Patient factors associated with telehealth quality and experience among adults with chronic conditions.

Objective: To evaluate patient-reported experiences of telehealth and disparities in access, use, and satisfaction with telehealth during the COVID-19 pandemic. Materials and methods: We examined data from the fifth wave of the COVID-19 & Chronic Conditions (C3) study conducted between December 2020 and March 2021. Results: Of the 718 participants, 342 (47.6%) reported having a telehealth visit within the past 4 months. Participants who had a recent telehealth visit were younger, reported worse overall health and chronic illness burden, and living below poverty level. Among participants who had a telehealth visit, 66.7% reported telephone visits and most participants (57.6%) rated telehealth quality as better-or-equal-to in-person visits. Inadequate health literacy was associated with lower likelihood of reporting telehealth quality and usefulness. In multivariable analyses, lower patient activation (adjusted odds ratio (AOR) 0.19, 95% CI, 0.05-0.59) and limited English proficiency (AOR 0.12, 95% CI, 0.03-0.47) were less likely to report telehealth as being better than in-person visits; lower patient activation (AOR 0.06, 95% CI, 0.003-0.41) and income below poverty level (AOR 0.36, 95% CI, 0.13-0.98) were associated with difficulty remembering telehealth visit information. Discussion: Most participants reported usefulness and ease of navigating telehealth. Lower socioeconomic status, limited English proficiency, inadequate health literacy, lower educational attainment, and low patient activation are risks for poorer quality telehealth. Conclusion: The COVID pandemic has accelerated the adoption of telehealth, however, disparities in access and self-reported visit quality persist. Since telemedicine is here to stay, we identify vulnerable populations and discuss potential solutions to reduce healthcare disparities in telehealth use.

Exploratory pilot study to characterize the immune landscapes of malignant pleural effusions and their corresponding primary tumors from patients with breast carcinoma and lung adenocarcinoma.

INTRODUCTION: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples. MATERIALS AND METHODS: We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion-free survival. RESULTS: No MPE samples had positive programmed death-ligand 1 expression in malignant cells, although 3 of 11 PTs has positive programmed death-ligand 1 expression (more than 1% expression in malignant cells). Overall, in LADC samples, cluster of differentiation 3 (CD3)+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs versus PTs: 45.6% versus 40.7% and 4.7% versus 6.6%, respectively) compared with BC. CD68+ macrophages predominated in the BC samples (medians for MPEs 61.2% versus PTs for 57.1%) but not in the LADC samples. Generally in PTs, CD3+CD8+ forkhead box P3+ T cells and the median distances from the malignant cells to CD3+CD8+Ki67+ and CD3+ programmed cell death protein 1 + T cells correlated to earlier MPE after PT diagnosis. CONCLUSIONS: The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but different between BC versus LADC. An MPE analysis can potentially be used as a substitute for a PT analysis, but an expanded study of this topic is essential.

Novel syndromic neurodevelopmental disorder caused by de novo deletion of CHASERR, a long noncoding RNA.

Genes encoding long non-coding RNAs (lncRNAs) comprise a large fraction of the human genome, yet haploinsufficiency of a lncRNA has not been shown to cause a Mendelian disease. CHASERR is a highly conserved human lncRNA adjacent to CHD2-a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here we report three unrelated individuals each harboring an ultra-rare heterozygous de novo deletion in the CHASERR locus. We report similarities in severe developmental delay, facial dysmorphisms, and cerebral dysmyelination in these individuals, distinguishing them from the phenotypic spectrum of CHD2 haploinsufficiency. We demonstrate reduced CHASERR mRNA expression and corresponding increased CHD2 mRNA and protein in whole blood and patient-derived cell lines-specifically increased expression of the CHD2 allele in cis with the CHASERR deletion, as predicted from a prior mouse model of Chaserr haploinsufficiency. We show for the first time that de novo structural variants facilitated by Alu-mediated non-allelic homologous recombination led to deletion of a non-coding element (the lncRNA CHASERR) to cause a rare syndromic neurodevelopmental disorder. We also demonstrate that CHD2 has bidirectional dosage sensitivity in human disease. This work highlights the need to carefully evaluate other lncRNAs, particularly those upstream of genes associated with Mendelian disorders.

Concordance between pathologists and between specimen types in detection of HER2-low breast carcinoma by immunohistochemistry.

CONTEXT: Recent clinical trials indicate that HER2-targeted therapy may benefit HER2-low breast cancer patients including HER2 score 1+ or 2+ and no gene amplification. Concordance between pathologists and between core biopsy and surgical excision in establishing HER2-low status was evaluated. DESIGN: 57 patients with HER2 negative breast cancer (IHC 0, 1+, or 2+, no gene amplification) by core biopsy were included. Core biopsy and representative tumor from corresponding surgical excision was immunostained for HER2. Original HER2 IHC scores were interpreted using 2018 guidelines. Three pathologists independently interpreted again under 2023 guidelines. Kappa statistic evaluated agreement of HER2 IHC scores. RESULTS: Applying 2023 guidelines, HER2 IHC scores were concordant among study pathologists in 46 of 57 (81 %) core biopsy and 50 of 57 (88 %) surgical resections. Kappa statistics were 0.78 and 0.85 (substantial agreement), for inter-pathologist agreement of core biopsy and surgical resections under 2023 guidelines; 0.55 (moderate agreement) for agreement between first interpretation by 2018 guidelines and second interpretation by 2023 guidelines; and 0.13 (slight agreement) for agreement in HER2 consensus scores between outside core and surgical resection and 0.49 (moderate agreement) for inside core and surgical resection. Low HER2 expression was found in 28 of 57 (49 %) core biopsy and in 25 of 57 (44 %) surgical excisions. CONCLUSIONS: Interobserver agreement among study pathologists was good in core biopsy and surgical excisions, applying updated 2023 guidelines. Intratumoral heterogeneity in protein expression and preanalytical factors may result in variable identification of HER2-low status in core biopsy and surgical excision specimens.

Disparities in Patient Portal Use Among Adults With Chronic Conditions.

Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic. Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors. Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022. Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation. Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64). Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Complete genome sequences of nine Rhodococcus equi phages.

We report genomes of nine phages isolated from Actinobacteria Rhodococcus equi NRRL B-16538. Six of these phages belong to actinobacteriophage cluster CR, which otherwise contains Gordonia phages; two form the CF cluster; and one is a singleton. Genome lengths are 62,017-80,980 bp with 63.9%-67.3% GC content.

Pharmacokinetics, Safety, and Tolerability of Anti-SARS-CoV-2 Monoclonal Antibody, Sotrovimab, Delivered Intravenously or Intramuscularly in Japanese and Caucasian Healthy Volunteers.

BACKGROUND AND OBJECTIVE: Sotrovimab 500 mg administered by a single intravenous (IV) infusion has been granted special approval for emergency use in Japan for treatment of SARS-CoV-2 infection in adults and children aged ≥ 12 years weighing ≥ 40 kg. This Phase 1, single-dose study investigated the pharmacokinetics, safety, and tolerability of IV or intramuscular (IM) sotrovimab 500 mg doses versus placebo in healthy Japanese and Caucasian volunteers. METHODS: This was a two-part, Phase 1, randomized, placebo-controlled, single-blind study. In Part 1, participants received a single sotrovimab 500 mg IV infusion or matching placebo on Day 1. In Part 2, participants received a single sotrovimab 500 mg IM dose or matching placebo on Day 1, administered as two 4 mL injections. RESULTS: There was no effect of ethnicity on the peak or total serum exposure of IV sotrovimab through Week 18; after adjusting for body weight, the point estimate and 90 % confidence interval for the ratio of total exposure between Japanese and Caucasian participants fell within conventional bioavailability bounds (80-125%). Geometric mean Cmax and AUClast following a single IM administration of sotrovimab were higher in Japanese participants compared with Caucasian participants, even after adjustment for body weight. Overall, a single IV or IM dose of sotrovimab was well tolerated by both Japanese and Caucasian participants. CONCLUSIONS: After adjusting for body weight, exposures following a single IV dose of sotrovimab 500 mg were similar between Japanese and Caucasian participants, and higher in Japanese participants following IM administration. Higher exposures were not associated with any safety signals. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04988152.

Long-term impact of the COVID-19 pandemic on self-management of chronic conditions among high-risk adults in the USA: protocol for the C3 observational cohort study.

INTRODUCTION: COVID-19 is an unprecedented public health threat in modern times, especially for older adults or those with chronic illness. Beyond the threat of infection, the pandemic may also have longer-term impacts on mental and physical health. The COVID-19 & Chronic Conditions ('C3') study offers a unique opportunity to assess psychosocial and health/healthcare trajectories over 5 years among a diverse cohort of adults with comorbidities well-characterised from before the pandemic, at its onset, through multiple surges, vaccine rollouts and through the gradual easing of restrictions as society slowly returns to 'normal'. METHODS AND ANALYSIS: The C3 study is an extension of an ongoing longitudinal cohort study of 'high-risk' adults (aged 23-88 at baseline) with one or more chronic medical conditions during the COVID-19 pandemic. Five active studies with uniform data collection prior to COVID-19 were leveraged to establish the C3 cohort; 673 adults in Chicago were interviewed during the first week of the outbreak. The C3 cohort has since expanded to include 1044 participants across eight survey waves (T1-T8). Four additional survey waves (T9-T12) will be conducted via telephone interviews spaced 1 year apart and supplemented by electronic health record and pharmacy fill data, for a total of 5 years of data post pandemic onset. Measurement will include COVID-19-related attitudes/behaviours, mental health, social behaviour, lifestyle/health behaviours, healthcare use, chronic disease self-management and health outcomes. Mental health trajectories and associations with health behaviours/outcomes will be examined in a series of latent group and mixed effects modelling, while also examining mediating and moderating factors. ETHICS AND DISSEMINATION: This study was approved by Northwestern University's Feinberg School of Medicine Institutional Review Board (STU00215360). Results will be published in international peer-reviewed journals and summaries will be provided to the funders of the study.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome in a young patient presenting with a large uterus: A case report and review of the literature.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is a rare genetic disorder caused by a germline mutation in the fumarate hydratase (FH) gene. It is clinically characterized by cutaneous leiomyomas, uterine leiomyomas and renal cell cancer. A 31-year-old woman presented with severe abdominopelvic pain associated with severe menorrhagia which required a visit to the emergency department. Computed tomography (CT) showed a severe enlargement of the uterus with newly diagnosed fibroids. Magnetic resonance imaging (MRI) confirmed the finding of an enlarged uterus with mild left and moderate right hydronephrosis and hydroureter. The patient tried to manage the pain with oral over-the-counter medications and heat pads without significant relief. She was recommended to proceed with total abdominal hysterectomy and bilateral salpingectomy. She tolerated the procedure well and had an uneventful postoperative recovery. Pathology showed morphologic features, including the staghorn vessels, alveolar edema, eosinophilic cytoplasmic inclusions and prominent nucleoli which are characteristics for FH-deficient leiomyomas. Genetic testing was positive for a pathogenic variant in the FH gene associated with HLRCC. This case highlights the importance of proceeding with genetic testing in patients with personal and family history of leiomyomas and unusual pathology findings. Early identification of the syndrome can lead to appropriate screening for renal cell carcinoma.

The impact of underrepresented minority or marginalized identity status on training outcomes of MD-PhD students.

Dual-degree MD-PhD programs have historically lacked diversity of race, ethnicity, gender, sexual orientation, and other facets of identity. Like MD- and PhD-granting programs, MD-PhD program training environments are also marked by structural barriers that negatively impact measurable academic outcomes of underrepresented and/or marginalized students in academic medicine (racial and ethnic minority groups considered underrepresented by the National Institute of Health, sexual and gender minorities, individuals with disabilities, and individuals of low socioeconomic status). In this article, we review the existing literature on MD-PhD program disparities affecting students from these groups and provide recommendations grounded on the reviewed evidence. Our literature review identified four generalizable barriers that can impact the training outcomes of students from these marginalized and/or underrepresented groups: 1) discrimination and bias, 2) impostor syndrome and stereotype threat, 3) lack of identity-similar mentors, and 4) suboptimal institutional policies and procedures. We propose goal-oriented interventions that may begin to ameliorate the disparities present in MD-PhD program training environments that affect students from marginalized and/or underrepresented groups in academic medicine.

Pleomorphic Adenoma of the Breast: A Rare Benign Lesion Masquerading as a Metaplastic Breast Carcinoma on Core-Needle Biopsy.

We report a rare case of pleomorphic adenoma (benign mixed tumor) of the breast in a 66-year-old female. A 5.5 cm hypoechoic mass with lobulated margins was noted on ultrasound. A biopsy showed an atypical cartilaginous lesion, leading to a subsequent segmental mastectomy, which was initially interpreted as metaplastic breast carcinoma. On the second review at our tertiary care center, a diagnosis of a pleomorphic adenoma was favored due to the circumscription and the benign epithelial component. Due to unfamiliarity with this entity, this neoplasm has occasionally been misdiagnosed clinically and even been overcalled on core needle biopsies. Careful clinical, radiological, and pathological correlation is required to avoid unnecessarily aggressive surgery, and a differential diagnosis of pleomorphic adenoma must be included in cases of well-demarcated breast masses showing myxoid or cartilaginous changes on core-needle biopsy.

Association of polygenic risk score with response to deep brain stimulation in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson's Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations have been reported among factors that influence response to DBS. However, monogenic disease accounts for only a minority of patients with PD. The polygenic risk score (PRS) is an indication of cumulative genetic risk for disease. The PRS in PD has also been correlated with age of onset and symptom progression, but it is unknown whether correlations exist between PRS and DBS response. Here, we performed a pilot study to look for any such correlation. METHODS: We performed a retrospective analysis of 33 PD patients from the NIH PD Clinic and 13 patients from the Parkinson's Progression Markers Initiative database who had genetic testing and underwent bilateral subthalamic nucleus DBS surgery and clinical follow-up. A PD-specific PRS was calculated for all 46 patients based on the 90 susceptibility variants identified in the latest PD genome-wide association study. We tested associations between PRS and pre- and post-surgery motor and cognitive measures using multiple regression analysis for up to two years after surgery. RESULTS: Changes in scores on the Beck Depression Inventory (BDI) were not correlated with PRS when derived from all susceptibility variants, however, when removing pathogenic and high-risk carriers from the calculation, higher PRS was significantly associated with greater reduction in BDI score at 3 months and with similar trend 24 months after DBS. PRS was not a significant predictor of Unified Parkinson's Disease Rating Scale, Dementia Rating Scale, or phenomic and semantic fluency outcomes at 3- and 24-months after DBS surgery. CONCLUSIONS: This exploratory study suggests that PRS may predict degree of improvement in depressive symptoms after DBS, though was not predictive of motor and other cognitive outcomes after DBS. Additionally, PRS may be most relevant in predicting DBS outcomes in patients lacking pathogenic or high-risk PD variants. However, this was a small preliminary study and response to DBS treatment is multifactorial, therefore, more standardized high-powered studies are needed.

Early COVID-19 Attitudes and Behaviors and Their Associations With Later Infection: A Local Perspective From One U.S. City.

BACKGROUND: At the onset of the pandemic, there was poor public awareness and inaction in response to COVID-19; it is less known whether this translated to subsequent infections. OBJECTIVES: To explore whether adults who perceived COVID-19 as less of a threat and who were not taking early actions were more likely to become infected over the following year. RESEARCH DESIGN: Survey data from the ongoing (COVID-19 & Chronic Conditions (C3) anonymized for review) cohort study. PARTICIPANTS: Six hundred forty-two adults with a mean age of 63 and ≥1 chronic condition. MEASURES: Self-reported attitudes and behaviors regarding COVID-19 were assessed from March 13 to April 3, 2020, and COVID-19 infection status was captured between May 2020 and January 2021. Bivariate and multivariable analyses examined associations between early perceptions and behaviors with later infection. RESULTS: Approximately 7% reported infection with COVID-19 (N = 46). Adults who perceived the threat of COVID-19 less seriously at the initial outbreak were more likely to test positive over the following year [odds ratio (OR): 0.81, CI: 0.70-0.94; P = 0.006]. Those who were less likely to believe their actions would affect whether they would become infected were more likely to test positive (OR: 0.87, CI: 0.77-0.99; P = 0.03), as were adults who reported not changing their routines (OR: 0.45; CI: 0.24-0.85; P = 0.01). CONCLUSIONS: Adults with delayed responses in acknowledging the threat of COVID-19 and in changing behaviors were more likely to contract the virus. This investigation provides insight into the consequences of inadequate public understanding and response to COVID-19, and it highlights the importance of promoting early awareness among high-risk groups during public health crises.

Multi-institutional Assessment of Pathologist Scoring HER2 Immunohistochemistry.

The HercepTest was approved 20+ years ago as the companion diagnostic test for trastuzumab in human epidermal growth factor 2 (HER2) or ERBB2 gene-amplified/overexpressing breast cancers. Subsequent HER2 immunohistochemistry (IHC) assays followed, including the now most common Ventana 4B5 assay. Although this IHC assay has become the clinical standard, its reliability, reproducibility, and accuracy have largely been approved and accepted on the basis of concordance among small numbers of pathologists without validation in a real-world setting. In this study, we evaluated the concordance and interrater reliability of scoring HER2 IHC in 170 breast cancer biopsies by 18 breast cancer-specialized pathologists from 15 institutions. We used the Observers Needed to Evaluate Subjective Tests method to determine the plateau of concordance and the minimum number of pathologists needed to estimate interrater agreement values for large numbers of raters, as seen in the real-world setting. We report substantial discordance within the intermediate categories (<1% agreement for 1+ and 3.6% agreement for 2+) in the 4-category HER2 IHC scoring system. The discordance within the IHC 0 cases is also substantial with an overall percent agreement (OPA) of only 25% and poor interrater reliability metrics (0.49 Fleiss' kappa, 0.55 intraclass correlation coefficient). This discordance can be partially reduced by using a 3-category system (28.8% vs 46.5% OPA for 4-category and 3-category scoring systems, respectively). Observers Needed to Evaluate Subjective Tests plots suggest that the OPA for the task of determining a HER2 IHC score 0 from not 0 plateaus statistically around 59.4% at 10 raters. Conversely, at the task of scoring HER2 IHC as 3+ or not 3+ pathologists' concordance was much higher with an OPA that plateaus at 87.1% with 6 raters. This suggests that legacy HER2 IHC remains valuable for finding the patients in whom the ERBB2 gene is amplified but unacceptably discordant in assigning HER2-low or HER2-negative status for the emerging HER2-low therapies.

Pseudoangiomatous Stromal Hyperplasia: Radiologic-Pathologic Correlation.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. PASH is postulated to be hormonally induced and predominantly occurs in premenopausal women and postmenopausal women on menopausal hormone therapy. Clinical presentation varies from screen-detected lesions to palpable masses. Imaging findings of PASH are nonspecific. The most common mammographic findings are an oval or round circumscribed non-calcified mass or developing asymmetry. On US, PASH is often seen as an oval hypoechoic mass that may be circumscribed and can have an echogenic rim, or, when manifest as mammographic asymmetry, US may show a corresponding non-mass focal area of echogenic tissue. Limited studies have investigated the MRI appearance, with PASH most often manifesting as non-mass enhancement, or, less often, as an oval or irregular mass with persistent kinetics. Histopathologically, PASH can be mistaken for a fibroadenoma or phyllodes tumor and has features overlapping low-grade angiosarcoma. Assessment of radiologic-pathologic concordance is particularly important as PASH is often an incidental finding, adjacent to the targeted lesion at histopathology. Surgical excision or repeat core-needle biopsy is necessary for discordant suspicious cases. After a benign, concordant diagnosis of PASH, the patient may resume routine screening.

First-in-human study with SAR445088: A novel selective classical complement pathway inhibitor.

SAR445088 is an anti-C1s humanized monoclonal antibody that inhibits activated C1s in the proximal portion of the classical complement system and has the potential to provide clinical benefit in the treatment of complement-mediated diseases. A phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of SAR445088 was conducted in 93 healthy participants to evaluate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles. Single (intravenous [i.v.] and subcutaneous [s.c.]) ascending doses (SAD) and multiple (s.c.) ascending doses (MAD) of SAR445088 were well-tolerated. The PK of SAR445088 was characterized by slow absorption after the s.c. dose and a long half-life (mean terminal half-life [t1/2 ] 8-15 weeks). Two PD assays were used to measure inhibition of the classical complement pathway (CP): Wieslab CP and complement mediated hemolytic capacity (CH50). The estimated half-maximal inhibitory concentration (IC50 ) and 90% inhibitory concentration (IC90 ) for the Wieslab CP assay were 96.4 and 458 µg/ml, respectively, and 16.6 and 57.0 µg/ml, respectively, for the CH50 assay. In summary, SAR445088 was well-tolerated and had favorable PK and PD profiles after SAD (i.v. or s.c.) and MAD (s.c.) in humans. These findings warrant further clinical investigations in patients with classical complement-mediated disorders.

Association between medication regimen complexity and glycemic control among patients with type 2 diabetes.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and comorbid conditions require patients to take complex medication regimens. Greater regimen complexity has been associated with poorer T2DM management; however, the relationship between overall regimen complexity and glycemic control is unclear. OBJECTIVES: Our objectives were: (1) to examine associations between regimen complexity (with the Medication Regimen Complexity Index [MRCI]) and glycemic control (A1C), and (2) to compare overall MRCI with other measures of regimen complexity (overall and diabetes-specific medication count) and diabetes-specific MRCI. METHODS: This was a secondary data analysis of cross-sectional data from a parent trial. Participants were patients with T2DM taking at least 3 chronic medications followed in safety net clinics in the Chicago area. The MRCI measures complexity based on dosing frequency, route of administration, and special instructions for prescribed medications. MRCI scores were created for overall regimens and diabetes-specific medications. Sociodemographics and outpatient visit utilization were included in models as covariates. Linear regression was used to examine the associations between variables of interest and hemoglobin A1C. RESULTS: Participants (N = 432) had a mean age of 56.9 years, most were female (66.0%), and Hispanic or Latino (73.3%). Regimen complexity was high based on overall medications (mean = 6.6 medications, SD: 3.09) and MRCI (mean = 21.4, SD: 11.3). Higher diabetes-specific MRCI was associated with higher A1C in bivariate and multivariable models. In multivariable models, overall MRCI greater than 14, fewer outpatient health care visits, male gender, and absence of health insurance were independently associated with higher A1C. The variance in A1C explained by MRCI was higher compared to medication count for overall and diabetes-specific regimen complexity. CONCLUSIONS: More complex regimens are associated with worse A1C and measuring complexity with MRCI may have advantages. Deprescribing, increasing insurance coverage, and promoting engagement in health care may improve A1C among underserved populations with complex regimens.

Biliblanket Utilization for Outpatient Treatment of Newborn Jaundice.

Hyperbilirubinemia is a common neonatal diagnosis. Biliblankets have the potential to reduce readmission for hyperbilirubinemia. The study purpose was to characterize home biliblanket treatment for hyperbilirubinemia using retrospective medical record review of newborns with total serum bilirubin of 0.1 to 3 mg/dL below inpatient threshold seen at 9 pediatric clinics (N = 359). The main outcomes were whether a biliblanket was used and whether the usage impacted readmissions. Home biliblankets were used for 44% of newborns. Nine percent of newborns were readmitted for hyperbilirubinemia. Four percent of newborns treated with a biliblanket were readmitted compared with 13% of those not treated with a biliblanket (P = .002). Newborns treated with a biliblanket (odds ratio [OR] = 0.16; 95% confidence interval [CI] = 0.06-0.44) and newborns 3 days or older (OR = 0.16; 95% CI = 0.06-0.43) were less likely to be readmitted than newborns not treated with a biliblanket and 2-day-old newborns. We found that home biliblanket use was associated with lower odds of hospital readmission for newborn jaundice.

Breast Angiosarcoma: Imaging Features With Histopathologic Correlation.

Breast angiosarcoma is a rare malignancy of endothelial origin that can be categorized as primary angiosarcoma (PAS) or secondary angiosarcoma (SAS) based on etiology. Primary angiosarcoma typically affects younger women with no known risk factors, whereas SAS of the breast typically develops in older women who have undergone breast cancer treatment. There are two types of SAS, one that develops in the setting of chronic lymphedema and one that develops as a radiation-associated neoplasm after breast-conserving therapy (BCT). Clinically, PAS often presents as a palpable mass that may be rapidly growing, whereas SAS presents with skin changes such as erythematous plaques or nodules or with areas of skin discoloration. Mammographically, the appearance of PAS can be nonspecific and may be obscured by the dense tissue that is characteristic of the young patient population it typically affects. Cases of mammographically occult PAS have been visible at US and MRI. Mammography and US have been found to be less sensitive than MRI for the diagnosis of secondary radiation-associated angiosarcoma. Angiosarcomas, both PAS and SAS, are graded, depending on degree of differentiation, as low, intermediate, or high grade. Endothelial markers such as ERG and CD31 immunohistochemical stains are used to support the diagnosis of angiosarcomas. In this article, we review the clinical presentation, imaging findings, associated histopathology, and treatment of primary and secondary breast angiosarcoma.

A pilot study: Comparison of TRPS1 and GATA3 immunoperoxidase staining using cytologic smears in entities reportedly positive for GATA3.

BACKGROUND: Metastatic breast carcinoma (mBC) is frequently encountered and may be challenging to diagnose as the tumor cells can morphologically resemble carcinomas of other primary origins. An additional challenge is that direct smears are often the only sample type available for immunostaining studies in cytology. Trichorhinophalangeal syndrome GATA-binding type 1 1 (TRPS1) is a highly sensitive marker for BC compared to the commonly used marker GATA3, especially in triple-negative BC (TNBC), in histologic samples. However, its sensitivity and specificity in mBC and other GATA3-positive tumors have not been studied. METHODS: The authors identified the following cytology cases: 37 GATA3-positive mBC cases and 19 available cases that were deemed mBC but were GATA3-negative during the original case workup and five cases of each of eight epithelioid entities known to have high rates of GATA3 positivity and commonly seen in cytology practice. Immunostainings of TRPS1 and GATA3 were performed on the chosen smears following standard protocols. RESULTS: TRPS1 was positive in all 37 GATA3-positive mBC cases and in 18 of the 19 GATA3-negative mBC cases. TRPS1 was negative in all five of the seven frequently GATA3-positive epithelioid entities, with the exception of salivary duct carcinomas where GATA3 was positive in a rate ranging 60%-100% among them. CONCLUSIONS: TRPS1 is as sensitive as GATA3 in GATA3-positive mBC and is more sensitive than GATA3 in TNBC. TRPS1 is negative in most GATA3-positive nonbreast tumors. Thus, the combination of TRPS1 and GATA3 could be used to differentiate breast primary from others in most situations.