Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

Persistent Sleep Quality Deterioration among Post-COVID-19 Patients: Results from a 6-Month Follow-Up Study.

Background: To date, evidence about sleep disturbances among post-COVID-19 patients is limited. This study aimed to evaluate sleep quality after hospitalization due to SARS-CoV-2 infection. Methods: In-person follow-up was conducted in patients with prior hospitalization due to COVID-19 1(Τ1), 3(Τ2), and 6 (Τ3) months after hospital discharge. Patients were asked to complete questionnaires concerning sleep quality: the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Athens Insomnia Scale (AIS), the Fatigue Severity Scale (FSS), and the Stop-BANG (S-B) questionnaire. Results: In total, 133 patients were enrolled (mean age: 56.0 ± 11.48 years, 59.4% males). The most frequently reported comorbidity was arterial hypertension (29.8% of patients), while 37.4% of patients had no comorbidities. The majority of participants exhibited poor sleep quality (global PSQI ≥ 5) at T1 (84.3%), T2 (75.7%), and T3 (77.4%). Insomnia was observed in 56.5%, 53.5%, and 39.2% of participants, respectively (AIS ≥ 6). An FSS score ≥ 4 was observed in 51.2%, 33.7%, and 29.1% of participants at T1, T2, T3, respectively. Elapsed time was found to be negatively and independently associated with the global PSQI, PSQI C5-Sleep disturbance, PSQI C7-Daytime dysfunctions, FSS, and AIS after adjustment for possible confounders. No significant difference was found between groups with good and poor sleep quality (based on the global PSQI) with respect to gender (p = 0.110), age (p = 0.528), BMI (p = 0.816), smoking status (p = 0.489), hypertension (p = 0.427), severity of disease (p = 0.224), the Charlson Comorbidity Index (p = 0.827), or the length of hospital stay (p = 0.162). Participants with excessive daytime sleepiness (EDS) and patients with severe fatigue (FSS ≥ 4) were significantly younger. Females presented a higher rate of insomnia symptoms (55.7% vs. 44.3%, p < 0.001). Conclusions: Several sleep disturbances were observed after hospital discharge for COVID-19 pneumonia at certain time points; However, the improvement over time was remarkable in most domains of the assessed questionnaires.

Modification Tadalafil and Macitentan tablets to aerosol.

INTRODUCTION: Aerosolised drugs have been approved for several diseases such as cystic fibrosis and diabetes. Moreover; there are already drugs for pulmonary hypertension in aerosol form already on the market. MATERIALS AND METHODS: Two drugs for pulmonary hypertension (Tadalafil and Macitentan) were milled and transformed from tablets to powder. Three different jet-nebulizers with seven different residual cups were combined. Moreover, we used 3 different ultrasound nebulizers with two different release methods. RESULTS: The drug and residual cup designs produce alone or jointly different MMAD diameters. The three large (10 mls) residual cups with the jet-nebulisers produced the smallest aerosol droplets. Both ultrasound nebulisers are capable of producing optimal size aerosol droplets ≤5 µm mmad. CONCLUSIONS: These two drugs can be easily administered as aerosol and an vivo clinical study will prove the safety for the airways.

Effects of oxygen supplementation in autonomic nervous system function during exercise in patients with idiopathic pulmonary fibrosis and exertional desaturation.

INTRODUCTION: Patients with idiopathic pulmonary fibrosis (IPF) have reduced exercise capacity and often present exertional dyspnea and desaturation. The role of autonomic nervous system (ANS) as a pathogenetic contributor to this dysfunction has not been evaluated. OBJECTIVE: To evaluate whether improvement of arterial oxygen saturation (SpO2 ) via oxygen supplementation results to ANS function improvement, during steady state submaximal exercise. METHODS: This is a secondary analysis of a single-blind, randomized, placebo-controlled, cross-over trial, including 12 IPF patients, with isolated exertional desaturation. Following a maximal cardiopulmonary test, participants underwent two submaximal steady state tests during which they received either supplementary oxygen or medical air. Continuous beat-to-beat blood pressure measurements were recorded (Finapres Medical Systems, Amsterdam, The Netherlands). Autonomic function was assessed non-invasively by heart rate variability (HRV); root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Entropy and detrended fluctuation analysis (DFA) were also used. RESULTS: During rest, oxygen supplementation did not significantly alter RMSSD and SD1. During exercise, subjects presented no significant alterations compared with baseline, in most HRV indices examined. There was no improvement of this behavior with O2 -supplementation. Approximate-entropy increased during exercise, with no differences between protocols. CONCLUSIONS: IPF patients presented an inadequate adaptive response of their ANS to exercise and recovery. Although oxygen supplementation significantly prolonged exercise duration and prevented the substantial exertional desaturation, the blunted vagal response to steady-state exercise in these patients was not improved, suggesting that acute oxygen supplementation does not sufficiently improve ANS dysfunction in these patients.

Pulmonary rehabilitation for cystic fibrosis: A narrative review of current literature.

Pulmonary rehabilitation is a key component in cystic fibrosis care.  This review summarizes the recent evidence in the area of pulmonary rehabilitation for cystic fibrosis in the form of questions and answers regarding interventions, indications, benefits and risks of pulmonary rehabilitation. Pulmonary rehabilitation includes airway clearance techniques, exercise training, education and behaviour change and can improve patients' exercise capacity, muscle strength, quality of life and nutritional status. Airway clearance techniques have beneficial effects for clearing mucous. Over the past years, evidence for the beneficial effects of exercise training on exercise capacity and overall lung health is growing. In cystic fibrosis, multiple factors result in reduced exercise capacity. All modalities of pulmonary rehabilitation should be offered to patients with cystic fibrosis, as the benefits in most cases outweigh the risks, though the optimal regimens need to be yet defined.

Exertional Desaturation in Idiopathic Pulmonary Fibrosis: The Role of Oxygen Supplementation in Modifying Cerebral-Skeletal Muscle Oxygenation and Systemic Hemodynamics.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF) with isolated exertional desaturation, there are limited data regarding the effectiveness of oxygen supplementation during exercise training; the underlying mechanisms that contribute to these responses are unknown. OBJECTIVES: To examine in these IPF patients the effects of oxygen supplementation during submaximal exercise (vs. medical air) on cerebral/skeletal muscle oxygenation and systemic hemodynamics. METHODS: In this randomized, cross-over, placebo-controlled trial, IPF patients (n = 13; 63.4 ± 9.6 years) without resting hypoxemia but a significant desaturation during maximal cardiopulmonary exercise testing underwent 2 steady-state exercise trials (65% peak-work-load), breathing either oxygen-enriched or medical air. Cerebral/skeletal muscle oxygenation (near-infrared spectroscopy) and beat-by-beat hemodynamics (photoplethysmography) were monitored. RESULTS: In the air protocol, from the initial minutes of submaximal exercise, patients exhibited a marked decline in cerebral oxygenated hemoglobin (O2Hb) and an abrupt rise in deoxygenated hemoglobin (HHb). Oxygen supplementation alleviated desaturation, lessened dyspnea, and prolonged exercise duration (p < 0.01). Oxygen supplementation during exercise (i) attenuated cerebral deoxygenation (cerebral-HHb: 0.7 ± 1.9 vs. 2.5 ± 1.5 µmol/L, O2 and air protocol; p = 0.009) and prevented cerebral-Hbdifference decline (2.1 ± 2.7 vs. -1.7 ± 2.0 µmol/L; p = 0.001), (ii) lessened the decline in muscle O2-saturation index, and (iii) at isotime exercise, it resulted in lower muscle-HHb (p = 0.05) and less leg fatigue (p < 0.05). No differences between protocols were observed in exercise cardiac output and vascular resistance. CONCLUSIONS: IPF patients with isolated exertional hypoxemia exhibit an inability to increase/maintain cerebral oxygenation during submaximal exercise. Correcting desaturation with O2 supplementation prevented the decline in brain oxygenation, improved muscle oxygenation, and lessened dyspnea, suggesting an efficacy of acute oxygen supplementation during exercise training in protecting brain hypoxia in these IPF patients.

Longitudinal changes in exercise capacity among adult cystic fibrosis patients.

INTRODUCTION: Longitudinal data regarding changes in exercise capacity among adult cystic fibrosis (CF) patients are currently scarce. The aim of this brief report was to assess changes in exercise capacity among adult CF patients with stable and mild-to-moderate disease eight years after their initial evaluation. MATERIAL AND METHODS: Maximum cardiopulmonary exercise testing (CPET) was utilized. Other assessments included Doppler echocardiography, the 6-minute walking test, spirometry, and lung volume evaluation. RESULTS: Eleven (6 male, 5 female) patients completed both evaluations (initial and after eight years). During follow-up, indices of ventilatory impairment (such as ventilatory reserve; p=0.019, and ventilatory equivalent for carbon dioxide; p = 0.047) deterio-rated significantly following a decline in respiratory function measurements. Peak oxygen uptake (VO2), both as an absolute (26.6 ± 8.46 vs 23.89 ± 6.16 mL/kg/min; p = 0.098) and as a % of predicted value (71.21 ± 16.54 vs 70.60 ± 15.45; p = 0.872), did not deteriorate. This is also true for oxygen pulse (p = 0.743), left heart ejection fraction (p = 0.574), and pulmonary artery systolic pressure (p = 0.441). However, the anaerobic threshold, both as an absolute (p = 0.009) and as a % of predicted value (p = 0.047), was significantly lower during follow-up. CONCLUSION: In adult CF patients with stable, mild-to-moderate disease, a peak VO2 may be preserved for several years. However, even in these patients, deconditioning is present.

Nicotine treatment and smoking cessation in the era of COVID-19 pandemic: an interesting alliance.

In the era of this pandemic, the role of medicinal nicotine in the prevention and treatment of #COVID19 disease should be evaluated in placebo-controlled trials, while smoking cessation should be further promoted as a general public health measure https://bit.ly/3fpsBdq.

Tyrosine Kinase Inhibitors for the Elderly.

Until few years ago non-specific cytotoxic agents were considered the tip of the arrow as first line treatment for lung cancer. However; age > 75 was considered a major drawback for this kind of therapy. Few exceptions were made by doctors based on the performance status of the patient. The side effects of these agents are still severe for several patients. In the recent years further investigation of the cancer genome has led to targeted therapies. There have been numerous publications regarding novel agents such as; erlotinib, gefitinib and afatinib. In specific populations these agents have demonstrated higher efficiency and this observation is explained by the overexpression of the EGFR pathway in these populations. We suggest that TKIs should administered in the elderly, and with the word elderly we propose the age of 75. The treating medical doctor has to evaluate the performance status of a patient and decide the best treatment in several cases indifferent of the age. TKIs in most studies presented safety and efficiency and of course dose modification should be made when necessary. Comorbidities should be considered in any case especially in this group of patients and the treating physician should act accordingly.

Apparent Diffusion Coefficient Quantification in Determining the Histological Diagnosis of Malignant Liver Lesions.

PURPOSE: Diffusion Weighted Imaging is an established diagnostic tool for accurate differential diagnosis between benign and malignant liver lesions. The aim of our study was to evaluate the role of Histogram Analysis of ADC quantification in determining the histological diagnosis as well as the grade of malignant liver tumours. To our knowledge, there is no study evaluating the role of Histogram Analysis of ADC quantification in determining the histological diagnosis as well as the grade of malignant liver tumours. METHODS: During five years, 115 patients with known liver lesions underwent Diffusion Weighted Imaging in 3Tesla MR scanner prior to core needle biopsy. Histogram analyses of ADC in regions of interest were drawn and were correlated with biopsy histological diagnosis and grading. RESULTS: Histogram analysis of ADC values shows that 5th and 30th percentile parameters have statistically significant potency of discrimination between primary and secondary lesions groups (p values 0.0036 and 0.0125 respectively). Skewness of the histogram can help discriminate between good and poor differentiated (p value 0.17). Discrimination between primary malignancy site in metastases failed for the present number of patients in each subgroup. CONCLUSION: Statistical parameters reflecting the shape of the left side of the ADC histogram can be useful for discriminating between primary and secondary lesions and also between well differentiated versus moderate or poor. For the secondary malignancies, they failed to predict the original site of tumour.

Drug Eluting Stents for Malignant Airway Obstruction: A Critical Review of the Literature.

Lung cancer being the most prevalent malignancy in men and the 3(rd) most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement.

Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report.

Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient's history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long-term survival.

Radial Endobronchial Ultrasound (EBUS) Guided Suction Catheter-Biopsy in Histological Diagnosis of Peripheral Pulmonary Lesions.

BACKGROUND: EBUS guided trans-bronchial biopsy became routine in diagnosis of peripheral pulmonary lesions (PPL). Suction catheter-biopsy is a technique for obtaining a tissue sample from peripheral lung parenchyma. Aim of this study was to evaluate diagnostic efficiency, feasibility and safety of EBUS guided suction catheter-biopsy (SCB) in comparison to trans-bronchial biopsy (TBB) in diagnosis of PPL. The main intention was to demonstrate non-inferiority of the technique over trans-bronchial biopsy, especially when used under navigation of the EBUS. METHODS: Radial EBUS probe (UM-3R, Olympus Co, Japan.) without guiding sheath was used to navigate suction catheter and TBB forceps to the PPL. The catheter was connected to the collection canister via vacuum pump. The SCB specimens were fixed with 10% buffered formalin. RESULTS: There were 168 patients enrolled in this study; 69.9% males and 30.1% females. Main lesion diameter was 4.1±1.9 cm. Majority of patients, 131(77.9%) were diagnosed with lung cancer. Per-biopsy calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EBUS-SCB were 92.4%, 100%, 100% and 67.7%, respectively. Corresponding values for EBUS-TBB were 92.3%, 100%, 100% and 69.7%. Only the size of the lesion significantly influenced (p=0.005) diagnostic performance. Complications occurred in 2 patients; one pneumothorax and one excessive bleeding. CONCLUSION: EBUS guided SCB is efficient, feasible and safe in diagnosis of peripheral lung cancer. The technique is complementary to trans-bronchial biopsy.

Prophylactic antibiotic administration for post cardiothoracic surgery sternal wounds: a retrospective study.

BACKGROUND: Cardiothoracic surgery sternal infections are difficult to treat situations. Until now there are no clear guidelines which or if an antibiotic could be used as prophylactic treatment. PATIENTS AND METHODS: We collected retrospectively data from 535 patients from our hospital which underwent cardiothoracic surgery and recorded several biological parameters and technical aspects of the surgery. RESULTS: It was observed that patients to whom vancomycin was administered had less post surgery infection than those to whom begalin was administered. Male who were treated with vancomycin it was observed that they had 1.67 chances to be treated properly than female. Patients which were hospitalized for more than 7 days before surgery had 62.6% higher chances for post surgery infection. CONCLUSIONS: It was observed that vancomycin can be used as a prophylactic treatment for cardiothoracic surgeries acting efficiently against sternal wounds.

Minimally invasive procedures.

Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small "ports" from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry-meaning only one small incision, like the "uniport" video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional "open" surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery.

Pneumothorax from diagnosis to treatment, hands on course: Part II.

Pneumothorax is a situation where air is inserted in the pleural space that separates the lung from the chest wall. Pneumothorax can be primary or secondary. There is also a third type called; tensioned. Based on the concentration of air and type of pneumothorax the proper treatment has to be selected. There are cases where the concentration is minimal and observation is enough and more severe cases where surgery is required. Currently there are many techniques used for the biopsy of lung lesions. The bronchoscope (forceps, fine needle aspiration), fine needle aspiration under computed tomography scan and endobronchial ultrasound (EBUS) are commonly used. However, all these techniques have in common a possible side effect; pneumothorax. In our current issue we will focus on the different minimally invasive techniques of pneumothorax management. Moreover, a presentation will be made for several systems that are being used for air or fluid aspiration.

Pacemaker insertion.

A pacemaker (PM) (or artificial PM, so as not to be confused with the heart's natural PM) is a medical device that uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart. The primary purpose of this device is to maintain an adequate heart rate, either because the heart's natural PM is not fast enough, or there is a block in the heart's electrical conduction system. Modern PMs are externally programmable and allow the cardiologist to select the optimum pacing modes for individual patients. Some combine a PM and defibrillator in a single implantable device. PMs can be temporary or permanent. Temporary PMs are used to treat short-term heart problems, such as a slow heartbeat that's caused by a heart attack, heart surgery, or an overdose of medicine. Permanent PMs are used to control long-term heart rhythm problems. A PM can relieve some arrhythmia symptoms, such as fatigue and fainting. A PM also can help a person who has abnormal HRs resume a more active lifestyle. In the current mini review we will focus on the insertion of a PM and the possible pneumothorax that can be caused.

Thoracocentesis: from bench to bed.

Lung cancer can be diagnosed with minimal interventional procedures such as: bronchoscopy, endobronchial ultrasound (EBUS), fine needle aspiration under CT guidance and esophageal ultrasound. In our current editorial we will provide a definition and current up to date information regarding fine needle aspiration under CT guidance. We will focus on pneumothorax and treatment methods.

Open thoracotomy for pneumothorax.

A thoracotomy is an incision into the pleural space of the chest. It is performed by surgeons (or emergency physicians under certain circumstances) to gain access to the thoracic organs, most commonly the heart, the lungs, or the esophagus, or for access to the thoracic aorta or the anterior spine. This surgical procedure is a major surgical maneuver it is the first step in many thoracic surgeries including lobectomy or pneumonectomy for lung cancer and as such requires general anesthesia with endotracheal tube insertion and mechanical ventilation, rigid bronchoscope can be also used if necessary. Thoracotomies are thought to be one of the most difficult surgical incisions to deal with post-operatively, because they are extremely painful and the pain can prevent the patient from breathing effectively, leading to atelectasis or pneumonia. In the current review we will present the steps of this procedure.