Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.

BACKGROUND: The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. METHODS: We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results. RESULTS: Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). CONCLUSION: Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

Transbronchial cryobiopsy for small peripheral pulmonary lesions using endobronchial ultrasonography and an ultrathin bronchoscope.

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.

Virtual Reality Simulation for Minimally Invasive Coronary Artery Bypass Grafting With Aortic No-Touch Total Arterial Grafting Technique.

OBJECTIVE: Virtual reality can be applied preoperatively by surgeons to gain precise insights into a patient's anatomy for planning minimally invasive coronary artery bypass grafting (CABG) with in situ arterial grafts. This study aimed to examine virtual reality simulation for minimally invasive CABG with in situ arterial grafts. METHODS: Preoperative stereolithographic files in 35 in situ arterial grafts were converted using 320-slice computed tomography and workstation. The accurate length and direction of each graft were confirmed through virtual reality glasses. The simulation of graft designs was performed by using an immersive virtual reality platform. RESULTS: The mean harvested lengths of in situ left internal thoracic artery (n = 17), right internal thoracic artery (n = 12), and gastroepiploic artery (n = 6) grafts predicted by virtual reality simulation were 21.4 ± 3.4 cm, 21.2 ± 3.6 cm, and 22.8 ± 4.8 cm. The required lengths of these grafts predicted by virtual reality simulation were 15.8 ± 2.3 cm, 16.4 ± 2.1 cm, and 14.5 ± 4.4 cm. Minimally invasive CABG using virtual reality simulation was completed in 17 patients, of whom 16 patients underwent aortic no-touch total arterial CABG. The surgical strategy was adjusted in 11.8% of the cases due to the 3-dimensional virtual reality-based anatomy evaluation. The early mortality and morbidity were 0%, and the patency of the graft was 100%. The median time to return to full physical activity was 7.1 days. CONCLUSIONS: This study demonstrated the successful development and clinical application of the first dedicated virtual reality platform for planning aortic no-touch total arterial minimally invasive CABG. Virtual reality simulation can allow the accurate preoperative understanding of anatomy and appropriate planning of the graft design with acceptable postoperative outcomes.

Morphological changes of the tricuspid valve complex in functional tricuspid regurgitation on contrast-enhanced computed tomography.

BACKGROUND: Whether it is possible to perform morphological evaluation of functional tricuspid regurgitation (FTR) on contrast-enhanced computed tomography (CT) was examined by evaluating the relationships between the parameters measured on contrast-enhanced CT and TR severity on transthoracic echocardiography. METHODS: Fifty patients underwent contrast-enhanced CT. Tricuspid annulus area (TAA), tricuspid annulus circumference (TAC), right ventricular volume (RVV), and the distances between the tips and bases of the papillary muscles were measured on contrast-enhanced CT in diastole and systole. The 50 cases were divided into 34 in the TR ≤ mild group (no TR: 3 cases, trivial TR: 24 cases, mild TR: 7 cases), and 16 in the TR ≥ moderate group (moderate TR: 8 cases, severe TR: 8 cases) using the TR grade measured by transthoracic echocardiography, and then differences between the groups were examined. RESULTS: Significant differences were found in TAA, TAC, and RVV (p < 0.01) and the distances between the tips of the anterior and posterior papillary muscles (p < 0.05) in both diastole and systole. Since the septal papillary muscle could not be identified in 18 cases (36.0%), only the distance between the anterior and posterior papillary muscles was measurable in all cases. On receiver-operating characteristic (ROC) curve analysis, the areas under the ROC curves (AUCs) of TAA, TAC, and RVV were all > 0.7, and the maximum AUC was 0.925 for dRVV. CONCLUSIONS: TAA, TAC, RVV, and the distance between the tips of the anterior and posterior papillary muscles measured on contrast-enhanced CT were shown to be significantly increased in the TR ≥ moderate group. Detailed morphological assessment of FTR is possible by contrast-enhanced CT.

Unexpected haemorrhage from lateral thoracic artery following the removal of a pleural drainage tube.

Pulmonologists must be aware of the possible arterial bleeding even during the removal of a safely inserted drain.

A novel approach to the selection of an appropriate pacing position for optimal cardiac resynchronization therapy using CT coronary venography and myocardial perfusion imaging: FIVE STaR method (fusion image using CT coronary venography and perfusion SPECT applied for cardiac resynchronization therapy).

BACKGROUND: Nearly one-third of patients with advanced heart failure (HF) do not benefit from cardiac resynchronization therapy (CRT). We developed a novel approach for optimizing CRT via a simultaneous assessment of the myocardial viability and an appropriate lead position using a fusion technique with CT coronary venography and myocardial perfusion imaging. METHODS AND RESULTS: The myocardial viability and coronary venous anatomy were evaluated by resting Tc-99m-tetrofosmin myocardial perfusion imaging (MPI) and contrast CT venography, respectively. Using fusion images reconstructed by MPI and CT coronary venography, the pacing site and lead length were determined for appropriate CRT device implantations in 4 HF patients. The efficacy of this method was estimated by the symptomatic and echocardiographic functional parameters. In all patients, fusion images using MPI and CT coronary venograms were successfully reconstructed without any misregistration and contributed to an effective CRT. Before the surgery, this method enabled the operators to precisely identify the optimal indwelling site, which exhibited myocardial viability and had a lead length necessary for an appropriate device implantation. CONCLUSIONS: The fusion image technique using myocardial perfusion imaging and CT coronary venography is clinically feasible and promising for CRT optimization and enhancing the patient safety in patients with advanced HF.

Radiation sensitivities in the terminal stages of megakaryocytic maturation and platelet production.

These studies examined the effects of X radiation and interleukin 3 (IL-3), which is an effective cytokine for the generation of megakaryocytopoiesis from X-irradiated hematopoietic stem/progenitor cells, on the terminal process of human megakaryocytopoiesis and thrombopoiesis. Mature megakaryocytes were induced by culturing CD34(+) cells from normal human peripheral blood in a serum-free liquid culture stimulated with thrombopoietin. The experiments contained the following groups: control cultures with nonirradiated cells incubated for 15 days; cultures treated with IL-3 on day 7 or day 11, cultures irradiated with 2 Gy on day 7 or day 11, and cultures treated with IL-3 immediately after X irradiation. The nonirradiated control cultures produced megakaryocytes from day 7, and both the megakaryocyte and platelet generation reached a peak on day 12-13. When X irradiation was performed on day 7, both the megakaryocyte and platelet numbers decreased remarkably, while no significant effect was observed on those numbers when cultures were X-irradiated on day 11. IL-3 showed neither protective nor promoting effects on the terminal stages of megakaryocytic maturation and platelet production. The results demonstrated that mature megakaryocytes are radiosensitive but that the radiosensitivity decreased with the terminal stages of megakaryocytic maturation, especially for the megakaryocytes entering into proplatelet formation.