Chronic kidney disease and cardiovascular disease reduce survival rates after burn injury: A retrospective study over 20 years.

BACKGROUND: The Abbreviated Burn Severity Index and comparable scores are used to assess the probability of survival in burned patients. These scores may be useful during the initial management of the patient and in addition to the clinical evaluation. As current models do not include the influence of chronic diseases, we evaluated the impact of comorbidities on survival probability, aiming to improve the existing scoring systems and survival probability accuracy further. METHODS: In this retrospective single-center study, patient data from a center for Severe Burn Injury were collected. Over a period of 20 years (2000-2019), a total of 1,193 patients were recorded. The influence of comorbidities (chronic kidney disease, diabetes mellitus type II, and cardiovascular diseases) on the survival probability was analyzed using regression models. These analyses were stratified for sex and period. RESULTS: Pre-existing chronic kidney disease, as well as pre-existing cardiovascular disease, had a significant influence on the survival of patients. For chronic kidney disease, the influence was stronger in men than in women. Women were more likely to survive a burn injury with a history of chronic renal insufficiency. An improved Abbreviated Burn Severity Index model, which assigns an additional point for chronic kidney disease, best-described survival probability in our patient cohort. CONCLUSION: Cardiovascular disease and chronic kidney disease both have an impact on the survival probability of severely burned patients, but this impact is more severe for chronic kidney disease. An additional Abbreviated Burn Severity Index point for chronic kidney disease would be a proposed adaptation to predict the outcome of burn patients better.

Aberrant DNA Methylation, Expression, and Occurrence of Transcript Variants of the ABC Transporter ABCA7 in Breast Cancer.

The ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for specific epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5-intron 5 boundary aberrantly methylated in a molecular subtype-specific manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic field cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5-intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-specific and intron-flanking primers, we identified intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtype-specific nor directly correlated with DNA methylation at the respective exon-intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicin or paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with significant dysregulation of splicing factors linked to alternative splicing.

A Single-Center 10-Year Experience of 180 Transmasculine Patients Undergoing Gender-Affirming Mastectomy While Continuing Masculinizing Hormone Replacement Therapy.

BACKGROUND: Gender-affirming mastectomy is a fundamental step in the transition process of transmasculine patients following the initiation of hormone replacement therapy. Its perioperative management, however, remains underreported and controversial. In this study, a large series of mastectomies in transmen maintaining hormonal therapy is presented. METHODS: Over a 10-year study period, a consecutive series of 180 transmasculine patients undergoing chest masculinizing surgery was evaluated. Demographical and surgical data were collected and analyzed for potential factors influencing outcome. RESULTS: The overall rate of complications was 15.5%. Patients who underwent periareolar incision mastectomy were significantly more likely to develop any type of complication than patients with a sub-mammary incision (28.6% vs. 13.2%, p = 0.045). Hematoma was the most common reason for surgical revision. It occurred significantly more often among the periareolar group (21.4% vs. 7.9%, p = 0.041). Duration and type of hormonal therapy did not differ between patients with or without complications. In a multivariate regression analysis, smoking and type of incision were identified as significant predictors of the all-cause complication rate, whereas the influence of BMI and resection weight diminished after adjusting for confounding factors. CONCLUSION: There is scarcity of information concerning the influence of perioperative hormonal therapy in patients undergoing chest wall masculinization. The observed complication rates-with special regard to hematoma-were comparable to current reports; yet further research is needed to profoundly evaluate this topic and provide evidence-based recommendations for the perioperative management of HRT of transmasculine patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

BMI Specific Complications Following Implant-Based Breast Reconstruction after Mastectomy.

BACKGROUND: Breast reconstruction has a positive impact on body image and quality of life for women after experiencing the physically and psychologically demanding process of mastectomy. Previous studies have presented body mass index (BMI) as a predictor for postoperative complications after breast reconstruction, however, study results vary. This retrospective study aimed to investigate the impact of patients' BMI on postoperative complications following implant-based breast reconstruction. METHODS: All implant-based breast reconstructions performed at the Department of Plastic, Reconstructive and Aesthetic Surgery at the Medical University of Vienna from January 2001 to March 2018 were evaluated. A total of 196 reconstructed breasts among 134 patients met eligibility criteria. Demographic data, surgical techniques, as well as major and minor complications within a one-year follow-up period were analyzed. RESULTS: Patients' BMI did not show a significant impact on complication rates. The overall incidence of postoperative complications was 30.5% (40/131) of which 17.6% required reoperation. Impaired wound healing (18.3%), seroma (6.1%), hematoma (4.6%), capsular contraction (4.6%) and infection (3.8%) were the most common complications. CONCLUSION: In our study cohort, BMI was not associated with a significantly higher risk of complications. However, postoperative complications significantly increased with a longer operative time and resulted in an extended length of hospital stay.

Discrimination between 34 of 36 Possible Combinations of Three C>T SNP Genotypes in the MGMT Promoter by High Resolution Melting Analysis Coupled with Pyrosequencing Using A Single Primer Set.

Due to its cost-efficiency, high resolution melting (HRM) analysis plays an important role in genotyping of candidate single nucleotide polymorphisms (SNPs). Studies indicate that HRM analysis is not only suitable for genotyping individual SNPs, but also allows genotyping of multiple SNPs in one and the same amplicon, although with limited discrimination power. By targeting the three C>T SNPs rs527559815, rs547832288, and rs16906252, located in the promoter of the O6-methylguanine-DNA methyltransferase (MGMT) gene within a distance of 45 bp, we investigated whether the discrimination power can be increased by coupling HRM analysis with pyrosequencing (PSQ). After optimizing polymerase chain reaction (PCR) conditions, PCR products subjected to HRM analysis could directly be used for PSQ. By analyzing oligodeoxynucleotide controls, representing the 36 theoretically possible variant combinations for diploid human cells (8 triple-homozygous, 12 double-homozygous, 12 double-heterozygous and 4 triple-heterozygous combinations), 34 out of the 36 variant combinations could be genotyped unambiguously by combined analysis of HRM and PSQ data, compared to 22 variant combinations by HRM analysis and 16 variant combinations by PSQ. Our approach was successfully applied to genotype stable cell lines of different origin, primary human tumor cell lines from glioma patients, and breast tissue samples.

Differences between Primary and Revision Rhinoplasty: Indications, Techniques, Grafts, and Outcomes.

BACKGROUND: The nose is at the center of the face and has essential functional and aesthetic properties. Over recent years, rhinoplasty has gained increasing popularity through the influence of "selfies" and social media. As a result, a growing demand for secondary correction has also emerged. Revision rhinoplasty is more complex than primary cases and often requires the use of extranasal grafting material. The authors sought to analyze the indications, techniques, and outcomes after primary and revision rhinoplasty. METHODS: A total of 245 patients (153 primary cases and 92 revisions) undergoing surgery at the authors' specialized clinic for facial plastic surgery were included. All patients were treated by an experienced facial plastic surgeon according to the authors' established clinic standards. A retrospective data analysis was performed to evaluate the differences between the groups regarding the indications, intraoperative techniques, and postoperative outcomes. RESULTS: Although more patients sought revision surgery for aesthetic reasons alone than isolated functional issues, almost two-thirds of the revision patients had functional and aesthetic problems in combination. Complex reconstructive techniques, extracorporeal septoplasties, and extranasal grafts were more commonly used in revision cases. The occurrence of another revision during the follow-up period was significantly higher after revision surgery compared to primary rhinoplasty cases (primary rhinoplasty, 10.5 percent; revision surgery, 23.9 percent; p = 0.006). CONCLUSIONS: There are differences between primary and revision rhinoplasty that must be appreciated by the treating surgeon. The patient should be informed about the increased complexity of the secondary procedure, the possible need for extranasal grafts, and the increased risk of a further revision. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Tissue distribution of epirubicin after severe extravasation in humans.

PURPOSE: As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose-toxicity relation. METHODS: From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject). RESULTS: After extravasation, tissue concentrations were highly variable with an individual anthracycline distribution pattern ranging from a few nanograms up to 17 µg per 100 mg tissue, which indicated a substantial difference in tissue sensitivity among patients. The resection borders coincided with the extension of the erythema and guided the surgical intervention after demarcation of the lesion, which occurred usually 2 or 3 weeks after extravasation. At that time, drug was hardly detected at the resection borders. Wound drains were negative for the extravasated drugs while showing a time profile of vascular growth factors and inflammatory cytokines, which was highly similar to routine surgery. In all six patients, surgical debridement with immediate wound closure led to healing within approximately 2 weeks, when therapy was resumed in all patients with reasonable time delay. CONCLUSION: Surgical intervention after demarcation of the extravasation lesion allows for almost uninterrupted continuation of treatment independent of the amount of extravasated anthracycline. As even minor amounts of the vesicants may trigger tissue necrosis, preventive measures merit the highest priority.

The secretome of stressed peripheral blood mononuclear cells increases tissue survival in a rodent epigastric flap model.

Reconstructive surgery transfers viable tissue to cover defects and to restore aesthetic and functional properties. Failure rates after free flap surgery range from 3 to 7%. Co-morbidities such as diabetes mellitus or peripheral vascular disease increase the risk of flap failure up to 4.5-fold. Experimental therapeutic concepts commonly use a monocausal approach by applying single growth factors. The secretome of γ-irradiated, stressed peripheral blood mononuclear cells (PBMCsec) resembles the physiological environment necessary for tissue regeneration. Its application led to improved wound healing rates and a two-fold increase in blood vessel counts in previous animal models. We hypothesized that PBMCsec has beneficial effects on the survival of compromised flap tissue by reducing the necrosis rate and increasing angiogenesis. Surgery was performed on 39 male Sprague-Dawley rats (control, N = 13; fibrin sealant, N = 14; PBMCsec, N = 12). PBMCsec was produced according to good manufacturing practices (GMP) guidelines and 2 ml were administered intraoperatively at a concentration of 2.5 × 107 cells/ml using fibrin sealant as carrier substance. Flap perfusion and necrosis (as percentage of the total flap area) were analyzed using Laser Doppler Imaging and digital image planimetry on postoperative days 3 and 7. Immunohistochemical stainings for von Willebrand factor (vWF) and Vascular Endothelial Growth Factor-receptor-3 (Flt-4) were performed on postoperative day 7 to evaluate formation of blood vessels and lymphatic vessels. Seroma formation was quantified using a syringe and flap adhesion and tissue edema were evaluated clinically through a cranial incision by a blinded observer according to previously described criteria on postoperative day 7. We found a significantly reduced tissue necrosis rate (control: 27.8% ± 8.6; fibrin: 22.0% ± 6.2; 20.9% reduction, p = .053 vs. control; PBMCsec: 19.1% ± 7.2; 31.1% reduction, p = .012 vs. control; 12.9% reduction, 0.293 vs. fibrin) together with increased vWF+ vessel counts (control: 70.3 ± 16.3 vessels/4 fields at 200× magnification; fibrin: 67.8 ± 12.1; 3.6% reduction, p = .651, vs. control; PBMCsec: 85.9 ± 20.4; 22.2% increase, p = .045 vs. control; 26.7% increase, p = .010 vs. fibrin) on postoperative day 7 after treatment with PBMCsec. Seroma formation was decreased after treatment with fibrin sealant with or without the addition of PBMCsec. (control: 11.9 ± 9.7 ml; fibrin: 1.7 ± 5.3, 86.0% reduction, 0.004 vs. control; PBMCsec: 0.6 ± 2.0; 94.8% reduction, p = .001 vs. control; 62.8% reduction, p = .523 vs. fibrin). We describe the beneficial effects of a secretome derived from γ-irradiated PBMCs on tissue survival, angiogenesis, and clinical parameters after flap surgery in a rodent epigastric flap model.

40 Years of Total Extracorporeal Septal Reconstruction: The Past, Present, and Future.

BACKGROUND: Even today, severe septal deformities are a challenging problem for any rhinoplasty surgeon. Standard techniques are often not able to achieve satisfactory long-term results regarding function or aesthetic form. In such severe cases, a partial or total extracorporeal septal reconstruction may be used, as these techniques provide reliable and lasting results. METHODS: The aim of this work is to present the authors' experience with the technique of total extracorporeal septal reconstruction and its development to today's standard and to prove its effectiveness in the long-term follow-up. RESULTS: This article presents 40 years of clinical experience in this field and describes the technical changes that have evolved. Low complication rates, safe techniques, and favorable long-term outcomes of the total extracorporeal septal reconstruction show the benefits of this technique. CONCLUSION: The indication for a total extracorporeal septal reconstruction has been limited by the development of less complex surgical procedures, but it still represents the best technique to achieve long-term functional and aesthetic results in patients with very complex septal deformities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Does obesity impact the outcome of severely burned patients?

Although obesity appears to be an important predictor of mortality and morbidity, little data about the impact of body mass index (BMI) on the outcome of severely burned patients are available. Patients admitted to the General Hospital Vienna between 1994 and 2014, who underwent surgery because of burn injuries, were enrolled in this study. BMI was used to divide patients into five groups: BMI 18.5 to 24.9, 25 to 29.9, 30 to 34.9, 35 to 39.9, and > 40. The groups were compared in terms of difference of mortality and morbidity. Of 460 patients, 34.3% (n = 158) died. Mortality rates were the lowest in patients with obesity class III and the highest in patients with BMI 35 to 39.9 (BMI 18.5-24.9: 30.5%, BMI 25-29.9: 31.5%, BMI 30-34.9: 41.3%, BMI 35-39.9: 55.5%, BMI > 40: 30%; P = .031). BMI was not found to be an independent risk factor when corrected with age, percent total body surface area burned, full-thickness burns, and inhalation injury. No significant differences in length of stay, inhalation trauma, pneumonia, wound infection, sepsis, and invasive ventilation were observed. BMI as an independent risk factor for severely burned patients could not be confirmed via multivariate analysis.

Bony Fixation of the Nasal Framework.

The importance of a straight and stable central framework is beyond dispute. Many authors allude to technical aspects how to achieve the above-mentioned requirements. Far less is said about the contact zones of the framework and how to achieve a long-lasting and solid fixation. In the authors' patient group, they found the need to work on the septum/the central framework in approximately 84% of the cases. In 61% of the patients, the authors had to operate on the fixation point. Of course, there is a great variety of anatomical findings. So the required techniques differ immensely. The surgeon must be prepared for all kinds of different situations. Especially the dorsal fixation and the anchoring on the maxilla without having a standard anterior nasal spine can be a great challenge. In their daily routine, suture techniques (e.g., the transcutaneous transosseous cerclage suture) have become the authors' working horse for these complex fixation situations.

Neo-glans reconstruction for penile cancer: Description of the primary technique using autologous testicular tunica vaginalis graft.

Partial penectomy (glansectomy with/or without distal corporectomy) is an acceptable alternative for smaller distal pT3 penile carcinoma lesions in highly motivated and compliant patients. The authors describe a novel technique of neo-glans reconstruction using a tunica vaginalis (TV) testis allograft. However, due to an unclear resection margin on final histology, the patient underwent re-do surgery with a neo-glans revision using the well-established mesh split-thickness skin graft (STSG) technique. The penile length was preserved and the penile and bulbar part of the urethra was additionally mobilised in order to obtain a natural and aesthetic result for the meatus. Neo-glans reconstruction with TV coverage may be another promising alternative, which certainly requires further evaluation. We believe that the donor-site associated morbidity is minimal when compared to other harvesting sites. However, this is just an assumption, because direct comparison data on grafting techniques and neo-glans reconstruction are not available. Nevertheless, we think that for re-do procedures a standardised approach using a STSG technique should be the treatment method of choice.

Hypermethylation of CDKN2A exon 2 in tumor, tumor-adjacent and tumor-distant tissues from breast cancer patients.

BACKGROUND: Breast carcinogenesis is a multistep process involving genetic and epigenetic changes. Tumor tissues are frequently characterized by gene-specific hypermethylation and global DNA hypomethylation. Aberrant DNA methylation levels have, however, not only been found in tumors, but also in tumor-surrounding tissue appearing histologically normal. This phenomenon is called field cancerization. Knowledge of the existence of a cancer field and its spread are of clinical relevance. If the tissue showing pre-neoplastic lesions is not removed by surgery, it may develop into invasive carcinoma. METHODS: We investigated the prevalence of gene-specific and global DNA methylation changes in tumor-adjacent and tumor-distant tissues in comparison to tumor tissues from the same breast cancer patients (n = 18) and normal breast tissues from healthy women (n = 4). Methylation-sensitive high resolution melting (MS-HRM) analysis was applied to determine methylation levels in the promoters of APC, BRCA1, CDKN2A (p16), ESR1, HER2/neu and PTEN, in CDKN2A exon 2 and in LINE-1, as indicator for the global DNA methylation extent. The methylation status of the ESR2 promoter was determined by pyrosequencing. RESULTS: Tumor-adjacent and tumor-distant tissues frequently showed pre-neoplastic gene-specific and global DNA methylation changes. The APC promoter (p = 0.003) and exon 2 of CDKN2A (p < 0.001) were significantly higher methylated in tumors than in normal breast tissues from healthy women. For both regions, significant differences were also found between tumor and tumor-adjacent tissues (p = 0.001 and p < 0.001, respectively) and tumor and tumor-distant tissues (p = 0.001 and p < 0.001, respectively) from breast cancer patients. In addition, tumor-adjacent (p = 0.002) and tumor-distant tissues (p = 0.005) showed significantly higher methylation levels of CDKN2A exon 2 than normal breast tissues serving as control. Significant correlations were found between the proliferative activity and the methylation status of CDKN2A exon 2 in tumor (r = -0.485, p = 0.041) and tumor-distant tissues (r = -0.498, p = 0.036). CONCLUSIONS: From our results we can conclude that methylation changes in CDKN2A exon 2 are associated with breast carcinogenesis. Further investigations are, however, necessary to confirm that hypermethylation of CDKN2A exon 2 is associated with tumor proliferative activity.

Patient satisfaction, body image, and quality of life after lower body lift: a prospective pre- and postoperative long-term survey.

BACKGROUND: Body contouring surgery after massive weight loss remains a fast growing field due to the rising number of postbariatric surgery patients, and it can improve patients' quality of life substantially. Patient expectations in these procedures are very high, but only little is known as to whether these procedures have a long lasting influence on body image, patient satisfaction, and quality of life. SETTING: University hospital, Austria. METHODS: We evaluated 40 consecutive female patients who underwent a lower body lift between 2009 and 2013. Patients took part in a prospective pre- and postoperative questionnaire survey inquiring about their psychological and physical wellbeing. The mean postoperative follow up interval was 61±14 months. We used 2 validated (Body Image Questionnaire and Body Appraisal Inventory) and one self-designed questionnaires (body lift follow-up questionnaire). The postoperative response rate in January 2016 was 72.5%. RESULTS: Lower body lift significantly reduced dismissive body ratings and increased long-term feelings of attractiveness and self-esteem, and significantly reduced discomfort associated with excess skin. Patients reported feeling happier, more attractive, and more self-confident. The procedure enhanced their physical wellbeing, even years after surgery. CONCLUSION: Lower body lift satisfied patients' expectations and improved long-term quality of life. Therefore, it is an essential component in the treatment of patients who have experienced massive weight loss.

Promoter methylation patterns of ABCB1, ABCC1 and ABCG2 in human cancer cell lines, multidrug-resistant cell models and tumor, tumor-adjacent and tumor-distant tissues from breast cancer patients.

Overexpression of ABCB1, ABCC1 and ABCG2 in tumor tissues is considered a major cause of limited efficacy of anticancer drugs. Gene expression of ABC transporters is regulated by multiple mechanisms, including changes in the DNA methylation status. Most of the studies published so far only report promoter methylation levels for either ABCB1 or ABCG2, and data on the methylation status for ABCC1 are scarce. Thus, we determined the promoter methylation patterns of ABCB1, ABCC1 and ABCG2 in 19 human cancer cell lines. In order to contribute to the elucidation of the role of DNA methylation changes in acquisition of a multidrug resistant (MDR) phenotype, we also analyzed the promoter methylation patterns in drug-resistant sublines of the cancer cell lines GLC-4, SW1573, KB-3-1 and HL-60. In addition, we investigated if aberrant promoter methylation levels of ABCB1, ABCC1 and ABCG2 occur in tumor and tumor-surrounding tissues from breast cancer patients.Our data indicates that hypomethylation of the ABCC1 promoter is not cancer type-specific but occurs in cancer cell lines of different origins. Promoter methylation was found to be an important mechanism in gene regulation of ABCB1 in parental cancer cell lines and their drug-resistant sublines. Overexpression of ABCC1 in MDR cell models turned out to be mediated by gene amplification, not by changes in the promoter methylation status of ABCC1. In contrast to the promoters of ABCC1 and ABCG2, the promoter of ABCB1 was significantly higher methylated in tumor tissues than in tumor-adjacent and tumor-distant tissues from breast cancer patients.