Citations

Abstract Purpose: Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody–drug conjugates (ADC). Experimental Design: TROP-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EPCAM or TROP-2–positive circulating tumor cells (CTC) were captured from peripheral blood for comparison of protein (n = 15) and gene expression signatures of treatment resistance (n = 40). We assessed the efficacy of TROP-2–targeting agents in a mouse xenograft model generated from prostate cancer cell lines. Results: We demonstrated that TACSTD2 is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in TACSTD2 expression, whereas patients with detectable AR-V7 expression showed increased expression. We observed that TROP-2 can serve as a cell surface target for isolating CTCs, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti–TROP-2 agents in vivo. Conclusions: These results support further studies on TROP-2 as a therapeutic and diagnostic target for mCRPC.

Background The recognition of venous sinus stenosis as a contributing factor in the majority of patients with idiopathic intracranial hypertension coupled with increasing cerebral venography and venous sinus stenting experience have dramatically improved our understanding of the pathophysiologic mechanisms driving this disease. There is now a dense, growing body of research in the neurointerventional literature detailing anatomical and physiological mechanisms of disease which has not been widely disseminated among clinicians. Methods A literature search was conducted, covering the most recent neurointerventional literature on idiopathic intracranial hypertension, the pathophysiology of idiopathic intracranial hypertension, and management strategies (including venous sinus stenting), and subsequently summarized to provide a comprehensive review of the most recently published studies on idiopathic intracranial hypertension pathophysiology and management. Conclusion Recent studies in the neurointerventional literature have greatly improved our understanding of the pathophysiologic mechanisms causing idiopathic intracranial hypertension and its associated conditions. The ability to make individualized, patient-specific treatment approaches has been made possible by advances in our understanding of how venous sinus stenosis and cerebral venous hypertension fundamentally contribute to idiopathic intracranial hypertension.

9 Background: The efficacy of neoadjuvant platinum-based chemotherapy (NAPC) in penile squamous cell carcinoma (PSCC) was provided by small clinical trials, leaving clinicians with scant evidence-based guidance. Thus, we aimed to analyze real-world outcomes of patients with PSCC who received NAPC prior to surgical resection. Methods: Patients from 9 tertiary care centers who had undergone NAPC prior surgical resection for PSCC were included with locally advanced (cTany, cN+), non-metastatic (M0) disease. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), Response was determined via best overall response measured with RECIST 1.1 criteria. Results: 167 patients were included, 137 (84%), of which received TIP prior to surgical resection. Ninety-two (55%) patients died during follow up, and the mean follow up for survivors was 57 months. The median OS was 42 months, while the median PFS was 17 months. The table details the response rates to NAPC, the associated survival, and Cox Proportional Hazards Modelling of OS and PFS. Predictors for OS and RFS included lymphovascular invasion, positive number of lymph nodes, extranodal extension, downstaging, best overall response, and ypN status. Figure 1 demonstrates OS outcomes by RECIST best response after chemotherapy, presence of downstaging after NAPC, ypN stage, and presence of extranodal extension. Conclusions: Upfront NAPC is effective in patients with lymph node metastases from penile carcinoma. Unsurprisingly, patients who demonstrated a robust response to therapy had improved survival outcomes compared to those who had not—as measured by RECIST criteria, tumor downstaging, pN staging, and presence of extranodal extension. This study represents the largest conglomeration of multi-institutional penile carcinoma patients treated with NAPC, and provides further supportive data for multimodal therapy for advanced penile cancer patients while prospective clinical trials complete accrual. [Table: see text]

There is limited literature analyzing pediatric hurdle injuries based on sex and age. This study compares hurdle-related injury types, injured body parts, and injury mechanisms by age and sex in pediatrics. Hurdle-related injury data from the National Electronic Injury Surveillance System were used to retrospectively review the injuries of hurdlers 18 years and under. Differences in injured body parts, injury types, and mechanisms were analyzed by age (pre-high school vs. high school) and sex (male vs. female). A total of 749 cases were extracted. Fractures were more common in pre-high schoolers (34.1% vs. 21.5%, p = 0.001), while more sprains were identified in high schoolers (29.6%) than pre-high schoolers (22.8%, p = 0.036). Males suffered more fractures than females (35.1% vs. 24.3%, p = 0.001). Females sustained more joint sprains (29.1% vs. 21.0%, p = 0.012) and contusions/hematomas (12.7% vs. 7.5%, p = 0.020). Ankle injuries were more common in females (24.0%) than males (12.0%, p = 0.001), while wrist injuries were more prevalent in males (11.7% vs. 7.2%, p = 0.034). The most common injury mechanism was apparatus-related, with no differences based on age or sex. Injury types and injured body parts differed depending on age and sex in pediatric hurdle injuries seen in emergency departments. These findings may be helpful for injury prevention and medical care for pediatric hurdlers.

Purpose: To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED). Methods: A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED. Results: Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1–4) and reached an average peak of 5.0 during the active phase of the disease (4–7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease. Conclusions: Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves’ disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.

Background: Exposure to hyperoxia, a high arterial partial pressure of oxygen (PaO2), may be associated with worse outcomes in patients receiving extracorporeal membrane oxygenator (ECMO) support. We examined hyperoxia in the Extracorporeal Life Support Organization Registry among patients receiving venoarterial ECMO for cardiogenic shock. Methods: We included Extracorporeal Life Support Organization Registry patients from 2010 to 2020 who received venoarterial ECMO for cardiogenic shock, excluding extracorporeal CPR. Patients were grouped based on PaO2 after 24 hours of ECMO: normoxia (PaO2 60–150 mmHg), mild hyperoxia (PaO2 151–300 mmHg), and severe hyperoxia (PaO2 >300 mmHg). In-hospital mortality was evaluated using multivariable logistic regression. Results: Among 9959 patients, 3005 (30.2%) patients had mild hyperoxia and 1972 (19.8%) had severe hyperoxia. In-hospital mortality increased across groups: normoxia, 47.8%; mild hyperoxia, 55.6% (adjusted odds ratio, 1.37 [95% CI, 1.23–1.53]; P <0.001); severe hyperoxia, 65.4% (adjusted odds ratio, 2.20 [95% CI, 1.92–2.52]; P <0.001). A higher PaO2 was incrementally associated with increased in-hospital mortality (adjusted odds ratio, 1.14 per 50 mmHg higher [95% CI, 1.12–1.16]; P <0.001). Patients with a higher PaO2 had increased in-hospital mortality in each subgroup and when stratified by ventilator settings, airway pressures, acid-base status, and other clinical variables. In the random forest model, PaO2 was the second strongest predictor of in-hospital mortality, after older age. Conclusions: Exposure to hyperoxia during venoarterial ECMO support for cardiogenic shock is strongly associated with increased in-hospital mortality, independent from hemodynamic and ventilatory status. Until clinical trial data are available, we suggest targeting a normal PaO2 and avoiding hyperoxia in CS patients receiving venoarterial ECMO.

Abstract Purpose The intravenous (IV) medication compounding workflow has long been associated with preventable medication errors. This has led to the development of technologies designed to enhance the safety of IV compounding workflows. Digital image capture is a component of this technology about which there is relatively limited published literature. This study evaluates image capture implemented within an electronic health record’s existing first-party IV workflow solution. Methods A retrospective case-control study was conducted to measure IV preparation times before and after digital imaging implementation. Preparations during 3 periods (preimplementation, ≤1 month post implementation, and &gt;1 month post implementation) were matched for 5 variables. A less stringent analysis with matching for 2 variables, as well as an unmatched analysis, were performed post hoc. An employee survey assessed satisfaction with the digital imaging workflow, and revised orders were reviewed to identify new problems introduced by image capture. Results A total of 134,969 IV dispenses were available for analysis. Median preparation time in the preimplementation and &gt;1 month post implementation cohorts was unchanged in the 5-variable matched analysis (6.87 minutes vs 6.58 minutes, P = 0.14) and increased in the 2-variable matched analysis (6.98 minutes vs 7.35 minutes, P &lt; 0.001) and unmatched analysis (6.55 minutes vs 8.02 minutes, P &lt; 0.001). A large majority of survey respondents (92%) felt that image capture improved patient safety. Of the 105 postimplementation preparations identified as requiring revisions by the checking pharmacist, 24 (22.9%) required revisions directly related to camera functionality. Conclusion Implementation of digital image capture likely increased preparation times. Most IV room staff felt that image capture increased preparation times and were satisfied with how the technology improved patient safety. Image capture introduced camera-specific issues that led to preparations requiring revisions.