RESUMO
Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy. Patients and Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification. Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4-51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity. Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN.
RESUMO
We aimed to investigate haemodynamics during active and passive recovery following repeated bouts of supramaximal exercise. Seven male athletes underwent two sessions of supramaximal exercise which consisted of a warm-up and of five bouts of cycling at the maximum speed possible for 30 s against a resistance equivalent to 150% of the maximum workload achieved in a previous incremental test. Bouts were separated by 1 min of recovery and followed by 10 min of recovery which was either active (pedalling at 40 W) or passive (completely rest seated on the cycle). Haemodynamic variables were evaluated by means of impedance cardiography. Heart rate (HR), stroke volume (SV), cardiac output (CO), mean blood pressure (MBP), thoracic electrical impedance (Z0) as an inverse index of central blood volume, and systemic vascular resistance (SVR) were assessed. The main findings were that active recovery, with respect to passive recovery, induced higher changes from baseline in HR (+29.1 +/- 4.5 versus +15.6 +/- 2.9 beats min(-1) at the 10th minute of recovery, P < 0.05), SV (+19.9 +/- 5.6 versus -6.4 +/- 3.3 ml, P < 0.01) and CO (+3.8 +/- 1.2 versus +0.4 +/- 0.2 l min(-1), P < 0.01). Furthermore, MBP was similar between the two kinds of recovery despite an increase in Z0 during passive compared to active recovery. These results suggest that the faster haemodynamic recovery towards baseline and the decrease in cardiac preload during passive recovery may be successfully prevented by cardiovascular regulatory mechanisms which include an increase in SVR, thus avoiding a drop in blood pressure.