Salvage of Nipple-Areolar Complex Ischemia With Dimethyl Sulfoxide: A Case Series.

BACKGROUND: Nipple-areolar complex (NAC) necrosis is a known risk of breast surgery, particularly mastectomy. Disruption of the underlying blood supply to the NAC can lead to ischemia and subsequent necrosis. Nitroglycerin paste is currently used to combat NAC ischemia but has limited efficacy and an unfavorable side effect profile. Topical dimethyl sulfoxide (DMSO) has been shown to increase tissue perfusion in microsurgery and various skin flaps, but its role in the treatment and prevention of NAC ischemia has not been reported. Through a prospective case series, this study aims to introduce DMSO as a safe treatment for NAC ischemia after breast surgery. METHODS: Patients treated by 2 breast surgeons and a single plastic surgeon who underwent nipple-sparing mastectomy or breast reduction and developed NAC ischemia were identified via a prospectively maintained database. Ischemic changes were diagnosed, and treatment to the affected NAC with DMSO was initiated at the conclusion of the procedure, or postoperative day 1 in most cases, and continued 4 times daily until ischemic changes had resolved clinically. Collected demographic, surgical, and outcome variables were analyzed using descriptive statistics. RESULTS: Eleven patients with a mean age of 47.8 ± 9.5 years (range, 35-61 years) and mean body mass index of 26.0 ± 4.4 kg/m2 (range, 20.7-33.4 kg/m2) were identified. The mean duration of time between surgery and the clinical diagnosis of NAC ischemia was 1.3 ± 2.8 days (range, 0-7 days). The average length of time from DMSO initiation to clinical improvement or resolution of NAC ischemia was 7.5 ± 2.5 days (range, 5-12 days). All patients demonstrated significant improvement or complete resolution of NAC ischemia following serial topical DMSO application. CONCLUSIONS: This study demonstrates DMSO is a safe treatment for threatened NACs. All patients in this series showed either dramatic improvement or resolution of NAC ischemia after DMSO application, and threatened NACs of all 11 patients were successfully salvaged. These promising results set the basis for ongoing randomized controlled studies to determine the efficacy of DMSO treatment for NAC ischemia.

Healing Exposed Calvarial Hardware Using Negative-Pressure Wound Therapy and Vashe Wound Solution: Case Report.

OBJECTIVE: The management of cranioplasty infections has historically been explantation followed by delayed reimplantation/reconstruction. This treatment algorithm necessitates surgery, tissue expansion, and prolonged disfigurement. In this report, the authors describe a treatment approach consisting of serial vacuum-assisted closure (VAC) with hypochlorous acid (HOCl) solution (Vashe Wound Solution; URGO Medical) as a salvage strategy. METHODS: A 35-year-old man who sustained head trauma, neurosurgical complications, and severe syndrome of the trephined (SOT; devastating neurologic decline treated by cranioplasty) underwent titanium cranioplasty with free flap. Three weeks postoperation, he presented with pressure-related wound dehiscence/partial flap necrosis, exposed hardware, and bacterial infection. Given the severity of his precranioplasty SOT, hardware salvage was critical. He was treated with serial VAC with HOCl solution for 11 days followed by VAC for 18 days and definitive split-thickness skin graft placement over resulting granulation tissue. Authors also conducted a literature review of cranial reconstruction infection management. RESULTS: The patient remained healed 7 months postoperatively without recurrent infection. Importantly, his original hardware was retained, and his SOT remained resolved. Findings from the literature review support the use of conservative modalities to salvage cranial reconstructions without hardware removal. CONCLUSIONS: This study investigates a new strategy for managing cranioplasty infections. The VAC with HOCl solution regimen was effective in treating the infection and salvaging the cranioplasty, thus obviating the complications associated with explantation, new cranioplasty, and recurrence of SOT. There is limited literature on the management of cranioplasty infections using conservative treatments. A larger study to better determine the efficacy of VAC with HOCl solution is underway.

Cigarette smoke exposed airway epithelial cell-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder most commonly secondary to a single mutation in the SERPINA1 gene (PI*Z) that causes misfolding and accumulation of alpha-1 antitrypsin (AAT) in hepatocytes and mononuclear phagocytes which reduces plasma AAT and creates a toxic gain of function. This toxic gain of function promotes a pro-inflammatory phenotype in macrophages that contributes to lung inflammation and early-onset COPD, especially in individuals who smoke cigarettes. The aim of this study is to determine the role of cigarette exposed AATD macrophages and bronchial epithelial cells in AATD-mediated lung inflammation. METHODS: Peripheral blood mononuclear cells from AATD and healthy individuals were differentiated into alveolar-like macrophages and exposed to air or cigarette smoke while in culture. Macrophage endoplasmic reticulum stress was quantified and secreted cytokines were measured using qPCR and cytokine ELISAs. To determine whether there is "cross talk" between epithelial cells and macrophages, macrophages were exposed to extracellular vesicles released by airway epithelial cells exposed to cigarette smoke and their inflammatory response was determined. RESULTS: AATD macrophages spontaneously produce several-fold more pro-inflammatory cytokines as compared to normal macrophages. AATD macrophages have an enhanced inflammatory response when exposed to cigarette smoke-induced extracellular vesicles (EVs) released from airway epithelial cells. Cigarette smoke-induced EVs induce expression of GM-CSF and IL-8 in AATD macrophages but have no effect on normal macrophages. Release of AAT polymers, potent neutrophil chemo attractants, were also increased from AATD macrophages after exposure to cigarette smoke-induced EVs. CONCLUSIONS: The expression of mutated AAT confers an inflammatory phenotype in AATD macrophages which disposes them to an exaggerated inflammatory response to cigarette smoke-induced EVs, and thus could contribute to progressive lung inflammation and damage in AATD individuals.

Myofibroma mimicking peripheral nerve sheath tumour with ulnar nerve compression symptoms.

We report a case of myofibroma encasing the ulnar nerve on the medial aspect of the left arm with motor and sensory deficit secondary to compression. Initially, the tumour appeared to be a benign peripheral nerve sheath tumour based on preoperative imaging, with clinical examination positive for left hand clawing and a positive Wartenberg's and Froment's sign. However, intraoperative dissection demonstrated that the mass did not originate from the ulnar nerve proper, lowering suspicion for a peripheral nerve sheath tumour. Histopathological analysis showed spindle cell neoplasm, consistent with myofibroma. The patient underwent hand occupational therapy subsequently, with improvement of grip strength from 5 lb to 12 lb by 4 months postoperatively and resolution of clawing of the hand postoperatively. We discuss differentiating features for this rare occurrence of solitary adult myofibroma, where the final diagnosis was only made after formal histopathological analysis.

Novel SERPINA1 Alleles Identified through a Large Alpha-1 Antitrypsin Deficiency Screening Program and Review of Known Variants.

The SERPINA1 gene encodes the serine protease inhibitor alpha-1 antitrypsin (AAT) and is located on chromosome 14q31-32.3 in a cluster of homologous genes likely formed by exon duplication. AAT has a variety of anti-inflammatory properties. Its clinical relevance is best illustrated by the genetic disease alpha-1 antitrypsin deficiency (AATD) which is associated with an increased risk for chronic obstructive pulmonary disease (COPD) and cirrhosis. While 2 single nucleotide polymorphisms (SNPs) , S and Z, are responsible for more than 95% of all individuals with AATD, there are a number of rare variants associated with deficiency and dysfunction, as well as those associated with normal levels and function. Our laboratory has identified a number of novel AAT alleles that we report in this manuscript. We screened more than 500,000 individuals for AATD alleles through our testing program over the past 20 years. The characterization of these alleles was accomplished by DNA sequencing, measurement of AAT plasma levels and isoelectric focusing at pH 4-5. We report 22 novel AAT alleles discovered through our screening programs, such as Zlittle rock and QOchillicothe, and review the current literature of known AAT genetic variants.

Hardware Salvage in the Lower Extremity after Flap Coverage: 10-Year Single Center Outcomes Analysis.

An unanswered question with open tibial fractures is whether the type of flap used affects hardware retention. Flap survival may not equate hardware retention or limb salvage. In this study, we performed a 10-year single institution review and analysis of all patients who had placement of hardware for open tibial fractures followed by flap coverage. Methods: Inclusion criteria consisted of patients who underwent pedicled or free flap coverage of Gustilo IIIB or IIIC tibial fractures requiring open reduction and internal fixation. Outcomes and complications were statistically analyzed based on flap type. Flap type was stratified into free versus pedicled flaps and muscle versus fasciocutaneous flaps. Primary outcome measures included hardware failure and infection requiring hardware removal. Secondary outcome measures included limb salvage, flap success, and fracture union. Results: Overall primary outcome measures were better for pedicled flaps (n = 31), with lower rates of hardware failure and infection (25.8%; 9.7%) compared with free flaps (n = 27) (51.9%; 37.0%). Limb salvage and flap success was not different comparing pedicled and free flaps. There was no significant difference in outcomes between muscle and fasciocutaneous flaps. Multivariable analysis showed that patients who had free versus pedicled flaps or muscle versus fasciocutaneous flaps had a higher chance of hardware failure. A formal orthoplastic team was established in the period from 2017 to 2022, after which flap numbers were higher and hardware failure less for pedicled and fasciocutaneous flaps. Conclusions: Pedicled flaps were associated with lower rates of hardware failure and infection requiring hardware removal. A formal orthoplastic team improves hardware-related outcomes.

Closed Incision Negative Pressure Therapy in Oncoplastic Surgery Prevents Delays to Adjuvant Therapy.

Breast reductions, including oncoplastic breast surgery (OBS), have high postoperative wound healing complication (WHC) rates, ranging from 17% to 63%, thus posing a potential delay in the onset of adjuvant therapy. Incision management with closed incision negative pressure therapy (ciNPT) effectively reduces postoperative complications in other indications. This retrospective analysis compares postoperative outcomes and delays in adjuvant therapy in patients who received ciNPT on the cancer breast versus standard of care (SOC) after oncoplastic breast reduction and mastopexy post lumpectomy. Methods: Patient demographics, ciNPT use, postoperative complication rates, and time to adjuvant therapy were analyzed from the records of 150 patients (ciNPT = 29, SOC = 121). Propensity score matching was used to match patients based on age, body mass index, diabetes, tobacco use, and prior breast surgery. Results: In the matched cohort, the overall complication rate of ciNPT-treated cancerous breasts was 10.3% (3/29) compared with 31% (9/29) in SOC-treated cancerous breasts (P = 0.096). Compared with the SOC-treated cancerous breasts, the ciNPT breasts had lower skin necrosis rates [1/29 (3.4%) versus 6/29 (20.7%); P = 0.091] and dehiscence rates [0/29 (0%) versus 8/29 (27.6%); P = 0.004]. In the unmatched cohort, the total number of ciNPT patients who had a delay in adjuvant therapy was lower compared to the SOC group (0% versus 22.5%, respectively; P = 0.007). Conclusion: Use of ciNPT following oncoplastic breast reduction effectively lowered postoperative wound healing complication rates and, most importantly, decreased delays to adjuvant therapy.