Chronic Thromboembolic Pulmonary Hypertension: An Observational Study.

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) has a high mortality. The treatment of CTEPH could be balloon pulmonary angioplasty (BPA), medical (MT) or pulmonary endarterectomy (PEA). This study aims to assess the clinical characteristics of CTEPH patients, surgically or medically treated, in a pulmonology referral center. Materials and Methods: A total of 124 patients with PH with suspected CTEPH (53 male subjects and 71 female subjects; mean age at diagnosis 67 ± 6) were asked to give informed consent and then were evaluated. The presence of CTEPH was ascertained by medical evaluations, radiology and laboratory tests. Results: After the evaluation of all clinical data, 65 patients met the inclusion criteria for CTEPH and they were therefore enrolled (22 males and 43 females; mean age at diagnosis was 69 ± 8). 26 CTEPH patients were treated with PEA, 32 with MT and 7 with BPA. There was a statistically significant age difference between the PEA and MT groups, at the time of diagnosis, the PEA patients were younger than the MT patients, whereas there was no statistically significant difference in other clinical characteristics (e.g., smoking habit, thrombophilia predisposition), as well as functional and hemodynamic parameters (e.g., 6-min walk test, right heart catheterization). During three years of follow-up, no patients in the PEA groups died; conversely, eleven patients in the MT group died during the same period (p < 0.05). Furthermore, a significant decrease in plasma BNP values and an increase in a meter at the six-minute walk test, 1 and 3 years after surgery, were observed in the PEA group (p < 0.05). Conclusions: This study seems to confirm that pulmonary endarterectomy (PEA) can provide an improvement in functional tests in CTEPH.

Advances in systemic therapy for malignant mesothelioma: future perspectives.

Malignant mesothelioma is a rare and aggressive form of cancer affecting the mesothelium. This mainly occupational disease is becoming more common in those countries where asbestos has been used for industrial applications. Notwithstanding the progress made in the field, patients do not survive more than 12 months on average with standard treatment. With the advent of next generation sequencing, it is now possible to study the mutational landscape of each tumor with the aim of identifying the genetic aberrations driving tumorigenesis. This review encompasses the latest research in the field, with particular attention to new chemotherapy combinatorial regimens, molecular targets and immunotherapies, providing a comprehensive picture of the current and future treatment options for malignant mesothelioma patients.

Chronic Thromboembolic Pulmonary Hypertension: An Update.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease observed in a small proportion of patients after acute pulmonary embolism (PE). CTEPH has a high morbidity and mortality rate, related to the PH severity, and a poor prognosis, which mirrors the right ventricular dysfunction involvement. Pulmonary endarterectomy (PEA) reduces pulmonary vascular resistance, making it the treatment of choice and should be offered to operable CTEPH patients, as significant symptomatic and prognostic improvement has been observed. Moreover, these patients may also benefit from the advances made in surgical techniques and pulmonary hypertension-specific medication. However, not all patients are eligible for PEA surgery, as some have either distal pulmonary vascular obstruction and/or significant comorbidities. Therefore, surgical candidates should be carefully selected by an interprofessional team in expert centers. This review aims at making an overview of the risk factors and latest developments in diagnostic tools and treatment options for CTEPH.

TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance.

Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere (ALT) maintenance pathway in cancer cells are poorly understood. Using human lung cancer cells and tumor organoids we show that formation of the 2,2,7-trimethylguanosine (TMG) cap structure at the human telomerase RNA 5' end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. TGS1 depletion or inhibition by the natural nucleoside sinefungin impairs telomerase recruitment to telomeres leading to Exonuclease 1 mediated generation of telomere 3' end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Our work introduces a targetable pathway of telomere maintenance that holds relevance for telomere-related diseases such as cancer and aging.

High-frequency percussive ventilation improves perioperatively clinical evolution in pulmonary resection.

OBJECTIVE: During thoracotomy, positive end-expiratory pressure is applied to the dependent lung and continuous positive airway pressure (CPAP) inflates the nondependent lung to avoid hypoxemia. These methods do not allow the removal of produced secretions. We hypothesized that high-frequency percussive ventilation(HFPV) can improve both conditions and reduce hospital length of stay in these patients. DESIGN: Randomized prospective study. SETTING: University Hospital. PATIENTS: Fifty-three consecutive patients undergoing elective pulmonary partial resection were enrolled. Nine were excluded because of surgical reasons. INTERVENTIONS: The nondependent lung was ventilated with HFPV in 22 patients and other 22 received CPAP. In both groups,the dependent lung was ventilated with continuous mechanical ventilation. MEASUREMENT AND MAIN RESULTS: Cardiocirculatory variables and blood gas analysis were measured during surgery. Postoperatively,all patients underwent chest physiotherapy, and SpO2,body temperature, the amount of sputum produced, and chest radiography were recorded. Before nondependent lung re-expansion,HFPV patients presented higher PaO2 than CPAP group (p = 0.020). The amount of secretions was higher in chronic obstructive pulmonary disease patients treated with HFPV than in those who received CPAP (199 and 64 mL, respectively, p = 0.028). HFPV increased by 5.28 times the chance of sputum production by chronic obstructive pulmonary disease patients (chi(2) = 46.66, p < 0.0001; odds ratio = 5.28). A patient treated with HFPV had a 3.14-fold larger chance of being discharged earlier than a CPAP-treated subject (likelihood ratio = 11.5, p = 0.0007). CONCLUSIONS: Under the present settings, HFPV improved oxygenation in one-lung ventilation during pulmonary resection. Postoperatively, it decreased the length of stay and increased the removal of secretions in comparison with CPAP.

Circumferential mucosal dissection and esophageal perforation in a patient with eosinophilic esophagitis.

A young man with a previous history of episodes of mild solid food dysphagia was admitted with a total dysphagia. The esophagogastroduodenoscopy (EGDS) showed an extensive disruption of mucosal layer with a cul-de-sac in the lower part of the esophagus. Soon after the procedure, the patient suffered from an acute chest pain and subsequent CT scan demonstrated an intramural circumferential dissection of thoracic esophagus, and a mediastinal emphysema. An emergency right thoracotomy was performed, followed by a total esophagectomy with esophagogastroplasty and jejunostomy. The histopathology confirmed that mucosal and submucosal layers were circumferentially detached from muscular wall and showed an eosinophilic infiltration of the whole organ with necrosis and erosions of mucosal, submucosal and muscular layers. The diagnosis was esophageal perforation in eosinophilic esophagitis.

An Educational Intervention to Train Professional Nurses in Promoting Patient Engagement: A Pilot Feasibility Study.

Introduction: Growing evidence recognizes that patients who are motivated to take an active role in their care can experience a range of health benefits and reduced healthcare costs. Nurses play a critical role in the effort to make patients fully engaged in their disease management. Trainings devoted to increase nurses' skills and knowledge to assess and promote patient engagement are today a medical education priority. To address this goal, we developed a program of nurse education training in patient engagement strategies (NET-PES). This paper presents pilot feasibility study and preliminary participants outcomes for NET-PES. Methods: This is a pilot feasibility study of a 2-session program on patient engagement designed to improve professional nurses' ability to engage chronic patients in their medical journey; the training mainly focused on passing patient engagement assessment skills to clinicians as a crucial mean to improve care experience. A pre-post pilot evaluation of NET-PES included 46 nurses working with chronic conditions. A course specific competence test has been developed and validated to measure patient engagement skills. The design included self-report questionnaire completed before and after the training for evaluation purposes. Participants met in a large group for didactic presentations and then they were split into small groups in which they used role-play and case discussion to reflect upon the value of patient engagement measurement in relation to difficult cases from own practice. Results: Forty-six nurses participated in the training program. The satisfaction questionnaire showed that the program met the educational objectives and was considered to be useful and relevant by the participants. Results demonstrated changes on clinicians' attitudes and skills in promoting engagement. Moreover, practitioners demonstrated increases on confidence regarding their ability to support their patients' engagement in the care process. Conclusions: Learning programs teaching nurses about patient engagement strategies and assessment measures in clinical practice are key in supporting the realization of patient engagement in healthcare. Training nurses in this area is feasible and accepted and might have an impact on their ability to engage patients in the chronic care journey. Due to the limitation of the research design, further research is needed to assess the effectiveness of such a program and to verify if the benefits envisaged in this pilot are maintained on a long-term perspective and to test results by employing a randomized control study design.

Asbestos and SV40 in malignant pleural mesothelioma from a hyperendemic area of north-eastern Italy.

AIMS AND BACKGROUND: Malignant mesothelioma is a fatal cancer of increasing incidence in north-eastern Italy. Together with asbestos, the polyomavirus SV40 was hypothesized to contribute to the onset of malignant mesothelioma. To investigate the putative role of SV40 in the individual susceptibility to asbestos-induced malignant mesothelioma, we conducted a molecular epidemiological study on a series of malignant mesothelioma patients from an area in north-eastern Italy hyperendemic for malignant pleural mesothelioma. METHODS AND STUDY DESIGN: We collected 63 mesothelioma samples from incidence cases of patients diagnosed with malignant pleural mesothelioma in the period 2009-2010. DNA was extracted from patients' tissue biopsies using the BioRobot EZ1 Qiagen workstation. SV40 sequence detection and quantification was performed by specific real time PCR. The 74.6% of the 63 enrolled patients had a history of asbestos exposure. The epithelioid histotype was more prevalent in males (64.0%) and the mixed in females (61.5%) who showed significantly higher cancer co-morbidity (46.1% vs 12%, P = 0.005). SV40 was detected in 22% of MM tumors, with a low viral load. In SV40-positive patients, a threefold increased risk of asbestos exposure was observed, more evident in females (OR 4.32) than in males (OR 1.20). CONCLUSIONS: Our findings indicate that a high prevalence of SV40 was present in malignant mesothelioma incident cases from an area hyperendemic for malignant mesothelioma in north-eastern Italy. Although asbestos is considered the main risk factor in malignant mesothelioma onset, a role for SV40 could be hypothesized.