Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Is generative pre-trained transformer artificial intelligence (Chat-GPT) a reliable tool for guidelines synthesis? A preliminary evaluation for biologic CRSwNP therapy.

INTRODUCTION: Biologic therapies for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) have emerged as an auspicious treatment alternative. However, the ideal patient population, dosage, and treatment duration are yet to be well-defined. Moreover, biologic therapy has disadvantages, such as high costs and limited access. The proposal of a novel Artificial Intelligence (AI) algorithm offers an intriguing solution for optimizing decision-making protocols. METHODS: The AI algorithm was initially programmed to conduct a systematic literature review searching for the current primary guidelines on biologics' clinical efficacy and safety in treating CRSwNP. The review included a total of 12 studies: 6 systematic reviews, 4 expert consensus guidelines, and 2 surveys. Simultaneously, two independent human researchers conducted a literature search to compare the results. Subsequently, the AI was tasked to critically analyze the identified papers, highlighting strengths and weaknesses, thereby creating a decision-making algorithm and pyramid flow chart. RESULTS: The studies evaluated various biologics, including monoclonal antibodies targeting Interleukin-5 (IL-5), IL-4, IL-13, and Immunoglobulin E (IgE), assessing their effectiveness in different patient populations, such as those with comorbid asthma or refractory CRSwNP. Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, demonstrated significant improvement in nasal symptoms and quality of life in patients with CRSwNP in several randomized controlled trials and systematic reviews. Similarly, mepolizumab and reslizumab, which target IL-5, have also shown efficacy in reducing nasal polyp burden and improving symptoms in patients with CRSwNP, particularly those with comorbid asthma. However, additional studies are required to confirm the long-term efficacy and safety of these biologics in treating CRSwNP. CONCLUSIONS: Biologic therapies have surfaced as a promising treatment option for patients with severe or refractory CRSwNP; however, the optimal patient population, dosage, and treatment duration are yet to be defined. The application of AI in decision-making protocols and the creation of therapeutic algorithms for biologic drug selection, could offer fascinating future prospects in the management of CRSwNP.

A Supplement with Ribes Nigrum, Boswellia Serrata, Bromelain and Vitamin D to Stop Local Inflammation in Chronic Sinusitis: A Case-Control Study.

Although chronic sinusitis widely affects the adult population, the treatments currently used did not always satisfactorily solve the symptoms. Traditional therapy with steroids and antibiotics presents risks and benefits and the new drugs, i.e., monoclonal antibody, are valid solutions despite being quite expensive. Natural molecules could be a valid treatment that combines good efficacy and low price. We conducted a case -control study to evaluate the benefit of an oral supplement with Ribes nigrum, Boswellia serrata, Bromelain and Vitamin D on chronic sinusitis symptoms. 60 patients were randomly assigned to one of the three groups: control using nasal steroids only, treatment 1 using nasal steroid and 1 dose of the oral supplement for 30 days and treatment 2 in which patients used nasal steroid and two oral supplement doses daily for 15 days. Conditions of the nasal mucosa and a blood sample (WBC, IgE and CRP) were analyzed at T0, T1 (15 days after treatment) and T2 (30 days after treatment. Patients treated with the supplement improved their nasal findings (hyperemia of mucosa and rhinorrhea) with statistically significant differences from the control. Our preliminary data suggest that the addition of supplement containing Ribes nigrum, Boswellia serrata, Vitamin D and Bromelain to the traditional local therapy (nasal spray with cortisone) can be a supporting therapy to modulate the local inflammation in the nose in patients affected by chronic sinusitis.

Use of Nutraceuticals in Elderly to Fight Inflammation and Immuno-Senescence: A Randomized Case-Control Study.

Elderly people are at high risk of suffering from infection and being affected by severe forms of disease because their immunosystem suffers from aging. The alteration of normal immune functions causes the increase of pro-inflammatory cytokines which can expose these people to increased risk of developing pathologies as cancer, diabetes, and/or arthritis. Some supplements could be helpful for restoring normal immune functions. We conducted a case-control study to evaluate the efficacy of a supplement containing Sambucus nigra, zinc, tyndallized Lactobacillus acidophilus (HA122), arabinogalactans, vitamin D, vitamin E, and vitamin C to improve the inflammatory levels (IL-6 and CRP) and to modulate the lymphocytes growth. Additionally, we analyzed wellness by self-questionnaire. This study had two control group: a young group and an elderly one. Our study showed that treating elderly patients with the supplement for 30 days improved IL-6, CRP, and lymphocytes levels; the result was independent from the dosage of the supplements used. Elderly patients, despite the improvement, were not able to reach the same conditions of young patients; however, most of the patients (>70%) claimed to "feel better" after the use of the supplement. The use of this supplement should be considered at a low dosage for a prolonged period to reduce inflammation and modulate immune senescence in patients over 60 years old.

Single-Center-Single-Blinded Clinical Trial to Evaluate the Efficacy of a Nutraceutical Containing Boswellia Serrata, Bromelain, Zinc, Magnesium, Honey, Tyndallized Lactobacillus Acidophilus and Casei to Fight Upper Respiratory Tract Infection and Otitis Media.

Some nutraceuticals have been studied as supportive treatment for fighting upper respiratory tract infection and middle ear disease. Our study aims at evaluating the effect of a specific oral supplementation in the treatment of pediatric otits media. The subjects were randomly assigned by the physician (single-blinded study) to one of three groups: Control Group (CG), Treatment Group 1 (TG1), or Treatment Group 2 (TG2). Both TG were treated with Flogostop Duo (for 20 days-TG1 or 30 days-TG2) in combination with the standard treatment, while CG underwent standard treatment only. The standard treatment was nasal aerosol with Fluticasone and Mucolytic, and nasal washing with hypertonic solution. All patients were analyzed by otoscopy, impedance, fibroscopy, and pure auditory test at the baseline (T0), after 20 days (T1) and 35 days (T2). 120 children were included in the study, 40 in the CG, 40 in the TG1, and 40 in the TG2. Both TG1 and TG2 presented statistically significant differences with respect to controls in otoscopy, impedance, fibroscopy, and PTA at T2. The otoscopy improved at T2 with statistically significant value only in TG2. The impedance and fibroscopy improved at T1 both in TG1 and TG2 compared to CG. A statistically significant improvement was observed in TG2 at T2 in comparison to both CG and TG1. Statistically significant differences were observed in PTA at T2 only compared with controls. This study confirmed the efficacy of nutraceutical as supporting therapy in the upper respiratory tract infection in children. In particular, the supplement containing Boswellia serrata and Bromelain, which are molecules with strong anti-inflammatory and pain-control capacities, could add the benefit without the adverse effects which are related to NSAID use.

Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial.

BACKGROUND: Olfactory training is the only evidence-based treatment for post-viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate antiinflammatory/ neuroprotective agents. OBJECTIVE: To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. METHODS: Multicenter double-blinded randomized placebo-controlled clinical trial was held. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction or other sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin' Sticks assessments were used to test the patients at baseline and 90 days. RESULTS: A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. CONCLUSION: Among individuals with olfactory dysfunction post-COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer.

Lung cancer (LC) represents a global threat, being the tumor with the highest mortality rate. Despite the introduction of novel therapies (e.g., targeted inhibitors, immune-checkpoint inhibitors), relapses are still very frequent. Accordingly, there is an urgent need for reliable predictive biomarkers and therapeutically druggable targets. Yin-Yang 1 (YY1) is a transcription factor that may work either as an oncogene or a tumor suppressor, depending on the genotype and the phenotype of the tumor. The Raf Kinase Inhibitory Protein (RKIP), is a tumor suppressor and immune enhancer often found downregulated in the majority of the examined cancers. In the present report, the role of both YY1 and RKIP in LC is thoroughly explored through the analysis of several deposited RNA and protein expression datasets. The computational analyses revealed that YY1 negatively regulates RKIP expression in LC, as corroborated by the deposited YY1-ChIP-Seq experiments and validated by their robust negative correlation. Additionally, YY1 expression is significantly higher in LC samples compared to normal matching ones, whereas RKIP expression is lower in LC and high in normal matching tissues. These observed differences, unlike many current biomarkers, bear a diagnostic significance, as proven by the ROC analyses. Finally, the survival data support the notion that both YY1 and RKIP might represent strong prognostic biomarkers. Overall, the reported findings indicate that YY1 and RKIP expression levels may play a role in LC as potential biomarkers and therapeutic targets. However, further studies will be necessary to validate the in silico results.

Local Bacteriotherapy - a promising preventive tool in recurrent respiratory infections.

INTRODUCTION: Children with recurrent respiratory infections (RRI) represent a social issue for the economic burden and the negative family impact. Local Bacteriotherapy is an attractive therapeutic strategy that could be potentially effective in preventing infections. The current article remarks on the existing evidence of preventing RRI by Local Bacteriotherapy. AREAS COVERED: The literature search methodology was based on the articles cited by PubMed from 1980 to 2020. Respiratory infections include rhino-pharyngitis, otitis media, rhinosinusitis, pharyngo-tracheitis, bronchitis, and pneumonia. Several studies were performed to investigate the effects of Local Bacteriotherapy in children with RRI. Both intranasal and oral Local Bacteriotherapy were evaluated. The findings showed that Local Bacteriotherapy significantly reduced the number of RI episodes, their severity, the use of antibiotics, and school absences. EXPERT OPINION: Local Bacteriotherapy is a promising approach to RRI prevention and could be a profitable strategy to contrast infections in the future.

Inflammation, infection, and allergy of upper airways: new insights from national and real-world studies.

The upper airways (UA) should be considered as a functional unit. Current functional anatomy divides URT in three, mutually dependent, "junction boxes": i) the ostio-meatal complex (OMC), ii) the spheno-ethmoidal recess (SER), and iii) the rhinopharynx (RP). Correct ventilation and effective mucociliary clearance of these sites significantly affect the healthy physiology of the entire respiratory system. The OMC, SER, and RP obstruction is the first pathogenic step in the inflammatory/infectious cascade of UA disorders. The inflammation of the respiratory mucosa is the main pathogenic factor for airway obstruction. Moreover, bacterial biofilm (a strategy modality of bacterial survival) is an important local cause of systemic antibiotic ineffectiveness, recurrent infections, and antibiotic resistance. Health microbiota guarantees UA wellness; on the contrary, dysbiosis promotes and worsens UA infections. Allergy, namely type 2 inflammation, is a common cause of UA obstruction such as promoting in turn infections. Fiberoptic endoscopy is a mandatory diagnostic tool in clinical practice. Nasal cytology, mainly concerning flow cytometry, allows defining rhinitis phenotypes so allowing a precision medicine approach. Several conventional therapeutic approaches are available, but efficacy and safety should be ever properly considered before the prescription. Also, complementary medicine plays a fruitful role in the management of UA diseases. National and real-world studies are reported and discussed as they may be useful in daily clinical practice.

The nutraceuticals: a new therapeutic strategy in the management of digestive and respiratory disorders.

Nutraceuticals represents an intriguing challenge in clinical practice. They are currently used worldwide in all fields of Medicine. The present Supplement reports two Italian surveys concerning a probiotic mixture employed in patients with chronic intestinal disorders and a Medical Device used in patients with upper respiratory diseases. These surveys were conducted on a group of Italian gastroenterologists and on a group of Italian otolaryngologists respectively. Both surveys demonstrated that these compounds may represent a useful therapeutic option in clinical practice.

Broncalt®, class II medical device, in patients with acute upper airways disease: a survey in clinical practice.

Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL) disorders. Broncalt® is a class II Medical Device containing: thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It has been reported that it exerted a safe and effective anti-inflammatory, washing, and antimicrobial activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients with acute upper airways disease. The 3,533 (1,797 males, mean age 43.5 years) patients were evaluated at baseline (T0) and after a 2-week treatment (T1) with or without Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly and safely diminished the clinical features in all sub-groups (p<0.001 for all). Interestingly, Broncalt® significantly induced a faster symptom relief already within 3 days after the start of the treatment. In conclusion, Broncalt® is a class II Medical Device able to exert a safe and effective activity in patients with acute ORL disorders.

Broncalt®, class II medical device, in patients with chronic upper airways disease: a survey in clinical practice.

Inflammation and infection are common pathogenic mechanisms involved in many otorhinolaryngological (ORL) chronic diseases. Broncalt® is a class II Medical Device containing: thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It could exert a safe and effective anti-inflammatory, washing, and antimicrobial activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients with chronic upper airways disease. The 1,817 (958 males, mean age 49 years) patients were evaluated at baseline (T0) and after one (T1) and two (T2) weeks of treatment, they were treated or not treated with Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly, quickly, and safely diminished the clinical features in all sub-groups (p<0.001 for all). In conclusion, Broncalt® is a class II Medical Device able to exert a safe, quick, and effective activity in patients with chronic ORL disorders.

Broncalt®, class II medical device, in patients with chronic relapsed upper airways disease: a survey in clinical practice.

Inflammation and infection are common pathogenic mechanisms involved in many otorhinolaryngological (ORL) chronic diseases. Broncalt® is a class II Medical Device containing: thermal water (Medesano, PR, Italy), hyaluronic acid, and grapefruit seed extract. It could exert a safe and effective anti-inflammatory, washing, and antimicrobial activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients with chronic upper airways disease. The 1,817 (958 males, mean age 49 years) patients were evaluated at baseline (T0) and after one (T1) and two (T2) weeks of treatment, they were treated or not treated with Broncalt®. Signs and symptoms severity were measured by visual analogue scale. Broncalt® significantly, quickly, and safely diminished the clinical features in all sub-groups (p<0.001 for all). In conclusion, Broncalt® is a class II Medical Device able to exert a safe, quick, and effective activity in patients with chronic ORL disorders.

VAS for assessing the perception of antihistamines use in allergic rhinitis.

The quantification of the antihistamines' consumption is particularly relevant in clinical practice, since their remarkable use is usually associated with severe symptoms. The aim of the study was to measure the visual analogue scale (VAS) for assessing the patient's perception about antihistamines use in patients with allergic rhinitis. 103 patients (49 males, mean age 35.9 years) with allergic rhinitis due to Parietaria pollen were evaluated retrospectively. They recorded monthly the number of antihistamine tables they took during the pollen season (lasting for about 5 months). There was a strong relationship (r= 0.921 Pearson; p<0.0001) between the number of tablets and the VAS score. The assessment of the perception of the antihistamines use by VAS could be an easy and quick tool in the management of patients with allergic rhinitis in clinical practice.

Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a oral spray for children with recurrent streptococcal pharyngotonsillitis: a randomized placebo-controlled clinical study.

PURPOSE: Group A beta-hemolytic Streptococcus (GABHS) causes a recurrent acute pharyngotonsillitis (RAPT) in children. Moreover, the repeated use of antibiotics contributes to its resistance. However, S. Salivarius 24SMB and S. oralis 89a were effective probiotics in other infections. Thus, we decided to evaluate this combination efficacy compared to placebo in RAPT. METHODS: Patients with microbiologically confirmed GABHS were enrolled in this randomized, placebo-controlled trial. They received the aforementioned combination or placebo as an oral spray. We investigated episodes of frequency and duration, need for antibiotics, school days lost, the treatment impact on life quality, treatment compliance and side effects during a 90-day treatment and a 6-month follow-up. RESULTS: We included 41 patients in each group. The mean number of GABHS infection was significantly lower during both study periods for the two groups. However, our treatment group showed a lower rate. Moreover, the probiotic group had a lower mean number and a shorter median duration of GABHS episodes during both study periods than controls. Furthermore, the mean duration of antibiotic treatment was lower in the probiotic group during the 90-day and 6-month follow-up periods. Similarly, patients in the probiotic group showed a significantly lower mean number of absence days from school but higher EQ-VAS score. Indeed, all patients included were compliant to treatment. CONCLUSIONS: We identified potential probiotics, possessing desirable features against GABHS pharyngotonsillitis. Our findings represent the first evidence which throws the light on using these probiotics that can reduce antibiotics use which did not have efficient results regarding recurrence.