|Kidney transplantation: New strategies for longer organ preservation
These strategies include the most innovative approach to date, which is investigated by Thomas Wekerle (University Department of Surgery): as well as the kidney, bone marrow from the donor is also transplanted into the recipient to get tolerance: this …
Topoisomerase II alpha (TOP2A) and thymidylate synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of TOP2A and TS mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II–III disease and 38 of them received adjuvant mitotane. Twenty-six patients with metastatic disease received the EDP-M (etoposide, doxorubicin, Adriamycin, cisplatin plus mitotane). TOP2A and TS expression in ACC tissue was directly correlated with the clinical data. Both markers were not associated with either disease free survival (DFS) or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy. Disease response or stabilization to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing tumors (P = 0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS expressing ACC, respectively (P = 0.049). High TOP2A expression was significantly associated with longer time to progression (TTP) after EDP-M. TOP2A and TS proteins assessed by immunohistochemistry significantly correlated with mRNA expression. Immunohistochemical TOP2A expression was associated with a non-significant better response and longer TTP after EDP-M. TOP2A and TS were neither prognostic nor predictive of mitotane efficacy in ACC patients. The predictive role of TOP2A expression of EDP-M activity suggests a significant contribution of Adriamycin and etoposide for the efficacy of the EDP scheme.
The NF-B inflammatory pathway plays a major role in cancer development and clinical progression. Activation of NF-B signaling is promoted by NFKB1 and inhibited by NFKBIA. The present study aimed to determine the relevance of NFKB1 rs4648068 and NFKBIA rs2233406 genetic variants for non-medullary thyroid cancer (NMTC) susceptibility, progression and clinical outcome. This case–control and cohort study consists of a Romanian discovery cohort (157 patients and 258 controls) and a Dutch validation cohort (138 patients and 188 controls). In addition, patient cohorts were analyzed further for the association of genetic variants with clinical parameters. Functional studies were performed on human peripheral blood mononuclear cells. No associations were observed between the studied genetic variants and TC susceptibility. Although no statistically significant associations with clinical parameters were observed for NFKB1 rs4648068, the heterozygous genotype of NFKBIA rs2233406 was correlated with decreased radioactive iodide sensitivity requiring higher cumulative dosages to achieve clinical response. These findings were discovered in the Romanian cohort (P < 0.001) and confirmed in the Dutch cohort (P = 0.01). Functional studies revealed that this NFKBIA rs2233406 genotype was associated with elevated TLR4-mediated IL-1β production. In conclusion, genetic variation in NFKBIA, an inhibitor of NF-B signaling, is associated with clinical response to RAI therapy and with increased production of the pro-inflammatory cytokine IL-1β, providing a potential mechanism for the observed clinical associations. These data suggest that NF-B signaling is involved in NMTC pathogenesis and that the inflammatory tumor microenvironment could contribute to RAI resistance.
Hemorrhage is the main cause of maternal death during pregnancy. This study aims to evaluate incidence and outcomes of Severe Ante Partum Hemorrhage (SAPH) during the third trimester of pregnancy prior to deli…
Selective upper-airway stimulation (UAS) is a novel therapy for patients with obstructive sleep apnea (OSA). The aim of this study was to compare changes in sleep architecture during the diagnostic polysomnography and the post-implantation polysomnography in UAS in patients with OSA.
Twenty-six patients who received a UAS device (Inspire Medical Systems) were included. Treatment outcome was evaluated 2 and 3 months after surgery. Data collection included demographics, body mass index (BMI), apnea hypopnea index (AHI), oxygen saturation and desaturation index (ODI), Epworth sleepiness score (ESS), arousal parameter, and sleep patterns.
The mean age was 60.2 years, 25 patients were male, 1 patient was female. Mean BMI was 29.0 kg/m2. The mean pre-implantation AHI of 33.9/h could be reduced to 9.1/h at 2 months post-implantation (p < 0.001). The amount of time spent in N1-sleep could be reduced from 23.2% at baseline to 16.0% at month 3 post-implantation. The amount of time spent in N2- and N3-sleep did not change during the observation period. A significant increase of the amount of REM sleep at month 2 (15.7%) compared to baseline (9.5%; p = 0.010) could be observed. A reduction of the number of arousals and the arousal index could be observed.
In conclusion, significant changes in sleep architecture of patients with OSA and sufficient treatment with UAS could be observed. A reduction of the amount of time spent in N1-sleep could be caused by treatment with UAS and the rebound of REM sleep, observed for the first time in a study on UAS, is also a potential marker of the efficacy of UAS on sleep architecture.