Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update.

INTRODUCTION: Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications. OBJECTIVES: The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private. RESULTS: We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses. CONCLUSIONS: This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme.

Open-path measurement of stable water isotopologues using mid-infrared dual-comb spectroscopy.

We present an open-path mid-infrared dual-comb spectroscopy (DCS) system capable of precise measurement of the stable water isotopologues H216O and HD16O. This system ran in a remote configuration at a rural test site for 3.75 months with 60% uptime and achieved a precision of < 2‰ on the normalized ratio of H216O and HD16O (δD) in 1000s. Here, we compare the δD values from the DCS system to those from the National Ecological Observatory Network (NEON) isotopologue point sensor network. Over the multi-month campaign, the mean difference between the DCS δD values and the NEON δD values from a similar ecosystem is < 2‰ with a standard deviation of 18‰, which demonstrates the inherent accuracy of DCS measurements over a variety of atmospheric conditions. We observe time-varying diurnal profiles and seasonal trends that are mostly correlated between the sites on daily timescales. This observation motivates the development of denser ecological monitoring networks aimed at understanding regional- and synoptic-scale water transport. Precise and accurate open-path measurements using DCS provide new capabilities for such networks.

Removing biases in dual frequency comb spectroscopy due to digitizer nonlinearity.

Operation of any dual-comb spectrometer requires digitization of the interference signal before further processing. Nonlinearities in the analog-to-digital conversion can alter the apparent gas concentration by multiple percent, limiting both precision and accuracy of this technique. This work describes both the measurement of digitizer nonlinearity and the development of a model that quantitatively describes observed concentration bias over a range of conditions. We present hardware methods to suppress digitizer-induced bias of concentration retrievals below 0.1%.

Open-path dual-comb spectroscopy of methane and VOC emissions from an unconventional oil well development in Northern Colorado.

We present results from a field study monitoring methane and volatile organic compound emissions near an unconventional oil well development in Northern Colorado from September 2019 to May 2020 using a mid-infrared dual-comb spectrometer. This instrument allowed quantification of methane, ethane, and propane in a single measurement with high time resolution and integrated path sampling. Using ethane and propane as tracer gases for methane from oil and gas activity, we observed emissions during the drilling, hydraulic fracturing, millout, and flowback phases of well development. Large emissions were seen in drilling and millout phases and emissions decreased to background levels during the flowback phase. Ethane/methane and propane/methane ratios varied widely throughout the observations.

Validation of open-path dual-comb spectroscopy against an O2 background.

Dual-comb spectroscopy measures greenhouse gas concentrations over kilometers of open air with high precision. However, the accuracy of these outdoor spectra is challenging to disentangle from the absorption model and the fluctuating, heterogenous concentrations over these paths. Relative to greenhouse gases, O2 concentrations are well-known and evenly mixed throughout the atmosphere. Assuming a constant O2 background, we can use O2 concentration measurements to evaluate the consistency of open-path dual-comb spectroscopy with laboratory-derived absorption models. To this end, we construct a dual-comb spectrometer spanning 1240 nm to 1700nm, which measures O2 absorption features in addition to CO2 and CH4. O2 concentration measurements across a 560 m round-trip outdoor path reach 0.1% precision in 10 minutes. Over seven days of shifting meteorology and spectrometer conditions, the measured O2 has -0.07% mean bias, and 90% of the measurements are within 0.4% of the expected hemisphere-average concentration. The excursions of up to 0.4% seem to track outdoor temperature and humidity, suggesting that accuracy may be limited by the O2 absorption model or by water interference. This simultaneous O2, CO2, and CH4 spectrometer will be useful for measuring accurate CO2 mole fractions over vertical or many-kilometer open-air paths, where the air density varies.

A monkeypox virus infection mimicking primary syphilis.

Given the current monkeypox virus (MPXV) outbreak in at-risk men who have sex with men (MSM), clinicians should consider MPXV a differential diagnosis of syphilis, in any patient with a solitary painless genital nodule.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil / Diretriz para o uso dos imunobiológicos em rinossinusite crônica com pólipo nasal (RSCcPN) no Brasil

Abstract Introduction Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. Objective To review the current status of biologic treatment indications in chronic rhinosinusitis. Methods The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. Results Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. Conclusion The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Resumo Introdução A rinossinusite crônica com pólipos nasais grave não controlada impacta negativamente na qualidade de vida do indivíduo. Para esses casos, novos imunobiológicos têm surgido, para uso em fenótipos específicos da rinossinusite crônica, e mudaram os paradigmas de seu tratamento. Objetivo Revisar o estado atual das indicações de imunobiológicos em rinossinusite crônica. Método A Academia Brasileira de Rinologia reuniu diferentes especialistas para sugerir uma conduta que considerasse suas particularidades e seus aspectos relacionados à realidade nacional. Resultados De particular interesse para a tomada de decisão serão a identificação dos subgrupos de pacientes refratários às opções de tratamento pré-existentes e a construção de uma estratégia que realmente melhore a qualidade de vida deles, dentro da melhor relação custo-benefício. Conclusão O uso de imunobiológicos é uma opção válida para tratamento em casos mais graves. Essa estratégia deve ser mais bem compreendida e aprimorada no futuro, com mais estudos e maior experiência clínica.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil.

INTRODUCTION: Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. OBJECTIVE: To review the current status of biologic treatment indications in chronic rhinosinusitis. METHODS: The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. RESULTS: Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. CONCLUSION: The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Clinical outcomes of catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy: Insights from the Johns Hopkins ARVC Program.

BACKGROUND: Previous studies of radiofrequency catheter ablation (RFA) of ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), relying on limited numbers of procedures, have not reported VT-free survival in parallel for single and multiple procedures (ie, after the last procedure). Data regarding the impact of RFA on VT burden are scarce. OBJECTIVE: The purpose of this study was to provide new insights on clinical outcomes based on a large series of VT ablation procedures from the current era in ARVC patients. METHODS: We evaluated consecutive patients with definite ARVC who underwent RFA procedures between 2009 and 2019 at our center. We assessed VT-free survival, for single and multiple procedures, and changes in VT burden and antiarrhythmic drugs (AADs) after RFA. RESULTS: Among 116 patients, there were 166 RFA procedures, 106 (63.9%) of which involved epicardial ablation. Cumulative freedom from VT after a single procedure was 68.6% and 49.8% at 1 and 5 years, respectively. Cumulative VT-free survival after multiple procedures was 81.8% and 69.6% at 1 and 5 years, respectively. VT burden per RFA was reduced after vs before ablation (mean 0.7 vs 10.0 events/year; P <.001). Furthermore, VT burden per patient was reduced after last ablation vs before first ablation (mean 0.5 vs 10.9 events/year; P <.001). Use of AADs decreased after ablation (22.2% vs 51.9%; P <.001). CONCLUSION: In ARVC patients, RFA provided good VT-free survival after a single procedure, with multiple procedures required for more sustained freedom from VT recurrence. Marked reduction in VT burden permitted discontinuation of AADs.

Precise multispecies agricultural gas flux determined using broadband open-path dual-comb spectroscopy.

Advances in spectroscopy have the potential to improve our understanding of agricultural processes and associated trace gas emissions. We implement field-deployed, open-path dual-comb spectroscopy (DCS) for precise multispecies emissions estimation from livestock. With broad atmospheric dual-comb spectra, we interrogate upwind and downwind paths from pens containing approximately 300 head of cattle, providing time-resolved concentration enhancements and fluxes of CH4, NH3, CO2, and H2O. The methane fluxes determined from DCS data and fluxes obtained with a colocated closed-path cavity ring-down spectroscopy gas analyzer agree to within 6%. The NH3 concentration retrievals have sensitivity of 10 parts per billion and yield corresponding NH3 fluxes with a statistical precision of 8% and low systematic uncertainty. Open-path DCS offers accurate multispecies agricultural gas flux quantification without external calibration and is easily extended to larger agricultural systems where point-sampling-based approaches are insufficient, presenting opportunities for field-scale biogeochemical studies and ecological monitoring.

Long-Term Outcomes of Bilateral Cardiac Sympathetic Denervation for Refractory Ventricular Tachycardia.

OBJECTIVES: This study sought to explore the long-term arrhythmic outcomes of bilateral cardiac sympathetic denervation (BCSD). BACKGROUND: BCSD has been associated with improved arrhythmic outcomes in patients with refractory ventricular arrhythmias. However, whether BCSD antiarrhythmic effects are sustained long after the procedure is still uncertain. METHODS: We included consecutive patients who underwent BCSD because of refractory ventricular tachycardia (VT) and had at least 18 months of follow-up. VT recurrence after BCSD was evaluated to assess arrhythmic outcomes. The occurrence of VT episodes within the first 12 weeks after the procedure was assessed to explore the impact of early VT recurrence on late arrhythmia-free survival. RESULTS: Twenty patients (42 ± 16 years; 55% male) were included in the analysis. Nineteen (95%) patients had structural heart disease (left ventricular ejection fraction: 0.46 ± 0.14). Class I or class III drugs failed for all patients, and the mean number of VT ablation procedures was 2.5 ± 1.6. Over a mean follow-up of 1,300 ± 321 days (median: 1,276 days [Interquartile range (IQR): 1,181 to 1,480 days), 11 (55%) patients remained VT free after sympathectomy. Freedom from sustained VT or implantable cardioverter-defibrillator shock was 60% (95% confidence interval: 0.35 to 0.77) and 54.5% (95% confidence interval: 0.31 to 0.73) after BCSD at 1 and 4 years. Early VT recurrence was not associated with worse late arrhythmia-free survival rates. CONCLUSIONS: BCSD was associated with longstanding antiarrhythmic effects in patients with refractory ventricular arrhythmias. The occurrence of VT episodes early after the procedure was not associated with worse late arrhythmic outcomes.

Efficacy of catheter ablation for premature ventricular contractions in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Premature ventricular contractions (PVCs) may be found in any stage of arrhythmogenic right ventricular cardiomyopathy (ARVC) and have been associated with the risk of sustained ventricular tachycardia (VT). OBJECTIVE: To investigate the role of PVC ablation in ARVC patients. METHODS: We studied consecutive ARVC patients who underwent PVC ablation due to symptomatic high PVC burden. Mean daily PVC burden and antiarrhythmic drug (AAD) use were assessed before and after the procedure. Complete long-term success was defined as more than 80% reduction in PVC burden off of membrane-active AADs. RESULTS: Eight patients (37 ± 15 years; 4 males) underwent PVC ablation. The mean daily PVC burden before ablation ranged from 5.4% to 24.8%. A total of 7 (87.5%) patients underwent epicardial ablation. Complete acute elimination of PVCs was achieved in 4 (50%) patients (no complications). The mean daily PVC burden variation ranged from an 87% reduction to a 26% increase after the procedure. Over a median follow-up of 345 days (range: 182-3004 days), only one (12.5%) patient presented complete long-term success, and 6 (75%) patients either maintained or increased the need for Class I or Class III AADs. A total of 2 (25%) patients experienced sustained VT for the first time following the ablation procedure, requiring repeat ablation. No death or heart transplantation occurred. CONCLUSION: PVC ablation was not associated with a consistent reduction of the PVC burden in ARVC patients with symptomatic, frequent PVCs. PVC ablation may be reserved for highly symptomatic patients who failed AADs. Additional investigation is required to improve the efficacy of PVC ablation in ARVC patients.

Effects of High-Flow Transesophageal Dry Air on Core Temperature: A Novel Method of Therapeutic Hypothermia.

Therapeutic hypothermia (TH) is one of the few proven neuroprotective modalities in clinical practice. However, current methods to achieve TH are suboptimal. We investigated a novel esophageal device that utilizes high-flow transesophageal dry air to achieve TH via evaporating cooling. Seven Yorkshire pigs (n = 7) underwent hypothermia therapy using a novel esophageal device that compartmentalizes a segment of esophagus through which high-flow dry air freely circulates in and out of the esophagus. Efficacy (primary objective) and safety (secondary objective) were evaluated in all animals. Safety assessment was divided into two sequential phases: (1) acute safety assessment (n = 5; terminal studies) to evaluate adverse events occurring during therapy, and (2) chronic safety assessment (n = 2; survival studies) to evaluate adverse events associated with therapy within 1 week of follow-up. After 1 hour of esophageal cooling (mean airflow rate = 64.2 ± 3.5 L/min), a significant reduction in rectal temperature was observed (37.3 ± 0.2°C → 36.3 ± 0.4°C, p = 0.002). The mean rectal temperature reduction was 1 ± 0.4°C. In none of the seven animals was oral or pharyngeal mucosa injury identified at postprocedural visual examination. In the two animals that survived, no reduction of food ingestion, signs of swallowing dysfunction or discomfort, or evidence of gastrointestinal bleeding was observed during the 1-week follow-up period. Open-chest visual inspection in those two animals did not show damage to the esophageal mucosa or surrounding structures. A novel esophageal device, utilizing high-flow transesophageal dry air, was able to efficiently induce hypothermia despite external heating. Therapy was well-tolerated, and no acute or chronic complications were found.

Epicardial Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by progressive fibrofatty replacement of the myocardium, right ventricular enlargement, and malignant ventricular arrhythmias. Ventricular tachycardia (VT) may be seen in all stages of the disease and is associated with sudden cardiac death. In patients who failed anti-arrhythmic medical therapy, catheter ablation has become an attractive therapeutic option to reduce VT burden and implantable cardioverter-defibrillator interventions. In this article, the authors aim to address the overall concepts of epicardial catheter ablation in ARVC, focusing on substrate characterization and ablation strategies.