Qualification of a multiplexed tissue imaging assay and detection of novel patterns of HER2 heterogeneity in breast cancer.

Emerging data suggests that HER2 intratumoral heterogeneity (ITH) is associated with therapy resistance, highlighting the need for new strategies to assess HER2 ITH. A promising approach is leveraging multiplexed tissue analysis techniques such as cyclic immunofluorescence (CyCIF), which enable visualization and quantification of 10-60 antigens at single-cell resolution from individual tissue sections. In this study, we qualified a breast cancer-specific antibody panel, including HER2, ER, and PR, for multiplexed tissue imaging. We then compared the performance of these antibodies against established clinical standards using pixel-, cell- and tissue-level analyses, utilizing 866 tissue cores (representing 294 patients). To ensure reliability, the CyCIF antibodies were qualified against HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) data from the same samples. Our findings demonstrate the successful qualification of a breast cancer antibody panel for CyCIF, showing high concordance with established clinical antibodies. Subsequently, we employed the qualified antibodies, along with antibodies for CD45, CD68, PD-L1, p53, Ki67, pRB, and AR, to characterize 567 HER2+ invasive breast cancer samples from 189 patients. Through single-cell analysis, we identified four distinct cell clusters within HER2+ breast cancer exhibiting heterogeneous HER2 expression. Furthermore, these clusters displayed variations in ER, PR, p53, AR, and PD-L1 expression. To quantify the extent of heterogeneity, we calculated heterogeneity scores based on the diversity among these clusters. Our analysis revealed expression patterns that are relevant to breast cancer biology, with correlations to HER2 ITH and potential relevance to clinical outcomes.

Measuring transition readiness in adolescents and young adults with sickle cell disease using the transition readiness assessment questionnaire.

BACKGROUND/OBJECTIVES: Adolescents and young adults (AYA) with sickle cell disease (SCD) face challenges related to the disease and its treatment. The Transition Readiness Assessment Questionnaire (TRAQ) is a self-report tool for assessing transition readiness for youth with special health care needs (YSHCN), including SCD. This study uses the TRAQ to understand transition readiness in patients with SCD treated at the Boston Medical Center and evaluates associations between TRAQ scores and transition outcomes (e.g., emergency department reliance [EDr] and emergency department utilization [EDu]). METHODS: We reviewed electronic medical records of AYA with SCD who completed the TRAQ in the pediatric hematology clinic between January 1, 2019, and March 1, 2020, and categorized healthcare encounters to calculate EDu and EDr.  We used t tests and ANOVA models to analyze mean TRAQ scores, sex, age, genotype, EDu, and EDr. RESULTS: The sample was 45 AYA patients with SCD between 13 and 22 years old. The mean TRAQ score for the overall patient sample was 3.67. Mean TRAQ scores did not significantly vary by sex or genotype but did significantly increase with age. TRAQ scores did not correlate to EDu or EDr. CONCLUSIONS: AYA patients with SCD have low transition readiness. The age of 18 may not be the most reliable attribute of readiness, though older patients do have higher readiness. The relationship between TRAQ scores, EDr, and EDu is not clear and requires further evaluation.

Soft Tissue Extramedullary Plasmacytoma Leading to Cauda Equina Syndrome: Case Presentation and Clinical Considerations.

Cauda equina syndrome (CES) is a rare neurological emergency that requires prompt diagnosis and immediate surgical intervention for the best potential patient outcome. CES results from the compression of spinal roots along the lower spine usually at the level of L2 or below. It typically presents with severe low back pain, pain radiating to lower extremities, motor weakness, sensory loss, saddle anesthesia, bladder and bowel dysfunction. It is most commonly caused by a large central intervertebral disc herniation or central canal spinal stenosis but can also occur on occasion from abscesses, neoplasms, and inflammatory conditions. If the patient's symptoms are overlooked and surgical intervention is delayed there is a risk for long-term damage to neurological function. Here, we will present a case of a 46-year-old female with a long-standing history of back pain that presented to her primary care office with worsening back pain symptoms as well as a new presentation of urinary incontinence. A prompt MRI confirmed CES and the patient was advised to report to the nearest ED. At the hospital, neurosurgeons performed a laminectomy and found a mass along L3 that was compressing the cauda equina and associated nerve roots. The pathology of the mass revealed an extramedullary plasmacytoma (EMP) that was later determined to originate from the right psoas muscle. The case provides insight into the patient's presentation of CES and the key differentiating factors that led the medical care team to order the appropriate work up and prevent the long-term complications associated with an untreated CES.

Household material hardships impact emergency department reliance in pediatric patients with sickle cell disease.

BACKGROUND: In sickle cell disease (SCD), high emergency department (ED) utilization is associated with worse outcomes and increased costs. A metric called ED reliance (EDr), the percentage of healthcare visits that occur in the ED, attempts to identify ED overutilization. It is unknown if household material hardships (HMH)-housing, utility, or food insecurity-impact reliance on the ED. As these may represent modifiable risk factors for high ED utilization, we aimed to estimate the association between HMH and EDr in pediatric patients with SCD. METHODS: We reviewed the electronic medical records of pediatric patients with SCD who received care in the Boston Medical Center network in Massachusetts, USA, to collect data on HMH and healthcare utilization. Using linear regression to control for potential confounders, we modeled the association between material hardships and EDr. RESULTS: Of 101 eligible patients, 60 (59%) reported one or more HMH. The mean EDr was 12% overall, with significant differences between those with and without HMH (15.9 vs 5.9, P = 0.0001). Each additional hardship experienced was associated with an increased average EDr of 7.7 percentage points (R2  = 0.34, P < 0.0001). Housing and utility hardships were each independently associated with increased EDr. CONCLUSION: HMH are associated with significantly increased EDr in children with SCD, independent of transportation hardship or insurance type. Through screening for HMH, providers and health systems could identify at-risk patients with modifiable risk factors for high EDr in order to provide them additional support.