The Effect of Continuous Positive Airway Pressure (CPAP) Therapy on Serum Caspase-3 Level in Patients with Obstructive Sleep Apnea (OSA).

INTRODUCTION: Intermittent hypoxemia has an important role in the physiopathogenesis of obstructive sleep apnea (OSA) complications. Increased apoptosis due to intermittent hypoxemia may be an important clinical entity in OSA. In this study, we aimed to evaluate caspase-3 enzyme level, which is an indirect marker of increased apoptosis in patients with OSA and to evaluate the effect of OSA treatment with continuous positive airway pressure on caspase-3 enzyme level. MATERIALS AND METHODS: This study included 141 consecutive patients admitted to the sleep-disordered breathing laboratory within 6 months. Caspase-3 was measured in routine blood samples obtained on the morning of polysomnography (PSG) performed at night. The compliance of the patients to CPAP treatment was evaluated and caspase-3 levels were checked again after treatment. RESULTS: A total of 141 patients, 39 females (27,7%) and 102 males (72,3%) were included in the study. The mean age of the patients was 49 ± 12 years (min-17, max-77). According to PSG results, OSA was detected in 95.7% (135/141) of the cases. Mild OSA was 35 (24.8%), moderate OSA 39 (27.7%) and severe OSA 61 (43.3%) cases. Median caspase-3 enzyme levels were similar in men and women in the study group. There was no statistically significant difference in hemogram parameters and caspase-3 enzyme levels between the groups divided according to the presence and severity of OSA. It was determined that caspase-3 enzyme level did not change significantly after 3 months of CPAP treatment in OSA compared to pretreatment. Caspase-3 was found to have a negative correlation with both the percentage of daily use of CPAP therapy and the percentage of CPAP device use for more than 1 h per night. It was found that the control caspase-3 level decreased statistically significantly as the percentage of daily use of CPAP therapy increased (r = -0.397, p = 0.030). It was found that the control caspase-3 level decreased statistically significantly as the percentage of CPAP therapy use for more than 1 h per night increased (r = -0.411, p = 0.024). CONCLUSION: The results of this study did not reveal a relationship between the severity of OSA and caspase-3 levels. However, blood caspase-3 levels decreased as treatment compliance increased, suggesting that CPAP treatment may correct increased apoptosis in OSA. There is a need for more comprehensive studies on this issue.

An Investigation of Latex Sensitivity and Respiratory Complaints in Workers in a Rubber-Based Material Manufacturing Industry.

OBJECTIVE: To present study aimed to investigate the prevalence of latex sensitivity in a workplace that produced rubber-based vehicle seals. METHOD: The serum latex-specific IgE levels, respiratory complaints, PFT, serum interleukin (IL)-4, IL-5, IL-8, IL-10, IL-13 levels of all male workers (n = 108) exposed to latex in the workplace, which produced rubber seals, were compared with the control group (n = 52). RESULTS: The rates of latex-specific IgE >0.10 kU/L in the workers and control group were 12.3% and 4.1%, respectively ( P = 0.147). There was no difference in IL-4, IL-5, IL-10, and IL-13 levels between latex-specific IgE-positive, and -negative participants. CONCLUSION: Latex sensitivity was higher in workers who used rubber as a raw material than in the control group but it was not statistically significant.

Evaluation of both expression and serum protein levels of caspase-8 and mitogen-activated protein kinase 1 genes in patients with different severities of COVID-19 infection.

AIM: The current study aimed to evaluate the effects of caspase-8 (CASP8) and mitogen-activated protein kinase 1 (MAPK1) gene expression levels and their products on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A total of 40 patients (men, 15 [37.5%]; women, 25 [62.5%]) with COVID-19 infection were included in the current study. The patients were divided into four main groups based on disease severity: mild (n = 7), moderate (n = 10), severe (n = 14), and critical (n = 9). Individuals aged < 18 years and pregnant women were excluded. Patients were classified according to the World Health Organization (WHO) classification system (WHO/2019-nCoV/clinical/2021.1). RESULTS: Considering all groups, statistically significant differences were detected among all groups for both CASP82-ΔΔCt (p = 0.006) and MAPK1 2-ΔΔCt values (p = 0.015). Moreover, statistically significant differences were detected between mild and moderate (p = 0.013), moderate and critical (p = 0.018), and severe and critical (p = 0.023) groups for lymphocytes. CONCLUSION: The CASP8/MAPK1 expression levels and/or its products are essential in preventing injury caused by COVID-19 infection. They play crucial roles in maintaining cellular homeostasis and viability. Furthermore, CASP8/MAPK1 levels can provide information about disease severity.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

Characteristics of our hypoxemic COVID-19 pneumonia patients receiving corticosteroids and mortality-associated factors.

BACKGROUND: COVID-19 is a disease associated with diffuse lung injury that has no proven effective treatment yet. It is thought that glucocorticoids may reduce inflammation-mediated lung injury, disease progression, and mortality. We aimed to evaluate our patient's characteristics and treatment outcomes who received corticosteroids for COVID-19 pneumonia. METHODS: We conducted a multicenter retrospective study and reviewed 517 patients admitted due to COVID-19 pneumonia who were hypoxemic and administered steroids regarding demographic, laboratory, and radiological characteristics, treatment response, and mortality-associated factors. RESULTS: Of our 517 patients with COVID-19 pneumonia who were hypoxemic and received corticosteroids, the mortality rate was 24.4% (n = 126). The evaluation of mortality-associated factors revealed that age, comorbidities, a CURB-65 score of ≥ 2, higher SOFA scores, presence of MAS, high doses of steroids, type of steroids, COVID-19 treatment, stay in the intensive care unit, high levels of d-dimer, CRP, ferritin, and troponin, and renal dysfunction were associated with mortality. CONCLUSION: Due to high starting and average steroid doses are more associated with mortality, high-dose steroid administration should be avoided. We believe that knowing the factors associated with mortality in these cases is essential for close follow-up. The use of CURB-65 and SOFA scores can predict prognosis in COVID-19 pneumonia.

Clinical and polysomnographic evaluation of sleep-related breathing disorders in patients with sarcoidosis.

OBJECTIVE: This study aimed to evaluate the frequency of obstructive sleep apnea (OSA) in patients with sarcoidosis and related clinical factors. MATERIALS AND METHOD: Consecutive patients diagnosed with sarcoidosis in our clinic were evaluated for OSA risk during sleep using the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Pittsburgh Sleep Quality Index, Berlin questionnaire, STOP and STOP-BANG questionnaires, and polysomnography (PSG). RESULTS: A total of 60 sarcoidosis patients (mean age: 50 ± 11 years, 45 (75%) women) were included in the study. Polysomnography was performed in 54 cases and revealed the diagnosis of OSA in 70% (38/54) of the patients. The mean age was higher in patients with sarcoidosis and OSA (54 ± 11 vs. 47 ± 13, p = 0.041) and body mass index values were significantly higher as well (31.9 ± 4.4 vs, 29.0 ± 4.6 kg/m2, p = 0.034). Polysomnography revealed a higher rate of OSA in patients with sarcoidosis who had high-risk scores in Pittsburgh Sleep Quality Index, STOP questionnaire, and STOP-BANG questionnaire (p = 0.024, p < 0.001, and p < 0.001, respectively). Based on polysomnography, OSA was detected in 39% (5/13) with stage 1 sarcoidosis, 78% (28/36) with stage 2, and in all cases (5/5) with stage 3. OSA frequency and apnea-hypopnea index (AHI) were determined to increase with advanced sarcoidosis stage (p = 0.003, p = 0.043, respectively). AHI was positively correlated with sarcoidosis stage (p = 0.003, r = 0.391). The prevalence of OSA was significantly higher in patients receiving treatment compared to treatment-naïve patients (88% vs. 57%, p = 0.018). Multivariate logistic regression analysis revealed the stage of the disease (p = 0.026) to be the single independent risk factor associated with increased risk of OSA in patients with sarcoidosis. CONCLUSION: High rates of OSA were detected in sarcoidosis, increasing with the advanced disease stage. The findings suggest that patients with sarcoidosis and advanced age, obesity, steroid treatment, and involvement of lung parenchyma (stages 2 and 3) should be evaluated for OSA risk. Further investigations are needed to establish the potential causes of the high prevalence of OSA in sarcoidosis.

The evaluation of both the expression and serum protein levels of Caspase-3 gene in patients with different degrees of SARS-CoV2 infection.

To evaluate the effects of Caspase-3 (CASP3) gene expression and serum levels on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 41 individuals (male: 21; female: 20) with SARS-CoV-2 infection were included in the current study. Hemograms were examined from patient blood samples, and CASP3 gene expression levels were detected. Also, human CASP3 levels were determined from the serum samples of patients. The mean age of patients was 56.220 ± 18.937 years. Significant differences were detected among all groups for CASP3  2-ΔΔCt (p = 0.014) and CASP3 concentration (p = 0.024). The relationship between CASP3 2-ΔΔCt levels and hemoglobin (p = 0.023), between CASP3 2-ΔΔCt levels and C-reactive protein (CRP) (p = 0.001), between CASP3 2-ΔΔCt levels and ferritin (p = 0.003), between CASP3 2-ΔΔCt levels and lactate dehydrogenase (p = 0.001), and between CASP3 2-ΔΔCt levels and SpO2 (p = 0.006) were statistically significant. Also, the relationship between CASP3 concentration levels and SpO2 was statistically significant (p < 0.046). The CASP3 gene and/or its products have an important function to prevent injury caused by SARS-CoV-2 infection. They play crucial roles in maintaining cellular homeostasis and viability. Perhaps CASP3 levels may provide information about the severity of the disease.

Comparison of pirfenidone and corticosteroid treatments at the COVID-19 pneumonia with the guide of artificial intelligence supported thoracic computed tomography.

AIM: We aimed to investigate the effect of short-term pirfenidone treatment on prolonged COVID-19 pneumonia. METHOD: Hospital files of patients hospitalised with a diagnosis of critical COVID-19 pneumonia from November 2020 to March 2021 were retrospectively reviewed. Chest computed tomography images taken both before treatment and 2 months after treatment, demographic characteristics and laboratory parameters of patients receiving pirfenidone + methylprednisolone (n = 13) and only methylprednisolones (n = 9) were recorded. Pulmonary function tests were performed after the second month of the treatment. CT involvement rates were determined by machine learning. RESULTS: A total of 22 patients, 13 of whom (59.1%) were using methylprednisolone + pirfenidone and 9 of whom (40.9%) were using only methylprednisolone were included. When the blood gas parameters and pulmonary function tests of the patients were compared at the end of the second month, it was found that the FEV1, FEV1%, FVC and FVC% values were statistically significantly higher in the methylprednisolone + pirfenidone group compared with the methylprednisolone group (P = .025, P = .012, P = .026 and P = .017, respectively). When the rates of change in CT scans at diagnosis and second month of treatment were examined, it was found that the involvement rates in the methylprednisolone + pirfenidone group were statistically significantly decreased (P < .001). CONCLUSION: Antifibrotic agents can reduce fibrosis that may develop in the future. These can also help dose reduction and/or non-use strategy for methylprednisolone therapy, which has many side effects. Further large series and randomised controlled studies are needed on this subject.

COVID-19 related acute respiratory distress syndrome: Pathological, radiological and clinical concordance.

Severe coronavirus 2019 disease (COVID-19) represents viral pneumonia from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to acute respiratory distress syndrome (ARDS). However, when ARDS occurs as part of COVID-19, it has different features. The strategy of breathing support is very important in treating COVID-19 related ARDS (CARDS). Though it meets the CARDS Berlin definition, COVID-19 pneumonia is a specific disease with different phenotypes. Recently, it has been suggested that CARDS has two phenotypes, type L (Type 1 or non-ARDS) and type H (Type 2, ARDS), and these phenotypes respond differently to respiratory support treatments. In this review, after mentioning the pathophysiology and radiological relationship of CARDS, the definition and treatment approaches of two different forms of CARDS were discussed.

Corticosteroid use in COVID-19 pneumonia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has a 1-2% fatality rate, where no specific treatment has yet been defined. Although corticosteroids are recommended for selected COVID-19 patients without acute respiratory distress syndrome (ARDS) and septic shock, there is no consensus regarding patient subgroups, dose, and duration. In this study, it was aimed to examine the contribution of corticosteroid treatment to the management of COVID-19 pneumonia without ARDS, septic shock both in acute and recovery setting. MATERIALS AND METHODS: The study population was divided into two as those who used corticosteroids during the recovery phase (who did not develop sufficient radiological or clinical improvement) and those who did so during the activation phase (non-ARDS/septic shock condition, clinical, laboratory or radiological progression). RESULT: We identified 47 patients, 26 of which were males, and mean age was 60.5 ± 16.5 years. Seventeen patients were found to receive corticosteroids during the recovery phase and the rest (n= 30) during the activation period. After corticosteroid therapy, we found reduction of increased pre-treatment levels of D-dimer, ferritin, fibrinogen, CRP, increment of decreased pre-treatment lymphocyte count and saturation. Complete symptomatic improvement was detected in 6.9% and 17.6% of the patients in the activation phase and recovery phase, respectively. Complete radiological improvement was found in 11.5% and 35.3% of the patients in the activation phase and recovery phase, respectively. While corticosteroid treatment was initiated on day 4.2 ± 2.6 and continued for a mean of 5.9 ± 2.8 days in the activation group, it was started on day 8.1 ± 11.3 and administered for 7.8 ± 3.8 days in the recovery group. In both groups, methylprednisolone was given at a median dose of 40 mg/day. CONCLUSIONS: Short-term low-dose corticosteroid therapy may improve clinical, radiological, laboratory outcomes in the management of COVID-19 pneumonia during the activation period without ARDS and non-septic shock and during recovery period with no satisfactory response. Further randomized controlled studies will be useful in demonstrating its efficacy.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Endogenous Carboxyhemoglobin Concentrations in Predicting Prognosis of Patients with COVID-19 Pneumonia.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has caused great difficulties in providing healthcare services worldwide. Accurate and useful indicators are needed for the effective use of resources. Carbon monoxide (CO) is also produced endogenously without exogenous exposure. Studies confirm that endogenous CO increases in conditions such as pneumonia, sepsis, and trauma. This study aimed to compare patients diagnosed with COVID-19 pneumonia and healthy people to reveal whether endogenous carboxyhemoglobin (COHb) levels differ. It was also to determine whether it could be a helpful indicator for the clinician in predicting disease severity in combating the COVID-19 pandemic. METHODS: The study included 72 patients admitted to the hospital during the COVID-19 pandemic and diagnosed with COVID-19 pneumonia and a control group of 75 healthy people. The research data was collected retrospectively in a tertiary emergency department. The patients' demographic data, pneumonia severity index (PSI) score, CURB-65 score, 30-day mortality, hospitalization, need for mechanical ventilation (MV), and COHb levels were recorded. RESULTS: While the COHb level was 0.9% (min-max, 0.1 - 4.0) in patients with COVID-19 pneumonia, it was 1% (min-max, 0.1 - 2.6) in the control group. No significant difference was found between the patients and the control group in terms of COHb levels (p = 0.341). Also, there was no correlation between COHb levels and PSI and CURB-65 scores. No significant difference was detected between COHb levels and patients diagnosed with COVID-19 pneumonia in terms of mortality, need for MV, or hospitalization (p > 0.05). CONCLUSIONS: We concluded that COHb levels alone could not be used to diagnose COVID-19 pneumonia or predict disease severity. Besides, in COVID-19 pneumonia, the COHb level was not a useful indicator of mortality, need for MV, or hospitalization decision. Further studies are needed to find useful indicators to assist clinicians in their decision-making process in tackling the COVID-19 pandemic.

The role of mesenchymal stem cells in COVID-19 treatment.

The novel coronavirus (SARS-CoV-2) pandemic has created a sense of global panic and the medical community started to search for rapid answers. Pharmaceuticals and research labs across the world are racing to find vaccines and treatments for the new coronavirus, using a variety of different technological ways. With Coronavirus disease (COVID-19), it is observed that asymptomatic symptoms turn out to be severe and fatal. By raising pyrexia, sepsis, acute respiratory distress syndrome (ARDS), and multiple organ failure are observed to develop which are not only associated with coronavirus. The treatment of the virus and the systemic inflammatory response it causes are also very important. The rapid response to infection has been well defined and comprises a complex interaction of cytokine storm, endothelial dysfunction, inflammation, and pathologic coagulation. Since the effective therapies are missing and immunological treatments may be deficient, mesenchymal stem cells (MSCs), by reason of their potent immunomodulatory ability, can have useful results in order to prevent the cytokine storm and reduce morbidity and mortality for COVID-19. The aim of this article is to discuss the potential effect of MSCs types in COVID-19 infection without definite treatment.

Is sarcoidosis related to metabolic syndrome and insulin resistance?

Aim: To investigate the relationship between sarcoidosis and metabolic syndrome (MetS) and insulin resistance (IR).Method: In our study, 47 patients with sarcoidosis who applied to our outpatient clinic and 45 healthy individuals without chronic disease were included. All patients were evaluated for MetS according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) criteria. The presence of three of the five factors defined by ATP III for MetS was accepted as a diagnosis of MetS. IR is calculated using the HOMA-IR index.Results: The mean age of the 47 patients with sarcoidosis was 50.7 ± 12.2 years and the mean age of the 45 control groups was 42.9 ± 14.4 years. Almost 80% of the patients were diagnosed as stage 2 sarcoidosis. Distribution of the patients according to the use of steroid is; almost half of the patients (47%) received steroid previously or recently. Patients with sarcoidosis have a 7.66 relative risk for MetS, whereas they also have a 5.48 relative risk of insulin resistance development.Conclusion: This study shows that MetS is associated with increased sarcoidosis risk. MetS and IR diagnosis was higher in patients with sarcoidosis.

Do the levels of particulate matters less than 10 µm and seasons affect sleep?

Background: There are few studies showing that the increase in particulate matters less than 10 µm (PM10) values increases the apnea-hypopnea index (AHI). We aimed to investigate relationship between air quality parameters and the seasons with the AHI.Methods: This was a retrospective study that included 500 adults. Polysomnography (PSG) was performed on all patients. Oxygen saturation, air temperature, relative humidity, and PM10 values were recorded in Düzce for every year. The parameters of the national air quality network and sleep parameters of 500 individuals hospitalized between 2015 and 2017 were checked.Results: A total of 500 patients were included in the study, of whom 316 (63.2%) were male and 184 (36.8%) were female. While the AHI value of patients who presented during 2016 was 27.5, it had significantly declined to 20.2 in 2017 (p = .024). A significant decline was observed in AHI values of OSA patients from 2016 to 2017 (p = .043). A significant positive correlation was observed between REM-related AHI and relative humidity (r = 0.183, p = .002). Conclusions: This study showed a clear relationship between AHI and PM10 during winter when air pollution parameters are high in the region. PM10 emerged as a parameter that substantially increases the relative risk for OSA.

The effects of non-invasive mechanic ventilator modes on intraocular pressure in COPD patients with hypercapnic respiratory failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is not fully reversible disease that is characterized by progressive restricting airflow. Non-invasive mechanical ventilation (NIMV) treatment can be used in COPD patients who had type 2 respiratory failure. This study aimed to determine the effect of BPAP S/T and AVAPS modes on intraocular pressure (IOP), central corneal thickness (CCT) in 40 type 2 respiratory failure patients with COPD. METHODS: Forty patients with type 2 respiratory failure who were hospitalized between June and December 2018 with the diagnosis of COPD exacerbations were included to the study. Patients followed up without NIMV for 12 hours after the end of exacerbations treatments end. After IOP, visual acuity and CCT were measured in all patients at the same time (11.00 am), same NIMV treatment was applied to the patients for 4 hours (AVAPS-BPAP S/T). Then the measurements were repeated. The effects of these NIMV modes on IOP were evaluated. RESULTS: After NIMV treatment, it was observed that the mean IOP increased statistically significantly (13.3 vs 12.3 mm Hg; P = 0.001). After treatment with NIMV, there was a decrease for CCT close to statistical significance (P = 0.057) CONCLUSION: As a result; increased IOP and thinning of CCT after NIMV treatment has been shown. The type of NIMV and the level of inspiratory pressure needed in hypercapnic respiratory failure seem to affect IOP and it should be cautiously used to increase IOP.