Faculty Bibliography

OBJECTIVE:Controversy persists regarding the optimal management of gout in routine primary care. There is a lack of clarity on whether treating to a target serum urate (TTT-SU) versus treating to avoid symptoms (TTASx) is more effective. METHODS:We designed a randomized controlled comparative effectiveness trial aimed at patients in primary care who have known gout, have elevated SU levels, and had at least one flare in the previous 12 months. The trial was designed to be pragmatic and incorporated structured input from primary care physicians, rheumatologists, and patients. The TTASx strategy group will receive weeklong courses of typical therapies for gout flares, such as colchicine, naproxen, or an oral glucocorticoid. The TTT-SU strategy group will receive urate-lowering therapy (primarily allopurinol) with dose titration to maintain an SU level <6 mg/dL, colchicine (or naproxen) prophylaxis for the first six months of urate-lowering therapy, and access to the same flare therapies as the TTASx group. Two clinicians (nurses or physicians) per site will be trained in each strategy to manage the patients in each arm without contamination. Gout flares are the primary outcome and are assessed every two weeks by trained study staff masked to treatment assignment using a validated questionnaire. The secondary outcome is quality of life. Blood pressure control, kidney function, glycemic control, and coronary atherosclerosis are exploratory secondary outcomes. RESULTS:Several sites have started prescreening using automated search strategies in their patients' electronic health records. Of the first 1,381 patients found in primary care practices with a history of gout, 691 patients (50%) passed prescreening checks. These potentially eligible participants have a median age of 67 years, 85% are men, median SU levels are 7.2 mg/dL, and 18% are taking low dosages of allopurinol. These patients have been targeted for recruitment efforts that are underway now. CONCLUSION/CONCLUSIONS:This randomized controlled active comparator strategy trial will answer a key question in the treatment of patients with gout in primary care: the comparative effectiveness of TTT-SU versus TTASx in gout. Secondary and exploratory outcomes will add important information regarding the broader extra-articular and quality-of-life effects of lowering SU levels.

There are multiple etiologies for revision anterior cruciate ligament reconstruction (ACLR), including but not limited to infection, arthrofibrosis, and graft failure, which should be distinguished before revision ACLR. Graft failure occurs when the reconstructed ligament does not restore knee stability, and it includes both graft rupture and functional failure in the setting of an intact graft. The causes of graft failure following ACLR can be divided into surgeon-controllable factors (ie, tunnel position, graft choice, alignment) and patient-centric factors (ie, patient age, tissue quality from systemic disease or smoking, compliance/traumatic reruptures). The purpose of this review is to propose an organized, easy-to-remember algorithm for the workup of surgeon-controlled ACLR graft failure etiologies, represented by the acronym "FATAL Graft."

BACKGROUND/UNASSIGNED:Chronic pain affects 20.5% of the US population, costing $296 billion annually in lost productivity. Spinal cord stimulation (SCS) has become a key treatment for refractory neuropathic and nociceptive pain, with increasing usage due to technological advancements. However, the durability of SCS therapy, including explantation rates, remains a concern. Understanding explantation causes is essential for improving patient selection and device effectiveness. This study aims to analyze SCS explantation rates and reasons, as well as evaluate the financial burden of these procedures on the healthcare system. METHODS/UNASSIGNED:Three primary screening methods were used: manual search with keywords, MeSH term query, and reference list screening. The search covered PubMed, Cochrane, and Web of Science databases from inception to November 2024, yielding 719 articles. After applying eligibility criteria, 72 articles were identified, and 25 were selected for analysis. Data extraction was done by independent reviewers, with a second reviewer ensuring accuracy. Discrepancies were resolved by the corresponding editor. RESULTS/UNASSIGNED:We reviewed data from 13,026 patients who underwent permanent SCS implantation between 1984 and 2024, across 25 studies. A total of 1882 patients (9.82%) underwent explantation. The most common reason was lack of efficacy and inadequate pain relief (38%), followed by lead failure (15%) and infection (14%). While SCS is generally effective, issues related to device longevity and patient satisfaction persist, with explantation rates due to technical failures and lack of efficacy being concerns. CONCLUSION/UNASSIGNED:SCS efficacy varies, with explantation rates reaching up to 38%, often due to inadequate pain relief. Most explantations occur within the first year, despite SCS being a safe and effective treatment. High implantation costs ($35,000 to $70,000) and revision costs ($15,000 to $25,000) raise concerns among payors. The hardware-driven model limits waveform flexibility, highlighting the need for innovation.

BACKGROUND:Osteoporosis is a significant cause of morbidity and mortality in the aging population. Individuals with type 2 diabetes mellitus (T2D) typically have higher bone density yet also a higher rate of fractures. Blacks, meanwhile, have a lower incidence of osteoporosis compared to European Americans. Serum bicarbonate may be a risk factor for bone loss, but studies are conflicting, and little is known about this relationship in T2D or Blacks. METHODS:We examined the longitudinal relationship between serum bicarbonate and change in bone density in 300 participants with T2D in the African American-Diabetes Heart Study (AA-DHS). Serum bicarbonate was measured at baseline, and bone density was assessed using CT volumetric bone mineral density (vBMD) scans of the thoracic and lumbar vertebrae at baseline and after five years of follow-up. Multivariate linear regression models assessed associations between baseline serum bicarbonate and longitudinal change in vBMD, adjusted for multiple confounders. RESULTS:, p < 0.001), without a clear threshold effect or differences by sex. CONCLUSIONS:In this cohort of Blacks with T2D, higher baseline serum bicarbonate levels were associated with improved changes in bone density over time. Further studies are needed to determine if alkali supplementation would ameliorate loss of bone density in this population.

OBJECTIVE/UNASSIGNED:To investigate potential disparities in hearing aid use among urban and rural populations with hearing loss. STUDY DESIGN/UNASSIGNED:Cross-sectional analysis. METHODS/UNASSIGNED:We used pooled data from the 2017 and 2018 rounds of the Medicare Current Beneficiary Survey (MCBS). Our analytic sample was restricted to 8107 participants with hearing loss (those who reported little to a lot of trouble hearing) and with a full set of covariates. Multivariate logistic regression models for the probability of hearing aid use were estimated using a participant's place of residence (rural/urban) and household income relative to the Federal Poverty Level (low and middle income ≤ 200% of Federal Poverty Level (FPL); high income > 200% FPL) as main exposures. RESULTS/UNASSIGNED:In models using place of residence as the main exposure, we found no statistically significant difference in hearing aid use between rural and urban populations. In models combining place of residence with income, we found that respondents in the rural high-income group were at the highest odds for hearing aid use (odds ratio (OR): 1.99, 95% confidence interval (CI): 1.52-2.59) when compared to the rural low and middle-income group and, similarly, for the urban high-income (OR: 1.57, 95% CI: 1.26-1.96) and urban low and middle-income groups (OR: 1.31, 95% CI: 1.02-1.69). CONCLUSIONS/UNASSIGNED:There are potential interactions of metro status and income regarding hearing aid use that are more pronounced in rural populations. This might allow policymakers to target interventions for hearing loss to rural and low-income populations. LEVEL OF EVIDENCE/UNASSIGNED:3.

Although platelets play a critical pathogenic role in myocardial infarction (MI), few studies have characterized the MI platelet transcriptome in the acute or chronic setting in women. We report that transcripts associated with the actin cytoskeleton, Rho family GTPases, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n = 40, MI; n = 38, control) and do not significantly change over time. Furthermore, 79 platelet genes chronically elevated or suppressed after MI are associated with future cardiovascular events in an independent high-risk cohort (n = 135). Compared with women with MI with nonobstructive coronary arteries, platelets from women with MI and obstructive coronary artery disease were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased tumor necrosis factor (TNF)-α signaling. Hierarchic clustering of the MI transcriptomic profile identified 3 subgroups with distinctive biological pathways and MI correlates. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients in the acute and chronic settings and reveal a platelet transcriptomic signature with distinct clinical features.

BACKGROUND:Four-dimensional computed tomography is routinely used to localize parathyroid disease, with consistently excellent parathyroid gland localization rates reported. This study evaluated whether pairing 4-dimensional computed tomography results with preoperative clinical variables can accurately predict single-gland disease in primary hyperparathyroidism. METHODS:Patients with primary hyperparathyroidism who underwent both 4-dimensional computed tomography imaging and parathyroidectomy between January 2019 and September 2021 at a large academic health system were included. Patient demographics, preoperative characteristics, and peri- and postoperative data were collected. The accuracy of 4-dimensional computed tomography in correctly identifying patients with single-gland disease with and without preoperative calcium and parathyroid hormone levels was calculated. Single-gland disease was defined by intraoperative parathyroid hormone decrease >50% and a hypercellular gland on pathology. RESULTS:One hundred seventy-five patients had 4-dimensional computed tomography results suggestive of single gland disease. One hundred fifty-two patients (87%) were predicted correctly to have single-gland disease. The predictive accuracy increased when stratifying by preoperative calcium (≥10.5 mg/dL, ≥11 mg/dL, and ≥12 mg/dL) and parathyroid hormone levels (≥65 pg/mL, ≥100 pg/mL, and ≥200 pg/dL). The accuracy further increased when stratifying by age (≤50 years). Accuracy for single gland disease was 100% when combined with any of the following: (1) calcium ≥12 mg/dL, (2) parathyroid hormone ≥200 pg/dL, or (3) calcium ≥11 mg/dL in patients ≤50 years. CONCLUSION/CONCLUSIONS:Four-dimensional computed tomography alone accurately predicted single gland disease in 87% of patients with primary hyperparathyroidism. When combined with preoperative calcium, parathyroid hormone and age thresholds, predictive accuracy for single-gland disease approached 100%. Given the high likelihood of single-gland disease in these scenarios, clinicians may consider offering focused unilateral parathyroidectomy without intraoperative parathyroid hormone monitoring in selected patients.