Management of acute exacerbations of COPD in the emergency department and its associations with clinical variables.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause for emergency department (ED) visits. Still, large scale studies that assess the management of AECOPD in the ED are limited. Our aim was to evaluate treatment characteristics of AE-COPD in the ED on a national scale. A prospective study as part of the COPD Israeli survey, conducted between 2017 and 2019, in 13 medical centers. Patients hospitalized with AECOPD were included and interviewed. Clinical data related to their ED and hospital stay were collected. 344 patients were included, 38% females, mean age of 70 ± 11 years. Median (IQR) time to first ED treatment was 59 (23-125) minutes and to admission 293 (173-490) minutes. Delayed ED treatment (> 1 h) was associated with older age (p = 0.01) and lack of a coded diagnosis of COPD in hospital records (p = 0.01). Long ED length-of-stay (> 5 h) was linked with longer hospitalizations (p = 0.01). Routine ED care included inhalations of short-acting bronchodilators (246 patients, 72%) and systemic steroids (188 patients, 55%). Receiving routine ED care was associated with its continuation during hospitalization (p < 0.001). In multivariate analysis, predictors for patients not receiving routine care were obesity (adjusted odds ratio 0.5, 95% CI 0.3-0.8, p = 0.01) and fever (AOR 0.3, 95% CI 0.1-0.6, p < 0.01), while oxygen saturation < 91% was an independent predictor for ED routine treatment (AOR 3.6, 95% CI 2.1-6.3, p < 0.01). Our findings highlight gaps in the treatment of AECOPD in the ED on a national scale, with specific predictors for their occurrence.

Asymptomatic Dysphagia and Aspiration in Patients with Idiopathic Bronchiectasis.

PURPOSE: Although considered contributors to idiopathic bronchiectasis (IB), neither dysphagia nor silent aspiration have been systematically evaluated in IB patients. We aimed to explore the prevalence of asymptomatic dysphagia and silent aspiration in IB patients and to identify parameters predictive of their presence. METHODS: This prospective cohort study included IB patients from our Pulmonary Institute without prior history of dysphagia and without prior dysphagia workup. Swallowing function was assessed by the Eating Assessment Tool (EAT-10) questionnaire and by the Fiberoptic Endoscopic Evaluation of Swallowing (FEES) test. RESULTS: Forty-seven patients (31 females, mean age 67 ± 16 years) were recruited. An EAT-10 score ≥ 3 (risk for swallowing problems) was present in 21 patients (44.6%). Forty-two patients (89.3%) had at least one abnormal swallowing parameter in the FEES test. Six patients (12.7%) had a penetration aspiration score (PAS) in the FEES of at least 6, indicating aspiration. An EAT-10 score of 3 was found to be the ideal cutoff to predict aspiration in the FEES, with a good level of accuracy (area under the curve = 0.78, 95% CI 0.629-0.932, p = 0.03) and sensitivity of 83%. This cutoff also showed a trend towards a more severe disease using the FACED (forced expiratory volume, age, colonization with pseudomonas, extension of lung involvement, dyspnea) score (p = 0.05). CONCLUSION: Dysphagia is prevalent in IB and may be undiagnosed if not specifically sought. We recommend screening all patients with IB for dysphagia by the EAT-10 questionnaire and referring all those with a score of ≥ 3 to formal swallowing assessment.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

Impulse Oscillometry as an Alternative Lung Function Test for Hospitalized Adults.

BACKGROUND: Impulse oscillometry (IOS) is a noninvasive technique that measures lung physiology independently of patient effort. In the present study, we aimed to investigate the utility of IOS parameters in comparison with pulmonary function testing (PFT) among hospitalized subjects, with emphasis on obstructive and small airway diseases. METHODS: Sixty-one subjects hospitalized either with unexplained dyspnea or for pre-surgery evaluation were included in the study. All subjects underwent PFTs and IOS test. The correlation between IOS results and PFTs was examined in different subgroups. The ability of IOS parameters to predict abnormal PFTs was evaluated using the area under the receiver operating characteristic (ROC) curve, and optimal cutoff values were calculated. RESULTS: IOS results were found to correlate with PFT values. Subgroup analysis revealed that these correlations were higher in younger (age < 70) and non-obese (body mass index < 25kg/m2) subjects. The resonant frequency was an independent predictor and had the best predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.732 [95% CI 0.57-0.90], optimal cutoff 17 Hz, 87% sensitivity, 62% specificity) and abnormal forced expiratory flow during the middle half of the FVC maneuver (area under the ROC curve 0.667 [95% CI 0.53-0.81], optimal cutoff 15 Hz, 77% sensitivity, 54% specificity). Area of reactance and the difference in respiratory resistance at 5 Hz and 20 Hz also showed a good predictive ability for abnormal FEV1/FVC (area under the ROC curve 0.716 and 0.730, respectively). CONCLUSIONS: We found that the IOS performed well in diagnosing small airway and obstructive diseases among hospitalized subjects. IOS might serve as an alternative to standard PFTs in non-cooperative or dyspneic hospitalized patients.

The humoral response to COVID-19 vaccinations can predict the booster effect on health care workers-toward personalized vaccinations?

BACKGROUND: Waning immunity after the coronavirus disease 2019 (COVID-19) vaccinations creates the constant need of boosters. Predicting individual responses to booster vaccines can help in its timely administration. We hypothesized that the humoral response to the first two doses of the BNT162b2 vaccine can predict the response to the booster vaccine. METHODS: A prospective cohort of hospital health care workers (HCW) that received three doses of the BNT162b2 vaccine. Participants completed serological tests at 1 and 6 months after the second vaccine dose and 1 month after the third. We analyzed predictive factors of antibody levels after the booster using multivariate regression analyses. RESULTS: From 289 eligible HCW, 89 (31%) completed the follow-up. Mean age was 48 (±10) and 46 (52%) had daily interaction with patients. The mean (±standard deviation) antibody level 1 month after the second vaccine was 223 (±59) AU/ml, and 31 (35%) had a rapid antibody decline (>50%) in 6 months. Low antibody levels 1 month after the second vaccine and a rapid antibody decline were independent predictors of low antibody levels after the booster vaccine. CONCLUSIONS: The characteristics of the humoral response to COVID-19 vaccinations show promise in predicting the humoral response to the booster vaccines.

Transition of care interventions to manage severe COVID-19 in the ambulatory setting: a systematic review.

BACKGROUND: Severe COVID-19, with the need in supplemental oxygen and hospitalization, leads to major burden on patients and healthcare systems. As a result, safe and effective ambulatory treatment strategies for severe COVID-19 are of urgent need. In this systematic review, we aimed to evaluate interventions to transition care to the ambulatory setting for patients with active severe COVID-19 that required supplemental oxygen. METHODS: We searched Medline, Scopus, Web of Science, and DOAJ databases to identify articles with original data published until the 1st of April 2023. Characteristics and outcomes of interventions to transition care to home management were reviewed. Given the heterogeneous settings and outcomes studied, a meta-analysis was not performed. RESULTS: Of the 235 studies identified, 11 observational studies, with 2645 patients, were included. The interventions were initiated from the emergency department, observation units or inpatient units, and included continuous home telemonitoring (n = 8), mobile applications (n = 2), and patient-initiated medical contact (n = 3). Included patients had an overall short length of hospital stay, high readmission rates, and positive patients' feedback. There was a lack of prospective controlled data and cost-effectiveness analyses. CONCLUSION: Our findings highlight the potential in treating severe COVID-19 at the ambulatory setting and the lack of high-quality data in this field. Dedicated medical teams, adjusted monitoring methods, improving clinical trajectory, and correct inclusion settings are needed for safe and effective transition of care.

Management of acute COPD exacerbations in the internal medicine departments in Israel-a national survey.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Acute exacerbations of COPD (AECOPD) drastically affect the clinical course of the disease. We aimed to evaluate the treatment of AECOPD in the internal medicine departments in Israel, nationwide. Methods: The COPD Israeli survey (COPDIS) is the first national survey of patients admitted with AECOPD to internal medicine departments between 2017 and 2019. The survey includes prospective (n = 344) and retrospective (n = 1,166) data from 13 medical centers. We analyzed the pre-hospital, in-hospital, and pre-discharge care. Hospital evaluation, outcomes and discharge recommendations were assessed as well. Results: The mean (±SD) age was 74 (±8) years, and 54% were males. 74% had comorbidities, and 88% had a diagnosis of COPD in their history. 70% of the patients received systemic steroids and antibiotics during their hospitalization, yet upon discharge, a lower rate of antibiotics prescription (10%) was found. Treatment with most long-acting bronchodilators dramatically dropped during admission, compared with their pre-hospital use. Overall, a long-acting bronchodilator (LABD) was used by 47% before admission, 28% in-hospital, and was prescribed to 54% at discharge. The discharge plan included a referral to pulmonary rehabilitation in only 11% and a smoking cessation recommendation in 43% of active smokers. The in-hospital mortality was 3% and the 1-year mortality rate was 25%. In multivariate analysis, performing a chest X-ray (adjusted OR 0.64, 95% CI 0.46-0.90) and prescribing LABD at discharge (AOR 0.73, 95% CI 0.57-0.95) were independent predictors for lower 1-year mortality. Conclusion: Our results demonstrate AECOPD characteristics in Israel, and highlight several important gaps in AECOPD healthcare, which must be addressed to improve patient care.

Transbronchial Cryobiopsy Is Superior to Forceps Biopsy for Diagnosing both Fibrotic and Non-Fibrotic Interstitial Lung Diseases.

BACKGROUND: Interstitial lung disease (ILD) evaluation often requires lung biopsy for definite diagnosis. In recent years, transbronchial cryobiopsy (TBCB) emerged as a procedure with higher diagnostic yield than transbronchial forceps biopsy (TBFB), especially for fibrotic ILDs. Nonetheless, studies comparing these modalities in non-fibrotic ILDs and for specific ILD diagnoses are scarce. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield and safety of TBCB and TBFB in patients with fibrotic and non-fibrotic ILDs. METHOD: An observational retrospective multicenter study including patients with ILD diagnosis by multidisciplinary discussion that underwent TBCB or TBFB between 2017 and 2021. Chest CT scans were reviewed by a chest radiologist. Biopsy specimens were categorized as diagnostic (with specific histological pattern), nondiagnostic, or without lung parenchyma. Nondiagnostic samples were reassessed by a second lung pathologist. TBCB and TBFB diagnostic yields were analyzed by multivariate regression. Procedural complications were evaluated as well. RESULTS: 276 patients were included, 116 (42%) underwent TBCB and 160 (58%) TBFB. Fibrotic ILDs were present in 148 patients (54%). TBCB diagnostic yield was 78% and TBFB 48% (adjusted odds ratio [AOR] 4.2, 95% CI: 2.4-7.6, p < 0.01). The diagnostic yield of TBCB was higher than TBFB among patients with fibrotic ILD (AOR 3.8, p < 0.01), non-fibrotic ILD (AOR 5.8, p < 0.01), and across most ILD diagnoses. TBCB was associated with higher risk for significant bleeding (10% vs. 3%, p < 0.01), but similar risk for pneumothorax. CONCLUSIONS: Diagnostic yield of TBCB was superior to that of TBFB for both fibrotic and non-fibrotic ILDs, and across most diagnoses.

Interactions and clinical implications of serological and respiratory variables 3 months after acute COVID-19.

Medical follow-up of symptomatic patients after acute Coronavirus Disease 2019 (COVID-19) results in major burdens on patients and healthcare systems. The value of serological markers as part of this follow-up remains undetermined. We aimed to evaluate the clinical implications of serological markers for follow-up of acute COVID-19. For this purpose, we conducted an observational cohort study of patients 3 months after acute COVID-19. Participants visited a respiratory-clinic between October 2020 and March 2021, and completed pulmonary function tests (PFTs), serological tests, symptom-related questionnaires, and chest CT scans. Overall, 275 patients were included at a median of 82 days (IQR 64-111) post infection. 162 (59%) patients had diffusing capacity for carbon monoxide corrected for hemoglobin (DLCOc) below 80%, and 69 (25%) had bilateral chest abnormalities on CT scan. In multivariate analysis, anti-S levels were an independent predictor for DLCOc (ß = - 0.14, p = 0.036). Anti-S levels were also associated with severe COVID-19 and older age, and correlated with anti-nucleocapsid (r = 0.30, p < 0.001) and antibodies to receptor binding domain (RBD, r = 0.37, p < 0.001). Other serological variables were not associated with clinical outcomes. In conclusion, symptomatic patients 3-months after COVID-19 had high respiratory symptomatic burden, in which anti-S levels were significantly associated with previous severe COVID-19 and DLCOc.

Real-Life Diagnostic Performance of the Hypersensitivity Pneumonitis Guidelines: A Multicenter Cohort Study.

Hypersensitivity pneumonitis (HP) is a heterogeneous interstitial lung disease (ILD) that may be difficult to confidently diagnose. Recently, the 2020 ATS/JRS/ALAT HP diagnostic guidelines were published, yet data validating their performance in real-life settings are scarce. We aimed to assess the diagnostic performance of the HP guidelines compared to the gold-standard multidisciplinary discussion (MDD). For this purpose, we included consecutive ILD patients that underwent diagnostic bronchoscopy between 2017 and 2020 in three large medical centers. Four diagnostic factors (antigen exposure history, chest computed tomography pattern, bronchoalveolar lavage lymphocyte count, and histology results) were used to assign guidelines-based HP diagnostic confidence levels for each patient. A sensitivity analysis was performed, with MDD diagnosis as the reference standard. Overall, 213 ILD patients were included, 45 (21%) with an MDD diagnosis of HP. The guidelines' moderate (≥70%) confidence threshold produced optimal performance with 73% sensitivity for HP, 89% specificity, and a J-index of 0.62. The area under the receiver operating characteristic curve (AUC) for a correct guidelines-based diagnosis was 0.86. The guidelines had better performance for non-fibrotic than fibrotic HP (AUC 0.92 vs. 0.82). All diagnostic factors, except bronchoalveolar lavage lymphocyte count, were independent predictors for MDD diagnosis of HP in a multivariate analysis. In conclusion, the HP guidelines exhibited a good diagnostic performance compared to MDD diagnosis in real-life setting.

Assessment of a close respiratory follow-up schedule at 3 and 6 months after acute COVID-19 and its related investigations.

BACKGROUND: Respiratory sequela after acute COVID-19 is common and requires medical follow-up. Considering its vast economic impact, there is still no consensus regarding the mid-term follow-up plan after recovery. OBJECTIVE: To evaluate the necessity of a close pulmonary follow-up schedule after acute COVID-19 and its related investigations. METHODS: A prospective cohort study including adult patients after acute COVID-19 pneumonia. Patients were invited or referred to a 3- and 6-month follow-up visits at a large pulmonary institute in a tertiary center. Before each visit, patients completed demographic and clinical questionnaires, pulmonary function tests (PFTs), and chest CT scans. RESULTS: 168 patients were included after completing both visits (medians of 80 and 177 days). Their mean age was 58 ± 15 and 52% recovered from severe or critical COVID-19. Between the two visits, there was no change in DLCOc (mean 73 ± 18 %predicted in both visits) and FVC (mean 90 ± 16 vs. 89 ± 16 %predicted). The COPD assessment tool and modified Medical Research Council scale had inverse correlations with the DLCOc, and similarly did not change between the visits. Occupational exposures were the only factor associated with a change in DLCOc during follow-up (3% decrease, p = 0.04). An improvement in chest CT findings at the second visit was not associated with a change in PFTs. CONCLUSIONS: Most clinical variables did not change during a close follow-up schedule in the first six months after acute COVID-19. Such a follow-up plan does not appear necessary and should be personalized to limit excessive costs and resources.

Nanoparticles in induced sputum - a window to airway inflammation among active smokers.

Aims: To evaluate the role of nanoparticles (NP) in sputum samples of active smokers as markers of inflammation and disease. Materials & methods: 29 active smokers were included (14 with chronic obstructive pulmonary disease [COPD]) and underwent clinical assessment, pulmonary function tests, sputum induction (with NP analysis) and blood sampling. Results: Higher particle and NP concentrations and smaller mean size directly correlated with clinical parameters such as the COPD Assessment Test score and impulse oscillometry results. Similar correlations were found between NPs and increased sputum IL-1ß, IL-6 and TNF-α. Among COPD patients, higher IL-8 and lower IL-10 serum levels also correlated with NP concentrations. Conclusion: This proof-of-concept study shows the potential of sputum NPs as markers of airway inflammation and disease.

What is this article about? Identifying markers of lung inflammation and diseases could offer early diagnosis and treatment. In this study, we questioned whether nanoparticles in the sputum of active smokers correlate with lung inflammation and disease. What were the results? We found that higher nanoparticle concentration in the sputum and lower mean nanoparticle size correlated with different clinical parameters and inflammatory markers. What do the results mean? This proof-of-concept study suggests that nanoparticle analysis in the sputum of active smokers has potential as a marker that correlates with lung inflammation and disease. Our results should encourage additional research in this field to better understand the role of nanoparticles in the diagnosis, prognosis and treatment of active smokers.

One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: A third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination. METHODS: A prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4-6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded. RESULTS: Seventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months. CONCLUSIONS: A third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.

Inhaled CD24-Enriched Exosomes (EXO-CD24) as a Novel Immune Modulator in Respiratory Disease.

Acute Respiratory Distress Syndrome (ARDS) is a major health concern with urgent unmet need for treatment options. There are three million new ARDS cases annually, and the disease's mortality rate is high (35-46%). Cluster of differentiation 24 (CD24), a long-known protein with multifaceted functions, is a small, heavily glycosylated, membrane-anchored protein which functions as an immune checkpoint control. CD24 allows for immune discrimination between Damage-Associated Molecular Patterns and Pathogen-Associated Molecular Patterns derived from pathogens. Exosomes are intraluminal vesicles which play an important role in intercellular communication. Exosomes offer the advantage of targeted delivery, which improves safety and efficacy. The safety and efficacy of EXO-CD24 is promising, as was shown in >180 ARDS patients in phase 1b/2a, phase 2b, and compassionate use. CD24 binds Damage-associated molecular patterns (DAMPs) and inhibits the activation of the NF-ĸB pathway, a pivotal mediator of inflammatory responses. In contrast to anti-inflammatory therapies that are cytokine-specific or steroids that shut down the entire immune system, EXO-CD24 acts upstream, reverting the immune system back to normal activity. Herein, the safety and efficacy of mEXO-CD24 is shown in murine models of several pulmonary diseases (sepsis, allergic asthma, Chronic Obstructive Pulmonary Disease(COPD), fibrosis). EXO CD24 can suppress the hyperinflammatory response in the lungs in several pulmonary diseases with a significant unmet need for treatment options.

The Added Value of Bronchoalveolar Lavage for Pulmonary Tuberculosis Diagnosis in High-Risk Hospitalized Patients with Negative Sputum Samples.

Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative sputum samples, bronchoscopy with bronchoalveolar lavage (BAL) is often sought. Still, evidence of the added value of BAL in this patient population is scarce. To address this issue, we included consecutive HS-PTB patients with negative sputum samples who underwent BAL between 2017 and 2018. Chest X-rays (CXR) and CT scans were evaluated by a chest radiologist blind to the final diagnosis. Independent predictors for PTB were assessed by multivariate regression, using all positive PTB patients between 2017 and 2019 (by sputum or BAL) as a control group (n = 41). Overall, 42 HS-PTB patients were included (mean age 51 ± 9, 36% female). BAL was a viable diagnostic for PTB in three (7%) cases and for other clinically relevant pathogens in six (14%). Independent predictors for PTB were ≥2 sub-acute symptoms (adjusted OR 3.18, 95% CI 1.04-9.8), CXR upper-lobe consolidation (AOR 8.70, 95% CI 2.5-29), and centrilobular nodules in chest CT (AOR 3.96, 95% CI 1.20-13.0, p = 0.02). In conclusion, bronchoscopy with BAL in hospitalized patients with HS-PTB had a 7% added diagnostic value after negative sputum samples. Our findings highlight specific predictors for PTB diagnosis that could be used in future controlled studies to personalize the diagnostic evaluation.

Importance of physician history taking in complementing patient-reported interstitial lung disease questionnaire.

BACKGROUND: Patient-reported interstitial lung disease (ILD) questionnaires are commonly used for the evaluation of ILD patients. However, research to test their performance is scarce. METHODS: This study aimed to assess the performance of the Chest Questionnaire in consecutive ILD patients presenting to a tertiary ILD center. The results of Chest Questionnaires routinely filled by patients were analyzed together with clinical and demographic data retrieved from the patients' medical records. The ability of each questionnaire item to detect positive findings, such as environmental and occupational exposures, was examined relative to any additional findings detected by physician-acquired history. History was obtained by an experienced ILD pulmonologist who had access to the results of the questionnaire during the clinic visit. RESULTS: The final cohort for analysis included 62 patients. Shortness of breath frequency and duration were the questionnaire items with the lowest probability of being filled out by patients. The questionnaire performed well in identifying 96.2% of patients with a positive family history and 90.9% of patients with occupational exposures. However, exposures to mold or birds were frequently missed, self-reported by only 53.1% of exposed patients. Questionnaire's performance was also lower for other exposures associated with ILD (48.3%). An ILD-related exposure was less likely to be identified by the questionnaire in males (p = 0.03), while age had no such effect. CONCLUSIONS: The Chest Questionnaire performed well in several domains, while failing to detect some relevant exposures. Therefore, its use should be accompanied by careful history taking by the physician.

Assessment of Predictors for SARS-CoV-2 Antibodies Decline Rate in Health Care Workers after BNT162b2 Vaccination-Results from a Serological Survey.

Background: SARS-CoV-2 is a novel human pathogen causing Coronavirus Disease 2019 that has caused widespread global mortality and morbidity. Since health workers in Israel were among the first to be vaccinated, we had a unique opportunity to investigate the post-vaccination level of IgG anti-S levels antibodies (Abs) and their dynamics by demographic and professional factors. Methods: Prospective Serological Survey during December 2020−August 2021 at Barzilai Medical Center among 458 health care workers (HCW) followed for 6 months after the second BNT162b2 vaccine dose. Results: Antibody levels before the second dose, and 30, 90 and 180 days after were 57.1 ± 29.2, 223 ± 70.2, 172.8 ± 73.3 and 166.4 ± 100.7 AU/mL, respectively. From GEE analysis, females had higher Abs levels (ß = 26.37 AU/mL, p = 0.002). Age was negatively associated with Abs, with a 1.17 AU/mL decrease for each additional year (p < 0.001). Direct contact with patients was associated with lower Abs by 25.02 AU/mL (p = 0.009) compared to working with no such contact. The average decline rate overall for the study period was 3.0 ± 2.9 AU/mL per week without differences by demographic parameters and was faster during the first 3 months after vaccination than in the subsequent 3 months. Conclusions: All demographic groups experienced a decline in Abs over time, faster during the first 3 months. Findings of overall Abs lower in males, workers with direct contact with patients, and older workers, should be considered for policy-making about choosing priority populations for additional vaccine doses in hospital settings.

Rh2-enriched Korean ginseng (Ginseng Rh2+) inhibits tumor growth and development of metastasis of non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: While there are multiple studies on the anti-tumoral effects of Panax ginseng as active ingredients (one or more ginsenosides derived from the extract) or as a whole plant extract, there is a lack of studies to assess the effects Panax ginseng's of active ingredients combined with the whole plant extract. Our aim was to study the effect of whole ginseng, enriched in the anti-tumoral Rh2 component and other ginsenosides (Ginseng Rh2+), on the metastatic capacity of non-small cell lung cancer (NSCLC). METHODS: We evaluated the effects of Ginseng Rh2+ on survival, migration and motility, induction of apoptosis, and expression of its apoptosis-related proteins in non-small cell lung cancer (NSCLC) cells in vitro and on primary tumor growth and metastatic capacity in a syngeneic mouse lung cancer model in vivo. The effects of Ginseng Rh2+ on NSCLC cells were studied in vitro using: a colorimetric tetrazolium salt (XTT) assay, annexin V-FITC/PI, western blotting, wound healing motility assay, Transwell migration and cell adhesion assays. In vivo, mice were inoculated with Lewis mouse lung carcinoma cells subcutaneously to evaluate local tumor growth, or intravenously to evaluate the effects of Ginseng Rh2+ on development of experimental metastases. Mice were treated by intraperitoneal administration of Ginseng Rh2+ (0.005-0.5 g kg-1) on days 6, 10, and 14 after tumor injection. RESULTS: We found that Ginseng Rh2+ increased the apoptosis of NSCLC cells in vitro, demonstrating dose dependent down-regulation of the Bcl-2 anti-apoptotic gene and concurrent up-regulation of the Bax pro-apoptotic gene. Ginseng Rh2+ inhibited the tumor cells' capacity to attach to the ECM-related matrix and reduced cell migration. In vivo, Ginseng Rh2+ inhibited local tumor growth and reduced the development of experimental lung metastases. CONCLUSION: Our study suggests that Ginseng Rh2+ may potentially be used as a therapeutic agent for treatment of NSCLC.