Description of an activity-based enzyme biosensor for lung cancer detection.

BACKGROUND: Lung cancer is associated with the greatest cancer mortality as it typically presents with incurable distributed disease. Biomarkers relevant to risk assessment for the detection of lung cancer continue to be a challenge because they are often not detectable during the asymptomatic curable stage of the disease. A solution to population-scale testing for lung cancer will require a combination of performance, scalability, cost-effectiveness, and simplicity. METHODS: One solution is to measure the activity of serum available enzymes that contribute to the transformation process rather than counting biomarkers. Protease enzymes modify the environment during tumor growth and present an attractive target for detection. An activity based sensor platform sensitive to active protease enzymes is presented. A panel of 18 sensors was used to measure 750 sera samples from participants at increased risk for lung cancer with or without the disease. RESULTS: A machine learning approach is applied to generate algorithms that detect 90% of cancer patients overall with a specificity of 82% including 90% sensitivity in Stage I when disease intervention is most effective and detection more challenging. CONCLUSION: This approach is promising as a scalable, clinically useful platform to help detect patients who have lung cancer using a simple blood sample. The performance and cost profile is being pursued in studies as a platform for population wide screening.

Lung cancer is responsible for more deaths worldwide than all other cancers. It is often detected with the appearance of symptoms when treatment is limited and outcomes for the patient are much worse. While imaging chest scans can detect disease, they are poorly used even in the United States where it is an approved screening method. When cancer is present, protease enzymes are responsible for making space and modifying the lung tissue for the growing tumor. This report describes a panel of 18 sensors that release a fluorescent signal when these enzymes are present in a blood sample. The signal acts like a fingerprint of activity that can be used to identify people with lung cancer. This sensor platform can detect patients with curable lung cancer and could provide a platform for screening very large populations of at-risk individuals.

Is Pulmonary Capillary Wedge Pressure a Reliable Indicator of Postcapillary Pulmonary Hypertension?

Although current pulmonary hypertension (PH) guidelines recommend a pulmonary capillary wedge pressure (PCWP) >15 mm Hg for the detection of a postcapillary component, the rationale of this recommendation may not be quite compatible with the peculiar hemodynamics of PH. We hypothesize that a high PCWP alone does not necessarily indicate left-sided disease, and this diagnosis can be improved using left ventricle transmural pressure difference (∆ PTM). In this 2-center, retrospective, observational study, we enrolled 1,070 patients with PH who underwent heart catheterization, with the final study population comprising 961 cases. ∆ PTM was calculated as PCWP minus right atrial pressure. The patients with group II PH had significantly higher ∆ PTM values (12.6 ± 6.6 mm Hg) compared with the other groups (1.1 ± 4.8 in group I, 12.4 ± 6.6 in group II, 2.5 ± 6.4 in group III, and 0.8 ± 8.0 in group IV, p <0.001) despite overlapping PCWP values. A ∆ PTM cutoff of 7 mm Hg identifies left heart disease when PCWP is >15 (area under curve 0.825, 95% confidence interval 0.784 to 0.866, p <0.001). Five-year mortality was significantly higher in patients with high ∆ PTM and PCWP subgroups compared with low ∆ PTM plus high PCWP (26.1% vs 18.5%, p = 0.027) and low ∆ PTM and PCWP subgroups (26.1% vs 15.6%, p <0.001). ∆ PTM has supplementary discriminatory power in distinguishing patients with and without postcapillary PH. In conclusion, a new approach utilizing ∆ PTM may improve our understanding of PH pathophysiology and may identify a subpopulation that may potentially benefit from PH-specific treatments.

Angiographic findings of pulmonary arterial involvement in Behcet's Disease: Do they correlate with symptoms and acute phase response?

INTRODUCTION: Behcet's disease (BD) is a chronic inflammatory disorder with arterial vasculitis. Although, pulmonary artery aneurysm (PAA) is accepted as the prototypic arterial disorder, an increasing presence of pulmonary artery thrombosis (PAT) with or without aneurysms was also reported in recent studies. In this study, we aimed to describe computed tomography pulmonary angiography (CTPA) findings of pulmonary involvement and its correlation with symptoms and acute phase response in BD. METHOD: In this retrospective study, 153 CTPA of BD patients were assessed by two radiologists. Clinical and laboratory data were collected from the patient files. Pulmonary artery involvement (PAI) was defined as thrombus or aneurysm in CT angiography. RESULTS: Most of (85.6 %) our patients were male and median age was 33.7 ± 10 years during angiographic assessments. Sixty-two (40.5 %) angiographies presented a thrombus: 14 subsegmental, 29 segmental, 13 lobar and 6 main branches. Among these, 82.3 % (n = 51) had bilateral involvement. Isolated PAT was present in 58 (93.5 %) angiographies with only 4 (2.6 %) angiographies displaying an aneurysm together with a thrombus. Pulmonary infarction was detected in 9 angiographies. Forty-four (29.3 %) patients, almost all of them under immunosuppressive treatments for other indications, were screened for asymptomatic pulmonary involvement (without any symptoms or increased acute-phase response (APR)), and one fourth of these were diagnosed as having a segmental or subsegmental PAT. CONCLUSION: Our results show that isolated pulmonary thrombosis is the main form of PAI, and isolated pulmonary aneurysm formation is rare in our BD cases. In the presence of pulmonary symptoms with or without increased APRs, involvement of segmental or more proximal parts of pulmonary arteries is most commonly detected. We also observed that PAI may be seen in about one fourth of especially male BD patients without symptoms or increased APR. Our results suggest that BD patients with pulmonary symptoms should be screened by CTPA for PAI, however, further research is needed to clarify the role of routine CTPA screening in asymptomatic BD patients.

Results of surgical treatment of pulmonary artery sarcomas: Does histology affect survival?

Background: In this study, we aimed to describe our experience with primary pulmonary artery sarcoma in patients who underwent pulmonary endarterectomy and to evaluate clinical features, treatment, outcomes, and survival rates according to the histological subtypes of this malignant disease. Methods: Between March 2011 and May 2022, a total of 13 patients (7 males, 6 females; mean age: 52.6±13.0 years; range, 30 to 69 years) who underwent pulmonary endarterectomy and diagnosed with a pulmonary artery sarcoma were retrospectively analyzed. The diagnosis was confirmed histopathologically in all patients. Data including demographics, clinical characteristics, intra- and postoperative complications, length of hospital stay, morbidity, mortality, and short-term and long-term outcomes were recorded. Operative mortality was defined as death in the hospital or within 30 days of surgery. Results: Mortality was observed in one patient due to massive hemoptysis. Morbidity developed in two patients due to acute respiratory distress. Pulmonary vascular resistance improved significantly from 508 dyn/s/cm-5 to 191 dyn/s/cm-5 (p<0.004). All patients received chemotherapy following surgery. Median followup was 14 months. Median survival for the entire series was 18 months. One-year and three-year survival rates were 60.6% and 30.3%, respectively. Median survival for leiomyosarcomas (n=6) was seven months, while it was 44 months for intimal sarcomas (p=0.004). Three-year survival was 66.7% for intimal sarcomas and 0% for leiomyosarcomas. Conclusion: Pulmonary artery sarcoma may mimic chronic thromboembolic pulmonary hypertension. Patients with a suspected diagnosis of pulmonary artery sarcoma should be referred to expert pulmonary endarterectomy centers for surgery where a multidisciplinary team is available. Pulmonary endarterectomy has both diagnostic and therapeutic value and may improve survival and quality of life. Patients with intimal sarcoma have longer survival compared to those with leiomyosarcoma.

Relationship of muscle thickness, strength, and diaphragm function in adults with cystic fibrosis.

Objectives: This study aimed to evaluate the muscle thickness, strength, and diaphragmatic function and relate them with clinical findings. Patients and methods: The cross-sectional study was conducted with 54 participants (27 males, 27 females; mean age; 24.5±5.3 years; range, 18 to 45 years) between January 2017 and October 2017. Of the participants, 31 were adult CF patients, and 23 were age-and sex-matched controls. Patient demographics, 6-min walk distance, body mass index (BMI), and fat-free mass index (FFMI) were evaluated. Each patient underwent pulmonary function tests. Quadriceps femoris thickness and diaphragm thickening fraction were assessed by ultrasonography. Upper extremity strength was measured with a handheld dynamometer. Results: There was no difference between the patients' and controls' BMI (p=0.052). However, patients' FFMI was lower than the controls' (p=0.010). The FFMI correlated with pulmonary function tests. Patients' both right and left quadriceps femoris muscles were thinner than the controls (p=0.001 and p=0.001, respectively). Patients with pancreatic insufficiency had thinner muscles than patients without pancreatic insufficiency. The control group had a stronger handgrip than CF patients (33.5±10.1 vs. 24.5±9.2 kg, p=0.003). Conclusion: Peripheral muscle wasting and weakness and lower functional capacity are highly prevalent in CF patients.

Anxiety, Depression, and Sleep Disorders After COVID-19 Infection.

Introduction As of December 2019, the COVID-19 infection had spread rapidly across the globe, causing a pandemic. Although the virus primarily affects the respiratory and circulatory systems, neuropsychiatric disorders have been reported in a significant number of infected individuals. The aim of this study is to identify anxiety, depression, and sleep disturbances in the early post-COVID period, as well as potential risk factors. Method Symptomatic cases whose COVID-19 diagnosis was confirmed by polymerase chain reaction (PCR) positivity within the previous three months were evaluated in the COVID-19 follow-up clinic, where they were observed for at least four weeks after the diagnosis. Cases with no suspicious symptoms and no documented PCR positivity were selected as the control group. All participants completed the Hospital Anxiety Depression Scale (HADS) questionnaire and the Pittsburgh sleep quality questionnaire. The laboratory parameters of hospitalized patients with infection were recorded. Results A total of 283 patients were included in the study. While the median age of 144 patients with COVID-19 infection was 44 years, and 104 of them (72.2%) were female, the median age of the controls without COVID-19 infection was 52 years, and 65 of them (46.8%) were female. About 89 (61.8%) of the 144 patients with COVID-19 infections were hospitalized. When the results of the applied HADS questionnaire were analyzed, the median total value of all study participants was 10 points, whereas it was 13 in cases with COVID-19 and nine in those who did not have it (p<0.001). Taking into account the subgroups of the anxiety and depression questionnaires, both results are statistically significantly higher (p<0.001 and p=0.022, respectively) in post-COVID patients. When the hospitalization status of COVID-19 patients was compared, there was no difference in the development of anxiety (p=0.23), but depression(p<0.024) and poor sleep quality(p<0.001) were prevalent in hospitalized patients. The median PSQI score of the entire study population was five points, while it was seven points in cases with COVID-19 infection and four points in cases who did not have it (p<0.001). Sleep latency (p<0.003), sleep disturbances (p<0.001), and daytime dysfunction (p<0.001) were statistically significantly worse in COVID-19-infected patients. Female gender (p<0.01) and the presence of past anxiety-depression symptoms (p<0.013) were found to be as risk factors in patients with infection. The correlation between the total HADS score, the PSQI, and the results of the complete blood count and biochemical analysis at the time of diagnosis in hospitalized patients was also investigated. CRP (CI 0.26-0.58) p<0.001 vs (CI 0.09-0.45) p=0.004 and ferritin (CI 0.05-0.43) p=0.017 vs (CI 0.01-0.40) p=0.047exhibited a positive correlation. Similarly, lymphocyte count (CI -0.65 to -0.37) p<0.001 vs (CI -0.39 to -0.01) p<0.001 and lymphocyte percentage (-0.57 to -0.24) p=0.001 vs (-0.65 to -0.37) p=0.039 were negatively correlated. Conclusion Early post-infection anxiety, depression, and sleep disturbances increased significantly in COVID-19 patients. Female gender and previous symptoms of anxiety and depression are risk factors, and inpatient treatment increases depression and poor sleep quality. High HADS and poor sleep quality scores are positively correlated with inflammatory parameters and should be evaluated in post-infection in particular.

Lung Cavitation as a Long-Term Imaging Pattern of COVID-19.

Background A wide variety of radiological imaging findings, especially CT findings, have been reported in patients with COVID-19 pneumonia during the pandemic surge. Generally, on control chest imaging, individuals who have been cured of the disease usually show complete remission; however, in severe cases, residual pulmonary fibrosis, other abnormalities, and, rarely, lung cavitation can be observed. In this retrospective descriptive study, we aimed to describe the clinical, radiological, and laboratory characteristics of patients who developed lung cavitation in the course of SARS-CoV-2 disease recovery. Methodology Over a period of five months from March 1, 2021, to August 1, 2021, 15 consecutive patients who developed cavitary lesions on chest CT during the course of recovery from COVID-19 were recruited as the study population. All patients had a history of a SARS-CoV-2 infection diagnosed with a positive real-time polymerase chain reaction test. Patients who already had cavitary lesions in chest CT during the start of COVID-19 symptoms were excluded. Results In this study, 14 patients were male (93.3%). The only female patient was the only severely obese patient in the study population, with a body mass index was 40.4 kg/m2. The median (range) age of the patient population was 61 (42-79) years. Eight patients (53.3%) required intensive care unit admission during the hospitalization period. Three patients who required intensive care unit were intubated and needed invasive mechanical ventilation. Two patients died during hospitalization. Conclusions Lung cavitation remains a rare occurrence in the course of COVID-19. Bronchoscopic evaluation and scanning for pulmonary embolism should be done in appropriate patients to determine secondary reasons for cavitation. Although this descriptive study showed that cavitary lesions can develop in patients with severe disease, more comprehensive studies with a control group are needed to reach a definitive conclusion.

The Impact of Cystic Fibrosis- and Noncystic Fibrosis-Bronchiectasis on Pulmonary Artery Wall Thickness and Right Heart Functions Assessed by Speckle-Tracking Echocardiography.

BACKGROUND: Right heart functions are affected in patients with bronchiectasis as a result of pulmonary hypertension induced by chronic hypoxemia. Pulmonary artery wall thickness has recently been introduced as a sign of intensive and prolonged inflammation. The aim of this study was to analyze right ventricular and right atrial functions and to mea-sure pulmonary artery wall thickness in patients with cystic fibrosis-bronch iecta sis in comparison to those with noncystic fibrosis-bronchiectasis and healthy individuals. METHODS: We studied 36 patients with cystic fibrosis-bronchiectasis, 34 patients with noncystic fibrosis-bronchiectasis, and 32 age- and sex-matched control subjects. Lung function tests were performed. All subjects underwent comprehensive echocardiographic evaluation including conventional, tissue Doppler, speckle-tracking, and pulmonary artery wall thickness measurements. RESULTS: Right ventricular global longitudinal strain and global longitudinal right atrial strain during ventricular systole decreased in cystic fibrosis-bronchiectasis group compared with noncystic fibrosis-bronchiectasis and control groups (P <.001, both). Conversely, pulmonary artery wall thickness was increased in cystic fibrosis-bronchiectasis group in comparison to other groups (P <.001). Moreover, right ventricular global longitudinal strain was lower and pulmonary artery wall thickness was higher in patients with airflow obstruction (P <.001 and P =.025, respectively) than in those without. Only right ventricular global longitudinal strain was significantly correlated with pulmonary function test parameters. The negative effect of cystic fibrosis on right ventricular and right atrial functions was independent of age, gender, and disease duration. CONCLUSION: Our study showed that right ventricular and right atrial functions were deteriorated and pulmonary artery wall was thickened in cystic fibrosis-bronchiectasis patients more than noncystic fibrosis-bronchiectasis patients. Right ventricular global longitudinal strain detected subclinical right ventricular dysfunction and was associated with the severity of pulmonary disease.

Pre-existing Immunocompromised Status as a Preventer of Mortality in COVID-19 Patients: Friend or Foe?

Objective COVID-19 has been negatively impacted by a number of comorbidities. Aside from that, some conditions or treatments that cause immunosuppression can alter the course of the disease, leading to worse outcomes. The primary goal of this study is to compare the clinical presentation, laboratory analysis, radiological findings, and outcomes of patients with COVID-19 with and without immunosuppression. Materials and methods The study includes patients with pre-existing immunosuppression and COVID-19 infection who were admitted and received inpatient treatment at Marmara University Hospital, Istanbul, Pulmonary Medicine ward between April 2020 and June 2020. Data on demographics, epidemiology, clinical course, laboratory analysis, radiological findings, length of hospital stay, morbidity, and mortality were collected from all patients. Results The study group consisted of 23 patients who had pre-existing immunosuppression, and the control group consisted of 207 immunocompetent patients, making a total of 230 patients. Significant differences in lymphocyte count, ROX (respiratory-rate oxygenation) index on Day 0, and fibrinogen levels were discovered between the two groups. SARI (severe acute respiratory infection) was more common in the control group than in the study group (p<0.022), but there was no difference in mortality. Conclusion The mean number and percentage of lymphocytes were lower in immunocompromised COVID-19 patients at the time of diagnosis. Higher ROX index values and a lower risk of developing SARI could explain the hypothesis that these patients may be benefiting from a pre-existing corticosteroid regimen. Additional research with larger numbers of patients may be beneficial in drawing a more definitive conclusion.

The angiogenic gene profile of pulmonary endarterectomy specimens: Initial study.

Objectives: The underlying mechanisms for the development of chronic thromboembolic pulmonary hypertension and prognostic biomarkers are not clear yet. Thus, our aim is to assess and identify new biomarkers for the expression of 84 key genes linked to angiogenesis. Methods: Patients who had levels more than 1000 dynes·sec·cm-5 were included in the test group, and the other patients were included in the control group. Twelve specimens were taken from the patients. RT2 Profiler PCR Array (Qiagen) was used to quantify the expression of the 84 key genes. Results: Eight patients (6 male, 2 female, median age 54.4 ± 13.1 years) who underwent pulmonary endarterectomy were included. Pulmonary vascular resistance improved significantly from 811 ± 390 dyn/s/cm-5 to 413.3 ± 144.9 dyn/s/cm-5 (P < .005). A difference was also detected in median mean pulmonary arterial pressure, which decreased from 49.8 ± 9 mm Hg to 32.62 ± 2.50 mm Hg (P > .005) after surgery. Median length of hospital stay was 11.62 ± 2.97 days. The test group had a distinct pattern of impaired angiogenic and antiangiogenic genes. The expression levels of TGFA, TGFB1, THBS2, THBS1, TGFBR1, SERPINE1, SERPINF1, TGFB2, TIMP2, VEGFC, IFNA1, TNF, CXCL10, NOS3, IGF1, and MMP14 were downregulated in the specimens from the patients who had higher pulmonary vascular resistance values, whereas some genes, including PDGFA, showed upregulation that was statistically nonsignificant in the same group. Conclusions: These results can lead to the development of new markers that could predict adverse outcomes of patients with CTEPH. Identification of new markers that are related to worse outcomes would enable screening patients for early diagnosis and treatment.

Surgical Treatment of Another Sequalae of COVID-19: Post-COVID CTEPH.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still an ongoing entity and every day we face new sequalae of the disease. We hereby present surgical results of patients who are treated for post-COVID chronic thromboembolic pulmonary hypertension. METHODS: Data were collected among patients who underwent pulmonary endarterectomy and had a diagnosis of post-COVID chronic thromboembolic pulmonary hypertension. All data were retrospectively reviewed from a prospectively conducted database. Operative mortality was described as death in hospital or within 30 days of surgery. RESULTS: Eleven patients (seven males, four females; median age, 52 [22-63] years) were identified. Pulmonary vascular resistance improved significantly from 572 dyn/s/cm-5 (240-1,192) to 240 (195-377) dyn/s/cm-5 (p < 0.005). Significant difference was also detected in median mPAP, as it decreased from 40 mm Hg (24-54) to 24 mm Hg (15-36) following surgery (p < 0.005). Mortality was observed in one patient due to sepsis on the fifth postoperative day. Median time from COVID-19 disease to surgery was 12 months (6-24). Median length of hospital stay of the survivors was 10 days (8-14). CONCLUSION: In the new era of chronic thromboembolic pulmonary hypertension, hybrid approach including surgery, balloon pulmonary angioplasty, and medical treatment has been recommended. pulmonary endarterectomy is still the only curative treatment when the disease is surgically accessible. We hereby report the first publication of post-COVID chronic thromboembolic pulmonary hypertension patients who were surgically treated. As we see a lot of long-term symptoms and clinical manifestations in patients who had COVID-19, we should always remember chronic thromboembolic pulmonary hypertension in the differential diagnosis.

Are Guideline-recommended Risk Classification Schemes in Pulmonary Hypertension Adequately Robust to Guide the Real-world Setting?

Background: Pulmonary hypertension is a complex syndrome that encompasses a diverse group of pathophysiologies predisposed by different environmental and genetic factors. It is not clear to which extent the universal risk classification schemes can be applied to cohorts in individual pulmonary hypertension centers with differing environmental backgrounds, genetic pools, referral networks. Aims: To explore whether the recommended risk classification schemes could reliably be used for mortality prediction in an unselected pulmonary hypertension population of a tertiary pulmonary hypertension center. Study Design: A retrospective cross-sectional study. Methods: We retrospectively screened our hospital database for the patients with pulmonary hypertension between 2015 and 2022. The grouping of pulmonary hypertension was made as follows in accordance with current guidelines: Group 1: patients with pulmonary arterial hypertension, Group 2: patients with pulmonary hypertension associated with left heart disease, Group 3: patients with pulmonary hypertension associated with lung disease and/or hypoxia, and Group 4: patients with pulmonary hypertension associated with pulmonary artery obstructions. Then, we compared the predicted and observed mortality rates of four different risk classification schemes (REVEAL, REVEAL-Lite, ESC/ERS and COMPERA). Results: We identified 723 cases in our pulmonary hypertension database, the final study population consisted of 549 patients. The REVEAL, REVEAL-Lite and European Society of Cardiology/European Respiratory Society risk scores significantly underestimated the mortality risk in the low-risk stratum (5.3% vs. 1.9%, P < 0.001; 5.3% vs. 2.9%, P = 0.015 and 6.3% vs. 1%, P < 0.001, respectively) and overestimated the mortality risk in the high-risk stratum (11.8% vs. 25.8%, P < 0.001; 10.4% vs. 25.1%, P < 0.001 and 13.2% vs. 30%, P < 0.001, respectively). Although the COMPERA 4-strata model significantly underestimated the risk in low- and intermediate-low risk strata (4.9% vs. 1.5%, P < 0.001 and 6.8% vs. 2.8%, P = 0.001, respectively), it was accurate in intermediate-high and high-risk groups (10.1% vs. 8.7%, P = 0.592 and 15.6% vs. 22%, P = 0.384, respectively). The analyses limited only to group 1 pulmonary hypertension patients gave similar results. Conclusion: The established risk classification schemes may not perform as good as expected in unselected pulmonary hypertension populations and this may have important implications on management decisions. Tertiary centers should not uncritically accept the published risk prediction models and consider modifying current risk scores according to their own patient characteristics.

Right Ventricular Energy Failure Predicts Mortality in Patients With Pulmonary Hypertension.

Right ventricular (RV) failure has a significant adverse impact on pulmonary hypertension (PH) prognosis. None of the currently used parameters directly assess whether RV fails to provide enough energy output to propel the blood through diseased pulmonary vascular system. Furthermore, most of the current parameters are affected by the volume status of the patient. We aimed to explore whether RV energy failure has a predictive power for mortality on top of the established prognostic risk parameters in patients with PH. We screened 723 cases from our database. A total of 3 sets of binary regression analyses were executed to determine the hazard ratios (HRs) of RV energy failure for 5-year mortality in clinical, echocardiographic, and hemodynamic context, using adjustment variables chosen according to previous studies. The final study population encompassed 549 cases. A total of 77 patients died during the 5-year follow-up (14%). RV energy failure was observed in 146 of 549 patients (26.6%). In the univariate model, RV energy failure strongly associated with increased long-term mortality (HR 4.25, 95% confidence interval [CI] 2.58 to 7.00, p <0.001). It also emerged as a significant predictor of long-term mortality in clinical and hemodynamic multivariate models (HR 2.59, 95% CI 1.43 to 4.67, p = 0.002 and HR 2.05, 95% CI 1.15 to 3.63, p = 0.015, respectively). In conclusion, our study indicates that the presence of RV energy failure independently predicts long-term mortality in PH.

Diagnostic performance of lactate dehydrogenase (LDH) isoenzymes levels for the severity of COVID-19.

Background: Lactate dehydrogenase (LDH) levels predict coronavirus disease 2019 (COVID-19) severity. We investigated LDH isoenzyme levels to identify the tissue responsible for serum LDH elevation in patients with COVID-19. Methods: Hospitalised COVID-19 patients with serum LDH levels exceeding the upper reference limit included. LDH isoenzymes were detected quantitatively on agarose gels. The radiological severity of lung involvement on computed tomography was scored as 0-5 for each lobe (total possible score, 0-25). Disease severity was determined using the World Health Organization (WHO) clinical progression scale. Results: In total, 111 patients (mean age, 59.96 ± 16.14), including 43 females (38.7%), were enrolled. The serum levels of total LDH and all five LDH isoenzymes were significantly higher in the severe group. The levels of all LDH isoenzymes excluding LDH5 positively correlated with the WHO score. LDH3 levels correlated with chest computed tomography findings (r2 = 0.267, p = 0.005). On multivariate analysis, LDH3 was an independent risk factor for the deterioration of COVID-19. Conclusions: LDH3 appears to be an independent risk factor for deterioration in patients with COVID-19. LDH elevation in patients with COVID-19 predominantly resulted from lung, liver and muscle damage.

Pulmonary arterial wall thickness increased in Behçet's disease patients with major organ involvement: Is it a sign of severity?

OBJECTIVES: Behçet's disease (BD) is a unique systemic vasculitis mainly involving veins, in contrast to other vasculitides. Prior studies have shown that pulmonary arteries (PAs) have a similar structure to systemic veins. In this study we aimed to assess PA wall thickness by transthoracic echocardiography (TTE) in BD patients compared with healthy controls (HCs) and patients with non-inflammatory pulmonary embolism (NIPE). METHODS: Patients with BD (n = 77) and NIPE (n = 33) and HCs (n = 57) were studied. PA wall thickness was measured from the mid-portion of the main PA with TTE by two cardiologists blinded to cases. RESULTS: PA wall thickness was significantly lower in HCs [3.6 mm (s.d. 0.3)] compared with NIPE [4.4 mm (s.d. 0.5)] and BD [4.4 mm (s.d. 0.6)] (P < 0.001 for both). PA wall thickness was similar between BD and NIPE (P = 0.6). Among patients with BD, PA wall thickness was significantly higher in patients with major organ involvement compared with mucocutaneous limited disease [4.7 mm (s.d. 0.4) vs 3.7 (0.4), P < 0.001], HCs and NIPE (P < 0.001 and P = 0.006, respectively). PA wall thickness was comparable between patients with vascular and non-vascular major organ involvement [4.6 mm (s.d. 0.5) vs 4.7 (0.3), P = 0.3]. CONCLUSION: We observed that PA wall thickness was significantly higher in BD with major organ involvement compared with patients with only mucocutaneous limited disease, HCs and NIPE. These results suggest that increased PA wall thickness may be a sign of severe disease with major organ involvement in BD.

Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

Objective: This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic. Materials and Methods: We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. Results: The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p<0.001), number of comorbidities (HR=1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p<0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p=0.02). The C-index of the model was 0.92. Conclusion: Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced. Graphic Abstract: Graphic Abstract.

Frequency of Obstructive Sleep Apnea in Patients With Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis and Its Association With Clinical Findings.

OBJECTIVE: This study was designed to assess obstructive sleep apnea (OSA) in adult patients with cystic fibrosis (CF) and non-CF bronchiectasis (BE) and to relate it with clinical characteristics. METHODS: Thirty-five CF (27 years) and 35 non-CF (24 years) BE patients were included. Demographic characteristics, medications, comorbidities, BMI, dyspnea scales, pulmonary functions, sputum cultures, exacerbations, and hospitalizations were recorded. The Epworth Sleepiness Scale (ESS) questionnaire was filled and polysomnography was performed for each patient. RESULTS: ESS scores did not show any significant difference between CF and non-CF BE patients. Thirty-seven (53%) of all patients had OSA. There was no significant difference in OSA risk between CF and non-CF BE patients (54% vs 51%, respectively). Male gender was found to be a risk factor for OSA (68% of males vs 41% of females, respectively, p:0.026). Total sleep time, sleep efficiency, sleep latency, time spent awake after falling asleep, oxygen desaturation index, apnea-hypopnea-index (AHI), AHI in the supine position, and rapid eye movement phase did not show any significant difference between CF and non-CF patients. CF patients had significantly lower mean oxygen saturation (p:0.001) and lowest oxygen saturation (p:0.0024) levels and higher heart rate (p:0.02) compared to non-CF BE patients. Multiple logistic regression analysis of all patients revealed male gender and disease duration as risk factors for OSA (p:0.023 and p:0.041 respectively). CONCLUSION: It is remarkable that more than half of the patients in both CF and non-CF bronchiectasis groups had OSA. Male gender and disease duration were found as risk factors for OSA.

Potentially inappropriate medications based on TIME criteria and risk of in-hospital mortality in COVID-19 patients.

OBJECTIVE: This study aimed to evaluate the relationship between hospital admission potentially inappropriate medications use (PIM) and in-hospital mortality of COVID-19, considering other possible factors related to mortality. METHODS: The Turkish inappropriate medication use in the elderly (TIME) criteria were used to define PIM. The primary outcome of this study was in-hospital mortality. RESULTS: We included 201 older adults (mean age 73.1±9.4, 48.9% females). The in-hospital mortality rate and prevalence of PIM were 18.9% (n=38) and 96% (n=193), respectively. The most common PIM according to TIME to START was insufficient vitamin D and/or calcium intake per day. Proton-pump inhibitor use for multiple drug indications was the most prevalent PIM based on TIME to STOP findings. Mortality was related to PIM in univariate analysis (p=0.005) but not in multivariate analysis (p=0.599). Older age (hazards ratio (HR): 1.08; 95% confidence interval (CI): 1.02-1.13; p=0.005) and higher Nutritional Risk Screening 2002 (NRS-2002) scores were correlated with in-hospital mortality (HR: 1.29; 95%CI 1.00-1.65; p=0.042). CONCLUSION: Mortality was not associated with PIM. Older age and malnutrition were related to in-hospital mortality in COVID-19.

Outcome of solid and cavitary pulmonary nodules in rheumatoid arthritis patients-case series.

BACKGROUND: Rheumatoid pulmonary nodule can be detected in up to 32% of rheumatoid arthritis (RA) patients and approximately one-third of nodules may cavitate. We aimed to evaluate characteristics of patients with RA developing cavitary pulmonary nodular (CPN) lesions under disease-modifying antirheumatic drugs (DMARDs), follow-up of both cavitary and solid nodules, and their outcome with the treatment. METHODS: RA patients who presented with CPN lesions during follow-up were recruited retrospectively in this case series analysis. Total numbers and mean diameters of cavitary and solid nodules in each thorax computed tomography (CT) have been determined and followed up by two experienced pulmonary physicians. Moreover, changes in treatment after the development of the CPN lesions and characteristics of cavitary nodules were collected. RESULTS: Eleven patients with CPN lesions were reported. At the time of CPN diagnosis, more patients were taking leflunomide than methotrexate (81% vs 19%). Half of the patients were receiving biologic therapy and only 18% were taking anti-TNF drugs. After a median of 24 (3-65) months of follow-up, the regression of CPN lesions was determined in 45% (5/11) of patients. Four of these 5 (80%) patients were switched to a treatment regimen without leflunomide and three of them to nonanti-TNF biologic treatment or targeted synthetic DMARDs (tocilizumab, tofacitinib, and rituximab). DISCUSSION: CPN lesions seen in RA patients are often pulmonary manifestations of the underlying disease; however, one must rule out malignancies or infections. If lesions progress under DMARDs, it is advised to discontinue synthetic DMARDs (LEF/MTX) and switch to another biological DMARD with different modes of action.

The Effects of Iron Replacement on Functional Capacity in Patients with Group 1 and Group 4 Pulmonary Hypertension.

OBJECTIVE: Abnormal iron handling complicates pulmonary hypertension (PH), causes functional limitation and poor outcomes. Although preliminary results in group 1 PH patients support the use of iron replacement, whether this applies to other PH subgroups is not known. METHODS: A total of 58 patients with an established diagnosis of group 1 or 4 PH, who had a serum ferritin of <100 ng/mL or 100 to 300 ng/mL in combination with a transferrin saturation (TSAT) <20% and received 500 to 1000 mg of ferric carboxymaltose (FCM) were included in the study. The change in ferritin levels and TSAT were calculated at 12- and 24-weeks follow-up. A six-minute walk test (6MWT) is undertaken at the first, 12-week and 24-week follow-up visits. RESULTS: In group 1 PH patients, ferritin levels increased from 14 ng/mL-1 to 133 and 90 ng/mL-1 at 12- and 24-weeks, respectively ( P < .001 for both). In group 4 PH patients, ferritin levels increased from 22.1 ng/mL-1 to 145 and 88.9 ng/mL-1 at 12- and 24-weeks, respectively ( P < .001 for both). 6MWT distances were 356, 412, and 350 m in group 1 PH patients and 260, 315 and 290 m in group 4 PH patients. Although the difference between baseline and 12-week 6MWT was significant in both groups ( P < .001 for both), this difference was lost at 24-week. CONCLUSION: Our study indicates that there is no difference in response to iron replacement in patients with group 1 and group 4 PH patients, in terms of treatment success and functional status.