Plasma Cytokine and Growth Factor Profiling during Free Flap Transplantation

Ischemia and reperfusion (I/R) is an unavoidable condition during free flap transplantation. Restoration of blood flow is usually associated with a profound inflammatory response. Cytokines and growth factors are the functional proteins which exert their specific influence on injury or repair during the healing period. Plasma concentrations of 18 cytokines and growth factor proteins (IL6, IL8, IP10, TNFα, MCP1, Fractalkine, GRO, bFGF, GMCSF, IFNg, MIP1a, VEGF, sCD40L, IL10, TGFα, IL1β, IL12P40, and TNFβ) have been analyzed with respect to I/R status during microsurgery tissue transplantation in both, artery and vein, from patients by multiplexed immunoassay. Both technical feasibility and biostatistics data analysis approaches were thoroughly assessed. It has been found that, from all investigated proteins, the venous plasma levels of IL6 significantly increased during the ischemia period and mostly sustained their high levels during reperfusion, while venous plasma levels of IL8 showed in general a significant increase in the ischemia period followed by a rapid decrease in the reperfusion period. In conclusion, these findings direct toward an active involvement of tissue-resting leukocytes which may become therapeutic targets for concomitant medication in flap surgery to improve wound healing

Comparison of venous couplers versus hand-sewn technique in 4577 cases of DIEP-flap breast reconstructions – A multicenter study

Introduction Venous anastomosis remains to be a challenging step in microsurgical tissue transfer and venous complications constitute to a common reason for free flap failure. While several studies have compared mechanical vs. hand-sewn venous anastomoses, there is no large-series study comparing the type of anastomosis exclusively in DIEP flap breast reconstructions. Patients and Methods Between 2011 and 2019, 3926 female patients underwent 4577 free DIEP-flap breast reconstructions in 22 different breast cancer centers. Patient data was collected via an online database, files were screened and cases were divided into a hand- (HA) and a coupler-anastomosis (CA) group. Complications were accounted for and the two groups were then compared. Results Mean ischemia time was significantly shorter in the CA group (46.88 +/- 26.17 vs. 55.48 +/- 24.70 min; p < .001), whereas mean operative time was comparable (316 +/- 134.01 vs. 320.77 +/- 120.29 minutes; p = .294). We found no significant difference between both groups regarding the rate of partial (CA: 1.0% vs. HA: 1.3%) and total flap loss (CA: 2.2% vs. HA: 1.8%). However, revision rates were significantly higher in the CA group (CA: 10.5% vs. HA: 7.9%; p = .003), with higher numbers of arterial (2.3 vs. 0.9%; p < .001) and venous thromboses (3.4 vs. 1.8%; p = .001) accounting for this finding. Conclusions All taken into account, our findings do support the feasibility of venous coupler anastomoses in principle, however the inflationary use of coupler devices should be evaluated critically

Overall complication rates of DIEP flap breast reconstructions in Germany – a multi-center analysis based on the DGPRÄC prospective national online registry for microsurgical breast reconstructions

While autologous breast reconstruction has gained momentum over recent years, there is limited data on the structure and quality of care of microsurgical breast reconstruction in Germany. Using the breast reconstruction database established by the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC), the presented study investigated the overall outcomes of deep inferior epigastric perforator (DIEP) flap reconstructions in Germany. Data of 3926 patients and 4577 DIEP flaps performed by 22 centers were included in this study. Demographics, patient characteristics, perioperative details and postoperative outcomes were accounted for. Centers performing < Ø 40 (low-volume (LV)) vs. ≥ Ø 40 (high-volume (HV)) annual DIEP flaps were analyzed separately. Overall, total and partial flap loss rates were as low as 2.0% and 1.1% respectively, and emergent vascular revision surgery was performed in 4.3% of cases. Revision surgery due to wound complications was conducted in 8.3% of all cases. Mean operative time and length of hospital stay was significantly shorter in the HV group (LV: 385.82 min vs. HV: 287.14 min; LV: 9.04 (18.87) days vs. HV: 8.21 (5.04) days; both p < 0.05). The outcome and complication rates deduced from the national registry underline the high standard of microsurgical breast reconstruction on a national level in Germany

Cognitive&ndash;Emotional Aspects of Post-Traumatic Stress Disorder in the Context of Female Genital Mutilation

Around 200 million women and girls worldwide are affected by female genital mutilation/cutting (FGM/C). FGM/C is a procedure that harms or alters the external female genitals for non-medical reasons, and is usually performed on children. Often, this procedure leads to severe consequences for the women&rsquo;s physical and mental health. In a cross-sectional sample of 112 women seeking medical counseling, physical and mental health characteristics associated with FGM/C were examined and possible predictors for the development of post-traumatic stress disorder (PTSD) in women affected by FGM/C were identified. A total of 55.4% (n = 66) of the women reported symptom levels of probable PTSD. Predictors for higher PTSD symptomology were an older age at the time of the FGM/C procedure, feelings of guilt and the centrality of the event in the woman&rsquo;s life. Thus, cognitive&ndash;emotional processing was found to play an important role in the emergence of PTSD in women suffering from FGM/C. However, interventions taking into consideration these characteristics are mostly lacking and need to be investigated further in the context of FGM/C

Regenerative potential of adipocytes in hypertrophic scars is mediated by myofibroblast reprogramming

Abstract: Abnormal scarring is a major challenge in modern medicine. The central role of myofibroblasts and TGF-β signaling in scarring is widely accepted, but effective treatment options are missing. Autologous fat grafting is a novel approach that has led to significant improvements in the functionality and appearance of scar tissue. While the underlying mechanism is unknown, the potential role of paracrine effects of adipocytes has been discussed. Hence, with the aim of unraveling the regenerative potential of adipocytes, their effects on in vitro differentiated myofibroblasts and on fibroblasts from hypertrophic scars were investigated. Exposure to adipocyte-conditioned medium significantly decreased the expression of the myofibroblast marker α-SMA and ECM components, indicating the occurrence of myofibroblast reprogramming. Further analysis demonstrated that myofibroblast reprogramming was triggered by BMP-4 and activation of PPARγ signaling initiating tissue remodeling. These findings may pave the way for novel therapeutic strategies for the prevention or treatment of hypertrophic scars. Key messages: Adipocytes induce distinct regenerative effects in hypertrophic scar tissue.Adipocytes secrete several proteins which are involved in wound healing and regeneration.Adipocytes secrete BMP-4 which activates myofibroblast reprogramming.Mediators secreted by adipocytes directly and indirectly activate PPARγ which exerts distinct anti-fibrotic effects.These findings may pave the way for novel therapeutic strategies for the prevention or treatment of hypertrophic scars

Mass spectrometric characterization of limited proteolysis activity in human plasma samples under mild acidic conditions

We developed a limited proteolysis assay for estimating dynamics in plasma-borne protease activities using MALDI ToF MS analysis as readout. A highly specific limited proteolysis activity was elicited in human plasma by shifting the pH to 6. Mass spectrometry showed that two singly charged ion signals at m/z 2753.44 and m/z 2937.56 significantly increased in abundance under mild acidic conditions as a function of incubation time. For proving that a provoked proteolytic activity in mild acidic solution caused the appearance of the observed peptides, control measurements were performed (i) with pepstatin as protease inhibitor, (ii) with heat-denatured samples, (iii) at pH 1.7, and (iv) at pH 7.5. Mass spectrometric fragmentation analysis showed that the observed peptides encompass the amino acid sequences 1-24 and 1-26 from the N-terminus of human serum albumin. Investigations on peptidase specificities suggest that the two best candidates for the observed serum albumin cleavages are cathepsin D and E. Reproducibility, robustness, and sensitivity prove the potential of the developed limited proteolysis assay to become of clinical importance for estimating dynamics of plasma-borne proteases with respect to associated pathophysiological tissue conditions

Effect of Radiation Therapy on Microsurgical Deep Inferior Epigastric Perforator Flap Breast Reconstructions

Introduction Breast reconstruction with autologous tissue is a state-of-the art procedure. Several patient-related factors have been identified with regard to the safety and efficacy of these reconstructions. The presented study investigates the impact of prereconstruction radiation on outcomes of deep inferior epigastric perforator (DIEP) free-flap breast reconstructions using largest database available in Europe. Materials and Methods Between 2011 and 2019, 3926 female patients underwent 4577 DIEP flap breast reconstructions in 22 different German breast cancer centers. The cases were divided into a no-radiation (NR) and a radiation (R) group, according to radiation status before reconstruction. Groups were compared with regard to surgical complications and free-flap outcome. Results Overall, there was no significant difference between the groups regarding the rate of total flap loss [1.9% (NR) vs 2.1% (R), P = 0.743], partial flap loss [0.9% (NR) vs 1.5 (R), P = 0.069], and revision surgery [vascular revision: 4.4% (NR) vs 4.1% (R), P = 0.686; wound revision: 7.6% (NR) vs 9.4% (R), P = 0.122]. However, the patients had a significantly higher risk of developing wound healing disturbances at the recipient site [1.2% (NR) vs 2.1% (R), P = 0.035] and showed significantly longer hospitalization {8 [SD, 8.4 (NR)] vs 9 [SD, 15.4 {R}] days, P = 0.006} after prereconstruction radiation. Conclusions Our findings suggest that DIEP flap reconstruction after radiation therapy is feasible. Women with a history of radiation therapy should, however, be informed in detail about the higher risk for wound healing disturbances at the recipient site

Comparing 200,000 Breast Implants and 85,000 Patients over Four National Breast Implant Registries

Background: Growing awareness about breast implant-related adverse events has stimulated the demand for large, independent data resources. For this, data from breast implant registries could be combined. However, that has never been achieved yet. Methods: Real-world data from four currently active national breast implant registries were used. All permanent breast implants from the Australian, Dutch, Swedish, and American registries were included. A subpopulation present across all registries between 2015 and 2018 was subsequently selected, including only permanent breast implants inserted during primary surgery for breast reconstruction or augmentation in patients without previous breast device surgery. Nationwide coverage, patient and implant characteristics, infection control measures, and revision incidences were analyzed. Results: A total of 207,189 breast implants were registered. Nationwide coverage varied between 3% and 98%. The subpopulation included 111,590 implants (7% reconstruction, 93% augmentation). Across the registries, mean patient age varied between 41 and 49 years (P &lt; 0.001) for reconstruction and 31 and 36 years (P &lt; 0.001) for augmentation. Variation was observed in implant preferences across the countries and over the years. Infection control measures were most frequently registered in Australia. Cumulative revision incidence at 2 years ranged from 6% to 16% after reconstruction and from 1% to 4% after augmentation. Conclusions: For the first time, independent, national, registry-based data from four breast implant registries were combined. This is a powerful step forward in optimizing international breast implant monitoring, evidence-based decision-making, and patient safety.</p