ABSTRACT
Genome-wide sequencing of human populations has revealed substantial variation among genes in the intensity of purifying selection acting on damaging genetic variants1. Although genes under the strongest selective constraint are highly enriched for associations with Mendelian disorders, most of these genes are not associated with disease and therefore the nature of the selection acting on them is not known2. Here we show that genetic variants that damage these genes are associated with markedly reduced reproductive success, primarily owing to increased childlessness, with a stronger effect in males than in females. We present evidence that increased childlessness is probably mediated by genetically associated cognitive and behavioural traits, which may mean that male carriers are less likely to find reproductive partners. This reduction in reproductive success may account for 20% of purifying selection against heterozygous variants that ablate protein-coding genes. Although this genetic association may only account for a very minor fraction of the overall likelihood of being childless (less than 1%), especially when compared to more influential sociodemographic factors, it may influence how genes evolve over time.
Subject(s)
Reproduction , Selection, Genetic , Chromosome Mapping , Female , Heterozygote , Humans , Male , Phenotype , Reproduction/geneticsABSTRACT
Mutations in the germline generates all evolutionary genetic variation and is a cause of genetic disease. Parental age is the primary determinant of the number of new germline mutations in an individual's genome1,2. Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 individuals with a hypermutated genome with between two and seven times more de novo single-nucleotide variants than expected. In most families (9 out of 12), the excess mutations came from the father. Two families had genetic drivers of germline hypermutation, with fathers carrying damaging genetic variation in DNA-repair genes. For five of the families, paternal exposure to chemotherapeutic agents before conception was probably a key driver of hypermutation. Our results suggest that the germline is well protected from mutagenic effects, hypermutation is rare, the number of excess mutations is relatively modest and most individuals with a hypermutated genome will not have a genetic disease.
Subject(s)
Genetic Diseases, Inborn , Germ Cells , Germ-Line Mutation , Age Factors , Genetic Diseases, Inborn/genetics , Germ-Line Mutation/genetics , Humans , Male , Mutagenesis/genetics , Mutation , Parents , Polymorphism, Single NucleotideABSTRACT
Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing1,2. Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.
Subject(s)
Cell Lineage/genetics , Embryo, Mammalian/cytology , Embryo, Mammalian/metabolism , Embryonic Development/genetics , Mutation , Brain/metabolism , Chromosomes, Human, Y/genetics , Clone Cells/metabolism , Germ-Line Mutation/genetics , Humans , Male , Mosaicism , Organ Specificity/genetics , Polymorphism, Single Nucleotide/geneticsABSTRACT
Over the course of an individual's lifetime, normal human cells accumulate mutations1. Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage2, and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.
Subject(s)
Germ Cells/metabolism , Germ-Line Mutation , Mutation Rate , Organ Specificity/genetics , Aged , Clone Cells/metabolism , Female , Health , Humans , Male , Microdissection , Middle Aged , Oxidative Stress , Spermatogonia/metabolismABSTRACT
Recent evidence from proteomics and deep massively parallel sequencing studies have revealed that eukaryotic genomes contain substantial numbers of as-yet-uncharacterized open reading frames (ORFs). We define these uncharacterized ORFs as novel ORFs (nORFs). nORFs in humans are mostly under 100 codons and are found in diverse regions of the genome, including in long noncoding RNAs, pseudogenes, 3' UTRs, 5' UTRs, and alternative reading frames of canonical protein coding exons. There is therefore a pressing need to evaluate the potential functional importance of these unannotated transcripts and proteins in biological pathways and human disease on a larger scale, rather than one at a time. In this study, we outline the creation of a valuable nORFs data set with experimental evidence of translation for the community, use measures of heritability and selection that reveal signals for functional importance, and show the potential implications for functional interpretation of genetic variants in nORFs. Our results indicate that some variants that were previously classified as being benign or of uncertain significance may have to be reinterpreted.
ABSTRACT
We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.
Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Florida/epidemiology , Hospitalization , Humans , SARS-CoV-2ABSTRACT
BACKGROUND: While COVID-19 immunization programs attempted to reach targeted rates, cases rose significantly since the emergence of the delta variant. This retrospective cohort study describes the correlation between antispike antibodies and outcomes of hospitalized, breakthrough cases during the delta variant surge. METHODS: All patients with positive SARS-CoV-2 polymerase chain reaction hospitalized at Mayo Clinic Florida from 19 June 2021 to 11 November 2021 were considered for analysis. Cases were analyzed by vaccination status. Breakthrough cases were then analyzed by low and high antibody titers against SARS-CoV-2 spike protein, with a cut-off value of ≥132 U/ml. Outcomes included hospital length of stay (LOS), need for intensive care unit (ICU), mechanical ventilation, and mortality. We used 1:1 nearest neighbor propensity score matching without replacement to assess for confounders. RESULTS: Among 627 hospitalized patients with COVID-19, vaccine breakthrough cases were older with more comorbidities compared to unvaccinated. After propensity score matching, the unvaccinated patients had higher mortality (27 [28.4%] vs. 12 [12.6%], p = 0.002) and LOS (7 [1.0-57.0] vs. 5 [1.0-31.0] days, p = 0.011). In breakthrough cases, low-titer patients were more likely to be solid organ transplant recipients (16 [34.0%] vs. 9 [12.3%], p = 0.006), with higher need for ICU care (24 [51.1%] vs. 22 [11.0%], p = 0.034), longer hospital LOS (median 6 vs. 5 days, p = 0.013), and higher mortality (10 [21.3%] vs. 5 [6.8%], p = 0.025) than high-titer patients. CONCLUSIONS: Hospitalized breakthrough cases were more likely to have underlying risk factors than unvaccinated patients. Low-spike antibody titers may serve as an indicator for poor prognosis in breakthrough cases admitted to the hospital.
Subject(s)
Antibodies, Viral , COVID-19 , Hospitalization , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Vaccines , Humans , Retrospective Studies , SARS-CoV-2ABSTRACT
Endovascular coiling has revolutionized intracranial aneurysm treatment; however, recurrence continues to represent a major limitation. The hydrogel coil was developed to increase packing density and improve neck healing and therefore decrease recurrence rates. In this paper, we review treatment outcomes of first- (1HCs) and second-generation (2HCs) hydrogel coils and compare them to those of bare platinum coils (BPC). A query of multiple databases was performed. Articles with at least 10 aneurysms treated with either 1HC or 2HC were selected for analysis. Collected data included aneurysm size, rupture status, initial occlusion, initial residual neck/aneurysm, packing density, mortality, morbidity, recurrence, and retreatment rates. The primary endpoint was recurrence at final follow-up. Secondary endpoints included residual neck and dome rates as well as procedure-related complications and functional dependence at final follow-up. Studies that compared 1HC to BPC showed significant lower recurrence (24% vs. 30.8%, p = 0.02) and higher packing density (58.5% vs. 24.1%, p < 0.001) in 1HC but no significant difference in initial occlusion rate (p = 0.08). Studies that compared 2HC to BPC showed lower recurrence (6.3% vs. 14.3%, p = 0.007) and retreatment rates (3.4% vs. 7.7%, p = 0.010) as well as higher packing density (36.4% vs. 29.2%, p = 0.002) in 2HC, with similar initial occlusion rate (p = 0.86). The rate of complications was not statistically different between HC (25.5%) and BPC (22.6%, p = 0.06). Based on our review, the 1HC and 2HC achieved higher packing density and lower recurrence rates compared to BPC. The safety profile was similar between both groups.
Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm , Humans , Hydrogels/therapeutic use , Intracranial Aneurysm/surgery , Platinum , Treatment OutcomeABSTRACT
Early pancreas loss in simultaneous pancreas-kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post-transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18-1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23-3.06, p = 0.77). One- and 2-year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.
Subject(s)
Kidney Transplantation , Pancreas Transplantation , Allografts , Graft Rejection/etiology , Graft Survival , Humans , Kidney , Kidney Transplantation/adverse effects , PancreasABSTRACT
BACKGROUND: During the past decade, a growing number of women have pursued medical careers, including in plastic surgery. However, female physicians have tended to be underrepresented in a variety of leadership roles in their respective specialties. OBJECTIVES: The authors sought to evaluate the representation of female plastic surgeons on the editorial boards of high-impact plastic surgery journals. METHODS: The gender of editorial board members on 3 high-impact plastic surgery journals was evaluated from 2009 and 2018. The number of women on each editorial board was then compared with the number of board-certified female plastic surgeons (BCFPS) and board-certified female academic plastic surgeons (BCFAPS), a subgroup of BCFPS. RESULTS: There were 555 unique editorial board members from Plastic and Reconstructive Surgery, Aesthetic Surgery Journal, and Annals of Plastic Surgery from 2009 to 2018. During that period, 72 editors (13.0%) were women. At the beginning of the study, there were significantly fewer female editors than expected based on proportionate representation of BCFPS and BCFAPS to all board-certified plastic surgeons (Pâ =â 0.007 and 0.007, respectively). During the study, there was a 177% increase in women holding editorial board positions. At study end, women were adequately represented on all 3 editorial boards compared with their population data (BCFPS and BCFAPS). CONCLUSIONS: During the 10 years of this study (2009-2018), editorial boards have overcome the underrepresentation of women on, and female plastic surgeons are currently adequately represented on the top 3 high-impact journal editorial boards.
Subject(s)
Physicians, Women , Plastic Surgery Procedures , Surgeons , Surgery, Plastic , Female , Humans , United StatesABSTRACT
Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
Subject(s)
HLA Antigens/genetics , HLA-DQ alpha-Chains/genetics , Streptococcal Infections/immunology , Adult , Case-Control Studies , Female , Gene Frequency , Genes, MHC Class II , Genetic Predisposition to Disease/genetics , HLA Antigens/immunology , HLA-DQ alpha-Chains/metabolism , Haplotypes , Histocompatibility Antigens Class I/genetics , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Risk Factors , Streptococcus pyogenes/genetics , Streptococcus pyogenes/pathogenicityABSTRACT
PURPOSE: To assess whether labral size is predictive of labral repair failure or shows an association with patient outcomes after hip arthroscopy. METHODS: We performed a retrospective chart review of patients who underwent arthroscopic hip labral repair. Labral size was measured in 4 quadrants with an arthroscopic probe. The average size across torn labral segments was assessed for failure as determined by the change in patient-reported outcomes, the rate at which subjects achieved the minimal clinically important difference and patient acceptable symptomatic state, and the need for additional surgery. Outcomes were evaluated for any continuous correlation as well as significant differences between the middle 50% of labral sizes and classes of labral sizes derived from upper and lower quartile and decile ranges. Included hips were those from patients aged between 18 and 55 years with 2-year postoperative follow-up and lateral center-edge angles between 25° and 40°. RESULTS: The study included 571 hips. Labral width did not show a significant difference between hips requiring revision and those not requiring revision (P = .4054). No significant correlation was found between labral width and the change in the International Hip Outcome Tool 12 score (R2 = 0.05780), modified Harris Hip Score (R2 = 0.19826), or Nonarthritic Hip Score (R2 = 0.23543) from preoperatively to 2 years postoperatively. Hips with labral sizes in the upper decile of our cohort showed significantly decreased improvement in the International Hip Outcome Tool 12 score (P = .0287) and Nonarthritic Hip Score (P = .0490) compared with the middle 50% of labral sizes. No statistically significant difference was found in the rate at which the groups achieved the minimal clinically important difference or patient acceptable symptomatic state. CONCLUSIONS: Hypertrophic labra in the largest 10th percentile showed lower postoperative outcome scores. However, no detectable clinical benefit was found in terms of patient-perceived clinical difference or acceptable symptomatic state. For most patients, labral size does not appear to significantly alter patient outcomes or the need for arthroplasty. LEVEL OF EVIDENCE: Level IV, retrospective case series.
Subject(s)
Acetabulum/anatomy & histology , Acetabulum/surgery , Arthroscopy/methods , Adolescent , Adult , Arthroplasty, Replacement, Hip/statistics & numerical data , Cohort Studies , Female , Hip/surgery , Hip Joint/surgery , Humans , Linear Models , Male , Middle Aged , Minimal Clinically Important Difference , Patient Reported Outcome Measures , Patient Satisfaction , Postoperative Period , Retrospective Studies , Risk Assessment , Treatment Outcome , Young AdultABSTRACT
PURPOSE: The purpose of this investigation is to assess the incidence of rotator cuff tears in cases of calcific tendonitis and evaluate for differences in the incidences of rotator cuff tears by magnetic resonance imaging (MRI) between calcific lesions of different morphology, size, or location. METHODS: This single-center study involved a retrospective chart review searching for patients from January 2010 to April 2017 with a diagnosis of calcific tendonitis of the shoulder based on review of all MRI reads done on patients with shoulder pain. Anteroposterior radiographic and MRI studies were reviewed by a musculoskeletal radiologist to assess calcific tendonitis morphology, size, distance from cuff insertion, and any rotator cuff tear. An additional radiologist evaluated calcific tendonitis size, morphology, and location to evaluate the reliability of these variables. RESULTS: In the final cohort of 318 shoulders with calcific tendonitis, the incidence of concomitant rotator cuff tears was 56%. Of all 177 tears, 164 (93%) were partial-thickness and 13 (7%) were complete. Type III calcification morphology (cloudy with soft contour) was most frequently associated with rotator cuff tears and demonstrated an increased odds of tear by a factor of 1.8 (CI95% 1.1-2.9).There was no statistical difference regarding calcification size or location prognosticating rotator cuff tears or tear thickness. Intraclass correlation coefficients for calcification size, morphology, and location were 0.78, 0.30, and 0.50, respectively. CONCLUSIONS: The incidence of rotator cuff tears in cases of calcific tendonitis in this cohort of patients who underwent MRI is higher than previously reported. Cloudy-appearing calcified lesions showed a significant association with rotator cuff tears with an odds ratio of 1.8. Specific locations or sizes of calcified lesions do not appear to be reliable factors to predict concomitant rotator cuff tears. Interobserver agreement for these radiographic variables ranged from fair to substantial and prompt a cautious interpretation of these results. LEVEL OF EVIDENCE: IV Retrospective Case Series.
Subject(s)
Calcinosis/diagnostic imaging , Magnetic Resonance Imaging , Rotator Cuff Injuries/diagnostic imaging , Tendinopathy/diagnostic imaging , Adult , Aged , Aged, 80 and over , Calcinosis/classification , Female , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective StudiesABSTRACT
BACKGROUND: To lessen the financial burden of total joint arthroplasty (TJA) and encourage shorter hospital stays, the Centers for Medicare and Medicaid Services (CMS) recently removed TKA from the inpatient-only list. This policy change now requires providers and institutions to apply the two-midnight rule (TMR) to short-stay (1-midnight) inpatient hospitalizations (SSIH). METHODS: The National Inpatient Sample from 2012 through 2016 was used to analyze trends in length of stay following elective TJA. Using publically-available policy documentation, published median Medicare payments, and National Inpatient Sample hospital costs, we analyzed the application of the TMR to SSIHs and compared the results to the previous policy environment. Specifically, we modeled 3 scenarios for all 2016 Medicare SSIHs: (1) all patients kept an extra midnight to satisfy the TMR, (2) all patients discharged as an outpatient, and (3) all patients discharged as an inpatient. RESULTS: The overall percentage of Medicare SSIHs increased significantly from 2.7% in 2012 to 17.8% in 2016 (P < .0001). Scenario 1 resulted in no change in out-of-pocket (OOP) costs to patients, no change in CMS payments, and hospital losses of $117.0 million. Scenario 2 resulted in no change in patient OOP costs, reduction in payments from CMS of $181.8 million, and hospital losses of $357.3 million. Scenario 3 resulted in no change in patient OOP costs, no change in CMS payments, and an estimated $1.71 billion of SSIH charges at risk to hospitals for audit. CONCLUSION: The results of this analysis reveal the conflict between length of stay trends following TJA and the imposition of the TMR.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Aged , Centers for Medicare and Medicaid Services, U.S. , Humans , Medicaid , Medicare , United StatesABSTRACT
BACKGROUND: Osteoarthritis (OA) is the leading cause of disability among adults in the United States. As the diagnosis is based on the accurate interpretation of knee radiographs, use of a convolutional neural network (CNN) to grade OA severity has the potential to significantly reduce variability. METHODS: Knee radiographs from consecutive patients presenting to a large academic arthroplasty practice were obtained retrospectively. These images were rated by 4 fellowship-trained knee arthroplasty surgeons using the International Knee Documentation Committee (IKDC) scoring system. The intraclass correlation coefficient (ICC) for surgeons alone and surgeons with a CNN that was trained using 4755 separate images were compared. RESULTS: Two hundred eighty-eight posteroanterior flexion knee radiographs (576 knees) were reviewed; 131 knees were removed due to poor quality or prior TKA. Each remaining knee was rated by 4 blinded surgeons for a total of 1780 human knee ratings. The ICC among the 4 surgeons for all possible IKDC grades was 0.703 (95% confidence interval [CI] 0.667-0.737). The ICC for the 4 surgeons and the trained CNN was 0.685 (95% CI 0.65-0.719). For IKDC D vs any other rating, the ICC of the 4 surgeons was 0.713 (95% CI 0.678-0.746), and the ICC of 4 surgeons and CNN was 0.697 (95% CI 0.663-0.73). CONCLUSIONS: A CNN can identify and classify knee OA as accurately as a fellowship-trained arthroplasty surgeon. This technology has the potential to reduce variability in the diagnosis and treatment of knee OA.
Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Surgeons , Adult , Fellowships and Scholarships , Humans , Neural Networks, Computer , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/surgery , Retrospective Studies , United StatesABSTRACT
BACKGROUND: Deep venous thrombosis and pulmonary embolism, collectively known as venous thromboembolism (VTE), are among the most feared yet preventable surgical complications. Although many recommendations exist to reduce the risk of VTE, the actual VTE prophylaxis practices of aesthetic plastic surgeons remain unknown. OBJECTIVES: The primary aim of this study was to elucidate plastic surgeons' experiences with VTE, preferred VTE prophylaxis practices, and areas in which VTE prevention may be improved. METHODS: Members of The Aesthetic Society were queried via a 55-question electronic survey regarding their experience with VTE as well as their VTE prophylaxis practices. Anonymous responses were collected and analyzed by the Mayo Clinic Survey Research Center. RESULTS: The survey was sent to 1729 of The Aesthetic Society members, of whom 286 responded. Fifty percent, 38%, and 6% of respondents reported having had a patient develop a deep venous thrombosis, pulmonary embolism, or death secondary to VTE, respectively. Procedures performed on the back or trunk were associated with the highest rate of VTE. Lower extremity procedures were associated with a significantly higher rate of VTE than expected. Over 90% of respondents reported utilizing a patient risk stratification assessment tool. Although at least one-half of respondents reported that the surgical facility in which they operate maintains some form of VTE prophylaxis protocol, 39% self-reported nonadherence with these protocols. CONCLUSIONS: Considerable variability exists in VTE prophylaxis practices among The Aesthetic Society responders. Future efforts should simplify guidelines and tailor prophylaxis recommendations to the aesthetic surgery population. Furthermore, education of plastic surgeons performing aesthetic surgery and more diligent surgical venue supervision is needed to narrow the gap between current recommendations and actual practices.
Subject(s)
Surgeons , Surgery, Plastic , Venous Thromboembolism , Humans , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Practice Patterns, Physicians' , Risk Factors , Surgery, Plastic/adverse effects , Surveys and Questionnaires , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & controlABSTRACT
AIMS/HYPOTHESIS: Circulating succinate and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were recently shown to promote brown adipocyte thermogenesis and protect against metabolic disorders in rodents. This study aimed to evaluate the associations between plasma levels of these metabolites and adiposity and metabolic profile in humans. METHODS: Fasting plasma succinate and 12,13-diHOME levels were quantified using ultra HPLC-tandem MS in 2248 individuals (50% female, mean age 41.3 ± 5.9 years, mean BMI 26.1 ± 4.6 kg/m2) in addition to fasting plasma biochemistry. Total and regional adiposity were assessed with dual-energy x-ray absorptiometry. An age- and sex-adjusted linear regression model was used to determine the associations between succinate and 12,13-diHOME levels and body composition and metabolic profile. Two-sample Mendelian randomisation was used to assess the associations between genetically determined BMI and metabolic traits with circulating plasma succinate and 12,13-diHOME. RESULTS: A one-SD higher plasma succinate and 12,13-diHOME concentration was associated with a 0.15 SD (95% CI 0.28, 0.03) and 0.08 SD (0.15, 0.01) lower total fat mass respectively. Additionally, a one-SD higher plasma 12,13-diHOME level was associated with a 0.09 SD (0.16, 0.02) lower fasting plasma insulin and 0.10 SD (0.17, 0.04) lower plasma triacylglycerol. In Mendelian randomisation analyses, genetically determined higher BMI, fasting hyperinsulinaemia and elevated lipid levels were not associated with changes in either plasma succinate or plasma 12,13-diHOME concentrations. No indications of bias due to directional pleiotropy were detected in the Mendelian randomisation analyses. CONCLUSIONS/INTERPRETATION: Our findings tentatively suggest that plasma succinate and 12,13-diHOME may play a role in the regulation of energy metabolism and brown adipose tissue activation in humans. Further studies encompassing direct assessment of brown adipose tissue activity and dietary supplementation are necessary to investigate the potential beneficial effects of these metabolites on systemic metabolism.
Subject(s)
Adiposity , Oleic Acids/metabolism , Succinic Acid/chemistry , Thermogenesis , Adipocytes/metabolism , Adipose Tissue, Brown/metabolism , Adult , Body Mass Index , Cross-Sectional Studies , Energy Metabolism , Female , Humans , Insulin Resistance , Male , Mendelian Randomization Analysis , Middle Aged , ObesityABSTRACT
PURPOSE: To determine the degree of correlation of radiographic measurements, degree of correlation of intraoperative pathology, and difference in outcomes between sides of patients requiring staged bilateral hip arthroscopy. METHODS: Two high-volume hip preservation centers retrospectively reviewed hip preservation databases for staged bilateral hip arthroscopies conducted between 2008 and 2015. Patients were separated into those who presented with bilateral hip pain and those that presented with unilateral pain and developed contralateral pain >2 years later. Patients were analyzed for radiographic correlation (alpha angle, lateral center edge angle, anterior center edge angle, magnetic resonance imaging alpha angle, Tönnis grade) and correlation of intraoperative pathology (acetabular labrum articular disruption grade, Outerbridge grade/location, Villar class ligamentum teres tears, labral tear location, symmetry of Seldes tear types, and the differences between operative procedures). Patient-reported outcomes were analyzed (modified Harris Hip Score, Non-Arthritic Hip Score, International Hip Outcome Tool-12, hip outcome score-sport specific subscale, visual analog scale, patient satisfaction). Correlative tests included Pearson and Spearman; univariate and multivariate analysis for differences included χ-square test and Student t tests for ordinal and continuous variables respectively. RESULTS: A total of 133 of 2,705 patients (4.6%) underwent bilateral hip arthroscopy. Radiographic alpha angle, magnetic resonance imaging alpha angle, lateral center edge angle, and anterior center edge angle demonstrated strong correlation (Pearson's coefficients 0.651, 0.648, 0.644, 0.667, respectively, P < .0001). Tönnis grade was weakly correlated (Pearson's coefficient 0.286, P = .001). Intraoperative pathology was moderately correlated (Pearson's coefficients for acetabular Outerbridge location, 0.300, P = .0170; acetabular labrum articular disruption, 0.490, P < .0001; acetabular Outerbridge; 0.530; P < .0001; femoral head Outerbridge, 0.459, P < .0001; Villar class, 0.393, P < .0001; and labral tear location, 0.468, P < .0001). Labral tear Seldes type was compared with Bowker's symmetry test and there was no significant difference between sides. There were no significant differences in surgical interventions performed between sides. Patients with bilateral hip arthroscopies significantly improved in all measured patient-reported outcomes and had a high patient satisfaction after both procedures. Final patient-reported outcomes and change in patient-reported outcomes were not different between procedures; follow up ranged from 3 months to 8 years. CONCLUSIONS: This study demonstrated an incidence of 4.6% of patients who require bilateral hip arthroscopy. These patients can expect significant improvement after surgical intervention. Patients that had 1 side done gained similar improvement when the contralateral side was performed. Preoperative radiographic, intraoperative pathology, and procedures performed were similar between hips. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
Subject(s)
Arthroscopy/methods , Femoracetabular Impingement/surgery , Hip Joint/surgery , Acetabulum/surgery , Adult , Arthroscopy/adverse effects , Cartilage, Articular/surgery , Female , Femoracetabular Impingement/complications , Femoracetabular Impingement/diagnostic imaging , Femoracetabular Impingement/pathology , Hip Joint/diagnostic imaging , Hip Joint/pathology , Humans , Male , Pain/etiology , Pain Measurement/methods , Patient Reported Outcome Measures , Patient Satisfaction , Postoperative Complications/etiology , Radiography , Retrospective Studies , Round Ligaments/injuries , Rupture , Treatment Outcome , Visual Analog ScaleABSTRACT
BACKGROUND: The American Academy of Orthopedic Surgeons clinical practice guideline currently recommends repeat joint aspiration when workup of periprosthetic joint infection (PJI) reveals conflicting data. This guideline is based on a single study of 31 patients published 25 years ago. We sought to determine the correlation between first and second aspirations and factors that may play a role in variability between them. METHODS: Sixty patients with less than 90 days between aspirations and no intervening surgery were identified at our institution and classified by Musculoskeletal Infection Society (MSIS) criteria as infected, not infected, or not able to determine after both aspirations. Culture results from both aspirations were recorded. The rates of change and correlation in clinical diagnosis and culture results between aspirations were determined. RESULTS: Repeat aspiration changed the diagnosis in 26 cases (43.3%, 95% confidence interval 31.6-55.9, kappa coefficient 0.32, P < .001), and the culture results in 25 cases (41.7%, 95% confidence interval 30.1-54.3, kappa coefficient 0.27, P < .01). Among patients initially MSIS negative, the proportion who changed to MSIS positive was greater for those with a history of prior PJI compared to those without (66.7% vs 0%, P < .05), and the first aspiration mean volume was higher for those changed to MSIS positive compared to those that remained MSIS negative (12.0 vs 3.0 mL, P < .01). Among patients initially MSIS positive, the proportion of patients who changed to MSIS negative was greater for those with a history of adverse local tissue reaction (ALTR) to metal debris compared to patients without suspicion of ALTR (100% vs 7.7%, P < .05). CONCLUSION: Repeat aspiration is particularly useful in patients with conflicting clinical data and prior history of PJI, suspicion of ALTR, or with high clinical suspicion of infection.
Subject(s)
Arthritis, Infectious/diagnosis , Hip Prosthesis/adverse effects , Prosthesis-Related Infections/diagnosis , Aged , Aged, 80 and over , Arthritis, Infectious/microbiology , Biopsy, Needle/statistics & numerical data , Female , Hip Joint/microbiology , Humans , Male , Middle Aged , Prosthesis-Related Infections/microbiology , Retrospective StudiesABSTRACT
BACKGROUND: Relationships between companies in the biomedical industry and authors submitting scientific articles for publication has been an issue of some concern for many years. It has been frequently demonstrated that these financial relationships can influence the manner in which research findings are presented. The National Physician Payment Transparency Program, also known as the Open Payment Program or the Sunshine Act, was legislated to expose potential conflicts of interest (COIs). Likewise, most peer-reviewed journals require disclosure of any potential COIs. OBJECTIVES: The purpose of this paper was to compare the information published in the Open Payment Database to authors' self-disclosed COIs in their published articles. METHODS: An analysis was performed by one of the authors (P.S.B.) of all articles published in Aesthetic Surgery Journal (ASJ) and Plastic and Reconstructive Surgery (PRS) from August 2013 through December 2016. Financial disclosures reported in these articles were compared with the physician payment information provided by the biomedical industry and published in the Open Payments Database in 2013 and 2018. RESULTS: A total of 1346 articles were included in the study, from which 320 authors and 899 total authorships were eligible for analysis. Out of 782 authorships with noted discrepancies, 96% were related to potential COIs found in the Open Payments database but not disclosed in the journal publication. CONCLUSIONS: Our data suggest major discordance between authors' self-reported COIs in the plastic surgery literature and industry payments published in the Open Payments database.