Pulmonary function tests reveal unrecognised lung dysfunction and have independent prognostic significance in patients with systemic AL amyloidosis.

BACKGROUND: Lung involvement in AL amyloidosis is not very common, but post-mortem data and retrospective studies suggest it is likely underrecognized. AIM: To perform a comprehensive evaluation of lung function with pulmonary function tests (PFTs) in patients with newly diagnosed AL amyloidosis. METHODS: A prospective, non-interventional study of 139 consecutive patients with newly diagnosed AL amyloidosis. RESULTS: PFTs indicated normal breathing physiology in 68% of patients, obstructive in 9% and restrictive in 23%; the latter was associated with worse survival (28.6 vs 76 months for obstructive/normal physiology, p = 0.002) and remained significant after adjustment for Mayo stage and abnormal chest-CT. Forced vital capacity <80% of predicted value, forced expiratory volume <80% of predicted value, and carbon monoxide diffusion capacity <70% were independently associated with poorer survival. Respiratory muscle strength (as assessed by maximal expiratory (Pe) and inspiratory (Pi) pressure) was affected in most patients (64% had Pi < 55% and 57% had Pe < 70% of predicted values). Pe% was an independent prognostic factor for survival (HR: 0.984 per 1% unit increase, p = 0.007). CONCLUSIONS: Pulmonary dysfunction, as assessed with PFTs, is common and underrecognized in patients with systemic AL amyloidosis, with significant prognostic and potentially therapeutic implications, independent of the degree of cardiac dysfunction or chest-CT findings.

Small airways dysfunction in patients with systemic sclerosis and interstitial lung disease.

Background: A number of studies report small airways involvement in patients with systemic sclerosis (SSc). Furthermore, small airways dysfunction is increasingly recognized in patients with interstitial lung disease (ILD) of idiopathic or autoimmune etiology. The objectives of this study were to evaluate small airways function in SSc patients with ILD and explore the effect of treatment on small airways function by using conventional and contemporary pulmonary function tests (PFTs). Methods: This single-center, prospective, observational study included a total of 35 SSc patients, with and without ILD based on HRCT scan, evaluated by a special radiologist blindly. Clinical data were collected from all patients who were also assessed for HRCT findings of small airways disease. Small airways function was assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide, body plethysmography, single breath nitrogen washout (N2SBW) and impulse oscillometry (IOS). The prevalence of small airways dysfunction according to R5-R20, phase III slopeN2SBW and CV/VC methodologies was calculated in the total SSc population. Pulmonary function tests were compared between: (a) SSc-ILD and non-ILD patients and (b) two time points (baseline and follow up visit) in a subset of SSc-ILD patients who received treatment for ILD and were re-evaluated at a follow up visit after 12 months. Results: Phase III slopeN2SBW and R5-R20 showed the highest diagnostic performance for detecting small airways dysfunction among SSc patients (61 and 37.5%, respectively). Twenty three SSc patients were found with ILD and 14 of them had a 12-month follow up visit. SSc-ILD patients compared to those without ILD exhibited increased phase III slopeN2SBW ≥120% (p = 0.04), R5-R20 ≥0.07 kPa/L/s (p = 0.025), airway resistance (Raw) (p = 0.011), and special airway resistance (sRaw) (p = 0.02), and decreased specific airway conductance (sGaw) (p = 0.022), suggesting impaired small airways function in the SSc-ILD group. Radiographic features of SAD on HRCT were observed in 22% of SSc-ILD patients and in none of SSc-non-ILD patients. Comparison of PFTs between baseline and follow-up visit after 12 months in the 14 SSc-ILD treated patients, showed improvement of phase III slopeN2SBW (p = 0.034), R5-R20 (p = 0.035) and Raw (p = 0.044) but not sRaw and sGaw parameters. Conclusion: Phase III slopeN2SBW and R5-R20 may reveal small airways dysfunction in SSc associated ILD before structural damage and may be partially improved in a subset of patients receiving treatment for ILD.

Cardiopulmonary Exercise Physiology in AL Amyloidosis Patients with Cardiac Involvement and Its Association with Cardiac Imaging Parameters.

Background: Cardiopulmonary exercise testing (CPET) has been widely used for the functional evaluation of patients with heart failure. Patients with amyloidosis and cardiac involvement typically present with heart failure with preserved or mildly reduced ejection fraction. We sought to evaluate the use of CPET parameters in patients with AL amyloidosis for the assessment of disease severity and prognosis and their association with cardiac imaging findings. Methods: A single-center prospective analysis was conducted, which included 23 consecutive ambulatory patients with AL amyloidosis with cardiac involvement, not requiring hospitalization or intravenous diuretics. Patient evaluation included CPET, laboratory testing, echocardiography and cardiac MRI. The cohort was divided according to the presence of high-risk CPET characteristics (below median peak VO2 and above median VE/VCO2). Results: Patients with AL amyloidosis and cardiac involvement (median age was 60 years (56.5% males) had median peak relative VO2 (VO2/kg) of 17.8 mL/kg/min, VE/VCO2 slope of 39.4 and circulatory power of 2362.5 mmHg⋅mL/kg/min. Peak relative VO2 gradually declined across Mayo stages (p = 0.046) and exhibited a significant inverse correlation with NT-proBNP levels (r = −0.52, p = 0.01). Among imaging parameters, peak VO2 positively correlated with global work efficiency (r = 0.61, p < 0.001), and global work index (r = 0.45, p = 0.04). The group of patients with high-risk CPET findings showed evidence of more advanced disease, such as higher NT-proBNP levels (p = 0.007), increased septal and posterior left ventricular wall thickness (p = 0.043 and p = 0.033 respectively) and decreased global work efficiency (p = 0.027) without substantial differences in cardiac MRI parameters. In this group of patients, peak VO2 and VE/VCO2 were not associated significantly with overall survival and cardiac response at one year. Conclusion: In patients with AL amyloidosis, evaluation of exercise capacity with CPET identified a group of patients with more advanced cardiac involvement. The potential of CPET as a risk stratification tool in AL amyloidosis with cardiac involvement warrants further research.

"Peculiar" Snoring in a 40-Year-Old Patient: A Case Report and Review of Literature.

This is a case description of a patient with previously diagnosed rapid eye movement sleep behavior disorder (RBD) and nocturnal enuresis, who complained about a "peculiar sound" while sleeping and, occasionally, while awake during intensive exercise, for the last three months. A home audio recording, which his wife obtained while he was sleeping, showed a high-pitched sound identified as stridor. Full video polysomnography revealed no apneas or hypopneas. The flow-volume loop yielded an inspiratory plateau, indicating variable extrathoracic obstruction. The upper and lower respiratory system computed tomography did not show any anomalies or mechanical lesions (e.g., masses and scars). Fiberoptic laryngoscopy revealed an abnormal activity of the vocal cord abductor during quiet breathing and inspiration in a supine position, leading to partial obstruction. A positive dopamine transporter scan and the coexistence of stridor, RBD, and nocturnal enuresis were diagnostic for multiple system atrophy. The patient was treated with continuous positive airway pressure as a symptomatic therapy for stridor and levodopa.

A COVID-19 Patient with Simultaneous Renal Infarct, Splenic Infarct and Aortic Thrombosis during the Severe Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a high incidence of arterial and venous thrombotic complications. However, thromboembolic events in unusual sites such as limb and visceral arterial ischemia are reported rarely in the literature. Herein, we describe a rare case of a patient with severe coronavirus disease 2019 (COVID-19) infection who experienced severe abdominal pain during the hospitalization and presented simultaneously renal artery, splenic artery and vein as well as aortic thrombi despite prophylactic antithrombotic treatment. Information about his follow-up post discharge is also provided. This case report raises significant clinical implications regarding the correct dose of antithrombotic treatment during the acute phase of the severe COVID-19 infection and highlights the need for incessant vigilance in order to detect thrombosis at unusual sites as a possible diagnosis when severe abdominal pain is present in severe COVID-19 patients.

Cardiopulmonary exercise testing and prognosis in patients with systemic sclerosis without baseline pulmonary hypertension: a prospective cohort study.

Cardiopulmonary Exercise Testing (CPET) is a standardized, non-invasive procedure assessing pulmonary, cardiovascular, hematopoietic, and skeletal muscle functions during a symptom-limited test. Few studies have examined whether CPET is of prognostic value in Systemic Sclerosis (SSc), a disease characterized by highly increased cardiorespiratory morbidity and mortality. To examine the prognostic value of CPET in SSc patients without baseline pulmonary hypertension (PH). Sixty-two consecutive SSc patients underwent CPET, Pulmonary Function Tests (PFTs) and echocardiography at baseline. Four patients with Right Ventricular Systolic Pressure ≥ 40 mmHg, were excluded. Participants repeated PFTs approximately every 3 years. At the end of the follow-up period [median (IQR): 9.79 (2.78) years] patient vital status was recorded. Cox Regression analysis was used to identify predictors of deterioration of PFTs and 10-year survival. Median (IQR) age of 58 patients (90% women) at baseline was 54.0 (15.0) years, whereas 10-year survival was 88%. Baseline respiratory Oxygen uptake (VO2max) predicted PFT deterioration, defined either as a decline in FVC ≥ 10% or a combined decline in FVC 5%-9% plus DLCO ≥ 15%, during follow-up, after correction for age, gender and smoking status (HR: 0.874, 95%CI: 0.779-0.979, p = 0.021). In addition, lower baseline VO2max (HR = 0.861, 95%CI:0.739-1.003, p = 0.054) and DLCO (HR = 0.957, 95%CI: 0.910-1.006 p = 0.088), as well as male gender (HR = 5.68, 95%CI: 1.090-29.610 p = 0.039) and older age (HR = 1.069, 95%CI: 0.990-1.154, p = 0.086) were associated, after adjustment, with an increased risk for death. In the absence of baseline PH, CPET indices may predict pulmonary function deterioration and death in SSc patients during a nearly 10-year follow-up period.

Visceral leishmaniasis and COVID-19 coinfection - A case report.

As the COVID-19 pandemic spreads across the globe, it will undoubtedly cross paths with long endemic infectious diseases in different areas. Interactions between SARS-CoV2 and well-known pathogens will likely give rise to unfamiliar clinical presentations, depending on complex and as yet unknown immunological interactions. We present a case of coinfection with COVI19 and visceral leishmaniasis and discuss recent reports regarding coexistence of SARS-CoV2 and Leishmania spp. to date.

A Pilot Study About the Dysfunction of Adipose Tissue in Male, Sleep Apneic Patients in Relation to Psychological Symptoms.

Introduction: Obstructive sleep apnea (OSA) and its cardiometabolic alterations are closely associated with visceral obesity. Patients with OSA frequently present with symptoms of depression and anxiety. Although these subjective symptoms of OSA are the result of complex biological dysregulation, it remains unclear if they have a direct effect on the dysfunction of adipose tissue. Methods: In a pilot, prospective, randomized study, we evaluated 10 recently diagnosed male patients with severe OSA by full polysomnography (PSG) and 4 male non-apneic subjects matched for age and body mass index (BMI) with abdomen adipose tissue biopsies. Subjects with diabetes/prediabetes and cardiovascular and psychiatric diseases and who are current smokers were excluded. All patients underwent anthropometric measurements and completed the following questionnaires: Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Fasting venous blood samples were collected on the day after PSG, between 8:00 and 9:00 a.m., after an overnight fast. Fat biopsies were performed at the same time periods and adipose tissue samples of 300 mg were obtained from abdominal fat. Fat cell size, extent of fibrosis, vascularity, leukocyte common antigen inflammatory infiltration, and tissue macrophage accumulation were microscopically evaluated. Results: The mean age of the group was 47.4 ± 13.8 years, with mean BMI of 35.8 ± 4.8 kg/m2 and mean apnea-hypopnea index of 79.4 ± 46.1 events per hour of sleep (severe OSA). HADS-A and HADS-D scores were 5.8 ± 2.3 (3.0-8.0) and 4.7 ± 2.3 (2.0-8.0), respectively. HADS-A score correlated positively with macrophage accumulation in fat biopsy (r = 0.82, p = 0.047), whereas ESS, FSS, and HADS-D did not. Severity of fibrosis correlated largely with waist circumference (r = -0.66, p = 0.038) and neck circumference (r = -0.790, p = 0.006). Respiratory events correlated negatively with the extent of vascularization of adipose tissue (r = -0.614, p = 0.05). Conclusions: In the preliminary results of our pilot study, we assessed that the symptoms of anxiety mainly contribute to macrophage accumulation, whereas the increased number of respiratory events reduces the extent of vascularization in visceral fat in OSA. Based on this observation, further larger studies are required to verify if anxious OSA patients are more vulnerable to the metabolic manifestations of the syndrome.

Clinical Characteristics of Obstructive Sleep Apnea in Psychiatric Disease.

Patients with serious psychiatric diseases (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia and psychotic disorder) often complain about sleepiness during the day, fatigue, low energy, concentration problems, and insomnia; unfortunately, many of these symptoms are also frequent in patients with Obstructive Sleep Apnea (OSA). However, existing data about the clinical appearance of OSA in Psychiatric Disease are generally missing. The aim of our study was a detailed and focused evaluation of OSA in Psychiatric Disease, in terms of symptoms, comorbidities, clinical characteristics, daytime respiratory function, and overnight polysomnography data. We examined 110 patients (56 males and 54 females) with stable Psychiatric Disease (Group A: 66 with MDD, Group B: 34 with BD, and Group C: 10 with schizophrenia). At baseline, each patient answered the STOP-Bang Questionnaire, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS) and underwent clinical examination, oximetry, spirometry, and overnight polysomnography. Body Mass Index (BMI), neck, waist, and hip circumferences, and arterial blood pressure values were also measured. The mean age of the whole population was 55.1 ± 10.6 years. The three groups had no statistically significant difference in age, BMI, hip circumference, and systolic and diastolic arterial blood pressure. Class II and III obesity with BMI > 35 kg/m2 was observed in 36 subjects (32.14%). A moderate main effect of psychiatric disease was observed in neck (p = 0.044, η2 = 0.064) and waist circumference (p = 0.021, η2 = 0.078), with the depression group showing the lowest values, and in pulmonary function (Forced Vital Capacity (FVC, %), p = 0.013, η2 = 0.084), with the psychotic group showing the lowest values. Intermediate to high risk of OSA was present in 87.37% of participants, according to the STOP-Bang Questionnaire (≥3 positive answers), and 70.87% responded positively for feeling tired or sleepy during the day. An Apnea-Hypopnea Index (AHI) ≥ 15 events per hour of sleep was recorded in 72.48% of our patients. AHI was associated positively with male sex, schizophrenia, neck, and waist circumferences, STOP-Bang and ESS scores, and negatively with respiratory function. A large main effect of psychiatric medications was observed in waist circumference (p = 0.046, η2 = 0.151), FVC (%) (p = 0.027, η2 = 0.165), and in time spend with SaO2 < 90% (p = 0.006, η2 = 0.211). Our study yielded that patients with Psychiatric Disease are at risk of OSA, especially men suffering from schizophrenia and psychotic disorders that complain about sleepiness and have central obesity and disturbed respiratory function. Screening for OSA is mandatory in this medical population, as psychiatric patients have significantly poorer physical health than the general population and the coexistence of the two diseases can further negatively impact several health outcomes.

Pulmonary function abnormalities are common in patients with multiple myeloma and are independently associated with worse outcome.

Pre-existing pulmonary disease may affect treatment choices, toxicity, and survival of patients with multiple myeloma (MM). However, data on the prognostic value of pulmonary function tests (PFTs) in myeloma patients' outcome, at the time of initial assessment of newly diagnosed patients, are scarce. Here, we prospectively performed PFTs in 121 newly diagnosed MM patients, before initiation of treatment, and we evaluated possible associations of lung function with their outcomes. Fifty-four patients (44.63%) had either obstructive or restrictive pulmonary function defects, even among those not reporting a history of lung disease. The survival was significantly worse in those with obstructive pulmonary defect (median OS 32.8 months) vs. those with restrictive (median OS 52.5 months) or normal lung function (median not reached, 3-year survival 76%) (p = 0.013), independently of other myeloma-related factors. Forced vital capacity (FVC) (lt) (p = 0.012), forced expiratory volume in 1 s (FEV1) (lt) (p = 0.018), peak expiratory flow (PEF) (lt/min) (p = 0.008), carbon monoxide diffusion capacity (DLCO) (p = 0.012), and expiratory/inspiratory pressures (Pe) (kPa) (p = 0.032)/(Pi) (kPa) (p = 0.023) were significantly associated with OS. Myeloma-related factors associated with survival included ISS stage (p = 0.008), hypercalcemia (p = 0.064), and high-risk cytogenetics (p = 0.004). In the multivariate analysis, only the presence of high-risk cytogenetics and presence of either or both PEF and DLCO < 65% of predicted were independent prognostic factors. We conclude that PEF and DLCO could be useful in the initial assessment of newly diagnosed MM patients as significant predictors of survival. Further research is needed to evaluate if respiratory screening should be included in the routine initial evaluation of myeloma patients, despite the presence or absence of respiratory symptoms or abnormal clinical respiratory examination.

Sleepiness, fatigue, anxiety and depression in Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea - Overlap - Syndrome, before and after continuous positive airways pressure therapy.

Patients with Chronic Obstructive Pulmonary Disease (COPD) and / or Obstructive Sleep Apnea (OSA) often complain about sleepiness, fatigue, anxiety and depression. However, common screening questionnaires, like Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS) have not been previous evaluated in patients with overlap-coexisting COPD and OSA-syndrome versus patients with OSA alone. Our study compared ESS, FSS and HADS between patients with overlap syndrome and patients with OSA, before and after treatment with Continuous Positive Airways Pressure (CPAP). We examined 38 patients with coexisting COPD and OSA versus 38 patients with OSA-only and 28 subjects without respiratory disease, serving as controls. All patients underwent pulmonary function tests (PFTs), oximetry and overnight polysomnography and completed the questionnaires, before and after 3 months of CPAP therapy. The two patient groups did not differ significantly in terms of age, Body Mass Index (BMI), neck, waist and hip circumferences, and arterial blood pressure values. They also had similar comorbidities. They differed significantly, as expected, in PFTs (Forced Vital Capacity-FVC, 2.53±0.73 vs 3.08±0.85 lt, p = 0.005, Forced Expiratory Volume in 1sec-FEV1, 1.78±0.53 vs 2.60±0.73 lt/min, p<0.001) and in daytime oximetry (94.75±2.37 vs 96.13±1.56%, p = 0.007). ESS, HADS-Anxiety and HADS-Depression scores did not differ statistically significant between these two groups, whereas overlap syndrome patients expressed significantly more fatigue (FSS) than OSA-only patients, a finding that persisted even after 3 months of CPAP therapy. We conclude that sleepiness, anxiety and depression were similar in both groups, whereas fatigue was more prominent in patients with overlap syndrome than in sleep apneic patients and did not ameliorate after treatment.

Convex-probe endobronchial ultrasound for thyroid biopsy a new hybrid method.

Nowadays we use novel diagnostic equipment for lung cancer. Bronchoscopy was the tip of the arrow for diagnosis, however; ultrasound systems have brought a revolution. We have the radial-endobronchial ultrasound for peripheral lesions and the convex probe endobronchial ultrasound for central lesions. Ultrasound endoscopic systems can be used for the diagnosis of any lesion that can be approached from the airways. In the current manuscript we will present two methods for the biopsy of thyroid gland. The first method is using anesthisiological tools and the second tools from the ear, nose and throat department.

Successful treatment of postoperative massive pulmonary embolism with paradoxal arterial embolism through extracorporeal life support and thrombolysis.

Pulmonary embolism is a common clinical entity related to high mortality. About 200,000 to 300,000 patients die every year due to pulmonary embolism. The purpose of this article is to describe a case of a patient who on the second postoperative day after undergoing thromboembolectomy of the left femoral artery, manifested a massive pulmonary embolism. Due to cardiorespiratory collapse a combined treatment via extracorporeal life support (ECLS) and parallel catheter thrombolysis was decided and performed. By cardiorespiratory improvement and final stabilization the patient was successfully weaned from ECLS and the system was successfully removed. After a reasonable postoperative time the patient was dismissed in good overall condition.

Hamman's syndrome (spontaneous pneumomediastinum presenting as subcutaneous emphysema): A rare case of the emergency department and review of the literature.

Pneumomediastinum is a rare clinical entity that concerns the clinicians in the emergency department. We present a case of a patient with spontaneous pneumomediastinum (Hamman's syndrome) that presented to our hospital's emergency department with cervical subcutaneous emphysema. A conservative treatment with observation was performed. The patient after 24 hours of observation was discharged with a suggested follow-up.

A new mode of ventilation for interventional pulmonology. A case with EBUS-TBNA and debulking.

Lung cancer is still underdiagnosed mainly due to lack of symptoms. Most patients are diagnosed in a late stage where unfortunately only systematic therapy can be applied. Fortunately in the last five years several novel therapies and combinations have emerged. However; in certain situations local therapeutics modalities have to be applied in order to solve emergency problems as in the case that we will present. Convex-EBUS probe was used along with a novel method of ventilation which keeps PCO2 concentration satisfyingly low.

Immunotherapy "Shock" with vitiligo due to nivolumab administration as third line therapy in lung adenocarcinoma.

Non-small cell lung cancer is still diagnosed at late stage due to the lack of early symptoms and methods of diagnostic prevention. In the past ten years several targeted therapies have been introduced or explored. Tyrosine kinase inhibitors and immunotherapy are currently considered the most effective and safe therapies in comparison to the non-specific cytotoxic agents. Regarding tyrosine kinase inhibitors the adverse effects have been fully explored, however; on the other hand for immunotherapy there are still several issues to be clarified. We report a rare case of a patient with lung cancer adenocarcinoma who developed vitiligo throughout his body after nivolumab administration.

Endobronchial ultrasound convex probe for lymphoma, sarcoidosis, lung cancer and other thoracic entities. A case series.

Endobronchial ultrasound endoscopy is a state of the art diagnostic endoscopic procedure for the thorax. Firstly it was designed mainly for the staging of lung cancer and of course for the diagnosis of suspicious findings in large central airways. The main limitation of the equipment is the diameter of the instrument and therefore it can only be guided through large airways. However; the diameter of the working channel also provides a large tissue sample nowadays with the 19G biopsy needle. We will provide our experience with the 22G needle of the endobronchial convex-probe in several medical situations of the thorax.

Immunotherapy "Shock" a case series of PD-L1 100% and pembrolizumab first-line treatment.

In this decade a "bloom" of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

EGFR or PD-L1 decision for first line therapy in a case series of EGFR positive and PD-L1 >50.

Targeted therapies are on the market for the past five years and recently pembrolizumab was approved as first line treatment for patients with PD-L1 >50%. We present three cases of patients which had epidermal growth factor receptor positive expression and programmed death-ligand 1 (PD-L1), PD-L1 >50% overexpression.