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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 -
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 -
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 -
Otolaryngology--head and Neck Surgery :... Mar 2024The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this Meta-analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation.
DATA SOURCES
Ovid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax.
REVIEW METHODS
Outcome data for the meta-analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta-analysis was performed using the DerSimonian-Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta-analysis.
RESULTS
Thirty-six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta-analysis of the various outcome variables. Our pooled meta-analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17-1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36).
CONCLUSION
Our pooled Meta-analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.
Topics: Humans; Overweight; Leptin; Rhinosinusitis; Obesity; Sinusitis; Chronic Disease
PubMed: 38108590
DOI: 10.1002/ohn.612 -
Gastrointestinal Endoscopy Mar 2023The true rate of gastric cancer (GC) in juvenile polyposis syndrome (JPS) is unknown because of its rarity and ascertainment bias in published literature. To better... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The true rate of gastric cancer (GC) in juvenile polyposis syndrome (JPS) is unknown because of its rarity and ascertainment bias in published literature. To better assess this, we conducted a systematic review and meta-analysis.
METHODS
MEDLINE, Embase, and Scopus databases were searched for the key words juvenile polyposis syndrome, juvenile polyps, stomach cancer, GC, SMAD4, BMPR1A, hamartomatous polyposis syndrome, hamartomas, and hereditary cancers for studies reporting upper GI manifestations in JPS. The primary outcome was the reported occurrence of GC in JPS. We then compared GC occurrence based on the presence or absence of pathogenic germline variants (PGVs) and in untested patients.
RESULTS
Eleven studies including 637 patients were included. The pooled occurrence of GC was 3.5% (95% confidence interval [CI], 1.8-5.2; I = 12.3%) at a median age of 42.5 years (range, 15-57.6). The pooled occurrence of GC in patients with SMAD4 PGV was 10.1% (95% CI, 3.2-16.8%; I = 54.7%). GC was reported in only 1 BMPR1A PGV carrier and was not reported in patients without an identifiable PGV. In patients with prior germline testing, the risk of GC was higher in SMAD4 PGV carriers (odds ratio, 11.6; 95% CI, 4.6-29.4; I = 18.3%) compared with patients without SMAD4 PGV. In JPS patients with unknown status of germline testing, pooled occurrence of GC was 7.5% (95% CI, 0-15.5). There was an overall moderate risk of bias in the studies.
CONCLUSIONS
GC is highest in SMAD4-associated JPS and was not reported in patients without identifiable PGVs. The value of GC surveillance in BMPR1A PGV carriers and JPS patients without an identifiable PGV is questionable. Germline testing should be performed in all JPS patients to inform GC risk discussion and utility of surveillance.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Stomach Neoplasms; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Germ-Line Mutation; Intestinal Polyps; Smad4 Protein; Hamartoma
PubMed: 36265529
DOI: 10.1016/j.gie.2022.10.026 -
Surgical Endoscopy Mar 2022This paper aimed to elucidate the etiologies of all primary ileostomy site malignancies published in the literature. (Review)
Review
BACKGROUND
This paper aimed to elucidate the etiologies of all primary ileostomy site malignancies published in the literature.
METHODS
A review of the literature was conducted following PRISMA guidelines by querying PubMed, Global Health, and Web of Science for articles published before November 2020. Search criteria contained broad terminology for ileostomy site neoplasms without language, date, or publication limitations. A full-text review of the abstracts confirmed primary malignant pathologies and was evaluated for study inclusion.
RESULTS
Literature search discovered 858 publications, with 76 meeting eligibility criteria. The final sample contained 91 patients, with equal males and females. The mean age of patients with ileostomy site malignancy was 62.0 ± 12.2, with an average ileostomy age of 29.4 ± 12.4. The most common indications for ileostomy creation were inflammatory bowel disease (IBD) (73.6%) and familial adenomatous polyposis (FAP) (20.9%). There was a total of eight ileostomy malignant pathologies reported, with adenocarcinoma being the most common (76.9%), followed by squamous cell carcinoma (SCC) (11.0%). Adenocarcinoma was diagnosed at a younger age than SCC (59.7 vs. 72.3) and developed over a shorter time (28.8 vs. 37.0). Patients with FAP almost exclusively developed adenocarcinoma (94.4%) at a younger stoma age (25.8 vs. 31.4) than those with IBD who developed seven diverse pathologies. With a median follow-up of 0.75 years, four patients developed disease recurrence and received oncologic resection of their cancer less often than the 55 negative patients (p = 0.04).
CONCLUSION
Ileostomy site malignancies are late-appearing complications that require curative surgery. Their presentation is associated with ileostomy duration and creation indication, such as FAP or IBD. We recommend screening at a stoma age ≥ 20 or patient age ≥ 50 for patients with FAP, while stoma age ≥ 25 or patient age ≥ 60 for IBD patients.
Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Female; Humans; Ileostomy; Male; Neoplasm Recurrence, Local; Surgical Stomas
PubMed: 34997348
DOI: 10.1007/s00464-021-08847-7 -
Current Medical Research and Opinion Nov 2020We conducted a systematic literature review (SLR) of randomized controlled trials and real-world evidence (RWE) studies to determine the humanistic (e.g....
OBJECTIVES
We conducted a systematic literature review (SLR) of randomized controlled trials and real-world evidence (RWE) studies to determine the humanistic (e.g. health-related/disease-specific quality of life [QOL]) and economic (e.g. direct and indirect costs) burdens of chronic rhinosinusitis with nasal polyposis (CRSwNP).
METHODS
The SLR adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, MEDLINE and Evidence-Based Medicine Reviews databases were searched using OVID. Relevant studies involving adult patients with CRSwNP published between 1 January 2008 and 16 February 2019 were included, with relevant conference abstracts from 1 January 2017, onward.
RESULTS
Sino-Nasal Outcomes Test (SNOT)-22 was the most frequently used disease-specific health-related QOL/patient-reported outcomes instrument for patients with CRSwNP. Baseline SNOT-22 scores ranged from 25 to 73 for surgical candidates and from 14 to 56 for medically managed patients with CRSwNP. Mean baseline EuroQol-5 Dimensions (EQ-5D) index for patients with CRSwNP ranged from 0.81 to 0.86, and mean baseline Short Form-6 Dimensions (SF-6D) ranged from 0.67 to 0.75. Three months (EQ-5D) and 5 years (SF-6D) post-endoscopic sinus surgery (ESS), rates increased from 0.81 to 0.89 and from 0.69 to 0.80, respectively. One year post-diagnosis, patients with CRSwNP had significantly more systemic prescriptions, underwent significantly more medical procedures, demonstrated greater health care resource utilization and had significantly greater mean health care costs compared with matched controls (all < .001). Overall, for patients with initial ESS, CRSwNP was associated with higher disease-related expenditures compared with CRS without nasal polyposis (NP), even for patients who did not undergo revision surgery.
CONCLUSIONS
This SLR identified substantial humanistic burden among surgery candidates. RWE shows that surgeries were used to treat relatively more severe CRSwNP patients as recommended by guidelines. Patient QOL is improved significantly after surgery; however, there is a lack of evidence on patients with revision surgery. Surgery is also associated with higher costs, and the presence of NP was a predictor of revision surgery. Patients with CRSwNP demonstrate greater health care resource utilization and costs compared to those with CRS without NP. Costs associated with different severity of CRSwNP and revision surgery need to be assessed further.
Topics: Chronic Disease; Cost of Illness; Endoscopy; Health Care Costs; Health Expenditures; Humans; Nasal Polyps; Patient Acceptance of Health Care; Patient Reported Outcome Measures; Quality of Life; Randomized Controlled Trials as Topic; Reoperation; Rhinitis; Sinusitis
PubMed: 32851882
DOI: 10.1080/03007995.2020.1815683