Preoperative frailty screening in elderly patients with non-small cell lung cancer surgery: an essential step for a good surgical outcome.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is a disease commonly diagnosed in the elderly, often in advanced stages. However, elderly patients with lung cancer can benefit from surgery, provided that postoperative risks are assessed appropriately before surgery. Frailty is a measure of age-related impaired functional status and a predictor of mortality and morbidity. However, its importance as a preoperative marker is not well defined. AREAS COVERED: This systematic review discusses the importance of preoperative frailty screening in elderly patients with NSCLC. A literature search was performed on the MEDLINE database in June 2023, and relevant studies on frailty or preoperative assessment of NSCLC which were published between 2000 and 2023 were retained and discussed in this review. EXPERT OPINION: Among the types of existing methods used to assess frailty those on the geriatric assessment seem to be the most appropriate; however, they are unable to fully capture the 'surgical' frailty; thus, other instruments should be developed and validated in NSCLC.

Navafenterol for chronic obstructive pulmonary disease therapy.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a prevalent disease of the airways in which inhaled bronchodilators can be given as monotherapy or fixed dose combination, in order to better control disease symptoms and to reduce its morbidity. A novel bronchodilator approach is represented by bifunctional molecules such as navafenterol, which exert dual synergic bronchodilator effects as a monotherapy. Navafenterol is currently being investigated for COPD. AREAS COVERED: This review summarizes the preclinical data regarding navafenterol synthesis and in vitro and in vivo testing. Clinical data coming from phase I and II studies are also discussed. Navafenterol was found to improve lung function, dyspnea, and cough severity and was well tolerated, and its effect was comparable with that of fixed-dose combinations in patients with moderate-to-severe COPD. EXPERT OPINION: Despite clinical evidence of efficacy for navafenterol is still limited, the existing data prompts further clinical evaluation and also consideration of other inhalation approaches such as pressure metered-dose inhalers (pMDIs) or nebulization. Other interesting approach would be combination with another bifunctional molecule such as ensifentrine.

Development and Validation of a Questionnaire to Assess Knowledge and Attitudes toward COVID-19 Preventive Measures in Romania.

The World Health Organization warns about the threat of the COVID-19 sixth wave. Our aim was to propose the first validated Romanian questionnaire to assess people's level of education and attitudes towards general measures to protect against COVID-19 infection. Our study was conducted on a sample of 194 people. The first version of the questionnaire consisted of 40 items. Items that did not meet psychometric criteria were removed. Latent components/factors were identified through exploratory factorial analysis (EFA). The Cronbach's alpha coefficient was used to assess internal fidelity. The EFA identified three factors. Factor 1 was named "Compliance with protective measures", factor 2 was "Attitudes toward vaccination" and factor 3 was "Attitudes regarding potential COVID-19 therapies". The final version of the questionnaire consists of 16 items. The test's final score predicted the presence of vaccination with an accuracy of 0.773. The questionnaire score, the diagnosis of diabetes, the advice provided by healthcare workers and the medical profession proved to be significant predictors of vaccination. The implementation of our questionnaire within national programs could identify populational areas that need specific interventions to reach vaccination targets and prevent a full-blown sixth wave of the COVID-19 pandemic in Romania.

Immune senescence in non-small cell lung cancer management: therapeutic relevance, biomarkers, and mitigating approaches.

INTRODUCTION: Lung cancer and mainly non-small cell lung cancer (NSCLC) still remain a prevalent malignancy worldwide despite sustained screening approaches. Furthermore, a significant proportion of the cases are diagnosed at advanced stages when conservative therapy is often unsuccessful. Cell senescence is an endogenous antitumor weapon but when it is upregulated exerts opposite activities favoring tumor metastasizing and poor response to therapy. However, little is known about this dangerous relationship between cell senescence and NSCLC outcome or on potential approaches to mitigate its unfavorable consequences. AREAS COVERED: We discuss cell senescence focusing on immune senescence, its cell and humoral effectors (namely immune senescence associated secretory phenotype-iSASP), its impact on NSCLC outcome, and its biomarkers. Senotherapeutics as mitigating approaches are also considered based on the availability of experimental data pertinent to NSCLC. EXPERT OPINION: Characterization of NSCLC subsets in which immune senescence is a risk factor for poor prognosis and poor therapeutic response might be very helpful in supporting the addition of senotherapeutics to conventional cancer therapy. This approach has the potential to improve disease outcome but more studies in this area are necessary.

Determinants of the Hesitancy toward COVID-19 Vaccination in Eastern European Countries and the Relationship with Health and Vaccine Literacy: A Literature Review.

Herd immunity is necessary to control the coronavirus disease 2019 (COVID-19) pandemic. However, a low proportion of vaccinated people and low levels of vaccine acceptance have been noted in Eastern Europe. Our paper aimed to review the central attitudes associated with the hesitancy toward COVID-19 vaccination specific to Eastern European countries. The main Eastern European determinants of COVID-19 vaccine acceptance identified from the included studies are: public confidence in the vaccines' safety and efficacy, vaccine literacy, and public trust in the government and the medical system. Each of these determinants is discussed along with possible improvement measures. Variables specific to Eastern Europe that predict the willingness to vaccinate have also been highlighted. The specific attitudes and their context as identified by our review should be incorporated into local public health programs, with the ultimate goal of reducing viral spreading, mutation emergence, and COVID-19 morbidity and mortality both within the borders of Eastern Europe and beyond.

Romanian Guidelines for the Diagnosis and Treatment of GERD-induced Respiratory Manifestations.

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common condition present in daily practice with a wide range of clinical phenotypes. In this line, respiratory conditions may be associated with GERD. The Romanian Societies of Gastroenterology and Neurogastroenterology, in association with the Romanian Society of Pneumology, aimed to create a guideline regarding the epidemiology, diagnosis and treatment of respiratory conditions associated with GERD. METHODS: Delphi methodology was used and eleven common working groups of experts were created. The experts reviewed the literature according to GRADE criteria and formulated 34 statements and recommendations. Consensus (>80% agreement) was reached for some of the statements after all participants voted. RESULTS: All the statements and the literature review are presented in the paper, together with their correspondent grade of evidence and the voting results. Based on >80% voting agreement, a number of 22 recommendations were postulated regarding the diagnosis and treatment of GERD-induced respiratory symptoms. The experts considered that GERD may cause bronchial asthma and chronic cough in an important number of patients through micro-aspiration and vagal-mediated tracheobronchial reflex. GERD should be suspected in patients with asthma with suboptimal controlled or after exclusion of other causes, also in nocturnal refractory cough which needs gastroenterological investigations to confirm the diagnosis. Therapeutic test with double dose proton pump inhibitors (PPI) for 3 months is also useful. GERD induced respiratory conditions are difficult to treat; however,proton pump inhibitors and laparoscopic Nissen fundoplication are endorsed for therapy. CONCLUSIONS: This guideline could be useful for the multidisciplinary management of GERD with respiratory symptoms in current practice.

Smoking Obstructive Sleep Apnea: Arguments for a Distinctive Phenotype and a Personalized Intervention.

BACKGROUND: This is the first study that aims to define smoking, with obstructive sleep apnea (OSA), as a phenotype (SOSA). Moreover, we wanted to demonstrate the deleterious effects of the continuation of smoking on OSA. METHODS: The cross-sectional study highlighted four dimensions of SOSA: the demographic and anthropometric features, the symptoms, the comorbidities, and the sleep study parameters. This study compared these characteristics between current smokers (CS), those who have never smoked (NS), and ex-smokers (ES) with OSA. RESULTS: More men (83.95% in CS, versus 66.67% in NS) and an earlier onset of OSA (average age = 50.05 in CS, versus 52.26 in NS, p = 0.04) were recorded among CS. The distinguishing symptom of CS was daytime sleepiness, with an Epworth score that was significantly higher than in NS. Chronic obstructive pulmonary disease (COPD) was significantly more prevalent in CS (38.27%) than in NS (1.51%) (p < 0.001). The severity of OSA, consisting of a higher apnea-hypopnea index, a higher oxygen desaturation index, and a longer time spent below 90% oxygen saturation during sleep was significantly influenced by smoking. CONCLUSIONS: The SOSA phenotype includes younger male patients with a higher waist circumference, suggesting central obesity. They have a higher prevalence of COPD and a greater severity of OSA, in correlation with the number of pack-years of smoking.

Primary Non-Hodgkin Uterine Lymphoma of the Cervix: A Literature Review.

Introduction: Non-Hodgkin lymphomas (NHL) comprise 85% of the total lymphomas diagnosed, with the histological type of diffuse large B-cell lymphomas (DLBCL) being the most prevalent in adults. In about 40% of cases, the location is extranodal. Uterine cervix lymphomas of this type are extremely rare (0.5-1.5%) and represent a diagnostic challenge. A case of DLBCL of the cervix is presented here along with a review of the literature. Materials and methods: A 75-year-old patient was referred with a bleeding vegetant tumour occupying her entire vagina. The histological and pathological investigations performed following the tumour biopsy indicated a malignant, diffuse, vaguely nodular lymphoid tumour proliferation. The immunohistochemistry results were in favour of a diffuse B-cell non-Hodgkin lymphoma (DLBCL). CHOP (Cyclophosphamide, Hydroxydaunorubicin (also called doxorubicin or adriamycin), Oncovin (vincristine), Prednisone or Prednisolone) polychemotherapy and radiotherapy were effective and resulted in tumour regression (from 3.4 cm to tumour disappearance, with the cervix returning to normal size). Conclusions: The uterine cervix lymphoma prognosis is more conservative than that for a nodal lymphoma, mainly due to a later diagnosis determined via immunohistochemistry. Chemotherapy is the main treatment.

Treatment of fibrous dysplasia: focus on denosumab.

INTRODUCTION: Fibrous dysplasia (FD) is a rare bone disease that is associated with various endocrine conditions, such as McCune Albright syndrome. It manifests as abnormal osteolysis, multiple fractures, or deformities that are reported during disease course. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) pathway is upregulated in FD and can be targeted with denosumab, a blocking monoclonal antibody. AREAS COVERED: Preclinical and clinical data on the scientific rationale for using denosumab in FD and on the efficacy and safety of this therapy for this condition have been reviewed, in addition to other therapies. EXPERT OPINION: Denosumab is a potential therapeutic agent against FD. A combined synergic approach involving theranostics might increase its therapeutic potential.

Inhaled interferons beta and SARS-COV2 infection: a preliminary therapeutic perspective.

INTRODUCTION: SARS-COV2 infection represents a therapeutic challenge due to the limited number of effective therapies available and due to the fact that it is not clear which host response in terms of inflammation pattern is the most predictive for an optimal (and rapid) recovery. Interferon ß pathway is impaired in SARS-COV2 infection and this is associated with a bigger disease burden. Exogenous inhaled interferon might be beneficial in this setting. AREAS COVERED: Nebulized interferon-ß is currently investigated as a potential therapy for SARS-COV2 because the available data from a phase II study demonstrate that this medication is able to accelerate the recovery from disease. EXPERT OPINION: Further clinical studies are needed in order to better document the efficacy of this therapy especially in severe forms of COVID-19, the optimal duration of therapy and if such a medication is appropriate for domiciliary use. Also combined regimens with antivirals or with compounds which are able to enhance the endogenous production of interferon might be of promise.

COVID-19 vaccination in patients with multiple sclerosis receiving disease-modifying therapies: pragmatic issues.

The SARS-COV-2 pandemic has been a global public health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes management problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown variability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies. Existing data on the efficacy of COVID-19 vaccination in patients with MS undergoing disease-modifying treatment are summarized and critically evaluated in this article.

Marine-Derived Compounds for the Potential Treatment of Glucocorticoid Resistance in Severe Asthma.

One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets. On the other hand, in the last decade, many studies described the potentially anti-inflammatory effects of marine-derived biologically active compounds. Analyzing the underlying anti-inflammatory mechanisms of action for these marine-derived biologically active compounds, we observed some of the targeted pathogenic molecular mechanisms similar to those described in glucocorticoid (GC) resistant asthma. This article gathers the marine-derived compounds targeting pathogenic molecular mechanism involved in GC resistant asthma and provides a basis for the development of effective marine-derived drugs.

Challenges in Diagnosing Occupational Chronic Obstructive Pulmonary Disease.

Occupational chronic obstructive pulmonary disease (oCOPD) represents 15-20% of the global burden of this disease. Even if industrial bronchitis has long been known, new occupational hazards continue to emerge and enlarge the number of people exposed to risk. This review discusses the challenges related to the early detection of oCOPD, in the context of new exposures and of limited usage of methods for an efficient disease occupational screening. It underlines that a better translation into clinical practice of the new methods for lung function impairment measurements, imaging techniques, or the use of serum or exhaled breath inflammation biomarkers could add significant value in the early detection of oCOPD. Such an approach would increase the chance to stop exposure at an earlier moment and to prevent or at least slow down the further deterioration of the lung function as a result of exposure to occupational (inhaled) hazards.

Frailty, a Dimension of Impaired Functional Status in Advanced COPD: Utility and Clinical Applicability.

Background and Objectives: In advanced chronic obstructive pulmonary disease (COPD), functional status is significantly impaired mainly as a result of disease related respiratory symptoms such as dyspnea or as a result of fatigue, which is the extra-respiratory symptom the most prevalent in this setting. "Physical" frailty, considered to be an aging phenotype, has defining traits that can also be considered when studying impaired functional status, but little is known about this relationship in advanced COPD. This review discusses the relevance of this type of frailty in advanced COPD and evaluates it utility and its clinical applicability as a potential outcome measure in palliative care for COPD. Materials and Methods: A conceptual review on the functional status as an outcome measure of mortality and morbidity in COPD, and an update on the definition and traits of frailty. Results: Data on the prognostic role of frailty in COPD are rather limited, but individual data on traits of frailty demonstrating their relationship with mortality and morbidity in advanced COPD are available and supportive. Conclusions: Frailty assessment in COPD patients is becoming a relevant issue not only for its potential prognostic value for increased morbidity or for mortality, but also for its potential role as a measure of functional status in palliative care for advanced COPD.

Corticosteroids in SARS-COV2 infection: certainties and uncertainties in clinical practice.

INTRODUCTION: The SARS-COV-2 pandemic is a worldwide public health problem due to the large medical burden and limited number of therapies available. Corticosteroids have a rather unclear efficacy in viral non-SARS-COV-2 pneumonias and therefore their use is not universally recommended. In SARS-COV-2 pneumonia however, it is expected that they can reduce the deleterious consequences of the virus-related systemic inflammation. AREAS COVERED: a MEDLINE search covering the period 1995-2020 was completed to identify relevant papers. SARS-COV-2 pathogenesis is very complex and is represented by the interplay of many cytokine-driven inflammation pathways. Its most severe form so called cytokine storm, is an exaggerate reaction of the host infected by the virus rapidly resulting in multiple organ dysfunction (MODS). Corticosteroids have the potential to blunt the inflammation response in such patients, but their efficacy is not the same for all patients. Further on the certainties and uncertainties regarding the efficacy of this therapy in SARS-COV-2 pneumonia are discussed. EXPERT OPINION: In patients with severe SARS-COV-2 pneumonia, corticosteroids can be efficacious, but it is still not clear if they can be safely used in patients with comorbid cardiovascular disease or how the optimal duration of therapy can be established.

Pharmacological strategies for smoking cessation in patients with chronic obstructive pulmonary disease: a pragmatic review.

Introduction: Chronic obstructive pulmonary disease (COPD) is progressive inflammatory disease of the lungs in which smoking plays a significant pathogenic role. Smoking cessation is the only therapeutic intervention which was demonstrated to interfere with disease progression. Smoking cessation intervention can benefit from pharmacological therapies such as nicotine replacement therapies, bupropion, or varenicline which can be given individually or in combination, their effectiveness being demonstrated in various clinical trials enrolling COPD patients.Areas covered: The authors provide a pragmatic discussion of the clinical data of the main studies evaluating therapies for smoking cessation within COPD starting with the seminal Lung Health Study and continuing with more recent ones.Expert opinion: Smoking cessation is one of the most difficult therapeutic interventions in COPD, despite having the highest impact on disease progression and despite the demonstrated benefit of the discussed pharmacological therapies. Potential approaches to maximize its chance of success might be represented by prolonging the time of administration, combinational options, or sequential pharmacotherapy.

Checkpoint inhibitors in NSCLC for the elderly: current challenges and perspectives.

Introduction: In the elderly non-small cell lung cancer (NSCLC) is more commonly diagnosed in advanced stages. Conservative therapy including chemotherapy in this age group might be challenging because one of the criteria for its indication is the appropriate functional status, and in the elderly this is more difficult to ascertain. Checkpoint inhibitors are recent therapies found to be effective alone or in combinations in patients with advanced NSCLC, but little is known about their efficacy and their safety in such patients.Areas covered: We review clinical studies of checkpoint inhibitors in patients with advanced NSCLC in an attempt to identify peculiarities related to their use in the elderly. The clinical studies discussed enrolled a significant proportion of elderly patients and for some compounds, post-hoc analysis in the elderly was performed. Efficacy data supports the use of such compounds in the elderly and the safety profile is acceptable for all molecules discussed.Expert opinion: In the elderly with advanced NSCLC, checkpoint inhibitors are efficacious and well tolerated and may be appropriate for use in patients with an increased impaired functional status. Furthermore, in this category of patients this therapy may be used as a neoadjuvant therapy in order to improve the resectability of the tumor.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Pharmacotherapy options in pulmonary alveolar proteinosis.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a heterogeneous group of rare diseases characterized by the abnormal production and impaired degradation of pulmonary surfactant as a result of malfunctioning of alveolar macrophages. This is due to the downstream dysregulation of the GM-CSF pathway, which can be caused by specific autoantibodies (autoimmune, aPAP formerly known as idiopathic iPAP), direct injury to alveolar macrophages (e.g. by toxic inhaled agents.), or by genetic defects (hereditary or congenital PAP). Few pharmacotherapy options are currently available to treat this disease. AREA COVERED: The authors discuss the exogenous administration of GM-CSF, rituximab, and the potential role of cholesterol lowering medications in this review. The authors, furthermore, provide their opinion on the available pharmacotherapeutic options and give their future perspectives. EXPERT OPINION: Inhaled GM-CSF remains the most commonly used therapy in patients with iPAP but other inhaled therapies such as PPARγ activators should be considered, especially in patients who are partially responsive or unresponsive to traditional treatments.