Prolonged antibiotic prophylaxis in tissue reconstruction using autologous fat grafting: Is there a benefit for wound healing?

Fat grafting is a well-established method in plastic surgery. Despite many technical advances, standardised recommendations for the use of prophylactic antibiotics in fat grafting are not available. This retrospective multicentre study aims to analyse the use of prophylactic antibiotics in fat grafting and to compare complication rates for different protocols. A retrospective medical chart review of 340 patients treated with fat grafting of the breast from January 2007 to March 2019 was performed in three plastic surgery centres. Complications, outcomes, and antibiotic regimes were analysed. The Clavien-Dindo classification was applied. All patients received perioperative antibiotic prophylaxis: 33.8% (n = 115) were treated with a single shot (group 1), 66.2% (n = 225) received a prolonged antibiotic scheme (group 2). There was no significant difference in the number of sessions (P = .475). The overall complication rate was 21.6% (n = 75), including graft resorption, fat necrosis, infection, and wound healing problems. Complication rates were not significantly different between groups. Risk factors for elevated complication rates in this specific patient group are smoking, chemotherapy, and irradiation therapy. The complication rate for lipografting of the breast is low, and it is not correlated to the antibiotic protocol. The use of prolonged prophylactic antibiotics does not lower the complication rate.

Sector Irradiation vs. Whole Brain Irradiation After Resection of Singular Brain Metastasis-A Prospective Randomized Monocentric Trial.

To minimize recurrence following resection of a cerebral metastasis, whole-brain irradiation therapy (WBRT) has been established as the adjuvant standard of care. With prolonged overall survival in cancer patients, deleterious effects of WBRT gain relevance. Sector irradiation (SR) aims to spare uninvolved brain tissue by applying the irradiation to the resection cavity and the tumor bed. 40 were randomized to receive either WBRT (n = 18) or SR (n = 22) following resection of a singular brain metastasis. Local tumor control was satisfactory in both groups. Recurrence was observed earlier in the SR (median 3 months, 1-6) than in the WBRT cohort (median 8 months, 7-9) (HR, 0.63; 95% CI, 0.03-10.62). Seventeen patients experienced a distant intracranial recurrence. Most relapses (n = 15) occurred in the SR cohort, whereas only two patients in the WBRT group had new distant tumor manifestation (HR, 6.59; 95% CI, 1.71-11.49; p = 0.002). Median overall survival (OS) was 15.5 months (range: 1-61) with longer OS in the SR group (16 months, 1-61) than in the WBRT group (13 months, 3-52), without statistical significance (HR, 0.55; 95% CI, 0.69-3.64). Concerning neurocognition, patients in the SR group improved in the follow-up assessments, while this was not observed in the WBRT group. There were positive signals in terms of QOL within the SR group, but no significant differences in the global QLQ and QLQ-C30 summary scores were found. Our results indicate comparable efficacy of SR in terms of local control, with better maintenance of neurocognitive function. Unsurprisingly, more distant intracranial relapses occurred. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01667640.

The prognostic value of Presepsin for postoperative complications following pancreatic resection: A prospective study.

BACKGROUND: Presepsin is involved in binding lipopolysaccharides and previous studies have confirmed its value as a marker for early diagnosis and prediction of severity in sepsis. Comparable studies assessing the predictive potential regarding postoperative complications and mortality following pancreatic resection are lacking. METHODS: This prospective study included 70 patients undergoing pancreatic resection from December 2017 until May 2019. Presepsin was measured preoperatively, on postoperative day 1, 3 and 8 (POD1/3/8) and correlated with the clinical course and mortality. RESULTS: Severe complications (Clavien-Dindo ≥3a) occurred in 28 patients (40%), postoperative pancreatic fistula (POPF) grade B/C occurred in 20 patients (28.6%), infectious complications in 28 (40%), and four patients (5.7%) died during hospital stay. Presepsin levels at any timepoint did not correlate with further development of postoperative complications or in-hospital mortality whereas CRP levels on postoperative day (POD) 3 were significantly associated with clinically relevant POPF (AUC 0.664, 95%CI 0.528-0.800; p = 0.033). Preoperative Presepsin levels as well as Presepsin on POD1 were significantly elevated in patients with malignant compared to benign underlying disease (299pg/ml vs. 174pg/ml and 693.5pg/ml vs. 294pg/ml; p = 0.009 and 0.013, respectively). CONCLUSION: In our cohort, Presepsin was not eligible to predict the postoperative course following pancreatic resection. However, Presepsin levels were significantly elevated in patients with malignant disease, this finding warrants further investigation.

A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation.

Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants performed between 08/2015 and 12/2019 (n = 347) were propensity score (PS) matched for cold ischemia time (CIT), extended criteria donor (ECD), gender mismatch, cytomegalovirus (CMV) mismatch, re-transplantation and Eurotransplant (ET) senior program. A total of 103 HMP and 103 SCS instances fitted the matching criteria. Prior to PS matching, the CIT was longer in the HMP group (17.5 h vs. 13.3 h; p < 0.001), while the delayed graft function (DGF) rates were 29.8% and 32.3% in HMP and SCS, respectively. In the PS matched groups, the DGF rate was 64.1% in SCS vs. 31.1% following HMP: equivalent to a 51.5% reduction of the DGF rate (OR 0.485, 95% CI 0.318-0.740). DGF was associated with decreased 1- and 3-year graft survival (100% and 96.3% vs. 90.8% and 86.7%, p = 0.001 and p = 0.008) or a 4.1-fold increased risk of graft failure (HR = 4.108; 95% CI: 1.336-12.631; p = 0.014). HMP significantly reduces DGF in kidney transplantation. DGF remains a strong predictor of graft survival.

Cerebrospinal beta-amyloid peptides(1-40) and (1-42) in severe preeclampsia and HELLP syndrome - a pilot study.

During pregnancy, substantial alterations in cerebral plasticity, vascular remodeling and neuronal growth occur in the maternal brain. We investigated whether concentrations of selected neurodiagnostic biomarkers in the cerebrospinal fluid of women with preeclampsia/HELLP syndrome differ from those in healthy controls using enzyme-linked immunosorbent assay technique. We found that tau protein concentrations (p = 0.016) and phospho-tau/tau ratio (p < 0.001) in cerebrospinal fluid were significantly lower in 39 preeclamptic women compared to 44 healthy controls during third trimester of pregnancy. Beta-amyloid(1-40)/(1-42) ratio was significantly higher in HELLP syndrome than in severe preeclampsia (8.49 + 2.73 vs. 4.71 + 1.65; p = 0.007). We conclude that beta-amyloid(1-40)/(1-42) ratio in cerebrospinal fluid can discriminate severe preeclampsia and HELLP syndrome. High beta-amyloid peptide and low tau protein concentrations are associated with impaired development of the materno-feto-placental unit and correlate with placental dysfunction.

Risk factors and complications after body-contouring surgery and the amount of stromal vascular fraction cells found in subcutaneous tissue.

Body contouring surgery following massive weight loss is often prone to complications. Subcutaneous adipose tissue is a rich source of stromal vascular fraction (SVF) cells, and moreover it plays an important role in the pathophysiology of obesity, metabolic syndrome, and wound healing. In this retrospective, single-centred appraisal, complications are examined and correlated with individual SVF numbers in abdominal subcutaneous fat tissue. We analysed whether the weight loss method affected complications. Eighty seven massive weight loss patients undergoing body contouring surgery between 2010 and 2017 were included in the study. In total, 57 cases with at least one complication were recorded (65.5%). Maximum lifetime weight was 109.6 kg (range 48-184 kg). Half of the complications (50.8%) were minor complications without the need for surgical revision. The mean number of SVF found in the resected tissue was 714 997.63 cells/g fat tissue. We found no statistical difference in complication rates dependent on cell numbers. Smoking (P = .049) and a high BMI at the time point of surgery (P = .031) led to significantly more complications. Also, a high resection weight (P = .057) showed a tendency for impaired wound healing. However, there was no difference in complication rates following body contouring procedures attributable to the method of weight loss in this study.

N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium.

Common polymorphisms in the N-acetyltransferase 2 gene (NAT2) modify the association between cigarette smoking and bladder cancer and have been hypothesized to determine whether active cigarette smoking increases breast cancer risk. The authors sought to replicate the latter hypothesis in a prospective analysis of 6,900 breast cancer cases and 9,903 matched controls drawn from 6 cohorts (1989-2006) in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. Standardized methods were used to genotype the 3 most common polymorphisms that define NAT2 acetylation phenotype (rs1799930, rs1799931, and rs1801280). In unconditional logistic regression analyses, breast cancer risk was higher in women with more than 20 pack-years of active cigarette smoking than in never smokers (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17, 1.39), after controlling for established risk factors other than alcohol consumption and physical inactivity. However, associations were similar for the slow (OR = 1.25, 95% CI: 1.11, 1.39) and rapid/intermediate (OR = 1.24, 95% CI: 1.08, 1.42) acetylation phenotypes, with no evidence of interaction (P = 0.87). These results provide some support for the hypothesis that long-term cigarette smoking may be causally associated with breast cancer risk but underscore the need for caution when interpreting sparse data on gene-environment interactions.

Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer.

Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). There was no statistically significant association between the SNPs and PC risk regardless of the model of inheritance (dominant, codominant and recessive). The associations were not modified by disease aggressiveness, circulating levels of steroid sex hormones, or IGFs or BMI. We conclude that polymorphisms in the FOXO3 gene that are associated with longevity are not major risk factors for PC risk, in this population of Caucasian men.

Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium.

BACKGROUND: Recently, several genome-wide association studies have identified various genetic susceptibility loci for breast cancer. Relatively little is known about the possible interactions between these loci and the established risk factors for breast cancer. METHODS: To assess interactions between single-nucleotide polymorphisms (SNPs) and established risk factors, we prospectively collected DNA samples and questionnaire data from 8576 breast cancer case subjects and 11 892 control subjects nested within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). We genotyped 17 germline SNPs (FGFR2-rs2981582, FGFR2-rs3750817, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, CASP8-rs1045485, LSP1-rs3817198, COL1A1-rs2075555, COX11-rs6504950, RNF146-rs2180341, 6q25-rs2046210, SLC4A7-rs4973768, NOTCH2-rs11249433, 5p12-rs4415084, 5p12-rs10941679, RAD51L1-rs999737), and odds ratios were estimated by logistic regression to confirm previously reported associations with breast cancer risk. We performed likelihood ratio test to assess interactions between 17 SNPs and nine established risk factors (age at menarche, parity, age at menopause, use of hormone replacement therapy, family history, height, body mass index, smoking status, and alcohol consumption), and a correction for multiple testing of 153 tests (adjusted P value threshold = .05/153 = 3 × 10(-4)) was done. Case-case comparisons were performed for possible differential associations of polymorphisms by subgroups of tumor stage, estrogen and progesterone receptor status, and age at diagnosis. All statistical tests were two-sided. RESULTS: We confirmed the association of 14 SNPs with breast cancer risk (P(trend) = 2.57 × 10(-3) -3.96 × 10(-19)). Three SNPs (LSP1-rs3817198, COL1A1-rs2075555, and RNF146-rs2180341) did not show association with breast cancer risk. After accounting for multiple testing, no statistically significant interactions were detected between the 17 SNPs and the nine risk factors. We also confirmed that SNPs in FGFR2 and TNRC9 were associated with greater risk of estrogen receptor-positive than estrogen receptor-negative breast cancer (P(heterogeneity) = .0016 for FGFR2-rs2981582 and P(heterogeneity) = .0053 for TNRC9-rs3803662). SNP 5p12-rs10941679 was statistically significantly associated with greater risk of progesterone receptor-positive than progesterone receptor-negative breast cancer (P(heterogeneity) = .0028). CONCLUSION: This study does not support the hypothesis that known common breast cancer susceptibility loci strongly modify the associations between established risk factors and breast cancer.

Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC).

The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele) = 0.85, 95% CI 0.78-0.94, p = 1.3 x 10⁻³ for rs546950 and OR(allele) = 0.84, 95% CI 0.76-0.93, p = 5.6 x 10⁻4 for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.

Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC).

A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.

Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC).

AMP-activated protein kinase (AMPK) is an energy sensing/signalling intracellular protein which is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. Once activated, AMPK inhibits fatty acid synthesis and the Akt-mTOR pathway, and activates the p53-p21 axis. All these molecular mechanisms are thought to play a key role in breast carcinogenesis. We investigated the genetic variability of four genes encoding AMPK (PRKAA1, PRKAA2, PRKAB1 and PRKAB2). Using a tagging approach and selecting SNPs we covered all the common genetic variation of these genes. We tested association of tagging SNPs in our four candidate genes with breast cancer (BC) risk in a study of 1340 BC cases and 2536 controls nested into the European Prospective Investigation into Cancer and Nutrition (EPIC). Given the relevance of AMPK on fatty acid synthesis and the importance of body fatness as a BC risk factor, we tested association of SNPs and body-mass index as well. We observed no statistically significant association between the SNPs in the PRKAs genes and BC risk and BMI after correction for multiple testing.