Background:Standard isolation of adipose stromal vascular fraction (SVF) requires the use of collagenase and is considered more than “minimally manipulated” by current good manufacturing practice requirements. Alternatively, nonenzymatic isolation methods have surfaced using physical forces to separate cells from the adipose matrix. The purpose of this study was to review the literature on the use of mechanical isolation protocols and compare the results. The implication for use as a standard procedure in practice is discussed.Methods:A systematic review of the literature was performed on mechanical isolation of SVF with a search of six terms on PubMed and Medline databases. One thousand sixty-six articles were subject to evaluation by predetermined inclusion and exclusion criteria.Results:Two level 2 evidence articles and 7 in vitro studies were selected. SVF was isolated using automated closed systems or by subjecting the lipoaspirate to centrifugation only or by shaking or vortexing followed by centrifugation. Six articles reported isolation in laboratory settings and three inside the operating room. Stromal vascular cells expressed CD34, and CD44, CD73, CD90, and CD105, and differentiated along adipogenic and osteogenic lineages. When compared with enzymatic methods, mechanical isolation required less time but yielded fewer cells. Both case–control studies reported improved volume retention with cell-supplemented fat grafts for breast reconstruction.Conclusions:Mechanical isolation methods are alternatives to circumvent safety issues posed by enzymatic protocols. However, randomized comparative studies with long-term clinical outcomes using mechanically isolated stromal vascular cells are needed to identify their ideal clinical applications.

Background Postmastectomy radiation therapy (PMRT) decreases loco-regional recurrence and improves survival in patients with locally advanced breast cancer. Autologous free flap reconstruction, while more durable in the setting of radiation than alloplastic reconstruction, is still susceptible to radiation-induced fibrosis, contracture, fat necrosis, volume loss, and distortion of breast shape. Options for reconstruction timing (immediate vs. delayed) have been discussed to mitigate these effects, but a clear optimum is not known. Methods A systematic review of the literature was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using search terms “breast reconstruction AND (radiation OR irradiation OR radiotherapy)” were used. Inclusion criteria consisted of studies reporting complications for free flap breast reconstruction in the setting of PMRT. Patients who underwent PMRT were pooled into two groups: those who underwent immediate free flap reconstruction prior to PMRT and those who underwent delayed reconstruction after PMRT. Results Out of the 23 studies, 12 focused on immediate reconstruction, seven focused on delayed reconstruction, and four studies included both groups. Overall, 729 patients underwent immediate reconstruction, while 868 underwent delayed reconstruction. Complete and partial flap loss rates were significantly higher in patients undergoing delayed reconstruction, while infection and wound-healing complication rates were higher in those undergoing immediate reconstructions. Rates of unplanned reoperations, vascular complications, hematoma/seroma, and fat necrosis did not differ significantly between the two groups. However, rates of planned revision surgeries were higher in the delayed reconstruction group. Conclusion Immediate free flap breast reconstruction is associated with superior flap survival compared with delayed reconstruction. Rates of complications are largely comparable, and rates of revision surgeries are equivalent. The differences in long-term aesthetic outcomes are not, however, clearly assessed by the available literature. Even in the face of PMRT, immediate free flap breast reconstruction is an effective approach.

Background Despite improvements in microsurgical techniques, hypercoagulable patients remain a reconstructive challenge. Thrombophilias are a relatively common problem with potentially catastrophic results including free flap loss. The aim of this study was to assess the available literature on free tissue transfer in patients with known hypercoagulability to develop recommendations for management. Methods A systematic review of the PubMed, EBSCO, and Cochrane databases was performed in June 2018. Inclusion criteria were assessment of outcomes of free tissue transfer in patients with established hypercoagulability. Exclusion criteria were review articles, case reports, and studies lacking detailed discussion of anticoagulation regimens and surgical outcomes. Data collected included the number of hypercoagulable patients, anticoagulation regimens, thrombotic complications, flap success, and bleeding complications. Statistical analysis was performed using independent samples t-tests. Results Of 147 total results, four articles were included for analysis. One relevant article published after search completion was included. In total, 185 free tissue transfers were performed in 155 thrombophilic patients. Anticoagulation regimens varied widely but often included intraoperative continuous heparin, with or without additional bolus, followed by postoperative and outpatient anticoagulation. Hypercoagulable patients often developed late postoperative thromboses. Of the intraoperative thromboses, 36.4% were successfully salvaged. No flaps with postoperative thrombosis were salvaged. Preemptive therapeutic anticoagulation improved outcomes but increased the bleeding risk. Conclusion Free tissue transfer may be successful in hypercoagulable patients. High-risk patients identified preoperatively should receive therapeutic anticoagulation initiated intraoperatively unless contraindicated. Salvage after postoperative thrombosis is poor. Ultimately, the benefits of free tissue transfer must be considered with the potential morbidity of bleeding complications on a case-by-case basis when developing a reconstructive plan. Initiating anticoagulation based on the presence of intraoperative risk factors may prevent unnecessary intervention.

Therapeutic, IV.

Background Feminizing and masculinizing hormone treatments are established components of management in transgender patients. Exogenous hormones have been associated with hemostatic effects, which are well-studied in cis-gender individuals on hormone replacement therapy (HRT). Unfortunately, comprehensive understanding of their effects on venous thromboembolism (VTE) risk in the transgender population is lacking. Aim This manuscript aims to identify the risk of VTE among transgender individuals undergoing cross-sex hormone therapy. Methods A Systematic review of the literature was performed in March 2020 for studies reporting VTE rates in transgender patients undergoing hormone treatment and rates in cis-gender patients on HRT. Data regarding demographics, hormone therapy, and VTE incidence were collected and pooled for analysis. Outcome The primary outcome of interest was the development of a VTE event in association with concurrent hormone administration. RESULTS Overall, 22 studies were included with 11 reporting VTE rates among transgender patients, 6 in cis-female patients, and 5 in cis-male patients. Data from 9,180 transgender patients (6,068 assigned male at birth [AMAB] and 3,112 assigned female at birth [AFAB]) undergoing hormone treatment and 103,713 cis-gender patients (18,748 female and 84,965 male) undergoing HRT were pooled. The incidence of VTE was higher in AMAB patients compared to AFAB patients (42.8 vs 10.8 VTE per 10,000 patient years; P = .02). The rate of VTE incidences in AMAB patients appears similar or higher than the rate demonstrated in cis-females on HRT. VTE incidence in AFAB patients, however, is similar to the published rates in cis-males on HRT. Clinical Implications AMAB patients on hormone therapy have higher VTE rates than AFAB patients. AMAB and AFAB patients may have similar VTE incidence to cis-female and cis-male patients on hormone replacement therapy, respectively. Strengths & Limitations This is the first study to aggregate and quantify the development of VTE events in association with hormone therapy in transgender patients. It places these values in the context of rates published in more widely studied populations. It is limited by its retrospective data and heterogenic data. CONCLUSION Surgical planning regarding perioperative and postoperative VTE prophylaxis or cessation of hormone therapy should take into account each patient’s Caprini risk assessment and the nature of each intervention.

Frostbite is a cold injury that results in soft tissue loss and can lead to amputation. Vascular thrombosis following injury causes ischemic tissue damage. Despite understanding the pathology, its treatment has remained largely unchanged for over 30 years. Threatened extremities may be salvaged with thrombolytics to restore perfusion. The authors performed a systematic review to determine whether thrombolytic therapy is effective and to identify patients who may benefit from this treatment. The Pubmed, EBSCO, and Google Scholar databases were queried using the key words “thrombolytics,” “frostbite,” “fibrinolytics,” and “tPA.” Studies written after 1990 in English met inclusion criteria. Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as administration of tPA, alteplase, urokinase, or streptokinase. Forty-two studies were identified and 17 included. Included were 1 randomized trial, 10 retrospective studies, 2 case series, and 4 case reports. One thousand eight hundred and forty-four limbs and digits in 325 patients were studied and 216 patients treated with thrombolytics and 346 amputations performed. The most common means of thrombolysis was intra-arterial tPA. The most common duration of therapy was 48 hours. Limb salvage rates ranged from 0% to 100% with a weighted average of 78.7%. Thrombolytics are a safe and effective treatment of severe frostbite. They represent the first significant advancement in frostbite treatment by preventing otherwise inevitable amputations warranting both greater utilization and further research to clarify the ideal thrombolytic protocol.

Mesenchymal stem cells (MSCs) are a population of multipotent cells that can be isolated from various adult and fetal tissues, including adipose tissue. These cells contain enormous clinical and basic research appeal due to their plasticity to differentiate into cells of all germ layers in vitro, cross allogeneic barriers in vivo, and suppress inflammation. Methods to isolate adipose-derived MSCs (ADSCs) primarily rely on enzymatic digestion of the adipose tissue using harsh enzymes such as collagenase. However, these harsh enzymes are expensive and can have detrimental effects on the ADSCs, including risks of using xenograft components in clinical application. This chapter focuses on methods of isolating ADSCs from adipose tissue without enzymatic digestion.

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