Sex Differences in Alcohol Use: Is It All About Hormones?

Risky alcohol use and alcohol use disorders (AUD) are a rising problem in women, yet a major disparity in our understanding of what drives alcohol consumption in women remains. Historically biomedical research has focused on male subjects; however, recent increases in reporting of females, have highlighted major differences between the sexes. Here we review the current literature of the effect of gonadal steroid hormones (estrogens, androgens, and progestins), neurosteriods, and neurobiological factors on alcohol use in clinical and preclinical studies of both sexes. Further, we briefly discuss how fundamental sex differences in genetics, metabolism, neuroimmune, and stress responses may influence sex differences in alcohol intake. Comparing the sexes could aid in the discovery of novel therapeutics to treat AUD, and implementation of current treatment options in women.

Emerging GPCR targets for AUD: Insights from preclinical studies.

G protein-coupled receptors (GPCRs) are the largest group of membrane receptors in the central nervous system and one of the key proteins for signal transduction between cells. Currently, many drugs available on the market act via GPCRs and these receptors remain attractive targets for the treatment of brain disorders, including alcohol use disorder (AUD). Here, we describe the most recent literature, with a primary focus on the past 5 years, on GPCR targets with the potential for reducing behaviours associated with excessive alcohol intake. Specifically, we focus on preclinical evidence of compounds with attractive pharmacological profiles and potential for future clinical investigation for the treatment of AUD.

Metformin use and survival in people with ovarian cancer: A population-based cohort study from British Columbia, Canada.

OBJECTIVES: There is an active debate regarding whether metformin use improves survival in people with ovarian cancer. We examined this issue using methods designed to avoid immortal time bias-as bias that occurs when participants in a study cannot experience the outcome for a certain portion of the study time. METHODS: We used time-dependent analyses to study the association between metformin use for all 4,951 patients diagnosed with ovarian cancer in 1997 through 2018 in the province of British Columbia, Canada. Cox proportional hazards models were run to estimate the association between metformin and survival in the full cohort of ovarian cancer patients and among a cohort restricted to patients with diabetes. RESULTS: Metformin use was associated with a 17 % better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.83 (95 %CI 0.67, 1.02)), and a 16 % better ovarian cancer survival for serous cancers patient's cohort (aHR = 0.84 (95 %CI 0.66, 1.07)), although both were not significant. However, a statistically significant protective effect was observed when restricting to the diabetic cohort (aHR = 0.71 (95 %CI 0.54-0.91)), which was also seen among serous cancers (aHR = 0.73 (95 %CI 0.54-0.98)). CONCLUSION: Metformin use was associated with improved ovarian cancer survival. The lack of statistical significance in the full cohort may reflect that diabetes is associated with reduced cancer survival, and thus diabetes itself may offset the benefit of metformin when examining the full cohort. Future research should examine metformin use among non-diabetic ovarian cancer patients.

Integrating risks and benefits: pretransplant assessment and patient selection for heart transplantation in adult congenital heart disease.

PURPOSE OF REVIEW: The number of adult congenital heart disease (ACHD) patients presenting for consideration of heart transplantation continues to grow. Comprehensive pretransplant assessment and thoughtful patient selection are of critical importance to mitigate perioperative and posttransplant morbidity and mortality in this population. RECENT FINDINGS: There is increasing evidence that patient outcomes after the onset of heart failure in the ACHD population are poor while overall transplant outcomes for ACHD patients have improved over time. Delineation of factors associated with better versus worse posttransplant outcomes is an area of ongoing research. Several studies have found that delayed patient referral, anatomic complexity and the presence of noncardiac organ dysfunction may increase peri-transplant and posttransplant risk. SUMMARY: Pretransplant assessment and patient selection in ACHD patients should focus on mitigating perioperative and early posttransplant risk. Anatomic complexity, noncardiac organ dysfunction, and referral timing after the onset of heart failure can contribute to poor posttransplant outcomes and should inform patient selection.

Understanding sex differences and the translational value of models of persistent substance use despite negative consequences.

Persistent substance use despite negative consequences is a key facet of substance use disorder. The last decade has seen the preclinical field adopt the use of punishment to model adverse consequences associated with substance use. This has largely involved the pairing of drug use with either electric foot shock or quinine, a bitter tastant. Whilst at face value, these punishers may model aspects of the physical and psychological consequences of substance use, such models are yet to assist the development of approved medications for treatment. This review discusses progress made with animal models of punishment to understand the behavioral consequences of persistent substance use despite negative consequences. We highlight the importance of examining sex differences, especially when the behavioral response to punishment changes following drug exposure. Finally, we critique the translational value these models provide for the substance use disorder field.

A corpus of GA4GH Phenopackets: case-level phenotyping for genomic diagnostics and discovery.

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present phenopacket-store. Version 0.1.12 of phenopacket-store includes 4916 phenopackets representing 277 Mendelian and chromosomal diseases associated with 236 genes, and 2872 unique pathogenic alleles curated from 605 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

Determinants of sub-optimal glycemic control among patients enrolled in a medicine dispensing programme in KwaZulu-Natal: A cohort study, 2018-2021.

BACKGROUND:  The Central Chronic Medicines Dispensing and Distribution (CCMDD) programme facilitates clinically stable patients to collect their chronic medication from community-based pick-up points. AIM:  We determined baseline glycaemic control and rates and predictors of becoming sub-optimally controlled for type 2 diabetes mellitus (T2DM) CCMDD-enrolled patients. SETTING:  The setting of the study was eThekwini, KwaZulu-Natal, South Africa. METHODS:  We performed a cohort study (April 2018- December 2021). We linked T2DM CCMDD-enrolled patients to glycated haemoglobin (HbA1c) data from the National Health Laboratory Service. We selected patients optimally controlled at their baseline HbA1c, with ≥ 1 repeat-test available. We used Kaplan-Meier analysis to assess survival rates and extended Cox regression to determine associations between time to sub-optimal control (HbA1c 7%) and predictors. Adjusted hazard ratios (aHRs), 95% confidence interval (CI), and p-values are reported. RESULTS:  Of the 41145 T2DM patients enrolled in the CCMDD programme, 7960 (19%) had a HbA1c result available. Twenty-seven percent (2147/7960) were optimally controlled at their baseline HbA1c. Of those controlled at baseline, 695 (32%) patients had a repeat test available, with 35% (242/695) changing to sub-optimal status. The HbA1c testing frequency as per national guidelines was associated with a lower hazard of sub-optimal glycaemic control (aHR: 0.46; 95% CI: 0.24-0.91; p-value = 0.024). Patients prescribed dual-therapy had a higher hazard of sub-optimal glycaemic control (aHR: 1.50; 95% CI: 1.16-1.95; p-value = 0.002) versus monotherapy. CONCLUSIONS:  The HbA1c monitoring, in-line with testing frequency guidelines, is needed to alert the CCMDD programme of patients who become ineligible for enrolment. Patients receiving dual-therapy require special consideration.Contribution: Addressing identified shortfalls can assist programme implementation.

Development of a bioelectrical impedance analysis-based prediction equation for body composition of rural children aged 4-8 years in Myanmar.

Background: Reliable and accurate estimates of body composition are essential when studying the various health correlates of disease. Bioelectrical impedance analysis (BIA) is an affordable and feasible body composition assessment technique for clinical and field settings. Total body water (TBW) and hence fat-free mass is estimated by predictive regression algorithms using anthropometric measurements plus the resistance index. Aim: The study aimed to develop a BIA prediction equation for TBW in children in Myanmar using the deuterium dilution technique as the reference method. Methods: The study design was cross-sectional in a school setting with convenience sampling of participants. One hundred and two healthy children (57 boys and 45 girls) with aged 4 and 8 years participated; randomly divided into the prediction group (29 boys and 22 girls) and cross-validation group (28 boys and 23 girls). Whole-body impedance, anthropometric and TBW (by D2O dilution) measurements. The prediction equation was cross-validated using a split-group design and compared to published equations for contemporaneous populations. Results: TBW could be predicted by the following equation. TBW = 0.4597 * Weight (kg) + 0.1564 * Impedance index + 0.6075 (R2 = 0.891, P < 0.0001) with a correlation coefficient of 0.942 and limits of agreement of 0.98 kg TBW on cross-validation. Conclusions: This equation can be used to predict body composition in young (aged 4-8 years) children in Myanmar but because the age range of the participants in the present study was relatively narrow, more research in different age groups is required to establish its broader applicability.

Neuroanatomical distribution of fluorophores within adult RXFP3 Cre-tdTomato/YFP mouse brain.

Relaxin-family peptide 3 receptor (RXFP3) is activated by relaxin-3 in the brain to influence arousal and related functions, such as feeding and stress responses. Two transgenic mouse lines have recently been developed that co-express different fluorophores within RXFP3-expressing neurons: either yellow fluorescent protein (YFP; RXFP3-Cre/YFP mice) or tdTomato (RXFP3-Cre/tdTomato mice). To date, the characteristics of neurons that express RXFP3-associated fluorophores in these mice have only been investigated in the bed nucleus of the stria terminalis and the hypothalamic arcuate nucleus. To better determine the utility of these fluorophore-expressing mice for further research, we characterised the neuroanatomical distribution of fluorophores throughout the brain of these mice and compared this to the published distribution of Rxfp3 mRNA (detected by in situ hybridisation) in wildtype mice. Coronal sections of RXFP3-Cre/YFP (n = 8) and RXFP3-Cre/tdTomato (n = 8) mouse brains were imaged, and the density of fluorophore-expressing cells within various brain regions/nuclei was qualitatively assessed. Comparisons with our previously reported RXFP3 mRNA distribution revealed that of 212 brain regions that contained either fluorophore or RXFP3 mRNA, approximately half recorded densities that were within two qualitative measurements of each other (on a 9-point scale), including hippocampal dentate gyrus and amygdala subregions. However, many brain areas with likely non-authentic, false-positive, or false-negative fluorophore expression were also detected, including the cerebellum. Therefore, this study provides a guide to which brain regions should be prioritized for future study of RXFP3 in these mice, to better understand the neuroanatomy and function of this intriguing, neuronal peptide receptor.

Determination of resistance at zero and infinite frequencies in bioimpedance spectroscopy for assessment of body composition in babies.

Objective. Bioimpedance spectroscopy (BIS) is a popular technique for the assessment of body composition in children and adults but has not found extensive use in babies and infants. This due primarily to technical difficulties of measurement in these groups. Although improvements in data modelling have, in part, mitigated this issue, the problem continues to yield unacceptably high rates of poor quality data. This study investigated an alternative data modelling procedure obviating issues associated with BIS measurements in babies and infants.Approach.BIS data are conventionally analysed according to the Cole model describing the impedance response of body tissues to an appliedACcurrent. This approach is susceptible to errors due to capacitive leakage errors of measurement at high frequency. The alternative is to model BIS data based on the resistance-frequency spectrum rather than the reactance-resistance Cole model thereby avoiding capacitive error impacts upon reactance measurements.Main results.The resistance-frequency approach allowed analysis of 100% of data files obtained from BIS measurements in 72 babies compared to 87% successful analyses with the Cole model. Resistance-frequency modelling error (percentage standard error of the estimate) was half that of the Cole method. Estimated resistances at zero and infinite frequency were used to predict body composition. Resistance-based prediction of fat-free mass (FFM) exhibited a 30% improvement in the two-standard deviation limits of agreement with reference FFM measured by air displacement plethysmography when compared to Cole model-based predictions.Significance.This study has demonstrated improvement in the analysis of BIS data based on the resistance frequency response rather than conventional Cole modelling. This approach is recommended for use where BIS data are compromised by high frequency capacitive leakage errors such as those obtained in babies and infants.

Comparison of Volume Measurements and Bioimpedance Spectroscopy Using A Stand-on Device for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer related lymphedema (BCRL) may be assessed through objective measurement of limb swelling with common techniques including volumetric measurement using a tape measure or perometry, and measurement of extracellular water using bioimpedance spectroscopy (BIS). This study aimed to evaluate the performance of a stand-on BIS device for detection of BCRL, introduce a novel graphical method to compare volumetric and BIS methods alongside traditional specificity and sensitivity analysis, and determine and compare BIS thresholds with those published previously. Materials and Methods: Female participants with indocyanine green lymphography confirmed unilateral arm lymphedema (n = 197) and healthy controls (n = 267) were assessed using a cross-sectional study design. BIS and volumetric measures were obtained in a single session. Results: The BIS lymphedema index (L-Dex) method had a significantly higher sensitivity than the excess volume approach (area under the curve = 0.832 vs. 0.649, p = 0.0001). A threshold of L-Dex 6.5 had a higher true positive rate (70.6%) than L-Dex 10 (68.5%) although false positive rate increased from 0.4% to 2.6%. A threshold of 5% excess volume improved the true positive rate (68.5%) compared with 10% excess volume (49.7%) however the false positive rate increased to an unacceptable 47%. The L-Dex ranges in this study were not significantly different from previously published ranges. Conclusion: BIS was superior for identifying BCRL compared with volume measurements, reaffirming the value of this technique. However, it is recommended that BIS be used in conjunction with comprehensive evaluation of symptoms and clinical presentation. The proposed graphical method provides a simple and easily interpretable approach to compare and define concordance between the two commonly used methods for BCRL assessment namely limb volume and BIS L-Dex indices. The existing BIS (L-Dex) thresholds for presence of BCRL were also validated.

Development and validation of age-specific predictive equations for total energy expenditure and physical activity levels for older adults.

BACKGROUND: Predicting energy requirements for older adults is compromised by the underpinning data being extrapolated from younger adults. OBJECTIVES: To generate and validate new total energy expenditure (TEE) predictive equations specifically for older adults using readily available measures (age, weight, height) and to generate and test new physical activity level (PAL) values derived from 1) reference method of indirect calorimetry and 2) predictive equations in adults aged ≥65 y. METHODS: TEE derived from "gold standard" methods from n = 1657 (n = 1019 females, age range 65-90 y), was used to generate PAL values. PAL ranged 1.28-2.05 for males and 1.26-2.06 for females. Physical activity (PA) coefficients were also estimated and categorized (inactive to very active) from population means. Nonlinear regression was used to develop prediction equations for estimating TEE. Double cross-validation in a randomized, sex-stratified, age-matched 50:50 split, and leave one out cross-validation were performed. Comparisons were made with existing equations. RESULTS: Equations predicting TEE using the Institute of Medicine method are as follows: For males, TEE = -5680.17 - 17.50 × age (years) + PA coefficient × (6.96 × weight [kilograms] + 44.21 × height [centimeters]) + 1.13 × resting metabolic rate (RMR) (kilojoule/day). For females, TEE = -5290.72 - 8.38 × age (years) + PA coefficient × (9.77 × weight [kilograms] + 41.51 × height [centimeters]) + 1.05 × RMR (kilojoule/day), where PA coefficient values range from 1 (inactive) to 1.51 (highly active) in males and 1 to 1.44 in females respectively. Predictive performance for TEE from anthropometric variables and population mean PA was moderate with limits of agreement approximately ±30%. This improved to ±20% if PA was adjusted for activity category (inactive, low active, active, and very active). Where RMR was included as a predictor variable, the performance improved further to ±10% with a median absolute prediction error of approximately 4%. CONCLUSIONS: These new TEE prediction equations require only simple anthropometric data and are accurate and reproducible at a group level while performing better than existing equations. Substantial individual variability in PAL in older adults is the major source of variation when applied at an individual level.

Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation.

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

Longitudinal changes in body composition and diet after acute spinal cord injury.

OBJECTIVE: Spinal cord injury (SCI) is associated with low muscle mass and adiposity, however, to our knowledge, few studies have monitored the trajectory of changes over time. This study aimed to evaluate the timing, rate, magnitude, and site-specific changes in body composition and related changes in diet after SCI. METHODS: We assessed 39 patients with SCI. The analysis included five women. Of the participants, 51% had American Spinal Injury Association Impairment Scale (AIS) criteria A/B (motor complete) injuries, 18% had AIS C (sensory/motor incomplete) injuries, and 31% had AIS D (motor incomplete) injuries. The mean age of the patients was 43.2 y. They were 48.1 d post-injury and had their weight, diet, and body composition (bioimpedance spectroscopy) assessed every 2 wk. RESULTS: No significant linear changes were observed for any body composition measure. Total body fat mass (FM) changed 0.01 kg/2 wk when fitted to a quadratic model (P = 0.004), decreasing to week 15 and returning to baseline at week 28. Subgroup analysis revealed that arm lean tissue mass (LTM) increased in paraplegic versus tetraplegic participants (0.05 versus -0.01 kg/2 wk, P = 0.007). Participants with AIS A/B injuries lost FM (-0.17 kg; P = 0.010), whereas those with AIS C injuries gained appendicular LTM (ALTM; 0.15 kg; P = 0.017) and leg LTM (0.12 kg; P = 0.008) every 2 wk. Body composition remained stable in the AIS D group. Mean fortnightly changes were greater in the AIS A/B group than the C group for weight (mean difference -0.30 kg; P = 0.021), FM (-0.25 kg; P = 0.002), and leg LTM (-0.11 kg; P = 0.021) and AIS A/B versus D for FM (-0.42 kg; P = 0.013). Baseline energy and protein intakes were 2150 kcal (±741) and 102 g (±40) and decreased by 21.5 kcal (P = 0.016) and 1.3 g (P = 0.004) every 2 wk but were not associated with body composition changes. CONCLUSIONS: Neurologic level and severity of SCI, but not changes in diet, were the main determinants of heterogeneous body composition changes.

Facing Eating Disorder Fears: An Open Trial Adapting Prolonged Exposure to the Treatment of Eating Disorders.

Eating disorders (EDs) are maintained by core fears, which lead to avoidance behaviors, such as food avoidance or compensatory behaviors. Previously tested exposure-based treatments for EDs have generally focused on proximal outcomes (e.g., food), rather than addressing core fears (e.g., fear of weight gain and its consequences). The current study tested the feasibility and initial clinical efficacy of 10 sessions of imaginal and in vivo exposure for core ED fears (termed "Facing Eating Disorder Fears"), mainly fear of weight gain and its associated consequences. Participants were 36 adults with anorexia nervosa (AN), bulimia nervosa, or other specified feeding and eating disorders determined by semistructured diagnostic interviews. ED symptoms, fears, and body mass index (BMI) were assessed at pretreatment, posttreatment, and 1-month follow-up. Treatment involved 10 sessions of imaginal and in vivo exposure to ED fears in combination with in vivo exposures to feared and avoided situations as homework. ED symptoms and fears decreased from pre- to posttreatment and at 1-month follow-up. BMI increased significantly from pre- to posttreatment, particularly for those with AN. Effect sizes ranged from small to very large. ED symptoms and fears decreased and BMI increased following exposure. Increases in BMI occurred without any direct intervention on eating, suggesting that weight gain can be achieved without a specific focus on food during ED treatment. Facing Eating Disorder Fears may be a feasible stand-alone intervention for EDs. Future research must test comparative efficacy through randomized controlled trials.

Emphasizing Sexual Orientation and Gender Identity Data Capture for Improved Cardiovascular Care of the LGBTQ+ Population.

Importance: The rising self-identifying lesbian, gay, bisexual, transgender, and queer (LGBTQ+) population makes understanding the unique health care needs of sexual and gender minoritized patients an urgent one. The interaction between minority stress and cardiovascular disease has been well described among underrepresented minoritized populations. The underrepresentation of minoritized populations in clinical research is partly responsible for worse cardiovascular outcomes in these populations. The absence of sexual orientation and gender identity and expression (SOGIE) data makes it difficult to understand the cardiovascular health of LGBTQ+ adults, thereby widening health care disparities in this population. Advancing cardiovascular health equity for LGBTQ+ patients must begin with careful and accurate SOGIE data collection. Observations: Current SOGIE data capture remains inadequate despite federal mandates. Challenges in data collection include political and regulatory discrimination, patient/practitioner hesitancy, lack of supportive guidance on SOGIE data collection, improper terminology, regulatory inertia, and inadequate and often incorrect integration of SOGIE data into electronic health records (EHRs). Additional challenges include grouping participants as "others" for statistical significance. The inclusion of SOGIE data has demonstrated an impact in other fields like cancer survivorship and surgery. The same needs to be done for cardiology. Conclusions and Relevance: Potential solutions for improving much-needed SOGIE data collection include (1) implementing LGBTQ+ inclusive policies, (2) integrating SOGIE data into the EHR, (3) educating health care professionals on the relevance of SOGIE to patient-centered care, and (4) creating a diverse cardiovascular workforce. These steps can substantially enhance the ability to collect SOGIE data to address LGBTQ+ cardiovascular health care disparities.

Bioelectrical impedance analysis as a clinical marker of health status in adult patients with benign gastrointestinal disease: A systematic review.

BACKGROUND: Body composition reflects nutritional status, disease status and progression, and treatment responses. Mounting evidence supports the use of bioelectrical impedance analysis (BIA) as a non-invasive tool to assess body composition. Patients with benign gastrointestinal (GI) disease experience disease-related alterations in their body composition, and bioimpedance outcomes in patients with benign GI diseases have not previously been summarized. We aimed to evaluate BIA as a clinical body composition marker for benign GI diseases and describe its association with physical health status. METHODS: We systematically searched PubMed, Scopus, Web of Science, Embase, and CINAHL from inception to October 2023 (PROSPERO registration: CRD42021265866). Of 971 screened studies, 26 studies were included in the final analysis, comprising a total of 2398 adult patients with benign GI disease. The main outcome was raw impedance data. RESULTS: The most frequently reported BIA outcome was phase angle (PhA) (reported in 18 of 26 studies), followed by fat-free-mass (FFM) (reported in 13 of 26 studies). The consensus view of the included studies illustrates that BIA can be a useful tool for evaluating body composition in patients with benign GI diseases, and low PhA and FFM were associated with increased nutritional risk, abnormal physical characteristics, and increased mortality risk. CONCLUSION: To fully utilize BIA as a clinical marker of health in patients with benign GI disease, standardized protocols specific to this population are needed and prospective studies testing cut-offs and ranges, accuracy, and other raw BIA parameters for classifying disease status.

Heterotopic Ossification and Platelet-Rich Plasma in Core Muscle Injuries: A Single-Institution Experience Over 6 Years.

BACKGROUND: A 2015 study of platelet-rich plasma (PRP) for groin injuries in National Football League (NFL) players alerted the authors to the possibility that PRP is associated with heterotopic ossification (HO). The current study of athletes seen between 2014 and 2019 provides a more comprehensive analysis of that observation. PURPOSE/HYPOTHESIS: This report describes the early results of groin surgery for athletes who had experienced failed PRP therapy performed by different practitioners and with an assortment of PRP techniques. The primary goal of this cohort study was to determine short-term clinical outcomes after surgery of PRP-treated patients. It was hypothesized that previous PRP treatment would be associated with the presence of HO among patients with core muscle injuries (CMIs). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All athletes seen at 1 institution and identified at their first visit as having received PRP for a CMI were followed and compared with patients with a CMI who had not previously received PRP. Although in many cases HO was observed on clinical examination or imaging, HO was identified intraoperatively in all surgical cases and confirmed pathologically. Successful surgery was defined as return to play at previously high levels of performance or greater as determined by the athletes' own assessments. All patients who had received PRP were followed for ≥2 years. RESULTS: Among 3642 patients with a new CMI seen between 2014 and 2019, 68 (1.9%) patients developed HO within the core muscles and/or adjacent soft tissues. Of the 68 patients, 60 (88.2%) were men, and the mean age was 34.5 years. Of the 68 patients, 62 (91.2%) were athletes and 44 (64.7%) had been treated previously with PRP. HO was observed in 24 (0.7%) patients without previous PRP treatment. Three athletes who received PRP retired early from sports because of HO and scar issues. In total, 22 of 28 (78.6%) NFL players who received PRP developed HO, compared with 0 (0%) of 28 randomly selected, age-, position-, and injury-matched NFL players. After surgical repair, 3-month success rates were 67.9% and 96.4%, respectively, in the PRP and non-PRP groups (P = .006). By 6 months postoperatively, PRP-treated patients were back to similarly high success rates compared with the non-PRP cohort. Scar tissue issues played a prominent role in the relative delay in definitive success. CONCLUSION: The present, more comprehensive study confirms the previous preliminary analysis that treating CMIs with PRP may be associated with HO.