Implant-Based Breast Reconstruction after Mastectomy, from the Subpectoral to the Prepectoral Approach: An Evidence-Based Change of Mind?

Over the last years, prepectoral implant-based breast reconstruction has undergone a renaissance due to several technical advancements regarding mastectomy techniques and surgical approaches for the placement and soft tissue coverage of silicone implants. Initially abandoned due to the high incidence of complications, such as capsular contraction, implant extrusion, and poor aesthetic outcome, the effective prevention of these types of complications led to the prepectoral technique coming back in style for the ease of implant placement and the conservation of the pectoralis muscle function. Additional advantages such as a decrease of postoperative pain, animation deformity, and operative time contribute to the steady gain in popularity. This review aims to summarize the factors influencing the trend towards prepectoral implant-based breast reconstruction and to discuss the challenges and prospects related to this operative approach

Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis

Bromelain has previously been shown to prevent ischemia-induced necrosis in different types of tissues. In the present study, we, therefore, evaluated for the first time, the tissue-protective effects of bromelain in musculocutaneous flaps in mice. Adult C57BL/6N mice were randomly assigned to a bromelain treatment group and a control group. The animals were treated daily with intraperitoneal injections of 20 mg/kg bromelain or saline (control), starting 1 h before the flap elevation throughout a 10-day observation period. The random-pattern musculocutaneous flaps were raised on the backs of the animals and mounted into a dorsal skinfold chamber. Angiogenesis, nutritive blood perfusion and flap necrosis were quantitatively analyzed by means of repeated intravital fluorescence microscopy over 10 days after surgery. After the last microscopy, the flaps were harvested for additional histological and immunohistochemical analyses. Bromelain reduced necrosis of the critically perfused flap tissue by ~25%. The bromelain-treated flaps also exhibited a significantly higher functional microvessel density and an elevated formation of newly devel oped microvessels in the transition zone between the vital and necrotic tissues when compared to the controls. Immunohistochemical analyses demonstrated a markedly lower invasion of the myeloperoxidase-positive neutrophilic granulocytes and a significantly reduced number of cleaved caspase 3-positive apoptotic cells in the transition zone of bromelain-treated musculocutaneous flaps. These findings indicate that bromelain prevents flap necrosis by maintaining nutritive tissue perfusion and by suppressing ischemia-induced inflammation and apoptosis. Hence, bromelain may represent a promising compound to prevent ischemia-induced flap necrosis in clinical practice

Microvascular Fragments Protect Ischemic Musculocutaneous Flap Tissue from Necrosis by Improving Nutritive Tissue Perfusion and Suppressing Apoptosis

Microvascular fragments (MVF) derived from enzymatically digested adipose tissue are functional vessel segments that have been shown to increase the survival rate of surgical flaps. However, the underlying mechanisms have not been clarified so far. To achieve this, we raised random-pattern musculocutaneous flaps on the back of wild-type mice and mounted them into dorsal skinfold chambers. The flaps were injected with MVF that were freshly isolated from green fluorescent protein-positive (GFP+ ) donor mice or saline solution (control). On days 1, 3, 5, 7, and 10 after surgery, intravital fluorescence microscopy was performed for the quantitative assessment of angiogenesis, nutritive blood perfusion, and flap necrosis. Subsequently, the flaps were analyzed by histology and immunohistochemistry. The injection of MVF reduced necrosis of the ischemic flap tissue by ~20%. When compared to controls, MVF-injected flaps also displayed a significantly higher functional capillary density and number of newly formed microvessels in the transition zone, where vital tissue bordered on necrotic tissue. Immunohistochemical analyses revealed a markedly lower number of cleaved caspase-3+ apoptotic cells in the transition zone of MVF-injected flaps and a significantly increased number of CD31+ microvessels in both the flaps’ base and transition zone. Up to ~10% of these microvessels were GFP+ , proving their origin from injected MVF. These findings demonstrate that MVF reduce flap necrosis by increasing angiogenesis, improving nutritive tissue perfusion, and suppressing apoptosis. Hence, the injection of MVF may represent a promising strategy to reduce ischemia-induced flap necrosis in future clinical practice

Improved Vascularization and Survival of White Compared to Brown Adipose Tissue Grafts in the Dorsal Skinfold Chamber

Fat grafting is a frequently applied procedure in plastic surgery for volume reconstruction. Moreover, the transplantation of white adipose tissue (WAT) and brown adipose tissue (BAT) in creasingly gains interest in preclinical research for the treatment of obesity-related metabolic defects. Therefore, we herein directly compared the vascularization capacity and survival of WAT and BAT grafts. For this purpose, size-matched grafts isolated from the inguinal WAT pad and the interscapu lar BAT depot of C57BL/6N donor mice were syngeneically transplanted into the dorsal skinfold chamber of recipient animals. The vascularization and survival of the grafts were analyzed by means of intravital fluorescence microscopy, histology, and immunohistochemistry over an observation period of 14 days. WAT grafts showed an identical microvascular architecture and functional mi crovessel density as native WAT. In contrast, BAT grafts developed an erratic microvasculature with a significantly lower functional microvessel density when compared to native BAT. Accordingly, they also contained a markedly lower number of CD31-positive microvessels, which was associated with a massive loss of perilipin-positive adipocytes. These findings indicate that in contrast to WAT grafts, BAT grafts exhibit an impaired vascularization capacity and survival, which may be due to their higher metabolic demand. Hence, future studies should focus on the establishment of strategies to improve the engraftment of transplanted BAT

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

Relevance of the Scaphoid Shift Test for the Investigation of Scapholunate Ligament Injuries

Background: Although it is part of the common clinical examination of scapholunate ligament pathologies, there are only little data on the diagnostic value of the scaphoid shift test. The aim of this study was to evaluate the scaphoid shift test in a large cohort of patients. Materials and Methods: We retrospectively analysed 447 patients who underwent the scaphoid shift test and wrist arthroscopy because of various suspected injuries of the wrist, correlating the results of clinical examination with data obtained during the wrist arthroscopy. Sensitivity, specificity, and positive and negative predictive values were calculated and evaluated. Results: The sensitivity of the scaphoid shift test was low (0.50) when examining the whole cohort. In a subgroup of patients specifically referred for suspected scapholunate ligament injury, the sensitivity was higher (0.61), but the specificity was low (0.62). In detecting more serious lesions (Geissler 3 + 4), the scaphoid shift test demonstrated higher sensitivity (0.66). Conclusions: An isolated scaphoid shift test may only be of limited value in the diagnosis of scapholunate ligament lesions and should, therefore, be viewed as a useful tool for a preliminary assessment, but a negative test should not prevent the surgeon from indicating a more extensive diagnostic workup

Implant-Based Breast Reconstruction after Mastectomy, from the Subpectoral to the Prepectoral Approach: An Evidence-Based Change of Mind?

Over the last years, prepectoral implant-based breast reconstruction has undergone a renaissance due to several technical advancements regarding mastectomy techniques and surgical approaches for the placement and soft tissue coverage of silicone implants. Initially abandoned due to the high incidence of complications, such as capsular contraction, implant extrusion, and poor aesthetic outcome, the effective prevention of these types of complications led to the prepectoral technique coming back in style for the ease of implant placement and the conservation of the pectoralis muscle function. Additional advantages such as a decrease of postoperative pain, animation deformity, and operative time contribute to the steady gain in popularity. This review aims to summarize the factors influencing the trend towards prepectoral implant-based breast reconstruction and to discuss the challenges and prospects related to this operative approach

Long-term pre- and postconditioning with low doses of erythropoietin protects critically perfused musculocutaneous tissue from necrosis

It has been shown that pre- and postconditioning of ischemically challenged tissue with erythropoietin (EPO) is able to reduce necrosis in a dose-dependent manner. The aim of this study was to determine the tissue-protective effects of different EPO dosages and administration regimes. Three groups of six C57Bl/6-mice each were analyzed: (1) pre- and postconditioning with initial high doses of EPO (starting at 2500 I.U./kg bw i.p.) followed by low doses of EPO (125 I.U./kg bw i.p.) (EPO-high-dose); (2) pre- and postconditioning with low doses of EPO (125 I.U./kg bw i.p.) (EPO-low-dose); and (3) untreated control group. Randomly perfused musculocutaneous flaps were mounted on dorsal skinfold chambers undergoing acute persistent ischemia and developing ∼50% necrosis without treatment. Intravital epifluorescence microscopy was performed at days 1, 3, 5, 7, and 10 after surgery, assessing flap necrosis, microcirculation, and angiogenesis. The hematocrit was measured at days 0, 3, 7, and 10. Only the EPO-low-dose regimen was associated with a significant reduction of necrosis when compared to untreated controls. EPO-low-dose showed a higher increase in both arteriolar diameter and velocity, thereby resulting in a significantly increased arteriolar blood flow and a hence higher functional capillary density (FCD) of the critically perfused zone. EPO-induced angiogenesis was significantly increased in EPO-low-dose at days 7 and 10. Only EPO-high-dose reached a significant hematocrit increase by day 10. Tissue pre- and postconditioning with low doses of EPO protects the critically perfused musculocutaneous tissue by maintaining capillary perfusion because of increased arteriolar blood flow mediated by nitric oxide (NO) expression

Bromelain Protects Critically Perfused Musculocutaneous Flap Tissue from Necrosis

Bromelain has previously been shown to prevent ischemia-induced necrosis in different types of tissues. In the present study, we, therefore, evaluated for the first time, the tissue-protective effects of bromelain in musculocutaneous flaps in mice. Adult C57BL/6N mice were randomly assigned to a bromelain treatment group and a control group. The animals were treated daily with intraperitoneal injections of 20 mg/kg bromelain or saline (control), starting 1 h before the flap elevation throughout a 10-day observation period. The random-pattern musculocutaneous flaps were raised on the backs of the animals and mounted into a dorsal skinfold chamber. Angiogenesis, nutritive blood perfusion and flap necrosis were quantitatively analyzed by means of repeated intravital fluorescence microscopy over 10 days after surgery. After the last microscopy, the flaps were harvested for additional histological and immunohistochemical analyses. Bromelain reduced necrosis of the critically perfused flap tissue by ~25%. The bromelain-treated flaps also exhibited a significantly higher functional microvessel density and an elevated formation of newly developed microvessels in the transition zone between the vital and necrotic tissues when compared to the controls. Immunohistochemical analyses demonstrated a markedly lower invasion of the myeloperoxidase-positive neutrophilic granulocytes and a significantly reduced number of cleaved caspase 3-positive apoptotic cells in the transition zone of bromelain-treated musculocutaneous flaps. These findings indicate that bromelain prevents flap necrosis by maintaining nutritive tissue perfusion and by suppressing ischemia-induced inflammation and apoptosis. Hence, bromelain may represent a promising compound to prevent ischemia-induced flap necrosis in clinical practice