Translating the biology of ß common receptor-engaging cytokines into clinical medicine.

The family of cytokines that comprises IL-3, IL-5, and GM-CSF was discovered over 30 years ago, and their biological activities and resulting impact in clinical medicine has continued to expand ever since. Originally identified as bone marrow growth factors capable of acting on hemopoietic progenitor cells to induce their proliferation and differentiation into mature blood cells, these cytokines are also recognized as key mediators of inflammation and the pathobiology of diverse immunologic diseases. This increased understanding of the functional repertoire of IL-3, IL-5, and GM-CSF has led to an explosion of interest in modulating their functions for clinical management. Key to the successful clinical translation of this knowledge is the recognition that these cytokines act by engaging distinct dimeric receptors and that they share a common signaling subunit called ß-common or ßc. The structural determination of how IL-3, IL-5, and GM-CSF interact with their receptors and linking this to their differential biological functions on effector cells has unveiled new paradigms of cell signaling. This knowledge has paved the way for novel mAbs and other molecules as selective or pan inhibitors for use in different clinical settings.

A Decade of Clinical Advances in Chronic Rhinosinusitis: 2012-2022.

The field of chronic rhinosinusitis (CRS) is constantly evolving. In the past 10 years, key advancements in basic and translational research as well as clinical studies have improved our understanding and management of CRS. Notably, treatment options have expanded to include novel therapeutic drugs, devices, and surgical techniques. Assessments of patient symptoms and their impact on quality of life have become more standardized. Progress has also been made in both determining the true prevalence of CRS and recognizing comorbidities that can impact CRS severity. Practice guidelines have also shifted from expert opinion to more data-driven analyses. This review highlights major clinical advancements made in the field of CRS over the past 10 years as well as identifies current gaps in knowledge that can form the basis for new areas of study over the next decade.

Study of capsule endoscopy delivery at scale through enhanced artificial intelligence-enabled analysis (the CESCAIL study).

AIM: Lower gastrointestinal (GI) diagnostics have been facing relentless capacity constraints for many years, even before the COVID-19 era. Restrictions from the COVID pandemic have resulted in a significant backlog in lower GI diagnostics. Given recent developments in deep neural networks (DNNs) and the application of artificial intelligence (AI) in endoscopy, automating capsule video analysis is now within reach. Comparable to the efficiency and accuracy of AI applications in small bowel capsule endoscopy, AI in colon capsule analysis will also improve the efficiency of video reading and address the relentless demand on lower GI services. The aim of the CESCAIL study is to determine the feasibility, accuracy and productivity of AI-enabled analysis tools (AiSPEED) for polyp detection compared with the 'gold standard': a conventional care pathway with clinician analysis. METHOD: This multi-centre, diagnostic accuracy study aims to recruit 674 participants retrospectively and prospectively from centres conducting colon capsule endoscopy (CCE) as part of their standard care pathway. After the study participants have undergone CCE, the colon capsule videos will be uploaded onto two different pathways: AI-enabled video analysis and the gold standard conventional clinician analysis pathway. The reports generated from both pathways will be compared for accuracy (sensitivity and specificity). The reading time can only be compared in the prospective cohort. In addition to validating the AI tool, this study will also provide observational data concerning its use to assess the pathway execution in real-world performance. RESULTS: The study is currently recruiting participants at multiple centres within the United Kingdom and is at the stage of collecting data. CONCLUSION: This standard diagnostic accuracy study carries no additional risk to patients as it does not affect the standard care pathway, and hence patient care remains unaffected.

Evaluation of incidence and prognosis of COVID-19 in patients with Nasal Polyps

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Type 2 immune response accompanied by type 2 cytokines such as IL-4, IL-5, IL-13, and eosinophilic inflammation, may have a potential protective effect against COVID-19 in chronic rhinosinusitis patients with nasal polyps (CRS + P). In the study, it was aimed to investigation the prevalence and prognosis of COVID-19 in chronic rhinosinusitis patients with nasal polyps (CRS + P). Materials and Methods: Patients between the ages of 15-65 operated for CRS + P and were compared with the control group in terms of incidence and disease severity. Results: Covid RT-PCR test was positive in 5.04% of CRS + P patients. This rate was 8.96% in the control group, and the difference between both groups was statistically significant. When the two groups were compared in terms of disease severity, no significant difference was found. Conclusions: The incidence of COVID-19 was lower in patients with CRS + P. However, further prospective studies are needed to research the relationship between nasal polyp and COVID-19.

Smell improvement by anti-IgE and anti-IL 5 biologics in patients with CRSwNP and severe asthma. A real life study.

BACKGROUND AND OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by partial (hyposmia) or total (anosmia) loss of smell, is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), worsens disease severity and quality of life. Objectives. The objective of this study was to determine whether, in real-life conditions, biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare smell improvement in N-ERD and non-N-ERD subgroups. METHODS: A multicenter, non-interventional, retrospective, observational study was performed, including 206 patients with severe asthma undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab) with CRSwNP. RESULTS: Improved olfaction was found after treatment with all monoclonal antibodies: omalizumab (35.8%), mepolizumab (35.4%), reslizumab (35.7%), and benralizumab (39.1%), with no differences between groups. Patients with atopy, greater use of short course systemic corticosteroids, and larger polyp size were more likely to experience improvement in smell. The proportion of patients experiencing smell improvement was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSION: This is the first study to compare real-life improvement in sense of smell among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in sense of smell (with non-significant differences between biologic drugs). No differences were found in smell improvement between the N-ERD and non-N-ERD group.

Outcomes of Cricothyroid Visor Maneuver (CVM) for Treatment of Vocal Polyp: A Case Report.

OBJECTIVE: The aim of the study is the clinical investigation of a patient with a vocal fold polyp, and the visual, acoustical, perceptual, and self-report changes before and after using the cricothyroid visor manoeuvre (CVM). DESIGN: A 48-year-old female university professor, gynecologist, and obstetrician with a history of laryngopharyngeal reflux and a left vocal polyp participated. Treatment was provided in 10 sessions. Pre- and post-treatment audio recordings of sustained vowels, selected sentences, and connected speech samples were submitted to auditory-perceptual and acoustical analysis to assess the effects of the two-treatment program. Also, laryngoscopic images, perceptions by the patient about her voice quality and quality of life before and after therapy were assessed. RESULTS: Improvements in acoustic parameters were obtained especially in perturbation and CCPS parameters. The overall voice quality scores on the CAPE-V were moderate before therapy and became mild after therapy. Laryngoscopy images demonstrated improvement in the glottis closure configuration in two phases (open and close) in pre- and post- CVM therapy and a decrease in polyp size. The patient had improvement in VAS, IVQLP, and VRQOL scores. CONCLUSION: The CVM therapy used in the study resulted in positive changes in acoustic and perceptual-auditory aspects of voice production, self-report, and QOL for the patient. The CVM approach appears to have been effective for this case in decreasing the polyp size or its regression or for vocal adaptation.

Safety Profile of Dupilumab Approved for Chronic Rhinosinusitis with Nasal Polyposis: Analysis from the European Spontaneous Adverse Event Reporting System: An International Journal of Medical Toxicology and Drug Experience

Introduction: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by a type 2 pattern of inflammation resulting in the production of some cytokines such as interleukin (IL)-4, IL5, and IL13. Options for treatment-resistant CRSwNP include aspirin desensitization, recurrent topic and systemic corticosteroid use, and functional endoscopic sinus surgery (FESS). However, frequent relapses after medical and surgical treatment have been observed. Thus, dupilumab, a human recombinant monoclonal IgG4 antibody, changes radically the treatment of CRSwNP because of its binding effects on major drivers of human type 2 inflammatory processes [1-3]. Considering its recent approval, it may be useful to evaluate its safety profile. Objective: The aim of this study was to describe better adverse drug reactions (ADRs) related to dupilumab in the treatment of CRSwNP analyzing all individual case safety reports (ICSRs) collected into the European Spontaneous Reporting System (SRS) database. Methods: All ICSRs recorded starting from the drug approval up to 31 December 2021 with dupilumab reported as suspected and having the specific indication of CRSwNP were considered. A descriptive analysis was conducted to assess demographic characteristics and dupilumab-related variables. Results: Out of 10,400 ICSRs related to dupilumab, only 481 (4.6%) had CRSwNP indication, of which 68.2% were related to adults and 54.3% to females. The 68.4% were serious;however, ICSRs mainly led to a completely or partial recovering (25.4%) and 8 cases were fatal (1.7%). The time to onset (TTO) of ADRs was 25 (1-84.75) days while the time to resolution (TTR) was 5 (1.75-15.75) days. Analyzing ADRs by System Organ Classes (SOCs), the most reported were general and administration site conditions (36.4%) followed by injuries (21.6%), infections (21.2%), respiratory (19.1%), skin (16.6%), and nervous system disorders (16.4%). Looking at Preferred Terms (PTs), arthralgia (7.3%), eosinophilia (6.9%), COVID-19 (6.0%), pyrexia (5.8%), asthenia (5.6%), rash (5.4%), and dyspnoea (5.2%) were the most reported. The 7.5% of ICSRs described an aggravated condition with persistent nasal polyps: in 4 cases (0.8%) a nasal polypectomy was required. Considering fatal ICSRs, two cases were related to progression of COVID-19, one to road traffic accident, one to accidental death and the others were not fully specified. Conclusion: These results showed that dupilumab-related ICSRs are not commonly reported in CRSwNP. However, given the good treatment response and the minimal adverse effects observed, clinicians should consider treating CRSwNP with dupilumab. Moreover, additional analyses are necessary to better outline the safety profile of dupilumab in this particular setting.

The role of microvesicles as biomarkers in the screening of colorectal neoplasm.

BACKGROUND: Colorectal cancer (CRC) is the second cause of cancer death worldwide. The role of circulating microvesicles as a screening tool is a novel, yet effective approach that warrants prioritised research. METHODS: In a two-gate diagnostic accuracy study, 35 patients with benign colorectal polyps (BCRP) (n = 16) and colorectal cancer (CRC) (n = 19) were compared to 17 age-matched healthy controls. Total annexin-V positive microvesicles and sub-populations positive for selected biomarkers relevant to bowel neoplasm were evaluated in patients' plasma using flow cytometry. Statistical methods including factor analysis utilising two component factors were performed to obtain optimal diagnostic accuracy of microvesicles in identifying patients with colorectal neoplasms. RESULTS: Total plasma microvesicles, and sub-populations positive for CD31, CD42a, CD31+/CD42a-, EPHB2, ICAM and LGR5 (component factor-1) were able to identify patients with BCRP and CRC with a receiver operator curve (AUC) accuracy of a 100% (95% CI: 100%-100%) and 95% (95% CI: 88%-100%), respectively. To identify patients with BCRP, a cut-off point value of component factor-1761 microvesicles/µl demonstrated a 100% sensitivity, specificity and negative predictive value (NPV) and a 93% positive predictive value (PPV). To identify patients with CRC, a cut-off value of component factor-1 3 439 microvesicles/µl demonstrated a 100% sensitivity, specificity and NPV and a 65% PPV. CEA+ microvesicles sub-population were significantly (p < 0.02) higher in CRC in comparison to BCRP. CONCLUSIONS: Microvesicles as biomarkers for the early and accurate detection of CRC is a simple and effective tool that yields a potential breakthrough in clinical management.

In this issue: Graphical abstract

After 52 weeks of treatment, 53.1% of patients had a complete response and 75.8% of patients had cumulative complete responses. Tobias Zahn, Ines Mhedhbi, Sascha Hein, Jan Raupach, Csaba Miskey, Younes Husria, Kathrin Bayanga, Detlef Bartel, Stefan Vieths, Zoltan Ivics, Doris Oberle, Brigitte Keller-Stanislawski, Marie-Luise Herrlein, Thorsten Jürgen Maier, Eberhard Hildt This study shows three long-term SARS-CoV-2 PCR-positive patients persistently producing infectious virus for up to 37 days without lasting symptoms. Patients displayed low antibody titers and decreased binding of IgG against sequential epitopes of spike protein in comparison with patients that fully recovered from mild COVID-19. [Extracted from the article] Copyright of Allergy is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Impact of COVID-19 pandemic on colonoscopy results - an overview.

<b>Aim:</b> Colorectal cancers are common cancers. Colonoscopy procedure, which is applied in the early diagnosis and treatment of this disease, has a very important role. In this study, we aimed to examine the effect of the COVID-19 pandemic period on our colonoscopic procedures. </br></br> <b> Material and methods:</b> In this observational study, the data of the patients who underwent colonoscopy in our General Surgery Endoscopy Unit, between March 11, 2019 and March 12, 2021 were scanned retrospectively. Patients under 18 years of age were excluded. The patients were divided into 2 groups. 1. Group patients between 11 March 2019-11 March 2020; patients in the pre-COVID-19 period, Group 2, on March 12, 2020-March 12, 2021; Grouped as the COVID-19 era. </br></br> <b>Results:</b> Data of 8285 patients were analyzed. A total of 4889 patients in Group 1 and 3396 patients in Group 2 were included in the study. The detection of precancerous polyps between the groups was found to be significantly higher in group 1 (p < 0.05) (4.3% vs 2.1). Similarly, the presence of precancerous polyps over the age of 65 was found to be significantly higher in the pre-covid group. In group 1, no significant difference was found in the evaluation of cancer patients according to gender (p > 0.05) (F/M: 1.2%/1.6%). In group 2, cancer patients were found to be significantly higher in males. </br></br> <b>Conclusions:</b> The COVID-19 pandemic has had negative effects in many areas, as well as on our colonoscopic procedures. Experienced centers continue to work to minimize these negative effects.

Original Article Highlights From This Issue

Airway eosinophil rather than neutrophil count is the independent predictor of the longitudinal change in all lung function measures, even in patients who are being treated with inhaled or oral corticosteroids or antieosinophilic biologics. In future clinical trials that are investigating eosinophils targeting therapies, the addition of small airway function markers to the routinely used FEV1 might be more appropriate for the evaluation of lung function. The patients with IIA should be carefully monitored after the occupational asthma diagnosis, and the poor asthma outcomes highlight the need for preventive actions.As-Needed Use of Short-Acting β2-Agonists Alone Versus As-Needed Use of Short-Acting β2-Agonists Plus Inhaled Corticosteroids in Pediatric Patients with Mild Intermittent (Step 1) Asthma: A Cost-Effectiveness Analysis Rodríguez-Martínez et al 1563 What is already known about this topic? What does this article add to our knowledge? A remote intervention can produce at least a 5% weight loss in a significant proportion of people with obesity and poorly controlled asthma, and this degree of weight loss is associated with improved asthma control.

SWOT Analysis of Chronic Rhinosinusitis Care Anno 2022.

Chronic rhinosinusitis (CRS) is a prevalent chronic condition with dynamic developments in diagnostic and therapeutic approaches given the recent updated guidelines and novel therapeutic approaches. A critical reflection on clinical practice of CRS care in 2022 is needed, hence providing hints for better care. This review provides an overall evaluation of the current approach of CRS care, including strengths, weaknesses, opportunities, and threat related to the current care pathways in most regions worldwide. Strengths of current CRS care are mainly related to effective treatment options allowing personalized care, with preventive and curative goals included in the current guidelines. However, a large portion of patients with CRS remain uncontrolled given the multiple weaknesses in CRS care, related to several factors such as underdiagnosis, undertreatment, and suboptimal coordination of care among health care providers. The opportunities for better care are ample given the possibility of implementing optimal care following guidelines, including preventive interdisciplinary strategies and patient-oriented treatment plans. In 2022, CRS represents a chronic condition that is subject to a (r)evolution of care with good opportunities for better outcomes and health economic savings.

Association of Chronic Rhinosinusitis with Risk of COVID-19 Infection

Chronic inflammatory diseases that affect the upper respiratory tract may be a risk factor for COVID19 infection. The current descriptive study is to investigate the existence of a relationship between chronic Rhinosinusitis disease (CRS) and infection with Covid 19. A descriptive study was conducted on 1125 participants who came to the specialized outpatient clinic of otolaryngology in Kirkuk) Iraq (, for the period between August and October of 2021. The results confirmed that the incidence of CRS among the participants was 11%, while the co-infection with COVID-19 was developed in 18 % of CRS patients. The incidence of hyposmia was 24 (18.0%) in CRS with COVID-19 patients versus 9 (6.0%) in non-Covid-19 patients. On the other hand, the proportion of nasal polyps was 41% among CRS patients infected with COVID-19. It was concluded that there is a risk relationship between chronic nasal inflammation and infection with Covid 19, so we recommend paying attention and conducting more accurate studies on this topic.

Deviated nasal septum and nasal polyps in COVID-19 patients: A case control study in DHQ Teaching Hospital, Mirpur, Azad Jammu and Kashmir Pakistan

Objective: To correlate the prevalence of COVID-19 and the rhinopathological conditions simultaneously in the population visiting the hospital of Mirpur, Azad Jammu and Kashmir. Study Design: Case-control study. Setting: District Head Quarter (DHQ) Teaching Hospital Located in Mirpur, Azad Jammu and Kashmir. Period: September 2020 to February 2021. Material & Methods: Patients visiting the DHQ teaching hospital, Mirpur, Azad Jammu and Kashmir for their COVID-19 related symptoms were included in the study. Demographic data was obtained. Prevalence of DNS and nasal polyps was recorded for further statistical analysis of the symptoms in the population. The obtained patient data was evaluated for the rhinopathological conditions that exists with the prevailing COVID-19 or may even aggravate the situation. Although nasal polyps and DNS are not among the typical symptoms of the COVID-19 but they may add to the results of PCR testing following swab testing. Conclusion: Despite being a significant relationship, there lies a chance of misleading results of swab testing as these rhinopathies obstruct the airway hindering the path. Therefore, while carrying out a confirmation test for the infection it is important to consider the chances of rhinopathies in patients beforehand. [ FROM AUTHOR] Copyright of Professional Medical Journal is the property of Professional Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Post-polypectomy colonoscopy surveillance: Can we improve the diagnostic yield?

Although adenomas and serrated polyps are the preneoplastic lesions of colorectal cancer, only few of them will eventually progress to cancer. This review provides a comprehensive overview of the present and future of post-polypectomy colonoscopy surveillance. Post-polypectomy surveillance guidelines have recently been updated and all share the aim towards more selective and less frequent surveillance. We have examined these current guidelines and compared the recommendations of each of them. To improve the diagnostic yield of post-polypectomy surveillance it is important to find predictors of metachronous polyps that better identify high-risk individuals of developing advanced neoplasia. For this reason, we have also conducted a literature review of the molecular biomarkers of metachronous advanced colorectal polyps. Finally, we have discussed future directions of post-polypectomy surveillance and identified possible strategies to improve the use of endoscopic resources with the COVID-19 pandemic.

Long-Term Follow-Up of a Severe Eosinophilic Asthmatic Patient With Comorbid Nasal Polyposis Hospitalized for SARS-CoV-2 Infection While Receiving Benralizumab: A Case Report.

We report a case of a patient affected by severe eosinophilic asthma with nasal polyps (SEA+NP) who developed coronavirus disease 2019 (COVID-19) six months after starting benralizumab as add-on therapy. Both SEA and NP were under control with no exacerbations at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient was hospitalized for four months, during which the treatment with benralizumab was interrupted. Despite the onset of bilateral interstitial pneumonia, developed as a consequence of the SARS-CoV-2 infection, the patient was discharged without complications, with a significant improvement in the chest CT scan following the administration of systemic corticosteroids (SCS) and low-flow oxygen therapy. The treatment with benralizumab was reintroduced at the regular dosing regimen immediately after his discharge. Lung function was assessed three months after the discharge and showed normal levels as before the development of COVID-19 symptoms. A long-term follow-up after 26 months from the introduction of benralizumab showed a normal lung function and well-controlled asthma, without exacerbations or the need for corticosteroid bursts.

Original Article Highlights From This Issue

Identification of patients who are at risk and bilateral collaboration among different specialists involved in caring for pregnant women should be established to support preventive strategies.Serum Inhaled Corticosteroid Detection for Monitoring Adherence in Severe Asthma Alahmadi et al 4279 What is already known about this topic? Blood detection of inhaled corticosteroids merits further testing as a potential measure of adherence in severe asthma.Risk of Neuropsychiatric Diseases According to the Use of a Leukotriene Receptor Antagonist in Middle-Aged and Older Adults with Asthma: A Nationwide Population-Based Study Using Health Claims Data in Korea Shim et al 4290 What is already known about this topic? Insight into IPV, a prevalent but underaddressed public health issue, elucidates potential etiologies behind difficult-to-control asthma, and will help to improve tailored evaluation and therapies.The Feasibility of a Lifestyle Physical Activity Intervention for Black Women with Asthma Nyenhuis et al 4312 What is already known about this topic? The eosinophil phenotype gradient algorithm will enable primary care physicians to identify and categorize asthma patients into those with and without eosinophilic asthma, and when appropriate, refer patients for phenotype-targeted treatment.Benralizumab Effectiveness in Severe Eosinophilic Asthma with and without Chronic Rhinosinusitis with Nasal Polyps: A Real-World Multicenter Study Nolasco et al 4371 What is already known about this topic?

Respiratory Nasal Mucosa in Chronic Rhinosinusitis with Nasal Polyps versus COVID-19: Histopathology, Electron Microscopy Analysis and Assessing of Tissue Interleukin-33.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most studied rhinological disorders. Modifications of the respiratory nasal mucosa in COVID-19 patients are so far unknown. This paper presents a comparative morphological characterization of the respiratory nasal mucosa in CRSwNP versus COVID-19 and tissue interleukin (IL)-33 concentration. (2) Methods: We analyzed CRSwNP and COVID-19 samples through histopathology, scanning and transmission electron microscopy and performed proteomic determination of IL-33. (3) Results: Histopathologically, stromal edema (p < 0.0001) and basal membrane thickening (p = 0.0768) were found more frequently in CRSwNP than in COVID-19. Inflammatory infiltrate was mainly eosinophil-dominant in CRSwNP and lymphocyte-dominant in COVID-19 (p = 0.3666). A viral cytopathic effect was identified in COVID-19. Scanning electron microscopy detected biofilms only in CRSwNP, while most COVID-19 samples showed microbial aggregates (p = 0.0148) and immune cells (p = 0.1452). Transmission electron microscopy of CRSwNP samples identified biofilms, mucous cell hyperplasia (p = 0.0011), eosinophils, fibrocytes, mastocytes, and collagen fibers. Extracellular suggestive structures for SARS-CoV-2 and multiple Golgi apparatus in epithelial cells were detected in COVID-19 samples. The tissue IL-33 concentration in CRSwNP (210.0 pg/7 µg total protein) was higher than in COVID-19 (52.77 pg/7 µg total protein) (p < 0.0001), also suggesting a different inflammatory pattern. (4) Conclusions: The inflammatory pattern is different in each of these disorders. Results suggested the presence of nasal dysbiosis in both conditions, which could be a determining factor in CRSwNP and a secondary factor in COVID-19.