Citations

Abstract Introduction Understanding factors that impact outcomes of total hip arthroplasty (THA) can aid clinical decision-making and patient counselling. The purpose of this study was to investigate functional outcomes, complications, and reoperation rates among patients undergoing primary THA after hip arthroscopy (HA-THA) compared to a matched cohort of primary THA patients without prior arthroscopy (THA-only). Methods A retrospective review was performed to identify all patients who underwent primary THA after prior hip arthroscopy from 2009-2022 at a single institution. Patients with a history of revision arthroscopy were excluded. Cases were propensity-matched with primary THA controls in a 1:4 ratio by age at time of THA, sex, body mass index, surgical approach, and year of surgery. At minimum 2-year follow-up, patient-reported outcomes (PROs) including Forgotten Joint Score (FJS), Modified Harris Hip Score (mHHS), Hip Disability and Osteoarthritis Outcome Score Pain (HOOS pain), and Visual Analog Pain Scale (VAS) were analyzed. Results Sixty-three hips in 60 patients (age: 47.3±9.4 years, BMI: 29.8±6.2 kg/m2) were matched to 252 THA-only hips, with patients converting to THA at a mean 3.1 years (range 0.3-10.3) following hip arthroscopy. While both HA-THA and THA patients demonstrated significant (p<0.001) postoperative improvements in PROs, HA-THA patients reported significantly lower postoperative FJS, mHHS, HOOS pain, and VAS pain scores (p<0.001) as compared to THA-only controls. At mean 6.6±3.2 years follow-up, HA-THA patients with preoperative Tönnis grades 2-3 reported significantly increased FJS, mHHS, and HOOS pain compared to those with preoperative Tönnis grades of 0-1 (p≤0.03). Additionally, HA-THA patients with preoperative Tönnis grades 0-1 exhibited worse PROs (p<0.001) as compared to THA-only controls. While there were no differences in complication rates between HA-THA patients and THA-only controls (8% vs. 5%, p=0.49), all-cause reoperation was greater amongst HA-THA patients compared to THA-only (10% vs. 2%, p=0.01). Conclusion While improved compared to preoperatively, patients undergoing THA after prior hip arthroscopy demonstrated inferior outcomes at mid-term follow up as compared to a demographically age-matched cohort without prior arthroscopy. When considering conversion to THA following arthroscopy, clinicians should consider counseling patients regarding improved outcomes in the setting of advanced radiographic osteoarthritis, and potentially increased all-cause reoperation.

Abstract Background Femoral version plays a critical role in pre-arthritic hip pain, particularly in femoroacetabular impingement (FAI). Variations in femoral version may contribute to hip instability or impingement. This study examines the outcomes of hip arthroscopy for FAI across different femoral version groups. Methods A prospective multicenter cohort of 677 FAI patients undergoing primary hip arthroscopy was collected, with 603 patients in this study based on recorded femoral version. Inclusion criteria were patients aged 14-45 years with idiopathic FAI, while previous ipsilateral hip procedures, associated disorders, or Tönnis 2 or greater osteoarthritis were excluded. Femoral version was measured on low-dose computed tomography (CT) utilizing the Yoshioka oblique method and categorized into five subgroups: <5°, 6°-15°, 16°-25°, 26°-35°, 35°+. Patient-reported outcomes (PROs) were obtained at minimum one-year follow-up. The modified Harris hip score (mHHS) was assessed relative to minimal clinically important difference (MCID) of 8 and patient acceptable symptom state (PASS) of 74. Additional PROs included HOOS Pain and Sports/Recreation subscores and iHOT-12 score. Composite failure was defined as reoperation for persistent symptoms or failure to achieve either the mHHS MCID or PASS. Results Males had statistically lower femoral version than females (14.0 vs 18.0; p<0.001). In females, 38.0% had a femoral version of 16°-25°, 17.9% between 26°-35°, and 3.6% greater than 35°, compared to 27.6%, 9.2%, and 1.8% in males, respectively (all p<0.001). Increased or decreased femoral versions appear to have similar outcomes to normal version. The mildly increased femoral anteversion groups of 16°-25° and 26°-35° demonstrated the best outcomes with changes in HOOS pain and sports subscores being significantly higher. Severely increased femoral anteversion, >35°, only present in 2.8% of patients, demonstrated a higher composite failure rate (15.4%) compared to moderately increased, 26°-35°, femoral version (3.1%). The decreased femoral version group, ≤5°, had a composite failure of 10.4% compared to normal femoral version, 16°-25° (10.2%). Conclusions The general anatomy differences between males and females lends males to be more in retroversion while females tend to be more anteverted. Overall, outcomes did not seem to differ between increased or decreased femoral versions but were superior at mildly increased femoral versions.

Objective The incidence of hip osteoarthritis (OA) is increasing with the aging population, leading to interest in intra-articular orthobiologic injections to alleviate symptoms and potentially slow disease progression. This systematic review aims to evaluate the clinical outcomes associated with six orthobiologic therapies for hip OA: hyaluronic acid (HA), platelet-rich plasma (PRP), autologous cells therapy (ACT), microfragmented adipose tissue (MFAT), and bone marrow aspirate (BMA) and its concentration (BMAC). Methods We conducted a literature search according to the PRISMA guidelines. Studies were included in our review if they used at least one of the four orthobiologic therapies and reported on the clinical outcome using patient reported outcome measures (PROMs). Since there is a large variability among clinical outcomes, we focused on the three most utilized PROMs (VAS, WOMAC, and HHS) and the latest follow-up time point. Results Of the 716 studies reviewed, thirty-six studies (n=36) fit inclusion criteria. There were 21 studies examining HA, 11 on PRP, 3 for MFAT, 2 for ACT, and 3 on BMA/BMAC. Eight studies were randomized controlled trials and 28 were cohort studies. The mean age of the patient population ranged from 45 ± 17.0 to 74 ± 8.0. The baseline grade of osteoarthritis ranged from 1-4 but was most reported as moderate (2-3). Overall, there was an improvement in PROMs at the latest follow-up after receiving orthobiologic interventions. Discussion Orthobiologic injections have shown promise for improving PROMs in patients with hip OA. Future studies should evaluate long-term efficacy and include randomized trials to establish efficacy.

Abstract Context Adult growth hormone (GH) deficiency (GHD) is characterized by metabolic abnormalities caused by insufficient GH production. Lonapegsomatropin, a prodrug administered once weekly, was designed to provide sustained release of unmodified somatropin to reduce the burden of daily somatropin injections. Objective This work aimed to evaluate the efficacy and safety of lonapegsomatropin vs placebo as treatment for adults with GHD. Methods The foresiGHt trial was a multicenter, randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial (NCT04615273) conducted at 116 centers in North America, Europe, and Asia-Pacific. The trial randomly assigned and dosed 259 adults with GHD. Participants were randomly assigned 1:1:1 to receive once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin for 38 weeks. The primary efficacy end point was change from baseline in trunk percent fat at week 38. Secondary efficacy end points included change from baseline in trunk fat mass and total body lean mass. Results At week 38, lonapegsomatropin significantly reduced trunk percent fat (−1.68% vs +0.37%; least squares [LS] mean difference −2.04%; P < .001), increased total body lean mass (+1.60 kg vs −0.11 kg; LS mean difference 1.70 kg; P < .0001), and reduced trunk fat mass (−0.48 kg vs +0.22 kg; LS mean difference −0.70 kg; P = .0053) vs placebo. The safety and tolerability profile of lonapegsomatropin was comparable to somatropin. Conclusion The foresiGHt trial met its primary efficacy end point by demonstrating superiority of lonapegsomatropin vs placebo with similar safety and tolerability, supporting its potential as a once-weekly treatment option for adults with GHD.

Abstract The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer’s disease to explore the brain asymmetry within the Alzheimer’s disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and APOE ε4 status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. APOE3/3 carriers showed greater asymmetry than other APOE genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer’s disease progression in autosomal dominant Alzheimer’s disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.

Autoantibodies contribute to many autoimmune diseases, yet there is no approved therapy to neutralize them selectively. A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here, we report the finding of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens. Single-cell RNA sequencing reveals that these cells produce nonaffinity-matured IgG antibodies. These include pathogenic antibodies competing for shared binding space on MOG’s extracellular domain. Interestingly, the synthetic anti-MOG antibody 8-18C5 can prevent the binding of pathogenic antibodies from either EAE mice or people with MOG antibody disease. Moreover, an 8-18C5 variant carrying the NNAS mutation, which inactivates its effector functions, can reduce EAE severity and promote functional recovery. In brief, this study provides not only a comprehensive characterization of the humoral response in EAE models but also a proof of concept for a therapy to antagonize pathogenic anti-MOG antibodies.

Approximately 80% of invasive breast cancers are classified as human epidermal growth factor receptor 2 (HER2)-negative; however, many of these tumors have detectable levels of HER2 surface expression. Trastuzumab deruxtecan (T-DXd) is a HER2-directed antibody-drug conjugate with a membrane-permeable payload that is cytotoxic to both HER2-expressing tumor cells and neighboring cells via the bystander antitumor effect. T-DXd has shown significant antitumor activity in clinical trials for patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) breast cancer. In addition, the results of the DESTINY-Breast04 trial demonstrated the clinical benefit of T-DXd in patients with HER2-low (IHC 1+ or IHC 2+/ISH−) breast cancer after receiving prior chemotherapy. DESTINY-Breast06 demonstrated the clinical benefit of T-DXd in patients with hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH−), and HER2-ultralow (IHC 0 with membrane staining) metastatic breast cancer who had not received prior chemotherapy in the advanced setting. These results validate the need for a standard-of-care diagnostic test to identify HER2-low and HER2-ultralow expression levels in patients with metastatic breast cancer to guide therapeutic decision-making. Furthermore, effective treatment sequencing strategies and adverse event management are essential for maximizing patient benefit. This review presents the identification of HER2-low and HER2-ultralow breast cancer, sequencing of T-DXd with other treatments, and management of common or clinically significant adverse events reported with T-DXd.

Abstract Background Small vessel vasculitides (SVV) comprise a heterogeneous group of cutaneous SVV (CSVV) that can be skin‐limited or systemic. Given their diverse forms and symptoms and the lack of a standardized diagnostic approach, it is crucial to establish clear and consensus‐driven recommendations for diagnosis. Objectives To standardize diagnosis for the detection of the type, extent, potential causes or underlying conditions of CSVV. Methods International experts comprised the panel. The Delphi panel data was collected through two rounds of questionnaires. Agreement was measured using an 11‐point Likert scale (0 = strongly disagree, 10 = strongly agree). A 7‐vote minimum was required for agreement on each statement. Delphi panel statements scoring 3–7 were discussed during the meeting. Results 20 experts participated in the first round of the Delphi panel, while 17 experts took part in the second. They agreed that the diagnosis of CSVV relies on a combination of clinical manifestations, laboratory findings and histopathology. Palpable purpura on the lower extremities is recognized as the most reliable hallmark for most SVV and a sign of immune complex vasculitis. When the latter is suspected, a skin biopsy for direct immunofluorescence (DIF) should be obtained from an early, partially blanchable macule because the type of perivascular immunoglobulin is important for further diagnosis. The proper selection of biopsy sites for routine HE biopsy depends on the morphology of lesions. A comprehensive medical history and selected laboratory testing should be conducted to investigate organ involvement, potential causes and associated conditions. The extent of diagnostic procedures should be based on the severity, duration, systemic symptoms and recurrence of SVV. Conclusions Experts reached a strong consensus on the management of CSVV patients, culminating in the first International Consensus Statement for adult CSVV. This statement proposes a practical management algorithm and underscores the importance of collaboration in rare diseases management.

Abstract INTRODUCTION Brief digital cognitive measures may be a valuable and scalable alternative to traditional tests for improving early detection and disease monitoring in patients with early‐onset Alzheimer's disease (EOAD). METHODS We examined the convergent, diagnostic, and neuroanatomical validity of Tablet‐based Cognitive Assessment Tool (TabCAT) tests in the multisite Longitudinal Early‐Onset Alzheimer's Disease Study. Four hundred seventy‐five participants from 16 sites (83 cognitively unimpaired participants, 146 individuals diagnosed with mild cognitive impairment [MCI], and 246 with mild dementia) underwent TabCAT testing, including two executive/attentional tasks (Match and Flanker) and two visuospatial tasks (Line Length and Line Orientation). RESULTS TabCAT tests showed good convergent validity with traditional pen‐and‐paper tests. Match was the most accurate TabCAT test in differentiating among clinical groups (controls vs. MCI vs. dementia) and predicting amyloid positron emission tomography (PET) positivity in clinically impaired participants. TabCAT tests were associated with regional tau PET patterns. DISCUSSION TabCAT digital measures have promise for frontline identification of patients with EOAD. Highlights Four hundred seventy‐five participants from 16 US sites underwent tablet‐based cognitive assessment. Digital tests assessed executive function and visuospatial abilities. Digital tests correlated with traditional pen‐and‐paper cognitive tests. Match (test of executive function) differentiated clinical groups. Digital tests were associated with amyloid positron emission tomography (PET) status and regional tau PET patterns.