Idiopathic Granulomatous Mastitis: Imaging Findings and Outcomes with Nonsteroidal Treatment in a Predominantly Hispanic Population.

OBJECTIVE: We describe the demographics, clinical presentation, imaging findings, and treatment response among 235 cases of biopsy-proven idiopathic granulomatous mastitis (IGM) at a single institution. METHODS: An institutional review board-approved retrospective search of the breast imaging database was performed to select patients with biopsy-proven IGM between 2017 and 2022. Retrospective review evaluated clinical presentation, imaging findings with US and mammography, and treatment recommendations (antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], warm compresses, or observation only). Response to treatment was evaluated on follow-up US. A favorable treatment response was a decrease in size or resolution of disease on follow-up imaging. Statistical analysis using Poisson regression was performed to evaluate the clinical outcomes associated with each treatment. RESULTS: A total of 235 patients met the selection criteria with a mean age of 38 years (18 to 68). The majority of patients were Hispanic (95%, 223/235). Of all patients, 75.3% (177/235) received treatment (consisting of 1 or any combination of antibiotics, NSAIDs, warm compresses), 24.7% (58/235) were treated with observation, 78.7% (185/235) returned for follow-up imaging, and 21.3% (50/235) were lost to follow-up. Of those with follow-up imaging, disease improvement was seen in 70.3% (102/145) of patients who received treatment compared with 72.5% (29/40) of patients treated by observation alone. Multivariate analysis further showed no difference in clinical outcomes among the treatment of unifocal, multifocal, or recurrent IGM. CONCLUSION: Nonsteroidal treatment of IGM showed no significant improvement on follow-up imaging compared to treatment with observation alone in a predominantly Hispanic patient population.

Decoding Endothelial MPL and JAK2V617F Mutation: Insight Into Cardiovascular Dysfunction in Myeloproliferative Neoplasms.

BACKGROUND: Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN. METHODS: We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines. RESULTS: Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL (myeloproliferative leukemia virus oncogene) suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function. CONCLUSIONS: JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.

Factors Influencing Implementation of the Commission on Cancer's Breast Synoptic Operative Report (Alliance A20_Pilot9).

BACKGROUND: The technical aspects of cancer surgery have a significant impact on patient outcomes. To monitor surgical quality, in 2020, the Commission on Cancer (CoC) revised its accreditation standards for cancer surgery and introduced the synoptic operative reports (SORs). The standardization of SORs holds promise, but successful implementation requires strategies to address key implementation barriers. This study aimed to identify the barriers and facilitators to implementing breast SOR within diverse CoC-accredited programs. METHODS: In-depth semi-structured interviews were conducted with 31 health care professionals across diverse CoC-accredited sites. The study used two comprehensive implementation frameworks to guide data collection and analysis. RESULTS: Successful SOR implementation was impeded by disrupted workflows, surgeon resistance to change, low prioritization of resources, and poor flow of information despite CoC's positive reputation. Participants often lacked understanding of the requirements and timeline for breast SOR and were heavily influenced by prior experiences with templates and SOR champion relationships. The perceived lack of monetary benefits (to obtaining CoC accreditation) together with the significant information technology (IT) resource requirements tempered some of the enthusiasm. Additionally, resource constraints and the redirection of personnel during the COVID-19 pandemic were noted as hurdles. CONCLUSIONS: Surgeon behavior and workflow change, IT and personnel resources, and communication and networking strategies influenced SOR implementation. During early implementation and the implementation planning phase, the primary focus was on achieving buy-in and initiating successful roll-out rather than effective use or sustainment. These findings have implications for enhancing standardization of surgical cancer care and guidance of future strategies to optimize implementation of CoC accreditation standards.

Perspectives of Health Care Providers on Peer Support for Adolescents with Cancer in Pediatrics.

Health care providers (HCPs) play a key role in psychosocial care of adolescents with cancer (AWC) and present a unique perspective. This prospective study included a brief survey followed by an interview, seeking to understand HCPs' viewpoints on peer support needs of AWC. Participants were 10 multidisciplinary HCPs with 5-30 years of experience. Three key themes found were: observations made and relationships with AWC; challenges to providing support; and potential peer support interventions. HCPs want to provide peer support resources but lack adequate information. Next steps: interventions should include information dissemination to all HCPs caring for AWC.

Deciphering the differential impact of thrombopoietin/MPL signaling on hematopoietic stem/progenitor cell function in bone marrow and spleen.

Thrombopoietin (TPO) and its receptor MPL play crucial roles in hematopoietic stem cell (HSC) function and platelet production. However, the precise effects of TPO/MPL signaling on HSC regulation in different hematopoietic niches remain unclear. Here, we investigated the effects of TPO/MPL ablation on marrow and splenic hematopoiesis in TPO-/- and MPL-/- mice during aging. Despite severe thrombocytopenia, TPO-/- and MPL-/- mice did not develop marrow failure during a 2-year follow-up. Marrow and splenic HSCs exhibited different responses to TPO/MPL ablation and exogenous TPO treatment. Splenic niche cells compensated for marrow HSC loss in TPO-/- and MPL-/- mice by upregulating CXCL12 levels. These findings provide new insights into the complex regulation of HSCs by TPO/MPL and reveal a previously unknown link between TPO and CXCL12, two key growth factors for HSC maintenance. Understanding the distinct regulatory mechanisms between marrow and spleen hematopoiesis will help to develop novel therapeutic approaches for hematopoietic disorders.

Short-term and long-term financial toxicity from breast cancer treatment: a qualitative study.

PURPOSE: The rising cost of breast cancer treatment has increased patients' financial burden, intensifying an already stressful treatment process. Although researchers increasingly recognize the harmful impact of medical and nonmedical costs associated with cancer treatment, understanding patients' perspectives of financial toxicity is limited. We aimed to explore the topic of financial toxicity through the lived experiences of patients with breast cancer from groups at risk of social and economic marginalization. METHODS: We conducted semi-structured interviews with 50 women with breast cancer from four specific groups: Black women, Medicaid enrollees, rural residents, and women age ≤ 40. We transcribed, coded, and analyzed the data using deductive and inductive approaches. RESULTS: Two overarching themes captured patients' experiences of financial toxicity: short-term and long-term impacts. Short-term stressors included direct medical (e.g., co-pays, premiums), nonmedical (e.g., transportation, lodging), and indirect (e.g., job loss, reduced work hours) costs. Early in their treatments, patients' focus on survival took precedence over financial concerns. However, as the treatment course progressed, fear of consequences from compounding costs of care and financial distress negatively impacted patients' lifestyles and outlooks for the future. CONCLUSION: Programs addressing financial toxicity that look beyond early-phase interventions are needed. Specifically, patients struggling with the accumulation of treatment costs and the resultant stress require ongoing support. Long-term support is especially needed for groups vulnerable to financial instability and social marginalization.

Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.

Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness.

Could Some Patients With Fibromyalgia Potentially Have Hypophosphatasia? A Retrospective Single-Center Study.

OBJECTIVE: Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing low levels of ALP. Disease presentation is heterogeneous and can present as a chronic pain syndrome like fibromyalgia (FM). Our objective was to determine if there are any potential patients with HPP in the group of patients who were diagnosed with FM. Antiresorptive therapy use can trigger atypical femur fractures in patients with HPP. METHODS: We performed a retrospective chart review of all patients 18 years or older at a single academic center who were diagnosed with FM and had either a low or a normal ALP level. The following characteristics were reviewed: biological sex; age; history of fractures; diagnosis of osteoporosis, osteopenia, osteoarthritis, and chondrocalcinosis; genetic testing; vitamin B6 level testing; and medications. RESULTS: Six hundred eleven patients with FM were identified. Two hundred had at least one low ALP level, and 57 had at least three consecutively low measurements of ALP, 44% of which had a history of fractures. No patients had vitamin B6 levels checked. None of the patients had previous genetic testing for HPP or underwent testing for zinc or magnesium levels. CONCLUSION: The percentage of patients with FM who were found to have consistently low ALP levels was 9.3%. None had vitamin B6 level or genetic testing, suggesting that the diagnosis was not suspected. It is important to diagnose HPP given the availability of enzyme replacement therapy to prevent complications from HPP such as fractures. Our data support screening for this condition as a part of the initial workup of FM.

Unlocking the Role of Endothelial MPL Receptor and JAK2V617F Mutation: Insights into Cardiovascular Dysfunction in MPNs and CHIP.

Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential (CHIP) are at a significantly higher risk of cardiovascular diseases (CVDs). Endothelial cells (ECs) carrying the JAK2V617F mutation can be detected in many MPN patients. Here, we investigated the impact of endothelial JAK2V617F mutation on CVD development using both transgenic murine models and human induced pluripotent stem cell lines. Our findings revealed that JAK2V617F mutant ECs promote CVDs by impairing endothelial function and undergoing endothelial-to-mesenchymal transition (EndMT). Importantly, we found that inhibiting the endothelial thrombopoietin receptor MPL suppressed JAK2V617F-induced EndMT and prevented cardiovascular dysfunction caused by mutant ECs. These findings propose that targeting the endothelial MPL receptor could be a promising therapeutic approach to manage CVD complications in patients with JAK2V617F-positive MPNs and CHIP. Further investigations into the impact of other CHIP-associated mutations on endothelial dysfunction are needed to improve risk stratification for individuals with CHIP.

Invasive squamous cell carcinoma of the breast associated with breast augmentation implant capsule.

Primary squamous cell carcinoma (SCC) of the breast is rare, representing less than 0.1% of all breast cancers. To date, there have been 20 reported cases of SCC associated with breast augmentation, usually in patients with long-standing implants. A patient is reported here with primary squamous carcinoma of the breast associated with textured saline implants. Due to the paucity of cases, there is limited information on the incidence and management of implant-associated SCC of the breast.

Deciphering the Differential Impact of Thrombopoietin/MPL Signaling on Hematopoietic Stem Cell Function in Bone Marrow and Spleen.

Thrombopoietin (TPO) and its receptor MPL play crucial roles in hematopoietic stem cell (HSC) function and platelet production. However, the precise effects of TPO/MPL signaling on HSC regulation in different hematopoietic niches remain unclear. Here, we investigated the effects of TPO/MPL ablation on marrow and splenic hematopoiesis in TPO-/- and MPL-/- mice during aging. Despite severe thrombocytopenia, TPO-/- and MPL-/- mice did not develop marrow failure during a 2-year follow-up. Marrow and splenic HSCs exhibited different responses to TPO/MPL ablation and exogenous TPO treatment. Splenic niche cells compensated for marrow HSC loss in TPO-/- and MPL-/- mice by upregulating CXCL12 levels. These findings provide new insights into the complex regulation of HSCs by TPO/MPL and reveal a previously unknown link between TPO and CXCL12, two key growth factors for HSC maintenance. Understanding the distinct regulatory mechanisms between marrow and spleen hematopoiesis will help develop novel therapeutic approaches for hematopoietic disorders.

Beliefs, Experiences, and Openness Regarding Dietary Interventions: Data From an Urban Hispanic Population With Rheumatic Disease in the US.

OBJECTIVE: To obtain descriptive data on the beliefs, behaviors, and openness regarding dietary changes for rheumatic diseases in an urban US Hispanic patient population with rheumatic disease as foundational data for future intervention design. METHODS: We distributed a voluntary survey to our primarily Hispanic population at an outpatient rheumatology clinic for 19 weeks. This survey queried individuals' behaviors as they related to dietary intake used for the treatment of rheumatic disease, perceptions of the effect of food groups on rheumatic disease activity, barriers to physician-recommended diets, and willingness to try future interventions. We used descriptive statistics and Pearson's chi-square test to evaluate associations. RESULTS: More than 40% of survey respondents from our primarily (88%) Hispanic population noted a link between what they ate and their underlying rheumatic disease activity. More than one-third of patients had, at some point, modified dietary intake to affect their rheumatic disease. Vegetables, fruit, and white meats were commonly reported to improve disease, while red meat and processed foods were reported to worsen disease. Barriers to following a prespecified diet included cost and lack of knowledge. More than 70% of respondents indicated willingness to attempt certain eating patterns should it help their underlying rheumatic disease. CONCLUSION: In this primarily Hispanic rheumatic disease patient population, many have not only noted a correlation between dietary intake and rheumatic disease activity but are also open to future nutrition-related interventions. As this population experiences poor rheumatic disease outcomes and a high rate of lifestyle-related comorbidities, an intervention to optimize healthy eating patterns would likely be beneficial as well as acceptable.

Adalimumab-Induced Lupus Serositis: A Case Report and Review of the Literature.

Tumor necrosis factor-alpha (TNF-alpha) antagonist use is prevalent for the treatment of autoimmune diseases, including psoriasis, ankylosing spondylitis, and rheumatoid arthritis. Since the onset of its use over the last couple of decades, there have been increasing reports of drug-induced antibodies and antitumor necrosis factor-alpha-induced lupus (ATIL). Herein, we present a case of pericarditis induced by tumor necrosis factor-alpha antagonist, adalimumab. A 61-year-old male with psoriatic arthritis treated with adalimumab injections for five years presented with dyspnea, chest tightness, and three-pillow orthopnea. Echocardiogram showed moderate pericardial effusion with early signs of tamponade. Adalimumab was discontinued. He was started on colchicine and steroids for a high suspicion of drug-induced serositis. With the increased use of tumor necrosis factor-alpha antagonists, adverse reactions such as ATIL will become more common. Such cases need to be reported to spread awareness of this possible complication and avoid any delay in treatment and care.

Peer Support Perspectives of Parents of Adolescents with Cancer in Pediatrics.

Parents of adolescents with cancer (AWC) provide critical support throughout the cancer journey and could offer key insights into support needs. This prospective study aimed to obtain parent perspectives on peer support needs of AWC. Ten individual parents (9 mothers and 1 father) completed a survey and a semistructured interview. Four themes were identified: cancer journey challenges; emotions, reactions, and coping; personal support preferences; and AWC's support needs. Parents recognized that AWC require various support, but lacked insight into their specific peer support desires. Next step interventions should focus on peer support for AWC, while also incorporating peer support for parents.

JAK2V617F Mutant Megakaryocytes Contribute to Hematopoietic Aging in a Murine Model of Myeloproliferative Neoplasm.

Megakaryocytes (MKs) is an important component of the hematopoietic niche. Abnormal MK hyperplasia is a hallmark feature of myeloproliferative neoplasms (MPNs). The JAK2V617F mutation is present in hematopoietic cells in a majority of patients with MPNs. Using a murine model of MPN in which the human JAK2V617F gene is expressed in the MK lineage, we show that the JAK2V617F-bearing MKs promote hematopoietic stem cell (HSC) aging, manifesting as myeloid-skewed hematopoiesis with an expansion of CD41+ HSCs, a reduced engraftment and self-renewal capacity, and a reduced differentiation capacity. HSCs from 2-year-old mice with JAK2V617F-bearing MKs were more proliferative and less quiescent than HSCs from age-matched control mice. Examination of the marrow hematopoietic niche reveals that the JAK2V617F-bearing MKs not only have decreased direct interactions with hematopoietic stem/progenitor cells during aging but also suppress the vascular niche function during aging. Unbiased RNA expression profiling reveals that HSC aging has a profound effect on MK transcriptomic profiles, while targeted cytokine array shows that the JAK2V617F-bearing MKs can alter the hematopoietic niche through increased levels of pro-inflammatory and anti-angiogenic factors. Therefore, as a hematopoietic niche cell, MKs represent an important connection between the extrinsic and intrinsic mechanisms for HSC aging.

Imaging of Benign and Malignant Breast Lesions Using Contrast-Enhanced Ultrasound: A Pictorial Essay.

ABSTRACT: Contrast-enhanced ultrasound is a promising noninvasive imaging technique for evaluating benign and malignant breast lesions, as contrast provides information about perfusion and microvasculature. Contrast-enhanced ultrasound is currently off-label use in the breast in the United States, but its clinical and investigational use in breast imaging is gaining popularity. It is important for radiologists to be familiar with the imaging appearances of benign and malignant breast masses using contrast-enhanced ultrasound. This pictorial essay illustrates enhancement patterns of various breast masses from our own experience. Pathologies include subtypes of invasive breast cancer, fibroadenomas, papillary lesions, fibrocystic change, and inflammatory processes. Contrast-enhanced ultrasound pitfalls and limitations are discussed.

Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity.

Glioblastoma is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of glioblastoma have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned across glioblastoma's hallmark histomorphologic niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to distinct histologic patterns across 20 patients and propose diverse molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Moreover, we highlight differential drug sensitivities and relative chemoresistance in glioblastoma cell lines with enhanced KRAS programs. Importantly, these pharmacological differences are less pronounced in transcriptional glioblastoma subgroups suggesting that this model may provide insights for targeting heterogeneity and overcoming therapy resistance.

Characterizing breast masses using an integrative framework of machine learning and CEUS-based radiomics.

AIMS: We evaluated the performance of contrast-enhanced ultrasound (CEUS) based on radiomics analysis to distinguish benign from malignant breast masses. METHODS: 131 women with suspicious breast masses (BI-RADS 4a, 4b, or 4c) who underwent CEUS examinations (using intravenous injection of perflutren lipid microsphere or sulfur hexafluoride lipid-type A microspheres) prior to ultrasound-guided biopsies were retrospectively identified. Post biopsy pathology showed 115 benign and 16 malignant masses. From the cine clip of the CEUS exams obtained using the built-in GE scanner software, breast masses and adjacent normal tissue were then manually segmented using the ImageJ software. One frame representing each of the four phases: precontrast, early, peak, and delay enhancement were selected post segmentation from each CEUS clip. 112 radiomic metrics were extracted from each segmented tissue normalized breast mass using custom Matlab® code. Linear and nonlinear machine learning (ML) methods were used to build the prediction model to distinguish benign from malignant masses. tenfold cross-validation evaluated model performance. Area under the curve (AUC) was used to quantify prediction accuracy. RESULTS: Univariate analysis found 35 (38.5%) radiomic variables with p < 0.05 in differentiating between benign from malignant masses. No feature selection was performed. Predictive models based on AdaBoost reported an AUC = 0.72 95% CI (0.56, 0.89), followed by Random Forest with an AUC = 0.71 95% CI (0.56, 0.87). CONCLUSIONS: CEUS based texture metrics can distinguish between benign and malignant breast masses, which can, in turn, lead to reduced unnecessary breast biopsies.

A Murine Model With JAK2V617F Expression in Both Hematopoietic Cells and Vascular Endothelial Cells Recapitulates the Key Features of Human Myeloproliferative Neoplasm.

The myeloproliferative neoplasms (MPNs) are characterized by an expansion of the neoplastic hematopoietic stem/progenitor cells (HSPC) and an increased risk of cardiovascular complications. The acquired kinase mutation JAK2V617F is present in hematopoietic cells in a majority of patients with MPNs. Vascular endothelial cells (ECs) carrying the JAK2V617F mutation can also be detected in patients with MPNs. In this study, we show that a murine model with both JAK2V617F-bearing hematopoietic cells and JAK2V617F-bearing vascular ECs recapitulated all the key features of the human MPN disease, which include disease transformation from essential thrombocythemia to myelofibrosis, extramedullary splenic hematopoiesis, and spontaneous cardiovascular complications. We also found that, during aging and MPN disease progression, there was a loss of both HSPC number and HSPC function in the marrow while the neoplastic hematopoiesis was relatively maintained in the spleen, mimicking the advanced phases of human MPN disease. Different vascular niche of the marrow and spleen could contribute to the different JAK2V617F mutant stem cell functions we have observed in this JAK2V617F-positive murine model. These results indicate that the spleen is functionally important for the JAK2V617F mutant neoplastic hematopoiesis during aging and MPN disease progression. Compared to other MPN murine models reported so far, our studies demonstrate that JAK2V617F-bearing vascular ECs play an important role in both the hematologic and cardiovascular abnormalities of MPN.

Prospective pilot study protocol evaluating the safety and feasibility of robot-assisted nipple-sparing mastectomy (RNSM).

INTRODUCTION: Nipple-sparing mastectomy (NSM) can be performed for the treatment of breast cancer and risk reduction, but total mammary glandular excision in NSM can be technically challenging. Minimally invasive robot-assisted NSM (RNSM) has the potential to improve the ergonomic challenges of open NSM. Recent studies in RNSM demonstrate the feasibility and safety of the procedure, but this technique is still novel in the USA. METHODS AND ANALYSIS: This is a single-arm prospective pilot study to determine the safety, efficacy and potential risks of RNSM. Up to 12 RNSM will be performed to assess the safety and feasibility of the procedure. Routine follow-up visits and study assessments will occur at 14 days, 30 days, 6 weeks, 6 months and 12 months. The primary outcome is to assess the feasibility of removing the breast gland en bloc using the RNSM technique. To assess safety, postoperative complication information will be collected. Secondary outcomes include defining benefits and challenges of RNSM for both surgeons and patients using surveys, as well as defining the breast and nipple-areolar complex sensation recovery following RNSM. Mainly, descriptive analysis will be used to report the findings. ETHICS AND DISSEMINATION: The RNSM protocol was reviewed and approved by the US Food and Drug Administration using the Investigational Device Exemption mechanism (reference number G200096). In addition, the protocol was registered with ClinicalTrials.gov (NCT04537312) and approved by The Ohio State University Institutional Review Board, reference number 2020C0094 (18 August 2020). The results of this study will be distributed through peer-reviewed journals and presented at surgical conferences. TRIAL REGISTRATION NUMBER: NCT04537312.