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OBJECTIVE Pelvic incidence (PI) is a key parameter of sagittal alignment. While conventionally held to be fixed, increasing evidence suggests PI may be variable. This study aimed to identify predictors of change in PI with patient position and to assess the association of preoperative radiographic characteristics and intraoperative maneuvers with postoperative PI. METHODS Patients who underwent thoracolumbosacral fusion were identified, and data were gathered on preoperative spinopelvic parameters, patient demographic characteristics, and operative details. Preoperative spinopelvic parameters were measured on upright, supine, and prone radiographs. Univariable comparisons of PI between the different patient positions were performed. Multivariable analysis was performed to identify variables independently correlated with PI on 6-week postoperative radiographs. Change in PI was defined as ≥ 5° change between positions. RESULTS In total, 138 patients were identified (mean ± SD age 66.0 ± 8.7 years; 38.4% male). Statistically significant differences in PI were noted between preoperative standing and supine (mean −3.2° ± 4.2°, p < 0.001), preoperative supine and prone (3.5° ± 4.7°, p < 0.001), preoperative and 6-week postoperative standing (1.5° ± 6.2°, p = 0.01), and immediate and 6-week upright (1.1° ± 3.9°, p = 0.007) radiographs. Univariable comparisons showed PI decrease from standing to supine was predicted only by weight (87.0 ± 15.0 vs 81.1 ± 19.3 kg, p = 0.04); there were no significant predictors of increase in PI from standing to prone. Increase in PI from preoperative to 6-week standing radiographs was predicted by lower preoperative PI class (p < 0.001), L5/S1 interbody placement (74.4% vs 52.0%, p = 0.02), and change in PI from preoperative standing to supine (12.8% vs 39.8%, p = 0.002) and from standing to prone (51.3% vs 13.3%, p < 0.001). Multivariable analysis showed that 6-week postoperative PI was associated with only preoperative supine PI (B = 0.293, 95% CI 0.10–0.48, p = 0.003) and prone PI (B = 0.647, 95% CI 0.44–0.85, p < 0.001). CONCLUSIONS There are position-dependent changes in PI among patients without prior pelvic fixation. Statistically significant changes in PI are seen even after pelvic fixation with a single S2-alar-iliac screw bilaterally. Postoperative PI was best predicted by preoperative PI on supine and prone radiographs rather than upright radiographs, suggesting that preoperative prone and supine radiographs may provide surgeons with the best information for achieving PI–lumbar lordosis mismatch < 10°.

OBJECTIVE Transforaminal lumbar interbody fusion (TLIF) offers both indirect decompression and segmental correction through restoration of disc height. However, stresses exerted on the vertebral endplates by the interbody device can result in implant subsidence and loss of correction. The present time-to-event analysis aimed to identify predictors of interbody subsidence. METHODS Patients who underwent 1- or 2-level TLIF were identified. Data on demographics, surgical details, preoperative bone quality using CT-based Hounsfield units (HU), and pre- and postoperative lumbopelvic parameters were collected. Univariable analyses were conducted to identify predictors of subsidence (≥ 2-mm intrusion of interbody into cranial or caudal vertebrae) and significant subsidence (≥ 4-mm intrusion). Multivariable Cox regression was performed to identify independent predictors of subsidence, expressed as hazard ratios with 95% confidence intervals. RESULTS A total of 198 patients treated at 241 levels were included (median age 66.6 years, IQR 59.5, 73.7 years; 56.6% were women). In 92 levels (38.2%) there was some subsidence and in 25 (10.4%) there was significant subsidence. Implanted levels demonstrating subsidence (≥ 2 mm) were associated with lower HU in cranial and caudal vertebrae; had interbodies positioned farther from the anterior apophyseal ring; were implanted with taller, more lordotic interbodies; and underwent greater disc height restoration. Those showing significant subsidence (≥ 4 mm) were similarly associated with lower HU in the cranial and caudal vertebrae; had interbodies positioned farther from the anterior apophyseal ring of the caudal vertebrae; and underwent greater disc height restoration. Multivariable Cox regression showed that time to subsidence was predicted by greater implant height (HR 1.20/mm, 95% CI 1.05–1.38; p = 0.009), greater postoperative disc height (HR 1.21/mm, 95% CI 1.09–1.34; p < 0.001), and greater disc height restoration (HR 1.11/mm, 95% CI 1.04–1.19; p = 0.002). The time-to-subsidence analysis for significant (≥ 4 mm) subsidence showed that it was predicted by lower HU in the cranial vertebrae (HR 0.98/unit, 95% CI 0.97–0.99; p = 0.001); increasing number of levels instrumented (HR 1.26, 95% CI 1.04–1.52; p = 0.016); and greater disc height restoration (HR 1.33/mm, 95% CI 1.18–1.51; p < 0.001). CONCLUSIONS This time-to-event analysis suggests that interbody subsidence following TLIF is best predicted by implantation of a taller interbody and aggressive disc height restoration. Significant subsidence is similarly predicted by aggressive disc height restoration along with poor baseline bone quality. The results suggest the need to balance aggressive correction at the time of surgery against the increased risk of subsequent interbody subsidence.

Précis: In our study of the factors predictive of latanoprost response, we found that normotensive subjects with higher intraocular pressure, lower uveoscleral outflow, and higher body mass index had a greater response to 1-week treatment. Purpose: To evaluate relationships between variable intraocular pressure (IOP) responses to latanoprost and participant characteristics, baseline values and changes in aqueous humor dynamics (AHD) parameters. Methods: We assessed 226 eyes from 113 healthy participants. AHD parameters measured at baseline and after 1-week treatment with latanoprost included: IOP by pneumatonometry, episcleral venous pressure (EVP) by venomanometry, aqueous humor flow rate by fluorophotometry, outflow facility by 2-minute pneumatonography, and uveoscleral outflow calculated using the modified Goldmann equation. IOP responses were categorized into 4 groups: nonresponders (<10% reduction), all-responders (≥10% reduction), medium-responders (10%–20% reduction), and high-responders (≥20% reduction). Generalized estimating equation models were used to analyze treatment effects and compare groups. Results: Baseline IOP was higher in high-responders than medium-responders and nonresponders ( P =0.007 and P <0.001, respectively). Body mass index (BMI) was significantly higher in high-responders and all-responders compared with nonresponders ( P =0.02 and P =0.03, respectively). Responders had lower baseline uveoscleral outflow ( P =0.03). There were no significant differences in other baseline characteristics including EVP, outflow facility, and aqueous flow rate between the 4 groups. IOP decreased while outflow facility and uveoscleral outflow increased after latanoprost treatment in all responder groups but did not change in nonresponders. EVP and aqueous flow rate did not change significantly in any group. The change in uveoscleral outflow was greater in high-responders than in nonresponders ( P =0.004). Conclusions: In healthy subjects, higher baseline IOP, lower uveoscleral outflow and higher BMI are predictors of a greater IOP reduction by latanoprost. A greater increase in uveoscleral outflow is responsible for this larger response.

AbstractA diverse workforce in emergency medicine (EM) aims to improve patient care by addressing racism in health care, increasing representation in medicine, and improving the quality of training for all residents. Many EM residency programs have launched recruitment efforts to attract residents from diverse backgrounds. However, recruitment efforts only represent the first step in building a culturally responsible workforce. Trainees who are underrepresented in medicine must be welcomed into an inclusive training environment that has been thoughtfully constructed before they arrive. This type of supportive environment can be achieved by shifting away from majority‐serving ideals and building an informed infrastructure that functions to help all trainees succeed. We expand upon challenges and areas of opportunity at the individual, departmental, and institutional levels and describe common pitfalls when trying to create inclusive spaces for residents including lack of vision alignment, inadequate financial investment, and performative allyship. We also propose strategies that focus specifically on actionable changes that residency program, departmental, and institutional leadership can implement to mitigate these challenges.

Abstract The Phase 2 IMPRIME 1 study evaluated the combination of the pathogen-associated molecular pattern (PAMP) Imprime with the immune checkpoint inhibitor (ICI) pembrolizumab as second or later line of treatment (2 L+) for patients with metastatic triple-negative breast cancer (mTNBC). Eligible patients with mTNBC received weekly Imprime (4 mg/kg) intravenously in combination with pembrolizumab (200 mg every 3 weeks). Primary endpoints were overall response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression free survival (PFS), and overall survival (OS). Exploratory endpoints included correlations between immune cell activation markers in tumor tissues and blood and response to therapy. Of the 42 evaluable patients, six had a response (one complete, five partial), with an ORR of 14.3% by RECIST v1.1. Median PFS was 2.7 months, median OS was 16.4 months, and DCR was 54.8%, with responders achieving a median DoR of 15.2 months. Therapy was generally well tolerated and resulted in an increase of immune activation markers, with higher levels of activation in peripheral blood associated with response and improved survival. The combination of Imprime and pembrolizumab was safe and demonstrated immune activation in tumor tissues and peripheral blood in patients with TNBC. Improved response rates were observed compared to historical studies of ICI monotherapy in similar patient populations. Study number (ClinicalTrials.gov trial registration): NCT02981303.

Introduction: Bone health optimization is a key component of the preoperative management of spine surgery patients, as poor bone quality increases the odds of mechanical complications. The present study aimed to achieve the following: (1) compare the relative efficacy of current osteoporosis medications in improving bone quality; (2) identify factors influencing treatment response in preoperative spine surgery patients. Methods: Patients treated at a single, multisite institution who received osteoporosis treatment were identified. Data were gathered on pre- and post-treatment lumbar spine Hounsfield Unit (HU) measurements, patient demographics, frailty scores (modified Frailty Index/mFI, risk analysis index/RAI), and pharmacologic treatment details. The primary outcome was a ≥7 point improvement in lumbar HU, and baseline and logistic regression models were utilized to identify factors associated with this improvement. Medications were grouped as anabolic (teriparatide, romosozumab) and antiresorptive (denosumab, alendronate) therapies. Results: A total of 267 patients were included (median age: 74 years; IQR [66–81]; 67.3% female), with 127 (47.6%) improving by ≥7 HU. The treatment agents used were alendronate (95), denosumab (113), romosozumab (31), and teriparatide (28). Univariable comparisons revealed significant differences across medication groups in age (p < 0.001), sex (p < 0.001), mFI (p < 0.001), RAI (p = 0.004), BMI (p < 0.001), pre-treatment HU (p = 0.022), and treatment duration (p < 0.001). The highest HU improvement rates (ΔHU ≥ 7) were observed in patients receiving the anabolic medications romosozumab (67.7%) and teriparatide (60.7%). Univariable logistic regression identified male sex (OR 0.54, p = 0.019), higher pre-treatment HU (OR 0.99, p = 0.006), and longer treatment duration (OR 0.97, p = 0.003) as factors associated with lower odds of HU improvement. Only romosozumab was associated with significantly higher odds of HU improvement relative to alendronate (OR 3.02, p = 0.012). In our multivariable analysis, male sex (OR 0.53, p = 0.028) and higher pre-treatment HU (OR 0.99, p = 0.002) remained significant predictors of HU improvement. However, medication type was not significant in the multivariable analysis. Conclusions: Our study highlights that male sex and higher pre-treatment HU were independently associated with lower odds of HU improvement, while medication type was not a significant predictor. Additionally, anabolic agents offered superior improvement relative to antiresorptive therapies.

ABSTRACT Background Incident atrial functional mitral regurgitation (AFMR) is associated with mortality. Transcatheter edge‐to‐edge repair (TEER) has shown effectiveness in improving MR and symptoms in AFMR, but previous studies lacked comparison to conservative management. We aimed to study the association of AFMR severity and mitral TEER with symptoms, heart failure hospitalizations (HFH) and all‐cause mortality in moderate/severe AFMR. Methods Consecutive adults with moderate/severe AFMR managed conservatively or with TEER 2010−2023 were identified retrospectively. To ensure similar technique in evaluation in the two groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group. In addition to multivariable analysis, the association of TEER (vs. conservative management) with HFH and mortality was assessed using propensity‐score matched analyses; the propensity score was based on age, sex, EuroSCORE II, effective regurgitant orifice area, integrative MR severity, and NYHA class III/IV (vs. I/II). Results Among 230 patients with moderate/severe AFMR [mean age 77; 56% females], 46 were managed with TEER. Severe (vs. moderate) AFMR was independently associated with baseline NYHA class III/IV (multivariable OR 2.18 [95% CI 1.13−4.26]) and HFH [multivariable HR 2.75 (95% CI 1.25−6.03)] but not mortality ( p = 0.26). TEER improved MR to ≤ moderate in 93% but was not associated with lower HFH or death rates versus conservative management on multivariable or matched analysis. However, 1‐year NYHA improved more with TEER versus conservative management in patients with baseline NYHA class III/IV (62% vs. 27%, p = 0.03). Rhythm control was associated with improved survival (HR 0.38 [0.15−0.98]). Conclusions AFMR severity was associated with symptoms and HFH but not mortality. MR severity and NYHA class improved with TEER, but the association of TEER with HF hospitalizations or death remains unproven. Randomized studies are needed to evaluate the potential role of TEER and rhythm control on outcomes in AFMR.

Abstract Immune checkpoint inhibitors (ICIs) block immunoregulatory receptor-ligand interactions and robustly increase survival of cancer patients but frequently result in immune-related adverse events (irAEs). While rheumatologic toxicities are commonly reported as irAEs, the effect of immune checkpoint blockade on the underlying mechanisms of ICI-induced fractures and bone loss is controversial, with reports of both positive and negative effects on bone mass in preclinical models. However, no previous reports have investigated the impact of ICIs on females or aged mice, or on fracture risk in either sex. We report that global deletion of programmed cell death protein 1 (PD-1) broadly results in bone loss in skeletally mature male and female PD-1−/− mice, with a sexually divergent phenotype in adolescent mice, decreased bone strength in adult males and young females, and expansion of multiple T cell subsets in the bone marrow. In a model of pharmacologic PD-1 blockade, administration of α-PD-1 reduced bone mass, expanded multiple T cell subsets in the bone marrow, and increased osteoclast activity and resorptive capacity. T cell deficient mice were resistant to osteoclast-mediated bone loss following α-PD-1 therapy, suggesting that T cells in the bone marrow are necessary for bone loss in the setting of ICI therapy. These findings may be leveraged to identify patients at greater fracture risk following ICI therapy due to enrichment of effector T cell populations in the bone marrow.