Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

Lung and kidney perfusion deficits diagnosed by dual-energy computed tomography in patients with COVID-19-related systemic microangiopathy.

OBJECTIVES: There is increasing evidence that thrombotic events occur in patients with coronavirus disease (COVID-19). We evaluated lung and kidney perfusion abnormalities in patients with COVID-19 by dual-energy computed tomography (DECT) and investigated the role of perfusion abnormalities on disease severity as a sign of microvascular obstruction. METHODS: Thirty-one patients with COVID-19 who underwent pulmonary DECT angiography and were suspected of having pulmonary thromboembolism were included. Pulmonary and kidney images were reviewed. Patient characteristics and laboratory findings were compared between those with and without lung perfusion deficits (PDs). RESULTS: DECT images showed PDs in eight patients (25.8%), which were not overlapping with areas of ground-glass opacity or consolidation. Among these patients, two had pulmonary thromboembolism confirmed by CT angiography. Patients with PDs had a longer hospital stay (p = 0.14), higher intensive care unit admission rates (p = 0.02), and more severe disease (p = 0.01). In the PD group, serum ferritin, aspartate aminotransferase, fibrinogen, D-dimer, C-reactive protein, and troponin levels were significantly higher, whereas albumin level was lower (p < 0.05). D-dimer levels ≥ 0.485 µg/L predicted PD with 100% specificity and 87% sensitivity. Renal iodine maps showed heterogeneous enhancement consistent with perfusion abnormalities in 13 patients (50%) with lower sodium levels (p = 0.03). CONCLUSIONS: We found that a large proportion of patients with mild-to-moderate COVID-19 had PDs in their lungs and kidneys, which may be suggestive of the presence of systemic microangiopathy with micro-thrombosis. These findings help in understanding the physiology of hypoxemia and may have implications in the management of patients with COVID-19, such as early indications of thromboprophylaxis or anticoagulants and optimizing oxygenation strategies. KEY POINTS: • Pulmonary perfusion abnormalities in COVID-19 patients, associated with disease severity, can be detected by pulmonary DECT. • A cutoff value of 0.485 µg/L for D-dimer plasma levels predicted lung perfusion deficits with 100% specificity and 87% sensitivity (AUROC, 0.957). • Perfusion abnormalities in the kidney are suggestive of a subclinical systemic microvascular obstruction in these patients.

AI-Based Quantitative CT Analysis of Temporal Changes According to Disease Severity in COVID-19 Pneumonia.

OBJECTIVE: To quantitatively evaluate computed tomography (CT) parameters of coronavirus disease 2019 (COVID-19) pneumonia an artificial intelligence (AI)-based software in different clinical severity groups during the disease course. METHODS: From March 11 to April 15, 2020, 51 patients (age, 18-84 years; 28 men) diagnosed and hospitalized with COVID-19 pneumonia with a total of 116 CT scans were enrolled in the study. Patients were divided into mild (n = 12), moderate (n = 31), and severe (n = 8) groups based on clinical severity. An AI-based quantitative CT analysis, including lung volume, opacity score, opacity volume, percentage of opacity, and mean lung density, was performed in initial and follow-up CTs obtained at different time points. Receiver operating characteristic analysis was performed to find the diagnostic ability of quantitative CT parameters for discriminating severe from nonsevere pneumonia. RESULTS: In baseline assessment, the severe group had significantly higher opacity score, opacity volume, higher percentage of opacity, and higher mean lung density than the moderate group (all P ≤ 0.001). Through consecutive time points, the severe group had a significant decrease in lung volume (P = 0.006), a significant increase in total opacity score (P = 0.003), and percentage of opacity (P = 0.007). A significant increase in total opacity score was also observed for the mild group (P = 0.011). Residual opacities were observed in all groups. The involvement of more than 4 lobes (sensitivity, 100%; specificity, 65.26%), total opacity score greater than 4 (sensitivity, 100%; specificity, 64.21), total opacity volume greater than 337.4 mL (sensitivity, 80.95%; specificity, 84.21%), percentage of opacity greater than 11% (sensitivity, 80.95%; specificity, 88.42%), total high opacity volume greater than 10.5 mL (sensitivity, 95.24%; specificity, 66.32%), percentage of high opacity greater than 0.8% (sensitivity, 85.71%; specificity, 80.00%) and mean lung density HU greater than -705 HU (sensitivity, 57.14%; specificity, 90.53%) were related to severe pneumonia. CONCLUSIONS: An AI-based quantitative CT analysis is an objective tool in demonstrating disease severity and can also assist the clinician in follow-up by providing information about the disease course and prognosis according to different clinical severity groups.

Factors related to oxygen desaturation during flexible bronchoscopy and endobronchial ultrasound.

INTRODUCTION: Oxygen desaturation is a significant event during bronchoscopy. In this study, it was aimed to identify factors related to oxygen desaturation during flexible bronchoscopy (FB) and Endobronchial ultrasound (EBUS). MATERIALS AND METHODS: From 16 April 2019 to 14 February 2020, 196 consecutive patients (146 FB and 50 EBUS) undergoing bronchoscopy were evaluated retrospectively. The patients' oxygen saturations were monitored on admission and during the procedure by finger pulse oximetry. Desaturation was defined as saturation below 90%. Demographic characteristics, comorbidities, types of interventions, vitals before and during the procedure, amount of saturation decline, and sedative agents used were recorded. The data obtained were compared between the desaturated and non-desaturated groups in both FB and EBUS. We evaluated the risk factors for desaturation during bronchoscopic procedures. RESULT: The mean age of those who underwent FB was higher (62 [52-68] years vs. 55 [44-65] years, p= 0.05), and males were more frequent (54%, vs 19.2%, p<0.001) in the desaturated group. In FB, short lavage was more frequent in the non-desaturated group (28.8% vs. 9.5%, p<0.001). In EBUS, hypertension, diabetes mellitus and thyroid diseases were higher, and duration of procedure was longer (p= 0.02, p= 0.04, p= 0.01 and p<0.001 and p= 0.01, respectively), and SpO2 decline during procedures was higher (11% vs. 1% in FB, 18% vs. 3% in EBUS, p<0.001, each) in the desaturated group. CONCLUSIONS: This study suggested that baseline SpO2 and SpO2 decline during procedures as well as sex, hypertension, and concomitant endocrine - metabolic diseases, duration of procedure were factors associated with desaturation in patients who had undergone FB and EBUS.

Clinical implications of fungal isolation from sputum in adult patients with cystic fibrosis

Background/aim: Cystic fibrosis is an autosomal recessive disease with a defect in mucociliary activity that is characterized by recurrent pulmonary infections. Bacterial agents frequently implicated in airway colonization are Haemophilus influenzae, Staphylococcus spp., and Pseudomonas spp. Fungal isolation from sputum is common in adults. However, growth of fungal agent only in sputum culture in patients with cystic fibrosis is insufficient for the diagnosis of fungal diseases. There is limited data about the clinical significance of fungal isolation in sputum cultures. The aim of the study was to investigate the clinical outcomes andsignificance of fungal isolation from sputum samples in adult CF. Materials and methods: This retrospective study included patients who have been admitted between October 2017 and January 2019 in an adult cystic fibrosis unit. Patients were grouped according to fungal pathogenicity as; fungal disease group, colonization group, and nonisolated group. The data of the last one year, including demographics, clinical data, laboratory, treatment modalities, results of cultured bacteria and fungus from sputum samples, respiratory function parameters, frequency of exacerbation, and hospitalizationwere compared between groups. Results: A total of 330 sputum samples from 88 adult patients with CF were collected. Patients were divided into 3 groups, the fungal disease group (n = 10, 11.4%), colonization group (n = 49, 55.7%), and nonisolated group (n = 29, 32.9%). Presence of pulmonary exacerbation, number of admissions to emergency department, and the number of positive cultures for bacteria from sputum were higher in the fungal disease group (p = 0.03, p = 0.01 and p < 0.001). The fungal disease group had higher rate of antibiotics by parenteral routethan other groups (p = 0.001) whereas lung functions were similar. Use of nutritional supplementation and parenteral antibiotherapy were the factors associated with elevated risk of fungal isolation. Conclusion: Frequent use of parenteral antibiotics and use of nutritional supplementation were found to be independent risk factors for fungal isolation from sputum in adult CF.

The comparison of the survival rates of intensive and palliative care units.

INTRODUCTION: Palliative care is a multidisciplinary therapy formed by physical, social, psychological, cultural and spiritual support of patients and families. The aim of the present study is to compare the survival rates of the intensive care unit (ICU) and palliative care unit (PCU). MATERIALS AND METHODS: A retrospective observational cohort study was performed using the database of an intensive care unit. Patients with terminal illness admitted to the intensive care unit or palliative care unit were included in the study. Demographic data, comorbidities, time of admission, discharge and death were recorded. The survival estimation was completed using Kaplan Meier survival analysis. RESULT: A total of 112 patients were included in the study. Patients were divided into two groups where 60 patients (53.6%) were in Group ICU and 52 (46.4%) were in Group PCU. The Kaplan-Meier estimation of survival curves showed that the overall median time was 29 days. This result demonstrated that 50% of the patients was survived longer than 29 days, in which it was 12 days and 38 days for Group ICU and Group PCU, respectively (𝜒2= 3.475, p= 0.062). The cost of either intensive care unit or palliative care unit did not show any difference (p= 0.902). CONCLUSIONS: The present study showed that long-term survival rates are similar in intensive care unit and palliative care unit.

Factors associated with pulmonary function decline of patients in the cystic fibrosis registry of Turkey: A retrospective cohort study.

BACKGROUND: The decline in pulmonary function is a predictor of disease progression in patients with cystic fibrosis (CF). This study aimed to determine the decline rate of percent predicted forced expiratory volume in 1 s (ppFEV1) based on the data of the CF Registry of Turkey. The secondary aim was to investigate the risk factors related to the decline in ppFEV1. METHODS: A retrospective cohort study of CF patients over 6 years old, with pulmonary function data over at least 2 years of follow-up was extracted from the national CF registry for years 2017-2019. Patients were classified according to disease severity and age groups. Multivariate analysis was used to predict the decline in ppFEV1 and to investigate the associated risk factors. RESULTS: A total of 1722 pulmonary function test results were available from 574 patients over the study period. Mean diagnostic age was older and weight for age, height for age, and body mass index z scores were significantly lower in the group of ppFEV1 < 40, while chronic Pseudomonas aeruginosa (p < .001) and mucoid P. aeruginosa colonization (p < .001) were significantly higher in this group (p < .001). Overall mean annual ppFEV1 decline was -0.97% (95% confidence interval [CI] = -0.02 to -1.92%). The mean change of ppFEV1 was significantly higher in the group with ppFEV1 ≥ 70 compared with the other (ppFEV1 < 40 and ppFEV1: 40-69) two groups (p = .004). Chronic P. aeruginosa colonization (odds ratio [OR] = 1.79 95% CI = 1.26-2.54; p = .01) and initial ppFEV1 ≥ 70 (OR = 2.98 95% CI = 1.06-8.36), p = .038) were associated with significant ppFEV1 decline in the whole cohort. CONCLUSIONS: This data analysis recommends close follow-up of patients with normal initial ppFEV1 levels at baseline; advocates for early interventions for P. aeruginosa; and underlines the importance of nutritional interventions to slow down lung disease progression.

A case-control study of the effects of Aspergillus clinical phenotypes on pulmonary functions in patients with cystic fibrosis.

INTRODUCTION: There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively. METHODS: Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up. RESULTS: Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity  (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar. CONCLUSION: Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

BACKGROUND: We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV1) decline and LT candidates without rapid FEV1 decline in the last year to identify a preventable cause in patients with such rapid FEV1 decline. METHODS: All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV1 below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV1 decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. RESULTS: Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV1 in 2017 in Group 1 and between FEV1 values in 2017 and 2018 in Group 2. CONCLUSIONS: There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. METHODS: This retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. RESULTS: In 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. CONCLUSIONS: Patients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.

Association Between Known Close Contact History and Severity of COVID-19 Pneumonia: A Preliminary Evidence Supporting Importance of Filiation.

OBJECTIVE: The role of a known contact history in coronavirus disease 2019 severity in secondary cases is unknown. The study was aimed to investigate the relationship between the close contact history and the severity of the disease in coronavirus disease 2019 pneumonia. MATERIAL AND METHODS: Hospitalized patients diagnosed with coronavirus disease 2019 pneumonia were included. The demo- graphic, clinical, and laboratory data of the patients were collected retrospectively and patients with or without close contact history were analyzed with respect to the severity of pneumonia. RESULTS: In a total of 100 patients with coronavirus disease 2019 pneumonia, 54 (54%) were male and mean age was 42.28 ±17.13 years. Respiratory rate/min (P = .033) was higher, duration of hospitalization (P = .043) was longer, need for oxygen therapy (P < .001), intensive care unit admission (P = .001), and severe pneumonia (P < .001) were higher in the group without a close contact history (n = 50). Male gender (OR, 4.77; 95% CI, 1.06-21.32; P = .041), not having a close contact history (OR, 4.03; 95% CI, 1.00-16.13;P = .049), non-hospital-associated patients (OR, 9.59; 95% CI, 1.47-62.41; P = .018), and dyspnea (OR, 7.58; 95% CI, 1.64-34.93;P = .009) were found to be risk factors for severe pneumonia. CONCLUSION: Known close contact history was associated with non-severe pneumonia and was found to be an independent predic- tor of disease severity in coronavirus disease 2019 pneumonia. The study provides evidence that filiation may prevent severe disease.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

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.

Cuban Blue Scorpion Venom and Lung Carcinoma: Is it Always True What Does Not Kill Me Makes Me Stronger?

Historically snake, scorpion, and hymenoptera venom have been used to treat various diseases. It is well known that alternative and/or complementary treatment options are widely used, especially among cancer patients. The case we describe here has lung carcinoma and received blue scorpion venom as an alternative therapy. A 86 years old male patient was admitted complaining of dyspnea. Thorax computed tomography (CT) showed a mass lesion and intraparenchymal nodules on the left upper lobe. Percutaneous transthoracic biopsy was performed, and the diagnosis was reported to be an epidermoid carcinoma. After the shared decision, A shared decision with the family and oncology specialists, the patient decided to try Cuban blue scorpion venom oral drops. Initially, it was well tolerated. However on the sixth day of treatment, sudden death occurred. Scorpion venom has been considered as a natural source for cancer therapy. Rhopalurus junceus is an endemic scorpion species from Cuba. Although it belongs to the most dangerous species related to human scorpionism, and no fatal stings have been reported. Currently published articles investigate the composition and in vitro anticancer activity of the venom; there are no controlled clinical trials evaluating toxicity or effectiveness. Uncontrolled use of alternative treatment options may lead to unexpected interactions with concomitant medications.

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.

Correlation of thrombosed vessel location and clot burden score with severity of disease and risk stratification in patients with acute pulmonary embolism.

OBJECTIVE: Computed tomography pulmonary angiography (CTPA) is used for the main diagnosis in acute pulmonary embolism (APE). Determining the thrombus location in the pulmonary vascular tree is also important for predicting disease severity. This study aimed to analyze the correlation of the thrombus location and the clot burden with the disease severity and the risk stratification in patients with APE. METHODS: The study included patients with APE diagnosed by CTPA who were admitted to the hospital between January 28, 2016, and July 1, 2019. Data collected were markers of severity in APE, including patient demographics, comorbidities, length of hospital stay, pulmonary embolism severity index (PESI) score, modified PESI score, Wells score, risk stratification according to the American Heart Association, systolic blood pressure (SBP), right ventricle diameter to left ventricle diameter ratio, pulmonary arterial pressure, brain natriuretic peptide, troponin, D-dimer, and plasma lactate levels, and vessel location of the thrombus, clot burden score, ratio of the pulmonary artery trunk diameter/aortic diameter, superior vena cava diameter (SVC) by CTPA, and survival. All parameters were analyzed in correlation with clot load and vessel location. RESULTS: Thrombus vascular location was found to be correlated with risk stratification and negatively correlated with SBP. Simplified Mastora score was correlated with risk stratification, SVC diameter, and D-dimer and negatively correlated with SBP. Occlusion of both the pulmonary artery trunk and any pulmonary artery with thrombus was associated with massive APE. CONCLUSION: The level of the occluded vessel on CTPA may provide the ability to risk-stratify, and the clot burden score may be used for assessing both risk stratification and cardiac strain.

Risk factors of unfavorable outcomes in chronic obstructive pulmonary disease patients treated with noninvasive ventilation for acute hypercapnic respiratory failure.

BACKGROUND-AIM: Noninvasive mechanical ventilation (NIV) failure rate is reported to be 5%-60% of intensive care unit (ICU) patients. Despite all precautions and well-known reasons, the risk factors of NIV failure are unclear for chronic obstructive pulmonary disease (COPD) with acute respiratory failure (ARF). The aim of this study was to examine risk factors for NIV failure in COPD patients with ARF, other than well defined. METHODS: The retrospective cohort study was done in ICU of a chest disease hospital. All consecutive COPD patients with hypercapnic ARF were enrolled in study. Demographics, comorbidities, arterial blood gases, reasons of ARF and length of ICU stay were recorded. NIV success was defined as discharge from ICU and NIV failure was defined as need for intubation or died during NIV. Patients were grouped into; NIV failure and success. The groups were compared and NIV failure risk factors were analyzed. RESULTS: About 265 NIV success and 142 NIV failure patients were enrolled into the study. Logistic regression test showed the risk factors for NIV failure; higher APACHE-II (≥ 29) (OR:11.71, CI95%4.39-31.18, P < 0.001), culture positivity (OR:7.59, CI95%3.21-17.92, P < 0.001), sepsis (OR:6.53 CI95%3.59-11.85, P < 0.001) and pneumonia (OR:3.71 CI95%0.60-2.02, P < 0.043) significantly. COPD patients using home-based NIV had less risk for NIV failure (OR: 0.49 CI95%0.28-0.87, P < 0.014). CONCLUSIONS: APACHE II ≥ 29 score, culture positivity, sepsis and pneumonia are the risk factors for NIV failure in COPD patients with ARF. COPD patients previously on home-based NIV showed half times less risk for NIV failure.

Visual and software-based quantitative chest CT assessment of COVID-19: correlation with clinical findings.

PURPOSE: The aim of this study was to evaluate visual and software-based quantitative assessment of parenchymal changes and normal lung parenchyma in patients with coronavirus disease 2019 (COVID-19) pneumonia. The secondary aim of the study was to compare the radiologic findings with clinical and laboratory data. METHODS: Patients with COVID-19 who underwent chest computed tomography (CT) between March 11, 2020 and April 15, 2020 were retrospectively evaluated. Clinical and laboratory findings of patients with abnormal findings on chest CT and PCR-evidence of COVID-19 infection were recorded. Visual quantitative assessment score (VQAS) was performed according to the extent of lung opacities. Software-based quantitative assessment of the normal lung parenchyma percentage (SQNLP) was automatically quantified by a deep learning software. The presence of consolidation and crazy paving pattern (CPP) was also recorded. Statistical analyses were performed to evaluate the correlation between quantitative radiologic assessments, and clinical and laboratory findings, as well as to determine the predictive utility of radiologic findings for estimating severe pneumonia and admission to intensive care unit (ICU). RESULTS: A total of 90 patients were enrolled. Both VQAS and SQNLP were significantly correlated with multiple clinical parameters. While VQAS >8.5 (sensitivity, 84.2%; specificity, 80.3%) and SQNLP <82.45% (sensitivity, 83.1%; specificity, 84.2%) were related to severe pneumonia, VQAS >9.5 (sensitivity, 93.3%; specificity, 86.5%) and SQNLP <81.1% (sensitivity, 86.5%; specificity, 86.7%) were predictive of ICU admission. Both consolidation and CPP were more commonly seen in patients with severe pneumonia than patients with nonsevere pneumonia (P = 0.197 for consolidation; P < 0.001 for CPP). Moreover, the presence of CPP showed high specificity (97.2%) for severe pneumonia. CONCLUSION: Both SQNLP and VQAS were significantly related to the clinical findings, highlighting their clinical utility in predicting severe pneumonia, ICU admission, length of hospital stay, and management of the disease. On the other hand, presence of CPP has high specificity for severe COVID-19 pneumonia.

Unclear Issues Regarding COVID-19.

Scientists from all over the world have been intensively working to discover different aspects of Coronavirus disease 2019 (COVID-19) since the first cluster of cases was reported in China. Herein, we aimed to investigate unclear issues related to transmission and pathogenesis of disease as well as accuracy of diagnostic tests and treatment modalities. A literature search on PubMed, Ovid, and EMBASE databases was conducted, and articles pertinent to identified search terms were extracted. A snow-ball search strategy was followed in order to retrieve additional relevant articles. It was reported that viral spread may occur during the asymptomatic phase of infection, and viral load was suggested to be a useful marker to assess disease severity. In contrast to immune response against viral infections, cytotoxic T lymphocytes decline in SARS-CoV-2 infection, which can be partially explained by direct invasion of T lymphocytes or apoptosis activated by SARS-CoV-2. Dysregulation of the urokinase pathway, cleavage of the SARS-CoV-2 Spike protein by FXa and FIIa, and consumption coagulopathy were the proposed mechanisms of the coagulation dysfunction in COVID-19. False-negative rates of reverse transcriptase polymerase chain reaction varied between 3% and 41% across studies. The probability of the positive test was proposed to decrease with the number of days past from symptom onset. Safety issues related to infection spread limit the use of high flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP) in hypoxic patients. Further studies are required to elucidate the challenging issues, thus enhancing the management of COVID-19 patients.

Severity of acidosis affects long-term survival in COPD patients with hypoxemia after intensive care unit discharge.

Background: Patients admitted to the intensive care unit (ICU) with acute respiratory failure (ARF) due to COPD have high mortality and morbidity. Acidosis has several harmful effects on hemodynamics and metabolism, and the current knowledge regarding the relationship between respiratory acidosis severity on the short- and long-term survival of COPD patients is limited. We hypothesized that COPD patients with severe acidosis would have a poorer short- and long-term prognosis compared with COPD patients with mild-to-moderate acidosis. Patients and methods: This retrospective observational cohort study was conducted in a level III respiratory ICU of a tertiary teaching hospital for chest diseases between December 1, 2013, and December 30, 2014. Subject characteristics, comorbidities, ICU parameters, duration of mechanical ventilation, length of ICU stay, ICU mortality, use of domiciliary noninvasive mechanical ventilation (NIMV) and long-term oxygen therapy (LTOT), and short- and long-term mortality were recorded. Patients were grouped according to their arterial blood gas (ABG) values during ICU admission: severe acidotic (pH≤7.20) and mild-to-moderate acidotic (pH 7.21-7.35). These groups were compared with the recorded data. The mortality predictors were analyzed by logistic regression test in the ICU and the Cox regression test for long-term mortality predictors. Results: During the study period, a total of 312 COPD patients admitted to the ICU with ARF, 69 (72.5% male) in the severe acidosis group and 243 (79% male) in the mild-to-moderate acidosis group, were enrolled. Group demographics, comorbidities, duration of mechanical ventilation, and length of ICU stay were similar in the two groups. The severe acidosis group had a significantly higher rate of NIMV failure (60.7% vs 40%) in the ICU. Mild-to-moderate acidotic COPD patients using LTOT had longer survival after ICU discharge than those without LTOT. On the other hand, severely acidotic COPD patients without LTOT showed shorter survival than those with LTOT. Kaplan-Meier cumulative survival analysis showed that the 28-day and 1-, 2-, and 3-year mortality rates were 12.2%, 36.2%, 52.6%, 63.3%, respectively (p=0.09). The Cox regression analyses showed that older age, PaO2/FiO2 <300 mmHg, and body mass index ≤20 kg/m2 was associated with mortality of all patients after 3 years. Conclusion: Severely acidotic COPD patients had a poorer short- and long-term prognosis compared with mild-to-moderate acidotic COPD patients if acute and chronic hypoxemia was predominant.