Citations

AimsContemporary outcomes of primary total hip arthroplasties (THAs) with highly cross-linked polyethylene (HXLPE) liners in patients with inflammatory arthritis have not been well studied. This study examined the implant survivorship, complications, radiological results, and clinical outcomes of THA in patients with inflammatory arthritis.MethodsWe identified 418 hips (350 patients) with a primary diagnosis of inflammatory arthritis who underwent primary THA with HXLPE liners from January 2000 to December 2017. Of these hips, 68% had rheumatoid arthritis (n = 286), 13% ankylosing spondylitis (n = 53), 7% juvenile rheumatoid arthritis (n = 29), 6% psoriatic arthritis (n = 24), 5% systemic lupus erythematosus (n = 23), and 1% scleroderma (n = 3). Mean age was 58 years (SD 14.8), 66.3% were female (n = 277), and mean BMI was 29 kg/m2 (SD 7). Uncemented femoral components were used in 77% of cases (n = 320). Uncemented acetabular components were used in all patients. Competing risk analysis was used accounting for death. Mean follow-up was 4.5 years (2 to 18).ResultsThe ten-year cumulative incidence of any revision was 3%, and was highest in psoriatic arthritis patients (16%). The most common indications for the 15 revisions were dislocations (n = 8) and periprosthetic joint infections (PJI; n = 4, all on disease-modifying antirheumatic drugs (DMARDs)). The ten-year cumulative incidence of reoperation was 6.1%, with the most common indications being wound infections (six cases, four on DMARDs) and postoperative periprosthetic femur fractures (two cases, both uncemented femoral components). The ten-year cumulative incidence of complications not requiring reoperation was 13.1%, with the most common being intraoperative periprosthetic femur fracture (15 cases, 14 uncemented femoral components; p = 0.13). Radiological evidence of early femoral component subsidence was observed in six cases (all uncemented). Only one femoral component ultimately developed aseptic loosening. Harris Hip Scores substantially improved (p < 0.001).ConclusionContemporary primary THAs with HXLPE in patients with inflammatory arthritis had excellent survivorship and good functional outcomes regardless of fixation method. Dislocation, PJI, and periprosthetic fracture were the most common complications in this cohort with inflammatory arthritis.Cite this article: Bone Joint J 2023;105-B(7):768–774.

AbstractContextInhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).ObjectiveWe report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.DesignProof-of-concept (POC) and randomized, double-blind placebo-controlled trials.SettingMulticenter.ParticipantsPatients with moderate-to-severe, active TED.InterventionIn the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.Main OutcomeChange from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).ResultsThe randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P &lt; .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P &lt; .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P &lt; .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.ConclusionsThese results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.

Introduction and Aim: A growing body of evidence suggests a negative impact of obesity on the disease activity of inflammatory bowel disease (IBD). The primary aim of the study was to evaluate disease outcomes of IBD in patients after bariatric surgery (BS). Methods: Patients with IBD and morbid obesity who underwent BS were compared with patients with IBD and morbid obesity without BS in a retrospective, propensity-score matched cohort study using TriNetX, a multi-institutional database. The primary aim was to assess the 2-year risk of a composite of disease-related complications, which included intravenous steroid use or IBD-related surgery. Risk was expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: In all, 482 patients (3.4%) with IBD and morbid obesity underwent BS (mean age 46.9±11.2 y old, mean BMI 42.1±7.72 kg/m2, Crohn’s disease 60%). After propensity-score matching, the BS cohort had a lower risk (aOR 0.31, 95% CI 0.17-0.56) of a composite of IBD-related complications compared with the control cohort. After propensity-score matching, the BS cohort with sleeve gastrectomy had a decreased risk (aOR 0.45, 95% CI 0.31-0.66) of a composite of IBD-related complications. There was no difference in the risk (aOR 0.77, 95% CI 0.45–1.31) of a composite of IBD-related complications between the BS cohort with Roux-en-Y gastric bypass (RYGB) compared with the control cohort. Conclusion: Sleeve gastrectomy but not Roux-en-Y gastric bypass is associated with improved disease-specific outcomes in patients with IBD and morbid obesity.

This systematic review evaluated the animal and human evidence for pharmacomicrobiomics (PMx) interactions of antidepressant medications. Studies of gut microbiota effects on functional and behavioral effects of antidepressants in human and animal models were identified from PubMed up to December 2022. Risk of bias was assessed, and results are presented as a systematic review following PRISMA guidelines. A total of 28 (21 animal, 7 human) studies were included in the review. The reviewed papers converged on three themes: (1) Antidepressants can alter the composition and metabolites of gut microbiota, (2) gut microbiota can alter the bioavailability of certain antidepressants, and (3) gut microbiota may modulate the clinical or modeled mood modifying effects of antidepressants. The majority (n = 22) of studies had at least moderate levels of bias present. While strong evidence is still lacking to understand the clinical role of antidepressant PMx in human health, there is evidence for interactions among antidepressants, microbiota changes, microbiota metabolite changes, and behavior. Well-controlled studies of the mediating and moderating effects of baseline and treatment-emergent changes in microbiota on therapeutic and adverse responses to antidepressants are needed to better establish a potential role of PMx in personalizing antidepressant treatment selection and response prediction.

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

Background: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn’s disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Study: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Results: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Conclusions: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Background: Ethnic, racial, and sex disparities continue to persist in medicine despite efforts to diversify the profession. In competitive surgical specialties such as plastic surgery, those disparities are particularly pronounced. This study aims to evaluate racial, ethnic, and sex diversity in academic plastic surgery. Methods: We compiled a list of major plastic surgery professional societies, plastic surgery journal editorial boards, and plastic surgery accreditation boards to evaluate ethnic and sex diversity in society, research, and accreditation domains, respectively. Demographic data were collected and analyzed using the Mann–Whitney U test and the Kruskal–Wallis test. Results: White individuals are significantly overrepresented across the professional and research domains, and Asian individuals are overrepresented in the professional domain when compared to non-white races. White individuals make up a total of 74% of the society domain, 67% of the research domain, and 86% of the accreditation domain when compared to all non-white surgeons. Male surgeons made up 79% of the society domain, 83% of the research domain, and 77% of the accreditation domain when compared to all non-male surgeons. Conclusions: Ethnic, racial, and sex disparities persist in academic plastic surgery. This study, which looked at societies, editorial boards, and accreditation boards, demonstrated a persistent ethnic, racial, and sex homogeneity among leadership. Changes are required to continue to diversify the field and provide women and underrepresented minorities the tools needed to succeed.

Abstract ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia. We further characterize AEs of acalabrutinib and ibrutinib via post hoc analysis. Overall and exposure-adjusted incidence rate was assessed for common Bruton tyrosine kinase inhibitor–associated AEs and for selected events of clinical interest (ECIs). AE burden scores based on previously published methodology were calculated for AEs overall and selected ECIs. Safety analyses included 529 patients (acalabrutinib, n = 266; ibrutinib, n = 263). Among common AEs, incidences of any-grade diarrhea, arthralgia, urinary tract infection, back pain, muscle spasms, and dyspepsia were higher with ibrutinib, with 1.5- to 4.1-fold higher exposure-adjusted incidence rates. Incidences of headache and cough were higher with acalabrutinib, with 1.6- and 1.2-fold higher exposure-adjusted incidence rate, respectively. Among ECIs, incidences of any-grade atrial fibrillation/flutter, hypertension, and bleeding were higher with ibrutinib, as were exposure-adjusted incidence rates (2.0-, 2.8-, and 1.6-fold, respectively); incidences of cardiac events overall (the Medical Dictionary for Regulatory Activities system organ class) and infections were similar between arms. Rate of discontinuation because of AEs was lower for acalabrutinib (hazard ratio, 0.62; 95% confidence interval, 0.41-0.93). AE burden score was higher for ibrutinib vs acalabrutinib overall and for the ECIs atrial fibrillation/flutter, hypertension, and bleeding. A limitation of this analysis is its open-label study design, which may influence the reporting of more subjective AEs. Overall, event-based analyses and AE burden scores demonstrated higher AE burden overall and specifically for atrial fibrillation, hypertension, and hemorrhage with ibrutinib vs acalabrutinib. This trial was registered at www.clinicaltrials.gov as #NCT02477696.