Influence of Closed-incision Negative Pressure Wound Therapy on Abdominal Site Complications in Autologous Breast Reconstruction.

Background: Closed-incision negative pressure wound therapy (ciNPWT) has shown promise in reducing surgical wound complications. Among its numerous benefits, it allows for exudate management and tension offloading from wound edges. The purpose of this systematic review and meta-analysis was to assess the efficacy of prophylactic ciNPWT versus conventional dressings on abdominal donor site complications in microsurgical breast reconstruction (MR). Methods: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in January 2023. PubMed and Embase were searched to identify all relevant studies. Data collected included rates of total wound complications, wound dehiscence, infection, seroma, and length of hospital stay. Results: A total of 202 articles were screened, and eight studies (1009 patients) met the inclusion criteria. Use of ciNPWT was associated with a significantly lower rate of wound dehiscence (OR, 0.53; 95% confidence interval, 0.33-0.85; P = 0.0085, I2 = 0%). There was no significant difference in the rate of total wound complications [odds ratio (OR), 0.63; 95% CI, 0.35-1.14; P = 0.12, I2 = 69%], donor site infection (OR, 0.91; 95% CI, 0.42-1.50; P = 0.47, I2 = 13%), seroma (OR, 0.74; 95% CI, 0.22-2.49; P = 0.63, I2 = 57%), or length of hospital stay (SMD, 0.089; 95% CI, -0.13-0.35; P = 0.37, I2 = 29%). Conclusions: Although exudate management by ciNPWT fails to reduce surgical site infection, seroma formation, and overall length of stay, ciNPWT tension offloading properties seem to be associated with lower rates of wound dehiscence when compared with conventional dressings in abdominal-based autologous breast reconstruction.

The Impact of Postoperative Antibiotic and Duration After Implant-Based Breast Reconstruction on Resistance Among Cultured Species.

BACKGROUND: There is a growing presence of literature within plastic surgery that establishes best practice for postoperative antibiotics after implant-based breast reconstruction (IBBR), although it has not been widely adopted or translated into clinical practice. This study aims to determine how antibiotic and duration affects patient outcomes. We hypothesize that IBBR patients who receive a longer duration of postoperative antibiotics will demonstrate higher rates of antibiotic resistance as compared with the institutional antibiogram. METHODS: A retrospective chart review included patients who underwent IBBR between 2015 and 2020 at a single institution. Variables of interest included patient demographics, comorbidities, surgical techniques, infectious complications, and antibiograms. Groups were classified by antibiotic (cephalexin, clindamycin, or trimethoprim/sulfamethoxazole) and duration (≤7 days, 8-14 days, and >14 days). RESULTS: There were a total of 70 patients who experienced infections included in this study. Onset of infection did not differ based on antibiotic during either device implantation (postexpander P = 0.391; postimplant P = 0.234). Antibiotic and duration did not have an established relationship with explantation rate either (P = 0.154). In patients who had Staphylococcus aureus isolated, there was significantly increased resistance to clindamycin when compared with the institutional antibiogram (sensitivities of 43% and 68%, respectively). CONCLUSIONS: Neither antibiotic nor duration displayed a difference in overall patient outcomes, including explantation rates. In this cohort, S. aureus strains isolated in association with IBBR infections demonstrated a higher level of resistance to clindamycin compared with strains isolated and tested within the broader institution.

Extent of Tissue Washing Can Significantly Alter the Composition of Adipose-Derived Stromal Vascular Fraction Cell Preparations: Implications for Clinical Translation.

Stromal vascular fraction (SVF) cell preparations have recently attracted much interest as a form of autologous cell therapy. These heterogenous cell populations typically include some proportion of blood-derived cells (BDCs)-including both red blood cells (RBCs) and leukocytes (WBCs). The objectives of this paper were to evaluate the effects of tissue washing and hypotonic RBC lysis-separately and together-on BDC concentrations within SVF, and further to explore whether BDCs can confer detectable and modifiable effects on adipose-derived cell activity. Using various cell culture assays, flow cytometry and ELISA analysis of human-derived SVF preparations, we show that thorough washing of adipose tissue prior to enzymatic dissociation effectively removes RBCs from SVF preparations as well as standard lysis methods and significantly alters the type and relative quantities of WBCs. In addition, these studies demonstrate that potentially toxic RBC components are detectable for up to 1 week in cultures containing RBC lysate, but not those with intact RBCs, and, that culture-expanded cells proliferate significantly more in the presence of intact RBCs versus RBC lysis products or control media. Broadly, these data exemplify how different seemingly mundane tissue processing steps can significantly influence SVF identity/composition, purity, and potency. Based on the findings of this work, we propose that translational efforts in the field would benefit by a better understanding of the impact of RBCs, WBCs, and non-viable cells on the in vivo therapeutic activity of SVF therapies.

Examining albumin as a bioindicator of healing capability in patients with diabetic foot ulcers: a retrospective review.

INTRODUCTION: Identifying a bioindicator of healing capacity would be beneficial in guiding treatment of and reducing morbidity in patients with DFU. Hypoalbuminemia is a well-established risk factor for amputation and, thus, a promising candidate. OBJECTIVE: This study was conducted to examine whether albumin values over a 12-week treatment course for DFU correlated with ulcer size and outcomes. MATERIALS AND METHODS: A retrospective review was conducted of 793 patients who presented to the Atrium Health Wake Forest Baptist Wound Care and Hyperbaric Center between 2010 and 2022. Sixty-two patients met the inclusion criteria. Albumin values and wound size data were collected monthly over a 12-week treatment course. RESULTS: Initial albumin values were not significantly different between patients healed by 12 weeks compared with nonhealed patients. Healed proportion and average initial ulcer size in patients with at least 1 hypoalbuminemia value (<3.0 g/dL) were not significantly different from those in patients with normal albumin levels. Patients who trended from normoalbuminemia to hypoalbuminemia displayed significantly increased wound sizes compared to patients with albumin changes within the normal range (0.04 cm² and -1.17 cm², respectively; P < .05). Monthly changes in albumin correlated poorly with wound healing (r = 0.144, P = .240), and large negative albumin trends (>0.5 g/dL per month) did not correlate with increased wound sizes compared with stable or positive trends. CONCLUSION: Albumin's utility as a bioindicator of short-term healing capability is limited to below-normal values.

The Need for Additional Surgery after Passive versus Active Approaches to Syndromic Craniosynostosis: A Meta-analysis.

Endoscopically assisted craniofacial surgery (EACS) has numerous advantages over traditional, open approaches, such as fronto-orbital advancement in treating nonsyndromic craniosynostosis. However, several articles report high reoperation rates in syndromic patients treated with EACS. This meta-analysis and review examines undesirable outcome rates (UORs), defined as reoperation or Whitaker category III/IV, in syndromic patients undergoing primary EACS compared with procedures that actively expand the cranial vault. Methods: PubMed and Embase were searched in June 2022 to identify all articles reporting primary reoperation or Whitaker outcomes for syndromic patients undergoing cranial vault expanding surgery or suturectomy. A meta-analysis of proportions was performed comparing UORs, and a trim-and-fill adjustment method was used to validate sensitivity and assess publication bias. Results: A total of 721 articles were screened. Five EACS articles (83 patients) and 22 active approach articles (478 patients) met inclusion criteria. Average UORs for EACS and active approaches were 26% (14%-38%) and 20% (13%-28%), respectively (P = 0.18). Reoperation occurred earlier in EACS patients (13.7 months postprimary surgery versus 37.1 months for active approaches, P = 0.003). Relapse presentations and reason for reoperation were also reviewed. Subjectively, EACS UORs were higher in all syndromes except Apert, and Saethre-Chotzen patients had the highest UOR for both approaches. Conclusions: There was no statistically significant increase in UORs among syndromic patients treated with EACS compared with traditional approaches, although EACS patients required revision significantly sooner. Uncertainties regarding the long-term efficacy of EACS in children with syndromic craniosynostosis should be revisited as more data become available.

The effects of a mitochondrial targeted peptide (elamipretide/SS31) on BAX recruitment and activation during apoptosis.

OBJECTIVE: Elamipretide (SS31) is a mitochondria-targeted peptide that has reported functions of stabilizing mitochondrial cristae structure and improving mitochondrial bioenergetics. Several studies have documented cell protective features of this peptide, including impairment of intrinsic apoptosis by inhibiting the recruitment and activation of the pro-apoptotic BAX protein. We used live-cell imaging of ARPE-19 cells expressing fluorescently labeled BAX, cytochrome c, and a mitochondrial marker to investigate the effect of elamipretide on the kinetics of BAX recruitment, mitochondrial outer membrane permeabilization (as a function of cytochrome c release), and mitochondrial fragmentation, respectively. RESULT: In nucleofected and plated ARPE-19 cells, elamipretide accelerated the formation of larger mitochondria. In the presence of the apoptotic stimulator, staurosporine, cells treated with elamipretide exhibited moderately slower rates of BAX recruitment. Peptide treatment, however, did not significantly delay the onset of BAX recruitment or the final total amount of BAX that was recruited. Additionally, elamipretide showed no impairment or delay of cytochrome c release or mitochondrial fragmentation, two events associated with normal BAX activation during cell death. These results indicate that the protective effect of elamipretide is not at the level of BAX activity to induce pro-apoptotic mitochondrial dysfunction after the initiation of staurosporine-induced apoptosis.

Characteristics of intracellular propagation of mitochondrial BAX recruitment during apoptosis.

Recent advancements in live cell imaging technologies have identified the phenomenon of intracellular propagation of late apoptotic events, such as cytochrome c release and caspase activation. The mechanism, prevalence, and speed of apoptosis propagation remain unclear. Additionally, no studies have demonstrated propagation of the pro-apoptotic protein, BAX. To evaluate the role of BAX in intracellular apoptotic propagation, we used high speed live-cell imaging to visualize fluorescently tagged-BAX recruitment to mitochondria in four immortalized cell lines. We show that propagation of mitochondrial BAX recruitment occurs in parallel to cytochrome c and SMAC/Diablo release and is affected by cellular morphology, such that cells with processes are more likely to exhibit propagation. The initiation of propagation events is most prevalent in the distal tips of processes, while the rate of propagation is influenced by the 2-dimensional width of the process. Propagation was rarely observed in the cell soma, which exhibited near synchronous recruitment of BAX. Propagation velocity is not affected by mitochondrial volume in segments of processes, but is negatively affected by mitochondrial density. There was no evidence of a propagating wave of increased levels of intracellular calcium ions. Alternatively, we did observe a uniform increase in superoxide build-up in cellular mitochondria, which was released as a propagating wave simultaneously with the propagating recruitment of BAX to the mitochondrial outer membrane.

Targeting HDAC3 in the DBA/2J spontaneous mouse model of glaucoma.

High intraocular pressure (IOP) is the most common risk factor associated with glaucoma in humans. While lowering IOP is effective at reducing the rate of retinal ganglion cell (RGC) loss, to date, no treatment exists to directly preserve these cells affected by damage to the optic nerve. Recently, histone deacetylase-3 (HDAC3) has become a potential therapeutic target because it plays an important role in the early nuclear atrophic events that precede RGC death. Conditional knockout or inhibition of HDAC3 prevents histone deacetylation, heterochromatin formation, apoptosis, and eventual RGC loss following acute optic nerve injury. Using these approaches to repress HDAC3 activity, we tested whether targeting HDAC3 protects RGCs from ganglion cell-specific BRN3A expression loss, total somatic cell loss, and optic nerve degeneration in the DBA/2J mouse model of spontaneous glaucoma. Targeted ablation of Hdac3 activity did not protect RGCs from axonal degeneration or somatic cell death in the DBA/2J mouse model of glaucoma. However, inhibition of HDAC3 activity using RGFP966 conferred mild protection against somatic cell loss in the ganglion cell layer in aged DBA/2J mice. Further experimentation is necessary to determine whether other class I HDACs may serve as potential therapeutic targets in chronic models of glaucoma.

BAX-Depleted Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage.

Removal of the Bax gene from mice completely protects the somas of retinal ganglion cells (RGCs) from apoptosis following optic nerve injury. This makes BAX a promising therapeutic target to prevent neurodegeneration. In this study, Bax+/- mice were used to test the hypothesis that lowering the quantity of BAX in RGCs would delay apoptosis following optic nerve injury. RGCs were damaged by performing optic nerve crush (ONC) and then immunostaining for phospho-cJUN, and quantitative PCR were used to monitor the status of the BAX activation mechanism in the months following injury. The apoptotic susceptibility of injured cells was directly tested by virally introducing GFP-BAX into Bax-/- RGCs after injury. The competency of quiescent RGCs to reactivate their BAX activation mechanism was tested by intravitreal injection of the JNK pathway agonist, anisomycin. Twenty-four weeks after ONC, Bax+/- mice had significantly less cell loss in their RGC layer than Bax+/+ mice 3 weeks after ONC. Bax+/- and Bax+/+ RGCs exhibited similar patterns of nuclear phospho-cJUN accumulation immediately after ONC, which persisted in Bax+/- RGCs for up to 7 weeks before abating. The transcriptional activation of BAX-activating genes was similar in Bax+/- and Bax+/+ RGCs following ONC. Intriguingly, cells deactivated their BAX activation mechanism between 7 and 12 weeks after crush. Introduction of GFP-BAX into Bax-/- cells at 4 weeks after ONC showed that these cells had a nearly normal capacity to activate this protein, but this capacity was lost 8 weeks after crush. Collectively, these data suggest that 8-12 weeks after crush, damaged cells no longer displayed increased susceptibility to BAX activation relative to their naïve counterparts. In this same timeframe, retinal glial activation and the signaling of the pro-apoptotic JNK pathway also abated. Quiescent RGCs did not show a timely reactivation of their JNK pathway following intravitreal injection with anisomycin. These findings demonstrate that lowering the quantity of BAX in RGCs is neuroprotective after acute injury. Damaged RGCs enter a quiescent state months after injury and are no longer responsive to an apoptotic stimulus. Quiescent RGCs will require rejuvenation to reacquire functionality.