Correction: A Review of Medical Student First-Author Publications in Plastic Surgery.

[This corrects the article DOI: 10.7759/cureus.43025.].

A novel in vitro model of clinical cryoablation to investigate the transition zone for focal tumor ablation.

Cryoablation (CA) of solid tumors is highly effective at reducing tumor burden and eliminating small, early stage tumors. However, complete ablation is difficult to achieve and cancer recurrence is a significant barrier to treatment of larger tumors compared to resection. In this study, we explored the relationship between temperature, ice growth, and cell death using a novel in vitro model of clinical CA with the Visual-ICE (Boston Scientific) system, a clinically approved and widely utilized device. We found that increasing the duration of freezing from 1 to 2 min increased ice radius from 3.44 ± 0.13 mm to 5.29 ± 0.16 mm, and decreased the minimum temperature achieved from -22.8 ± 1.3 °C to -45.5 ± 7.9 °C. Furthermore, an additional minute of freezing increased the amount of cell death within a 5 mm radius from 42.5 ± 8.9% to 84.8 ± 1.1%. Freezing at 100% intensity leads to faster temperature drops and a higher level of cell death in the TRAMP-C2 mouse prostate cancer cell line, while lower intensities are useful for slow freezing, but result in less cell death. The width of transition zone between live and dead cells decreased by 0.4 ± 0.2 mm, increasing from one to two cycles of freeze/thaw cycles at 100% intensity. HMGB-1 levels significantly increased with 3 cycles of freeze/thaw compared to the standard 2 cycles. Overall, a longer freezing duration, higher freezing intensity, and more freeze thaw cycles led to higher levels of cancer cell death and smaller transition zones. These results have the potential to inform future preclinical research and to improve therapeutic combinations with CA.

A Review of Medical Student First-Author Publications in Plastic Surgery.

The integrated plastic surgery residency match is a highly competitive process. If performed wisely, medical research is an opportunity to differentiate applications from peers, and productivity is closely evaluated by residency programs. In this study, the authors aimed to characterize medical student research productivity for integrated plastic surgery residency programs and their respective medical schools. To this end, the authors performed a retrospective review of senior author publications from the 81 integrated plastic surgery programs from January 1, 2016, to December 31, 2020. The primary outcome was a publication with a medical student as the first author. Secondary outcomes included the number of faculty from each program, the geographic region of the program, and the ranking of associated medical schools. It was found that the average number of medical student first-author publications and faculty members per institution were 14.0 and 11.0, respectively. There was a positive correlation between the number of faculty members and several medical student first-author publications for a program (R = 0.54, P < 0.0001). The average number of medical student first-author publications was higher in the top 25 programs than for the remaining programs (P < 0.001), and most medical student first-author publications in the United States were produced by 10 plastic surgery programs. From these findings, it was concluded that these programs associated with higher-ranking medical schools produce greater numbers of medical student first-author publications. These analyses of medical student academic productivity should be a highly useful guide for current and future medical students as they strategize their successful match into plastic surgery.

Surgical Techniques for the Repair of Webbed Neck: A Scoping Review.

Webbed neck is a rare condition characterized by bilateral subcutaneous bands, which extend from approximately the mastoid to the acromion. Given its rarity, the literature lacks a review of the techniques used in the repair of this condition. We performed a scoping review to define and summarize the surgical techniques been used in the treatment of webbed neck, with the goal of better equipping the surgeons' armamentarium. Two databases, PubMed and Scopus, were searched from inception through December 27, 2021. Studies were considered for inclusion if they (1) described the webbed neck condition and (2) reported results of surgical correction of this condition. Surgical outcomes and follow-up durations were reported as available. Twenty-two manuscripts were analyzed and included data on 60 patients. The most common syndrome associated with webbed neck was Turner syndrome (48 patients). The most frequently documented procedure technique was a Z-Plasty (38 patients). Other procedures described included: butterfly correction, V-Y Plasty, posterior cervical lift, skin excision, tissue expansion plus skin excision, T to M rearrangement, and subcutaneous fascial excision. Documented complications included hypertrophy of procedure scars or webbed neck recurrence. In summary, we present the first full literature review of the surgical techniques used in the repair of webbed neck. When selecting the technique for repair of the webbed neck, function and cosmesis are important considerations. Future studies should collect standardized outcomes data to appropriately assess and compare the described procedures.

Comorbidities Associated With Increased Likelihood of Postoperative Surgical Site Infection in Patients Treated for Hand or Finger Fracture and/or Dislocations.

BACKGROUND: We aimed to determine the relationship between common preoperative comorbidities and subsequent incidence of postoperative surgical site infections (SSIs) in hand and finger fractures and/or dislocations. METHODS: We queried the American College of Surgeons National Safety and Quality Improvement Program from January 1, 2015 to December 31, 2019. Patients were included in our study if they were treated by open or percutaneous fixation for any hand or finger fracture and/or dislocation. Predictor variables were smoking status, diabetes mellitus status, and obesity (body mass index > 30) status. Primary outcome was incidence of postoperative SSI. RESULTS: There were a total of 9245 patients included in our study, and 148 patients (1.6%) experienced postoperative SSI. Of these, 59 patients (39.9%) were only smokers, 7 patients (4.7%) only had diabetes mellitus, and 55 patients (37.2%) were only obese. Overall, patients experienced greater odds of sustaining a postoperative SSI if they were a smoker or diabetic compared to non-smokers and non-diabetics, respectively. Considering only open fixation modality, patients with comorbidities were not at significantly increased odds of sustaining postoperative SSI. Considering only percutaneous fixation modality, patients experienced significantly greater odds of sustaining postoperative SSI if they were a smoker compared to non-smoker. CONCLUSIONS: Common preoperative comorbidities, including smoking status and diabetes mellitus, increase the likelihood of postoperative complication in patients with hand and finger fractures and/or dislocations undergoing surgical treatment. Further investigation into the different relationship of these comorbidities between open and closed fractures with larger sample sizes will be valuable.

Routine Preoperative Nutritional Optimization Not Required in Patients Undergoing Breast Reconstruction.

Purpose: There are no data describing the need for preoperative nutritional optimization in patients undergoing breast reconstruction surgery. The purpose of this research was to identify if preoperative breast reconstruction patients are grossly nutritionally deficient as defined by preoperative serum albumin and, thus, if routine preoperative nutrition screening and optimization is necessary in this patient population. Methods: Adult patients who underwent breast reconstruction surgery between 2015 and 2019 were identified within the National Safety and Quality Improvement Program database. Variables of interest for this group of patients were collected, and comparisons were made for these variables between three different breast reconstruction modalities (implant-based reconstruction [IBR], expander-based reconstruction [EBR], and free tissue-based reconstruction [FTBR]) with χ2 and ANOVA statistical tests. Results: A total of 14,509 patients were included. There was not a significant difference in preoperative serum albumin measurements between the three reconstruction modalities and mean measurements for the three reconstruction modalities were all within normal limits. Secondarily, when comparing groups, FTBR had higher incidence of superficial surgical site infection (SSI) (4.49% vs. 1.6% vs. 1.56%, respectively; p < 0.00001), deep SSI (1.57% vs. 0.48% vs. 0.94%, respectively; p < 0.00001), and wound disruption (2.16% vs. 0.78% vs. 0.94%, respectively; p < 0.00001) than IBR and EBR. Conclusion: Preoperative nutritional status was found to be grossly appropriate in a large population of breast reconstruction patients. Furthermore, the ordering of routine preoperative serum albumin is unnecessary and represents an extraneous healthcare cost that does not lead to improved outcomes in breast reconstruction. FTBR incurred the greatest risk of surgical complication independent of preoperative nutritional status.

Management of surgical soft tissue defects of the lower extremities.

Management of post-operative soft-tissue defects on the lower legs is challenging owing to arterial and venous insufficiency, poor skin quality including epidermal and dermal atrophy, insufficient tissue laxity, and increased risk of infection. This paper highlights the management of post-operative soft-tissue defects on the lower extremity that cannot be closed primarily or by reconstruction with a local flap. A systematic review of the literature was performed using the National Library of Medicine (NLM) PubMed online database. Articles were included if they reported the management of post-operative lower extremity soft-tissue defects with secondary intention healing, full-thickness skin graft, split-thickness skin grafts, or skin substitutes. Sixty-three articles were included for analysis. There are several options for managing surgical defects on the lower legs and the method chosen should depend on various factors, including the quality of the skin, vascularity and size of the defect, medical history of the patient, and the experience of the surgeon.

Alcohol and Drug Use While Cycling Significantly Increases the Likelihood of Facial Fractures.

PURPOSE: Substance use, including alcohol and drugs, has been found to amplify the risks associated with cycling. Our purpose was to determine the relationship between alcohol or drug use and facial injuries in a nationwide population of patients experiencing cycling trauma. METHODS: The authors report a cross-sectional study of patients reported to the National Electronic Injury Surveillance System from January 1, 2019 to December 31, 2019, in the United States. Patients were included in our study if they were evaluated in the emergency department for a cycling-related injury. Primary outcome was facial injury. RESULTS: There were a total of 6499 adult patients who experience an injury after cycling trauma reported by the National Electronic Injury Surveillance System-participating emergency departments during the study period. A total of 553 (553/6499; 8.5%) patients had a facial injury and 82 patients with facial injuries had alcohol/drug use recorded (82/553; 14.8%). The proportion of males with facial injuries was higher in the alcohol/drug group than the no alcohol/drug group (86.6% versus 76.4%, respectively; P = 0.04). Injured cyclists in the alcohol/drug group experienced greater odds of sustaining a facial injury (odds ratio: 2.21, 95% confidence interval: 1.71-2.84, P < 0.0001) and a facial fracture (odds ratio: 2.75, 95% confidence interval: 1.83-4.13, P < 0.0001) than injured cyclists in the no alcohol/drug group. CONCLUSIONS: Substance use while cycling is not safe and significantly increases the likelihood of a facial injury and of facial fractures. This prevalence of injuries would suggest that cycling under the influence should always be illegal, and the law strictly enforced.

Post-surgical pyoderma gangrenosum in otherwise healthy patient with history of COVID-19.

There are increasing reports of autoimmune and dermatologic sequelae of COVID-19. We describe an otherwise healthy patient with recent history of serious COVID-19 infection who developed post-surgical pyoderma gangrenosum following bilateral reduction mammoplasty and was successfully treated with infliximab, mycophenolic acid, and corticosteroids. We present this case to highlight the lingering systemic proinflammatory effects of COVID-19 infection that may increase the risk of rare autoimmune complications of surgery. As a complete understanding of the long-term effects of COVID-19 is poorly understood, patients with a history of COVID-19 infection should be appropriately counseled to these possible risks when discussing surgery.

Safe Placement of Intramedullary Nail and Inter-Physician Variability in Guidewire Placement in Retrograde Tibiotalocalcaneal Fusions.

Retrograde tibiotalocalcaneal arthrodesis is a salvage procedure for severe arthrosis and deformity of both the tibiotalar and subtalar joints and requires image-confirmed placement of a retrograde guidewire. The anatomical shape of the calcaneus creates a situation in which guidewire placement can be skewed on imaging based on the angle of either internal or external rotation. As a result, the aims of our study were to (1) determine the optimal angle(s) of rotation required to accurately depict guidewire placement on imaging and (2) evaluate and describe the effects angle of rotation has on physician assessment of guidewire placement. Using a C-arm x-ray, images of cadavers with both correctly and incorrectly placed guidewires were taken at 5° increments of internal and external rotation of the cadaveric lower extremity and assessed for accuracy of guidewire depiction. The images revealed that the correctly placed guidewire appeared displaced medially at angles of 35° and 40° of external rotation. Conversely, the incorrectly placed guidewire appeared to be correctly placed at between 10° and 40° of external rotation. These images were then disseminated to various physicians including orthopedic surgeons and podiatrists to determine the ability of physicians to correctly appreciate guidewire placement. Using the responses from 35 physicians, it was found that certain angles of internal and external rotation preclude physicians from correctly determining guidewire placement. We found, based on chi-square analysis, that we were able to reject our null hypothesis with a p value of <.001 leading to the conclusion that indeed angle of rotation and guidewire placement can lead to false depictions of guidewire placement. In conclusion, our study gave objective measurements to guide foot placement during tibiotalocalcaneal fusion to decrease the risk incorrectly depicted medial guidewire placement and subsequent incorrect intramedullary nail placement.

Engineered Biosensors from Dimeric Ligand-Binding Domains.

Biosensors are important components of many synthetic biology and metabolic engineering applications. Here, we report a second generation of Saccharomyces cerevisiae digoxigenin and progesterone biosensors based on destabilized dimeric ligand-binding domains that undergo ligand-induced stabilization. The biosensors, comprising one ligand-binding domain monomer fused to a DNA-binding domain and another fused to a transcriptional activation domain, activate reporter gene expression in response to steroid binding and receptor dimerization. The introduction of a destabilizing mutation to the dimer interface increased biosensor dynamic range by an order of magnitude. Computational redesign of the dimer interface and functional selections were used to create heterodimeric pairs with further improved dynamic range. A heterodimeric biosensor built from the digoxigenin and progesterone ligand-binding domains functioned as a synthetic "AND"-gate, with 20-fold stronger response to the two ligands in combination than to either one alone. We also identified mutations that increase the sensitivity or selectivity of the biosensors to chemically similar ligands. These dimerizing biosensors provide additional flexibility for the construction of logic gates and other applications.

Axillary Lymphadenectomy and Wound Complications in Implant-Based Breast Reconstruction.

BACKGROUND: The most common method of breast reconstruction in the United States today is implant-based reconstruction. However, reported complication rates are high, from 30% to 50%. Thus, it is important for reconstructive surgeons to identify factors associated with or contributing to wound complications after breast reconstruction. This study sought to identify associations between axillary lymph node dissection and postoperative wound complications in implant-based breast reconstruction. METHODS: A retrospective chart review was performed of subjects undergoing breast oncologic and reconstructive surgery by a single breast surgeon and reconstructive surgeon, respectively, from 2013 to 2016. Medical records were reviewed of 273 subjects with 338 reconstructed breasts. Data were recorded on the extent of axillary node dissection and subsequent wound complications including seroma requiring percutaneous drainage, seroma requiring open drainage, wound dehiscence requiring local wound care, wound dehiscence requiring operative revision, implant exposure, and implant loss. RESULTS: Analysis of the data demonstrated an increase in complication rates with extent of axillary lymph node dissection; however, these rates did not reach statistical significance. Statistically significant associations, however, were identified between wound complication rates and other known risk factors including increasing age and body mass index, as well as smoking status. CONCLUSIONS: Although an association between increasing complication rates and the extent of lymph node dissection has previously been reported, this study failed to demonstrate a statistically significant association with logistic regression analysis.

Cross-Sectional Area Measurement of the Central Tarsometatarsal Articulation: A Review of Computed Tomography Scans.

Currently, disagreement exists regarding the superior method for repairing a ligamentous Lisfranc injury regarding whether to use arthrodesis or open reduction internal fixation. The 2 procedures differ in the amount of articular cartilage destroyed. Arthrodesis removes all the articular cartilage, and open reduction internal fixation places transarticular screws, essentially destroying a portion of cartilage. We performed a review of 30 consecutive computed tomography scans that included both foot length and undamaged first, second, and third tarsometatarsal joints to quantify the amount of articular surface area destroyed by placement of standardized 4-mm diameter screws. Measurements were performed using a freeform tool. The calculated surface area of the screws was subtracted from the measured surface area of the joint to yield the amount of surface area occupied by the screws. Our results demonstrated that the average amount of articular surface area destroyed in the first, second, and third tarsometatarsal joints was 4.87%, 4.79%, and 4.86% respectively, with a standard deviation of <1% for each of the joints. Our results have demonstrated that screw placement accounts for only a small percentage of articular surface destroyed. They also showed that the articular surface damage was comparable among the first 3 tarsometatarsal joints. Additionally, our results were similar to the articular surface area calculated from cadaveric specimens in a previous biomechanical study, demonstrating that computed tomography can allow for reliable and accurate assessments of articular surface areas in the foot.

Basal cell carcinoma with intravascular invasion: A case report and review of the literature.

The significance of basal cell carcinoma (BCC) invading the intravascular space is unknown. We report a case of an infiltrative BCC on the scalp that showed evidence of both intravascular and perineural invasion. The tumor locally recurred in the bone marrow space 4.5 years following the initial procedure. Since recurrence and metastasis of BCC can be delayed for many years, we recommend long term follow-up for tumors showing aggressive features.

A Massively Parallel Fluorescence Assay to Characterize the Effects of Synonymous Mutations on TP53 Expression.

Although synonymous mutations can affect gene expression, they have generally not been considered in genomic studies that focus on mutations that increase the risk of cancer. However, mounting evidence implicates some synonymous mutations as driver mutations in cancer. Here, a massively parallel assay, based on cell sorting of a reporter containing a segment of p53 fused to GFP, was used to measure the effects of nearly all synonymous mutations in exon 6 of TP53 In this reporter context, several mutations within the exon caused strong expression changes including mutations that may cause potential gain or loss of function. Further analysis indicates that these effects are largely attributed to errors in splicing, including exon skipping, intron inclusion, and exon truncation, resulting from mutations both at exon-intron junctions and within the body of the exon. These mutations are found at extremely low frequencies in healthy populations and are enriched a few-fold in cancer genomes, suggesting that some of them may be driver mutations in TP53 This assay provides a general framework to identify previously unknown detrimental synonymous mutations in cancer genes.Implications: Using a massively parallel assay, this study demonstrates that synonymous mutations in the TP53 gene affect protein expression, largely through their impact on splicing.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/15/10/1301/F1.large.jpg Mol Cancer Res; 15(10); 1301-7. ©2017 AACR.

Contribution of extrasynaptic N-methyl-D-aspartate and adenosine A1 receptors in the generation of dendritic glutamate-mediated plateau potentials.

Thin basal dendrites can strongly influence neuronal output via generation of dendritic spikes. It was recently postulated that glial processes actively support dendritic spikes by either ceasing glutamate uptake or by actively releasing glutamate and adenosine triphosphate (ATP). We used calcium imaging to study the role of NR2C/D-containing N-methyl-d-aspartate (NMDA) receptors and adenosine A1 receptors in the generation of dendritic NMDA spikes and plateau potentials in basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. We found that NR2C/D glutamate receptor subunits contribute to the amplitude of synaptically evoked NMDA spikes. Dendritic calcium signals associated with glutamate-evoked dendritic plateau potentials were significantly shortened upon application of the NR2C/D receptor antagonist PPDA, suggesting that NR2C/D receptors prolong the duration of calcium influx during dendritic spiking. In contrast to NR2C/D receptors, adenosine A1 receptors act to abbreviate dendritic and somatic signals via the activation of dendritic K(+) current. This current is characterized as a slow-activating outward-rectifying voltage- and adenosine-gated current, insensitive to 4-aminopyridine but sensitive to TEA. Our data support the hypothesis that the release of glutamate and ATP from neurons or glia contribute to initiation, maintenance and termination of local dendritic glutamate-mediated regenerative potentials.

Patch-clamp recordings and calcium imaging followed by single-cell PCR reveal the developmental profile of 13 genes in iPSC-derived human neurons.

Molecular genetic studies are typically performed on homogenized biological samples, resulting in contamination from non-neuronal cells. To improve expression profiling of neurons we combined patch recordings with single-cell PCR. Two iPSC lines (healthy subject and 22q11.2 deletion) were differentiated into neurons. Patch electrode recordings were performed on 229 human cells from Day-13 to Day-88, followed by capture and single-cell PCR for 13 genes: ACTB, HPRT, vGLUT1, ßTUBIII, COMT, DISC1, GAD1, PAX6, DTNBP1, ERBB4, FOXP1, FOXP2, and GIRK2. Neurons derived from both iPSC lines expressed ßTUBIII, fired action potentials, and experienced spontaneous depolarizations (UP states) ~2 weeks before vGLUT1, GAD1 and GIRK2 appeared. Multisite calcium imaging revealed that these UP states were not synchronized among hESC-H9-derived neurons. The expression of FOXP1, FOXP2 and vGLUT1 was lost after 50 days in culture, in contrast to other continuously expressed genes. When gene expression was combined with electrophysiology, two subsets of genes were apparent; those irrelevant to spontaneous depolarizations (including vGLUT1, GIRK2, FOXP2 and DISC1) and those associated with spontaneous depolarizations (GAD1 and ERBB4). The results demonstrate that in the earliest stages of neuron development, it is useful to combine genetic analysis with physiological characterizations, on a cell-to-cell basis.

Dopamine receptors in human embryonic stem cell neurodifferentiation.

We tested whether dopaminergic drugs can improve the protocol for in vitro differentiation of H9 human embryonic stem cells (hESCs) into dopaminergic neurons. The expression of 5 dopamine (DA) receptor subtypes (mRNA and protein) was analyzed at each protocol stage (1, undifferentiated hESCs; 2, embryoid bodies [EBs]; 3, neuroepithelial rosettes; 4, expanding neuroepithelium; and 5, differentiating neurons) and compared to human fetal brain (gestational week 17-19). D2-like DA receptors (D2, D3, and D4) predominate over the D1-like receptors (D1 and D5) during derivation of neurons from hESCs. D1 was the receptor subtype with the lowest representation in each protocol stage (Stages 1-5). D1/D5-agonist SKF38393 and D2/D3/D4-agonist quinpirole (either alone or combined) evoked Ca(2+) responses, indicating functional receptors in hESCs. To identify when receptor activation causes a striking effect on hESC neurodifferentiation, and what ligands and endpoints are most interesting, we varied the timing, duration, and drug in the culture media. Dopaminergic agonists or antagonists were administered either early (Stages 1-3) or late (Stages 4-5). Early DA exposure resulted in more neuroepithelial colonies, more neuronal clusters, and more TH(+) clusters. The D1/D5 antagonist SKF83566 had a strong effect on EB morphology and the expression of midbrain markers. Late exposure to DA resulted in a modest increase in TH(+) neuron clusters (∼75%). The increase caused by DA did not occur in the presence of dibutyryl cAMP (dbcAMP), suggesting that DA acts through the cAMP pathway. However, a D2-antagonist (L741) decreased TH(+) cluster counts. Electrophysiological parameters of the postmitotic neurons were not significantly affected by late DA treatment (Stages 4-5). The mRNA of mature neurons (VGLUT1 and GAD1) and the midbrain markers (GIRK2, LMX1A, and MSX1) were lower in hESCs treated by DA or a D2-antagonist. When hESCs were neurodifferentiated on PA6 stromal cells, DA also increased expression of tyrosine hydroxylase. Although these results are consistent with DA's role in potentiating DA neurodifferentiation, dopaminergic treatments are generally less efficient than dbcAMP alone.

Physiological properties of neurons derived from human embryonic stem cells using a dibutyryl cyclic AMP-based protocol.

Neurons derived from human embryonic stem cells hold promise for the therapy of neurological diseases. Quality inspection of human embryonic stem cell-derived neurons has often been based on immunolabeling for neuronal markers. Here we put emphasis on their physiological properties. Electrophysiological measurements were carried out systematically at different stages of neuronal in vitro development, including the very early stage, neuroepithelial rosettes. Developing human neurons are able to generate action potentials (APs) as early as 10 days after the start of differentiation. Tyrosine hydroxylase (TH)-positive (putative dopaminergic, DA) neurons tend to aggregate into clumps, and their overall yield per coverslip is relatively low (8.3%) because of areas void of DA neurons. On the same in vitro day, neighboring neurons can be in very different stages of differentiation, including repetitive AP firing, single full-size AP, and abortive AP. Similarly, the basic electrophysiological parameters (resting membrane potential, input resistance, peak sodium, and peak potassium currents) are scattered in a wide range. Visual appearance of differentiating neurons, and number of primary and secondary dendrites cannot be used to predict the peak sodium current or AP firing properties of cultured neurons. Approximately 13% of neurons showed evidence of hyperpolarization-induced current (I(h)), a characteristic of DA neurons; however, no neurons with repetitive APs showed I(h). The electrophysiological measurements thus indicate that a standard DA differentiation (dibutyryl cyclic AMP-based) protocol, applied for 2-5 weeks, produces a heterogeneous ensemble of mostly immature neurons. The overall quality of human neurons under present conditions (survival factors were not used) begins to deteriorate after 12 days of differentiation.