Comparative Evaluation of the Electronic Residency Application Service Versus the Plastic Surgery Common Application to a Single Institution in the 2022 Integrated Plastic Surgery Match.

BACKGROUND: The Plastic Surgery Common Application (PSCA) has emerged as a low-cost alternative application portal to the Electronic Residency Application Service (ERAS) for integrated plastic surgery applicants. During the 2021 to 2022 application cycle, our plastic surgery residency program accepted both the PSCA and ERAS applications to help recruit candidates otherwise deterred by prohibitively high application costs. We sought to determine how the PSCA compared with the ERAS application in a standardized review of applications scores. METHODS: The PSCA and ERAS applications from 28 candidates who received interviews from the Keck School of Medicine were analyzed. These 56 applications were randomly assigned across 22 independent reviewers. Each reviewer scored applications on a scale of 1 to 5 with regard to communication skills, leadership, intellectual curiosity, compatibility with the program, service, and perseverance. Mean scores between the applications were compared using 2-tailed z tests, with statistical significance set at P < 0.05. RESULTS: The 56 residency applications had a combined mean score of 4.21 (95% confidence interval [CI], 4.13-4.29). The mean score of PSCA applications (4.19; 95% CI, 4.08-4.31) did not significantly differ from the mean score of ERAS applications (4.24; 95% CI, 4.12-4.35; P = 0.57). The PSCA and ERAS applications did not have a significant difference in the mean scores for any review category. CONCLUSION: There was no difference between the overall scores and the scores of each review category between the PSCA and ERAS applications, suggesting that the PSCA may be a reasonable alternative to ERAS for medical students applying to plastic surgery residency.

Measuring Biomechanical Properties Using a Noninvasive Myoton Device for Lymphedema Detection and Tracking: A Pilot Study.

Background: Improved techniques for lymphedema detection and monitoring of disease progression are needed. This study aims to use the noninvasive MyotonPRO Device to detect differences in biomechanical skin characteristics in patients with breast cancer-related lymphedema (BCRL). Methods: The handheld Myoton device was used to measure skin parameters including dynamic skin stiffness, oscillation frequency (tone), mechanical stress relaxation time, and creep in 11 women diagnosed with BCRL. Seven anatomical sites were measured bilaterally for each participant. The average values in the affected arms were compared with those in the contralateral unaffected arms. Results: Among the 11 female participants with unilateral BCRL Stages 0 to II, the combined averages for dynamic skin stiffness and frequency measurements were decreased in the affected arms when compared with those for the contralateral control arms (ratio < 1). The median ratio of stiffness (affected to unaffected control arm) was 0.91 (interquartile range [IQR] 0.78-1.03) while frequency was 0.94 (IQR 0.89-1.0). Skin relaxation time and creep averages were increased in the affected arms. The relaxation time median ratio (affected to unaffected control arm) was 1.07 (IQR 1.02-1.14) and the median ratio of creep was 1.06 (IQR 1.03-1.16). Conclusions: This study suggests the Myoton can detect differences in skin biomechanical parameters of the affected and unaffected arms in patients with BCRL. Larger studies are needed to draw strong conclusions.

Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis.

Clinical trials establish the standard of cancer care, yet the evolution and characteristics of the social dynamics between the people conducting this work remain understudied. We performed a social network analysis of authors publishing chemotherapy-based prospective trials from 1946 to 2018 to understand how social influences, including the role of gender, have influenced the growth and development of this network, which has expanded exponentially from fewer than 50 authors in 1946 to 29,197 in 2018. While 99.4% of authors were directly or indirectly connected by 2018, our results indicate a tendency to predominantly connect with others in the same or similar fields, as well as an increasing disparity in author impact and number of connections. Scale-free effects were evident, with small numbers of individuals having disproportionate impact. Women were under-represented and likelier to have lower impact, shorter productive periods (P < 0.001 for both comparisons), less centrality, and a greater proportion of co-authors in their same subspecialty. The past 30 years were characterized by a trend towards increased authorship by women, with new author parity anticipated in 2032. The network of cancer clinical trialists is best characterized as strategic or mixed-motive, with cooperative and competitive elements influencing its appearance. Network effects such as low centrality, which may limit access to high-profile individuals, likely contribute to the observed disparities.

Development and patterning of rib primordia are dependent on associated musculature.

The importance of skeletal muscle for rib development and patterning in the mouse embryo has not been resolved, largely because different experimental approaches have yielded disparate results. In this study, we utilize both gene knockouts and muscle cell ablation approaches to re-visit the extent to which rib growth and patterning are dependent on developing musculature. Consistent with previous studies, we show that rib formation is highly dependent on the MYOD family of myogenic regulatory factors (MRFs), and demonstrate that the extent of rib formation is gene-, allele-, and dosage-dependent. In the absence of Myf5 and MyoD, one allele of Mrf4 is sufficient for extensive rib growth, although patterning is abnormal. Under conditions of limiting MRF dosage, MyoD is identified as a positive regulator of rib patterning, presumably due to improved intercostal muscle development. In contrast to previous muscle ablation studies, we show that diphtheria toxin subunit A (DTA)-mediated ablation of muscle progenitors or differentiated muscle, using MyoDiCre or HSA-Cre drivers, respectively, profoundly disrupts rib development. Further, a comparison of three independently derived Rosa26-based DTA knockin alleles demonstrates that the degree of rib perturbations in MyoDiCre/+/DTA embryos is markedly dependent on the DTA allele used, and may in part explain discrepancies with previous findings. The results support the conclusion that the extent and quality of rib formation is largely dependent on the dosage of Myf5 and Mrf4, and that both early myotome-sclerotome interactions, as well as later muscle-rib interactions, are important for proper rib growth and patterning.

Advantages of a Fixation-Free Technique for Open Retromuscular Ventral Hernia Repair.

BACKGROUND: In open retromuscular ventral hernia repair, fixation-free mesh placement is increasingly prevalent and may minimize pain; the main concern with this technique is short-term technical failure and hernia recurrence. This study compared outcomes following mechanical mesh fixation (i.e., sutures, staples, tacks) versus fixation-free mesh placement. METHODS: Adults who underwent open, elective, retromuscular ventral hernia repair of 15 cm width or less with permanent synthetic mesh placement in a clean wound were identified. Propensity score matching was used to compare patients who received mechanical mesh fixation to those who received fixation-free mesh placement. Thirty-day hernia recurrence was the primary outcome, with secondary outcomes of 30-day hospital length of stay and 30-day rates of readmission, reoperation, wound events, pain, and abdominal wall function. One- and 2-year composite recurrence and 3-year cumulative composite recurrence were also evaluated. RESULTS: A 3:1 propensity score match was performed on 299 fixation-free patients identifying 897 mechanical fixation patients, with a mean body mass index of 31 kg/m and mean age of 57.5 years. There was no difference in 30-day recurrence between mechanical and fixation-free approaches (0.2 percent versus 0 percent; p = 1). Median length of stay was longer for mechanical fixation (4 versus 3 days; p = 0.002). In the mechanical fixation group, pain scores were higher (worse pain, 46 versus 44; p = 0.001), and abdominal wall function scores were lower (worse function, 47 versus 60; p = 0.003), with no differences in rates of hospital readmission, reoperation, or wound events. There were no differences in long-term outcomes of 1- and 2-year composite recurrence, or 3-year cumulative composite recurrence. CONCLUSION: For short-term technical durability, fixation-free mesh placement in open retromuscular ventral hernia repair is an acceptable alternative to mechanical fixation for hernia defects of 15 cm or less. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua.

The process of implantation, trophoblast invasion and placentation demand continuous adaptation and modifications between the trophoblast (embryonic) and the decidua (maternal). Within the decidua, the maternal immune system undergoes continued changes, as the pregnancy progress, in terms of the cell population, phenotype and production of immune factors, cytokines and chemokines. Human chorionic gonadotropin (hCG) is one of the earliest hormones produced by the blastocyst and has potent immune modulatory effects, especially in relation to T cells. We hypothesized that trophoblast-derived hCG modulates the immune population present at the maternal fetal interface by modifying the cytokine profile produced by the stromal/decidual cells. Using in vitro models from decidual samples we demonstrate that hCG inhibits CXCL10 expression by inducing H3K27me3 histone methylation, which binds to Region 4 of the CXCL10 promoter, thereby suppressing its expression. hCG-induced histone methylation is mediated through EZH2, a functional member of the PRC2 complex. Regulation of CXCL10 expression has a major impact on the capacity of endometrial stromal cells to recruit CD8 cells. We demonstrate the existence of a cross talk between the placenta (hCG) and the decidua (CXCL10) in the control of immune cell recruitment. Alterations in this immune regulatory function, such as during infection, will have detrimental effects on the success of the pregnancy.

Indication of Measures of Uncertainty for Statistical Significance in Abstracts of Published Oncology Trials: A Systematic Review and Meta-analysis.

IMPORTANCE: There is growing consensus that reliance on P values, particularly a cutoff level of .05 for statistical significance, is a factor in the challenges in scientific reproducibility. Despite this consensus, publications describing clinical trial results with P values near .05 anecdotally use declarative statements that do not express uncertainty. OBJECTIVES: To quantify uncertainty expression in abstracts describing the results of cancer randomized clinical trials (RCTs) with P values between .01 and .10 and examine whether trial features are associated with uncertainty expression. DATA SOURCES: A total of 5777 prospective trials indexed on HemOnc.org, as of September 15, 2019. STUDY SELECTION: Two-arm RCTs with a superiority end point with P values between .01 and .10. DATA EXTRACTION AND SYNTHESIS: Abstracts were evaluated based on an uncertainty expression algorithm. Ordinal logistic regression modeling with multiple imputation was performed to identify whether characteristics of study design, results, trial authors, and context P values were normalized by dividing by prespecified α value. MAIN OUTCOMES AND MEASURES: Uncertainty expression in abstracts as determined by the algorithm and its association with trial and publication characteristics. RESULTS: Of 5777 trials screened, 556 met analysis criteria. Of these, 222 trials (39.9%) did not express uncertainty, 161 trials (29.0%) expressed some uncertainty, and 173 trials (31.1%) expressed full uncertainty. In ordinal logistic regression with multiple imputation, trial features with statistically significant associations with uncertainty expression included later year of publication (odds ratio [OR], 1.70; 95% CI, 1.24-2.32; P < .001), normalized P value (OR, 1.36; 95% CI, 1.11-1.67; P = .003), noncooperative group studies (OR, 1.72; 95% CI, 1.12-2.63; P = .01), and reporting an end point other than overall survival (OR, 1.41; 95% CI, 1.01-1.96; P = .047). Funding source, number of authors, journal impact tier, author nationality, study of unapproved drugs, abstract word count, whether the marginal end point was a primary or coprimary end point, and effect size (in subgroup analysis) did not have statistically significant associations with uncertainty expression. CONCLUSIONS AND RELEVANCE: Published oncology articles with marginally significant results may often incompletely convey uncertainty. Although it appears that more uncertainty is expressed in recent abstracts, full uncertainty expression remains uncommon, and seemingly is less common when reporting overall survival, results with P values lower than α levels, and cooperative group studies.

Kaposi Sarcoma Updates.

Kaposi sarcoma (KS) is an angioproliferative mesenchymal neoplasm caused by Kaposi sarcoma-related herpesvirus. This review outlines our current understanding of the epidemiology, pathogenesis, clinical presentation, and staging for this disease. Recent research has informed a more comprehensive understanding of the epidemiology of KS in the post-antiretroviral therapy era, and highlights the continued need to better characterize the African endemic subtype. Advances in clinical oncology, including checkpoint inhibitors and new skin-directed therapies, have translated into exciting new developments for the future of KS treatment options.

Cost-Utility Analysis of Biologic and Biosynthetic Mesh in Ventral Hernia Repair: When Are They Worth It?

BACKGROUND: Biologic and biosynthetic meshes typically cost more than synthetic meshes for use in ventral hernia repair (VHR), with unknown comparative effectiveness. STUDY DESIGN: Cost-utility analysis was performed from a limited societal perspective assessing direct medical costs and outcomes for open, elective, retromuscular VHR. Short-term and 5-year major complications and costs were modeled using best available evidence from published studies, Healthcare Cost and Utilization Project data, and Americas Hernia Society Quality Collaborative data. Costs were analyzed in 2017 US dollars, and utilities were assessed using quality adjusted life years (QALYs). Sensitivity analyses were performed to determine threshold probabilities of long-term complications favoring particular mesh types. RESULTS: Synthetic mesh was the preferred strategy, with a cost of $15,620 and QALYs of 18.85, assuming a baseline 5.6% rate of long-term complications for all meshes. One-way sensitivity analysis demonstrated that biosynthetic and biologic mesh became the better choice as long-term complication rates for synthetic mesh increased to 15.5% and 26.2%, respectively. Two-way sensitivity analysis demonstrated that biologic and biosynthetic meshes became favorable as the cost of biologic mesh decreased and long-term synthetic mesh complication rates increased. Biologic and biosynthetic meshes also became more cost-effective when their relative long-term complication rates decreased and long-term synthetic mesh complication rates increased. CONCLUSIONS: Using modeling techniques, synthetic mesh is the best option for retromuscular VHR given currently available evidence. We established long-term complication thresholds, possibly justifying the higher up-front costs for biologic or biosynthetic meshes. This emphasizes the critical need to obtain long-term complication surveillance data to help individualize mesh choice in VHR.

MyoD-expressing progenitors are essential for skeletal myogenesis and satellite cell development.

Skeletal myogenesis in the embryo is regulated by the coordinated expression of the MyoD family of muscle regulatory factors (MRFs). MyoD and Myf-5, which are the primary muscle lineage-determining factors, function in a partially redundant manner to establish muscle progenitor cell identity. Previous diphtheria toxin (DTA)-mediated ablation studies showed that MyoD+ progenitors rescue myogenesis in embryos in which Myf-5-expressing cells were targeted for ablation, raising the possibility that the regulative behavior of distinct, MRF-expressing populations explains the functional compensatory activities of these MRFs. Using MyoD(iCre) mice, we show that DTA-mediated ablation of MyoD-expressing cells results in the cessation of myogenesis by embryonic day 12.5 (E12.5), as assayed by myosin heavy chain (MyHC) and Myogenin staining. Importantly, MyoD(iCre/+);R26(DTA/+) embryos exhibited a concomitant loss of Myf-5+ progenitors, indicating that the vast majority of Myf-5+ progenitors express MyoD, a conclusion consistent with immunofluorescence analysis of Myf-5 protein expression in MyoD(iCre) lineage-labeled embryos. Surprisingly, staining for the paired box transcription factor, Pax7, which functions genetically upstream of MyoD in the trunk and is a marker for fetal myoblasts and satellite cell progenitors, was also lost by E12.5. Specific ablation of differentiating skeletal muscle in ACTA1Cre;R26(DTA/+) embryos resulted in comparatively minor effects on MyoD+, Myf-5+ and Pax7+ progenitors, indicating that cell non-autonomous effects are unlikely to explain the rapid loss of myogenic progenitors in MyoD(iCre/+);R26(DTA/+) embryos. We conclude that the vast majority of myogenic cells transit through a MyoD+ state, and that MyoD+ progenitors are essential for myogenesis and stem cell development.