Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias.

The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used via i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate.

CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC).

(1) Background: HNSCC is a highly heterogeneous and relapse-prone form of cancer. We aimed to expand the immunological tool kit against HNSCC by conducting a functional screen to generate chimeric antigen receptor (CAR)-NK-92 cells that target HER1/epidermal growth factor receptor (EGFR). (2) Methods: Selected CAR-NK-92 cell candidates were tested for enhanced reduction of target cells, CD107a expression and IFNγ secretion in different co-culture models. For representative HNSCC models, patient-derived primary HNSCC (pHNSCC) cell lines were generated by employing an EpCAM-sorting approach to eliminate the high percentage of non-malignant cells found. (3) Results: 2D and 3D spheroid co-culture experiments showed that anti-HER1 CAR-NK-92 cells effectively eliminated SCC cell lines and primary HNSCC (pHNSCC) cells. Co-culture of tumor models with anti-HER1 CAR-NK-92 cells led to enhanced degranulation and IFNγ secretion of NK-92 cells and apoptosis of target cells. Furthermore, remaining pHNSCC cells showed upregulated expression of putative cancer stem cell marker CD44v6. (4) Conclusions: These results highlight the promising potential of CAR-NK cell therapy in HNSCC and the likely necessity to target multiple tumor-associated antigens to reduce currently high relapse rates.

Recurrent Life-threatening Pneumonitis in a 37-Year-Old Woman.

CASE PRESENTATION: A 37-year-old previously healthy and athletic woman presented to the ED in October 2018 with acute-onset high fever, dyspnea, and productive cough. Chest radiograph showed bilateral infiltrates that correlated with multifocal ground glass opacities in a thoracic CT scan (Fig 1). The patient was severely hypoxemic and required intensive care and oxygen administration via a high-flow nasal cannula. On admission, leucocyte counts were 23.3 k/µL; platelet counts were 518 k/µL; hemoglobin level was 12 g/dL; C-reactive protein was 83 mg/L, and procalcitonin was 0.7 µg/L. An auto-antibody panel that included antinuclear antibodies, extractable nuclear antigen (including anti-centromere-antibodies), antineutrophil cytoplasmic antibodies, and myositis- and granulocyte macrophage colony-stimulating factor-antibodies was negative, as was the rheumatoid factor. Immunoglobulins that included IgG1-4 and IgA and renal function were normal. Sicca symptoms like xerophthalmia and xerostomia were negated. The patient fully recovered after empiric administration of antibiotics and glucocorticoids (initially 500 mg methylprednisolone daily over 3 days with consecutive tapering).

Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic disease.

Symptomatic patients with residual pulmonary perfusion defects or vascular lesions but no pulmonary hypertension at rest are diagnosed with chronic thromboembolic disease (CTED). Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but data regarding the safety and efficacy of BPA in patients with CTED are lacking. We report a prospective series of ten consecutive patients with CTED who underwent 35 BPA interventions (median of four per patient) at two German institutions. All patients underwent a comprehensive diagnostic workup at baseline and 24 weeks after their last intervention. BPA was safe, with one pulmonary vascular injury and subsequent self-limiting pulmonary bleeding as the only complication (2.9% of the interventions, 10% of the patients). After the procedures, World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, and pulmonary arterial compliance improved, and NT-proBNP concentrations declined in 9/10 patients. BPA may be a new treatment option for carefully selected patients with CTED. A larger, prospective, international registry is required to confirm these results.

Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience.

Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).We report on a prospective series of 56 consecutive patients who underwent 266 BPA interventions (median, five per patient) at two German institutions. All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention.BPA resulted in improvements in WHO functional class, 6 min walk distance (mean change, +33 m), right ventricular function and haemodynamics, including a decline in mean pulmonary artery pressure by 18% and in pulmonary vascular resistance by 26%. Procedure-related adverse events occurred in 9.4% of the interventions. The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding. Most of these events were asymptomatic and self-limiting, but one patient died from pulmonary bleeding, resulting in a mortality rate of 1.8%.BPA resulted in haemodynamic and clinical improvements but was also associated with a considerable number of complications, including one fatal pulmonary bleeding. As the effects of BPA on survival are unknown, randomised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk-benefit assessments.

C-Arm Computed Tomography Adds Diagnostic Information in Patients with Chronic Thromboembolic Pulmonary Hypertension and a Positive V/Q SPECT.

Purpose To determine if C-Arm computed tomography (CACT) has added diagnostic value in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) with a positive mismatch pattern in ventilation/perfusion single photon emission computed tomography (V/Q SPECT). Materials and Methods 28 patients (23 men, 5 women, 62 ±â€Š18 years) with CTEPH who had undergone SPECT, followed by CACT and right heart catheterization (RHC) were included. Two independent readers reviewed SPECT and CACT. Findings indicating CTEPH and their location (segmental or sub-segmental) were identified (V/Q mismatch in SPECT and vascular pathologies in CACT). Inter-modality agreement was calculated (Cohen's Kappa). Findings were scored on a 3-point-scale. The sum of the score (pulmonary artery CTEPH severity score (PACSS)) was calculated for each patient and imaging modality, correlated to RHC (spearman's correlation) and compared to the final therapeutic decision of the CTEPH board (including the consensus of SPECT, selective pulmonary DSA and CACT). Results Overall, 504 pulmonary artery segments were assessed in SPECT and CACT. SPECT had identified 266/504 (53 %) arterial segments without and 238/504 (47 %) segments with a V/Q mismatch indicating CTEPH. CACT detected 131/504 (26 %) segments without abnormal findings and 373/504 (74 %) segments with findings indicating CTEPH. Inter-modality agreement was fair (ĸ = 0.38). PACSS of CACT correlated mildly significantly with the mean pulmonary artery pressure (PAPmean; rho = 0.48, p = 0.01), while SPECT missed significance (rho = 0.32, p = 0.1). Discrepant findings were mostly attributed to a higher frequency of sub-segmental pulmonary arterial pathologies on CACT (145 sub-segmental findings indicating CTEPH) rated as normal on SPECT. Conclusion In patients with CTEPH, contrast-enhanced CACT detects additional findings with a better correlation to the severity of PAPmean than V/Q SPECT. CACT indicates abnormalities even in segments without V/Q abnormalities. Key points · CACT has additional value in V/Q SPECT-positive CTEPH patients.. · SPECT may underestimate the extent of CTEPH.. · CACT indicates abnormalities even in segments without V/Q abnormalities.. Citation Format · Hinrichs JB, Werncke T, Kaireit T et al. C-Arm Computed Tomography Adds Diagnostic Information in Patients with Chronic Thromboembolic Pulmonary Hypertension and a Positive V/Q SPECT. Fortschr Röntgenstr.