Functional role of human leukocyte antigen-G up-regulation in renal cell carcinoma

The nonclassical HLA-G molecule exhibits a limited tissue distribution and exerts multiple immune regulatory functions. Recent studies indicate that HLA-G expression plays a key role in the induction of immune tolerance and may represent a novel immune escape mechanism of tumor cells. Despite a high frequency of tumor-infiltrating T lymphocytes in renal cell carcinoma (RCC) lesions, outgrowth of tumor cells occurs that might be attributable to abrogation-efficient antitumor responses. To delineate the potential role of HLA-G in RCC immunology, the HLA-G expression pattern and its functional consequences on immune responses were analyzed in cell lines and lesions derived from primary RCC lesions. A heterogeneous constitutive and IFN-gamma-inducible HLA-G mRNA and protein expression was found in 12.5% of RCC cell lines but not in autologous normal kidney cells. Western blot analysis of 37 primary RCC lesions revealed HLA-G protein expression in 27% of RCC lesions. Functional studies performed with alloreactive natural and lymphokine-activated killer cells as well as antigen-specific CD8(+) T-cell populations demonstrated that HLA-G expression inhibits lysis of RCC cells by these different immune effector cells, whereas HLA-G(-) normal kidney cells were recognized. Furthermore, the HLA-G-mediated counteraction of immune response could be restored by antibody blocking experiments. Thus, aberrant HLA-G expression is found at a relatively high frequency in RCC and might participate in evasion of these tumor cells from immunosurveillance.     

Differences in time to patient access to innovative cancer medicines in six European countries

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: −0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: −0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.     

Incidence of severe tracheobronchitis and pneumonia in laryngectomized patients: a retrospective clinical study and a European-wide survey among head and neck surgeons

Laryngectomized patients, lacking conditioning of the breathing air in the upper respiratory tract, have reported considerable pulmonary complaints. It is assumed that these patients also run a higher risk of developing severe respiratory infections. Unfortunately, there is little scientific information available about the occurrence of respiratory infections and related health costs in these patients with and without the use of an HME. Therefore, the occurrence of respiratory infections in laryngectomized patients was investigated in the Netherlands Cancer Institute and by means of a survey among head and neck oncology surgeons throughout Europe. The number of tracheobronchitis and/or pneumonia events was retrospectively scored between 1973 and 2013 in medical records of 89 laryngectomized patients treated in our institute. To assess expert experiences and opinions regarding these pulmonary problems, a study-specific survey was developed. The survey was sent by email to head and neck surgeons from ten different countries. In the medical record study, an average of 0.129 respiratory infections per patient/year was found in non-HME users and 0.092 in HME users. In the survey (response rate HN surgeons 20 %; countries 90 %) 0.285 episodes per patient/year in non-HME users was statistically higher than the 0.066 episodes per patient/year in HME users. The average mortality in the HME user group per entire career of each physician was estimated at 0.0045, and for the non-HME user group this was 0.0152. There is a tendency that the number of tracheobronchitis and pneumonia episodes in non-HME users is higher than in HME users.     

Mortality by decade in trauma patients with Glasgow Coma Scale 3

The aim of this study was to assess how increasing age affects mortality in trauma patients with Glasgow Coma Scale (GCS) 3. The Los Angeles County Trauma System Database was queried for all patients aged 20 to 99 years admitted with GCS 3. Mortality was 41.8 per cent for the 3306 GCS 3 patients. Mortality in the youngest patients reviewed, those in the third decade, was 43.5 per cent. After logistic regression analysis, patients in the third decade had similar mortality rates to patients in the sixth (adjusted OR, 0.88; CI, 0.68 to 1.14; P = 0.33) and seventh decades (adjusted OR, 0.96; CI, 0.70 to 1.31; P = 0.79). A significantly lower mortality rate, however, was noted in the fifth decade (adjusted OR, 0.76; CI, 0.61 to 0.95; P = 0.02). Conversely, significantly higher mortality rates were noted in the eighth (adjusted OR, 1.93; CI, 1.38 to 2.71; P = 0.0001) and combined ninth/tenth decades (adjusted OR, 2.47; CI, 1.71 to 3.57; P < 0.0001). Given the high survival in trauma patients with GCS 3 as well as continued improvement in survival compared with historical controls, aggressive care is indicated for patients who present to the emergency department with GCS 3.