Restraining Staphylococcus aureus Virulence Factors and Quorum Sensing through Lactic Acid Bacteria Supernatant Extracts.

The escalating prevalence of antibiotic-resistant bacteria poses a grave threat to human health, necessitating the exploration of novel alternatives to conventional antibiotics. This study investigated the impact of extracts derived from the supernatant of four lactic acid bacteria strains on factors contributing to the pathogenicity of three Staphylococcus aureus strains. The study evaluated the influence of lactic acid bacteria supernatant extracts on the growth, biofilm biomass formation, biofilm metabolic activity, and biofilm integrity of the S. aureus strains. Additionally, the impact on virulence factors (hemolysin and coagulase) was examined. Gas chromatography coupled with mass spectrometry was used to identify the bioactive compounds in the extracts, while molecular docking analyses explored potential interactions. Predominantly, the extracts contain eight 2,5-diketopiperazines, which are cyclic forms of peptides. The extracts demonstrated inhibitory effects on biofilm formation, the ability to disrupt mature biofilms, and reduce the biofilm cell metabolic activity of the S. aureus strains. Furthermore, they exhibited the ability to inhibit α-hemolysin production and reduce coagulase activity. An in silico docking analysis reveals promising interactions between 2,5-diketopiperazines and key proteins (SarA and AgrA) in S. aureus, confirming their antivirulence and antibiofilm activities. These findings suggest that 2,5-diketopiperazines could serve as a promising lead compound in the fight against antibiotic-resistant S. aureus.

Age-dependent high-yield isolation of primordial, primary, and early secondary follicles from the bovine ovarian cortex.

Primordial, primary, and secondary follicles (collectively defined as preantral follicles) constitute the most abundant source of gametes inside the mammalian ovarian cortex. The massive isolation of preantral follicles and the refinement of stage-specific protocols for in vitro follicle growth would provide a powerful tool to boost the rescue and restoration of fertility in assisted reproduction interventions in human medicine, animal breeding, and vulnerable species preservation. Nevertheless, together with an efficient culture system, the most significant limitation to implementing in vitro follicle growth is the lack of an efficient method to isolate viable and homogeneous sub-populations of primordial, primary, and secondary follicles suitable for in vitro culture. Our study provides a strategy for high-yielding mechanical isolation of primordial, primary, and early secondary follicles from a limited portion of the ovarian cortex in the bovine animal model. In the first part of the study, we refined a mechanical isolation protocol of preantral follicles, adopting specific methodological strategies to separate viable and distinct sub-populations of primordial (oblate and prolate forms), primary, and early secondary follicles from 0.16 cm3 of the ovarian cortex. In the second part of the study, we tested the effectiveness of the isolation protocol, considering the individual's age as a critical factor, bearing in mind the progressive decrease in the ovarian reserve that naturally accompanies the reproductive lifespan. Our study provides a way for designing quantitative and conservative fertility preservation approaches to preserve organ function and minimize the invasiveness of the interventions, also considering age-related differences.

Mucosal cyst aspiration in conjunction with maxillary sinus elevation: A clinical cohort study.

INTRODUCTION: Patients with mucosal cysts in the maxillary sinus require special consideration in patients who require implant therapy for the restoration when undergoing implant therapy for the restoration of the posterior maxillary dentition. Treatment strategies for these clinical situations remain controversial in the literature. Thus, this study seeks to describe a safe and effective therapeutic strategy for sinus augmentation in patients with pre-existing maxillary antral cysts. METHODS: A total of 15 patients and 18 sinuses were consecutively enrolled in this cohort study and underwent maxillary antral cyst treatment by needle aspiration and simultaneous maxillary sinus augmentation (MSA). During surgical procedures, threeimplants (Zimmer Biomet, Indiana, USA) were positioned in 11 sinuses and two implants (Zimmer Biomet, Indiana, USA) were positioned in 5 sinuses. RESULTS: Overall implant success and survival rates were 100% and 97.8%, respectively at 1 year and 5-year follow-ups. Crestal bone resorption averaged 0.3 ± 0.2 mm 5-year post-loading, showing bone stability. Implant survival rate at 5-year follow-up expressed predictability of the technique comparable to historical data when MSA was performed alone. Crestal bone resorption averaged 0.3 ± 0.2 mm 5 years post-loading and shows bone stability utilizing mucosal cyst aspiration with concomitant MSA procedures. Quality of life evaluation at 1-week post-op showed similar results to published historical data. In 81% (13 sinuses), the CBCT examination at 5-year follow-up showed no cyst reformation, in 19% (3 sinuses) cyst reformation was visible, but smaller in size when compared to the pre-op CBCT evaluation, and all the patients were asymptomatic. CONCLUSIONS: Maxillary sinus mucosal cyst aspiration with concomitant MSA, may be a viable option to treat maxillary sinus cyst.

UHPLC-MS/MS and GC-MS Metabolic Profiling of a Medicinal Flourensia Fiebrigii Chemotype.

The comparative metabolic profiling and their biological properties of eight extracts obtained from diverse parts (leaves, flowers, roots) of the medicinal plant Flourensia fiebrigii S.F. Blake, a chemotype growing in highland areas (2750 m a.s.l.) of northwest Argentina, were investigated. The extracts were analysed by GC-MS and UHPLC-MS/MS. GC-MS analysis revealed the presence of encecalin (relative content: 24.86 %) in ethereal flower extract (EF) and this benzopyran (5.93 %) together sitosterol (11.35 %) in the bioactive ethereal leaf exudate (ELE). By UHPLC-MS/MS the main compounds identified in both samples were: limocitrin, (22.31 %), (2Z)-4,6-dihydroxy-2-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-1-benzofuran-3-one (21.31 %), isobavachin (14.47 %), naringenin (13.50 %), and sternbin, (12.49 %). Phytocomplexes derived from aerial parts exhibited significant activity against biofilm production of Pseudomonas aeruginosa and Staphylococcus aureus, reaching inhibitions of 74.7-99.9 % with ELE (50 µg/mL). Notably, the extracts did not affect nutraceutical and environmental bacteria, suggesting a selective activity. ELE also showed the highest reactive species scavenging ability. This study provides valuable insights into the potential applications of this chemotype.

Global frequency and distribution of head and neck sarcomas in adulthood: a systematic review.

PURPOSE: Head and neck sarcomas (HNS) constitute a rare and heterogeneous cancer entity. Management remains a challenge due their rarity and different biological behaviour among tens of subtypes. This systematic review aimed to describe HNS global frequency and distribution in adulthood. METHODS: A systematic review was performed using PICOTS search strategies for qualitative question and it was written in accordance with PRISMA 2020 Statement. 70,653 publications were identified, and 15 variables were evaluated for a total of 2428 patients. RESULTS: We identified 47 studies from 21 different countries from 5 different continents. Most of studies (83.3%) were performed in single institutions and America and Asia overruled for number of papers included (21 and 10, respectivelly). Osteosarcoma was more frequent, followed by chondrosarcoma, angiosarcoma and malignant fibrous histiocytoma. Early stage accounted for almost 80% of cases; advanced stage prevailed in developing countries. 1783 patients (90.1%) underwent surgery and 780 (39.4%) had adjuvant therapy. 50.8% of patients experienced tumour recurrence and the lowest mortality rate was reported in Europe (29.9%). CONCLUSIONS: HNS holds a relative poor prognosis possibly explained by the heterogeneity of the disease. Treatment of HNS has shown to be highly diverse among different countries, underlining the importance of uniformed treatment guidelines to achieve better patient management and to improve survival outcomes.

Therapeutic approaches to sinonasal NUT carcinoma: a systematic review.

PURPOSE: Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks among the most unfavorable within the naso-sinusal district, with an overall survival of 9.7 months. This systematic review aimed to determine the best therapeutic strategy for SNUTC. METHODS: We reviewed eligible articles for patient demographics, TNM and stage at presentation, best response after primary treatment, disease-free survival and overall survival (OS) times, other following therapy lines, and final outcomes. RESULTS: Among 472 unique citations, 17 studies were considered eligible, with reported treatment data for 25 patients. Most studies (n = 12) were case reports. The most frequently administered treatment regimen was surgery as primary treatment and combined radiochemotherapy as second-line or adjuvant treatment. Four patients were alive at follow-up. CONCLUSION: Basing on the existing literature, a standardized line in the treatment of SNUTC is not yet well delineated. A self-personalized strategy of therapy should be drawn on each patient affected by SNUTC.

Method of Isolation and In Vitro Culture of Primordial Follicles in Bovine Animal Model.

The mammalian ovary is a substantial source of oocytes arranged into follicles at various stages of folliculogenesis, from the primordial to the ovulatory ones. Primordial follicles constitute the most abundant source of gametes inside the mammalian ovary at any given time.The isolation of a high number of primordial follicles, together with the development of protocols for in vitro follicle growth, would provide a powerful tool to fully exploit the female reproductive potential and boost the rescue and restoration of fertility in assisted reproduction technologies in human medicine, animal breeding, and preservation of threatened species. However, the most significant limitation is the lack of efficient methods for isolating a healthy and homogeneous population of viable primordial follicles suitable for in vitro culture. Here, we provide a fast and high-yield strategy for the mechanical isolation of primordial follicles from limited portions of the ovarian cortex in the bovine animal model.

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.

Switching of biological therapy to dupilumab in comorbid patients with severe asthma and CRSwNP.

PURPOSE: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. METHODS: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. RESULTS: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. CONCLUSIONS: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy.

Characteristics and outcomes of patients with tricuspid regurgitation and advanced heart failure.

AIMS: To evaluate the role of tricuspid regurgitation in advanced heart failure. METHODS: The multicenter observational HELP-HF registry enrolled consecutive patients with heart failure and at least one 'I NEED HELP' criterion evaluated at four Italian centers between January 2020 and November 2021. Patients with no data on tricuspid regurgitation and/or receiving tricuspid valve intervention during follow-up were excluded. The population was stratified by no/mild tricuspid regurgitation vs. moderate tricuspid regurgitation vs. severe tricuspid regurgitation. Variables independently associated with tricuspid regurgitation, as well as the association between tricuspid regurgitation and clinical outcomes were investigated. The primary outcome was all-cause mortality. RESULTS: Among the 1085 patients included in this study, 508 (46.8%) had no/mild tricuspid regurgitation, 373 (34.4%) had moderate tricuspid regurgitation and 204 (18.8%) had severe tricuspid regurgitation. History of atrial fibrillation, any prior valve surgery, high dose of furosemide, preserved left ventricular ejection fraction, moderate/severe mitral regurgitation and pulmonary hypertension were found to be independently associated with an increased likelihood of severe tricuspid regurgitation. Estimated rates of 1-year all-cause death were of 21.4, 24.5 and 37.1% in no/mild tricuspid regurgitation, moderate tricuspid regurgitation and severe tricuspid regurgitation, respectively (log-rank P  < 0.001). As compared with nonsevere tricuspid regurgitation, severe tricuspid regurgitation was independently associated with a higher risk of all-cause mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.01-1.88, P  = 0.042), whereas moderate tricuspid regurgitation did not. CONCLUSION: In a contemporary, real-world cohort of patients with advanced heart failure, several clinical and echocardiographic characteristics are associated with an increased likelihood of severe tricuspid regurgitation. Patients with severe tricuspid regurgitation have an increased risk of mortality.

Mechanical and fatigue resistance of restorations supported by welded-framework and realized using computer-aided designed prosthetic shells: In vitro pilot study.

Resin coating in implants rehabilitation cannot always be aesthetic, durable and comfortable for the patient mainly due to the limited dimensions of the final structure. Intraoral welding technique and computer-aided designed prosthetic shells may be a solution. This in vitro study evaluates the capacity of load and the weakest point of implant-supported provisional prosthesis using welded titanium framework. Twelve samples were produced to simulate an implant supported fixed prosthetic bridge. Two implants (Ankylos; Dentsply Sirona Implants; Germany) were inserted inside blocks of nanoceramic material produced with a stereolithographic 3D printer. A polymethylmethacrylate (PMMA) resin shell was performed with CAD/CAM and relined on welded framework. Six samples were produced with the same procedure reducing resin thickness. The samples were subjected to fatigue test (6,500,000 cycles) using ElectroForce 3310 fatigue machine (t1); subsequently a mechanical compression test using a universal Shimadzu AGS-X 10 machine (t2). The samples were analyzed with a photographic and radiographic documentation at t0, t1 and t2. The samples survived mechanical fatigue test without evidence of failure. The radiographic and photographic evaluation revealed the fracture of resin coating after the mechanical compression test. The samples with minimal resin thickness fractured first. Adequate assessment of the resin thickness is mandatory to improve the longevity of these rehabilitations. CAD-CAM digital prosthetic design allows us to optimize the thicknesses and the prosthetic shapes, allowing us to obtain good degrees of resistance even in the presence of reduced prosthetic spaces.

Reliability of large language models in managing odontogenic sinusitis clinical scenarios: a preliminary multidisciplinary evaluation.

PURPOSE: This study aimed to evaluate the utility of large language model (LLM) artificial intelligence tools, Chat Generative Pre-Trained Transformer (ChatGPT) versions 3.5 and 4, in managing complex otolaryngological clinical scenarios, specifically for the multidisciplinary management of odontogenic sinusitis (ODS). METHODS: A prospective, structured multidisciplinary specialist evaluation was conducted using five ad hoc designed ODS-related clinical scenarios. LLM responses to these scenarios were critically reviewed by a multidisciplinary panel of eight specialist evaluators (2 ODS experts, 2 rhinologists, 2 general otolaryngologists, and 2 maxillofacial surgeons). Based on the level of disagreement from panel members, a Total Disagreement Score (TDS) was calculated for each LLM response, and TDS comparisons were made between ChatGPT3.5 and ChatGPT4, as well as between different evaluators. RESULTS: While disagreement to some degree was demonstrated in 73/80 evaluator reviews of LLMs' responses, TDSs were significantly lower for ChatGPT4 compared to ChatGPT3.5. Highest TDSs were found in the case of complicated ODS with orbital abscess, presumably due to increased case complexity with dental, rhinologic, and orbital factors affecting diagnostic and therapeutic options. There were no statistically significant differences in TDSs between evaluators' specialties, though ODS experts and maxillofacial surgeons tended to assign higher TDSs. CONCLUSIONS: LLMs like ChatGPT, especially newer versions, showed potential for complimenting evidence-based clinical decision-making, but substantial disagreement was still demonstrated between LLMs and clinical specialists across most case examples, suggesting they are not yet optimal in aiding clinical management decisions. Future studies will be important to analyze LLMs' performance as they evolve over time.

Vein wall thickness and severity of pulmonary involvement due to sars n-cov2 virus infection.

BACKGROUND: An observational study involving patients recovered from COVID-19 was conducted in order to evaluate the presence/absence of vein wall thickness increasing, according to the severity of pulmonary involvement quantified with a CT-scoring system. METHODS: The venous wall thickness (VWT) of 31 patients (23 males and 8 females) with COVID 19 previously admitted to Federico II University Hospital of Naples was evaluated through ultrasound measurement of the common femoral Vein 1 cm proximal to the saphenous-femoral junction and the popliteal Vein 1 cm distal to the confluence of gemellary veins. Measurements were taken with an automated tool to avoid human error. All patients were evaluated in the supine position. Patients were then stratified into two groups, VWT > 1 mm and VWT < 1 mm. Lung damage was assessed through thoracic High Resolution Computer Tomography and subsequently quantified using the scoring system set out by Chung et al. CEAP-C class was calculated for all patients. RESULTS: The mean value of COVID score in VWT > 1 mm group was 7.4 (S.D. 4.83), whilst the mean value of the COVID score in the VWT < 1 mm group was 3.82 (S.D 3.34). These findings were determined to be statistically significant in a two-tie Student-T test. The linear regression test between VWT and Covid score values demonstrated a direct relationship between the two variables. CONCLUSION: These results demonstrate a link between two different aspects of the pathological effects on the vessels during a SARS-COV 2 infection. As such a common primum movens can be hypothesized in both micro-thrombotic and inflammatory processes relating to COVID 19.

ChatGPT-4 performance in rhinology: A clinical case series.

KEYPOINTS: Chatbot Generative Pre-trained Transformer (ChatGPT)-4 indicated more than twice additional examinations than practitioners in the management of clinical cases in rhinology. The consistency between ChatGPT-4 and practitioner in the indication of additional examinations may significantly vary from one examination to another. The ChatGPT-4 proposed a plausible and correct primary diagnosis in 62.5% cases, while pertinent and necessary additional examinations and therapeutic regimen were indicated in 7.5%-30.0% and 7.5%-32.5% of cases, respectively. The stability of ChatGPT-4 responses is moderate-to-high. The performance of ChatGPT-4 was not influenced by the human-reported level of difficulty of clinical cases.

Type IV optic nerve and Onodi cell: is there a risk of injury during sphenoid sinus surgery?

Objective: This study aims to determine the prevalence and types of Onodi cells through computed tomography and investigate the relationship between Onodi cell and the surrounding structures, paying particular attention to the risky proximity to the optic nerve canal. Methods: In this study, 430 computed tomography scans of paranasal sinuses were analysed to establish the prevalence and different types of Onodi cells. Furthermore, the relationship between Onodi cell and different patterns of sphenoid sinus pneumatisation and surrounding structures were investigated. Special attention was paid to the relationship between Onodi cell and the optic nerve canal, particularly in cases when the optic nerve canal was bulging by more than 50% into the Onodi cell (Type IV). Results: The Onodi cell was detected in 21.6% of cases, with the most common being Type I (48.5% right, 54.3% left). Type IV bulging of the optic nerve canal into the Onodi cell was observed in 47.1% of cases on the right side, 41.2% on the left side and bilateral in 11.7% of cases. Conclusions: In our series, we observed a high prevalence of Type IV optic nerve bulging into the Onodi cell. For this reason, we suggest that clinicians should always try to identify it in a pre-operative setting with computed tomography to avoid catastrophic consequences during endoscopic sinus surgery approaching the sphenoid area.

Clinical relevance of genetic variants in the von Willebrand factor according to in-silico methods.

Clinical interpretation of genetic variants in the context of the patient's phenotype is a time-consuming and costly process. In-silico analysis using in-silico prediction tools, and molecular modeling have been developed to predict the influence of genetic variants on the quality and/or quantity of the resulting translated protein, and in this way, to alert clinicians of disease likelihood in the absence of previous evidence. Our objectives were to evaluate the success rate of the in-silico analysis in predicting the disease-causing variants as pathogenic and the single-nucleotide variants as neutral, and to establish the reliability of in-silico analysis for determining pathogenicity or neutrality of von Willebrand factor gene-associated genetic variants. Using in-silico analysis, we studied pathogenicity in 31 disease-causing variants, and neutrality in 61 single-nucleotide variants from patients previously diagnosed as type 2 von Willebrand disease. Disease-causing variants and non-synonymous single-nucleotide variants were explored by in-silico tools that analyze the amino acidic sequence. Intronic and synonymous single-nucleotide variants were analyzed by in-silico methods that evaluate the nucleotidic sequence. We found a consistent agreement between predictions achieved by in-silico prediction tools and molecular modeling, both for defining the pathogenicity of disease-causing variants and the neutrality of single-nucleotide variants. Based on our results, the in-silico analysis would help to define the pathogenicity or neutrality in novel genetic variants observed in patients with clinical and laboratory phenotypes suggestive of von Willebrand disease.

Role of ejection fraction in patients at risk for advanced heart failure: insights from the HELP-HF registry.

AIMS: Patients with heart failure (HF) with reduced ejection fraction (EF) (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF) may all progress to advanced HF, but the impact of EF in the advanced setting is not well established. Our aim was to assess the prognostic impact of EF in patients with at least one 'I NEED HELP' marker for advanced HF. METHODS AND RESULTS: Patients with HF and at least one high-risk 'I NEED HELP' criterion from four centres were included in this analysis. Outcomes were assessed in patients with HFrEF (EF ≤ 40%), HFmrEF (EF 41-49%), and HFpEF (EF ≥ 50%) and with EF analysed as a continuous variable. The prognostic impact of medical therapy for HF in patients with EF < 50% and EF > 50% was also evaluated. All-cause death was the primary endpoint, and cardiovascular death was a secondary endpoint. Among 1149 patients enrolled [mean age 75.1 ± 11.5 years, 67.3% males, 67.6% hospitalized, median follow-up 260 days (inter-quartile range 105-390 days)], HFrEF, HFmrEF, and HFpEF were observed in 699 (60.8%), 122 (10.6%), and 328 (28.6%) patients, and 1 year mortality was 28.3%, 26.2%, and 20.1, respectively (log-rank P = 0.036). As compared with HFrEF patients, HFpEF patients had a lower risk of all-cause death [adjusted hazard ratio (HRadj ) 0.67, 95% confidence interval (CI) 0.48-0.94, P = 0.022], whereas no difference was noted for HFmrEF patients. After multivariable adjustment, a lower risk of all-cause death (HRadj for 5% increase 0.94, 95% CI 0.89-0.99, P = 0.017) and cardiovascular death (HRadj for 5% increase 0.94, 95% CI 0.88-1.00, P = 0.049) was observed at higher EF values. Beta-blockers and renin-angiotensin system inhibitors or sacubitril/valsartan were associated with lower mortality in both EF < 50% and EF ≥ 50% groups. CONCLUSIONS: Among patients with HF and at least one 'I NEED HELP' marker for advanced HF, left ventricular EF is still of prognostic value.

Effectiveness and rapidity on olfatory fuction recovery in CRS patients treated with Dupilumab: a real life prospective controlled study.

BACKGROUND: Recovery of olfactory function plays a prominent role in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). While rates and timing of such recovery vary, monoclonal antibodies might yield better results which we aimed at evaluating with this study. METHODOLOGY: A prospective controlled study was conducted at our tertiary otolaryngological center from April 1, 2021, to October 1, 2022, in CRSwNP patients. We included an active group (n = 60 patients) performing dupilumab treatment and a control group (n = 60 patients) treated with intranasal and oral corticosteroids. Primary endpoints were changes in smell visual analogical scale (VAS) and SS-I (Sniffin' Sticks-identification) scores, and olfactory recovery rate. The secondary efficacy endpoints were nasal obstruction, rhinorrhea, headache, SNOT-22, and nasal congestion score (NCS). RESULTS: At 6 months, the active group demonstrated better outcomes than control in SS-I scores (10.23 ± 4.21 vs.3.68 ± 3.08; p < 0.001). No significant differences were found in blood eosinophil count, SNOT-22, and NPS (p > 0.05 for all). Olfactory function in the treatment arm improved in 86.66% (52/60 cases), with normal scores in 48.33% (29/60), while the control group reported a lower recovery rate (3/60; 5%), with no normal olfaction cases. Log-rank comparison for Kaplan-Meier functions was statistically significant (p < 0.001), but no differences were found in subanalysis in the active group based on blood eosinophil count at baseline, SNOT-22, and NPS scores. CONCLUSIONS: Patients who receive dupilumab treatment may experience a faster recovery of olfactory function compared to those receiving corticosteroid therapy. This result would be maintained regardless of the severity of type 2 CRSwNP inflammation, the volume of the polyps, or the patient's subjective symptomatology.