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The Journal of Allergy and Clinical... Feb 2018The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the...
The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the broad field of allergy and immunology. This particular assignment was to cover the topic of eosinophils. In an attempt to highlight major ideas, themes, trends, and advances relevant to basic and clinical aspects of eosinophil biology, a search of articles published since 2015 in the Journal of Allergy and Clinical Immunology and other high-impact journals was performed. Articles were then reviewed and organized, and then key findings were summarized. Given space limitations, many outstanding articles could not be included, but the hope is that what follows provides a succinct overview of recently published work that has significantly added to our knowledge of eosinophils and eosinophil-associated diseases.
Topics: Eosinophils; Humans; Immune System Diseases
PubMed: 29045815
DOI: 10.1016/j.jaci.2017.09.022 -
The Journal of Allergy and Clinical... Apr 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
OBJECTIVE
We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP.
METHODS
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
RESULTS
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
CONCLUSIONS
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Aspirin; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Quality of Life; Sinusitis
PubMed: 34543652
DOI: 10.1016/j.jaci.2021.09.009 -
Journal of the European Academy of... Jun 2022Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be... (Review)
Review
Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that most frequently occurs in children, but it can also affect adults. Even though most AD cases can be managed with topical treatments, moderate-to-severe forms require systemic therapies. Dupilumab is the first human monoclonal antibody approved for the treatment of AD. Its action is through IL-4 receptor alpha subunit inhibition, thus blocking IL-4 and IL-13 signaling pathways. It has been shown to be an effective, well-tolerated therapy for AD, as well as for asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and eosinophilic esophagitis (EoE). However, an increasing incidence of dupilumab-induced ocular surface disease (DIOSD) has been reported in patients treated with dupilumab, as compared to placebo. The aim of this study was to summarize scientific data regarding DIOSD in AD patients treated with dupilumab. A search of PubMed and clinicaltrials.gov databases was performed. There was no limit to study design. All AD cases were moderate-to-severe. DIOSD was either dermatologist-, allergist-, or ophthalmologist-assessed. Evidence shows that DIOSD occurs most frequently in patients with atopic dermatitis and not in other skin conditions, neither in patients with asthma, CRSwNP, nor EoE who are on dupilumab treatment. Further studies are warranted in order to establish a causal relationship between dupilumab and ocular surface disease. Nevertheless, ophthalmological evaluations prior to dupilumab initiation can benefit AD patients with previous ocular pathology or current ocular symptomatology. Also, patch testing for ocular allergic contact dermatitis might be advantageous in patients with a history of allergic conjunctivitis. Furthermore, TARC, IgE, and circulating eosinophils levels might be important biomarkers for a baseline assessment of future candidates to dupilumab treatment. However, TARC measurements should be resumed for research purposes only.
Topics: Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Humans; Interleukin-4 Receptor alpha Subunit; Severity of Illness Index; Treatment Outcome
PubMed: 35122335
DOI: 10.1111/jdv.17981 -
Familial Cancer Oct 2022Desmoid tumours (DT) are one of the main causes of death in patients with familial adenomatous polyposis (FAP). Surgical trauma is a risk factor for DT, yet a colectomy... (Meta-Analysis)
Meta-Analysis Review
Desmoid tumours (DT) are one of the main causes of death in patients with familial adenomatous polyposis (FAP). Surgical trauma is a risk factor for DT, yet a colectomy is inevitable in FAP to prevent colorectal cancer. This systematic review and meta-analysis aimed to synthesize the available evidence on DT risk related to type, approach and timing of colectomy. A search was performed in MEDLINE, EMBASE and the Cochrane Library. Studies were considered eligible when DT incidence was reported after different types, approaches and timing of colectomy. Twenty studies including 6452 FAP patients were selected, all observational. No significant difference in DT incidence was observed after IRA versus IPAA (OR 0.99, 95% CI 0.69-1.42) and after open versus laparoscopic colectomy (OR 0.88, 95% CI 0.42-1.86). Conflicting DT incidences were seen after early versus late colectomy and when analysing open versus laparoscopic colectomy according to colectomy type. Three studies reported a (non-significantly) higher DT incidence after laparoscopic IPAA compared to laparoscopic IRA, with OR varying between 1.77 and 4.09. A significantly higher DT incidence was observed in patients with a history of abdominal surgery (OR 3.40, 95% CI 1.64-7.03, p = 0.001). Current literature does not allow to state firmly whether type, approach, or timing of colectomy affects DT risk in FAP patients. Fewer DT were observed after laparoscopic IRA compared to laparoscopic IPAA, suggesting laparoscopic IRA as the preferred choice if appropriate considering rectal polyp burden. PROSPERO REGISTRATION NUMBER: CRD42020161424.
Topics: Humans; Fibromatosis, Aggressive; Colectomy; Adenomatous Polyposis Coli; Laparoscopy; Incidence; Proctocolectomy, Restorative
PubMed: 35022961
DOI: 10.1007/s10689-022-00288-y -
Journal of Investigational Allergology... Jun 2021Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses that is often associated with nasal polyposis (CRSwNP) in the most severe...
Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses that is often associated with nasal polyposis (CRSwNP) in the most severe cases. As in other complex diseases, genetic factors are thought to play an important role in the risk and development of the disease. Environment may also modulate the epigenetic signature in affected patients. In the present systematic review, we aimed to compile all published data on genetic and epigenetic variations in CRSwNP since 2000. We found 104 articles, 24 of which were related to epigenetic studies. We identified more than 150 genetic variants in 99 genes involved in the pathogenesis of nasal polyposis. These were clustered into 8 main networks, linking genes involved in inflammation and immune response (eg, MHC), cytokine genes (eg, TNF), leukotriene metabolism, and the extracellular matrix. A total of 89 miRNAs were also identified; these are associated mainly with biological functions such as the cell cycle, inflammation, and the immune response. We propose a potential relationship between genes and the miRNAs identified that may open new lines of investigation. An in-depth knowledge of gene variants and epigenetic traits could help us to design more tailored treatment for patients with CRSwNP.
Topics: Chronic Disease; Epigenesis, Genetic; Gene Regulatory Networks; Humans; Immunity; MicroRNAs; Nasal Polyps; Polymorphism, Genetic; Rhinitis; Sinusitis
PubMed: 33502318
DOI: 10.18176/jiaci.0673 -
Digestive Surgery 2021The management of the pancreas in patients with duodenal trauma or duodenal tumors remains a controversial issue. Pancreas-preserving total duodenectomy (PPTD) requires...
BACKGROUND
The management of the pancreas in patients with duodenal trauma or duodenal tumors remains a controversial issue. Pancreas-preserving total duodenectomy (PPTD) requires a meticulous surgical technique. The most common indication is familial duodenal adenomatous polyposis (FAP). The aims of this study are to carry out a systematic review of the literature on the indications for PPTD and to highlight the risks and benefits compared with other more aggressive procedures.
SUMMARY
A systematic literature review was performed following PRISMA recommendations of studies published in PubMed, Embase, and Cochrane library until May 2019. Thirty articles describing 211 patients were chosen. The mean age was 48 years. The surgical indication in 75% of patients was FAP. The mean operating time was 329 min and mean intraoperative bleeding 412 mL. Postoperative morbidity rate was 49.7% (76% Clavien-Dindo
97.8%. Key Messages: PPTD is indicated for patients with benign and premalignant duodenal lesions without involvement of the pancreatic head. It is a feasible procedure offering an alternative to other more aggressive procedures in selected patients. Mortality is below 1.5%. Topics: Adenomatous Polyposis Coli; Digestive System Surgical Procedures; Duodenal Neoplasms; Duodenum; Humans; Pancreas; Postoperative Complications
PubMed: 34000717
DOI: 10.1159/000515718 -
Multidisciplinary Respiratory Medicine 2016The inflammatory diseases of the nose, rhino-pharynx and paranasal sinuses (allergic and non allergic rhinitis, NARES; rhinosinusitis with/without nasal polyposis,... (Review)
Review
UNLABELLED
The inflammatory diseases of the nose, rhino-pharynx and paranasal sinuses (allergic and non allergic rhinitis, NARES; rhinosinusitis with/without nasal polyposis, adenoidal hypertrophy with/without middle ear involvement) clinically manifest themselves with symptoms and complications severely affecting quality of life and health care expenditure. Intranasal administration of corticosteroids, being fast, simple, and not requiring cooperation, is the preferred way to treat the patients, to optimize their quality of life, at the same time minimizing the risk of exacerbations and complications. Among the different topical steroids available on the market, we performed a comparative analysis in terms of effectiveness and safety between mometasone furoate (MF) and its main competitors. Searching through Pub Med and Google Scholar and using as entries "mometasone furoate", "rhinitis", "sinusitis", "asthma", "polyposis", "otitis media with effusion", and "adenoid hypertrophy" we found 344 articles, 300 of which met the eligibility criteria. Taking into account relevance and date of publication, a sample of 40 articles was considered for the review. MF effectiveness for treatment and/or prophylaxis of nasal symptoms in seasonal and perennial allergic rhinitis has been fully established with a level of evidence Ia. Even though it has not been assessed for MF in particular, topical steroids are the most appropriate treatment in mixed rhinitis and NARES. In acute rhinosinusitis (ARS) evidences support their use as mono-therapy or as adjuvant to antibiotics for reducing the recurrence rate, and decrease the usage of related prescriptions and medical consultations. In chronic rhinosinusitis (CRS) with Nasal polyposis, MF reduces polyps size, nasal congestion, improves quality of life and sense of smell and it is also effective in the treatment of daytime cough. The topical use of MF has great efficacy in the management of adenoidal hypertrophy and otitis media of atopic children. As regards the safety, MF has demonstrated an excellent safety profile: pregnant women can safely use it; no systemic effects on growth velocity and adrenal suppression have been shown; no changes in epithelial thickness or atrophy have been observed after long term administration of the drug.
CONCLUSIONS
MF has been demonstrated to be effective in the treatment of the inflammatory diseases of the nose and paranasal sinuses; when compared to its competitors it shows a greater symptom control; it is a reliable treatment in the long term thanks not only to its proven efficacy, but also to its safety being on the market since more than 17 years.
PubMed: 27141307
DOI: 10.1186/s40248-016-0054-3 -
Clinical Otolaryngology : Official... Jul 2023To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS). (Review)
Review
OBJECTIVE
To investigate the association between laryngopharyngeal reflux (LPR), gastroesophageal reflux disease (GERD) and recalcitrant chronic rhinosinusitis (CRS).
DATA SOURCES
PubMed, Cochrane Library and Scopus.
REVIEW METHODS
Three investigators searched the specified databases for studies investigating the relationship between LPR, GERD and recalcitrant CRS with or without polyposis. The following outcomes were investigated with PRISMA criteria: age; gender; reflux and CRS diagnosis; association outcomes and potential treatment outcomes. The authors performed a bias analysis of papers and provided recommendations for future studies.
RESULTS
A total of 17 studies investigated the association between reflux and recalcitrant CRS. According to pharyngeal pH monitoring, 54% of patients with recalcitrant CRS reported hypo or nasopharyngeal acid reflux events. The number of hypo- and nasopharyngeal acid reflux events was significantly higher in patients compared to healthy individuals in 4 and 2 studies, respectively. Only one study did not report intergroup differences. The proportion of GERD was significantly higher in CRS patients compared to controls, with a prevalence ranging from 32% to 91% of cases. No author considered nonacid reflux events. There was significant heterogeneity in the inclusion criteria; definition of reflux and association outcomes, limiting the ability to draw clear conclusions. Pepsin was found in sinonasal secretions more frequently in CRS patients than controls.
CONCLUSION
Laryngopharyngeal reflux and GERD may be contributing factors of CRS therapeutic resistance, but future studies are needed to confirm the association considering nonacid reflux events.
Topics: Humans; Laryngopharyngeal Reflux; Esophagitis, Peptic; Pepsin A; Sinusitis
PubMed: 36895147
DOI: 10.1111/coa.14047 -
Clinical Gastroenterology and... Aug 2020Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer... (Review)
Review
BACKGROUND & AIMS
Somatic mosaicism, in which variants arise post-zygotically and are therefore not present in all cells in the body, may be an underestimated cause of colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes.
METHODS
We searched PubMed through March 2018 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other CRC susceptibility genes, and epigenetic mosaicism.
RESULTS
Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM).
CONCLUSIONS
We found that somatic mosaicism is underdiagnosed but critical for determining the clinical management of patients with de novo polyposis who possibly carry mosaic APC variants, and present a decision tree for the clinical management of these patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an underlying genetic cause, is complex and not fully understood.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Genetic Predisposition to Disease; Humans; Mosaicism; Neoplastic Syndromes, Hereditary
PubMed: 32147591
DOI: 10.1016/j.cgh.2020.02.049 -
The Journal of Pathology. Clinical... Jul 2016Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of... (Review)
Review
Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of colorectal cancer. Knowledge of the molecular characteristics of colonic lesions which develop in this syndrome is fragmented, making it difficult to understand the underlying genetic basis of this condition. We conducted a systematic review and meta-analysis of all studies which evaluated the molecular characteristics of colorectal neoplasms found in individuals with serrated polyposis. We identified 4561 potentially relevant studies, but due to a lack of consensus in the reporting of findings, only fourteen studies were able to be included in the meta-analysis. BRAF mutation was found in 73% (95% CI 65-80%) of serrated polyps, 0% (95% CI 0-3%) of conventional adenomas and 49% (95%CI 33-64%) of colorectal cancers. In contrast, KRAS mutation was present in 8% (95% CI 5-11%) of serrated polyps, 3% (95% CI 0-13%) of conventional adenomas and 6% (95% CI 0-13%) of colorectal cancers. Absence of MLH1 immunostaining was found in 3% (95% CI 0-10%) of serrated polyps and 53% (95% CI 36-71%) of colorectal cancers. Overall, microsatellite instability was found in 40% (95% CI 18-64%) of colorectal cancers arising in the setting of serrated polyposis. Our results indicate that diverse molecular pathways are likely to contribute to the increased predisposition for colorectal cancer in individuals with serrated polyposis. We also propose a set of minimum standards for the reporting of future research in serrated polyposis as this is a rare syndrome and collation of research findings from different centres will be essential to identify the molecular mechanisms involved in the pathogenesis of this condition.
PubMed: 27499922
DOI: 10.1002/cjp2.44