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In this study, the authors shed light on the underappreciated realm of head and neck lymphedema (HNL) amid the backdrop of significant advancements in extremity lymphedema management. Despite its prevalence and impact, HNL has long been overlooked, attributed to its subtle symptom presentation and lack of awareness among primary care providers. The study delves into the unique challenges associated with diagnosing and treating HNL, emphasizing the predominance of internal swelling over external manifestations. The authors advocate for the refinement and standardization of outcome measures and the integration of innovative techniques such as indocyanine green lymphography and patient-reported outcomes., Competing Interests: Disclosure None of the authors has any conflicts of interest or financial interest in any of the products, devices, or drugs mentioned in this study. The study was not financially supported by any grants., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Since randomized clinical trials currently do not support continuous positive airway pressure treatment of asymptomatic obstructive sleep apnea (OSA) we proposed the Obesity, Symptoms, and CARdiovascular assessment (OSCAR) algorithm to aid clinicians in the management of asymptomatic low-risk moderate-severe OSA, focusing on weight loss, symptoms and cardiovascular disease (CVD) risk assessment. Exploiting the data of the Sleep Heart Health Study we selected subjects with a body mass index (BMI) < 30 Kg/m 2 , no history of CVD or sleepiness and compared 552 patients with moderate-severe OSA (OSCAR(-)) to 916 individuals without OSA (No-OSA). After adjusting for age, gender, and BMI, there was no significant difference in the risk of major adverse cardiovascular events (MACE) between OSCAR(-) and No-OSA (1.05; 95%CI 0.81-1.37). The study suggests that low-risk moderate-severe OSA patients may not have a greater risk of MACE compared to those without OSA and highlights the need for further research on this topic., (© 2024. The Author(s).)

The American Heart Association considers sleep health an essential component of cardiovascular health, and sleep is generally a time of cardiovascular quiescence, such that any deviation from normal sleep may be associated with adverse cardiovascular consequences. Many studies have shown that both impaired quantity and quality of sleep, particularly with obstructive sleep apnea (OSA) and comorbid sleep disorders, are associated with incident cardiometabolic consequences. OSA is associated with repetitive episodes of altered blood gases, arousals, large negative swings in intrathoracic pressures, and increased sympathetic activity. Recent studies show that OSA is also associated with altered gut microbiota, which could contribute to increased risk of cardiovascular disease. OSA has been associated with hypertension, atrial fibrillation, heart failure, coronary artery disease, stroke, and excess cardiovascular mortality. Association of OSA with chronic obstructive lung disease (overlap syndrome) and morbid obesity (obesity hypoventilation syndrome) increases the odds of mortality., Competing Interests: Funding Support and Author Disclosures No funding was received for this study. Dr Shahrokh Javaheri is funded by the National Institutes of Health (NIH) for an oxygen trial; has received income related to medical education from Jazz and Idorsia Pharmaceutical; and has served as a consultant to ZOLL Respicardia. Dr Sogol Javaheri has received grant funding from Zoll, the Massachusetts Technology Collaborative, and an internal health equity grant from Harvard Medical School. Dr Somers is funded by the National Heart, Lung, and Blood Institute (HL65176 and HL160619); has served as a consultant for Bayer, Jazz Pharmaceuticals, Huxley, Apnimed, ResMed, Lilly, Wesper, and ZOLL; and is on the Sleep Number Scientific Advisory Board. Dr Gozal is funded by the NIH for research on sleep apnea, mineralocorticoid receptors, and Alzheimer disease, University of Missouri grants, and the Leda J. Sears Foundation. Dr Mehra is supported by American Academy of Sleep Medicine and American Heart Association grants; has received honorarium from the American Academy of Sleep Medicine for speaking; and has received royalties from UpToDate. Dr Zee is funded by the NIH; has served as a consultant to Eisai, Idorsia, Jazz, Harmony, and Sanofi; and reports grants to Northwestern University from Vanda. Dr Cistulli has an appointment to an endowed academic Chair at the University of Sydney that was established from ResMed funding; has received research support from ResMed and SomnoMed; is a consultant to ResMed, SomnoMed, Signifier Medical Technologies, Bayer, and Sunrise Medical; and has a pecuniary interest in SomnoMed related to a role in research and development (2004). Dr Malhotra is funded by the NIH; has received income related to medical education from Jazz, LivaNova, Eli Lilly, and Zoll; and ResMed provided a philanthropic donation to UC San Diego. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Many studies have shown an association of obstructive sleep apnea (OSA) with incident cardiovascular diseases, particularly when comorbid with insomnia, excessive sleepiness, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease. Randomized controlled trials (RCTs) have demonstrated that treatment of OSA with positive airway pressure devices (CPAP) improves systemic hypertension, particularly in those with resistant hypertension who are adherent to CPAP. However, large RCTs have not shown long-term benefits of CPAP on hard cardiovascular outcomes, but post hoc analyses of these RCTs have demonstrated improved hard outcomes in those who use CPAP adequately. In theory, low CPAP adherence and patient selection may have contributed to neutral results in intention-to-treat analyses. Only by further research into clinical, translational, and basic underlying mechanisms is major progress likely to continue. This review highlights the various treatment approaches for sleep disorders, particularly OSA comorbid with various other disorders, the potential reasons for null results of RCTs treating OSA with CPAP, and suggested approaches for future trials., Competing Interests: Funding Support and Author Disclosures ResMed provided a philanthropic donation to UC San Diego. Dr Shahrokh Javaheri has received income related to medical education from Res Med, Jazz, Idorsia, Eli Lilly, and Avadel Pharmaceutical; and is a consultant to Zoll-Respicardia. Dr Sogol Javaheri has received grant funding from Zoll and the Massachusetts Technology Collaborative; and is supported by an internal health equity grant from Harvard Medical School. Dr Mehra has received an honorarium from the American Academy of Sleep Medicine; has received funds for service on the American Board of Internal Medicine writing group; has received NIH funding; and has received royalties from Up to Date. Dr Somers is supported by National Institutes of Health (NIH) grant HL65176; has served as a consultant for Bayer, Jazz Pharmaceuticals, Huxley, Apnimed, ResMed, Lilly, and Respicardia; and is on the Sleep Number Scientific Advisory Board. Dr Zee is a consultant to Eisai, Idorsia, Jazz, and Harmony; and has received institutional grants from Vanda and Sleep Number. Dr Cistulli has an appointment to an endowed academic Chair at the University of Sydney that was established from ResMed funding; has received research support from ResMed and SomnoMed; is a consultant to ResMed, SomnoMed, Signifier Medical Technologies, Bayer, and Sunrise Medical; and has a pecuniary interest in SomnoMed related to a role in research and development (2004). Dr Malhotra is funded by the NIH; and has received income related to medical education from Powell Mansfield, Livanova, Eli Lilly, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Comprehensive antenatal care (ANC) must prioritize competent, evidence-based medical attention to ensure a positive experience and value for its users. Unfortunately, there is scarce evidence of implementing this holistic approach to ANC in low- and middle-income countries, leading to gaps in quality and accountability. This study assessed care competence, women's experiences during the first ANC visit, and the factors associated with these care attributes., Methods and Findings: The study analyzed cross-sectional baseline data from the maternal eCohort study conducted in Mexico from August to December 2023. The study adapted the Quality Evidence for Health System Transformation (QuEST) network questionnaires to the Mexican context and validated them through expert group and cognitive interviews with women. Pregnant women aged 18 to 49 who had their first ANC visit with a family physician were enrolled in 48 primary clinics of the Instituto Mexicano del Seguro Social across 8 states. Care competence and women's experiences with care were the primary outcomes. The statistical analysis comprised descriptive statistics, multivariable linear and Poisson regressions. A total of 1,390 pregnant women were included in the study. During their first ANC visit, women received only 67.7% of necessary clinical actions on average, and 52% rated their ANC experience as fair or poor. Women with previous pregnancies (adjusted regression coefficient [aCoef.] -3.55; (95% confidence intervals [95% CIs]): -4.88, -2.22, p < 0.001), at risk of depression (aCoef. -3.02; 95% CIs: -5.61, -0.43, p = 0.023), those with warning signs (aCoef. -2.84; 95% CIs: -4.65, -1.03, p = 0.003), common pregnancy discomforts (aCoef. -1.91; 95% CIs: -3.81, -0.02, p = 0.048), or those who had a visit duration of less than 20 minutes (<15 minutes: aCoef. -7.58; 95% CIs: -10.21, -4.95, p < 0.001 and 15 to 19 minutes: aCoef. -2.73; 95% CIs: -4.79, -0.67, p = 0.010) and received ANC in the West and Southeast regions (aCoef. -5.15; 95% CIs: -7.64, -2.66, p < 0.001 and aCoef. -5.33; 95% CIs: -7.85, -2.82, p < 0.001, respectively) had a higher probability of experiencing poorer care competence. Higher care competence (adjusted prevalence ratio [aPR] 1.004; 95% CIs:1.002, 1.005, p < 0.001) and receiving care in a small clinic (aPR 1.19; 95% CIs: 1.06, 1.34, p = 0.003) compared to a medium-sized clinic were associated with a better first ANC visit experience, while common pregnancy discomforts (aPR 0.94; 95% CIs: 0.89, 0.98, p = 0.005) and shorter visit length (aPR 0.94; 95% CIs: 0.88, 0.99, p = 0.039) were associated with lower women's experience. The primary limitation of the study is that participants' responses may be influenced by social desirability bias, leading them to provide socially acceptable responses., Conclusions: We found important gaps in adherence to ANC standards and that care competence during the first ANC visit is an important predictor of positive user experience. To inform quality improvement efforts, IMSS should institutionalize the routine monitoring of ANC competencies and ANC user experience. This will help identify poorly performing facilities and providers and address gaps in the provision of evidence-based and women-centered care., Competing Interests: MEK is a member of the Editorial Board of PLOS Medicine. SVD, CQF, MPC, DPM, VMG, LRGC, MCCM, VMG, MARG, GEA, CEPR, CAPA, and ASD are employed by the IMSS, yet IMSS played no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. RPC and CA have declared that no competing interests exist., (Copyright: © 2024 Doubova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Obstructive sleep apnea (OSA) and hypertension are two important modifiable risk factors for cardiovascular disease and mortality. Numerous studies have highlighted the interplay between these two conditions. We provide a critical review of the current literature on the role of the OSA as a risk factor for hypertension and its effect on blood pressure (BP). We discuss several key topics: the effect of OSA on nocturnal BP, BP response to continuous positive airway pressure (CPAP) treatment, CPAP effect on BP in refractory hypertension, the role of OSA in BP variability (BPV), and maladaptive cardiac remodeling mediated by OSA's effect on BP. Finally, we discuss the unique aspects of ethnicity and social determinants of health on OSA with a focus on Asian populations and the disparity in BP control and cardiovascular outcomes., (© 2024. The Author(s).)

Background: OSA has been associated with increased incidence and aggressiveness of melanoma. However, the long-term impact of OSA and CPAP treatment on the prognosis of melanoma remains unexplored., Research Question: Are OSA and CPAP treatment associated independently with a poor prognosis for cutaneous melanoma?, Study Design and Methods: Four hundred forty-three patients with a diagnosis of cutaneous melanoma (2012-2015) underwent a sleep study within 6 months of diagnosis. The main 5-year outcome of the study was a composite of melanoma recurrence, metastasis, or mortality. Patients were divided into four groups: baseline apnea-hypopnea index (AHI) of fewer than 10 events/h (no OSA; control group), OSA treated with CPAP and good adherence, untreated or poor CPAP adherence in moderate (AHI, 10-29 events/h), and severe OSA (AHI, ≥ 30 events/h). Survival analysis was used to determine the independent role of OSA and CPAP treatment on melanoma composite outcome., Results: Three hundred ninety-one patients (88.2%) were available for analysis at 5-year follow-up (mean age, 65.1 ± 15.2 years; 49% male; Breslow index, 1.7 ± 2.5 mm). One hundred thirty-nine patients had AHI of fewer than 10 events/h (control group); 78 patients with OSA were adherent to CPAP; and 124 and 50 patients had moderate and severe OSA, respectively, without CPAP treatment. Median follow-up was 60 months (interquartile range, 51-74 months). During follow-up, 32 relapses, 53 metastases, and 52 deaths occurred (116 patients showed at least one of the main composite outcomes). After adjusting for age, sex, sentinel lymph nodes affected at diagnosis, BMI, diabetes, nighttime with an oxygen saturation below 90%, Breslow index, Epworth sleepiness scale scores, and melanoma treatment, moderate (hazard ratio [HR], 2.45; 95% CI, 1.09-5.49) and severe OSA (HR, 2.96; 95% CI, 1.36-6.42) were associated with poorer prognosis of melanoma compared with the control group. However, good adherence to CPAP avoided this excess risk (HR, 1.66; 95% CI, 0.71-3.90)., Interpretation: Moderate to severe untreated OSA is an independent risk factor for poor prognosis of melanoma. Treatment with CPAP is associated with improved melanoma outcomes compared with untreated moderate to severe OSA., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the relationship between asthma and bronchiectasis, as well as the necessary conditions that this connection must meet for this group of patients to be considered a special phenotype., Data Sources: We performed a PubMed search using the MeSH terms "asthma" and "bronchiectasis." The literature research was limited to clinical trials, meta-analyses, randomized controlled trials, cohort studies, and systematic reviews, involving adult patients, published until November 30th, 2022., Study Selections: Selected papers were initially evaluated by the Authors, to assess their eligibility in contributing to the statements., Results: The prevalence of bronchiectasis is higher than expected in patients with asthma, particularly in those with more severe disease, and in some patients, between 1.4% and 7% of them, asthma alone could be the cause of bronchiectasis. Both diseases share etiopathogenic mechanisms, such as neutrophilic and eosinophilic inflammation, altered airway microbiota, mucus hypersecretion, allergen sensitization, immune dysfunction, altered microRNA, dysfunctional neutrophilic activity, and variants of the HLA system. Besides that, they also share comorbidities, such as gastroesophageal reflux disease and psychiatric illnesses. The clinical presentation of asthma is very similar to patients with bronchiectasis, which could cause mistakes with diagnoses and delays in being prescribed the correct treatment. The coexistence of asthma and bronchiectasis also poses difficulties for the therapeutic focus., Conclusions: The evidence available seems to support that the asthma-bronchiectasis phenotype really exists although longitudinal studies which consistently demonstrate that asthma is the cause of bronchiectasis are still lacking.

Background and Objectives: RYR1 -related myopathies are the most common congenital myopathies, but long-term natural history data are still scarce. We aim to describe the natural history of dominant and recessive RYR1 -related myopathies., Methods: A cross-sectional and longitudinal retrospective data analysis of pediatric cases with RYR1 -related myopathies seen between 1992-2019 in 2 large UK centers. Patients were identified, and data were collected from individual medical records., Results: Sixty-nine patients were included in the study, 63 in both cross-sectional and longitudinal studies and 6 in the cross-sectional analysis only. Onset ranged from birth to 7 years. Twenty-nine patients had an autosomal dominant RYR1 -related myopathy, 31 recessive, 6 de novo dominant, and 3 uncertain inheritance. Median age at the first and last appointment was 4.0 and 10.8 years, respectively. Fifteen% of patients older than 2 years never walked (5 recessive, 4 de novo dominant, and 1 dominant patient) and 7% lost ambulation during follow-up. Scoliosis and spinal rigidity were present in 30% and 17% of patients, respectively. Respiratory involvement was observed in 22% of patients, and 12% needed ventilatory support from a median age of 7 years. Feeding difficulties were present in 30% of patients, and 57% of those needed gastrostomy or tube feeding. There were no anesthetic-induced malignant hyperthermia episodes reported in this cohort. We observed a higher prevalence of prenatal/neonatal features in recessive patients, in particular hypotonia and respiratory difficulties. Clinical presentation, respiratory outcomes, and feeding outcomes were consistently more severe at presentation and in the recessive group. Conversely, longitudinal analysis suggested a less progressive course for motor and respiratory function in recessive patients. Annual change in forced vital capacity was -0.2%/year in recessive vs -1.4%/year in dominant patients., Discussion: This clinical study provides long-term data on disease progression in RYR1 -related myopathies that may inform management and provide essential milestones for future therapeutic interventions., (© 2023 American Academy of Neurology.)

Both chronic obstructive pulmonary disease and bronchiectasis are highly prevalent diseases. In both cases, inhaled corticosteroids (ICs) are associated with a decrease in exacerbations in patients with a high peripheral blood eosinophil count (BEC), but it is still not known what occurs in bronchiectasis-COPD overlap syndrome (BCOS). The present study aimed to assess the effect of ICs on various outcomes in patients with BCOS, according to BEC values. We undertook a post-hoc analysis of a cohort of 201 GOLD II-IV COPD patients with a long-term follow-up (median 74 [IQR: 40-106] months). All participants underwent computerized tomography and 115 (57.2%) had confirmed BCOS. A standardized clinical protocol was followed and two sputum samples were collected at each medical visit (every 3-6 months), whenever possible. During follow-up, there were 68 deaths (59.1%), and the mean rate of exacerbations and hospitalizations per year was 1.42 (1.2) and 0.57 (0.83), respectively. A total of 44.3% of the patients presented at least one pneumonic episode per year. The mean value of eosinophils was 402 (112) eosinophils/µL, with 27 (23.5%), 63 (54.8%), and 25 patients (21.7%) presenting, respectively, less than 100, 101-300, and more than 300 eosinophils/µL. A total of 84 patients (73.1%) took ICs. The higher the BEC, the higher the annual rate of exacerbations and hospitalizations. Patients with less than 100 eosinophils/µL presented more infectious events (incident exacerbations, pneumonic episodes, and chronic bronchial infection via pathogenic bacteria). Only those patients with eosinophilia (>300 eosinophils/µL) treated with ICs decreased the number (1.77 (1.2) vs. 1.08 (0.6), p < 0.001) and the severity (0.67 (0.8) vs. 0.35 (0.5), p = 0.011) of exacerbations, without any changes in the other infectious outcomes or mortality. In conclusion, ICs treatment in patients with BCOS with increased BEC decreased the number and severity of incident exacerbations without any negative influence on other infectious outcomes (incidence of pneumonia or chronic bronchial infection).

Bronchiectasis is a complex and heterogeneous disease with a myriad of pulmonary and extrapulmonary etiologies. Bronchiectasis has a predominantly neutrophilic inflammatory profile. However, eosinophilic inflammation has also been documented in both the airways and the systemic circulation. Various diseases (eg, asthma, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyps) characterized by heightened type 2 airway inflammatory responses, including blood or sputum eosinophilia, may coexist with bronchiectasis. Apart from those eosinophilic etiologies or comorbidities related to bronchiectasis, around 20% of patients with bronchiectasis have peripheral eosinophilia (at least 3% or 300 eosinophils/μL) with no identified concomitant disease (also termed "eosinophilic bronchiectasis"), whose roles have not been fully understood. The two key points regarding these observations are that eosinophils confer both bactericidal and antiviral properties against common pathogenic microorganisms that are usually detected in bronchiectasis, and that eosinophilic bronchiectasis has been associated with better therapeutic response to inhaled corticosteroids and other anti-T H 2 profile treatments. In this review, we summarize the most significant evidence regarding the role of eosinophils in patients with bronchiectasis, including the association of bronchiectasis with eosinophilic diseases (as etiologies or comorbidities), and existing data on eosinophilic bronchiectasis not related to eosinophilic disorders., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Bronchiectasis is a very heterogeneous disease. This heterogeneity has several consequences: severity cannot be measured by a single variable, so multidimensional scores have been developed to capture it more broadly. Some groups of patients with similar clinical characteristics or prognoses (clinical phenotypes), and even similar inflammatory profiles (endotypes), have been identified, and these have been shown to require a more specific treatment., Areas Covered: We comment on this 'stratified' model of medicine as an intermediate step toward the application of the usual concepts on which precision medicine is based (such as cellular, molecular or genetic biomarkers, treatable traits and individual clinical fingerprinting), whereby each subject presents certain specific characteristics and receives individualized treatment., Expert Opinion: True precision or personalized medicine is based on concepts that have not yet been fully achieved in bronchiectasis, although some authors are already beginning to adapt them to this disease in terms of pulmonary and extrapulmonary etiologies, clinical fingerprinting (specific to each individual), cellular biomarkers such as neutrophils and eosinophils (in peripheral blood) and molecular biomarkers such as neutrophil elastase. In therapeutic terms, the future is promising, and some molecules with significant antibiotic and anti-inflammatory properties are being developed.

Several epidemiological and clinical studies have suggested a relationship between obstructive sleep apnea (OSA) and a higher incidence or severity of cancer. This relationship appears to be dependent on a myriad of factors. These include non-modifiable factors, such as age and gender; and modifiable or preventable factors, such as specific comorbidities (especially obesity), the use of particular treatments, and, above all, the histological type or location of the cancer. Heterogeneity in the relationship between OSA and cancer is also related to the influences of intermittent hypoxemia (a hallmark feature of OSA), among others, on metabolism and the microenvironment of different types of tumoral cells. The hypoxia inducible transcription factor (HIF-1α), a molecule activated and expressed in situations of hypoxemia, seems to be key to enabling a variety of pathophysiological mechanisms that are becoming increasingly better recognized. These mechanisms appear to be operationally involved via alterations in different cellular functions (mainly involving the immune system) and molecular functions, and by inducing modifications in the microbiome. This, in turn, may individually or collectively increase the risk of cancer, which is then, further modulated by the genetic susceptibility of the individual. Here, we provide an updated and brief review of the different pathophysiological pathways that have been identified and could explain the relationship between OSA and cancer. We also identify future challenges that need to be overcome in this intriguing field of research.

Classically, the role of pulmonary infection in patients with chronic obstructive pulmonary disease (COPD) has focused on periods of exacerbation. However, in a clinically stable situation, little attention has been paid to the role play by the presence of potentially pathogenic micro-organisms (especially when they are repeatedly isolated, which is known as chronic bronchial infection [CBI]) in the pathogenesis, prognosis and disease treatment. In recent years, however, some evidence has been published on the deleterious effect of CBI in COPD since it has been associated to greater local inflammation, greater disease severity, poorer health-related quality of life, greater number and severity of exacerbations and cardiovascular events, presence of bronchiectasis, rapid decline of lung function, and even higher mortality (especially related to Pseudomonas aeruginosa infection). It is not known, however, what is the role of anti-inflammatory or antibiotic treatments on CBI in stable COPD patients. This review focused on the scientific evidence on this topic that exists up to now, from the very definition of IBC in COPD to the possible treatments that this situation entails, as well as the numerous future challenges it generates, especially the development of knowledge of the pulmonary microbiome, its alterations and its consequences., (© 2023 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

International guidelines on the treatment of bronchiectasis indicate that the use of inhaled antibiotics is effective, especially in symptomatic chronic bronchial infection (CBI) due to Pseudomonas aeruginosa (PA). To date, however, no such treatment has been approved by regulatory agencies. Of the inhaled antibiotics on the market, colistimethate sodium (colistin) is one of the most used in many countries, either in its nebulized presentation or as dry powder. Among the characteristics of this antibiotic, it is worth noting that its main target is the lipopolysaccharide in the outer membrane of the cell wall of gram-negative bacteria and that it has a low rate of resistance to PA (<1%). Most observational studies have shown that the use of colistin in patients with bronchiectasis and CBI due to PA results in a decrease in both the number and severity of exacerbations, an improvement in quality of life, a decrease in sputum volume and purulence, and a high rate of PA eradication, although there are no clear differences with respect to other inhaled antibiotics. However, the lack of randomized clinical trials (RCT) with positive results for its main variable (exacerbations) in an intention-to-treat analysis has prevented its approval by regulatory agencies as a formal indication for use in bronchiectasis. The PROMIS program, made up of two RCT with identical methodology, is currently underway. The first of these RCT (already concluded) has demonstrated a clearly positive effect on the group randomized to colistin in its main variable (number of annual exacerbations), while the results of the second are still pending. This review presents exhaustive information on the pharmacological and microbiological characteristics of colistin, the results of the studies carried out to date, and the future challenges associated with this treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 de la Rosa-Carrillo et al.)

The majority of the current international obstructive sleep apnea (OSA) guidelines base the recommendation to treat OSA with continuous positive airway pressure (CPAP) on the presence of symptoms (principally, albeit not exclusively on daytime hypersomnolence). In nonsleepy patients, even with severe OSA, controversies remain, as clear evidence supporting CPAP treatment of this subgroup of OSA patients is lacking. However, given the nonnegligible proportion of non-sleepy OSA patients, clinicians often face a serious dilemma since CPAP treatment in these patients may prove to be not cost-effective. Here, we propose a simple three-step-based algorithm that attempts to better phenotype non-sleepy OSA patients prior to reaching a CPAP treatment decision while also considering a series of clinically relevant elements in the process that may improve with CPAP therapy. Such algorithm focuses on the presence of several OSA symptoms that are susceptible to benefit from treatment and also relies on OSA phenotypes that need to be considered in an effort to achieve optimal cardiovascular prevention. Here, we attempt to establish a framework for clinicians who are evaluating severe nonsleepy OSA patients in their practices. However, the algorithm proposal needs to be extensively validated before being systematically implemented in clinical settings., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes., Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes., Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals., Exposures: Genetic test results., Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms., Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%)., Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Abstract: Bronchiectasis (BE) has been linked to past viral infections such as influenza, measles, or adenovirus. Two years ago, a new pandemic viral infection severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out and it still persists today, and a significant proportion of surviving patients have radiological and clinical sequelae, including BE. Our aim was to thoroughly review the information available in the literature on the bidirectional relationship between SARS-CoV-2 infection and the development of BE, as well as the impact of this infection on patients already suffering from BE. Available information indicates that only a small percentage of patients in the acute phase of coronavirus disease 2019 (COVID-19) pneumonia develop BE, although the latter is recognized as one of the radiological sequelae of COVID-19 pneumonia, especially when it is caused by traction. The severity of the initial pneumonia is the main risk factor for the development of future BE, but during the COVID-19 pandemic, exacerbations in BE patients were reduced by approximately 50%. Finally, the impact of BE on the prognosis of patients with COVID-19 pneumonia is not yet known., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Bronchiectasis is the third most common chronic inflammatory airway disease, after chronic obstructive pulmonary disease (COPD) and asthma with a prevalence clearly underestimated probably because of its clinical similitudes with other chronic airway diseases. Bronchiectasis can be caused by a dozen of pulmonary and extra-pulmonary diseases and a variable number and severity of exacerbations can appear throughout its natural history, usually with an infectious profile. The dilation of the airway and the inflammation/infection is their radiological and pathophysiological hallmarks. Primary Care should play an important play in many aspects of the bronchiectasis assessment. In this article, we will try to offer a series of important concepts and practical tips on some key aspects of the diagnosis and management of bronchiectasis in Primary Care: clinical suspicion, diagnostic methods, severity assessment, overlap with asthma and COPD and microbiological and therapeutic aspects., (© 2022. The Author(s).)

Competing Interests: Declaration of Competing Interest JMSP has not conflict of interest JLLC has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies and writing for publications for (in alphabetical order): AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, CSL Behring, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Megalabs, Novartis and Rovi. MAMG has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies and writing for publications for (in alphabetical order): AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Menarini, Novartis, Philips, Rovi and Vitalaire.

Up to 50% of patients with chronic obstructive pulmonary disease (COPD) in stable state may carry potentially pathogenic microorganisms (PPMs) in their airways. The presence of PPMs has been associated with increased symptoms, increased risk and severity of exacerbations, a faster decline in lung function and impairment in quality of life. Although some clinical trials have demonstrated a reduction in exacerbations in patients chronically treated with systemic antibiotics, particularly macrolides, the selection of patients was based on the previous frequency of exacerbations and not on the presence of PPMs in their airways. Therefore, unlike in bronchiectasis, there is a lack of evidence-based recommendations for assessment and treatment of the presence of PPMs in either single or repeated isolations in COPD. In this article, we propose that chronic bronchial infection (CBI) in COPD be defined as the isolation of the same PPM in at least three sputum samples separated by more than one month; we review the impact of CBI on the natural course of COPD and suggest a course of action in patients with a single isolation of a PPM or suspected CBI. Antibiotic treatment in stable COPD should be recommended based on four main criteria: a) the presence of comorbid bronchiectasis, b) the demonstration of a single or multiple isolation of the same PPM, c) the clinical impact of CBI on the patients, and d) the type of PPM, either Pseudomonas aeruginosa or non-pseudomonal PPM. These recommendations are derived from evidence generated in patients with bronchiectasis and, until new evidence specifically obtained in COPD is available, they may help in the management of these challenging patients with COPD. Existing evidence suggests that inhaled therapy is insufficient to manage patients with moderate-to-severe COPD, frequent exacerbations, and CBI. New studies must be conducted in this particularly demanding population., Competing Interests: Miguel Angel Martinez-Garcia has received fees from Chiesi, GlaxoSmithKline, Menarini, Rovi, Bial, Zambon, Vitalaire, TEVA, Grifols and Novartis, consulting fees from Grifols, Zambon and TEVA, and research grants from TEVA, Zambon and Vitalaire. Marc Miravitlles has received speaker fees from AstraZeneca, Atrina Therapeutics, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Johnson & Johnson, Mereo Biopharma, Palobiofarma SL, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi, ONO Pharma, Takeda, and Grifols and research grants from Grifols. The authors report no other conflicts of interest in this work., (© 2022 Martinez-Garcia and Miravitlles.)

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis., Competing Interests: Declaration of interests SA reports personal fees from AstraZeneca, Bayer Healthcare, Chiesi, GlaxoSmithKline, Grifols, Insmed, Menarini, Zambon, and ZetaCube; and grants from Chiesi, Fisher & Paykel, and Insmed, outside of the submitted work. AFB reports personal fees from Wolters Kluwer and UpToDate, during the conduct of the study. FB reports personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Grifols, Guidotti, Insmed, Menarini, Novartis, Pfizer, Vertex, and Zambon; and grants from AstraZeneca, Bayer, Chiesi, GlaxoSmithKline, Menarini, and Pfizer, outside of the submitted work. JDC reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Insmed, Janssen, Novartis, and Zambon; and grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Science, Insmed, and Novartis, outside of the submitted work. MLC reports personal fees from AstraZeneca, outside of the submitted work. ADS reports grants and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Forest Labs, GlaxoSmithKline, Grifols, Insmed, Teva, and Zambon, outside of the submitted work. PCG reports personal fees from AstraZeneca and GlaxoSmithKline; and grants and non-financial support from Chiesi, outside of the submitted work. CSH reports personal fees from Aradigm, CSL Behring, GlaxoSmithKline, Grifols, Insmed, International Biophysics, Janssen, Meiji, Mylan, Novartis, Teva, and Zambon; and grants from Insmed, International Biophysics, and Teva, outside of the submitted work. MSM reports non-financial support from Boehringer Ingelheim, Insmed, and Zambon; and personal fees from Zambon, outside of the submitted work. MRL reports personal fees from AstraZeneca, Grifols, and Insmed, outside of the submitted work. AEO'D reports personal fees from Electromed, Insmed, and Zambon; and grants from AstraZeneca, Insmed, Janssen, and Zambon, outside of the submitted work. EP reports grants from Chiesi and Grifols; and personal fees from CSL Behring, Chiesi, Shionogi, Insmed, Shire, Teva, and Zambon, during the conduct of the study. FCR reports personal fees from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Celtaxsys, Chiesi, Corbus, Grifols, InfectoPharm, Insmed, Novartis, PARI, Parion, Polyphor, Vertex, and Zambon; grants from Bayer Healthcare, Grifols, InfectoPharm, Insmed, Novartis, and PARI; and non-financial support from PARI, outside of the submitted work. MS reports personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Kamada, Novartis, Teva, Vertex, and Zambon; grants from GlaxoSmithKline and Novartis; and non-financial support from Actelion, GlaxoSmithKline, and Rafa, outside of the submitted work. HT reports personal fees from Insmed, Novartis, Thirona, and Vertex; and grants from the Cystic Fibrosis Foundation, Insmed, and Novartis, outside of the submitted work. In addition, HT's institution, Erasmus MC, receives license fees for the chest CT image analysis PRAGMA-CF software developed by Thirona (Nijmegen, Netherlands) and by Resonance Health (Perth, Australia) and for the chest CT image analysis AA-method software co-developed by Erasmus MC and Thirona (Nijmegen, Netherlands). HT contributed to the development and validation of this software. GT reports grants from the US Bronchiectasis and non-tuberculous mycobacteria Research Registry (which is funded by the COPD Foundation); and personal fees from AstraZeneca and Cipla, outside of the submitted work. MV reports non-financial support from Chiesi, GlaxoSmithKline, Novartis, and Zambon; and personal fees from Insmed, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians., Methods: We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the "COPD- [bronchiectasis] BE association".A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds., Results: 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of "COPD-BE association" was: "The coexistence of (1) specific radiological findings ( abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV 1 /[forced vital capacity] FVC <0.7), (3) at least two characteristic symptoms ( cough, expectoration, dyspnoea, fatigue, frequent infections ) and (4) current or past exposure to smoke ( ≥ 10 pack-years ) or other toxic agents (bi omass, etc. )". These criteria form the acronym "ROSE" (Radiology, Obstruction, Symptoms, Exposure)., Conclusions: The Delphi process formulated a European consensus definition of "COPD-BE association". We hope this definition will have broad applicability across clinical practice and research in the future., Competing Interests: Conflict of interest: L. Traversi has nothing to disclose. Conflict of interest: M. Miravitlles reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon and CSL Behring, grants and personal fees from Grifols, personal fees from Novartis, grants and personal fees from GlaxoSmithKline, and personal fees from Gebro Pharma, Kamada, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, PH Pharma and from Sanofi, outside the submitted work. Conflict of interest: M.A. Martinez-Garcia reports personal fees from Grifols, grants and personal fees from TEVA, personal fees from Novartis and Zambon, grants and personal fees from Philips and Vitalair, and personal fees from Chiesi, AZ and GSK, outside the submitted work. Conflict of interest: M. Shteinberg reports grants and personal fees from GSK and Novartis, grants from Trudell Pharma, and personal fees from Actelion, Boehringer Ingelheim, Rafa, AstraZeneca, TEVA, Kamada, Horizon Pharma and Vertex pharmaceuticals, outside the submitted work. Conflict of interest: A. Bossios reports personal fees from GlaxoSmithKline, TEVA, Novartis, Sanofi and AstraZeneca outside the submitted work. Conflict of interest: K. Dimakou reports personal fees from Chiesi, AstraZeneca, Pfizer, Boehringer Ingelheim, Novartis, GlaxoSmithKline and Menarini outside the submitted work. Conflict of interest: J. Jacob reports grants from Wellcome Trust Clinical Research Career Development, Roche, Boehringer Ingelheim, Novartis, GlaxoSmithKline and NHSX outside the submitted work. Conflict of interest: J.R. Hurst reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi and Novartis outside the submitted work. Conflict of interest: P.L. Paggiaro reports personal fees from Alk-Abellò, AstraZeneca, Chiesi, GSK, Guidotti, Menarini, Mundipharma, Novartis and Sanofi outside the submitted work. Conflict of interest: S. Ferri has nothing to disclose. Conflict of interest: G. Hillas reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, Innovis, GSK, Menarini, Novartis, Pharmaten and UCB outside the submitted work. Conflict of interest: J. Vogel-Claussen reports grants and personal fees from Siemens Healthineers, AstraZeneca, GSK, Novartis and Boehringer Ingelheim outside the submitted work. Conflict of interest: S. Dettmer has nothing to disclose. Conflict of interest: S. Aliberti reports personal fees from Bayer Helthcare, Grifols, AstraZeneca and Zambon, grants and personal fees from Chiesi and INSMED, personal fees from GlaxoSmithKline, Menarini and ZetaCube Srl, and grants from Fisher & Paykel, outside the submitted work. Conflict of interest: J.D. Chalmers reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi and GlaxoSmithKline, grants from Gilead Sciences, Novartis and Insmed, personal fees from Janssen and Zambon, and grants and personal fees from Grifols, outside the submitted work. Conflict of interest: E. Polverino reports personal fees from Bayer, grants and personal fees from Grifols, and personal fees from Insmed, Chiesi, Menarini, Zembon and Pfizer, outside the submitted work., (Copyright ©The authors 2021.)

Depression is common in women with obstructive sleep apnea (OSA), but objective markers of depression have not yet been explored in such patients. We hypothesized that inflammation and antioxidant biomarkers may be associated with depression in a cohort of OSA women. We conducted a multicentre, cross-sectional study in 247 women diagnosed with moderate-to-severe OSA. Depression was assessed by the depression subscale of the Hospital Anxiety and Depression Questionnaire (HAD-D) and defined as a score ≥11. Associations between tumour necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF) plasma levels and depression were assessed. The women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index (BMI) of 33.5 (29.0-38.3) Kg/m 2 , Epworth Sleepiness Scale (ESS) score of 10 (6-13) and apnea-hypopnea index (AHI) of 33.3 (22.8-49.3). Logistic regression analyses revealed that only IL6 levels were associated with the presence of depression (adjusted odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.34), whereas linear regression further confirmed that IL6 levels were significantly associated with HAD-D scores (β = .154; 95% CI, 0.03-0.30). Multivariate regression analysis showed that IL6 (OR, 1.22; 95% CI, 1.09-1.36), ESS (OR, 1.10; 95% CI 1.02-1.19) and physical activity <30 min/day (OR, 2.51; 95% CI, 1.25-5.05) were independent predictors of depression. Thus, we conclude that in a cohort of women with moderate-to-severe OSA, IL6 levels are independently associated with the presence of depression and correlate with depression scores. Low physical activity and higher ESS scores are also independent indicators of risk of depression in this population., (© 2020 European Sleep Research Society.)

Few large series describe the clinical characteristics, outcomes and costs of COVID-19 in Western countries. This cohort reports the first 1255 adult cases receiving anti-COVID-19 treatment at a Spanish hospital (1-24 March 2020). Treatment costs were calculated. A logistic regression model was used to explore risk factors on admission associated with ARDS. A bivariate Cox proportional hazard ratio (HR) model was employed to determine the HR between individual factors and death. We included 1255 patients (median age 65 years; 57.8% male), of which 92.3% required hospitalisation. The prevalence of hypertension, cardiovascular disease and diabetes mellitus (DM) was 45.1%, 31.4% and 19.9%, respectively. Lymphocytopenia (54.8%), elevated alanine aminotransferase (33.0%) and elevated lactate dehydrogenase (58.5%) were frequent. Overall, 36.7% of patients developed ARDS, 10.0% were admitted to an ICU and 21.3% died. The most frequent antiviral combinations were lopinavir/ritonavir plus hydroxychloroquine (44.2%), followed by triple therapy with interferon beta-1b (32.7%). Corticosteroids and tocilizumab were used in 25.3% and 12.9% of patients, respectively. Total cost of anti-COVID-19 agents was €511 825 (€408/patient). By multivariate analysis, risk factors associated with ARDS included older age, obesity, DM, severe hypoxaemia, lymphocytopenia, increased creatine kinase and increased C-reactive protein. In multivariate Cox model, older age (HR 1.07, 95% CI 1.06-1.09), cardiovascular disease (HR 1.34, 95% CI 1.01-1.79), DM (HR 1.45, 95% CI 1.09-1.92), severe hypoxaemia (HR 2.01, 95% CI 1.49-2.72), lymphocytopenia (HR 1.62, 95% CI 1.20-2.20) and increased C-reactive protein (HR 1.04, 95% CI 1.02-1.06) were risk factors for mortality., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Exacerbations are crucial events during bronchiectasis progression., Objectives: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations., Methods: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations., Results: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P<.05). Sputum interleukin-1β levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P<.05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P=.019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations., Conclusions: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Background: Exacerbations are crucial events during bronchiectasis progression., Objectives: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations., Methods: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations., Results: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ ( P  < .05). Sputum interleukin-1β levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P  < .05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations ( P  = .019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations., Conclusions: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens., (© 2020 Published by Elsevier España, S.L.U. on behalf of SEPAR.)

Bio-conjugated hydrogels merge the functionality of a synthetic network with the activity of a biomolecule, becoming thus an interesting class of materials for a variety of biomedical applications. This combination allows the fine tuning of their functionality and activity, whilst retaining biocompatibility, responsivity and displaying tunable chemical and mechanical properties. A complex scenario of molecular factors and conditions have to be taken into account to ensure the correct functionality of the bio-hydrogel as a scaffold or a delivery system, including the polymer backbone and biomolecule choice, polymerization conditions, architecture and biocompatibility. In this review, we present these key factors and conditions that have to match together to ensure the correct functionality of the bio-conjugated hydrogel. We then present recent examples of bio-conjugated hydrogel systems paving the way for regenerative medicine applications.