The Slavcleft: a three-center study of the outcome of treatment of cleft lip and palate. Nasolabial appearance.

Background There is a multitude of protocols of treatment of cleft lip and palate (CLP) worldwide differing in number of operations, surgical techniques, and timings of surgeries. Despite, facial appearance in subjects with CLP is rarely ideal and residual stigmata are easy to notice in many patients irrespective of the protocol. The prospective controlled investigations are optimal for comparing effectiveness of treatment protocols. Because prospective studies are very challenging to perform in CLP field, it is reasonable to retrospectively assess different surgical protocols to identify the promising ones and then to test them in a prospective way. Methods Our objective was to assess the nasolabial appearance in a preadolescent Slavic population with unilateral cleft lip and palate (UCLP) by using the 0-200 numeric scale with reference photographs. Patients treated in Warsaw, Poland (n = 32), Prague, Czech Republic (n = 26) and Bratislava, Slovakia (n = 17) were included in this retrospective study. Each cleft center used a unique surgical protocol. Two panels of professional raters (n = 7) and laypeople (n = 10) scored blindly the nasolabial esthetics on cropped frontal and profile images with cropped reference photograph present on the same slide. Intra- and inter-rater agreement was assessed with Cronbach's alpha, intraclass correlation coefficients, t-tests, and Bland-Altman plots. Inter-group differences were evaluated with one-way ANOVA and regression analysis. Results The agreement within and between raters was acceptable. We found that patients treated in Warsaw, Prague, and Bratislava showed comparable nasolabial appearance on frontal and profile photographs when judged by both professional raters (p > 0.05) and laypeople (p > 0.05). Regression analysis did not identify influence of gender, group (i.e., Warsaw, Prague, and Bratislava), age at lip repair, surgeon, and age at photographic assessment on esthetic outcome (p > 0.05). Conclusion This study showed that none of the surgical protocols showed superiority to produce good nasolabial appearance

The Slav-cleft: A three-center study of the outcome of treatment of cleft lip and palate. Part 1: Craniofacial morphology

Results of a comparison of the outcomes of treatment of cleft lip and palate can be affected by growth characteristics of populations from which subjects with the clefts are derived. Moreover, conventional cephalometric techniques used in cleft studies for analysis of facial morphology provide only a partial description of shape and are confounded by biases regarding the reference structures. In this retrospective comparison, craniofacial morphology of preadolescent patients with unilateral cleft lip and palate treated in Warsaw (n = 35, age = 10.6 years, SD = 1.2), Prague (n = 38, age = 11.6 years, SD = 1.4), and Bratislava (n = 26, age = 10.5 years, SD = 1.6) were evaluated on cephalograms with the cephalometric method used in the Eurocleft study and geometric morphometrics. We found that patients treated in Warsaw showed slightly more favorable outcomes than in Prague and Bratislava. The differences were related primarily to the position of maxillary alveolar process, cranial base, mandibular angle, and soft tissues. Although no association between a component of treatment protocol and the outcome was found, it is possible that organizational factors such as participation of high-volume, experienced surgeons contributed to these results. (C) 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved

The Slavcleft: A three-center study of the outcome of treatment of cleft lip and palate. Part 2: Dental arch relationships.

PURPOSE Our aim was to evaluate the dental arch relationship in a preadolescent Slavic population with unilateral cleft lip and palate (UCLP) by using the Goslon Yardstick. MATERIALS AND METHODS Patients treated in Warsaw, Poland (n = 32), Prague, Czech Republic (n = 33) and Bratislava, Slovakia (n = 30) were included in this retrospective study. Each cleft center used a unique surgical protocol. Three raters scored blindly the dental arch relationship on plaster models. Intra- and inter-rater agreement were assessed with kappa statistics, and differences between the groups were evaluated with one-way analysis of variance. Intra-rater agreement was very good (k > 0.825), while inter-rater agreement was either good or very good (kappa >0.703). RESULTS We found that patients treated in Warsaw showed a more favorable dental arch relationship (Goslon score = 2.58, SD = 0.77) than patients treated in Prague (Goslon score = 3.21, SD = 1.04). Patients treated in Bratislava showed an intermediate Goslon score (3.07; SD = 0.99). CONCLUSION This study showed that the dental arch relationships in patients treated in Warsaw with a one-stage repair were more favorable than in patients treated in Prague and Bratislava with a two-stage protocol and comparable to the best results obtained in the Eurocleft and Americleft studies

Suicide-Gene-Modified Extracellular Vesicles of Human Primary Uveal Melanoma in Future Therapies

Extracellular vesicles secreted from uveal melanoma (UM) cells are involved in the establishment of the premetastatic niche and display transforming potential for the formation of metastases, preferentially in the liver. In this study, we cultivated human primary UM cells and uveal melanoma-associated fibroblasts in vitro to be transduced by infection with a retrovirus containing the suicide gene—fused yeast cytosine deaminase::uracil phospho-ribosyl transferase (yCD::UPRT). A homogenous population of yCD::UPRT-UM cells with the integrated provirus expressed the gene, and we found it to continuously secrete small extracellular vesicles (sEVs) possessing mRNA of the suicide gene. The yCD::UPRT-UM-sEVs were internalized by tumor cells to the intracellular conversion of the prodrug 5-fluorocytosine (5-FC) to the cytotoxic drug 5-fluorouracil (5-FU). The host range of the yCD::UPRT-UM-sEVs was not limited to UMs only. The yCD::UPRT-UM-sEVs inhibited the growth of the human cutaneous melanoma cell line A375 and uveal melanoma cell line MP38, as well as other primary UMs, to various extents in vitro. The yCD::UPRT-UM-sEVs hold the therapeutic and prophylactic potential to become a therapeutic drug for UM. However, the use of yCD::UPRT-UM-sEVs must first be tested in animal preclinical studies

Detecting drug resistance in pancreatic cancer organoids guides optimized chemotherapy treatment

Drug combination therapies for cancer treatment show high efficacy but often induce severe side effects, resulting in dose or cycle number reduction. We investigated the impact of neoadjuvant chemotherapy (neoCTx) adaptions on treatment outcome in 59 patients with pancreatic ductal adenocarcinoma (PDAC). Resections with tumor-free margins were significantly more frequent when full-dose neoCTx was applied. We determined if patient-derived organoids (PDOs) can be used to personalize poly-chemotherapy regimens by pharmacotyping of treatment-naïve and post-neoCTx PDAC PDOs. Five out of ten CTx-naïve PDO lines exhibited a differential response to either the FOLFIRINOX or the Gem/Pac regimen. NeoCTx PDOs showed a poor response to the neoadjuvant regimen that had been administered to the respective patient in 30% of cases. No significant difference in PDO response was noted when comparing modified treatments in which the least effective single drug was removed from the complete regimen.Drug testing of CTx-naïve PDAC PDOs and neoCTx PDOs may be useful to guide neoadjuvant and adjuvant regimen selection, respectively. Personalizing poly-chemotherapy regimens by omitting substances with low efficacy could potentially result in less severe side effects, thereby increasing the fraction of patients receiving a full course of neoadjuvant treatment

Additional file 1 of Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold

Additional file 1