Multimorbidities in Allergic Rhinitis-Current Evidence from Epidemiological Studies, Treatment Trials, and Molecular Data.

PURPOSE OF REVIEW: Given that allergic rhinitis (AR) commonly coexists with other diseases, the present narrative review attempts a brief presentation of current theories on multimorbidities in relation to phenotypes, genotypes, age, and treatment responses with the term "multimorbidities" indicating the uncertainty regarding the primary defect, organ, or pathophysiologic mechanism involved. RECENT FINDINGS: Though age-related manifestations allow for the generation of several hypotheses on AR's specific mechanisms, the various theories regarding the initiation or the aggravation of atopic disorders have yet to be proved. Multimorbid AR seems to have a different genetic basis from "stand-alone" AR as well a more severe phenotype. Most studies on the treatment of AR and its multimorbidities focus on allergen immunotherapy, which improves the atopic symptoms and may play a preventive role in the onset of new allergen sensitizations. The use of biological factors may also have a beneficial effect, even though it has currently been approved only for some comorbidities of AR, such as asthma. Employing the use of phenotypes and genotypes concerning multimorbidity broadens current knowledge, but further research is needed to develop diagnostic, stratificational, and predictive algorithms for single and multimorbid allergic diseases (Fig. 1). The real-time data obtained by mobile apps and the new insights on the pathophysiology of AR and its comorbidities will permit both timed preventive measures and better individualized and effective antiallergic treatment. Fig. 1 Current concepts and future trends in diagnosis and management of multimorbid allergic rhinitis.

CYP1A2 polymorphisms modify the association of habitual coffee consumption with appetite, macronutrient intake, and body mass index: results from an observational cohort and a cross-over randomized study.

BACKGROUND/OBJECTIVES: Evidence regarding the influence of coffee on appetite and weight control is equivocal and the influence of covariates, such as genetic variation in caffeine metabolism, remains unknown. Herein, we addressed the novel hypothesis that genetic variation in CYP1A2, a gene responsible for more than 95% of caffeine metabolism, differentially impacts the association of coffee consumption with appetite and BMI among individuals with different genetic predispositions to obesity. SUBJECTS/METHODS: A cross-over randomized intervention study involving 18 volunteers assessed the effects of coffee consumption on dietary intake, appetite, and levels of the appetite-controlling hormones asprosin and leptin. Data on habitual coffee intake, BMI, and perceived appetite were obtained from an observational cohort of 284 volunteers using validated questionnaires. Participants were stratified according to a validated genetic risk score (GRS) for obesity and to the -163C > A (rs762551) polymorphism of CYP1A2 as rapid (AA), intermediate (AC), or slow (CC) caffeine metabolizers. RESULTS: Coffee consumption led to lower energy and dietary fat intake and circulating asprosin levels (P for interaction of rs762551 genotype*coffee consumption=0.056, 0.039, and 0.043, respectively) as compared to slow/intermediate metabolizers. High coffee consumption was more prevalent in rapid compared to slow metabolizers (P = 0.008 after adjustment for age, sex, and BMI) and was associated with lower appetite perception and lower BMI only in rapid metabolizers (P for interaction of rs762551 genotype*coffee consumption = 0.002 and 0.048, respectively). This differential association of rs762551 genotype and coffee consumption with BMI was more evident in individuals at higher genetic risk of obesity (mean adjusted difference in BMI = -5.82 kg/m2 for rapid versus slow/intermediate metabolizers who consumed more than 14 cups of coffee per week). CONCLUSIONS: CYP1A2 rs762551 polymorphism modifies the association of habitual coffee consumption with BMI, in part by influencing appetite, energy intake and circulating levels of the orexigenic hormone asprosin. This association is more evident in subjects with high genetic predisposition to obesity. ClinicalTrials.gov: registered Clinical Trial NCT04514588.

Multidisciplinary Care for Severe or Uncontrolled Chronic Upper Airway Diseases.

PURPOSE OF REVIEW: A multidisciplinary approach is regarded as the best practice for many chronic diseases, such as cancer and asthma, with well-documented value. There is also evidence that it may be beneficial to patients with chronic rhinosinusitis (CRS) and/or allergic airway disease presenting to tertiary referral centres. We discuss here whether and how organizing this kind of healthcare transition into a more integrated care pathway would benefit severe chronic upper airways disease (SCUAD) management. RECENT FINDINGS: Based on a recent related EUFOREA panel discussion, literature search, and review of the best overseas practices, an appropriate implementation strategy of multidisciplinary care and its potential results are presented. Organizational principles, hurdles, and challenges of the process, as well as envisaged solutions and results, are being reported. The efficiency of care and the quality control assessment are concepts that are currently gaining importance. At the same time, novel treatment options based on molecular and precision medicine advancements, such as biologics, are being increasingly prescribed. Appropriately organized multidisciplinary care teams can adapt to new demands, data, and discoveries to assure maximum benefit for both patients and healthcare professionals.

Imaging in chronic rhinosinusitis: A systematic review of MRI and CT diagnostic accuracy and reliability in severity staging.

BACKGROUND: Computerized tomography (CT) severity scores are frequently used as an objective staging tool in chronic rhinosinusitis (CRS). Magnetic resonance imaging (MRI) has also been proposed as a valid option in CRS imaging. PURPOSE: The aim of this systematic review was to briefly present the recent developments on sinus imaging utilized in clinical practice with regard to diagnostic accuracy of imaging and severity staging in CRS according to evidence-based medicine (EBM) principles. MATERIAL AND METHODS: This review paper has been assembled following PRISMA guidelines. A PubMed and Scopus (EMBASE) search using CRS, "severity staging", "diagnostic accuracy "and "imaging "resulted with 80 results. Of these, only 12 (59%) contained original data, constituting the synthesis of best-quality available evidence. RESULTS: CT is the most commonly used imaging technique for the severity staging of CRS, but a question of higher cumulative radiation dose should be taken into consideration when repeating CT examinations in evaluating treatment efficacy. MRI may be a complementary diagnostic and staging tool, especially when repeated examinations are required, or when paediatric CRS patients are evaluated. The severity staging system may be improved to better correlate with subjective scores. CONCLUSIONS: MRI may be utilized as a staging tool with comparable diagnostic accuracy, using the same staging systems as with CT examinations.

Warthin's tumour seems to be the most common benign neoplasm of the parotid gland in Germany.

PURPOSE: Recent reports indicate an increase in the prevalence of Warthin's tumours (adenolymphoma) with percentages which exceed that of pleomorphic adenomas (PA) in the same registries. The purpose of this study is to analyse a large cohort of benign parotid tumours in relation to various demographic and other patients' characteristics that might affect their incidence. METHODS: A retrospective review of prospective collected data was performed on all patients who have been operated for a parotid mass in the last 5 years. A total of 474 patients with benign lesion were included in the study. Age, gender, smoking status, histological diagnosis, site of lesion, and size of tumour were recorded. RESULTS: Warthin's tumours were the most common benign lesions, found in 201 (42.4%) parotic glands followed by pleomorphic adenomas found in 138 (29.1%) of these surgical cases. Patients with WT had a mean age of 61.6 years instead of 52 years for PA patients (t = 6.589, p < 0.001). The vast majority (93%) of patients with WT had a current or previous history of smoking compared with 47% of PA patients (p = 0.001). There was a male predominance regarding WT with a male:female (M:F) ratio of 2.3:1, whereas the corresponding ratio of PA was 1:1.4. CONCLUSIONS: This study confirms the increased regional prevalence of WT reported in studies mainly carried out in central Europe. This could affect future management of WT, which remains largely controversial due to the extremely low malignant potential reported, concurrently with its higher rates of multiplicity and recurrence, as well as the moderately accurate results of FNA biopsies.

Precision Medicine in Rhinosinusitis.

PURPOSE OF REVIEW: Our scope is the presentation of research and clinical progresses in relation to precision medicine that are expected to alter our clinical practice in relation to chronic rhinosinusitis (CRS). Current knowledge on phenotypes and endotypes, biomarkers, and clinical markers for diagnosis, medical and surgical therapy, and prognosis is presented as well as the role of precision medicine in United Airway Disease and SCUAD (severe-uncontrolled chronic upper airway inflammation). RECENT FINDINGS: Current technological progresses, mostly in relation to molecular biology and information technology, have permitted more detailed pathophysiological assessments and multidimensional approaches in airways diseases. Based on the concept of united airways diseases, new classification schemes, called endotypes, have been proposed for CRS. In addition, novel biological treatments that have been introduced for the treatment of asthma show great promise as well for severe uncontrolled cases of CRS with nasal polyps. Central to this approach are new biomarkers that are being examined in relation to complex bio-clinical traits of CRS. As this narrative review of the aforementioned precision medicine initiatives in relation to CRS advances, a modification of current practice is expected not only for severe chronic upper airways diseases in tertiary centers but also for milder and more common cases that are being encountered in the community.

On the history of modern tonsillectomy: the contribution of Nikolaos Taptas.

The earliest reports on removal of the entire tonsil using a method of careful dissection came in the early 1900 s by American and British otorhinolaryngologists. These descriptions are credited as the first of the so-called modern tonsillectomy. In this report we present a technique of tonsillectomy conceived by Nikolaos Taptas, a Greek physician and citizen of the Ottoman Empire, which was introduced at the same period with the ones previously mentioned. Taptas practiced his technique in the very early 1900 s. He used his own instruments and reported excellent post-operative results with very few complications. He should therefore be considered among the pioneers of modern tonsillectomy.

Genotype-guided dietary supplementation in precision nutrition.

Achieving adequate micronutrient status, while avoiding deficiencies, represents a challenge for people globally. Consequently, many individuals resort to oral nutrient supplementation (ONS) in order to correct suboptimal dietary intakes. Advances in the fields of nutrigenetics and nutritional genomics have identified differences in response to micronutrient supplementation according to genetic makeup, adding dietary supplement use to the clinician's toolkit in the precision nutrition era. This review focuses on published evidence linking genetic variants to the responses associated with some of the most popular dietary supplements. With an increasing number of health professionals becoming involved in the prescription of ONS, identifying and matching individuals to the appropriate dietary supplement according to their genotype is important for achieving optimal health benefits and micronutrient equilibrium, while reducing the adverse events and financial costs often associated with excessive ONS.

Clinical practice: diagnosis and treatment of childhood snoring.

Obstructive sleep-disordered breathing in children is a relatively common problem, presenting in various ways, from primary snoring, without an apparent decrease in quality of life, to obstructive sleep apnea with cognitive, cardiac, and growth abnormalities. History, clinical examination, radiologic evaluations, sleep studies, and other diagnostic modalities are reviewed. Since application and interpretation of these methods are not consistent in studies of snoring, a consensus on optimal treatment options has not been established. Traditionally, adenotonsillectomy has long been the treatment of choice. Treatment failures or recurrences as well as the existence of causes and contributing factors other than adenotonsillar hypertrophy, like obesity, facial malformations, and Down syndrome, have changed the concept of adenotonsillectomy as the ultimate cure. Several other treatment options have been proposed on their own or in combination. Continuous positive airway pressure, anti-inflammatory medications, maxillofacial, and orthodontic treatments are reviewed suggesting the need of a multidisciplinary approach in some cases. Finally, at the end of the chapter, a diagnostic and treatment work up based on current evidence is proposed for otherwise normal children or children with specific conditions.

The "Virtual Digital Twins" Concept in Precision Nutrition.

Nutritional and lifestyle changes remain at the core of healthy aging and disease prevention. Accumulating evidence underscores the impact of genetic, metabolic, and host gut microbial factors on individual responses to nutrients, paving the way for the stratification of nutritional guidelines. However, technological advances that incorporate biological, nutritional, lifestyle, and health data at an unprecedented scale and depth conceptualize a future where preventative dietary interventions will exceed stratification and will be highly individualized. We herein discuss how genetic information combined with longitudinal metabolomic, immune, behavioral, and gut microbial parameters, and bioclinical variables could define a digital replica of oneself, a "virtual digital twin," which could serve to guide nutrition in a personalized manner. Such a model may revolutionize the management of obesity and its comorbidities, and provide a pillar for healthy aging.

Evaluation of nasal mucociliary clearance after medical or surgical treatment of chronic rhinosinusitis.

An evaluation of mucociliary clearance, with the use of rhinoscintigraphy and other objectives and subjectives measures, in medically and surgically treated patients with chronic rhinosinusitis, as well in patients with or without nasal polyposis, can add to the understanding of ciliary function and its role in the pathogenesis of chronic rhinosinusitis. Thirty-four patients medically treated and 21 surgically treated (FESS) patients evaluated with rhinoscintigraphy, CT-scans, and SNOT-20. Nine of the surgically treated patients had nasal polyps and studied as a separate group. Although the various groups differ on Lund-Mackay scores (H = 11.659, P = 0.003) and SNOT-20 results (F = 26.904, P < 0.001), a statistically significant difference between mucociliary transport velocity (MTV) values could not be found. Moreover, multiple linear regression could not prove a statistically significant correlation between MTV and other variables. The various groups of chronic rhinosinusitis patients cannot be differentiated on the basis of possible nasal mucociliary clearance alternations.

Telomere length and genetic variations affecting telomere length as biomarkers for facial regeneration with platelet-rich fibrin based on the low-speed centrifugation concept.

BACKGROUND: Platelet-Rich Fibrin (PRF), a fibrin matrix produced by single blood centrifugation that contains leukocytes, platelets, and growth factors, is increasingly being utilized for facial regeneration purposes. However, our understanding of the involved pathophysiological mechanisms affecting regeneration is limited and current protocols require better optimization. Biomarkers that are related to skin aging such as telomere length (TL) have been proposed as a mean to analyze patients' stratification. OBJECTIVE: Our aim is to study whether the outcomes of a facial regeneration protocol performed with PRF are related to TL and genetic variations affecting TL. This can aid in the standardization of a surgical aesthetic protocol. PATIENTS AND METHODS: In all, 41 patients treated with PRF produced with the low-speed centrifugation concept were included in this observational study. The correlation between TL and genetic variations were assessed versus treatment outcomes, namely the number of sessions and aesthetic results utilizing the FACE-Q skin satisfaction questionnaire. RESULTS: In all, 39 of the 41 patients completed the treatment. TL correlated with the initial responses to FACE-Q (ρ = .33, P = .05). Genetic variations affecting TL was related to the change of FACE-Q (ρ = .35, P = .034) as well as to the number of treatment sessions (ρ = .38, P = .019). CONCLUSIONS: Telomere length (TL) was related to patient perceived facial skin appearance. In addition, genetic variations affecting TL were related to the final outcomes (number of sessions and improvements of FACE-Q results) and may be a useful biomarker for future regenerative procedures performed with PRF for facial regeneration.

Tonsillectomy versus tonsillotomy performed with scissors in children with tonsillar hypertrophy.

OBJECTIVE: We sought to determine the morbidity and the short and long-term effectiveness of tonsillotomy (partial tonsillectomy) performed with scissors compared with conventional cold knife (total) tonsillectomy. METHODS: We conducted a 2-year prospective non-randomized study at a tertiary children's hospital. One thousand and twenty-three children were recruited (243 in the tonsillotomy and 780 in the tonsillectomy group). Age, sex, weight, and time of operation, immediately post-operative complications and pain were recorded. Eighteen months after the operation data on weight, parents' satisfaction and recurrence of obstructed symptoms was obtained in 60 randomly selected children of each group. RESULTS: Post-operative complications rates were very low in both groups and their differences did not reach statistical significance. However, tonsillotomies were significantly better than tonsillectomies in relation to post-operative pain the 1st (P<0.001) and the 7th (P<0.001) post-operative day, and lasted an average of 2.5 min less. Concerning long-term effects, both methods resulted in an increase of patients' weight without the difference in weight increase be statistically significant. In addition, parents' satisfaction as well as oral malodour do not seem to differ significantly. Finally, although twice as many children in the tonsillotomy group had a recurrence of snoring compared to tonsillectomy group, only in about half of them was the problem regarded significant enough by their parents to require medical consultation or reoperation. At the end, an estimated 3.5% of the tonsillotomy group was offered a tonsillectomy in the long term. CONCLUSION: This trial shows that scissors tonsillotomy in combination with an adenoidectomy is a viable therapeutic option with less immediate post-operative morbidity than tonsillectomy in young children whose sleep disorder breathing is due to a combination of tonsilar and adenoid hypertrophy. However, parents should be informed of the possibility of regrowth and reoperation.

Is mucociliary transport velocity related to symptoms in chronic rhinosinusitis patients?

Mucociliary transport velocity (MTV) measured by rhinoscintigraphy is considered a reliable measure of mucociliary clearance, one of the mechanisms that are distorted in chronic rhinosinusitis (CRS). The aim of this study was to investigate possible correlation of MTV with the severity of patients' symptoms. We have studied thirty-seven CRS patients who completed the 20-item sinonasal outcome test (SNOT-20) form, a reliable measure of health related quality of life and were also examined by rhinoscintigraphy with technetium-99m macroaggregated albumin. Our findings showed that the MTV of our patients ranged from nil to 4.17mm/min with a mean value of 1.74+/-1.055 mm/min. The SNOT-20 scores varied from 0.3 to 3.7 with a mean of 1.6+/-0.922. The correlation between SNOT-20 score and MTV was not statistically significant (Spearman's r=-0.191). In conclusion, although rhinoscintigraphy is widely accepted as a reliable test of mucociliary velocity and clearance, it did not correlate with subjective measures of the severity of CRS.

Cutting-edge technologies for diagnosis and monitoring of snoring in children.

Snoring is a very common problem in children and may be an indication of obstructive sleep apnea (OSA). Appropriate diagnosis is of importance due to detrimental effects of OSA. Polysomnography is considered the gold standard for the diagnosis of OSA. However, it is impractical for several reasons and this is why other tests have been developed as alternatives to formal polysomnography (PSG) for the assessment of children with snoring. In this mini-review basic features of PSG as well as alternative tests are presented and future perspectives are provided in addition to current guideline for the diagnosis and monitoring of childhood snoring. The aim of this review is to highlight briefly currently developed technologies that seem promising for the evaluation of snoring.

Chronic rhinosinusitis: observation or treatment.

PURPOSE OF REVIEW: Several treatment options have been proposed for chronic rhinosinusitis (CRS). Our purpose is to present a protocol/tool to treat patient symptoms, which is initially independent of assessment for presence of CRS. RECENT FINDINGS: This protocol is called the Rational Patient Experiment (RPE), and its concept is largely based on the fact that CRS is overrepresented in incidence based on surveys, because symptoms of CRS are nonspecific and overlap multiple other disorders. Patients whose symptoms persist, despite the RPE, require further objective assessment of CRS with endoscopy and computed tomography. SUMMARY: This review outlines the RPE and the evidence base for observation versus treatment with saline washes, steroids, or antibiotics.

Two-flap palatoplasty: description of the surgical technique and reporting of results at a single center.

Two-flap palatoplasty is commonly used to treat cleft palate defects, but only a few reports on outcomes have been published in the literature. We conducted a retrospective analysis of 257 cases of cleft palate treated with two-flap palatoplasty at a single center in Greece over a 13-year period. Our outcomes data included surgical complication rates, the results of speech assessments, midface development, and other parameters. We found a low rate of short- and long-term complications that required revision surgery, such as symptomatic fistula (5.4%) and velopharyngeal insufficiency (5.3%). Speech outcomes in relation to intelligibility, hypernasality, and nasal emissions were satisfactory in 70 to 86% of patients. Dental arch relationships, as estimated by the 5-Year-Olds Index, were judged to be either good or excellent in 62% of those evaluated. A considerable proportion of patients (45%) who had otitis media with effusion experienced a spontaneous resolution without the use of tympanostomy tubes 2 to 8 months after their operation. We conclude that two-flap palatoplasty is an effective procedure that warrants further attention. We describe the surgical technique in detail. Our technique includes a modified intravelar veloplasty that incorporates near-total muscle retropositioning.

Impaired mucociliary clearance in allergic rhinitis patients is related to a predisposition to rhinosinusitis.

Although mucociliary clearance has been shown to be impaired in patients with allergic rhinitis and chronic rhinosinusitis, its exact role in relation to a predisposition to rhinosinusitis is unknown. To investigate this possible association, we conducted a prospective study of 125 patients with allergic rhinitis. Of this group, 23 patients were classified as being sinusitis-prone based on their history of antibiotic consumption for the treatment of rhinosinusitis; the remaining 102 patients were deemed to be not sinusitis-prone. The saccharine test was used to evaluate mucociliary clearance in all patients. Several variables-age, sex, smoking habits, rhinitis severity, and medication history-were examined. We found that the sinusitis-prone patients had a significantly greater mucociliary clearance time than did those who were not prone (median: 15 and 12 min, respectively; p = 0.02). No other statistically significant differences were seen between the 2 groups with respect to any other variables that might have affected mucociliary clearance. We conclude that impaired mucociliary clearance in allergic rhinitis patients is associated with a predisposition to rhinosinusitis.

Health needs in rural areas and the efficacy and cost-effectiveness of doctors and nurses.

OBJECTIVE: Because of a lack of GPs in rural areas of Greece it is mandatory for junior doctors to offer medical service in those areas for a year. The aim of this study is to determine the possibility of replacement of internships with nurses and to suggest the most cost-effective way of covering health needs in remote areas. DESIGN: Regional survey. SETTING AND PARTICIPANTS: Patients of primary care offices in two remote areas of Crete, Greece within a year. MAIN OUTCOME MEASURES: Comparative analysis of the level of preventive medicine (estimated by questionnaires) and health needs in the two areas. The reasons for visiting medical offices, references rates, percentages of glucose and blood pressure regulation are also studied. RESULTS: Prescription of drugs for chronic diseases and blood pressure counting were the main reasons for office visits (2868/4594). Respiratory track infections (364/4594) follow. Apart from the high percentages of uncontrolled patients with blood pressure (34%) and diabetes mellitus (14%) there is a high percentage of ignorance or wrong opinions concerning preventive medicine, for example only 63% knew the value of a pap test. CONCLUSIONS: More than two-thirds of "medical" visits in rural areas were for acts that nurses could easily do. The easy access to a junior doctor did not promote preventive medicine. Replacement of junior doctors with properly trained nurses cooperating with GPs responsible for greater regions would be more cost-effective than junior doctors improving health in rural areas. Legislation should change, mainly with regard to repeat prescriptions, in order to reduce house visits.