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Thyroid : Official Journal of the... Mar 2021Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association...
Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC. The specific clinical questions and topics addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of the Task Force members (authors of the guideline). Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, targeted/systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues, including end of life. The guidelines include 31 recommendations and 16 good practice statements. We have developed evidence-based recommendations to inform clinical decision-making in the management of ATC. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with ATC.
Topics: Consensus; Evidence-Based Medicine; Humans; Medical Oncology; Prognosis; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms
PubMed: 33728999
DOI: 10.1089/thy.2020.0944 -
Clinical Gastroenterology and... Apr 2022Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine... (Review)
Review
BACKGROUND & AIMS
Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine the clinical features, genetic profile, and previously used treatment strategies in monogenic IBD.
METHODS
A systematic review of MEDLINE articles published between January 2000 and December 2020 was conducted. A total of 750 individual monogenic IBD cases were identified from 303 eligible articles.
RESULTS
The most frequently reported monogenic IBD genes were IL10RA/B, XIAP, CYBB, LRBA, and TTC7A. In total, 63.4% of patients developed IBD before 6 years of age, 17.4% developed IBD between ages 10 and 17.9 years, and 10.9% developed IBD after age 18. There was a substantial difference between these age groups and the underlying monogenic disorders. Only 31.7% had any history of extraintestinal comorbidity (EIC) before IBD onset, but 76.0% developed at least 1 EIC during their clinical course. The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%). Bowel surgery, biologic therapy, and hematopoietic stem cell transplantation were performed in 27.1%, 32.9%, and 23.1% of patients, respectively.
CONCLUSIONS
Monogenic IBD cases, although rare, have varied extraintestinal comorbidities and limited treatment options including surgery and transplant. Early identification and improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is important for effective management.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Age of Onset; Colitis; Humans; Inflammatory Bowel Diseases; Proteins
PubMed: 33746097
DOI: 10.1016/j.cgh.2021.03.021 -
Current Diabetes Reviews 2020The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the...
BACKGROUND
The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan.
OBJECTIVE
Discuss the pathophysiology of type 2 DM in children and adolescents.
METHODS AND RESULTS
This is a comprehensive review of the literature on this topic. Type 2 DM in childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic predisposition, intrauterine environment, excessive food consumption, continued rapid weight gain, and poor lifestyle. Besides IR, this is compounded by multiple metabolic defects including β-cell dysfunction and inadequate insulin secretion, α-cell dysfunction, hyperglucagonemia and increased hepatic glucose production, lipotoxicity, inflammation, deficiencies in incretin production and action, and increased renal glucose reabsorption. The confluence of genetic and environmental factors underscores the complexity in disease progression.
CONCLUSION
A consistent single risk factor for type 2 DM is obesity and related IR and therefore it is essential to curtail the progression of obesity. It is important to investigate the role of stringent dietary and nutritional approaches, medications that enhance β-cell function and insulin sensitivity.
Topics: Adolescent; Child; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Pediatric Obesity; Risk Factors
PubMed: 29879890
DOI: 10.2174/1573399814666180608074510 -
Pediatric Critical Care Medicine : a... Jan 2022Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient,...
Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).
OBJECTIVES
Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients.
DESIGN
Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]).
SETTING
Not applicable.
PATIENTS
Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients.
CONCLUSIONS
The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.
Topics: Anemia; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Humans; Infant; Platelet Transfusion
PubMed: 34989711
DOI: 10.1097/PCC.0000000000002851 -
JAMA Oncology Jul 2019Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
OBJECTIVE
To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.
DATA SOURCES
PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.
STUDY SELECTION
Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.
DATA EXTRACTION AND SYNTHESIS
Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.
MAIN OUTCOMES AND MEASURES
Incidences of treatment-related adverse events and differences between different drugs and cancer types.
RESULTS
This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).
CONCLUSIONS AND RELEVANCE
Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Clinical Trials as Topic; Humans; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 31021376
DOI: 10.1001/jamaoncol.2019.0393 -
International Journal of Molecular... May 2023Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the blastocyst. ESCs have two distinctive properties: ability to proliferate indefinitely, a... (Review)
Review
Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the blastocyst. ESCs have two distinctive properties: ability to proliferate indefinitely, a feature referred as "self-renewal", and to differentiate into different cell types, a peculiar characteristic known as "pluripotency". Self-renewal and pluripotency of ESCs are finely orchestrated by precise external and internal networks including epigenetic modifications, transcription factors, signaling pathways, and histone modifications. In this systematic review, we examine the main molecular mechanisms that sustain self-renewal and pluripotency in both murine and human ESCs. Moreover, we discuss the latest literature on human naïve pluripotency.
Topics: Humans; Animals; Mice; Embryonic Stem Cells; Human Embryonic Stem Cells; Blastocyst; Signal Transduction; Transcription Factors; Cell Differentiation
PubMed: 37176093
DOI: 10.3390/ijms24098386 -
Biochimica Et Biophysica Acta.... Jan 2023DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and... (Review)
Review
DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.
Topics: Humans; DNA Methylation; Leukocytes, Mononuclear; Biomarkers, Tumor; Circulating Tumor DNA; Neoplasms; Cell-Free Nucleic Acids
PubMed: 36270476
DOI: 10.1016/j.bbadis.2022.166583 -
Aesthetic Plastic Surgery Aug 2023Skin and soft tissue aging has been an important topic of discussion among plastic surgeons and their patients. While botulinum toxin, facial fillers, chemical peels,... (Review)
Review
PURPOSE
Skin and soft tissue aging has been an important topic of discussion among plastic surgeons and their patients. While botulinum toxin, facial fillers, chemical peels, and surgical lifts preside as the mainstay of treatment to restore appearance of youth, emergent technologies, such as CRISPR-Cas9, proteostasis, flap biology, and stem cell therapies, have gained traction in addressing the aging process of skin and soft tissue. Several studies have introduced these advancements, but it remains unclear how safe and effective these therapeutics are in facial rejuvenation, and how they may fit in the existent treatment workflow for soft tissue aging.
MATERIALS/METHODS
A systematic literature review was conducted to identify and assess therapeutics utilized in addressing skin and soft tissue aging. Variables collected included year of publication, journal, article title, organization of study, patient sample, treatment modality, associated outcomes. In addition, we performed a market analysis of companies involved in promoting technologies and therapeutics within this space. PitchBook (Seattle, WA), a public market database, was utilized to classify companies, and record the amount of venture capital funding allocated to these categories.
RESULTS
Initial review yielded four hundred and two papers. Of these, thirty-five were extracted after applying inclusion and exclusion criteria. Though previous literature regards CRISPR-Cas9 technology as the most favorable anti-aging innovation, after reviewing the current literature, stem cell therapies utilizing recipient chimerism appeared to be the superior skin anti-aging technique when accounting for possible disadvantages of various techniques. The psychosocial and cosmetic outcomes from using cell therapy to modulate allograft survival and tolerance may confer more long-term proposed benefits than the technologies in CRISPR-Cas9, flap biology innovations, and autologous platelet-rich plasma use. Market analysis yielded a total of 87 companies, which promoted innovations in technology, biotechnology, biopharmaceuticals, cell-based therapies, and genetic therapy.
CONCLUSION
This review provides physicians and patients with relevant, usable information regarding how therapeutics can impact treatment regimen for facial aesthetics and skin rejuvenation. Furthermore, the goal of this research is to elucidate the varying therapeutics to restore appearance of youth, present associated outcomes, and in doing so, present plastic surgeons and their colleagues with greater insight on the role of these therapeutics and technologies in clinical practice. Future studies can further assess the safety and efficacy of these innovations and discuss how these may fit within surgical plans among patients seeking rejuvenation procedures.
LEVEL OF EVIDENCE III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Topics: Humans; Adolescent; Cosmetic Techniques; Aging; Skin Aging; Face; Rejuvenation; Esthetics
PubMed: 37154849
DOI: 10.1007/s00266-023-03322-1 -
Blood Advances Oct 2023Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell... (Meta-Analysis)
Meta-Analysis
Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; B-Cell Maturation Antigen; Immunotherapy; T-Lymphocytes; CD3 Complex
PubMed: 37467036
DOI: 10.1182/bloodadvances.2023010539 -
Nutrients Dec 2022Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage.... (Review)
Review
Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. This review aimed to evaluate the benefits of lycopene supplementation in cancer prevention and treatment based on the results of in vivo studies. We identified 72 human and animal studies that were then analysed for endpoints such as cancer incidence, improvement in treatment outcomes, and the mechanisms of lycopene action. We concluded that the results of most of the reviewed in vivo studies confirmed the anti-cancer activities of lycopene. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. The reported mechanisms of lycopene action in vivo included regulation of oxidative and inflammatory processes, induction of apoptosis, and inhibition of cell division, angiogenesis, and metastasis formation. The predominance of particular mechanisms seemed to depend on tumour organ localisation and the local storage capacity of lycopene. Finally, there is a need to look for predictive factors to identify a population that may benefit from lycopene supplementation. The potential candidates appear to be race, single nucleotide polymorphisms in carotene-cleaving enzymes, some genetic abbreviations, and insulin-like growth factor-dependent and inflammatory diseases.
Topics: Male; Animals; Humans; Lycopene; Carotenoids; Prostatic Neoplasms; Apoptosis; Dietary Supplements
PubMed: 36501182
DOI: 10.3390/nu14235152