Citations

Background: Porous metaphyseal cones are frequently utilized during revision total knee arthroplasty (TKA) procedures. The purpose of the present study was to evaluate 3D-printed metaphyseal cones used for revision TKA, with specific emphasis on implant survivorship, radiographic appearance, and clinical outcomes after short-term follow-up. Methods: We identified 740 cones (498 tibial, 242 femoral) that had been inserted during 533 revision TKA procedures that had been performed at a single tertiary care academic institution. Aseptic loosening (n = 199), periprosthetic joint infection (PJI) (n = 183), and instability (n = 84) were the most common reasons for the index revision. Type-2B or 3 bone loss was present in 67% of the knees. The mean age was 66 years, the mean body mass index was 34 kg/m 2 , and 55% of the patients were female. Serial radiographs were reviewed. The mean duration of follow-up was 4 years. Results: The 5-year cumulative incidence of cone revision for aseptic loosening was 1% (95% confidence interval [CI], 0% to 3%). The 5-year cumulative incidence of any cone revision or removal was 6% (95% CI, 4% to 9%). In total, 37 cones (19 femoral, 18 tibial) were revised, with PJI (n = 23; 14 recurrent), periprosthetic femoral fracture (n = 3), arthrofibrosis (n = 3), and aseptic loosening of the femoral component and femoral cone (n = 3) as the most common reasons for cone revision. The 5-year cumulative incidence of any TKA re-revision was 14% (95% CI, 11% to 18%). There were a total of 67 re-revisions, with PJI (n = 38), persistent drainage (n = 6), and extensor mechanism disruption (n = 3) being the most common reasons. Radiographically, 2 unrevised femoral cones and 1 unrevised tibial cone appeared to be possibly loose; all 3 cones were in knees with distal femoral replacements or hinged constructs. Conclusions: This large series showed that 3D-printed titanium metaphyseal cones were very durable at short-term follow-up, with a 5-year cumulative incidence of cone revision for aseptic loosening of 1%. PJI was the most common reason for cone revision and any revision. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct amyotrophic lateral sclerosis and frontotemporal dementia cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in silico tools. In addition, gene burden analyses in the 100 000 Genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls [odds ratio: 57.0847 (10.2−576.7); P = 4.02 ×10−7]. Taken together, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harbouring a predicted pathogenic TUBA4A missense mutation, including five confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from three patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organization and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes.

Background and Aims: We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer. Approach and Results: This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included adults who are treatment-naive with locally advanced/metastatic biliary tract cancer. Patients (N = 297) were randomized to receive an IV infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m 2 +cisplatin 25 mg/m 2 on days 1 and 8/3 wk; 8 cycles) (BA group, n = 148) or placebo+GemCis (placebo group, n = 149). The primary end point was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cutoff: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naive when 80 progression-free survival events had occurred and ≥ 19 weeks of follow-up had been completed (BA, n = 73; placebo, n = 77). Median OS (95% CI) for the BA (11.5 mo [9.3–not estimable]) and placebo (11.5 mo [10.0–not estimable]) groups was comparable (hazard ration 1.23 [95% CI 0.66–2.28]; p = 0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively. Conclusions: BA+GemCis did not provide a clinically meaningful benefit compared with GemCis alone as first-line treatment for biliary tract cancer, and the study was discontinued early (terminated: August 20, 2021).

Acute kidney injury (AKI) is a commonly encountered medical problem that is associated with poor health outcomes in AKI survivors, including increased mortality and re-admission to the hospital. Despite their high-risk status, only a small fraction (< 10%) of patients receive specialized nephrologist follow-up after AKI event. To address the gap in care for AKI patients, this work proposes an artificial intelligence (AI) based fusion technique that combines patient's single-lead electrocardiograph (ECG) and demographics to predict AKI recurrence 3-7 days before onset. The ECG data is analyzed with an on-chip reservoir-computer (RC) prototyped in 28nm CMOS process to create a compressed representation for predicting AKI onset from ECG. After fusion with demographics, the proposed technique is able to predict AKI recurrence 3-7 days before onset with 75.8% accuracy when evaluated on a retrospective patient dataset collected from Mayo Clinic Enterprise.

Abstract Background The United States Department of Health and Human Services has defined 21 chronic conditions lasting one year or greater and which require ongoing medical treatment. The presence of multiple chronic conditions (multimorbidity) is closely linked to greater physical disability, increased health care utilization, reduced quality of life, and higher mortality rates. In the general population, studies have shown the prevalence of multimorbidity to be greater in females compared to males. Recently, data has suggested that patients enrolled in cardiac rehabilitation (CR) have a significantly greater number of chronic conditions compared to the general population. Whether these same sex differences in the prevalence of individual chronic conditions are present in the CR population has not been examined. Purpose The purpose of this study is to determine whether differences exist in the prevalence of individual chronic conditions between male and female CR patients. We hypothesize that female CR patients will demonstrate greater prevalence of individual chronic conditions compared to men. Methods Using the local Epidemiology Project records-linkage system, we identified patients who attended (≥1) CR sessions from 1995-2019. The prevalence of 21 chronic conditions was extracted from the patients’ medical records at the time of enrollment in CR (Table 1). We conducted chi-squared analysis to identify differences in the prevalence of each individual chronic condition between the sexes. Statistical significance was defined by p≤0.05. Results Of the 13,056 CR patients identified (age: 65.7±12.8 yrs old), 4,107 (31.5%) were female. Male CR patients were significantly younger compared to female counterparts (64.8±12.1 yrs old vs. 67.6±13.6 yrs old; p≤0.001). Females demonstrated a greater number of total chronic conditions compared to males (median (IQR): 7.0 (5.0, 9.0) vs 6.0 (5.0, 8.0); p≤0.001). Females demonstrated a greater prevalence of the following 12 individual chronic conditions compared to males: HTN, CHF, ARR, STR, ART, CAN, CPD, HEP, OST, ANX, DEM, and DEP (p≤0.05, for all). There was a trend for greater prevalence of ARR in females compared to males (p=0.07). In contrast, males experienced a greater prevalence of the following four chronic conditions compared to females: CAD, LIP, AST, and SUB (p≤0.001, for all). There were no differences between sexes for CKD (p=0.87), SZO (p=0.70), or AUT (p=0.31). Conclusion Our data suggest the trend for greater prevalence of chronic conditions in females in the general population is consistent within the CR population. Specifically, 12 of 21 (57%) individual chronic conditions were significantly more prevalent in female CR patients whereas only 4 (19%) conditions were more prevalent in males. These data emphasize the need to better understand the relationship between sex and risk for individual chronic conditions, particularly in patients enrolled in CR.

Abstract Background Bicuspid aortic valve (BAv) is associated with increased oxidative stress and inflammation, resulting in valve fibrosis, calcification, and ultimately early degenerative valve disease, often necessitating premature aortic valve intervention. In recent years, growing evidence has been published supporting the role of lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, in the development of aortic valve disease in the general population. However, the specific influence of Lp(a) levels in patients with BAv remains to be firmly established. Purpose To assess the role of Lp(a) levels in the development of aortic valve disease and the necessity for aortic valve interventions among individuals with BAv. Methods This retrospective multicenter study encompassed consecutive patients diagnosed with BAv from January 1997 to December 2022, all of whom had undergone serum Lp(a) measurement. This study evaluated the association between Lp(a) concentrations and the occurrence of aortic valve interventions. A cutoff point of ≥30 mg/dl for high Lp(a) levels was established. Binary logistic regression was utilized to calculate the odds ratio (OR) for an aortic intervention according to high versus low Lp(a) levels. Additionally, Kaplan Meier curves were employed to estimate the cumulative requirement for an aortic valve replacement based on Lp(a) concentrations. Results A total of 452 patients with BAv and a Lp(a) measurement were included in the study, with a mean age of 37.2 ±10.5 years at the time of BAv diagnosis, with 71.2% being male. Among these, 101 (22.3%) patients underwent an aortic valve replacement. In 72 cases (71.3%) aortic stenosis was the primary indication for intervention, while aortic regurgitation accounted for 29 cases (28.7%). The presence of elevated Lp(a) levels (≥30 mg/dl) demonstrated a significant association with the requirement for an aortic valve intervention (OR 2.2, 95%CI 1.4-3.6, p&lt;0.001) in both the regression analysis and using the Kaplan-Meier estimator (Figure). High Lp(a) concentrations posed a risk factor for aortic valve replacements regardless of whether the primary indication for intervention was significant stenosis (OR 1.8, 95%CI 1.1-3.1, p=0.028) or regurgitation (OR 2.5, 95%CI 1.2-5.4, p=0.018). Conclusion Increased concentrations of Lp(a) may influence the clinical trajectory of patients with a BAv and may be a significant risk factor for aortic valve replacement, irrespective of the primary indication for intervention. Further investigations will be critical in unveiling the precise pathological mechanisms of Lp(a) in BAv. Confirming whether reducing Lp(a) levels could slow the progression of aortic disease in this demographic requires further exploration. Kaplan-Meier estimator.

Abstract Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [REG3α]) when measured at GVHD diagnosis are validated predictors of NRM risk but have never been assessed in the same patients using identical statistical methods. We measured the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts. The training cohort (n = 341) was used to develop algorithms for predicting the probability of 12-month NRM that contained all possible combinations of 1 to 3 biomarkers and a threshold corresponding to the concordance probability was used to stratify patients for the risk of NRM. Algorithms were compared with each other based on several metrics, including the area under the receiver operating characteristics curve, proportion of patients correctly classified, sensitivity, and specificity using only the validation cohort (n = 374). All algorithms were strong discriminators of 12-month NRM, whether or not patients were systemically treated (n = 321). An algorithm containing only ST2 + REG3α had the highest area under the receiver operating characteristics curve (0.757), correctly classified the most patients (75%), and more accurately risk-stratified those who developed Minnesota standard-risk GVHD and for patients who received posttransplant cyclophosphamide-based prophylaxis. An algorithm containing only AREG more accurately risk-stratified patients with Minnesota high-risk GVHD. Combining ST2, REG3α, and AREG into a single algorithm did not improve performance.

Abstract Background Home-based cardiac rehabilitation (HBCR) is emerging in the COVID era, but few studies have addressed "gamification", the use of game elements in non-game contexts. Purpose This pilot study investigates the applicability of gamification application to HBCR. Methods Patients who were hospitalized with acute coronary syndrome and agreed to undergo HBCR using a smartphone/smartwatch immediately after discharge were candidates for the study. The smartphone application included gamification, whereby the patients earned points for achieving exercise within an appropriate heart rate range and received feedback based on their points. The primary endpoint was the frequency of performing HBCR with the application from discharge to the date of the first outpatient visit. Secondary endpoints were the frequency of complications and correlations in several parameters of the application. Results The study included data from 16 patients. The mean duration of intervention was 29 ± 6 days. Total smartphone application use was 59.9% (282/471 days). Peak VO2 increased significantly after HBCR (18.4 ± 4.1 vs. 21.1 ± 5.4 mL/min/kg, p = 0.004) and the patients had no complications. Total application use was significantly positively correlated (r = 0.665, p = 0.007) with the application use persistence index (calculated by dividing the duration of application use in the second half of the intervention by the duration of use in the first half). Conclusion The smartphone application with gamification can be safely applied to HBCR. Continued use of the application creates a virtuous circle for patients, and gamification may be one of the keys to this.

Abstract Background Patients enrolled in cardiac rehabilitation (CR) demonstrate a greater burden of co-occurring chronic conditions (CC) compared to the general population. Studies have shown that the prevalence of multimorbidity among noninstitutionalized, civilian US adults is higher among women compared to men. These CC are often grouped and categorized as Cardiometabolic, Somatic, and Mental Health based on the origin and organ system the condition affects. Importantly, sex differences between categorizations of CC in patients undergoing CR has not been examined. Purpose Because patients enrolled in CR are known to have multiple Cardiometabolic conditions, the aim of this study is to examine sex differences in the prevalence of non-cardiometabolic conditions in the CR population. Methods We extracted data on all 21 CC defined by the US Department of Health and Human Services using the local Epidemiology Project records-linkage system. Our study population included participants who attended (≥1) CR sessions from 1995 to 2019. The CC were categorized into cardiometabolic (CMC), Somatic, and Mental health groups (Table 1), and as CMC only, CMC + Somatic only, CMC + Mental health only, and CMC + Somatic + Mental health groups (Table 2). The sex differences in the number of CC within these groups were analyzed by Kruskal-Wallis test and prevalence were analyzed by Pearson’s Chi-squared test, where p&lt;0.05 was significant. Results We identified 13,056 CR patients (68.5% males) who were ≥18 years old with a mean age of 65.7±12.7 yrs (67.6±13.6 yrs in females and 64.8±12.1 yrs in males). Median [Q1, Q3] number of CC was 7 [5,9], with females having a greater number (7 [5, 9]) than males (6 [5,8]), p&lt;0.001. Both sexes had at least 1 CMC with a median of 5 [3,5] CMC and no differences between sexes (p&gt;0.05); however, females demonstrated more somatic and mental health conditions compared to males (p&lt;0.001, for both, Table 1). When grouping categories of CC, females demonstrated a higher number of CC in CMC + Somatic + Mental health as well as CMC + Somatic only groups (p&lt;0.001, for both, Table 2), with a higher prevalence in the former group only. While the number of CC in CMC + Mental health group was similar between sexes, the prevalence was lower in females. In contrast, the CMC only grouping demonstrated a higher number of CC and prevalence among males (p&lt;0.05). Conclusion Our data suggest that females enrolled in CR demonstrate a significantly higher number of CC compared to males. Although males have a higher prevalence of CMC, the prevalence of Somatic ± Mental health conditions in addition to CMC is significantly greater in females. These data demonstrate the importance of considering sex differences in the prevalence of non-CMC when formulating individualized treatment plans for CR patients.