The translatability of research is highly dependent on models that recapitulate human tissues and organs. Here, we describe a procedure for the generation of human epidermis organotypic cultures ...(HEOCs) from primary keratinocytes isolated from foreskin and adult skin as well as from an immortalized keratinocyte cell line (KerTr). We tested several media conditions to develop a defined HEOC growing and expansion media. We characterized the HEOCs and show that in optimal culture conditions they express the proliferation marker Ki67, the basement membrane protein collagen 17 (col17) and the epidermal differentiation markers keratin 15 (K15), keratin 14 (K14), keratin 5 (K5), keratin 10 (K10), keratin 1 (K1), transglutaminase 1 (TGM1), transglutaminase 3 (TGM3) and filaggrin (FLG). Thus, they recapitulate the human epidermis and are stratified from the basal layer to the stratum corneum. These HEOC can be generated reproducibly on a large scale, making it an invaluable model for screening therapeutic compounds and also for the study of pathologies affecting the epidermis.
In aesthetic clinical practice, surgical outcome is best measured by patient satisfaction and quality of life. For many years, there has been a lack of validated questionnaires. Recently, the FACE-Q ...was introduced, and the authors present the largest series of face-lift patients evaluated by the FACE-Q with the longest follow-up to date.
Two hundred consecutive patients were identified who underwent high-superficial musculoaponeurotic system face lifts, with or without additional facial rejuvenation procedures, between January of 2005 and January of 2015. Patients were sent eight FACE-Q scales and were asked to answer questions with regard to their satisfaction. Rank analysis of covariance was used to compare different subgroups.
The response rate was 38 percent. Combination of face lift with other procedures resulted in higher satisfaction than face lift alone (p < 0.05). Patients who underwent lipofilling as part of their face lift showed higher satisfaction than patients without lipofilling in three subscales (p < 0.05).
Facial rejuvenation surgery, combining a high-superficial musculoaponeurotic system face lift with lipofilling and/or other facial rejuvenation procedures, resulted in a high level of patient satisfaction. The authors recommend the implementation of the FACE-Q by physicians involved in aesthetic facial surgery, to validate their clinical outcomes from a patient's perspective.
Humans lack the enzyme that produces the sialic acid N-glycolyl neuraminic acid (Neu5Gc), but several lines of evidence have shown that Neu5Gc can be taken up by mammalian food sources and replace ...the common human sialic acid N-acetyl neuraminic acid (Neu5Ac) in glycans. Cancer tissue has been shown to have increased the presence of Neu5Gc and Neu5Gc-containing glycolipids such as the ganglioside GM3, which have been proposed as tumor-specific antigens for antibody treatment. Here, we show that a previously described antibody against Neu5Gc-GM3 is binding to Neu5GC-containing gangliosides and is strongly staining different cancer tissues. However, we also found a strong intracellular staining of keratinocytes of healthy skin. We confirmed this staining on freshly isolated keratinocytes by flow cytometry and detected Neu5Gc by mass spectrometry. This finding implicates that non-human Neu5Gc can be incorporated into gangliosides in human skin, and this should be taken into consideration when targeting Neu5Gc-containing gangliosides for cancer immunotherapy.
Purpose
To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from ...the German, Austrian and Swiss societies of senology.
Methods
A total of 52 questions were addressed by electronic voting. The panel’s recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained.
Results
The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient.
Conclusions
When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.
Abstract
Aims
Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is ...urgently needed.
Methods and results
Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into ‘extra-cardiac’ if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and ‘cardiac’, further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45–98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis.
Conclusion
At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments.
Study registration
https://clinicaltrials.gov/ct2/show/NCT02573532.
Structured Graphical Abstract
Structured Graphical Abstract
At 1 year, most PMI aetiologies have unacceptably high rates of major adverse cardiac event and all-cause death, highlighting the need for more comprehensive management strategies, taking different aetiologies, their incidence, and their associated outcomes into consideration. PMI was defined as an absolute increase in cTn from pre-operative to post-operative concentrations of at least the upper limit of normal of the used assay (for high sensitivity cTnT this corresponds to an increase of at least +14 ng/L, e.g. from 10 ng/L pre-operatively to ≥24 ng/L post-operatively). cTn, cardiac troponin; PMI, perioperative myocardial infarction/injury.
Audio Abstract
10.1093/eurheartj/ehac798audio1
Audio Abstract
ehac798media1
6319325036112
Introduction
A range of behavioral testing paradigms have been developed for the research of central and peripheral nerve injuries with the help of small animal models. Following any nerve repair ...strategy, improved functional outcome may be the most important evidence of axon regeneration. A novel automated gait analysis system, the CatWalk™, can measure dynamic as well as static gait patterns of small animals. Of most interest in detecting functional recovery are in particular dynamic gait parameters, coordination measures, and the intensity of the animals paw prints. This article is designed to lead to a more efficient choice of CatWalk parameters in future studies concerning the functional evaluation of nerve regeneration and simultaneously add to better interstudy comparability.
Methods
The aims of the present paper are threefold: (1) to describe the functional method of CatWalk gait analysis, (2) to characterize different parameters acquired by CatWalk gait analysis, and to find the most frequently used parameters as well as (3) to compare their reliability and validity throughout the different studies.
Results
In the reviewed articles, the most frequently used parameters were Swing Duration (30), Print Size (27), Stride Length (26), and Max Contact Area (24). Swing Duration was not only frequently used but was also the most reliable and valid parameter. Therefore, we hypothesize that Swing Duration constitutes an important parameter to be chosen for future studies, as it has the highest level of reliability and validity.
Conclusion
In conclusion, CatWalk can be used as a complementary approach to other behavioral testing paradigms to assess clinically relevant behavioral benefits, with the main advantage that this system demonstrates both static and dynamic gait parameters at the same time. Due to limited reliability and validity of certain parameters, we recommend that only the most frequently assessed parameters should be used in the future.
A range of behavioral testing paradigms have been developed for the research of peripheral nerve injuries by small animal models. Following any nerve repair strategy, improved functional outcome may be the most important evidence of axon regeneration. The CatWalk can measure dynamic as well as static gait patterns of small animals in different study settings. This article is designed to lead to a more efficient choice of parameters in future studies concerning the functional evaluation of peripheral nerve regeneration to add to better interstudy comparability.
Background: Patients with advanced vulvoperineal cancer require a multidisciplinary treatment approach to ensure oncological safety, timely recovery, and the highest possible quality of life (QoL). ...Reconstructions in this region often lead to complications, affecting approximately 30% of patients. Flap design has evolved towards perforator-based approaches to reduce functional deficits and (donor site) complications, since they allow for the preservation of relevant anatomical structures. Next to their greater surgical challenge in elevation, their superiority over non-perforator-based approaches is still debated. Methods: To compare outcomes between perforator and non-perforator flaps in female vulvoperineal reconstruction, we conducted a systematic review of English-language studies published after 1980, including randomized controlled trials, cohort studies, and case series. Data on demographics and surgical outcomes were extracted and classified using the Clavien–Dindo classification. We used a random-effects meta-analysis to derive a pooled estimate of complication frequency (%) in patients who received at least one perforator flap and in patients who received non-perforator flaps. Results: Among 2576 screened studies, 49 met our inclusion criteria, encompassing 1840 patients. The overall short-term surgical complication rate was comparable in patients receiving a perforator (n = 276) or a non-perforator flap (n = 1564) reconstruction (p* > 0.05). There was a tendency towards fewer complications when using perforator flaps. The assessment of patients’ QoL was scarce. Conclusions: Vulvoperineal reconstruction using perforator flaps shows promising results compared with non-perforator flaps. There is a need for the assessment of its long-term outcomes and for a systematic evaluation of patient QoL to further demonstrate its benefit for affected patients.
Limited data exist regarding the effect of adjuvant radiochemotherapy on free flap volume in head and neck reconstruction. However, an adequate free flap volume is an important predictor of ...functional and patient-reported outcomes in head and neck reconstruction.
A systematic review of Medline, Embase, and the Cochrane Central Register of Controlled Trials was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 6710 abstracts were screened, and 36 full-text papers were reviewed. Nineteen studies met the inclusion criteria and were used to extract data for this analysis.
A meta-analysis of 14 two-arm studies comparing the impact of adjuvant radiotherapy versus no adjuvant radiotherapy was performed. The main analysis revealed that 6 months postoperatively, irradiated flaps showed a significant reduction of volume (average, 9.4%) compared to nonirradiated flaps. The average interpolated pooled flap volumes 6 months postoperatively were 76.4% in irradiated flaps and 81.8% in nonirradiated flaps. After a median postoperative follow-up of 12 months, the total flap volume was 62.6% for irradiated flaps and 76% for nonirradiated flaps. Four studies reported that chemotherapy had no significant impact on free flap volume.
Compared to nonirradiated flaps, irradiated flaps were significantly reduced in volume (range, 5% to 15.5%). Clinicians should take this into account when planning the surgical reconstruction of head and neck defects. Conducting large-scale prospective studies with standardized protocols and well-defined follow-up measurements could contribute to defining the ideal, personalized free flap volume for optimal function and patient-reported outcomes.
Problems with a variety of breast implants have emerged with consequences for patients' health and safety. The authors' goal was to follow up on their Poly Implant Prothèse patients after their ...implant exchange.
This single-center, single-surgeon, prospective cohort study lasted from 2012 until 2017. Implant size, implantation interval, surgical details, and complications were registered. The Clavien-Dindo classification was used to grade postoperative complications. Logistic regression was used to investigate whether rupture, interval between implantation and explantation, and new implant size were predictors of postexchange complications.
The authors explanted 808 implants in 404 patients. The rupture rate was 30.9 percent per patient and 20.2 percent per implant. The capsular contracture rate at the time of exchange was low, with 1.86 percent of implants and 2.7 percent of patients; 97.8 percent of patients elected implant exchange and only 2.2 percent just wanted their implants removed. The mean follow-up after implant exchange was 5.2 years, with the last mandatory outpatient appointment usually being scheduled 6 to 12 months after implant exchange. The authors found that 74 patients (18.3 percent) and 124 implants (15.3 percent) had postexchange complications, the majority of them minor (83 percent Clavien-Dindo grade I). Patients with a ruptured implant at the time of exchange were significantly more likely to develop postexchange complications than were patients without rupture.
This is the first study providing such a complete long-term postexchange follow-up of a single surgeon's Poly Implant Prothèse implant cohort. Implant rupture at the time of exchange had a high predictive value for postexchange complications in the authors' series of 808 implants and 404 Poly Implant Prothèse recall patients.
Therapeutic, IV.
Postoperative complications after breast cancer surgery may be associated with decreased quality of life. It remains unclear whether oncoplastic breast-conserving surgery or mastectomy with ...reconstruction lead to more postoperative complications than conventional breast surgery (CBS). As delayed wound healing (DWH) is one of the most frequent minor complications, we sought to investigate the significance of DWH for patient-reported outcomes after oncoplastic, reconstructive, and CBS.
Our study is a retrospective cohort study of consecutive patients with stage I-II breast cancer who underwent oncoplastic or CBS performed by three breast surgeons at a single tertiary referral hospital from June 2011 until May 2019. Patient-reported outcomes were evaluated postoperatively using the BREAST-Q questionnaire. Comparisons were made between patients with and without DWH.
A total of 229 patients who met the inclusion criteria and 28 (12%) of them developed DWH, 27/158 (17%) in the oncoplastic breast-conserving surgery and reconstruction group and 1/71 (1%) in the CBS group. The mean time from surgery to BREAST-Q assessment was comparable in both groups (29 months in the DWH vs. 33 months in the normal wound healing group). No statistically significant difference for any BREAST-Q scale was detected between patients with and without DWH. This includes physical (p = 0.183), psychosocial (p = 0.489), sexual well-being (p = 0.895), and satisfaction with breasts (p = 0.068).
Our study confirms that oncoplastic breast-conserving surgery and mastectomy with reconstruction lead to significantly more DWH than CBS. However, neither quality of life nor patient-reported outcomes following state-of-the-art reconstructive or oncoplastic breast-conserving surgery at a specialized center seem to be compromised.
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