Monocyte-to-High-Density Lipoprotein Cholesterol Ratio: a Candidate Parameter for a Risk Assessment Model in COVID-19.

BACKGROUND: COVID-19 has become a pandemic and threatened human public health across the world. Determining effective predictive biomarkers that can classify patients according to risk levels is critical to identify cases that can potentially progress to severe complications and death with the rapid progression of the disease. Therefore, we aimed to investigate the utility of the monocyte-to-high-density lipoprotein cholesterol ratio (MHR), a recently emerging inflammatory marker, as a clinically useful inflammation-based marker in determining patients at higher risk of decreased overall survival in patients with COVID-19. METHODS: The demographics, laboratory data, and MHR of 127 patients with laboratory confirmed COVID-19 were evaluated in terms of clinical outcomes. The patients discharged from the hospital constituted the survivor group, while those that died were evaluated as the non-survivor group. RESULTS: The MHR values were found to be significantly higher in the non-survivor group compared to the survivors (p < 0.05). The high-density lipoprotein cholesterol (HDL-C) values were significantly lower in the non-survivor group (p < 0.05), while there was no statistically significant difference in the monocyte values (p > 0.05). Spearman's analyses revealed no correlation between the MHR values and white blood cell, neutrophil, ferritin, D-dimer, and C-reactive protein (CRP) in the non-survivor group (p > 0.05). According to the binary logistic regression analysis model, the neutrophil, ferritin, D-dimer, CRP, and MHR values the most significant factors in predicting survival (p = 0.021, p = 0.004, p = 0.000, p = 0.001, and p = 0.016, respectively), and an increase in the neutrophil, ferritin, D-dimer, CRP and MHR values decreased the survival rate by 1.1, 1.5, 1.8, 1.6, and 1.7 times, respectively. CONCLUSIONS: MHR can help predict the severity of the COVID-19 disease and patient outcomes. Therefore, this parameter can serve as a clinically useful and potentially predictive inflammation-based marker for identifying patients with COVID-19 who are at higher risk of decreased overall survival. Considering the serious consequences of the current and possible future pandemics, the establishment of a risk assessment model, including MHR in COVID-19 and similar infections is of vital importance in reducing morbidity and mortality by identifying potential risk factors that can predict the course of the disease.

Ear nose throat-related symptoms with a focus on loss of smell and/or taste in COVID-19 patients.

PURPOSE: To determine the frequency and severity of general and ear nose throat (ENT)- related symptoms, especially smell and/or loss of sense of taste (STL) in COVID-19 disease, as well as to investigate the recovery process of STL. MATERIALS AND METHODS: Patients with a positive COVID-19 diagnosis were given a questionnaire consisting of general questions (age, sex, date of symptoms, smoking history, concomitant diseases), questions about the most obvious symptom at presentation (one option only), the severity and frequency of symptoms (general and ENT), and STL (recovery time and degree of recovery). RESULTS: The study population consisted of 172 patients, 18-65 years old (mean age, 37.8 ± 12.5 years; 51.2% female; 76.2% nonsmokers). Cough (n = 30, 17.4%) and loss of sense of smell (n = 18, 10.4%) were the most obvious general and ENT symptoms, respectively. Eighty-eight patients (51.2%) reported loss of sense of smell, and 81 patients (47.1%) reported loss of sense of taste. The mean recovery times for loss of sense of smell and loss of sense of taste were 8.02 ± 6.41 and 8.20 ± 7.07 days, respectively. The loss of sense of smell and loss of sense of taste were the unique symptoms in four (4.54%) and one (1.23%) patients, respectively. CONCLUSION: STL is a common symptom in COVID-19 and may be the first and/or only symptom of this disease. In patients presenting with STL complaints, surveillance for possible COVID-19 disease and screening tests will facilitate the struggle against the disease.

Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is characterized by diagnosis at an advanced stage, low rate of operability and poor survival. Therefore, there is a need for a biomarker in NSCLC patients to predict the likely outcome and to accurately stratify the patients in terms of the most appropriate treatment modality. To evaluate prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in NSCLC. A total of 124 NSCLC patients (mean ± standard deviation age: 60.7 ± 9.3 years, 94.4% were males) were included in this retrospective study. Data were retrieved from the hospital records. The association of NLR and PLR with clinicopathological factors and overall survival was analyzed. One-year, 2-year and 5-year survival rates were 59.2%, 32.0%, and 16.2%, respectively. Median duration of survival was shorter in patient groups with elevated NLR and PLR. Five-year survival rate was quite lower in patient groups with elevated NLR and PLR. Hazard rate (HR) for mortality was 1.76 (95% confidence interval [CI]: 1.19-2.61, P = .005) for NLR ≥ 3 over NLR < 3. HR was 1.64 (95%CI: 1.11-2.42, P = .013) for PLR ≥ 150 over PLR < 150. Cox-regression analysis revealed that, when adjusted for other independent predictors of survival, NLR and PLR still remain significant predictors of poorer survival. Our findings indicate that elevated pretreatment NLR and PLR are associated with advanced disease and poor survival in NSCLC patients, NLR and PLR values are correlated with each other.

How to Utilize CAT and mMRC Scores to Assess Symptom Status of Patients with COPD in Clinical Practice?

Objective: In this study, we aimed to investigate the compatibility of modified Medical Research Council (mMRC) and COPD assessment test (CAT) scores of chronic obstructive pulmonary disease (COPD) patients in terms of evaluation of their symptom status. Methods: The study was planned as a single-center, cross-sectional study. Statistically four separate receiver operating characteristic (ROC) curves of CAT scoring were generated for mMRC scores of 1 to 4. Results: Two hundred twenty eight patients with stable COPD, mean age 64.2±8.2 and 88.6% male were included. A strong positive correlation was detected between CAT and mMRC (r=0.60, p<0.001). However, it was observed that 32 patients had mMRC<2 but CAT≥10, while 21 patients had CAT<10 but mMRC≥2. Thus, in 53 patients CAT and mMRC scores were not identical in terms of assessed symptom status. According to the ROC analysis, the mMRC scores of 1 to 4 were most compatible with the CAT scores of 10, 10, 15, and 20, respectively. Conclusions: Expanding current data represents that CAT score of 10 could be more compatible with mMRC score of 1. Moreover we think although a high mMRC or CAT score may be sufficient to assign patients to high symptom groups, it is needed to evaluate mMRC and CAT together to assign a patient to a low symptom group. In this way misclassification of the patients with high symptoms due to insufficient symptom evaluation as if they have low symptoms can be prevented.

The clinical use of impulse oscillometry in neuromuscular diseases.

BACKGROUND: The patients with neuromuscular diseases (NMD) are very fragile and it is hard to evaluate respiratory involvement of the primary disease in this group. Therefore, our study aimed to reveal the relationship between pulmonary function tests (PFT) and impulse oscillometry (IOS) and their correlation with respiratory clinical findings in NMD. MATERIAL AND METHODS: A total of 86 consecutive patients with NMD were included. The clinical findings of respiratory involvement, PFT, and IOS results of the patients were analyzed. RESULTS: Forty patients out of 86 were female. There were 29 patients with amyotrophic lateral sclerosis, four patients with myasthenia gravis, and 53 patients with muscular dystrophies/myopathies. According to the PFT results, 47 patients had restrictive PFT. However, there was no difference in IOS parameters when we compared the patients according to restrictions in PFT. A positive correlation was found with FVC %pred and X5. PEF %pred values were positively correlated with X10, X15, and X20, and negatively correlated with AX and R5-20. The patients with worse swallowing capability had increased Rrs levels, and more negative Xrs levels. The shortness of breath led to lower FEV1 %pred., higher R5, AX and R5-20, and also more negative X10, X15, and X35. CONCLUSION: Clinically reported dysphagia, a decreased capability of coughing, and shortness of breath in patients with NMD make Rrs increase in general, but Xrs parameters, which mainly express rib cage elasticity, turn more negative. In patients with NMD, IOS monitoring may help in evaluating the regression in respiratory functions, however, future studies are needed to understand more.

Investigation of the effects of mir-219-1 gene variants on the development of disease in non-small cell lung cancer patients.

Background: Various variants of the miR-219-1 gene are one of the first genes associated with NSCLC prognosis in the literature. Objectives: We aimed to genotype two different variants of the miR-219-1 gene and to investigate to using of the result as a biomarker in the diagnosis and treatment of NSCLC. Materials and Methods: The patients were chosen according to International NSCLC criteria and genomic DNA was isolated from blood (138 patients and 100 healthy individuals). Then qRT-PCR was applied to determine the rs213210 and rs421446 variants of miR-219-1 gene polymorphisms. Allele and genotype frequencies were compared using Pearson's chi-square and Fisher's exact tests test. Results: We found that TT genotype (p=0,381) in rs213210 compared with CC genotype (p=0,165) and CC genotype (p=0,823) in rs421446 compared with TT genotype (p=0,537) did not show a significantly increased risk of NSCLC. There is no relationship between polymorphisms in miR-219-1 and the outcome of NSCLC. Conclusion: miRNA single nucleotide polymorphisms can be used as genetic biomarkers to predict cancer susceptibility, early diagnosis, and prognosis. Our study has shown that two variants of miR-219-1 were not related to NSCLC in the Turkish population. The reason for this can be differences in ethnicity, regions, and background of population and these differences could lead to various outcomes.

Bronchodilator efficacy of tiotropium/formoterol (18/12 µg once daily via a Discair inhaler), tiotropium alone (18 µg by Handihaler) or combined with formoterol (12 µg twice daily by Aerolizer) in adults with moderate-to-severe stable COPD.

Objectives: The bronchodilator efficacy of a once-daily fixed-dose combination of tiotropium/formoterol (18/12 µg administered via a dry-powder inhaler, Discair) [TIO/FORMfixed group] vs a single-dose of tiotropium (18 µg) by Handihaler1 alone [TIOmono group], or combined with formoterol 12 µg twice-daily by Aerolizer2 [TIO/FORMbid group] was compared in patients with moderate-to-severe stable COPD.Methods: COPD patients were randomized (28 patients/group) to receive TIO/FORMfixed, TIOmono, or TIO/FORMbid. AUC for the changes in FEV1 and FVC over a 24-h period; bronchodilator response (100 ml improvement in FEV1) in the first 30 min; maximum changes in FEV1 and FVC; and safety data were recorded. The primary endpoint was to confirm the non-inferiority of TIO/FORMfixed vs TIO/FORMbid in terms of the AUC for the changes in FEV1 over a 24-h period.Results: Changes in AUC0-24h for FEV1 and FVC were similar for TIO/FORMfixed and TIO/FORMbid, and were superior to TIOmono (p < 0.001). A positive bronchodilator response at 30 min was demonstrated in 50%, 64%, and 71% of patients in the TIOmono, TIO/FORMbid, and TIO/FORMfixed groups, respectively (NS). Maximum FEV1 and FVC changes were measured as 0.25/0.41 L, 0.32/0.49 L, and 0.37/0.53 L, for TIOmono, TIO/FORMbid, and TIO/FORMfixed, respectively (FEV1: TIO/FORMfixed vs TIOmono, p = 0.0017 and TIO/FORMfixed vs TIO/FORMbid, p = 0.4846); no differences were recorded between the combination groups.Conclusions: The 24-h bronchodilator efficacy of TIO/FORMfixed 18/12 µg once-daily by Discair3 was non-inferior to a combination of tiotropium 18 µg by Handihaler plus formoterol 12 µg twice-daily by Aerolizer, and superior to tiotropium 18 µg monotherapy by Handihaler.

Bronchodilator Efficacy of a Single-Dose 12/400-µg Formoterol/Budesonide Combination as a Dry Powder for Inhalation Delivered by Discair® in Adult Patients with Moderate-to-Severe Stable COPD: Open-Label, Single-Arm, Phase IV Trial.

BACKGROUND AND OBJECTIVES: A patient-friendly and easy-to-use multi-dose dry powder inhaler, Discair®, has been recently developed. The objective of this study was to evaluate the bronchodilator efficacy of a single-dose 12/400-µg formoterol plus budesonide combination as a dry powder for inhalation delivered by Discair® in adult patients with moderate-to-severe, stable, chronic obstructive pulmonary disease. METHODS: A total of 33 male patients with moderate-to-severe, chronic obstructive pulmonary disease were included in this single-arm, open-label, phase IV trial. The primary efficacy parameters were the average maximum change in forced expiratory volume in 1 s (FEV1, in L) and time to maximum FEV1 response. Absolute and percent change from baseline in FEV1 and forced vital capacity, maximum change and time to peak forced vital capacity response were also evaluated. RESULTS: The mean post-bronchodilator FEV1 maximum value was significantly higher than the pre-bronchodilator baseline FEV1 value [1.66 (standard deviation 0.43) vs. 1.32 (standard deviation 0.35), p < 0.001], with an absolute change of 0.34 (standard deviation 0.18) and a percent change of 26.0 (standard deviation 0.14) from baseline to maximum response. The average time to peak FEV1 response was 3.94 h (standard deviation 2.75), while the standardized area under the response-time curve from 0 to 12 h for FEV1 was 2.72 (standard deviation 1.84). The FEV1 and forced vital capacity values recorded at each time point during the 12-h post-bronchodilator period were also significantly higher than the baseline values (p < 0.001 for each). CONCLUSIONS: Our findings revealed significant changes from baseline in post-bronchodilator peak and average FEV1 and forced vital capacity responses, indicating bronchodilator efficacy of a single-dose 12/400 µg formoterol plus budesonide dry powder formulation delivered by Discair® in patients with chronic obstructive pulmonary disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03028701.

Bronchodilator efficacy of 18 µg once-daily tiotropium inhalation via Discair® versus HandiHaler® in adults with chronic obstructive pulmonary disease: randomized, active-controlled, parallel-group, open-label, Phase IV trial.

PURPOSE: To compare the bronchodilator efficacy of 18 µg once-daily tiotropium inhalation administered via Discair® versus HandiHaler® in adults with moderate-to-severe chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Fifty-eight patients with moderate-to-severe COPD were enrolled in this randomized, active-controlled, parallel-group, open-label, Phase IV non-inferiority trial. Patients were randomly assigned to a test group (n=29, inhalation with Discair) or a reference group (n=29, inhalation with HandiHaler). The primary efficacy parameter was the average maximum change in forced expiratory volume in 1 second (FEV1, in L). Change in forced vital capacity (FVC, in L), %FEV1 and %FVC, the standardized area under the response-time curve (AUC) for the absolute change in FEV1 and FVC, time to onset and peak of response, and safety data were also evaluated. RESULTS: The test inhaler was non-inferior to the reference inhaler in terms of maximum change in FEV1 at 24 h (unadjusted change: 0.0017 L [95% confidence interval [CI]: -0.0777, 0.0812]; change adjusted for time to reach maximum change in FEV1 and smoking in pack-years: 0.0116 L [95% CI: -0.0699, 0.0931]), based on a non-inferiority margin of 0.100 L. There were also no significant differences between the two groups in maximum change in FVC value from baseline (0.3417 L vs 0.4438 L, P=0.113), percent change from baseline (22.235 vs 20.783 for FEV1, P=0.662; 16.719 vs 20.337 for FVC, P=0.257), and AUC0-24 h (2.949 vs 2.833 L for FEV1, P=0.891; 2.897 vs 4.729 L for FVC, P=0.178). There were no adverse events, serious adverse events, or deaths. CONCLUSION: Our findings show that the Discair was non-inferior to the HandiHaler. More specifically, these devices had similar clinical efficacy in terms of time-dependent response over 24 h for patients with moderate-to-severe COPD.