Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

The effect of process variables on the physical properties and microstructure of HOPO nanoemulsion flakes obtained by refractance window.

Refractance window (RW) drying is considered an emerging technique in the food field due to its scalability, energy efficiency, cost and end-product quality. It can be used for obtaining flakes from high-oleic palm oil (HOPO) nanoemulsions containing a high concentration of temperature-sensitive active compounds. This work was thus aimed at studying the effect of temperature, thickness of the film drying, nanoemulsion process conditions, and emulsion formulation on the flakes' physical properties and microstructure. The results showed that HOPO flakes had good physical characteristics: 1.4% to 5.6% moisture content and 0.26 to 0.58 aw. Regarding microstructure, lower fractal dimension (FDt) was obtained when RW drying temperature increased, which is related to more regular surfaces. The results indicated that flakes with optimal physical properties can be obtained by RW drying of HOPO nanoemulsions.

Hydro-climatic changes of wetlandscapes across the world.

Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976-2015 in 25 wetlandscapes distributed across the world's tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world's land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes.

A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma.

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

Anesthesia and kidney transplantation.

INTRODUCTION: Chronic kidney disease (CKD) has diverse causes and the outcomes can change with renal transplantation, which has the potential to increase quality of life and improve survival. Because transplant recipients usually have comorbid conditions, presurgical assessment, optimization of health status, monitoring, and intraoperative anesthetic management are essential. OBJECTIVE: The objective of this study was to evaluate available medical literature concerning presurgical anesthetic assessment and intraoperative and postoperative anesthetic management of patients undergoing renal transplantation. REVIEW CRITERIA: A bibliographic search was made in MEDLINE, OVID, and LILIACS without language or design limits. Available evidence from February 1991 to February 2011 was taken. Articles about anesthesia in renal transplantation were included. Information quality was assessed according to design type with "Critical Appraisal Skills Program" (CASP-UK) tools. Epidemiological data in Colombia were obtained from the Social Protection Ministry and FOSYGA (Solidarity and Guarantee Fund) web pages. RESULTS: Regarding prognosis, CKD mortality increases with dialysis and with its duration, whereas transplantation reduces it and enhances survival. Recipient mortality, functionality, and graft lifespan are influenced by donor type (immediate diuresis with living donors, P < .05), hydration (60-90 mL/kg), early diuresis (13% mortality rate at 1 year if delayed and reduction of graft lifetime 20%-40%). When comparing diuresis, clearance creatinine, kidney perfusion, and function, there were no significant differences between general and regional anesthesia. Nevertheless, postoperative analgesia was better with epidural anesthesia. CONCLUSION: Examination of the patient and optimization of the overall health status contributes to graft optimal function and patient survival. Regional anesthesia has better control over postoperative pain, but it has no effect on the prognosis, The intraoperative maintenance of appropriate hydration enhances flux and renal perfusion, which allows early functionality of the graft. This, together with a living donor are considered good prognosis factors, moreover they reduce recipient mortality and improve graft lifetime.

Significance of cytomegalovirus prophylaxis strategies and development of cancer in kidney transplant recipients.

Cytomegalovirus (CMV) infection is one of the most common complications among kidney transplant recipients; two approaches preventing this complication are currently available: universal prophylaxis (UP) and pre-emptive therapy (PT). Despite some differences, similar effectiveness and safety have been proven in several studies for both strategies. However, Spinner et al compared both treatments in 115 renal transplant recipients showing deaths were more likely to occur in patients who received UP. Most of these deaths (2/4 cases) occurred because malignancies developed. This finding is paradoxical because CMV is considered a potentially oncogenic virus and, therefore, UP (a longer therapy compared with the PT) should not be linked with the emergence of a greater number of tumors. New evidence suggests that changes in host immune response triggered by CMV infection may have a mitigating effect on the development of tumors. It is now known CMV infection produces a clonal expansion of gamma delta T lymphocytes which can elicit an aggressive response against neoplastic cells. Currently, UP is the therapy most frequently used in Colombian transplant centers; however, doses administered vary depending on several clinical and laboratory factors. There are no clinical cohorts treated with PT. Reviewing the impact of different length dosing schemes is important for creating an immune response affecting malignancy development in kidney transplant recipients.