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.

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.

Pharmacokinetic characterization of favipiravir in patients with COVID-19.

This prospective observational study describes the pharmacokinetic characteristics of favipiravir in adult patients hospitalized for mild to moderate COVID-19 with a positive RT-PCR test. Favipiravir was administered for 5 days, with a loading dose of 3200 mg and a maintenance dose of 1200 mg/day. Serial blood samples were collected on Day 2 and Day 4 of the therapy. Laboratory findings of the patients (n = 21) and in-hospital mortality were recorded. Favipiravir concentrations exhibited substantial variability and a significant decrease during the treatment of COVID-19. The median favipiravir trough concentration (C0-trough ) on Day 2 was 21.26 (interquartile range [IQR], 8.37-30.78) µg/mL, whereas it decreased significantly to 1.61 (IQR, 0.00-6.41) µg/mL on Day 4, the area under the concentration-time curve decreased by 68.5%. Day 2 C0-trough of female patients was higher than male patients. Our findings indicate that favipiravir concentrations show significant variability during the treatment of COVID-19 and therapeutic drug monitoring may be necessary to maintain targeted concentrations.

Balloon Pulmonary Angioplasty in Patients With Inoperable or Recurrent/Residual Chronic Thromboembolic Pulmonary Hypertension: A Single-Centre Initial Experience.

BACKGROUND: Patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) are often treated with pulmonary arterial hypertension-specific drugs. However, most of these patients remain symptomatic, despite medical treatment. Balloon pulmonary angioplasty (BPA) is an emerging therapeutic intervention for patients with inoperable CTEPH. This study aimed to report the initial experience of BPA in a tertiary referral centre for CTEPH. METHODS: A total of 26 consecutive patients, who underwent 91 BPA sessions, were included in the study. All patients underwent a detailed examination, including 6-minute walking distance (6MWD), and right heart catheterisation at baseline and 3 months after the last BPA session. RESULTS: The mean age of the patients was 51±17 years. Fifteen (15) patients had inoperable CTEPH and 11 patients had residual or recurrent CTEPH post pulmonary endarterectomy (PEA). Functional class improved in 17 of 26 (65%) patients. The 6MWD increased from a mean 315±129 to 411±140 m (p<0.001), and NT pro-BNP reduced from a median 456 to 189 pg/mL (p=0.001). The number of patients who required supplemental oxygen decreased from 11 (42.3%) to five (19%) (p=0.031) after BPA treatment. The mean pulmonary artery pressure decreased from a mean 47.5±13.4 to 38±10.9 mmHg (p<0.001), the pulmonary vascular resistance decreased from a mean 9.3±4.7 to 5.8±2.8 Wood units (p<0.001), and the cardiac index increased from a mean 2.4±0.7 to 2.9±0.6 L/min/m2 (p=0.008). CONCLUSIONS: Balloon pulmonary angioplasty improved haemodynamics, 6MWD, and functional class, and reduced the requirement for supplemental oxygen, with an acceptable risk-benefit ratio in patients with inoperable CTEPH and with residual/recurrent CTEPH.

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.

Respiratory and peripheral muscle involvement in patients with pulmonary arterial hypertension due to congenital heart diseases.

Skeletal and respiratory muscle dysfunction has been previously described in patients with other etiologic subgroups of pulmonary arterial hypertension (PAH) but has never been investigated in patients with PAH due to congenital heart diseases (CHD). This study aims to show the involvement of skeletal and respiratory muscles in these patients. This cross-sectional study included patients with PAH due to CHD and healthy controls. Patients' demographic properties, six-minute walk tests; shoulder abduction, handgrip, knee extension, and ankle dorsiflexion muscle strength, maximum inspiratory (MIP) and expiratory pressures (MEP) were measured. Deltoid, flexor digitorum superficialis, and profundus, tibialis anterior and rectus femoris muscles were visualized with ultrasonography and their cross-sectional areas (CSA) were also measured in both groups. 12 patients and 12 controls were included. Mean MIP was 104.22±32.57 cm H2O for healthy participants while 61.33±29.74 cm H2O for patients (p<0.001). For mean MEP, it was 100.08±26.05 cm H2O in healthy participants and 69.75±39.79 cmH2O in controls (p=0.004). When the strength of skeletal muscles was compared, there were significant differences between the groups in all measurements except for bilateral grip strength. In the correlation analysis, MIP and MEP values showed no significant correlations with clinical parameters. They showed significant moderate correlations with skeletal muscle strength. When CSAs of the muscles were compared, there were significant differences in all measurements except for left FDS and FDP and bilateral rectus femoris. This study showed that in patients with pulmonary arterial hypertension due to CHD, respiratory muscle strength is significantly worse than healthy participants. Patients had also significantly worse skeletal muscle strength except for grip strength.

Risk of tuberculosis is increased in Behçet's disease compared to other rheumatological disorders after anti-TNFα treatments: a case series and review of the literature

Background/aim: Tumor necrosis factor-alfa (TNF-a) antagonists are extensively utilized in the treatment of inflammatory rheumatic diseases and also shown to be effective in Behçet's disease (BD) patients with major organ involvement. In this study, we aimed to re- evaluate the incidence of tuberculosis (TB) infection after anti-TNFa treatments and to reveal the risk of TB in BD. Methods: Data of patients who received anti-TNFa treatment between 2005 and 2018 were assessed retrospectively. Demographic features, TNF-a antagonist type/treatment time, tuberculosis skin test (TST) and QuantiFERON results, isoniazid prophylaxis status, and concomitant corticosteroid (CS) treatments were collected. Results: A total of 1277 (male/female = 597/680; median age = 49 years) patients were treated with TNF-a antagonist for a median of 33 months (Q1:12, Q3:62). Thirteen (1%) patients developed TB during the follow-up period. Within 13 TB-positive patients, 7 of them had pulmonary, and 7 had extrapulmonary TB. Although, the median time of (month) TNF-a antagonist treatment was higher in TB-positive patients than negative ones, the difference was not statistically significant (48 and 33 months, respectively, p = 0.47). Similarly, TB-positive patients were treated with CSs more than TB-negative patients (80% vs. 60%). Time from the initiation of TNF-a antagonist treatment to the diagnosis of TB had a median of 40 months (Q1-Q3: 22-56). There was a statistically significant increase of TB development in BD patients than non-BD patients after TNF-a antagonists (7.5% vs. 0.8%, respectively, p = 0.007). When we combined our patients with the other series from Turkey, among 12928 patients who received TNF-a antagonists, TB was positive in 12 (3.9%) of 305 BD patients compared to 112 (0.9%) of 12623 non-BD patients (p < 0.00001). Conclusion: Our results suggest a higher frequency of TB infections in BD patients with TNF-a antagonists. As biologic agents are increasingly used for major organ involvement in current practice for BD, screening mechanisms should be carefully implemented.

Endobronchial ultrasound transbronchial needle aspiration in elderly patients: safety and performance outcomes EBUS-TBNA in elderly.

AIM: Complication rates are low and endobronchial ultrasound guided needle aspiration (EBUS-TBNA) is generally regarded as a safe procedure, but there is a very limited number of studies evaluating the efficacy and safety of the procedure in advanced ages. The aim of this study is to assess the safety and performance outcomes of EBUS-TBNA in elderly. METHODS: It was a retrospective observational study; patients who received EBUS-TBNA between September 2016 and January 2018 were evaluated. We analyzed patient's characteristics, doses of midazolam, and lidocaine used, regions of lymph node biopsies, and complications. Also, functionality and general physical status of patients over 65 years of age were evaluated. RESULTS: During study period 132 cases of EBUS-TBNA were evaluated. 39 (29.5%) cases were aged 70 years, and over. There were more comorbidities in older group. Performance status of older group was worse. Furthermore, when evaluated according to American College of Cardiology (ACC)/American Heart Association (AHA) and American Society of Anesthesiologists (ASA), the older group was found to be composed of the riskier patients. When patients aged between 65 and 69, and over 70 compared, older patient's Barthel, EQ 5-D, SGA, and G8 scores were found to be worse. Despite that, there was no difference in the frequency, and types of complications between both groups. Diagnostic performance was not different between age groups. CONCLUSIONS: Independent from comorbidities, general health status, and functionality EBUS-TBNA procedure in 70-year-old and over patients is a safe minimally invasive procedure.

Clinical impact of depression and anxiety in patients with non-cystic fibrosis bronchiectasis.

INTRODUCTION: Bronchiectasis is a chronic suppurative disease characterized by abnormal bronchial dilatation. The nature of bronchiectasis may have negative impact on psychological status, however it is poorly studied in relation to clinical indices, particularly the severity of disease. Primary aim of this study is to detect depression and anxiety in patients with non-cystic fibrosis bronchiectasis and to evaluate its relationship with disease severity indexes. MATERIALS AND METHODS: Ninety (male/female= 37/53; median age 45 years) stable non-cystic fibrosis bronchiectatic adult patients were enrolled into this study. Dyspnea scores, number of exacerbations and hospital admissions within the last year, body-mass index, pulmonary function tests, sputum cultures, bronchiectasis disease severity indexes (BSI and FACED) were assessed. Anxiety and depression were evaluated by using the Turkish version of the hospital anxiety and depression scale questionaire. RESULT: Anxiety was diagnosed in 30% of patients and depression was diagnosed in 41% of the participants. Female participants had significantly higher rates of depression (55% vs. 22%; p= 0.002). Exacerbation rates within the last year were higher among the subjects with anxiety, moreover, patients with depression had shorter duration of disease. BSI and FACED severity indexes increased with longer duration of disease (5.6 ± 5.0 yrs in mild group vs. 10.1 ± 9.2 yrs in moderate-to-severe group, p= 0.035 and 5.7 ± 5.4 yrs in mild group vs. 12.1 ± 9.7 yrs in moderate-to-severe group, p= 0.001, respectively), however, anxiety and depression were not related with BSI and FACED severity indexes. CONCLUSIONS: Patients with non-cystic fibrosis bronchiectasis have an increased risk for depression and anxiety. Duration of disease and higher exacerbation rate are related with psychological status and indexes increased with longer duration of disease. Early detection and taking the necessary measures to improve the psychological state is necessary for the overall management of these patients.

Pleural effusion as an indicator of short term mortality in acute pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PE) is known as one of the major causes of cardiovascular morbidity and mortality. Identification of high risk patients for short term and long-term mortality is crucial. The purpose of this study is to demonstrate the prognostic importance of simplified pulmonary embolism severity index (sPESI), radiological investigations and comorbidities in terms of short-term mortality by simultaneous assessment of sPESI score, pulmonary computed tomography (CT) angiography findings and underlying comorbidities in patients diagnosed with acute pulmonary embolism. MATERIALS AND METHODS: We retrospectively evaluated 570 patients diagnosed with acute PE confirmed by computer tomography pulmonary angiography (CTPA). Comorbidities were recorded, pulmonary embolism severity index scores were calculated and CTPA data were evaluated as predictors for short-term mortality. RESULT: The study population consisted of 570 patients, 292 (51.2%) patients were female and 74 patients (12.9%) died within 30 days due to PE diagnosis. In univariate analysis male gender (p= 0.031), congestive heart failure (CHF)(p< 0.029), main pulmonary artery involvement (p= 0.045), presence of pleural effusion (p= 0.001) and pericardial effusion (p= 0.004) at time of diagnosis and high risk sPESI group (p< 0.001) had a significant influence on mortality. In the multivariate analysis, pleural effusions (HR, 1.67; CI, 1.05-2.66; p< 0.030) and sPESI high risk group (HR, 9.56; CI, 4.71-19.43; p< 0.001) were remained significant and independent prognostic factors for survival. CONCLUSIONS: The present study underlined that presence of pleural effusion at the time of diagnosis in patients with massive pulmonary embolism and a high sPESI score in other patients were significant predictors of short-term mortality.

Impact of Anxiety, Depression, and Coping Strategies on Health-Related Quality of Life in Patients with Cystic Fibrosis.

OBJECTIVE: With the significant increase in the life expectancy of cystic fibrosis (CF) patients, many individuals now reach adulthood and develop specific coping strategies to maintain their physical and mental well-being. This study aims to evaluate coping styles and their relationship with mental health and Health-Related Quality of Life (H-RQoL) in adult CF patients. MATERIALS AND METHODS: Thirty adult CF patients completed the Hospital Anxiety and Depression Scale to assess anxiety and depression, the Cystic Fibrosis Questionnaire-Revised to evaluate quality of life, and the Brief Coping Orientation to Problems Experienced questionnaire to assess coping strategies. RESULTS: Twelve individuals (40%) met the diagnostic criteria for being at risk of experiencing anxiety and/or depression. Anxiety risk group exhibited lower life quality scores in the domains of vitality, emotional functioning, and role limitations (P = .027, P = .001, and P = .001, respectively). Patients reporting depressive symptoms had lower scores in emotional functioning and role limitations domains of quality of life (P = .005 and P = .018, respectively). Multivariate analysis indicated that depression and anxiety scores were significant predictors of emotional quality of life. In terms of coping strategies, "acceptance" was the most commonly preferred, while "substance use" was the least preferred strategy among all participants. Patients at risk of anxiety and/or depression often chose "avoidance" as their coping strategy. CONCLUSION: Anxiety and depressive symptoms are prevalent and associated with poorer H-RQoL in adult CF patients. These patients preferred to employ giving up strategy when dealing with the disease. Therefore, it is essential to screen adult CF patients for mental health risks and to work on improving their coping strategies.

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.

Stem cell treatment reduces T cell apoptosis in COPD patients with chronic bronchitis but not with emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition. Mesenchymal stem cell (MSC) therapy is being explored to aid in the regeneration of lung cells and airway structure, aiming to restore lung function. AIM: To examine varied responses of MSCs when cultured with peripheral blood mononuclear cells (PBMCs) from different COPD phenotypes, patients were grouped into ACOS, emphysema, and chronic bronchitis categories. METHODS: PBMCs from these groups and controls were co-cultured with MSCs derived from dental follicles, revealing differing rates of apoptosis among COPD phenotypes compared to controls. RESULTS: While the chronic bronchitis group exhibited the least lymphocyte viability (p<0.01), introducing MSCs notably enhanced viability across all phenotypes except emphysema, with the chronic bronchitis group showing the most improvement (p<0.05). CONCLUSION: Stem cell therapy might reduce peripheral lymphocyte apoptosis in COPD, with varying responses based on phenotype, necessitating further research to understand mechanisms and optimize tailored therapies for each COPD subtype.

Clinical Pharmacist-Led Medication Review in Hospitalized Confirmed or Probable Patients with COVID-19 During the First Wave of COVID-19 Pandemic.

Objectives: Drug-related problems (DRPs) result in serious problems among hospitalized patients, high rates of morbidity and mortality, and increased healthcare costs. This study aimed to identify DRPs by clinical pharmacist-led medication review in hospitalized probable patients with coronavirus disease-2019 (COVID-19) during the first wave of the COVID-19 pandemic. Materials and Methods: This retrospective cross-sectional study was conducted at the COVID-19 inpatient services of a tertiary university hospital in Türkiye for 3 months (between March 2020 and June 2020) and included hospitalized confirmed or probable COVID-19 patients. The World Health Organization and Turkish Ministry of Health Guidelines case definitions were used to define confirmed and probable COVID-19 patients. Six clinical pharmacy residents provided medication review services during their education and training. DRPs were classified based on the Pharmaceutical Care Network Europe V9.00. The physician's acceptance rate of clinical pharmacists' recommendations was assessed. Results: Among 202 hospitalized patients with probable or confirmed COVID-19, 132 (65.3%) had at least one drug-related problem. Two hundred and sixty-four DRPs were identified. Drug selection (85.6%) and dose selection (9.2%) were the most common causes of these problems. Among the 80 clinical pharmacist interventions, 48.8% were accepted by the physicians. Conclusion: Clinical pharmacists identified a significant number of DRPs during the COVID-19 pandemic, particularly those related to drug interactions and drug safety, such as adverse drug reactions. This study highlights the importance of detecting and responding to DRPs in the COVID-19 pandemic.

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.

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.

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.

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.

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.