Citations

Background: With neck, aging the cervicomental angle becomes obtuse and may be influenced by hyoid bone aging. An understanding of hyoid position changes with aging will further our understanding of its role in neck contour changes. Methods: A 3D volumetric reconstruction of 282 neck computed tomography scans was performed. The cohort was categorized into three groups based on age: 20 years or older and younger than 40 years, 40 years or older and younger than 60 years, and 60 years or older and younger than 80 years. The vertical and horizontal hyoid distances in relation to the mandible were calculated for each patient. Results: A total of 282 patients (153 women, 129 men) were included in the cohort. The age groups were evenly distributed in men and women. Mean hyoid vertical and horizontal distances differed between women and men in all age groups. There was a significant difference in the hyoid vertical distance between 20–39 years old to 40–59 years old in men (P < 0.01), and 20–39 years old to 60–79 years old in both genders (women P = 0.005, men P < 0.01). Hyoid horizontal distance was not affected by age and sex (age and sex: P > 0.05), but rather by body mass index (BMI). Every 5 BMI points corresponded to a forward movement of 2 mm. Conclusions: As individuals age, the hyoid bone descends in both sexes, and an increase in BMI is associated with forward movement. Additional studies are needed to assess the correlation of the hyoid position between upright and supine positions.

Skeletal muscle is a highly plastic tissue, adapting its structure and metabolism in response to various stimuli like exercise. This study aimed to determine the plasticity of skeletal muscle DNA methylation in response to an acute exercise bout in volunteers with a range of insulin sensitivities. We studied 14 sedentary participants (7 male/7 female): age = 34.5 ± 3.1 years, body mass index = 29.3 ± 1.9 kg/m2 and HbA1c = 5.3 ± 0.1 %. We performed VO2peak tests to determine exercise capacity (VO2peak = 25.5 ± 1.6 mL per Kg per minute) and euglycemic hyperinsulinemic clamps (Rd value = 5.9 ± 0.8 mg per Kg per minute) with vastus lateralis muscle biopsies before and 30 minutes after a single 48-minute exercise bout. We extracted DNA from the muscle biopsies and performed reduced representation bisulfite sequencing. After performing quality control on the sequencing data, 1,034,947 sites were included for downstream analyses. MethylSig analysis revealed 17,030 differentially methylated cytosines (DMC), 9,020 increased and 8,010 decreased. To identify biologically meaningful DMCs, we used a mean change of >10%, which resulted in 1,179 and 1,436 increased and decreased sites, respectively. Pathway analysis of the increased DMCs revealed an enrichment in efferocytosis, leukocyte transendothelial migration, and FOXO-mediated transcription of oxidative stress pathways. In addition, pathway analysis of the decreased DMCs revealed an enrichment in metabolic (type 2 diabetes/ PI3K-Akt signaling), actin cytoskeleton, integrin/extracellular matrix and calcium signaling pathways. Our study reveals that an acute exercise bout induces alterations in the DNA methylation of skeletal muscle, impacting specific pathways in individuals with varying degrees of insulin sensitivity. Notably, our findings underscore the remarkable plasticity of skeletal muscle tissue. This research was funded by the National Institutes of Health, grant number R01DK094013 (Dawn Coletta). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Summary: Lymphaticovenous anastomosis (LVA) surgery is an effective surgery for the treatment of lymphedema in the extremities. Indocyanine green lymphography is the reference standard for visualizing lymphatics for LVA surgery, but it has several limitations; most notably, superficial dermal congestion can mask deeper lymphatic vessels. To overcome the limitations, we add contrast-enhanced ultrasound (CEUS) lymphography. We have previously reported that CEUS lymphography can identify lymphatic vessels for LVA surgery that indocyanine green lymphography does not. Here, we describe how we perform CEUS lymphography, including workflow, technique, and documentation. Before informed consent, the patient must be screened for possible adverse reactions to microbubbles. The procedure involves multiple intradermal injections of the microbubble agent at various sites along the extremity. After each injection, imaging for microbubble uptake by lymphatic vessels is performed using an ultrasound scanner with contrast-specific software. We use sulfur hexafluoride lipid-type A microspheres (Lumason/SonoVue; Bracco Suisse SA), but we are investigating the performance of other Food & Drug Administration–approved microbubble agents for CEUS lymphography. Having a systematic approach to marking the skin can mitigate the hindrance of marking over ultrasound coupling gel. Another benefit of CEUS lymphography is the rapid identification of neighboring veins compatible in size and location for anastomosis. We hold regular scheduled multidisciplinary meetings for coordination of care, discussion of outcomes, quality assurance, and ongoing innovation.

Summary: Aging of the face is the result of the interrelation of three-dimensional changes occurring over time among the 5 different layers of the face and its associated structures. Knowledge regarding the causes of these changes and identification of new key anatomic structures have helped elucidate one of the most complex areas of the human body. This has resulted in the introduction of pharmacologic agents to help stop, mitigate, or counteract signs of aging and restore the youthful appearance of the face. The authors performed a systematic search of the literature to review the current highest-level evidence of facial antiaging pharmacologic agents. Pharmacologic and minimally invasive antiaging treatments can target different components of facial aging and continue to evolve. With continuous research efforts, traditional treatments, such as botulinum toxin type A, injectable fillers, and chemical peels, are emerging in newer, more effective formulations, with longer lasting clinical results. However, for soft-tissue descent and facial volume loss, surgery remains the standard treatment. An adequate understanding of the three-dimensional process of facial aging over time (the fourth dimension), facial anatomy, and the pharmacologic properties of antiaging/rejuvenation agents are the sine qua non of facial antiaging treatment. The specific modality should be tailored to patient characteristics, preferences, and goals.

Abstract Background Abdominal wall reconstruction is challenging for surgeons and may be life altering for patients. There are scant high-quality studies on patient-reported outcomes following abdominal wall reconstruction. We assess long-term surgical and patient-reported outcomes of perforator-preserving open anterior component separation (OPP-ACS) following large ventral hernia repair. Methods A retrospective review of patients with large ventral hernia defects who underwent OPP-ACS performed by the authors (B.A.S., M.J.T.) was conducted between 2015 and 2019. Demographics, surgical history, operative details, outcomes, and complications were extracted. A validated questionnaire, Carolinas Comfort Scale (CCS), was used to assess postoperative quality of life. Results Twenty-two patients (12 males and 10 females) with a mean age and BMI of 60.9 ± 10 years and 28.9 ± 4.8 kg/m2, respectively, were included. Mean follow-up was 28.5 ± 16.3 months. All had prior abdominal surgery; 15 (68%) for abdominopelvic malignancy, 3 (14%) for previous failed hernia repair, and 8 (36%) had history of abdominopelvic radiation. Overall, 16 (73%) hernias were in the midline, 4 (18%) in the right lower quadrant, 1 (4.5%) in the right upper quadrant, and 1 (4.5%) in the left lower quadrant. Mean hernia defect surface area was 145 ± 112 cm2. A total of 9 patients (40.9%) underwent bilateral component separation, whereas 13 (59.1%) had unilateral. Bioprosthetic mesh was used in all patients as underlay. Mean mesh size and thickness were 545.6 ± 207.7 cm2 and 3.4 ± 0.5 mm, respectively. One patient presented with a minor wound dehiscence, and two presented with seromas not requiring aspiration/evacuation. One patient had hernia recurrence 22 months after surgery. One patient was readmitted for partial small bowel obstruction and one required wound revision. A total of 14 (65%) patients responded to the CCS questionnaire. At 12 months, mean score for all 23 items was 0.29 ± 0.21 (0.08–0.62), which corresponds to absence or minimal symptoms. Conclusion The OPP-ACS is a safe surgical option for large, complex ventral hernias. Our cases showed minimal complication rate and hernia recurrence, and our patients reported significant improvement in life quality.

Background Immediate implant-based breast reconstruction (IIBR) is the most commonly used method in breast reconstruction in the United States. However, postoperative surgical site infections (SSIs) can cause devastating reconstructive failure. This study evaluates the use of perioperative versus extended courses of antibiotic prophylaxis after IIBR for the prevention of SSI. Methods This is a single-institution retrospective study of patients who underwent IIBR between June 2018 and April 2020. Detailed demographic and clinical information was collected. Patients were divided into subgroups based on antibiotic prophylaxis regimen: group 1 consisted of patients who received 24 hours of perioperative antibiotics and group 2 consisted of patients who received ≥7 days of antibiotics. Statistical analyses were conducted using SPSSv26.0 with P ≤ 0.05 considered statistically significant. Results A total of 169 patients (285 breasts) who underwent IIBR were included. The mean age was 52.4 ± 10.2 years, and the mean body mass index (BMI) was 26.8 ± 5.7 kg/m2. Twenty-five percent of patients (25.6%) underwent nipple-sparing mastectomy, 69.1% skin-sparing mastectomy, and 5.3% total mastectomy. The implant was placed in the prepectoral, subpectoral, and dual planes in 16.7%, 19.2%, and 64.1% cases, respectively. Acellular dermal matrix was used in 78.7% of cases. A total of 42.0% of patients received 24-hour prophylaxis (group 1), and 58.0% of patients received extended prophylaxis (group 2). Twenty-five infections (14.8%) were identified, of which 9 (5.3%) resulted in reconstructive failure. In bivariate analyses, no significant difference was found between groups in rates of infection (P = 0.273), reconstructive failure (P = 0.653), and seroma (P = 0.125). There was a difference in hematoma rates between groups (P = 0.046). Interestingly, in patients who received only perioperative antibiotics, infection rates were significantly higher in those with BMI ≥ 25 (25.6% vs 7.1%, P = 0.050). There was no difference in overweight patients who received extended antibiotics (16.4% vs 7.0%, P = 0.160). Conclusions Our data demonstrate no statistical difference in infection rates between perioperative and extended antibiotics. This suggests that the efficacies of current prophylaxis regimens are largely similar, with choice of regimen based on surgeon preference and patient-specific considerations. Infection rates in patients who received perioperative prophylaxis and were overweight were significantly higher, suggesting that BMI should be taken into consideration when choosing a prophylaxis regimen.

Background: Early soft-tissue reconstruction of open fractures has been shown to decrease infection rates and improve rates of bony union. The purpose of this study was to compare the rates and time to union of open tibia fractures that underwent soft-tissue coverage. Methods: A retrospective chart review of 118 patients with open tibia fractures requiring soft-tissue reconstruction treated at a single level 1 trauma center was performed. Demographic data as well as flap type were collected. Union status was determined using modified Radiographic Union Scale in Tibia Fractures score greater than 11. Results: Limb salvage was achieved in 90% of patients. The overall rate of nonunion was 33%. Flap type significantly affected time to union, with local fasciocutaneous and keystone flaps having significantly longer time to union [202 days (SD 120.3)] than all other flap groups (P = 0.01). Free flaps had significantly shorter time to union than local flaps [115 days (SD 49.6) versus 149 days (SD 75.4); P = 0.02]. Muscle flaps had significantly shorter time to union than fasciocutaneous flaps [123 days (SD 52.4) versus 165 days (SD 104.1); P = 0.04]. This remained true after controlling for fracture location, patient age, need for second flap, and fixation method (P = 0.037). Patients who underwent an initial soft-tissue reconstruction with a local muscle flap were more likely to require a second flap to achieve wound closure (OR, 3.7; P = 0.008) and needing a second flap significantly increased time to union [162 days (SD 95.9) versus 122 days (SD 51.9); P = 0.03]. Conclusion: Flap type affects time to union but not nonunion rate in open tibia fractures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Background: Many insurance companies in the United States rely on the Schnur sliding scale to predict resection weights to determine medical necessity for breast reduction surgery. Accurate methods to predict resection weights are needed to avoid insurance denials. The authors compared the accuracy of formulas such as the Schnur, Appel, Descamps, and Galveston scales in predicting resection weights, and assessed whether they influence insurance coverage decision. Methods: A retrospective review of bilateral reduction mammaplasty procedures from June of 2017 to June of 2019 was performed at the Mayo Clinic, Rochester. Oncoplastic reduction operations were excluded. The accuracy of each formula-based estimate was evaluated with linear regression analysis. Results: One hundred fifty-four patients (308 breasts) were reviewed. The Schnur scale had low correlation with actual resection weight (r 2 = 0.381; b1 = 1.153; p < 0.001). The Appel scale was the most accurate (r 2 = 0.642; b1 = 1.01; p < 0.001), followed by the Descamps (r 2 = 0.572, b1 = 0.934, p < 0.001) and Galveston (r 2 = 0.672; b1 = 0.654; p < 0.001) scales. The Appel, Descamps, and Galveston scales were more accurate for resection weights of 500 g or greater, body mass index greater than 30 kg/m², and patients younger than 50 years. For resection weights of 500 g or greater, the median difference between the estimated and actual resection weight for the Schnur, Appel, Descamps, and Galveston scales was −211.4 ± 272.3, −17.5 ± 272.3, −9.6 ± 229.5, and −99.2 ± 238.5 g, respectively. No scale was accurate for resection weights less than 500 g. Insurance reimbursement was denied in 15.56 percent of patients; of these, 23 percent had resection weights less than 500 g. The Schnur scale overestimated the resection weights in 28.9 percent of patients. Conclusions: The Schnur scale is a poor predictor of breast resection weight. The Appel scale is the most accurate estimator, especially in the young and obese population with larger resections. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, I.

Abstract Background: Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer (BC) subtype. Cisplatin is one of the broad FDA-approved drugs to treat TNBC patients with recurrent and unresectable disease. However the treatment response is limited, and patients frequently develop resistance and recur locally and distantly. The aim of this study is to find molecular mechanisms driving cisplatin-resistance in TNBC. The ubiquitin proteasomal system (UPS) is a universal and conserved mechanism that helps to maintain cellular homeostasis. The aberrant expression of certain components of the UPS have been associated with cancer onset, progression, and metastasis as we and other groups have shown. UBQLN4 is part of the UPS and play a major role in controlling ubiquitinated proteins in response to genotoxic stress. BCL2-associated athanogene-6 (BAG6), alternately known as BAT3, is a chaperone that complex with other chaperones and ubiquitin ligases to regulate protein stability and insertion of tail-anchored membrane proteins into the endoplasmic reticulum. This is a critical step that reduce mislocalized proteins and proteotoxic stress. We hypothesized that UBQLN4 upregulation determine cisplatin-resistance in BC patients by targeting BAT3 for proteasomal degradation to reduce proteotoxic stress. Methods: TCGA BRCA database was utilized to determine clinical associations and outcomes in BC patients. A BC tissue microarray (TMA) was stained by IHC and protein levels quantified to confirm associations between UBQLN4 and TNBC patients. TNBC cell lines were CRISPR-engineered to generate UBQLN4 knockout (KO), and lentivirus transduction was used to recover the KO phenotype. Functional assays and confocal imaging were performed in BRCA mutant and wildtype human TNBC cell lines. Results: Increased UBQLN4 mRNA expression was observed in the TCGA BRCA database in primary BC tissues compared to normal adjacent tissues (p&lt;0.0001). Using PAM50 classification, the BC patients were stratified and compared for UBQLN4 expression. BC patients with basal-like tumors showed significantly higher UBQLN4 expression than normal-like subtype (p&lt; 0.0001). In the assessment of 5-years relapse-free survival (RFS), patients with high levels of UBQLN4 (n=221) showed significantly lower RFS rates compared to those with low UBQLN4 (n=221) (HR=1.67(1.21-2.3), log-rank test p&lt;0.0016). These results were further evaluated by IHC using a BC TMA. Patients with TNBC showed a significantly increased UBQLN4 H-scores values compared to normal adjacent breast tissues. KO of UBQLN4 significantly increased cisplatin sensitivity in TNBC cell lines (p&lt;0.0001). UBQLN4 overexpression restored the cisplatin-resistance in UBQLN4-KO cell line. In TGCA BRCA database, BAT3 was significantly upregulated in BC patients with basal-like tumors compared to normal-like subtype. Knockdown of BAT3 significantly increased cisplatin sensitivity in TNBC cell lines (p&lt;0.0001). In TCGA BRCA database, BAT3 and UBQLN4 mRNA levels positively correlated (r= 0.26, p&lt;0.0001). By using co-immunoprecipitation, endogenous BAT3 and UBQLN4 proteins interact in parental TNBC cell line, but only during cisplatin-treatment. These results were further validated using reciprocal co-immunoprecipitation and confocal imaging in TNBC cell lines with UBQLN4 overexpression. Conclusions: UBQLN4 expression controls cisplatin-resistance in TNBC cell lines. UBLQN4 interacts with BAT3 under cisplatin treatment. During cisplatin treatment, UBQLN4 targets BAT3 for proteasomal degradation to reduce proteotoxic stress induced by genotoxic cisplatin treatment. The UBQLN4 protein levels may represent a prognostic biomarker to predict RFS in TNBC patients. Citation Format: Yoshiaki Shoji, Takamichi Yokoe, Peter J Bostick, Yosef Shiloh, Dave SB Hoon, Matias A Bustos. UBQLN4 regulates cisplatin-resistance in triple-negative breast cancer by targeting BAT3 for proteasomal degradation [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-01-11.