Trends in Rhinoplasty Research: A 20-Year Bibliometric Analysis.

BACKGROUND: Rhinoplasty is a popular aesthetic and reconstructive surgical procedure. It is one of the top five surgical cosmetic procedures performed worldwide. OBJECTIVES: To evaluate global trends in rhinoplasty research spanning 20 years between 1994 and 2013. METHODS: The top 15 plastic surgery and otolaryngology journals containing rhinoplasty research were determined using impact factors (IF). A database of rhinoplasty articles from 1994 to 2013 was created to include the following classifications: IF, authors' geographic location, study design, level of evidence (LOE), and pertinence to aesthetic or reconstructive rhinoplasty. Productivity index and productivity share were calculated for each region. RESULTS: A total of 1244 rhinoplasty articles were included in the database. The mean IF among the 15 journals increased from 0.75 in 1994 to 1.90 in 2013 (p < 0.001). The majority of rhinoplasty publications were clinical in study design (91.0%) and were predominantly of weaker LOE (level IV: 42.4%; level V: 33.2%). The USA led in proportion of total rhinoplasty publications by volume and productivity index (37.9%, 41.2%), followed by Asia (29.1%, 28.2%) and Western Europe (18.8%, 18.2%). The majority of articles published were classified as aesthetic (60.4%), whereas 30.6% were reconstructive; there was a significant increase in the proportion of aesthetic rhinoplasty articles published per year (p = 0.009). CONCLUSIONS: The USA has consistently been the most productive country in rhinoplasty research. However, its lead has diminished over the last 20 years. The trend in rhinoplasty research appears to be toward aesthetic rather than reconstructive topics. Attention should be given to producing stronger LOE studies. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Deconstructing negative pressure wound therapy.

Since its introduction 20 years ago for the treatment of chronic wounds, negative pressure wound therapy use has expanded to a variety of other wound types. Various mechanisms of action for its efficacy in wound healing have been postulated, but no unifying theory exists. Proposed mechanisms include induction of perfusion changes, microdeformation, macrodeformation, exudate control and decreasing the bacterial load in the wound. We surmise that these different mechanisms have varying levels of dominance in each wound type. Specifically, negative pressure wound therapy is beneficial to acute open wounds because it induces perfusion changes and formation of granulation tissue. Post-surgical incisional wounds are positively affected by perfusion changes and exudate control. In the context of chronic wounds, negative pressure wound therapy removes harmful and corrosive substances within the wounds to affect healing. When skin grafts and dermal substitutes are used to close a wound, negative pressure wound therapy is effective in promoting granulation tissue formation, controlling exudate and decreasing the bacterial load in the wound. In this review, we elucidate some of the mechanisms behind the positive wound healing effects of negative pressure wound therapy, providing possible explanations for these effects in different wound types.

Current concepts related to hypertrophic scarring in burn injuries.

Scarring following burn injury and its accompanying aesthetic and functional sequelae still pose major challenges. Hypertrophic scarring (HTS) can greatly impact patients' quality of life related to appearance, pain, pruritus and even loss of function of the injured body region. The identification of molecular events occurring in the evolution of the burn scar has increased our knowledge; however, this information has not yet translated into effective treatment modalities. Although many of the pathophysiologic pathways that bring about exaggerated scarring have been identified, certain nuances in burn scar formation are starting to be recognized. These include the effects of neurogenic inflammation, mechanotransduction, and the unique interactions of burn wound fluid with fat tissue in the deeper dermal layers, all of which may influence scarring outcome. Tension on the healing scar, pruritus, and pain all induce signaling pathways that ultimately result in increased collagen formation and myofibroblast phenotypic changes. Exposure of the fat domes in the deep dermis is associated with increased HTS, possibly on the basis of altered interaction of adipose-derived stem cells and the deep burn exudate. These pathophysiologic patterns related to stem cell-cytokine interactions, mechanotransduction, and neurogenic inflammation can provide new avenues of exploration for possible therapeutic interventions.

Lipotransfer: the potential from bench to bedside.

The development of autologous fat grafting to augment or reconstruct tissue defects has become an increasingly popular modality among plastic surgeons. Despite its popularity, a standardized fat grafting protocol has yet to be developed. Great variations exist with regard to almost all the technical features, yielding a reported fat graft survivability that ranges from 40% to 80%. Recent bench approaches have been proposed to improve the long-term viability of fat grafts: although promising results have been shown, empirical evidence has yet to prove the superiority of one particular method. Nevertheless, currently available literature still provides some evidence for optimal results in differing clinical scenarios, in the wait of validating and ultimate studies.The issues of enriched fat grafting techniques and variations in harvesting and delivery in the background of US regulatory constraints demand alterations and variations in techniques. These only complicate the process of validation of any single technique. However, recent studies have brought us closer to making informed decisions on technical choices in lipotransfer. These are elaborated on in this review.

Neuromodulatory nerve regeneration: adipose tissue-derived stem cells and neurotrophic mediation in peripheral nerve regeneration.

Peripheral nerve injury requiring nerve gap reconstruction remains a major problem. In the quest to find an alternative to autogenous nerve graft procedures, attempts have been made to differentiate mesenchymal stem cells into neuronal lineages in vitro and utilize these cellular constructs for nerve regeneration. Unfortunately, this has produced mixed results, with no definitive procedure matching or surpassing traditional nerve grafting procedures. This review presents a different approach to nerve regeneration. The literature was reviewed to evaluate current methods of using adipose-derived stem cells (ADSCs) for peripheral nerve regeneration in in vivo models of animal peripheral nerve injury. The authors present cited evidence for directing nerve regeneration through paracrine effects of ADSCs rather than through in vitro nerve regeneration. The paracrine effects rely mainly, but not solely, on the elaboration of nerve growth factors and neurotrophic mediators that influence surrounding host cells to orchestrate in vivo nerve regeneration. Although this paradigm has been indirectly referred to in a host of publications, few major efforts for this type of neuromodulatory nerve regeneration have been forthcoming. The ADSCs are initially "primed" in vitro using specialized controlled medium (not for neuronal differentiation but for sustainability) and then incorporated into a hydrogel base matrix designed for this purpose. This core matrix is then introduced into a natural collagen-based nerve conduit. The prototype design concepts, evidence for paracrine influences, and regulatory hurdles that are avoided using this approach are discussed.

Non-typhoidal Salmonella soft-tissue infection after gender affirming subcutaneous mastectomy case report.

We present a case of a 32-year-old transgender male who underwent chest masculinization, complicated by purulent soft tissue infection of bilateral chest incisions. Cultures tested positive for non-typhoidal Salmonella, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa. Herein, we discuss multiple factors contributing to the complexity of treating this patient's clinical course.

Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas.

Promoter methylation of O6-methylguanine DNA methyltransferase (MGMT) is associated with a favorable prognosis in glioblastoma multiforme (GBM) and has been hypothesized to occur early in tumor transformation of glial cells. Thus, a possible link exists between the site of malignant transformation and MGMT promoter methylation status. Using the Analysis of Differential Involvement (ADIFFI) statistical mapping technique in a total of 358 patients with GBM, we demonstrate that human de novo GBMs occur in a high frequency contiguous with the posterior subventricular zone (SVZ); MGMT promoter methylated GBMs are lateralized to the left hemisphere, while MGMT unmethylated GBMs are lateralized to the right hemisphere; and tumors near the left temporal lobe have a significantly longer overall survival compared with tumors occurring elsewhere, independent of treatment or MGMT methylation status.

Comparison between intensity normalization techniques for dynamic susceptibility contrast (DSC)-MRI estimates of cerebral blood volume (CBV) in human gliomas.

PURPOSE: To compare "standardization," "Gaussian normalization," and "Z-score normalization" intensity transformation techniques in dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) estimates of cerebral blood volume (CBV) in human gliomas. DSC-MRI is a well-established biomarker for CBV in brain tumors; however, DSC-MRI estimates of CBV are semiquantitative. The use of image intensity transformation algorithms provides a mechanism for obtaining quantitatively similar CBV maps with the same intensity scaling. MATERIALS AND METHODS: The coefficient of variance (CV) in normal-appearing white matter and relative contrast between tumor regions and normal tissue was compared between the three CBV transformations across five different MR scanners in 96 patients with gliomas. RESULTS: The results suggest all normalization techniques improved variability and relative tumor contrast of CBV measurements compared with nonnormalized CBV maps. The results suggest Gaussian normalization of CBV maps provided slightly lower CV in normal white matter and provided slightly higher tumor contrast for glioblastomas (WHO grade IV) compared with other techniques. CONCLUSION: The results suggest Gaussian normalization of leakage-corrected CBV maps may be the best choice for image intensity correction for use in large-scale, multicenter clinical trials where MR scanners and protocols vary widely due to ease of implementation, lowest variability, and highest tumor to normal tissue contrast.

Quantification of edema reduction using differential quantitative T2 (DQT2) relaxometry mapping in recurrent glioblastoma treated with bevacizumab.

The purpose of the current study was to quantify the reduction in T2 signal abnormality accompanying administration of the anti-angiogenic drug bevacizumab in recurrent glioblastoma (GBM) patients using a voxel-wise differential quantitative T2 (DQT2) mapping technique. Twenty-six patients with recurrent GBM treated with bevacizumab were scanned before and 4-6 weeks after treatment on a 1.5T clinical MR scanner. Quantitative T2 maps were created from proton density and T2-weighted images acquired using a standard multi-echo fast-spin echo sequence. T2 maps after treatment were co-registered with T2 maps prior to treatment in the same patient, and then voxel-wise subtraction was performed to create DQT2 maps for each patient. Results suggest DQT2 maps allow visualization and quantification of voxel-wise T2 changes resulting from anti-VEGF therapy. Results demonstrated a significant decrease in T2 within pre-treatment T2 abnormal regions (mean reduction = 49.4 ms at 1.5T) following anti-VEGF treatment (Wilcoxon signed rank test, P < 0.0001). An elevated residual, post-treatment, median T2 was predictive of both progression-free (Log-rank, P = 0.0074) and overall survival (Log-rank, P = 0.0393).

A Call to Arms: Emergency Hand and Upper-Extremity Operations During the COVID-19 Pandemic.

PURPOSE: Limited data exist regarding volumetric trends and management of upper-extremity emergencies during periods of social restriction and duress, such as the coronavirus disease 2019 pandemic. We sought to study the effect of shelter-in-place orders on emergent operative upper-extremity surgery. METHODS: All patients undergoing emergent and time-sensitive operations to the finger(s), hand, wrist, and forearm were tracked over an equal number of days before and after shelter-in-place orders at 2 geographically distinct Level I trauma centers. Surgical volume and resources, patient demographics, and injury patterns were compared before and after official shelter-in-place orders. RESULTS: A total of 58 patients underwent time-sensitive or emergent operations. Mean patient age was 42 years; mean injury severity score was 9 and median American Society of Anesthesiologist score was 2. There was a 40% increase in volume after shelter-in-place orders, averaging 1.4 cases/d. Indications for surgery included high-energy closed fracture (60%), traumatic nerve injury (19%), severe soft tissue infection (15%), and revascularization of the arm, hand, or digit(s) (15%). High-risk behavior, defined as lawlessness, assault, and high-speed auto accidents, was associated with a significantly greater proportion of operations after shelter-in-place orders (40% vs 12.5%; P < .05). Each institution dedicated an average of 3 inpatient beds and one intensive care unit-capable bed to upper-extremity care daily. Resources used included an average of 115 minutes of daily operating room time and 8 operating room staff or personnel per case. CONCLUSIONS: Hand and upper-extremity operative volume increased after shelter-in-place orders at 2 major Level I trauma centers across the country, demanding considerable hospital resources. The rise in volume was associated with an increase in high-risk behavior. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Age and Number of Surgeries Increase Risk for Complications in Polytrauma Patients with Operative Maxillofacial Fractures.

BACKGROUND: Poly-trauma patients often sustain complex head/neck injuries requiring prolonged hospitalizations and multiple operations. Few studies have evaluated the associated injury patterns and risk factors for poor clinical outcomes. METHODS: Consecutive poly-trauma patients with operative maxillofacial fractures treated at a level 1 trauma medical center between 1995 and 2013 were evaluated. Concomitant head/neck injuries to identify potential injury patterns were numerated. Lastly, a multivariate analysis was performed to determine independent risk factors for complications during the acute hospitalization period. RESULTS: Totally, 232 poly-trauma patients presented with operative maxillofacial fractures, while 38.8% of patients had a secondary maxillofacial fracture, 16.4% had intracranial hemorrhage, 23.7% had skull fractures, and 12.1% had spinal fractures. The rate of complication during admission was 28.3%. Multivariate analysis revealed advanced patient age and increased number of operations to predict the rate of complication. Patients requiring more than one operation had a 1.8-fold increase in complication rate (p<0.01) and older patients had a 4.5% increase in complication rate (p<0.05) for every year of increased age. CONCLUSION: Poly-trauma patients have a high incidence of secondary maxillofacial fractures, concomitant head/neck injury, and inpatient complication rate. Knowledge of associated injury patterns can help increased awareness and can guide physician decision-making to avoid missed/delayed injuries.

Patient Race and Provider Predict Patient Satisfaction Following Post-Mastectomy Breast Reconstruction.

BACKGROUND: Post-mastectomy breast reconstruction is commonly performed in the United States with numerous options available to patients and providers. This study evaluated patient race and provider in prediction of patient satisfaction following post-mastectomy breast reconstruction. METHODS: The patient satisfaction for women who underwent post mastectomy breast reconstruction at University of California, Irvine Medical Center was evaluated between 2012 and 2014, randomly using Press Ganey Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys. Patient demographics and surgery related variables including type of reconstruction received were determined. RESULTS: Between 2012 and 2014, ninety breast reconstruction patients completed a HCAHPS satisfaction survey. Average satisfaction score was 9.67/10. Multivariate linear regression analyses revealed that 34% of the variability in satisfaction scores was accounted for by the variables included in our statistical model. Analyses revealed race/ethnicity and provider to be independent predictors of satisfaction (p<0.05). Satisfaction scores ranged from 6-10 and varied by 11.7% across different providers and 8.9% across different races. The following variables were included, but did not influence patient satisfaction: type, timing, or laterality of reconstruction, presence of post-operative complication, body mass index (BMI), age, presence of comorbidity, and insurance type. CONCLUSION: Achieving patient satisfaction is an important outcome of breast reconstruction. This study is one of the first to identify provider and race/ethnicity as predictors of patient satisfaction following breast reconstruction. The information provided here can help inform providers and improve satisfaction for patients undergoing breast reconstruction.

Deferred use of bevacizumab for recurrent glioblastoma is not associated with diminished efficacy.

BACKGROUND: The optimal timing to initiate bevacizumab (BV) therapy for recurrent glioblastoma (GBM) is currently unclear. To address this issue, we examined progression-free survival (PFS) and survival time (ST) in a large retrospective cohort of GBM patients treated with BV at different recurrences. METHODS: We identified 468 primary GBM patients who underwent biopsy or surgery followed by radiation therapy and temozolomide (RT/TMZ), and then received BV. PFS and ST were compared between patients stratified by the recurrence that BV was initiated (upfront, first recurrence, second recurrence, or 3+ recurrences). We also examined the effect on PFS and ST of the addition of chemotherapy to BV. In a larger cohort of GBM patients, we determined overall treatment continuation rates at each recurrence and identified variables predictive of inability to continue treatment. RESULTS: BV PFS was similar for all 3 recurrence groups (median, 4.1 months). There were no differences in BV ST (median, 9.8 months). The addition of chemotherapy to BV improved PFS but not ST. Analysis of treatment continuation rates indicated that the number of patients unable to undergo further treatments is modest, and that patients unable to tolerate BV delay can be identified by age ≥60 years and low extent of resection. CONCLUSIONS: Deferred use of bevacizumab is not associated with diminished efficacy. Analysis of treatment continuation rates identified patients who may be unable to delay BV therapy. Our findings suggest that there is a fixed survival after BV initiation and that delayed BV treatment is preferable for most patients.

Combined analysis of O6-methylguanine-DNA methyltransferase protein expression and promoter methylation provides optimized prognostication of glioblastoma outcome.

BACKGROUND: Promoter methylation of the DNA repair gene, O-6-methylguanine-DNA methyltransferase (MGMT), is associated with improved treatment outcome for newly diagnosed glioblastoma (GBM) treated with standard chemoradiation. To determine the prognostic significance of MGMT protein expression as assessed by immunohistochemistry (IHC) and its relationship with methylation, we analyzed MGMT expression and promoter methylation with survival in a retrospective patient cohort. METHODS: We identified 418 patients with newly diagnosed GBM at University of California Los Angeles Kaiser Permanente Los Angeles, nearly all of whom received chemoradiation, and determined MGMT expression by IHC, and MGMT promoter methylation by methylation-specific PCR (MSP) and bisulfite sequencing (BiSEQ) of 24 neighboring CpG sites. RESULTS: With use of the median percentage of cells staining by IHC as the threshold, patients with <30% staining had progression-free survival (PFS) of 10.9 months and overall survival (OS) of 20.5 months, compared with PFS of 7.8 months (P < .0001) and OS of 16.7 months (P < .0001) among patients with ≥30% staining. Inter- and intrareader correlation of IHC staining was high. Promoter methylation status by MSP was correlated with IHC staining. However, low IHC staining was frequently observed in the absence of promoter methylation. Increased methylation density determined by BiSEQ correlated with both decreased IHC staining and increased survival, providing a practical semiquantitative alternative to MSP. On the basis of multivariate analysis validated by bootstrap analysis, patients with tandem promoter methylation and low expression demonstrated improved OS and PFS, compared with the other combinations. CONCLUSIONS: Optimal assessment of MGMT status as a prognostic biomarker for patients with newly diagnosed GBM treated with chemoradiation requires determination of both promoter methylation and IHC protein expression.

Functional diffusion maps (fDMs) evaluated before and after radiochemotherapy predict progression-free and overall survival in newly diagnosed glioblastoma.

Functional diffusion mapping (fDM) has shown promise as a sensitive imaging biomarker for predicting survival in initial studies consisting of a small number of patients, mixed tumor grades, and before routine use of anti-angiogenic therapy. The current study tested whether fDM performed before and after radiochemotherapy could predict progression-free and overall survival in 143 patients with newly diagnosed glioblastoma from 2007 through 2010, many treated with anti-angiogenic therapy after recurrence. Diffusion and conventional MRI scans were obtained before and 4 weeks after completion of radiotherapy and concurrent temozolomide treatment. FDM was created by coregistering pre- and posttreatment apparent diffusion coefficient (ADC) maps and then performing voxel-wise subtraction. FDMs were categorized according to the degree of change in ADC in pre- and posttreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions. The volume fraction of fDM-classified increasing ADC(+), decreasing ADC(-), and change in ADC(+/-) were tested to determine whether they were predictive of survival. Both Bonferroni-corrected univariate log-rank analysis and Cox proportional hazards modeling demonstrated that patients with decreasing ADC in a large volume fraction of pretreatment FLAIR or contrast-enhancing regions were statistically more likely to progress earlier and expire sooner than in patients with a lower volume fraction. The current study supports the hypothesis that fDM is a sensitive imaging biomarker for predicting survival in glioblastoma.

Identification of retinol binding protein 1 promoter hypermethylation in isocitrate dehydrogenase 1 and 2 mutant gliomas.

BACKGROUND: Mutations in isocitrate dehydrogenase 1 (IDH1) and associated CpG island hypermethylation represent early events in the development of low-grade gliomas and secondary glioblastomas. To identify candidate tumor suppressor genes whose promoter methylation may contribute to gliomagenesis, we compared methylation profiles of IDH1 mutant (MUT) and IDH1 wild-type (WT) tumors using massively parallel reduced representation bisulfite sequencing. METHODS: Reduced representation bisulfite sequencing was performed on ten pathologically matched WT and MUT glioma samples and compared with data from a methylation-sensitive restriction enzyme technique and data from The Cancer Genome Atlas (TCGA). Methylation in the gene retinol-binding protein 1 (RBP1) was identified in IDH1 mutant tumors and further analyzed with primer-based bisulfite sequencing. Correlation between IDH1/IDH2 mutation status and RBP1 methylation was evaluated with Spearman correlation. Survival data were collected retrospectively and analyzed with Kaplan-Meier and Cox proportional hazards analysis. All statistical tests were two-sided. RESULTS: Methylome analysis identified coordinated CpG island hypermethylation in IDH1 MUT gliomas, consistent with previous reports. RBP1, important in retinoic acid metabolism, was found to be hypermethylated in 76 of 79 IDH1 MUT, 3 of 3 IDH2 MUT, and 0 of 116 IDH1/IDH2 WT tumors. IDH1/IDH2 mutation was highly correlated with RBP1 hypermethylation (n = 198; Spearman R = 0.94, 95% confidence interval = 0.92 to 0.95, P < .001). The Cancer Genome Atlas showed IDH1 MUT tumors (n = 23) to be RBP1-hypermethylated with decreased RBP1 expression compared with WT tumors (n = 124). Among patients with primary glioblastoma, patients with RBP1-unmethylated tumors (n = 102) had decreased median overall survival compared with patients with RBP1-methylated tumors (n = 22) (20.3 months vs 36.8 months, respectively; hazard ratio of death = 2.48, 95% confidence interval = 1.30 to 4.75, P = .006). CONCLUSION: RBP1 promoter hypermethylation is found in nearly all IDH1 and IDH2 mutant gliomas and is associated with improved patient survival. Because RBP1 is involved in retinoic acid synthesis, our results suggest that dysregulation of retinoic acid metabolism may contribute to glioma formation along the IDH1/IDH2-mutant pathway.

Post-transplantation primary central nervous system lymphoma: A case report and review of the literature.

BACKGROUND: Post-transplantation primary central nervous system lymphoma (PT-PCNSL) is a rare neoplasm that can develop within months to years after transplantation, and imaging often reveals multiple lesions with homogeneous or ring enhancement. The clinical and imaging presentation of PT-PCNSL can often be nonspecific and present a diagnostic challenge. CASE DESCRIPTION: A 56-year-old woman presented to a tertiary university emergency room with altered mental status 15 months after undergoing renal transplantation. On brain MRI, she was found to have three rim-enhancing mass lesions, and biopsy revealed PT-PCNSL. CONCLUSION: There has been a steady increase in the number of patients living following organ transplantation in the United States and an increasing likelihood that PT-PCNSL will increasingly be encountered in neurosurgical practice. We present here a case of PT-PCNSL and a brief review of the relevant clinical characteristics, treatment options, and prognosis of PT-PCNSL.

Graded functional diffusion map-defined characteristics of apparent diffusion coefficients predict overall survival in recurrent glioblastoma treated with bevacizumab.

Diffusion imaging has shown promise as a predictive and prognostic biomarker in glioma. We assessed the ability of graded functional diffusion maps (fDMs) and apparent diffusion coefficient (ADC) characteristics to predict overall survival (OS) in recurrent glioblastoma multiforme (GBM) patients treated with bevacizumab. Seventy-seven patients with recurrent GBMs were retrospectively examined. MRI scans were obtained before and approximately 6 weeks after treatment with bevacizumab. Graded fDMs were created by registering datasets to each patient's pretreatment scan and then performing voxel-wise subtraction between post- and pretreatment ADC maps. Voxels were categorized according to the degree of change in ADC within pretreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions of interest (ROIs). We found that the volume of tissue showing decreased ADC within both FLAIR and contrast-enhancing regions stratified OS (log-rank, P < .05). fDMs applied to contrast-enhancing ROIs more accurately predicted OS compared with fDMs applied to FLAIR ROIs. Graded fDMs (showing voxels with decreased ADC between 0.25 and 0.4 µm(2)/ms) were more predictive of OS than traditional (single threshold) fDMs, and the predictive ability of graded fDMs could be enhanced even further by adding the ADC characteristics from the fDM-classified voxels to the analysis (log-rank, P < .001). These results demonstrate that spatially resolved diffusion-based tumor metrics are a powerful imaging biomarker of survival in patients with recurrent GBM treated with bevacizumab.