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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 -
The Cochrane Database of Systematic... Dec 2023Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly.
OBJECTIVES
To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched other databases (Pubmed, Embase, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Virtual Health Library and ClinicalTrials.gov). Date of last search: 18 September 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing groups who underwent endoscopic sinus surgery and groups with medical treatment alone.
DATA COLLECTION AND ANALYSIS
The review authors independently selected studies, extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE. They contacted the authors of the included study for additional information.
MAIN RESULTS
We identified 66 publications relating to 50 studies from electronic searches. Only one study fulfilled the inclusion criteria, and only limited information was available. In this study, 28 participants aged 19 to 28 years were randomized in equal numbers to either nasal irrigation alone or nasal irrigation with surgery (endoscopic polypectomy with extended sinusotomy). The certainty of the evidence was very low according to the GRADE approach. We are uncertain whether, compared to medical treatment alone, the addition of surgical intervention improves nasal symptoms, or reduces bacterial colonization, the use of antibiotics and pulmonary exacerbations. We are also uncertain whether the addition of surgery to medical treatment leads to changes in pulmonary function. There was one episode of bleeding during surgery that was corrected during the procedure with no further consequences. The study did not report on survival.
AUTHORS' CONCLUSIONS
Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps.
Topics: Humans; Cystic Fibrosis; Nasal Polyps; Anti-Bacterial Agents; Sinusitis; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 38063253
DOI: 10.1002/14651858.CD014084.pub2 -
Journal of Pediatric Surgery Apr 2016A small percentage of pediatric solid cancers arise as a result of clearly identified inherited predisposition syndromes and nongenetic lesions. Evidence supports... (Review)
Review
OBJECTIVE
A small percentage of pediatric solid cancers arise as a result of clearly identified inherited predisposition syndromes and nongenetic lesions. Evidence supports preemptive surgery for children with genetic [multiple endocrine neoplasia type 2 (MEN2), familial adenomatous polyposis syndrome (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), and hereditary diffuse gastric cancer (HDGC) and nongenetic [thyroglossal duct cysts (TGDC), congenital pulmonary airway malformations (CPAM), alimentary tract duplication cysts (ATDC), and congenital choledochal cysts (CCC)] developmental anomalies. Our aim was to explore the utility of risk reduction surgery to treat and prevent cancer in children.
METHODS
A systematic review of the available peer-reviewed literature on PubMed was performed using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) search strategy, where possible. Search items included "risk reduction surgery", "hereditary cancer predisposition syndrome", "multiple endocrine neoplasia type 2", "familial adenomatous polyposis", "hereditary nonpolyposis colorectal cancer", "hereditary diffuse gastric cancer", "thyroglossal duct cysts", congenital pulmonary airway malformations", "alimentary tract duplication cysts", "malignant transformation", and "guidelines".
RESULTS
We identified 67 articles that met the inclusion criteria describing the indications for prophylactic surgery in surgical oncology. For the genetic predisposition syndromes, 7 studies were related to professional endorsed guidelines, 7 were related to surgery for MEN2, 11 were related to colectomy for FAP, 6 were related to colectomy for HNPCC, and 12 related to gastrectomy for HDGC. Articles for the nongenetic lesions included 5 for techniques related to TGDC resection, 9 for surgery for CPAMs, and 10 for resection of ATDCs. Guidelines and strategies varied significantly especially related to the extent and timing of surgical intervention; the exception was for the timing of thyroidectomy in children with MEN2.
CONCLUSION
Current evidence supporting prophylactic surgery in the management of pediatric cancer predisposition syndromes and nongenetic lesions is best delineated for thyroidectomy to prevent medullary thyroid cancer in children with MEN2 (Strength of Recommendation Grade B/C). Despite the lack of pediatric specific evidence-based recommendations regarding the appropriate extent and timing for risk-reduction surgery for FAP, HNPCC, HDGC and nongenetic anomalies, our review represents an opportunity towards understanding the postgenomic development of these lesions and provides current indications and techniques for preemptive cancer prevention surgery in children.
Topics: Child; Humans; Neoplastic Syndromes, Hereditary; Pediatrics; Prophylactic Surgical Procedures; Surgical Oncology; Treatment Outcome
PubMed: 26898681
DOI: 10.1016/j.jpedsurg.2016.01.004 -
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 -
Journal of Gastroenterology and... Mar 2016The oral manifestations of familial adenomatous polyposis (FAP) have been reported in the recent literature. Therefore, there has been growing interest in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
The oral manifestations of familial adenomatous polyposis (FAP) have been reported in the recent literature. Therefore, there has been growing interest in the characterization of the dento-osseous anomalies because they may precede colorectal cancer and may be used as a diagnostic marker. This systematic review and meta-analysis was performed to evaluate the published evidence for what are the oral manifestations of FAP and their frequency in affected individuals.
METHODS
The search was performed at Cochrane Library, EMBASE, LILACS, PubMed, Scopus, and Web of Science for articles published up to March 2015. A grey literature search was conducted through Google Scholar. Reference lists of the included articles and additional studies identified by expert were screened for potential relevant studies. The methodology of selected studies was evaluated using the risk of bias checklist of the Agency for Healthcare Research and Quality.
RESULTS
Twenty observational studies totalizing 1635 individuals affected by FAP met the inclusion criteria. Osseous, dental, and oral mucosa alterations were observed in FAP patients. The meta-analysis showed the frequency of osseous jaw lesions, and the dental anomalies were 65.35% and 30.48%, respectively, and two studies suggested that oral mucosa vascular density is a phenotypic manifestation in patients with FAP. Most of the studies were evaluated as moderate risk of bias.
CONCLUSION
The most frequent oral manifestation on FAP patients is osseous jaw alterations. In the future, well-designed studies are necessary to classify osseous and dental anomalies in order to demonstrate the true prevalence of each alteration separately.
Topics: Adenomatous Polyposis Coli; Blood Vessels; Databases, Factual; Female; Humans; Jaw; Male; Mouth Mucosa; Observational Studies as Topic; Prevalence; Risk; Tooth Abnormalities
PubMed: 26331960
DOI: 10.1111/jgh.13149 -
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