scholarly journals Non-Invasive Biomarkers for Earlier Detection of Pancreatic Cancer—A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2722
Author(s):  
Greta Brezgyte ◽  
Vinay Shah ◽  
Daria Jach ◽  
Tatjana Crnogorac-Jurcevic
Keyword(s):  
Clinical Setting ◽  
Selection Index ◽  
Reporting Quality ◽  
Standard Of Care ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Index Test ◽  
Delayed Presentation ◽  
Non Invasive ◽  
Study Selection

Pancreatic ductal adenocarcinoma (PDAC) carries a deadly diagnosis, due in large part to delayed presentation when the disease is already at an advanced stage. CA19-9 is currently the most commonly utilized biomarker for PDAC; however, it lacks the necessary accuracy to detect precursor lesions or stage I PDAC. Novel biomarkers that could detect this malignancy with improved sensitivity (SN) and specificity (SP) would likely result in more curative resections and more effective therapeutic interventions, changing thus the present dismal survival figures. The aim of this study was to systematically and comprehensively review the scientific literature on non-invasive biomarkers in biofluids such as blood, urine and saliva that were attempting earlier PDAC detection. The search performed covered a period of 10 years (January 2010—August 2020). Data were extracted using keywords search in the three databases: MEDLINE, Web of Science and Embase. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was applied for study selection based on establishing the risk of bias and applicability concerns in Patient Selection, Index test (biomarker assay) and Reference Standard (standard-of-care diagnostic test). Out of initially over 4000 published reports, 49 relevant studies were selected and reviewed in more detail. In addition, we discuss the present challenges and complexities in the path of translating the discovered biomarkers into the clinical setting. Our systematic review highlighted several promising biomarkers that could, either alone or in combination with CA19-9, potentially improve earlier detection of PDAC. Overall, reviewed biomarker studies should aim to improve methodological and reporting quality, and novel candidate biomarkers should be investigated further in order to demonstrate their clinical usefulness. However, challenges and complexities in the path of translating the discovered biomarkers from the research laboratory to the clinical setting remain and would have to be addressed before a more realistic breakthrough in earlier detection of PDAC is achieved.

A Single-Center Trial to Evaluate the Efficacy and Tolerability of Four Microneedling Treatments on Fine Lines and Wrinkles of Facial and Neck Skin in Subjects With Fitzpatrick Skin Types I-IV: An Objective Assessment Using Non-Invasive Devices and 0.33mm Microbiopsies

2021 ◽  
Author(s):  
Christine E Wamsley ◽  
Mikaela Kislevitz ◽  
Jennifer Barillas ◽  
Deniz Basci ◽  
Vishal Kandagatla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Objective Assessment ◽  
Standard Of Care ◽  
Transepidermal Water Loss ◽  
Post Treatment ◽  
Non Invasive ◽  
Muscle Formation ◽  
The Face ◽  
High Resolution Ultrasonography ◽  
Elastin Gene

Abstract Background While ablative techniques have been standard of care for the treatment of fine lines and wrinkles, microneedling is a minimally invasive alternative. Objectives The purpose of this study was to assess the efficacy of microneedling on facial and neck fine lines and wrinkles. Methods 35 subjects between 44 and 65 years old with Fitzpatrick skin types I-IV received four monthly microneedling treatments over the face and neck. Subjects returned one and three months post-treatment. At every visit, high-resolution ultrasonography, optical coherence tomography, transepidermal water loss and BTC-2000 were performed. 0.33mm microbiopsies were collected pre-treatment, before the fourth treatment and three months post-treatment. Results 32 subjects (93.75% female, 6.25% male) completed all seven visits. Facial dermal and epidermal density increased 101.86% and 19.28%, respectively from baseline at three months post-treatment. Facial elasticity increased 28.2% from baseline three months post-treatment. Facial attenuation coefficient increased 15.65% and 17.33% one and three months post-treatment. At study completion, blood flow 300µm deep decreased 25.8% in the face and 42.3% in the neck. Relative collagen type III and elastin gene expression was statistically higher three months post-treatment. However, total elastin protein levels unchanged compared to baseline. 58% of biopsies extracted three months post-treatment showed dermal muscle formation, compared to baseline 15.3%. Conclusions The results illustrate the effects of microneedling treatments. Non-invasive measurements and biopsy data showed changes in skin architecture and collagen/elastin gene expression suggesting skin rejuvenation, with new extracellular matrix production and muscle formation.

The Use of Sonography in Pediatrics: The Bioethical Concerns in Clinical and Research Practice

2021 ◽  
pp. 875647932110350
Author(s):  
Nicole Weikle
Keyword(s):  
Clinical Setting ◽  
Imaging Modality ◽  
Pediatric Population ◽  
Well Being ◽  
Ethical Principles ◽  
Pediatric Care ◽  
Research Practice ◽  
Ethical Guidelines ◽  
Non Invasive ◽  
Clinical Pediatric

Sonography has been widely used in both a clinical and non-clinical setting. This imaging modality is a common tool of choice for both physicians and researchers. Although sonography is a non-ionizing and non-invasive tool for imaging, special considerations need to be made when working with the pediatric population. Ethical guidelines for clinical pediatric care and research need to consider the varying ethical guidelines and bioethical concerns in children. As sonographers, researchers, educators and clinicians, pediatric care and research must balance the protection of children and the need for imaging to improve pediatric well-being. The discussion of this paper will delve into The Principles Approach developed by Beauchamp and Childress. Each principle will be explored and how those ethical principles could be considered in pediatric care.

scholarly journals Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Serum Samples ◽  
Tissue Samples ◽  
Non Invasive ◽  
Specific Symptoms ◽  
Generation Sequencing

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

Acute Diplopia Following Rhinoplasty: Clearing the Air

2021 ◽  
pp. 229255032110270
Author(s):  
Ashley N. Boustany ◽  
Carly D. Comer ◽  
Harsha Gopal ◽  
Samuel J. Lin ◽  
Sumner A. Slavin
Keyword(s):  
Rare Complication ◽  
Therapeutic Interventions ◽  
Medical Attention ◽  
Delayed Presentation ◽  
Patient Evaluation ◽  
Acute Stroke Patient ◽  
Dry Eyes ◽  
Orbital Emphysema ◽  
Complete History ◽  
Binocular Diplopia

Diplopia after rhinoplasty is a rare complication that requires immediate medical attention. Workup should include a complete history and physical examination, appropriate imaging, and consultation with ophthalmology. Diagnosis may be challenging due to the wide differential ranging from dry eyes to orbital emphysema to an acute stroke. Patient evaluation should be expedient, though thorough to facilitate time-sensitive therapeutic interventions. Here, we present a case of transient binocular diplopia presenting 2 days after closed septorhinoplasty. The visual symptoms were attributed to either intra-orbital emphysema or a decompensated exophoria. This is the second documented case of orbital emphysema after rhinoplasty presenting with diplopia. It is the only case with a delayed presentation as well as the only case that resolved after positional maneuvers.

scholarly journals BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Ryan J. Sullivan ◽  
Keith T. Flaherty
Keyword(s):  
Standard Of Care ◽  
Diagnostic Techniques ◽  
Therapeutic Interventions ◽  
Molecular Testing ◽  
Braf Inhibitors ◽  
Testing Methods ◽  
Braf Mutations ◽  
Initial Discovery ◽  
Braf Mutant ◽  
Mutant Braf

Since the initial discovery that a subset of patients with cutaneous melanoma harbor BRAF mutations, substantial research has been focused on determining the pathologic consequences of BRAF mutations, optimizing diagnostic techniques to identify these mutations, and developing therapeutic interventions to inhibit the function of this target in mutation-bearing tumors. Recently, advances have been made which are revolutionizing the standard of care for patients with BRAF mutant melanoma. This paper provides an overview on the pathogenic ramifications of mutant BRAF signaling, the latest molecular testing methods to detect BRAF mutations, and the most recent clinical data of BRAF pathway inhibitors in patients with melanoma and BRAF mutations. Finally, emerging mechanisms of resistance to BRAF inhibitors and ways of overcoming this resistance are discussed.

scholarly journals An open label trial of anakinra to prevent respiratory failure in COVID-19

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Evdoxia Kyriazopoulou ◽  
Periklis Panagopoulos ◽  
Symeon Metallidis ◽  
George N Dalekos ◽  
Garyphallia Poulakou ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Primary Outcome ◽  
Standard Of Care ◽  
Hazard Ratio ◽  
Open Label ◽  
Once Daily ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
Open Label Trial ◽  
Anakinra Treatment

Background It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.Methods 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.Results 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.Conclusions Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.Trial Registration: ClinicalTrials.gov, NCT04357366

scholarly journals Multiple-biological matrices metabolomics identified new metabolite biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis

2020 ◽  
Author(s):  
Xialin Luo ◽  
Jingjing Liu ◽  
Huaizhi Wang ◽  
Haitao Lu
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Setting ◽  
Time Frame ◽  
Therapeutic Interventions ◽  
Healthy Controls ◽  
Targeted Metabolomics ◽  
Normal Tissues ◽  
Glycocholic Acid ◽  
Tumor Tissues ◽  
Precise Diagnosis

AbstractPurposeTo improve clinical diagnosis and enhance therapeutic outcome, we figure out to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can easily, sensitively and efficiently diagnose the onsite progression, and metastasis of the disease.Experimental DesignWe employed the newly developed precision-targeted metabolomics method to validate that many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer from healthy controls. To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance.ResultsWe eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); Moreover, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages.ConclusionsTaken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficiently therapeutic interventions, which could largely improve the five-year survival rate of PC patients.

Temporomandibular Joint Kinematics of the Rabbit Model With Mechanically Disrupted Occlusion

2011 ◽  
Author(s):  
Sarah E. Henderson ◽  
Alejandro J. Almarza ◽  
Scott Tashman ◽  
Amy L. McCarty
Keyword(s):  
Temporomandibular Joint ◽  
Rabbit Model ◽  
Specific Pattern ◽  
Therapeutic Interventions ◽  
Irreversible Damage ◽  
Invasive Approach ◽  
Functional Changes ◽  
Factors Associated ◽  
Non Invasive ◽  
Injury Model

Degeneration of the articulating surfaces and pain associated with temporomandibular joint (TMJ) dysfunction are the primary symptoms of TMJ disorders (TMDs), where normal life activities such as eating, talking, and even sleeping may be drastically impaired [1–3]. To accelerate the discovery of effective therapeutic interventions for the treatment of TMD pain, we have been establishing a novel non-invasive approach for objectively assessing the presence of joint hypersensitivity. Our approach to identify chronic joint pain is based on evidence that all of the etiological factors associated with TMD pain implicate remodeling and degeneration of the joint in response to alterations in motion and loading. The injury model used for this study was a reversible, mechanical model through splint placement on the molars. It is hypothesized that arthrokinematic analysis will identify a specific pattern of functional changes that constitute a signature for the presence of irreversible damage.

Epigenetic dysregulation in myeloid malignancies

Blood ◽  
2021 ◽  
Author(s):  
Hsuan-Ting Huang ◽  
Maria Eugenia Figueroa
Keyword(s):  
Standard Of Care ◽  
Cytotoxic Agents ◽  
Therapeutic Interventions ◽  
Myeloid Malignancies ◽  
Sequencing Studies ◽  
Aberrant Dna Methylation ◽  
Relapsed Disease ◽  
Mouse Modeling ◽  
Generation Sequencing ◽  
General Standard

Epigenetic deregulation is now a well-recognized -though not yet fully understood- mechanism that contributes to the development and progression of myeloid malignancies. In the past 15 years, next generation sequencing studies have revealed patterns of aberrant DNA methylation, altered chromatin states, and mutations in chromatin modifiers across the spectrum of myeloid malignancies. Studies into the mechanisms that drive these diseases through mouse modeling have helped identify new avenues for therapeutic interventions, from initial treatment to resistant, relapsed disease. This is particularly significant when chemotherapy with cytotoxic agents remains the general standard of care. In this review, we will discuss some of the recent findings of epigenetic mechanisms and how these are informing the development of more targeted strategies for therapeutic intervention in myeloid malignancies.

Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Epigenetic Regulator ◽  
Novel Treatment Strategies

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

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