Variability of forced vital capacity in progressive interstitial lung disease: a prospective observational study.

BACKGROUND: Fibrotic interstitial lung disease (ILD) is often associated with poor outcomes, but has few predictors of progression. Daily home spirometry has been proposed to provide important information about the clinical course of idiopathic pulmonary disease (IPF). However, experience is limited, and home spirometry is not a routine component of patient care in ILD. Using home spirometry, we aimed to investigate the predictive potential of daily measurements of forced vital capacity (FVC) in fibrotic ILD. METHODS: In this prospective observational study, patients with fibrotic ILD and clinical progression were provided with home spirometers for daily measurements over 6 months. Hospital based spirometry was performed after three and 6 months. Disease progression, defined as death, lung transplantation, acute exacerbation or FVC decline > 10% relative was assessed in the cohort. RESULTS: From May 2017 until August 2018, we included 47 patients (IPF n = 20; non-IPF n = 27). Sufficient daily measurements were performed by 85.1% of the study cohort. Among these 40 patients (IPF n = 17; non-IPF n = 23), who had a mean ± SD age of 60.7 ± 11.3 years and FVC 64.7 ± 21.7% predicted (2.4 ± 0.8 L), 12 patients experienced disease progression (death: n = 2; lung transplantation: n = 3; acute exacerbation: n = 1; FVC decline > 10%: n = 6). Within the first 28 days, a group of patients had high daily variability in FVC, with 60.0% having a variation ≥5%. Patients with disease progression had significantly higher FVC variability than those in the stable group (median variability 8.6% vs. 4.8%; p = 0.002). Cox regression identified FVC variability as independently associated with disease progression when controlling for multiple confounding variables (hazard ratio: 1.203; 95% CI:1.050-1.378; p = 0.0076). CONCLUSIONS: Daily home spirometry is feasible in IPF and non-IPF ILD and facilitates the identification of FVC variability, which was associated with disease progression.

Feasibility and accuracy of SPECT myocardial perfusion imaging in end-stage lung disease.

BACKGROUND: Coronary artery disease (CAD) is associated with increased mortality in patients with chronic lung disease. However, non-invasive diagnostic of CAD is difficult, especially in patients with more advanced disease. Therefore, we aimed to assess the feasibility and accuracy of SPECT-myocardial perfusion imaging (MPI) stress testing with regadenoson in patients with end-stage lung disease (ELD) undergoing assessment of stable CAD. METHODS: Between January 2012 and May 2018, 102 patients with ELD, who were referred to our institution for lung transplant evaluation, were assessed retrospectively. All patients underwent both stress SPECT-MPI as well as coronary angiography. RESULTS: The mean age in our population was 57±6 years. All patients had severe pulmonary function impairment. During stress SPECT-MPI 14 patients (14%) reported regadenoson-related symptoms, but only 2 patients (2%) required medical treatment. Coronary angiography revealed obstructive CAD in 20 patients (20%). Among those, 5 patients had abnormal SPECT-MPI and PCI was performed in 3 patients accordingly. In 14 patients with obstructive CAD, revascularization was deferred based on normal SPECT-MPI findings. CONCLUSIONS: SPECT-MPI using regadenoson is well tolerated in patients with ELD and can help to make decisions about coronary revascularization before lung transplant.

[Mentorship in electrophysiology : What does it take? What's the advantage?] / Mentorship in der Rhythmologie : Was braucht es? Was bringt es?

Mentoring has long been a fundamental part of medical education. In this article, the term mentoring is defined and the requirements, advantages, and methods of structuring are discussed. Further, the use of mentoring in the context of education in electrophysiology will be highlighted. In this setting, requirements on the personal level of mentors and mentees as well as on the institutional level are outlined, and different phases and types of mentoring are discussed.

Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report.

Malignant mesothelioma is an aggressive cancer associated with prior exposure to asbestos and dismal prognosis. Immune checkpoint inhibitor therapy is currently approved by the Food and Drug Administration for pre-treated malignant pleural mesothelioma. We describe a 75-year-old patient with disseminated, progressive malignant mesothelioma receiving 2 cycles of pembrolizumab who presented with generalized muscle weakness, shortness of breath, double vision and ptosis. There was no previous history of cardiovascular disease. The clinical picture, supported by the detection of anti-titin autoantibodies suggested myasthenia gravis (MG). Also, cardiac biomarkers were elevated. Echocardiography showed new severely reduced ejection fraction. A 12-lead resting electrocardiogram (ECG) revealed ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. Because cardiac catheterization revealed no relevant coronary lesions, immune checkpoint inhibitor-associated myocarditis and MG were suspected. Management and Outcome: The patient was started on steroids. Within a few days of presentation respiratory failure set in and the patient was intubated. Recurrent arrhythmias followed, which were treated by repeated emergency electrical cardioversion. In order to relieve myasthenic symptoms, plasma exchange was initiated and 10 cycles were carried out. This consequently also led to an improvement of myocarditis. Upon discharge, the ejection fraction recovered. The patient recovered and was alive at 1-year follow-up, without relevant limitations to his quality of life. Discussion and Conclusion: The article further discusses the use of plasma exchange for immune checkpoint inhibitor-associated myocarditis based on a review of literature. We conclude that patients showing no improvement after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated for plasma exchange, which appears to be an effective treatment option.

Chemoradioimmunotherapy of inoperable stage III non-small cell lung cancer: immunological rationale and current clinical trials establishing a novel multimodal strategy.

Immune-checkpoint inhibitors (ICI) have dramatically changed the landscape of lung cancer treatment. Preclinical studies investigating combination of ICI with radiation show a synergistic improvement of tumor control probability and have resulted in the development of novel therapeutic strategies. For advanced non-small cell lung cancer (NSCLC), targeting immune checkpoint pathways has proven to be less toxic with more durable treatment response than conventional chemotherapy. In inoperable Stage III NSCLC, consolidation immune checkpoint inhibition with the PD-L1 inhibitor durvalumab after completion of concurrent platinum-based chemoradiotherapy resulted in remarkable improvement of progression-free and overall survival. This new tri-modal therapy has become a new treatment standard. Development of predictive biomarkers and improvement of patient selection and monitoring is the next step in order to identify patients most likely to derive maximal benefit from this new multimodal approach. In this review, we discuss the immunological rationale and current trials investigating chemoradioimmunotherapy for inoperable stage III NSCLC.

Letermovir for Difficult to Treat Cytomegalovirus Infection in Lung Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV)-infection remains a major cause of morbidity and mortality after lung transplantation. Treatment with currently available drugs poses treatment difficulties in some patients due to drug resistance or intolerability. METHODS: We report a series of 4 lung transplant recipients with CMV-infection and treatment failure upon standard care due to antiviral drug resistance and treatment-limiting side effects. As rescue therapy letermovir recently approved for the prophylaxis of CMV-infection in patients after hematopoietic stem cell transplantation was initiated. Patients received 480 mg/day for a follow up of 36.1 ± 12.9 weeks. Efficacy and tolerability were assessed retrospectively. RESULTS: Mild nausea, vomiting, and diarrhea were the only side effects of letermovir reported by a single patient. A small adjustment of the tacrolimus dose was mandatory upon treatment initiation with letermovir. CMV viral load could be decreased and cleared subsequently in all patients. CMV clearance was observed after 17.7 ± 12.6 weeks despite lack of CMV-immunity. CONCLUSIONS: CMV-infection and -disease were successfully managed with letermovir. Letermovir was well tolerated and effective in treating CMV-infections in lung transplant recipients failing on currently available antiviral agents.

Safety and Efficacy of Steroid Pulse Therapy for Acute Loss of FEV1 in Lung Transplant Recipients After Exclusion of Acute Cellular Rejection.

BACKGROUND: The standard treatment of acute cellular rejection after lung transplantation (LTx) is a high-dose steroid pulse therapy. In our center, this therapy is also the standard of care for LTx recipients with acute loss of forced expiratory volume in 1 second (FEV1), after excluding specific causes such as acute rejection on biopsy. The aim of this retrospective study was to evaluate the safety and efficacy of steroid pulse therapy. METHODS: From 2015 to 2018, 33 consecutive patients (17 male patients, mean age ± SD, 50.5 ± 12.5 years) were included. All patients underwent routine examinations to exclude acute cellular rejection and other specific causes. FEV1 was routinely measured after 5 days, and 1, 3, and 6 months. Positive response to steroid pulse therapy was defined by increase of FEV1 > 10%. RESULTS: The mean decrease ± SD from baseline in FEV1 at the start of steroid pulse therapy was 380 ± 630 mL (P = .02). FEV1 changed after 5 days by 170 ± 180 mL (P = .0007), and after 1 month by 140 ± 230 mL (P = .70), 3 months by -60 ± 240 mL (P = .15), and 6 months by -80 ± 290 mL (P = .73). A positive response was observed in 21% of patients after 3 months and 12% after 6 months. High bronchoalveolar lavage (BAL) eosinophil count correlated with a higher FEV1 after steroid pulse therapy. Serious complications were observed in 4 out of 33 patients (12%) with 1 fatal event (pneumonia). CONCLUSIONS: Only a minority of patients after LTx with loss of FEV1 after exclusion of acute cellular rejection benefit from steroid pulse therapy. Patients with BAL eosinophilia are more likely to respond. However, severe complications were observed.

Helical tomotherapy in patients with leptomeningeal metastases.

PURPOSE: Leptomeningeal metastasis (LM) is an increasingly common complication of late-stage systemic cancer, for which there is no standard treatment. We analyzed outcome and toxicity in patients with LM undergoing craniospinal irradiation via helical tomotherapy (HT-CSI) at our institution. PATIENTS AND METHODS: The charts of 15 patients diagnosed with LM and undergoing HT-CSI between 2006 and 2014 were retrospectively assessed. Main neoplasms included breast cancer, lung cancer, and lymphoma. All patients presented with cranial neuropathy due to LM. Follow-up was performed regularly. Survival analysis was performed by the Kaplan-Meier method, and prognostic factors were tested using the COX-regression model. RESULTS: Median survival by cancer type was 6 (breast cancer), 1 (lung cancer), and 2 months (lymphoma), respectively. Median overall survival and relapse-free survival were calculated to be between 2 and 3 months. Six- and 12-month survival was 30% (95% CI 0.08-0.5) and 20% (95% CI 0.05-0.4), respectively. Symptom palliation occurred in 53% of patients in general, but in 67% of breast cancer patients, in particular. Patients with lung cancer experienced no improvement. Most common acute treatment-related toxicity at different levels were hematological toxicity, multiple cranial neuropathy, fatigue, infections, nausea, and headache. CONCLUSION: HT-CSI can help meet the challenge of treating patients with LM, especially because it can palliate symptoms and improve neurological functions. One-year survival remains as disappointing as before.

Craniospinal irradiation using helical tomotherapy for central nervous system tumors.

The aim of this study was to describe early and late toxicity, survival and local control in 45 patients with primary brain tumors treated with helical tomotherapy craniospinal irradiation (HT-CSI). From 2006 to 2014, 45 patients with central nervous system malignancies were treated with HT-CSI. The most common tumors were medulloblastoma in 20 patients, ependymoma in 10 patients, intracranial germinoma (ICG) in 7 patients, and primitive neuroectodermal tumor in 4 patients. Hematological toxicity during treatment included leukopenia Grades 1-4 (6.7%, 33.3%, 37.8% and 17.8%, respectively), anemia Grades 1-4 (44.4%, 22.2%, 22.2% and 0%, respectively) and thrombocytopenia Grades 1-4 (51.1%, 15.6%, 15.6% and 6.7%, respectively). The most common acute toxicities were nausea, vomiting, fatigue, loss of appetite, alopecia and neurotoxicity. No Grade 3 or higher late toxicity occurred. The overall 3- and 5-year survival rates were 80% and 70%, respectively. Survival for the main tumor entities included 3- and 5-year survival rates of 80% and 70%, respectively, for patients with medulloblastoma, 70% for both in patients with ependymoma, and 100% for both in patients with ICG. Relapse occurred in 11 patients (24.4%): 10 with local and 1 with multifocal relapse. One patient experienced a secondary cancer. M-status and the results of the re-evaluation at the end of treatment were significantly related to survival. Survival after HT-CSI was in line with the existing literature, and acute treatment-induced toxicity resolved quickly. Compared with conventional radiotherapy, HT offers benefits such as avoiding gaps and junctions, sparing organs, and better and more homogeneous dose distribution and coverage of the target volume.