The transition to modernity and chronic disease: mismatch and natural selection.

The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.

Gene expression regulates metabolite homeostasis during the Crabtree effect: Implications for the adaptation and evolution of Metabolism.

A key issue in both molecular and evolutionary biology has been to define the roles of genes and phenotypes in the adaptation of organisms to environmental changes. The dominant view has been that an organism's metabolic adaptations are driven by gene expression and that gene mutations, independent of the starting phenotype, are responsible for the evolution of new metabolic phenotypes. We propose an alternate hypothesis, in which the phenotype and genotype together determine metabolic adaptation both in the lifetime of the organism and in the evolutionary selection of adaptive metabolic traits. We tested this hypothesis by flux-balance and metabolic-control analysis of the relative roles of the starting phenotype and gene expression in regulating the metabolic adaptations during the Crabtree effect in yeast, when they are switched from a low- to high-glucose environment. Critical for successful short-term adaptation was the ability of the glycogen/trehalose shunt to balance the glycolytic pathway. The role of later gene expression of new isoforms of glycolytic enzymes, rather than flux control, was to provide additional homeostatic mechanisms allowing an increase in the amount and efficiency of adenosine triphosphate and product formation while maintaining glycolytic balance. We further showed that homeostatic mechanisms, by allowing increased phenotypic plasticity, could have played an important role in guiding the evolution of the Crabtree effect. Although our findings are specific to Crabtree yeast, they are likely to be broadly found because of the well-recognized similarities in glucose metabolism across kingdoms and phyla from yeast to humans.

Geographic Variability of Genital Gender-Affirming Surgery Centers and Costs of Hospitalization.

PURPOSE: The cost of gender-affirming surgery (GAS) is an important component of healthcare accessibility for transgender patients. However, GAS is often prohibitively expensive, particularly as there are inconsistencies in insurance coverages. Variability in hospital costs has been documented for other types of nonplastic surgery procedures; however, this analysis has not been done for GAS. To better understand the financial barriers impairing access to equitable transgender care, this study analyzes the distribution of hospitals that perform genital GAS and the associated costs of inpatient genital GAS. METHODS: This is a study of the 2016-2019 National Inpatient Sample database. Transgender patients undergoing genital GAS were identified using International Classification of Diseases, Tenth Revision, diagnosis and procedure codes, and patients undergoing concurrent chest wall GAS were excluded. Descriptive statistics were done on patient sociodemographic variables, hospital characteristics, and hospitalization costs. χ2 test was used to assess for differences between categorical variables and Mood's median test was used to assess for differences between continuous variable medians. RESULTS: A total of 3590 weighted genital GAS encounters were identified. The Western region (50.8%) and Northeast (32.3%) performed the greatest proportion of GAS, compared with the Midwest (9.1%) and the South (8.0%) (P < 0.0001). The most common payment source was private insurance (62.8%), followed by public insurance (27.3%). There were significant differences in the variability of median hospital costs across regions (P < 0.0001). The South and Midwest had the greatest median cost for vaginoplasty ($19,935; interquartile range [IQR], $16,162-$23,561; P = 0.0009), while the West had the greatest median cost for phalloplasty ($26,799; IQR, $19,667-$30,826; P = 0.0152). Across both procedures, the Northeast had the lowest median cost ($11,421; IQR, $9155-$13,165 and $10,055; IQR, $9,013-$10,377, respectively). CONCLUSIONS: There is significant regional variability in the number of GAS procedures performed and their associated hospitalization costs. The identified disparities in insurance coverage present an area of possible future improvement to alleviate the financial burden GAS presents to gender-discordant individuals. The variability in cost suggests a need to evaluate variations in care, leading to cost standardization.

Patient Comfort with Before and After Photography at Plastic Surgery Offices.

BACKGROUND: Before and after (B&A) photographs are a sensitive part of patients' medical records, and the use of smartphones may pose risks to confidentiality and comfort. The purpose of this study was to assess patient comfort depending on the circumstances under which these photographs being taken. METHODS: Amazon's Mechanical Turk crowdsourcing service and REDCap's survey manager were used to recruit survey participants. An anonymous survey was distributed to ascertain demographics and comfort in various B&A scenarios using a five-point Likert scale. T tests and ANOVA testing were used to compare groups. RESULTS: There were 411 respondents with an average age of 36.1 years old. Of them, 46% were female and the majority were White (90%) and non-Hispanic (64%). Nearly one-third had previously undergone plastic surgery, with 80% receiving B&A photography. Surgeons took these photographs 51% of the time with similar rates of smartphone cameras use (47%) versus professional cameras (52%). The public had similar levels of comfort when a nurse or a surgeon took the clinical photographs (p = 0.08). Patients were significantly less comfortable when non-medically trained office staff captured their photographs (p = 0.0041). The public had similar comfort levels with the use of smartphones and professional cameras when dressed but were significantly less comfortable with the use of a smartphone when unclothed (p = < 0.001). CONCLUSION: To ensure the best patient experience, B&A photography should be taken by a medical professional. If photographs are to be taken when the patient is unclothed, the use of a professional-grade camera may help ease patient discomfort. 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 .

Rhinoplasty Preferences: Can the Public Detect Prior Surgery on Social Media?

BACKGROUND: The creation of postoperative rhinoplasty results that appear natural and proportional to the face are crucial for patient satisfaction. The purpose of this study was to assess the public's ability to detect a post-rhinoplasty result and preference of preoperative and postoperative rhinoplasty outcomes. METHODS: A survey was distributed using the Amazon Mechanical Turk online platform showing nine preoperative and postoperative rhinoplasty patients. Participants rated aesthetic appearance, identified areas of abnormality, and stated whether they believed the patient had undergone prior rhinoplasty. RESULTS: A total of 456 responses were included. On a scale of 1-5 with 5 being the most aesthetically pleasing, the highest rated nose was a postoperative patient without visible deformities (3.95, SD 1.07) followed by the postoperative patient with a resultant bulbous tip (3.48, SD 0.96). The lowest ranking noses were the prior rhinoplasty with resultant saddle nose deformity (3.02, SD 1.19) and the prior rhinoplasty with nasal trapezoid deformity (2.95, SD 1.04). The public was able to correctly determine if patients had prior rhinoplasty surgery only if there were resultant defects. When respondents believed that the patient had undergone prior rhinoplasty, their average rating was lower than those who believed they had not undergone surgery (3.74/5 vs. 4.15/5, p < 0.0001). CONCLUSIONS: The belief that someone had previously undergone rhinoplasty led the public to rate the aesthetic appearance of the nose lower. To provide optimal results following rhinoplasty, surgeons may therefore seek to provide a natural, "un-operated" look. LEVEL OF EVIDENCE IV: 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 . Differences for nasal aesthetic preferences exist and vary based on geographic region The public is unable to discern if a patient previously underwent rhinoplasty if the result does not show a postoperative defect, such as a dorsal hump, over-rotated tip, or mid-vault collapse Oppositely, the public can generally tell if patients have undergone rhinoplasty surgery if a postoperative deformity is present The belief that someone had rhinoplasty surgery negatively impacts the attractiveness ranking of the nose, even without any postoperative defects present.

Preferences and Barriers of Male Patients Seeking Aesthetic Procedures.

BACKGROUND: As social attitudes toward plastic surgery continue to evolve, the prevalence of men seeking plastic surgery has been increasing. By delving into the factors that encourage male patients to seek plastic surgery and the obstacles they encounter, this study aims to facilitate the development of more inclusive and effective approaches for this population. METHOD: An anonymous 41-question survey was conducted among adult men in the USA via the Amazon Mechanical Turk crowdsourcing platform. Questions assessed demographic information and identified factors that influenced males to seek plastic surgery care, the barriers they experienced while seeking care, and their preferences. Multivariate logistic regression was used to assess relationships between demographic variables and likelihood of undergoing cosmetic surgery. RESULTS: Four hundred and eleven complete responses were analyzed. The median (IQR) age of respondents was 32 (30, 40) years old. Of the respondents, 60% had undergone cosmetic surgery. Functional improvement (40%), personal aspiration (32%), and partners' opinions (22%) were the most commonly cited reasons for undergoing procedures. The most common barriers faced by this population were recovery time following a procedure (52%), perceived risk of complications (48%), cost (43%), fear of being identified as having had plastic surgery (32%), and surgeons not being able to meet expectations (31%). Eighty-nine percent of respondents who underwent plastic surgery procedures reported facing at least one barrier. Multivariate regression demonstrated that higher education levels were strongly associated with a likelihood of undergoing cosmetic surgery (p < 0.001). Income (p = 0.44) and region (p = 0.23) did not significantly affect the likelihood of undergoing plastic surgery. CONCLUSION: Despite improving societal stigma, many male patients continue to face barriers when obtaining plastic surgery care. Efforts may be made to alleviate these barriers and surgeons looking to expand their practice may benefit from increased outreach to male patients. This may be compounded with improved education targeting stigma and risks of procedures, increasing male-specific marketing communications to make them feel welcome in an industry predominantly focused on female patients, and offering male-tailored procedures. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Crural closure, not fundoplication, results in a significant decrease in lower esophageal sphincter distensibility.

INTRODUCTION: The esophagogastric junction (EGJ) is a complex anti-reflux barrier whose integrity relies on both the intrinsic lower esophageal sphincter (LES) and extrinsic crural diaphragm. During hiatal hernia repair, it is unclear whether the crural closure or the fundoplication is more important to restore the anti-reflux barrier. The objective of this study is to analyze changes in LES minimum diameter (Dmin) and distensibility index (DI) using the endoluminal functional lumen imaging probe (FLIP) during hiatal hernia repair. METHODS: Following implementation of a standardized operative FLIP protocol, all data were collected prospectively and entered into a quality database. This data were reviewed retrospectively for all patients undergoing hiatal hernia repair. FLIP measurements were collected prior to hernia dissection, after hernia reduction, after cruroplasty, and after fundoplication. Additionally, subjective assessment of the tightness of crural closure was rated by the primary surgeon on a scale of 1 to 5, 1 being the loosest and 5 being the tightest. RESULTS: Between August 2018 and February 2020, 97 hiatal hernia repairs were performed by a single surgeon. FLIP measurements collected using a 40-mL volume fill without pneumoperitoneum demonstrated a significant decrease in LES Dmin (13.84 ± 2.59 to 10.27 ± 2.09) and DI (6.81 ± 3.03 to 2.85 ± 1.23 mm2/mmHg) after crural closure (both p < 0.0001). Following fundoplication, there was a small, but also statistically significant, increase in both Dmin and DI (both p < 0.0001). Additionally, subjective assessment of crural tightness after cruroplasty correlated well with DI (r = - 0.466, p < 0.001) and all patients with a crural tightness rating ≥ 4.5 (N = 13) had a DI < 2.0 mm2/mmHg. CONCLUSION: Cruroplasty results in a significant decrease in LES distensibility and may be more important than fundoplication in restoring EGJ competency. Additionally, subjective estimation of crural tightness correlates well with objective FLIP evaluation, suggesting surgeon assessment of cruroplasty is reliable.

Anti-reflux mucosectomy (ARMS) results in improved recovery and similar reflux quality of life outcomes compared to laparoscopic Nissen fundoplication.

BACKGROUND: Anti-reflux mucosectomy (ARMS) is a new endoscopic procedure involving a hemi-circumferential endoscopic mucosal resection (EMR) around the gastroesophageal junction. We aim to compare perioperative and quality of life outcomes of patients with reflux who underwent ARMS to a comparable group who underwent laparoscopic Nissen fundoplication (NF). METHODS: A retrospective review of a prospectively maintained quality database was performed. All patients who underwent ARMS (n = 33) were matched with patients who underwent NF (n = 67). Clinical and quality of life (QOL) outcomes were collected preoperatively and up to two years postoperatively, measured by the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL), and Dysphagia Score. Outcomes were compared using the Wilcoxon rank-sum and Fisher's exact test. RESULTS: While 10 patients (30.3%) who underwent ARMS required additional laparoscopic anti-reflux operations, the ARMS group had shorter OR time (p<0.001), less estimated blood loss (p<0.001), shorter hospital stay (p<0.001), less pain at discharge (p = 0.007), earlier narcotic discontinuation (p<0.001), and earlier return to activities of daily living (p<0.001) compared to the NF group. There was no difference in 30-day complication rates, emergency room visits, or readmission rates between the groups. There was no difference between ARMS and NF groups in terms of GERD-HRQL, RSI, or Dysphagia scores at 3 weeks, 6 months, 1 year, or 2 years postoperatively. However, the ARMS group reported less symptoms of gas and bloating postoperatively at all time points (all p<0.05). Both groups reported increased dysphagia at 3 weeks postoperatively (p<0.01) but this did not persist at 6 months, 1 year, or 2 years. CONCLUSION: While ARMS had better perioperative outcomes compared to NF, reflux quality of life outcomes were comparable. ARMS can be an effective endoscopic intervention for GERD when performed on appropriately selected patients without limiting future laparoscopic anti-reflux interventions.

Using a standardized intra-operative endoflip protocol during fundoplication to identify factors that affect distensibility.

INTRODUCTION: The Endoluminal Functional Lumen Imaging Probe (Endoflip) can be used to provide objective measurements of the gastroesophageal junction during fundoplication, and recent publications have suggested that this device could improve surgical outcomes. However, the impact of operative variables has not been clearly reported. The aim of this study is to determine the effect of these variables on functional lumen imaging probe (FLIP) measurements. METHODS: Following implementation of a standardized operative FLIP protocol, all data were collected prospectively and entered into a quality database. This database was queried for patients undergoing hiatal hernia repair and fundoplication. The protocol utilized various balloon volumes (30 and 40 ml), patient positions (flat and reverse Trendelenburg) and amounts of insufflation (15 mmHg pneumoperitoneum and no pneumoperitoneum). RESULTS: Between August 2018 and February 2020, 97 fundoplications were performed by a single surgeon. Multivariable analysis without interactions demonstrated that a 40 ml volume fill resulted in significantly higher minimum diameter (Dmin), cross-sectional area (CSA), intra-balloon pressure (IBP) and distensibility index (DI) compared to a 30 ml volume fill (p < 0.001). While reverse Trendelenburg positioning resulted in a significantly higher Dmin, IBP and CSA compared to the flat position (all p < 0.05), there was little impact of positioning on DI. Lastly, pneumoperitoneum significantly increased IBP (p < 0.001) but did not affect Dmin (p = 0.697) or CSA (p = 0.757), which resulted in a significant decrease in DI (p < 0.001) when compared to measurements without pneumoperitoneum. Multivariable analysis allowing for interactions demonstrated significant two-way interactions between balloon volume and pneumoperitoneum (p = 0.047), as well as patient position and pneumoperitoneum (p < 0.001). CONCLUSION: Surgeons should consider balloon volume and the presence or absence of pneumoperitoneum when interpreting distensibility during or after fundoplication. Additionally, we suggest a formal standardized protocol for FLIP measurements to utilize a 40 ml volume fill in reverse Trendelenburg without pneumoperitoneum.

Frontiers in Molecular Evolutionary Medicine.

This paper surveys some of the important insights that molecular evolution has contributed to evolutionary medicine; they include phage therapy, cancer biology, helminth manipulation of the host immune system, quality control of gametes, and pathogen outbreaks. Molecular evolution has helped to revolutionize our understanding of cancer, of autoimmune disease, and of the origin, spread, and pathogenesis of emerging diseases, where it has suggested new therapies, illuminated mechanisms, and revealed historical processes: all have practical therapeutic implications. While much has been accomplished, much remains to be done.

Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy.

Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.

Evolutionary public health: introducing the concept.

The emerging discipline of evolutionary medicine is breaking new ground in understanding why people become ill. However, the value of evolutionary analyses of human physiology and behaviour is only beginning to be recognised in the field of public health. Core principles come from life history theory, which analyses the allocation of finite amounts of energy between four competing functions-maintenance, growth, reproduction, and defence. A central tenet of evolutionary theory is that organisms are selected to allocate energy and time to maximise reproductive success, rather than health or longevity. Ecological interactions that influence mortality risk, nutrient availability, and pathogen burden shape energy allocation strategies throughout the life course, thereby affecting diverse health outcomes. Public health interventions could improve their own effectiveness by incorporating an evolutionary perspective. In particular, evolutionary approaches offer new opportunities to address the complex challenges of global health, in which populations are differentially exposed to the metabolic consequences of poverty, high fertility, infectious diseases, and rapid changes in nutrition and lifestyle. The effect of specific interventions is predicted to depend on broader factors shaping life expectancy. Among the important tools in this approach are mathematical models, which can explore probable benefits and limitations of interventions in silico, before their implementation in human populations.

The importance of the timescale of the fitness metric for estimates of selection on phenotypic traits during a period of demographic change.

Although fitness is central to the evolutionary process, metrics vary by timescale. Different timescales may give rise to different estimates of selection, especially during demographic transitions caused by rapid environmental and socioeconomic change. In this study, we used a dataset of a human population in Finland from 1775 to 1950 to compare two fitness metrics and their estimates of selection pressures, before and during a demographic transition. Both metrics, lifetime reproductive success and an annual metric of individual performance, declined while selection on the ages at first and last reproduction remained nearly constant, favouring individuals with wider reproductive windows. The ability to partition the annual metric into contributions from reproduction and survival revealed the short-term effects of a famine and the reversal of selection pressure via the survival component of annual fitness. Although the metrics generally agreed, the annual metric detected the effects of environmental variation and demographic change occurring within a generation.

Measuring selection in contemporary human populations.

Are humans currently evolving? This question can be answered using data on lifetime reproductive success, multiple traits and genetic variation and covariation in those traits. Such data are available in existing long-term, multigeneration studies - both clinical and epidemiological - but they have not yet been widely used to address contemporary human evolution. Here we review methods to predict evolutionary change and attempts to measure selection and inheritance in humans. We also assemble examples of long-term studies in which additional measurements of evolution could be made. The evidence strongly suggests that we are evolving and that our nature is dynamic, not static.

Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects.

Opposite phenotypic and behavioural traits associated with copy number variation and disruptions to imprinted genes with parent-of-origin effects have led to the hypothesis that autism and schizophrenia share molecular risk factors and pathogenic mechanisms, but a direct phenotypic comparison of how their risks covary has not been attempted. Here, we use health registry data collected on Denmark's roughly 5 million residents between 1978 and 2009 to detect opposing risks of autism and schizophrenia depending on normal variation (mean ± 1 s.d.) in adjusted birth size, which we use as a proxy for diametric gene-dosage variation in utero. Above-average-sized babies (weight, 3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for autism spectrum (AS) and significantly lower risk for schizophrenia spectrum (SS) disorders. By contrast, below-average-sized babies (2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and significantly higher risk for SS disorders. This is the first study directly comparing autism and schizophrenia risks in the same population, and provides the first large-scale empirical support for the hypothesis that diametric gene-dosage effects contribute to these disorders. Only the kinship theory of genomic imprinting predicts the opposing risk patterns that we discovered, suggesting that molecular research on mental disease risk would benefit from considering evolutionary theory.

Association Between Posterior Tibial Slope and ACL Injury in Pediatric Patients: A Systematic Review and Meta-analysis.

BACKGROUND: The posterior tibial slope (PTS) has been proposed to be a radiographic risk factor for anterior cruciate ligament (ACL) injury in adults. However, this has not been well established in pediatric patients. PURPOSE: This systematic review and meta-analysis was performed to investigate any association between PTS and ACL tears in the pediatric population. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: A systematic review was performed to identify studies that examined the relationship between PTS, medial tibial slope (MTS), and lateral tibial slope (LTS) and ACL tears in children and adolescents aged ≤18 years. Full-text observational studies comparing PTS, MTS, and/or LTS values between pediatric (≤18 years of age) patients with and without ACL injury were included in this analysis. Review articles and case series were excluded. The authors calculated the mean difference (MD) via a restricted maximum-likelihood estimator for tau square and a Hartung-Knapp adjustment for random-effects model. RESULTS: A total of 348 articles were identified in the initial database search, yielding 10 for final inclusion and analysis. There was no statistically significant association between PTS (MD, 1.13°; 95% CI, -0.55° to 2.80°; P = .10), MTS (MD, 0.36°; 95% CI, -0.37° to 1.10°; P = .27), or LTS (MD, 1.41°; 95% CI, -0.20° to 3.02°; P = .075) and risk for ACL injury in this population. CONCLUSION: The current study found that unlike what has been shown in adult populations, increased PTS may not be a significant risk factor for ACL tears in pediatric and adolescent patents. LTS was the only measured parameter that neared statistical significance, perhaps suggesting a potential role for this measurement in determining ACL risk if further research is done in this population.

Surgical management of popliteal artery entrapment syndrome.

Introduction: Popliteal artery entrapment syndrome (PAES) is a rare condition in which the popliteal artery becomes compressed by adjacent soft tissue structures causing progressive claudication. Due to its low incidence, this disorder and its surgical management is poorly described in the literature. This study presents our institutional data surrounding PAES management to further optimize care of this syndrome. Methods: This retrospective study gathered demographic, surgical, and outcome data of all patients with PAES who underwent surgical decompression at our institution from 2015 to 2022. Patients were identified using CPT and ICD-9/10 codes. Summary statistics were calculated, with Chi-squared and T-test used for subgroup analysis. Results: 50 surgical patients with PAES were identified. On average, they were young (mean age: 20.7 years), mostly female (78 %), and predominately white (68 %). The vast majority were physically active, with 13 of the 50 patients being runners (26 %). Medically, the cohort was otherwise healthy, with 74 % reporting no comorbidities. Diagnosis was often delayed, with patients on average seeing 4.5 physicians over 2.0 years prior to arriving at our institution for care. In addition to popliteal artery release, the second most performed procedure was fasciotomy (82 %). Postoperatively, there was significant long-term subjective improvement, with 91 % of patients reporting they would repeat the operation and 65 % reporting improved activity. Conclusion: PAES is a rare condition affecting the lower limb that requires a nuanced surgical approach. From diagnosis to outcome, we hope to better inform surgeons of PAES so that these patients may receive the highest quality care.

Comparing Collagenase and Tissue Subcision for Cellulite Treatment of the Buttock and Thigh Regions: A Systematic Review and Meta-analysis.

Background: In this systematic review, we assessed the therapeutic efficacy and safety of Clostridium histolyticum collagenase (CCH) and tissue subcision (TS) for treating cellulite, which ranges from subtle to pronounced lesions. Methods: A systematic review was performed following PRISMA guidelines for CCH and TS treatment to the thigh and gluteal regions. A proportion meta-analysis was then conducted using Stata statistical software. Results: A total of 14 studies were incorporated into the final analysis. Nine focused on TS and five on CCH injection, collectively reporting outcomes for 1254 patients. Of these, 465 received CCH injection and 789 underwent subcision. For bruising, rates were 89% [95% confidence interval (CI), 71%-96%] with CCH injection and 99% (95% CI, 85%-99%) for subcision; pain requiring analgesic was reported at 74% (95% CI, 55%-87%) for CCH and 60% (95% CI, 43%-76%) for subcision; both showed induration at 7% (95% CI, 5%-11% for CCH, 95% CI, 2%-25% for subcision), whereas skin discoloration was higher post-CCH injection at 16% (95% CI, 10%-26%) compared with 7% (95% CI, 5%-10%) postsubcision. Conclusions: Both CCH and TS seem effective treatments for cellulite. However, upon evaluating the adverse outcomes between the two modalities, subcision demonstrated a higher incidence of bruising, albeit similar rates of induration compared with CCH injection. Conversely, the CCH injection group manifested a higher propensity for pain requiring analgesia and notably exhibited increased instances of skin discoloration compared with their subcision patient group. Further standardized research is crucial for more informed cellulite treatment decisions and for comparing efficacy, safety, and cost-effectiveness between TS and CCH.

Utilization of patient-reported outcome measures in plastic surgery clinical trials: A systematic review.

BACKGROUND: Patient-reported outcomes (PROs) have evolved to validated questionnaires assessing health-related quality of life. This systematic review evaluates the utilization of PROs in United States plastic and reconstructive surgery (PRS) clinical trials (CTs). METHODS: A medical librarian conducted a search strategy for PRS CTs from 2012 to 2022. CTs were identified and assessed for PRO utilization. Summary statistics were performed, and Fisher's exact test was used for subgroup analysis. RESULTS: Of the 3609 studies initially identified, 154 were PRS CTs. Approximately half (80 studies) employed PROs, encompassing 13,190 participants, 95% (12,229) of whom were female. Among the CTs, 37 (48%) were in the field of reconstruction, while 25 (32%) were cosmetic. Pain (35%) and patient satisfaction (24%) were the most common primary outcomes. Validated PROs were the main outcome in 61% of these trials, with the visual analog scale (19%) and BREAST-Q (15%) as the top instruments. Funding was primarily private (34%) or not reported (49%). No significant trend in validated PRO usage was observed over the examined decade. CONCLUSIONS: The use of PROs is relevant for healthcare delivery and improvement as they provide insight into the efficacy of treatments from a patient-centered viewpoint. PROs are reported in just over half of PRS CTs, and within those CTs, the use of validated questionnaires is inconsistent. Therefore, emerging CTs should strive to incorporate PRO measures and utilize the existing validated tools to assess novel interventions and ensure that the data reported is objective.

Colloquium papers: Natural selection in a contemporary human population.

Our aims were to demonstrate that natural selection is operating on contemporary humans, predict future evolutionary change for specific traits with medical significance, and show that for some traits we can make short-term predictions about our future evolution. To do so, we measured the strength of selection, estimated genetic variation and covariation, and predicted the response to selection for women in the Framingham Heart Study, a project of the National Heart, Lung, and Blood Institute and Boston University that began in 1948. We found that natural selection is acting to cause slow, gradual evolutionary change. The descendants of these women are predicted to be on average slightly shorter and stouter, to have lower total cholesterol levels and systolic blood pressure, to have their first child earlier, and to reach menopause later than they would in the absence of evolution. Selection is tending to lengthen the reproductive period at both ends. To better understand and predict such changes, the design of planned large, long-term, multicohort studies should include input from evolutionary biologists.