Faculty Bibliography

UNLABELLED:Pelvic fractures result in prolonged pain and immobility. In a randomized controlled trial of patients with pelvic fracture, whether abaloparatide (ABL) vs. placebo (PBO) improves healing at 3 months was evaluated. There was no significant difference in CT radiologic healing, physical performance, or change in pain in ABL vs. placebo. PURPOSE/OBJECTIVE:To determine if abaloparatide (ABL) vs. placebo (PBO) improves radiologic healing, pain, and functional outcome at 3 months in patients with pelvic fracture. METHODS:Postmenopausal women and men ≥ 50 years old, enrolled within 4 weeks of pelvic fracture (n = 48), were randomized to blinded ABL vs. PBO. The primary endpoint, fracture healing at 3 months, was assessed by two radiologists using a 5-point scale for cortical bridging from CT images comparing groups by Jonckheere-Terpstra test. The odds of healing (3 or 4 cortices bridged) were analyzed with Mantel-Haenszel relative risks (RR). Pain was assessed monthly by Numeric Rating Scale (NRS). The Short Physical Performance Battery (SPPB; walk speed, chair stands, and balance) evaluated functional mobility. RESULTS:Groups were balanced with a mean age = 82, 93% were female, 98% had multiple rami fractures, 67% had sacral fracture, and 36% had ≥ 1 displaced fracture. CT images at 3 months showed no significant difference in bridging score distribution (indicator of healing) in patients with ABL vs. PBO (p = 0.15) after adjusting for age, sacral fracture, displacement, or compliance. When evaluating individual fractures (n = 81), similar bridging scores were seen with ABL and PBO (p = 0.13). When patients were stratified as healed or not healed, 39% were healed with ABL and 64% healed with PBO (RR 0.61; 95% CI 0.33, 1.12). When looking at the 81 individual fractures, 47% were healed with ABL and 53% healed with PBO (RR = 0.88; 95% CI 0.55, 1.40). Using least square means controlling for age, sacral, and displaced fracture, NRS pain score was higher in the placebo than the ABL group at baseline (p < 0.05), but there were no further group differences in change in pain score SPPB and TUG scores improved over time in both groups without group differences. CONCLUSION/CONCLUSIONS:In this small study, there was no significant difference in CT radiologic healing, physical performance, or change in pain with ABL vs. placebo in patients with acute pelvic fracture. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT04249232 registered January 27, 2020.

BACKGROUND/UNASSIGNED:It is unknown how the increased range of motion and improved gait mechanics provided by total ankle arthroplasty (TAA) affects the progression of subtalar arthritis compared with ankle arthrodesis (AA). We hypothesized that patients treated with TAA would have a lower incidence of postoperative subtalar arthrodesis (SA) compared to AA. METHODS/UNASSIGNED: <.05. RESULTS/UNASSIGNED: > .05). In a multivariate analysis, AA remained associated with increased risk of requiring SA (OR = 1.90, CI = 1.01-3.56). CONCLUSION/UNASSIGNED:In this study, we found a significantly higher incidence of subtalar arthrodesis following AA compared with TAA. Surgeons may consider the risk of progression to SA when deciding between TAA and AA for patients with advanced ankle arthritis, particularly in preoperative counseling for patients without existing subtalar arthritis, as TAA may offer an opportunity to mitigate this risk. LEVEL OF EVIDENCE/UNASSIGNED:Level III, retrospective comparative study.

Glomerular injury secondary to infection is a well-documented phenomenon. While the incidence of classic acute post-streptococcal glomerulonephritis (APIGN) has declined in developed countries over the past few decades, IgA-dominant infection-associated glomerulonephritis (IgA PIGN) is emerging as a distinct renal pathology. Characterized by predominant deposition of IgA antibodies within the glomeruli following infection, IgA-dominant PIGN differs from classic PIGN, which typically involves IgG and C3 deposits. This condition is often associated with staphylococcal infections and carries a poor prognosis. It commonly affects older adults and presents with reduced glomerular filtration rate and heavy proteinuria. Due to its rarity and overlapping clinical features with other glomerular diseases, IgA PIGN can be challenging to diagnose, often progressing to end-stage renal disease (ESRD) in approximately 80 % of cases. Prompt diagnosis and management, often requiring renal biopsy, are crucial for improving outcomes. Here, we present a case of IgA-dominant postinfectious glomerulonephritis.

BACKGROUND:Social determinants of health (SDOH) influence cancer prevention and outcomes. Among SDOH, economic stability-including food insecurity, income, employment, and housing stability-has a major impact on health. However, data linking food security status with cancer screening completion remain limited. We examined whether lower food security status was associated with lower completion of colorectal, breast, cervical, and prostate cancer screening. METHODS:We performed a retrospective analysis of the 2018-2023 National Health Interview Survey. Analyses were limited to cancer-specific complete-case cohorts: colorectal (N = 59,849), breast (N = 30,867), cervical (N = 56,229), and prostate (N = 20,518). Food security was categorized as high, marginal, or low/very low. Screening completion was the dependent variable. Multivariable logistic regression estimated adjusted odds ratios (aORs) for screening by food security status, controlling for sociodemographic and clinical covariates. Sensitivity analyses used age-stratified eligibility definitions across survey years. RESULTS:Compared with high food security, marginal food security was associated with lower odds of screening across cancers (aOR range, 0.63-0.88), and low/very low food security showed similar or larger deficits (aOR range, 0.60-0.88). Associations were significant for all four cancers and were similar in sensitivity analyses. CONCLUSIONS:Lower food security status was associated with lower completion of cancer screening. Addressing food insecurity may improve screening equity and reduce cancer disparities. IMPACT/CONCLUSIONS:Lower food security status was associated with lower completion of guideline-recommended screening across four cancers, even after multivariable adjustment. Future work should test whether interventions addressing food insecurity can improve screening.

PURPOSE/OBJECTIVE:EA1181 (ClinicalTrials.gov identifier: NCT04266249) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point-3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)-will be reported when data mature. METHODS:Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS:A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER-]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER- and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER- tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION/CONCLUSIONS:Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER- and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

Microglia perform the function of CNS macrophages and act as the primary immune cells in the brain. They surveil the environment, phagocytose cellular debris, maintain homeostasis and respond to tissue damage. While under physiological conditions they play a role in supporting neurons, activated microglia participate directly in the degeneration of neurons in the substantia nigra, as the hallmark of the Parkinsons disease (PD). Their detrimental effects result from direct phagocytosis of dopaminergic neurons as well as via neuroinflammation and release of toxic reactive oxygen and nitrogen species. This pathological shift is driven by a complex interplay of genetic predispositions, such as LRRK2 and GBA mutations, and environmental triggers like toxins and gut dysbiosis.A central mechanism of this neurodegeneration involves extracellular α-synuclein acting as a danger signal (DAMP), which activates microglial Toll-like receptors (e.g., TLR2) to initiate a severe inflammatory cascade. Furthermore, the extreme biophysical stability of aggregated α-synuclein overwhelms the microglial endolysosomal network, leading to lysosomal failure, "frustrated phagocytosis," and the active propagation of the disease via exosomal shedding. Relieving this maladaptive chronic neuroinflammation is a primary therapeutic goal. Modern strategies aim to break this vicious cycle through precise interventions like NLRP3 inflammasome inhibition and autophagy enhancement. Concurrently, advanced fluid biomarkers, such as seed amplification assays (SAA), alongside multidimensional neuroimaging techniques (PET, SPECT, MRI), are proving crucial for detecting these early microglial and pathological changes to guide personalized, disease-modifying therapies of PD.

Nuisance property ordinances are municipal laws that penalize property owners or renters for alleged criminal activity or repeated disturbances, including emergency calls. As these laws have expanded, concerns have grown that they may disproportionately impact marginalized populations, including people who use drugs, by targeting drug-related activities and exacerbating chronic housing instability. This study examines the demographic and municipal-level characteristics associated with the presence of drug-related nuisance property ordinances (DNPOs) across major U.S. municipalities. Municipal codes were systemically analyzed for DNPOs across 482 municipalities in the U.S. DNPOs were classified as ordinances that list specific activities related to drugs, drug paraphernalia, or illegal activity as a nuisance. A chi-square test was used to compare proportions of demographic and socioeconomic characteristics between municipalities with and without DNPOs. 202 of 482 municipalities had DNPOs (41.9%). 73 of 202 municipalities, 36.1% of DNPOs, authorized eviction as a legal method of abatement. DNPOs were more likely to be found in municipalities with higher proportion of Black, non-Hispanic populations, lower median household income, higher poverty rates, higher unemployment rates, higher population density, higher proportions of renters, and moderate to higher rates of overdose (p < 0.05). DNPOs are prevalent across U.S. municipalities and frequently include eviction as a permitted or required abatement strategy. Our findings show that DNPOs are more likely to be present in socioeconomically disadvantaged communities. These findings underscore the need to further evaluate the health and equity consequences of nuisance property ordinances for people who use drugs.

BACKGROUND/UNASSIGNED:Despite recent improvements in radiation safety, interventionalists are increasingly exposed to radiation during cardiac catheterization laboratory (CCL) procedures. The RADPAD was designed as a protective scatter-radiation absorbing shield with early studies demonstrating a 20% to 62% reduction in scatter-radiation. The objective of this study was to examine the impact of the protective scatter-radiation absorbing shield in a large contemporary randomized controlled trial across multiple CCL procedures. METHODS/UNASSIGNED:The investigator-initiated, prospective, randomized, controlled ATTENUATE (rAdpad proTecTion drapE iN redUcing rAdiaTion Exposure) trial randomized CCL procedures 1:1 to use of the RADPAD vs no use of the RADPAD. The primary outcome of interest was the most proximal operator's dose area product (DAP)-normalized operator dose (E). RESULTS/UNASSIGNED:= .1094). CONCLUSIONS/UNASSIGNED:In the largest randomized controlled trial to date evaluating the RADPAD protective scatter-radiation absorbing shield, encompassing contemporary coronary and structural CCL procedures, use of the protective scatter-radiation absorbing shield led to a marked decrease in proximal operator radiation exposure when adjusted for the total radiation delivered during each procedure.