Prosocial motives underlie scientific censorship by scientists: A perspective and research agenda.

Science is among humanity's greatest achievements, yet scientific censorship is rarely studied empirically. We explore the social, psychological, and institutional causes and consequences of scientific censorship (defined as actions aimed at obstructing particular scientific ideas from reaching an audience for reasons other than low scientific quality). Popular narratives suggest that scientific censorship is driven by authoritarian officials with dark motives, such as dogmatism and intolerance. Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups. This perspective helps explain both recent findings on scientific censorship and recent changes to scientific institutions, such as the use of harm-based criteria to evaluate research. We discuss unknowns surrounding the consequences of censorship and provide recommendations for improving transparency and accountability in scientific decision-making to enable the exploration of these unknowns. The benefits of censorship may sometimes outweigh costs. However, until costs and benefits are examined empirically, scholars on opposing sides of ongoing debates are left to quarrel based on competing values, assumptions, and intuitions.

Epigenetic state determines inflammatory sensing in neuroblastoma.

Immunotherapy has revolutionized cancer treatment, but many cancers are not impacted by currently available immunotherapeutic strategies. Here, we investigated inflammatory signaling pathways in neuroblastoma, a classically "cold" pediatric cancer. By testing the functional response of a panel of 20 diverse neuroblastoma cell lines to three different inflammatory stimuli, we found that all cell lines have intact interferon signaling, and all but one lack functional cytosolic DNA sensing via cGAS-STING. However, double-stranded RNA (dsRNA) sensing via Toll-like receptor 3 (TLR3) was heterogeneous, as was signaling through other dsRNA sensors and TLRs more broadly. Seven cell lines showed robust response to dsRNA, six of which are in the mesenchymal epigenetic state, while all unresponsive cell lines are in the adrenergic state. Genetically switching adrenergic cell lines toward the mesenchymal state fully restored responsiveness. In responsive cells, dsRNA sensing results in the secretion of proinflammatory cytokines, enrichment of inflammatory transcriptomic signatures, and increased tumor killing by T cells in vitro. Using single-cell RNA sequencing data, we show that human neuroblastoma cells with stronger mesenchymal signatures have a higher basal inflammatory state, demonstrating intratumoral heterogeneity in inflammatory signaling that has significant implications for immunotherapeutic strategies in this aggressive childhood cancer.

Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice.

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.

Selective Liquid-Liquid Extraction of Thorium(IV) from Rare-Earth Element Mixtures.

One of the major challenges in processing rare-earth element (REE) materials arises from the large amounts of radioactive thorium (Th) that are often found within REE minerals, encouraging enhanced metal separation procedures. We report here a study aimed at developing improved systems for REE processing with the goal of efficient extraction of Th(IV) from acidic solution. A tripodal ligand, TRPN-CMPO-Ph, was prepared that utilizes carbamoylmethylphosphine oxide (CMPO) chelators tethered to a tris(3-aminopropyl)amine (TRPN) capping scaffold. The ligand and its metal complexes were characterized by using elemental analysis, NMR, Fourier transform infrared spectroscopy, mass spectrometry, and luminescence spectroscopy. Using a liquid-liquid metal extraction protocol, TRPN-CMPO-Ph selectively extracts Th(IV) at an efficiency of 79% from a mixture of Th(IV), UO22+, and all rare-earth metal cations (except promethium) dissolved in nitric acid into an organic solvent. Th(IV) extraction selectivity is maintained upon extraction from a mixture that approximates a typical monazite leach solution containing several relevant lanthanide ions, including two ions at higher concentration relative to Th(IV). Comparative studies with a tris(2-aminoethyl)amine (TREN)-capped derivative are presented and support the need for a larger TRPN capping scaffold in achieving Th(IV) extraction selectivity.

'Low' faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patients.

AIM: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. METHOD: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 µg Hb/g faeces. RESULTS: A single threshold of 10 µg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 µg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. CONCLUSION: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.

Psychometric Evidence That Paraphilia Is a Natural Kind.

Is the category paraphilia a natural kind? That is, do different paraphilias share anything scientifically interesting or are they classified together because they are unusual and sometimes problematic? We investigated this question systematically in 11 samples of paraphilic males (N = 4,617) and 11 samples of control males (N = 1,494). Primary data consisted of responses to the 11-item Paraphilic Interests Scale. Contrary to our initial hypothesis, the scale mean was similar for paraphilic and control samples. Using logistic regression and the same items, we derived three highly correlated measures that robustly discriminated paraphilic and control samples (ds ranging from 0.86 to 0.92). These successful measures capitalized on the unanticipated fact that some items (especially those assessing transvestism and masochistic humiliation) were positively associated with membership in paraphilic samples, while others (especially those assessing voyeurism) were negatively associated with such membership. Subsequent analyses focused on one of the measures, the Paraphilic Interests Scale Contrast (PISC). Consistent with prior findings distinguishing paraphilias and homosexual orientation, PISC was not elevated among homosexual males compared with heterosexual males among the control groups. Within four paraphilic samples, PISC was positively associated with additional paraphilic phenomena. Results provide tentative support for both the proposition that paraphilia is a natural kind and the usefulness of PISC as a measure of paraphilia.

Detransition and Desistance Among Previously Trans-Identified Young Adults.

Persons who have renounced a prior transgender identification, often after some degree of social and medical transition, are increasingly visible. We recruited 78 US individuals ages 18-33 years who previously identified as transgender and had stopped identifying as transgender at least six months prior. On average, participants first identified as transgender at 17.1 years of age and had done so for 5.4 years at the time of their participation. Most (83%) participants had taken several steps toward social transition and 68% had taken at least one medical step. By retrospective reports, fewer than 17% of participants met DSM-5 diagnostic criteria for Gender Dysphoria in Childhood. In contrast, 53% of participants believed that "rapid-onset gender dysphoria" applied to them. Participants reported a high rate of psychiatric diagnoses, with many of these prior to trans-identification. Most participants (N = 71, 91%) were natal females. Females (43%) were more likely than males (0%) to be exclusively homosexual. Participants reported that their psychological health had improved dramatically since detransition/desistance, with marked decreases in self-harm and gender dysphoria and marked increases in flourishing. The most common reason given for initial trans-identification was confusing mental health issues or reactions to trauma for gender dysphoria. Reasons for detransition were more likely to reflect internal changes (e.g., the participants' own thought processes) than external pressures (e.g., pressure from family). Results suggest that, for some transgender individuals, detransition is both possible and beneficial.

Outcomes of Total Knee Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Matched Cohort Study.

BACKGROUND: Total knee arthroplasty (TKA) is an excellent surgical option for patients who have end-stage knee osteoarthritis. While rates of major postoperative complications have steadily decreased with modern implants and operative techniques, contemporary outcome data for patients who have Ehlers-Danlos syndrome (EDS) are scarce. The goal of this study was to compare complication rates after primary TKA in patients who have EDS versus matched controls. METHODS: A large administrative database was used to identify patients who underwent primary TKA from 2009 to 2020. Patients who had a diagnosis of EDS were identified by International Classification of Diseases Coding. Propensity scores were utilized to match these patients with controls at a 1:4 ratio based on age, sex, and various comorbidities. Multivariable logistic regression analysis was used to compare the rates of medical and surgical complications at 90 days and 2 years. A total of 188 patients who had EDS and 752 controls were included in this study. RESULTS: After univariate analysis, Ehlers-Danlos patients exhibited significantly higher rates of wound complications (4.8 versus 0.9%, P = .001) at 90 days. When adjusted for comorbidities, Ehlers-Danlos patients still exhibited significantly increased odds of developing wound complications (odds ratio: 7.06; P < .001). CONCLUSIONS: Patients who have EDS undergoing TKA exhibited significantly higher rates of wound complications within 90 days postoperatively compared to matched controls. Rates of instability, manipulation under anesthesia, periprosthetic joint infection, aseptic loosening, and aseptic revision arthroplasty did not significantly differ between the cohorts. This study found generally favorable short-term outcomes of TKA in this population; however, the inability to control for implant type and other confounding variables may have influenced the lack of difference in complication rates at 2 years. Surgeons should monitor for the potentially increased risk of wound complications and consider the possible need for increased constraint in this population during preoperative planning.

Outcomes of Total Hip Arthroplasty in Patients Who Have Ehlers-Danlos Syndrome: A Matched Cohort Study.

BACKGROUND: Total hip arthroplasty (THA) is an effective surgical treatment for severe osteoarthritis of the hip. While THA is considered a reliable and safe procedure, outcome data on patients who have Ehlers-Danlos syndrome (EDS) is limited. The purpose of this study was to compare rates of postoperative complications after primary THA in patients who have EDS against matched controls. METHODS: A large national database was searched to identify patients who underwent THA between 2009 and 2020. Patients younger than 18 years, those who have a history of prior THA, and those undergoing THA for a hip fracture were excluded from analysis. Propensity score matching was utilized to match patients who had EDS with patients who did not have EDS at a 1:4 ratio. Rates of medical and surgical complications at 90 days and 2 years were queried and compared between the cohorts using multivariable logistic regression. We identified 118 patients who had EDS and underwent primary THA, who were then matched with 418 controls. RESULTS: At 90 days, the EDS cohort had greater rates of dislocation (8.5 versus 3.8%, P = 0.038). At 2 years, the EDS cohort had greater odds of dislocation (OR [odds ratio] 2.47, P = 0.018), aseptic loosening (OR 6.91, P = 0.002), and aseptic revision (OR 2.66, P = 0.02). CONCLUSIONS: Patients who have EDS possess significantly higher odds of complications after THA compared to matched controls, including dislocation, aseptic loosening, and aseptic revision. Careful surgical planning in these patients should be made to prevent dislocation and potentially minimize the risk of other prosthesis-related complications leading to revision.

Peptide Self-Assembly Controlled Photoligation of Polymers.

Highly efficient chemical ligations that operate in water under mild conditions are the foundation of bioorthogonal chemistry. However, the toolbox of suitable reactions is limited. Conventional approaches to expand this toolbox aim at altering the inherent reactivity of functional groups to design new reactions that meet the required benchmarks. Inspired by controlled reaction environments that enzymes provide, we report a fundamentally different approach that makes inefficient reactions highly efficient within defined local environments. Contrasting enzymatically catalyzed reactions, the reactivity controlling self-assembled environment is brought about by the ligation targets themselves─avoiding the use of a catalyst. Targeting [2 + 2] photocycloadditions, which are inefficient at low concentrations and readily quenched by oxygen, short ß-sheet encoded peptide sequences are inserted between a hydrophobic photoreactive styrylpyrene unit and a hydrophilic polymer. In water, electrostatic repulsion of deprotonated amino acid residues governs the formation of small self-assembled structures, which enable a highly efficient photoligation of the polymer, reaching ∼90% ligation within 2 min (0.034 mM). Upon protonation at low pH, the self-assembly changes into 1D fibers, altering photophysical properties and shutting down the photocycloaddition reaction. Using the reversible morphology change, it is possible to switch the photoligation "ON" or "OFF" under constant irradiation simply by varying the pH. Importantly, in dimethylformamide, the photoligation reaction did not occur even at 10-fold higher concentrations (0.34 mM). The self-assembly into a specific architecture, encoded into the polymer ligation target, enables a highly efficient ligation that overcomes the concentration limitations and high oxygen sensitivity of [2 + 2] photocycloadditions.

Genome-scale analysis of essential gene knockout mutants to identify an antibiotic target process.

We describe a genome-scale approach to identify the essential biological process targeted by a new antibiotic. The procedure is based on the identification of essential genes whose inactivation sensitizes a Gram-negative bacterium (Acinetobacter baylyi) to a drug and employs recently developed transposon mutant screening and single-mutant validation procedures. The approach, based on measuring the rates of loss of newly generated knockout mutants in the presence of antibiotic, provides an alternative to traditional procedures for studying essential functions using conditional expression or activity alleles. As a proof of principle study, we evaluated whether mutations enhancing sensitivity to the ß-lactam antibiotic meropenem corresponded to the known essential target process of the antibiotic (septal peptidoglycan synthesis). We found that indeed mutations inactivating most genes needed for peptidoglycan synthesis and cell division strongly sensitized cells to meropenem. Additional classes of sensitizing mutations in essential genes were also identified, including those that inactivated capsule synthesis, DNA replication, or envelope stress response regulation. The essential capsule synthesis mutants appeared to enhance meropenem sensitivity by depleting a precursor needed for both capsule and peptidoglycan synthesis. The replication mutants may sensitize cells by impairing division. Nonessential gene mutations sensitizing cells to meropenem were also identified in the screen and largely corresponded to functions subordinately associated with the essential target process, such as in peptidoglycan recycling. Overall, these results help validate a new approach to identify the essential process targeted by an antibiotic and define the larger functional network determining sensitivity to it.

Sexual Orientation, Sexual Motivation, and Erotic Target Identity Inversions in Male Adult Baby/Diaper Lovers.

Adult baby/diaper lovers (AB/DLs) enjoy role-playing as babies and/or wearing diapers. They also engage in other related activities, such as urinating or defecating themselves and having an adult care for them. Previous surveys have revealed that AB/DLs commonly report sexual motivation, a finding that is corroborated by case reports in the psychiatric literature and some media interviews. The fact that AB/DLs change their appearance and behavior to become more like babies raises the possibility that they have an erotic target identity inversion (ETII). In ETIIs, a person's external erotic target is inverted into the self, resulting in sexual arousal by the fantasy of being a member of the target class or by imitating one. If AB/DLs are sexually motivated by an ETII, they should experience both sexual attraction to babies and sexual arousal by the fantasy of being a baby. We surveyed 207 male AB/DLs recruited from the Internet about their sexual orientation, sexual motivation, and sexual interests for a primarily quantitative analysis. Consistent with past research, a substantial minority of participants reported non-heterosexual identities (42%), and a large majority reported some degree of sexual motivation for being AB/DLs (93%). Wearing diapers and urinating or defecating oneself were rated as especially sexual. Even though 40% of participants reported sexual arousal by the fantasy of being a baby, only 4% reported sexual attraction to babies. This pattern of results is contrary to predictions from the concept of ETIIs. Instead, participants indicated that physical or mental pain, humiliation, and an adult woman were important to their sexual fantasies of being a baby. Masochism appears to be a promising alternative to an ETII for explaining the sexual motivation of AB/DLs.

Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases.

During the past decade there has been a dramatic increase in adolescents and young adults (AYA) complaining of gender dysphoria. One influential if controversial explanation is that the increase reflects a socially contagious syndrome: Rapid Onset Gender Dysphoria (ROGD). We report results from a survey of parents who contacted the website ParentsofROGDKids.com because they believed their AYA children had ROGD. Results focused on 1655 AYA children whose gender dysphoria reportedly began between ages 11 and 21 years, inclusive. These youths were disproportionately (75%) natal female. Natal males had later onset (by 1.9 years) than females, and they were much less likely to have taken steps toward social gender transition (65.7% for females versus 28.6% for males). Pre-existing mental health issues were common, and youths with these issues were more likely than those without them to have socially and medically transitioned. Parents reported that they had often felt pressured by clinicians to affirm their AYA child's new gender and support their transition. According to the parents, AYA children's mental health deteriorated considerably after social transition. We discuss potential biases of survey responses from this sample and conclude that there is presently no reason to believe that reports of parents who support gender transition are more accurate than those who oppose transition. To resolve controversies regarding ROGD, it is desirable that future research includes data provided by both pro- and anti-transition parents, as well as their gender dysphoric AYA children.

Elaborating and Testing Erotic Target Identity Inversion Theory in Three Paraphilic Samples.

Some men sexually attracted to types of persons (e.g., women) or things (e.g., animals) also have internalized sexual attractions: sexual arousal by the idea of being the type of person or thing to whom they are attracted. Consequently, some of these men develop erotic target identity inversions, in which they imitate, yearn to be, or identify as an instance of their erotic target. Erotic Target Identity Inversion Theory predicts that for every external erotic target to which men are attracted, a subset of men will develop an internalized sexual attraction, which may cause an erotic target identity inversion. We examined these predictions in Internet surveys of three samples of men with paraphilic sexual interests: 322 men attracted to amputees, 1501 men attracted to animals, and 402 men attracted to severely obese persons. All samples included substantial minorities of men reporting internalized sexual attractions and erotic target identity inversions specific to their external sexual attractions (e.g., men attracted to amputees who are also aroused by the fantasy of being amputees and wish to become amputees). The correlation between degree of each internalized sexual attraction and degree of its corresponding erotic target identity inversion was approximately 1.0 after correction for attenuation. In each sample, participants' specific internalized sexual attraction was positively correlated with autogynephilia, likely the most common internalized sexual attraction in men. Erotic Target Identity Inversion Theory can potentially explain a variety of otherwise puzzling phenomena, including transgender identity among female-attracted natal males and men seeking amputations of healthy limbs.

Robust evidence for bisexual orientation among men.

The question whether some men have a bisexual orientation-that is, whether they are substantially sexually aroused and attracted to both sexes-has remained controversial among both scientists and laypersons. Skeptics believe that male sexual orientation can only be homosexual or heterosexual, and that bisexual identification reflects nonsexual concerns, such as a desire to deemphasize homosexuality. Although most bisexual-identified men report that they are attracted to both men and women, self-report data cannot refute these claims. Patterns of physiological (genital) arousal to male and female erotic stimuli can provide compelling evidence for male sexual orientation. (In contrast, most women provide similar physiological responses to male and female stimuli.) We investigated whether men who self-report bisexual feelings tend to produce bisexual arousal patterns. Prior studies of this issue have been small, used potentially invalid statistical tests, and produced inconsistent findings. We combined nearly all previously published data (from eight previous studies in the United States, United Kingdom, and Canada), yielding a sample of 474 to 588 men (depending on analysis). All participants were cisgender males. Highly robust results showed that bisexual-identified men's genital and subjective arousal patterns were more bisexual than were those who identified as exclusively heterosexual or homosexual. These findings support the view that male sexual orientation contains a range, from heterosexuality, to bisexuality, to homosexuality.

Concomitant Tibial Tubercle Osteotomy Reduces the Risk of Revision Surgery After Medial Patellofemoral Ligament Reconstruction for the Treatment of Patellar Instability.

PURPOSE: To compare postoperative complication rates between patients who underwent medial patellofemoral ligament reconstruction (MPFLR) and those who underwent MPFLR with tibial tubercle osteotomy (TTO) in a large-scale study. A secondary goal was to investigate demographic associations with outcomes. METHODS: Patients who underwent MPFLR (n = 3,480) or MPFLR-TTO (n = 615) for patellar instability were identified in the PearlDiver database. Rates of surgery for infection, procedures for knee stiffness, patellar fracture, and revision MPFLR within 2 years postoperatively were compared using multivariable logistic regression. Demographic associations with outcomes were also investigated. RESULTS: The MPFLR-TTO cohort exhibited a significantly lower rate of revision surgery at 2 years (0.8% vs 1.9%; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.10-0.80; P = .036) when compared with the MPFLR group. Independent of index procedure, patients younger than 21 years had significantly lower rates of requiring procedures for knee stiffness (OR, 0.35; 95% CI, 0.22-0.54; P < .001) and any complication at 2 years (OR, 0.59; 95% CI, 0.45-0.78; P < .001) when compared with older patients. Male patients displayed a significantly lower rate of requiring procedures for knee stiffness at 2 years than female patients (OR, 0.46; 95% CI, 0.25-0.78; P = .007). Tobacco use was associated with a significantly higher rate of postoperative infection at 2 years (OR, 2.35; 95% CI, 1.00-5.38; P = .046). CONCLUSIONS: The MPFLR cohort exhibited higher rates of revision surgery at 2 years compared with the MPFLR-TTO cohort. Patient age under 21 years was associated with lower rates of any complication and requiring procedures for knee stiffness, male sex was associated with a lower rate of requiring procedures for knee stiffness, and tobacco use was associated with a higher rate of surgery for postoperative infection. This information can assist surgeons when counseling patients before these procedures are performed. LEVEL OF EVIDENCE: Level III, retrospective, comparative prognostic trial.

How do the top 10 known offending drug classes associated with decreased bone mineral density affect total shoulder arthroplasty outcomes?

BACKGROUND: Many regularly prescribed classes of drugs are known to negatively impact bone health. However, it is unclear if perioperative use of these drugs impacts total shoulder arthroplasty (TSA) outcomes. The purpose of this study was to analyze the impact of perioperative use of 10 drug classes with known negative effects on bone health on prosthesis-related outcomes of TSA. METHODS: Patients who underwent primary TSA were retrospectively identified in the PearlDiver database. Within this population, patients prescribed proton pump inhibitors (PPIs), thiazolidinediones (TZDs), loop diuretics, glucocorticoids, aromatase inhibitors, calcineurin inhibitors, selective serotonin reuptake inhibitors (SSRIs), antiepileptic drugs (AEDs), first-generation antipsychotics (FGAs), and second-generation antipsychotics (SGAs) within 6 months before or 6 months after primary TSA were identified (n = 23,748). These patients were propensity score matched 1:1 with controls (n = 23,748) on age, sex, and several comorbidities. After matching, patients with perioperative drug exposure were divided into 10 subgroups (ie, 1 for each drug class). Rates of prosthesis-related complications among patients taking each medication class vs. controls were compared with multivariable logistic regression. RESULTS: Relative to controls, SGA exposure was associated with significantly higher rates of all-cause revision (odds ratio [OR] 1.68) and aseptic revision (OR 1.57). Loop diuretic exposure was associated with significantly higher rates of all-cause revision (OR 1.44) and aseptic revision (OR 1.43). Glucocorticoid exposure was associated with significantly higher rates of all-cause revision (OR 1.32) and aseptic revision (OR 1.30). SSRI exposure was associated with significantly higher rates of all-cause revision (OR 1.27) and aseptic revision (OR 1.24). Periprosthetic fracture, aseptic loosening, and septic revision was comparable for all drug cohorts compared to matched controls (all P > .05). Patients with perioperative exposure to PPIs, TZDs, FGAs, AEDs, aromatase inhibitors, and calcineurin inhibitors displayed comparable rates of all queried complications compared with controls (all P > .05). CONCLUSION: Compared with matched controls, patients with perioperative exposure to SGAs, loop diuretics, glucocorticoids and SSRIs exhibited significantly higher rates of all-cause and aseptic revisions following primary TSA. Several other medications that are risk factors for osteoporosis and fragility fractures did not demonstrate significant associations with any complications, including periprosthetic fracture. These results highlight the need for a thorough review of patients' medical history and current medication usage prior to preoperative risk counseling for patients seeking TSA.

Hepatitis C Is Associated With Higher Short-Term Complication Rates After Initial Aseptic and Septic Revision Total Hip Arthroplasty: A Matched Cohort Study.

BACKGROUND: It is unclear if hepatitis C virus (HCV) negatively impacts outcomes of revision total hip arthroplasty (rTHA). The purpose of this study is to trend recent rTHA utilization in patients who have HCV and compare postoperative complication rates versus a matched cohort. METHODS: All patients who underwent rTHA were retrospectively identified in a national database. Patients who had HCV (n = 1,746) were matched 1:3 with a matching group (n = 5,238) for age, gender, and several comorbidities. Cochran-Armitage tests were used to analyze trends in the annual proportion of rTHA performed in patients who had HCV from 2010 to 2019. Rates of 90-day medical and prosthesis-related complications within 2 years postoperatively were compared with multivariable logistic regressions. RESULTS: The annual proportion of rTHA performed in patients who had HCV significantly increased from 2010 to 2019 (P < .001). Patients who had HCV exhibited significantly higher rates of acute kidney injuries (7.6% versus 4.4%; odds ratio [OR] 1.50), transfusions (20.6% versus 14.6%; OR 1.38), and re-revisions for prosthetic joint infection (10.9% versus 6.5%; OR 1.73). In subgroup analyses, rates of re-revision for prosthetic joint infection after initial aseptic rTHA (7.1% versus 3.8%; OR 1.82) and periprosthetic fracture after initial septic rTHA (4.5% versus 1.6%; OR 2.77) were significantly higher in the HCV cohort. CONCLUSION: Similar to primary THA, patients who have HCV exhibit significantly increased complication rates after rTHA. With growing utilization in recent years, these data suggest that this population will comprise an increasingly larger proportion of rTHA procedures performed in the coming years.

The Impact of Epilepsy on Complication Rates After Total Joint Arthroplasty: A Propensity Score-Matched Cohort Study.

BACKGROUND: It is unclear how epilepsy may affect total joint arthroplasty outcomes. The purpose of this study is to analyze the impact of epilepsy on prosthesis-related complications following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A retrospective cohort study was conducted using a national database. Patients who have epilepsy underwent a primary THA (n = 6,981) and TKA (n = 4,987) and were matched 1:4 (THA, n = 27,924; TKA, n = 19,948). Rates of low-energy falls and prosthesis-related complications within 2 years postoperatively were compared for patients who did and did not have epilepsy with multivariable logistic regression. RESULTS: After primary TKA, patients who have epilepsy exhibited significantly higher rates of aseptic revision (4.3% versus 3.5%, odds ratio [OR] 1.21, P = .017) and revision for prosthetic joint infection (1.8% versus 1.3%, OR 1.29, P = .041). THA patients who have epilepsy exhibited significantly higher rates of prosthetic dislocation (3.2% versus 1.9%, OR 1.54, P < .001), periprosthetic fracture (2.2% versus 0.8%, OR 2.39, P < .001), and aseptic loosening (1.7% versus 1.1%, OR 1.40, P = .002). Rates of low-energy falls within 2 years after TKA (14.1% versus 6.4%, OR 2.19, P < .001) and THA (33.6% versus 7.5%, OR 5.95, P < .001) were also significantly higher for patients who have epilepsy. CONCLUSION: Epilepsy was associated with significantly higher rates of falls (P < .001) and prosthesis-related complications after primary THA (P < .05) and TKA (P < .05). Precautions should be implemented in this population during intraoperative and perioperative decision-making to reduce complication risk. LEVEL OF EVIDENCE: Level III.

The Effects of Gout Following total Knee Arthroplasty: A Retrospective Analysis.

BACKGROUND: The prevalence of gout is increasing along with the number of total knee arthroplasties (TKA) performed annually. The purpose of this study was to evaluate the incidence of gout following TKA in patients who had a previous history of gout and to determine if it is associated with an increased rate of postoperative joint complications. METHODS: Patients who did and did not have a preoperative diagnosis of gout and underwent a primary TKA were identified from a national database. The gout patients were matched 1:1 to patients who did not have gout and rates of postoperative gout diagnoses within 2 years of surgery were compared. Complication rates at mean 1 and 2 years were then compared for both patient cohorts using multivariable logistic regressions. A total of 17,463 patients with a prior diagnosis of gout were matched with 17,463 controls. RESULTS: There were 53.8% of patients who had previous gout and had a recurrence of gout within 2 years versus 3.6% of controls (Odds Ratios [OR]: 30.86). At mean 1-year, patients who had gout were significantly more likely to experience prosthetic joint infections (PJIs) and revision procedures. At mean 2 years, gout patients were at increased risk of prosthetic loosening, PJI, revision, and incision and debridement procedures. CONCLUSION: This study suggests that patients who had a prior diagnosis of gout are significantly more likely to experience recurrent episodes of gout after TKA. Gout attacks after TKA are associated with an increase in the rate of joint complications. LEVEL OF EVIDENCE: Level III.