this study was to evaluate rates and potential risk factors for endocarditis after transcatheter pulmonary valve replacement in the prospective Melody valve trials.

Methods: All patients in whom a transcatheter pulmonary valve (TPV) was implanted in the RVOT as part of 3 prospective multicenter studies comprised the analytic cohort. Read More

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December 2018
1 Read

Artificial disc replacement versus fusion in patients with cervical degenerative disc disease with radiculopathy: 5-year outcomes from the National Swedish Spine Register.

Authors:

J Neurosurg Spine 2018 Oct 1:1-9. Epub 2018 Oct 1.

OBJECTIVEThe long-term efficacy of artificial disc replacement (ADR) surgery compared with fusion after decompression for the treatment of cervical degenerative disc disease and radiculopathy has not previously been investigated in a population-based setting.METHODSAll patients with cervical degenerative disc disease and radiculopathy who were in the national Swedish Spine Registry (Swespine) beginning in January 1, 2006, were eligible for the study. Follow-up information was obtained up to November 15, 2017. Read More

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October 2018

PARPi triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCAness.

Cancer Res 2018 Nov 27. Epub 2018 Nov 27.

Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center

Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have shown remarkable therapeutic efficacy against BRCA1/2 mutant cancers through a synthetic lethal interaction. PARPi exert their therapeutic effects mainly through the blockade of single-stranded DNA damage repair, which leads to the accumulation of toxic DNA double-strand breaks specifically in cancer cells with DNA repair deficiency (BCRAness), including those harboring BRCA1/2 mutations. Here we show that PARPi-mediated modulation of the immune response contributes to their therapeutic effects independently of BRCA1/2 mutations. Read More

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November 2018

Sideline assessment of concussion.

Handb Clin Neurol 2018 ;158:75-80

Athletic Medicine, University Health Services, Princeton University, Princeton, NJ, United States.

The recognition and sideline evaluation of possible sport-related concussion are difficult tasks for a physician and other clinicians. Sideline assessment tools have continued to evolve over the years, but objective biomarkers of concussion do not currently exist. Sideline video review programs may aid in the recognition of possible concussion as additional information for the sideline athletic medicine staff. Read More

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January 2018
3 Reads

Noninvasive Assessment of Retinal Blood Flow Using a Novel Handheld Laser Speckle Contrast Imager.

Transl Vis Sci Technol 2018 Nov 14;7(6). Epub 2018 Nov 14.

Department of Ophthalmology and Visual Sciences, University of Maryland Baltimore, Baltimore, MD, USA.

Purpose: We assessed the image quality and reproducibility of blood flow measurements from a novel handheld laser speckle imager in handheld and stabilized use cases.

Methods: Eleven dilated human subjects were imaged with the XyCAM Handheld Retinal Imager investigational device (XyCAM HRI) in the handheld and stabilized use case in nine consecutive imaging sessions. Subjects then underwent standard color fundus photography using a Topcon TRC 50DX. Read More

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November 2018

Prognostic significance of tumor genotypes and CD8+ infiltrates in stage I-III colorectal cancer.

Oncotarget 2018 Nov 2;9(86):35623-35638. Epub 2018 Nov 2.

Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: We explored the clinical significance of tumor genotypes and immunophenotypes in non-metastatic colorectal cancer (CRC).

Methods: In primary tumors (paraffin blocks) from 412 CRC patients treated with adjuvant chemotherapy, we examined pathogenic mutations (panel NGS; 347 informative); mismatch repair (MMR) immunophenotype (360 informative); and CD8+ lymphocyte density (high - low; 412 informative). The primary outcome measure was disease-free survival (DFS). Read More

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November 2018
1 Read

NMDA Antagonists for Treatment-Resistant Depression.

Authors:
Nuri B Farber

Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.

Residency Training, Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.

Fifteen to thirty percent of patients with major depressive disorder do not respond to antidepressants that target the monoaminergic systems. NMDA antagonists are currently being actively investigated as a treatment for these patients. Ketamine is the most widely studied of the compounds. Read More

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November 2018

Fetal Arrhythmias: Genetic Background and Clinical Implications.

Authors:
Shi-Min Yuan

Pediatr Cardiol 2018 Nov 26. Epub 2018 Nov 26.

Department of Cardiothoracic Surgery, The First Hospital of Putian, Teaching Hospital, Fujian Medical University, 389 Longdejing Street, Chengxiang District, Putian, 351100, Fujian Province, People's Republic of China.

Fetal arrhythmias are a common phenomenon of pregnancies. However, debates remain with regard to the etiologies and early treatment of choices for severe fetal arrhythmias. The gene regulatory networks govern cardiac conduction system development to produce distinct nodal and fast conduction phenotypes. Read More

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November 2018
4 Reads

COMBImage: a modular parallel processing framework for pairwise drug combination analysis that quantifies temporal changes in label-free video microscopy movies.

BMC Bioinformatics 2018 Nov 26;19(1):453. Epub 2018 Nov 26.

Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.

Background: Large-scale pairwise drug combination analysis has lately gained momentum in drug discovery and development projects, mainly due to the employment of advanced experimental-computational pipelines. This is fortunate as drug combinations are often required for successful treatment of complex diseases. Furthermore, most new drugs cannot totally replace the current standard-of-care medication, but rather have to enter clinical use as add-on treatment. Read More

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November 2018
5 Reads

Efficacy and Safety of Abrilumab in a Randomized, Placebo-Controlled Trial for Moderate to Severe Ulcerative Colitis.

Gastroenterology 2018 Nov 22. Epub 2018 Nov 22.

University of Vienna, Vienna, Austria.

Background & Aims: αβ integrin is a validated target in inflammatory bowel disease. This randomized, phase 2b, placebo-controlled, double-blind study evaluated the efficacy and safety of the anti-αβ antibody abrilumab in patients with moderate-to-severe ulcerative colitis (UC) despite treatment with conventional therapies.

Methods: Patients (total Mayo Score 6-12, rectosigmoidoscopy score ≥2) with inadequate response or intolerance to conventional therapies were randomized to receive subcutaneous abrilumab (7, 21, or 70 mg) on day 1, weeks 2 and 4, and every 4 weeks; abrilumab 210 mg on day 1; or placebo. Read More

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November 2018
4 Reads

Incorporating Innovation and New Technology into Cardiothoracic Surgery.

Ann Thorac Surg 2018 Nov 21. Epub 2018 Nov 21.

New York University Langone Health, New York, NY.

The appropriate implementation of new technology, root cause analysis of "imperfect" outcomes and the continuous reappraisal of postgraduate training are needed to improve the care of tomorrow's patients. Healthcare delivery remains one of the most expensive sectors in the United States and the application of new and expensive technology that is necessary for the advancement of this complex specialty must be aligned with providing the best care for our patients. There are a several pathways to innovation; one is partnering with industry and the other is the investigational laboratory. Read More

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November 2018
4 Reads

Advancing nonclinical innovation and safety in pharmaceutical testing.

Drug Discov Today 2018 Nov 20. Epub 2018 Nov 20.

Physicians Committee for Responsible Medicine, 5100 Wisconsin Ave NW, Ste 400, Washington, DC 20016, USA.

Nonclinical tests are considered crucial for understanding the safety of investigational medicines. However, the effective translation from nonclinical to human application is limited and must be improved. Drug development stakeholders are working to advance human-based in vitro and in silico methods that may be more predictive of human efficacy and safety in vivo because they enable scientists to model the direct interaction of drugs with human cells, tissues, and biological processes. Read More

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November 2018

Investigational Hypoxia-Activated Prodrugs: Making Sense of Future Development.

Curr Drug Targets 2018 11 23. Epub 2018 Nov 23.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao. China.

Hypoxia, which occurs in most cancer cases, disrupts the efficacy of anticarcinogens. Fortunately, hypoxia itself is a potential target for cancer treatment. Hypoxia-activated prodrugs (HAPs) can be selectively activated by reductase under hypoxia. Read More

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November 2018
3 Reads

Long-term outcomes after transplantation after support with a pulsatile pediatric ventricular assist device.

J Heart Lung Transplant 2018 Oct 26. Epub 2018 Oct 26.

Division of Congenital Heart Surgery, Baylor College of Medicine, Houston, TX, US.

Background: There has been increasing use of durable ventricular assist devices (VAD) in children as a bridge to transplantation (BTT). The Berlin Heart investigational device exemption (IDE) trial was the first pediatric VAD trial to demonstrate excellent survival outcomes as a BTT.

Objectives: Our aim was to compare the expanded post-transplant outcomes for children enrolled in the Berlin Heart IDE trial to a matched Pediatric Heart Transplant Study (PHTS) cohort not requiring mechanical circulatory support (MCS). Read More

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October 2018
2 Reads

An Unsupervised Smart App-Optimized HIV Self-Testing Program in Montreal, Canada: Cross-Sectional Study.

J Med Internet Res 2018 Nov 27;20(11):e10258. Epub 2018 Nov 27.

Clinique Médicale L'Actuel, Montreal, QC, Canada.

Background: Although HIV self-testing strategies have been recommended by the World Health Organization, HIV self-tests are not yet approved in Canada. Currently approved HIV self-tests offer toll-free lines that are insufficient for initiating expedited linkages to counseling and care, accurate interpretation, and support during HIV self-testing. We developed an innovative, multilingual software app called HIVSmart! to plug these gaps. Read More

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November 2018
1 Read