Regional heterogeneity in determinants of atrial matrix remodeling and association with atrial fibrillation vulnerability postmyocardial infarction.

BACKGROUND: Left ventricular (LV) remodeling following a myocardial infarction (MI) is associated with new-onset atrial fibrillation (AF). LV remodeling post-MI is characterized by regional changes in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), causing extracellular matrix (ECM) remodeling. OBJECTIVE: The purpose of this study was to test the hypothesis that a shift in regional atrial MMP activity, MMP/TIMP expression, and ECM remodeling occurs post-MI, which cause increased vulnerability to AF. METHODS: MI was induced in pigs (weight 25 kg; coronary ligation; n = 9). At approximately 14 days post-MI, an atrial electrical stimulation protocol was performed, after which an MMP radiotracer was infused, MMP/TIMP mRNA profiling performed, and ECM collagen assessed by histochemistry. An additional 7 non-MI pigs served as controls. RESULTS: AF could be induced in 89% (8/9) of the post-MI pigs but none of the controls. MMP activity (MMP radiotracer uptake) increased by approximately 2-fold in most atrial regions post-MI, whereas fibrillar collagen content was unchanged or actually reduced in right atrial regions and increased in left atrial regions. MMP/TIMP profiles revealed a heterogeneous pattern from the left atrial appendage to right atrial regions. CONCLUSION: AF vulnerability early post-MI was associated with a heterogeneous pattern of atrial ECM remodeling, detectable by noninvasive molecular imaging. Detection of early atrial MMP activation post-MI may help define the myocardial substrate underlying AF.

Partial suturectomy for phenotypical craniosynostosis caused by incomplete fusion of cranial sutures: a novel surgical solution.

OBJECTIVE: Patients presenting with head shape changes phenotypical for craniosynostosis may have incomplete fusion of the involved sutures. The surgical literature is lacking in appropriate management strategies for these patients. In this paper, the authors evaluate their experience with a novel treatment strategy: suturectomy of only the fused portion followed by helmeting therapy in patients with skull deformity secondary to incomplete suture synostosis. METHODS: Patients with craniosynostosis with incomplete suture fusion requiring operative intervention between 2018 and 2020 were included for evaluation. Patients were selected for partial suturectomy if the patent portion of the suture had a normal appearance. All patients underwent craniectomy of the involved portion of the synostosed suture. Intraoperative ultrasound was used to reassess the degree of fusion at the time of surgery and incision planning. A 2- to 3-cm strip craniectomy was performed under direct visualization through a single minimal access incision. Postoperative helmeting was utilized for all patients. Demographic and perioperative data were collected, including laser scan data in the form of cranial index (CI) and cranial vault asymmetry (CVA), defined as the difference between two diagonal measurements, from the frontozygomaticus to the opposite eurion. RESULTS: Four males and 1 female with a mean age of 2.8 months (range 1.1-3.9 months) at presentation were included. All patients had incomplete sagittal synostosis (one patient also had an incomplete left lambdoid synostosis and another had an incomplete left coronal synostosis). The mean age at surgery was 3.5 months (range 2.0-4.7 months) without any major complications. All patients were compliant with postoperative helmeting. The average age at the last follow-up was 12.8 months (range 5.3-23.7 months) with a mean follow-up duration of 9.3 months (range 0.5-19.6 months). Final laser scan evaluations were available for 3 patients and showed an improvement of the CI from an average of 71.3 (range 70-73) to 84.3 (range 82-86). The CVA improved from an average of 9.67 mm (range 2-22 mm) to 1.67 mm (range 1-2 mm). CONCLUSIONS: Minimally invasive direct excision of the involved portion of fused cranial sutures followed by helmet therapy for phenotypical craniosynostosis is a safe and effective treatment strategy. This technique is suitable for very young patients and appears to offer similar outcomes to complete suturectomy. Further studies are required to see if this approach reduces the deformity severity for patients requiring vault remodeling later in life.

Targeted Injection of a Truncated Form of Tissue Inhibitor of Metalloproteinase 3 Alters Post-Myocardial Infarction Remodeling.

Infarct expansion can occur after myocardial infarction (MI), which leads to adverse left ventricular (LV) remodeling and failure. An imbalance between matrix metalloproteinase (MMP) induction and tissue inhibitors of MMPs (TIMPs) can accelerate this process. Past studies have shown different biologic effects of TIMP-3, which may depend upon specific domains within the TIMP-3 molecule. This study tested the hypothesis that differential effects of direct myocardial injections of either a full-length recombinant TIMP-3 (F-TIMP-3) or a truncated form encompassing the N-terminal region (N-TIMP-3) could be identified post-MI. MI was induced in pigs that were randomized for MI injections (30 mg) and received targeted injections within the MI region of F-TIMP-3 (n = 8), N-TIMP-3 (n = 9), or saline injection (MI-only, n = 11). At 14 days post-MI, LV ejection fraction fell post-MI but remained higher in both TIMP-3 groups. Tumor necrosis factor and interleukin-10 mRNA increased by over 10-fold in the MI-only and N-TIMP-3 groups but were reduced with F-TIMP-3 at this post-MI time point. Direct MI injection of either a full-length or truncated form of TIMP-3 is sufficient to favorably alter the course of post-MI remodeling. The functional and differential relevance of TIMP-3 domains has been established in vivo since the TIMP-3 constructs demonstrated different MMP/cytokine expression profiles. These translational studies identify a unique and more specific therapeutic strategy to alter the course of LV remodeling and dysfunction after MI. SIGNIFICANCE STATEMENT: Using different formulations of tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), when injected into the myocardial infarction (MI) region, slowed the progression of indices of left ventricular (LV) failure, suggesting that the N terminus of TIMP-3 is sufficient to attenuate early adverse functional events post-MI. Injections of full-length recombinant TIMP-3, but not of the N-terminal region of TIMP-3, reduced relative indices of inflammation at the mRNA level, suggesting that the C-terminal region affects other biological pathways. These unique proof-of-concept studies demonstrate the feasibility of using recombinant small molecules to selectively interrupt adverse LV remodeling post-MI.

The Use of Ultrasound Guidance for the Treatment of Raynaud Disease of the Hand With Botulinum Toxin.

BACKGROUND: This study sought to examine the feasibility and effectiveness of the use of ultrasound (US) as a clinical adjunct in the delivery of botulinum toxin for the treatment of Raynaud disease of the hand. METHODS: One cadaver hand was injected with a colored simulation material using the current traditional surface anatomy approach, whereas an additional cadaver hand was injected using US guidance. The hands were dissected and areas of distribution of the simulation material were evaluated. Five patients diagnosed with Raynaud disease were treated with botulinum toxin using US guidance and data using the Patient-Reported Outcomes Measurement Information System Upper Extremity were collected. RESULTS: The cadaver hand injected with a colored simulation material using US guidance demonstrated significantly reduced surface area of muscle infiltrated compared with the cadaver hand injected using the traditional surface anatomy approach (16 cm vs 37 cm, P < 0.001).All 5 patients treated with botulinum toxin using US guidance reported significant improvement in symptoms and function after injection (P < 0.05), where zero patients reported intrinsic hand weakness. CONCLUSIONS: The use of US significantly improves the accuracy of delivery of a surrogate dye in a cadaver model of Raynaud disease, whereas its use clinically results in at least as effective a treatment as the landmark approach, but with less botulinum toxin required to achieve the clinical effect.

Use of Sentinel Lymph Node Incision for Second Stage Implant-Based Breast Reconstruction After Radiation.

BACKGROUND: Staged expander to implant breast reconstruction is associated with a high complication rate when the patient has had postmastectomy radiation. With an increasing number of American women undergoing implant-based breast reconstruction after postmastectomy radiation, surgeons may find themselves operating in a radiated field with synthetic devices. We report the performance characteristics of a novel surgical modification to the second stage expander to implant exchange after adjuvant radiation using a transaxillary approach through a prior sentinel lymph node incision, a site remote from the breast implant pocket. METHODS: We performed a retrospective review of a prospectively maintained database to evaluate the surgical outcomes of serial patients undergoing second staged expander to implant exchange through the sentinel lymph node incision 6 months or more after completing whole breast radiation. A case matched cohort to age, body mass index, and comorbid status was used to compare outcomes between patients in the group of interest versus a traditional skin sparing incision on the anterior breast mound through the radiated skin envelope. All patients included demonstrated grade 1 or 2 skin changes on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema for the skin organ system. RESULTS: Nineteen breasts were reconstructed for 18 women after immediate tissue expander placement and adjuvant whole breast radiation were included in our group of interest. Forty-one case-matched second controls were identified for the comparison group. There were no intraoperative complications. Two postoperative complications were reported for the sentinel lymph node approach group (10.5%) with an average of 9 months of follow-up: 1 operative exploration for hematoma and 1 minor wound requiring recloser in the office. The case matched cohort demonstrated significantly more minor postoperative complications (P = 0.037) with a total complications rate of 41.4%. There were 31.7% of the patients that experienced a minor complication alone, whereas 9.7% of the case-matched cohort experienced a major complication. CONCLUSIONS: These data support the use of the existing axillary sentinel lymph node access incision for second stage placement of a gel implant after immediate expander and adjuvant radiation therapy. The sentinel lymph node incision approach facilitates layered closure over the breast pocket at a site remote from irradiated tissue, reducing the incidence of postoperative minor complications. Forthcoming long-term data will determine if differences in reported capsular contracture rates can be achieved with a remote transaxillary approach to second stage implant reconstruction after radiation.

The Use of Patient-Specific Three-Dimensional Printed Surgical Models Enhances Plastic Surgery Resident Education in Craniofacial Surgery.

PURPOSE: A significant challenge in surgical education is to provide a meaningful hands-on experience with the pathology the trainee will see in independent practice. Craniofacial anatomy is challenging and unfamiliar to the learner. METHODS: Using preoperative computed tomography data, the authors produced an accurately sized, three-dimensional (3D) printed model of the congenital craniofacial anatomy of patients treated by the same attending surgeon-PGY4 resident surgeon pair over the course of a 6-month rotation. A preoperative stepwise surgical plan was written by the attending and resident, and the plan was marked on the 3D model by the attending and resident separately. The written and marked plans were measured for accuracy and time to completion. The resident surgeon's applicable milestone levels were assessed. RESULTS: Seven congenital craniofacial anomalies met criteria for inclusion: 4 craniosynostosis cases, 2 mandibular distractions, and 1 LeFort I distraction. The number of inaccuracies of the written plan improved from 5 to 0 for sagittal synostosis and 4 to 0 for mandibular distraction. The time to complete the written plan decreased by 22% for sagittal synostosis and 45% for mandibular distraction. The number of inaccuracies of the marked plan decreased from 5 to 0 for sagittal synostosis and 2 to 0 for mandibular distraction. Time to completion of the marked plan decreased by 76% for sagittal synostosis and 50% for mandibular distraction. Milestone scores increased an average of 1.875 levels. CONCLUSION: Three-dimensional printed craniofacial models are a positive addition to resident training and have been objectively quantified to improve the accuracy and time to completion of the surgical plan as well as progression in the plastic surgery milestones.

Bone Graft Substitutes: Current Concepts and Future Expectations.

Owing to its osteoinductive and osteoconductive properties and the presence of osteogenic cells, freshly harvested autologous bone graft is the gold standard for skeletal reconstruction where there is inadequate native bone. Whereas these characteristics are difficult to replicate, engineered, commercially available bone graft substitutes aim to achieve a comparable osseoregenerative profile. This work furnishes the reader with an understanding of the predominant classes of bone graft substitutes available for reconstruction of upper extremity bone defects following trauma or oncological surgery. We review bone graft substitutes with respect to their mechanisms of action, their advantages and disadvantages, and their indications and contraindications. We provide examples of bone graft substitutes in clinical use and outline comparative costs. We also describe the future directions for this specific aspect of reconstructive surgery with a focus on the role of bioactive glass.