Perspective on Intradiscal Therapies for Lumbar Discogenic Pain: State of the Science, Knowledge Gaps, and Imperatives for Clinical Adoption.

Specific clinical diagnostic criteria have established a consensus for defining patients with lumbar discogenic pain. However, if conservative medical management fails, these patients have few treatment options short of surgery involving discectomy often coupled with fusion or arthroplasty. There is a rapidly-emerging research effort to fill this treatment gap with intradiscal therapies that can be delivered minimally-invasively via fluoroscopically guided injection without altering the normal anatomy of the affected vertebral motion segment. Viable candidate products to date have included mesenchymal stromal cells, platelet-rich plasma, nucleus pulposus structural allograft, and other cell-based compositions. The objective of these products is to repair, supplement, and restore the damaged intervertebral disc as well as retard further degeneration. In doing so, the intervention is meant to eliminate the source of discogenic pain and avoid surgery. Methodologically rigorous studies are rare, however, and based on the best clinical evidence, the safety as well as the magnitude and duration of clinical efficacy remain difficult to estimate. Further, we summarize the US Food and Drug Administration's (FDA) guidance regarding the interpretation of the minimal manipulation and homologous use criteria, which is central to designating these products as a tissue or as a drug/device/biologic. We also provide perspectives on the core evidence and knowledge gaps associated with intradiscal therapies, propose imperatives for evaluating effectiveness of these treatments and highlight several new technologies on the horizon.

Practical Guidance for the Development of Rosie, a Health Education Question-and-Answer Chatbot for New Mothers.

Communities of color experience higher maternal and infant mortality, as well as a host of other adverse outcomes, during pregnancy and postpartum. To address this, our team is developing a free, user-friendly, question-answering chatbot called Rosie. Chatbots have gained significant popularity due to their scalability and success in individualizing resources. In recent years, scientific communities and researchers have started recognizing this technology's potential to inform communities, promote health outcomes, and address health disparities. The development of Rosie is an interdisciplinary project, with teams focused on the technical build of the application (app), the development of machine learning models, and community outreach, making Rosie a chatbot built with the input from the communities it aims to serve. From June to October 2022, more than 20 demonstration sessions were conducted in Washington, District of Columbia, Maryland, and Virginia, where a total of 109 pregnant women and new mothers of color could interact with Rosie. Results from the live demonstrations showed that 75% of mothers searched for maternity and baby-related information at least once a week and more than 90% of participants expressed the likelihood to use the app. Most of the participants inquired about their baby's development, nutrition for babies, and identifying and addressing the causes of certain symptoms and conditions, accounting for about 80% of the total questions asked. Mother-related questions in the community demonstrations were mainly about pregnancy. The high level of interest in the chatbot is a clear indication of the need for more resources. Rosie aims to help close the racial gap in maternal and infant health disparities by providing new mothers with easy access to reliable health information.

Modeling-based prediction tools for preimplantation genetic testing of mitochondrial DNA diseases: estimating symptomatic thresholds, risk, and chance of success.

PURPOSE: Preimplantation genetic testing (PGT) has become a reliable tool for preventing the germline transmission of mitochondrial DNA (mtDNA) variants. However, procedures are not standardized across mtDNA variants. In this study, we aim to estimate symptomatic thresholds, risk, and chance of success for PGT for mtDNA pathogenic variant carriers. METHODS: We performed a systematic analysis of heteroplasmy data including 455 individuals from 187 familial pedigrees with the common m.3243A>G, m.8344A>G, or m.8993T>G pathogenic variants. We applied binary logistic regression for estimating symptomatic thresholds of heteroplasmy, simplified Sewell-Wright formula and Kimura equations for predicting the risk of disease transmission, and binomial distribution for predicting minimum oocyte numbers. RESULTS: We estimated the symptomatic thresholds of m.8993T>G and m.8344A>G as 29.86% and 16.15%, respectively. We could not determine a threshold for m.3243A>G. We established models for mothers harboring common and rare mtDNA pathogenic variants to predict the risk of disease transmission and the number of oocytes required to produce an embryo with sufficiently low variant load. In addition, we provide a table allowing the prediction of transmission risk and the minimum required oocytes for PGT patients with different variant levels. CONCLUSION: We have established models that can determine the symptomatic thresholds of common mtDNA pathogenic variants. We also constructed universal models applicable to nearly all mtDNA pathogenic variants which can predict risk and minimum numbers for PGT patients. These models have advanced our understanding of mtDNA disease pathogenesis and will enable more effective prevention of disease transmission using PGT.

A mixed methods systematic review of midwives' clinical practices related to prenatal care of women with obesity.

OBJECTIVE: Maternal obesity has been related to adverse maternal and infant outcomes. It is a persistent challenge of midwifery care worldwide and can present clinical challenges and complications. This review sought to identify evidence on the practice patterns of midwives related to prenatal care of women with obesity. METHODS: The databases Academic Search Premier, APA PsycInfo, CINAHL PLUS with Full Text, Health Source: Nursing/Academic Edition, and MEDLINE were searched November 2021. Search terms included weight, obesity, practices, and midwives. Inclusion criteria included quantitative, qualitative, and mixed method studies that addressed practice patterns of midwives related to prenatal care of women with obesity published in peer-reviewed journals, written in English. The recommended Joanna Briggs Institute approach to mixed methods systematic reviews was followed e.g. study selection, critical appraisal, data extraction, and a convergent segregated method of data synthesis and integration. RESULTS: Seventeen articles from 16 studies were included. The quantitative evidence showed a lack of knowledge, confidence, and support for midwives that would facilitate adequate management of pregnant women with obesity while the qualitative evidence revealed that midwives desire a sensitive approach to discussing obesity and the risks associated with maternal obesity. DISCUSSION: Quantitative and qualitative literature report consistent individual and system-level barriers to implementing evidence-based practices. Implicit bias training, midwifery curriculum updates, and the use of patient centered care models may help overcome these challenges.

Using the Meaningful Involvement of People Living with HIV/AIDS (MIPA) Framework to Assess the Engagement of Sexual Minority Men of Color in the US HIV Response: a Literature Review.

Black and Latino sexual minority men (SMM) continue to be disproportionately impacted by HIV. We utilized eight components of the Meaningful Involvement of People Living with HIV/AIDS (MIPA) framework to assess the engagement of Black and Latino SMM. Thirty-six (36) studies were included in the literature review. Forty-two percent of studies were Black SMM-specific, followed by Latino SMM-specific (31%) studies. Twenty-eight percent of studies were conducted among both groups. Most studies (72%) were intervention-related and focused on HIV prevention. The top five most common methods of community engagement were focus groups (39%), followed by interviews (36%), community-based participatory research (14%), the utilization of community advisory boards or peer mentorship (11%), and the establishment of multi-stakeholder coalitions, observations, or surveys (8%). We documented at least 7 MIPA components in 47% of the included studies. Community-based participatory research was more commonly utilized to engage Latino SMM. Researchers were more likely to initiate the engagement across all included studies. Few studies documented how Black and Latino SMM perceived the engagement. Engagement responsiveness was a well-documented MIPA component. In terms of engagement power dynamics, there were several examples of power imbalances, especially among Black SMM-specific studies. The inclusion of Black and Latino SMM had robust impacts on HIV research and interventions. There were limited examples of engagement capacity and maintenance. This is one of the first studies focused on utilizing MIPA to document the engagement of SMM of color. MIPA served as a useful framework for understanding the engagement of SMM of color in the US HIV response. The engagement of SMM of color is critical to reducing health inequities.

Pathogenic mitochondrial DNA 3243A>G mutation: From genetics to phenotype.

The mitochondrial DNA (mtDNA) m.3243A>G mutation is one of the most common pathogenic mtDNA variants, showing complex genetics, pathogenic molecular mechanisms, and phenotypes. In recent years, the prevention of mtDNA-related diseases has trended toward precision medicine strategies, such as preimplantation genetic diagnosis (PGD) and mitochondrial replacement therapy (MRT). These techniques are set to allow the birth of healthy children, but clinical implementation relies on thorough insights into mtDNA genetics. The genotype and phenotype of m.3243A>G vary greatly from mother to offspring, which compromises genetic counseling for the disease. This review is the first to systematically elaborate on the characteristics of the m.3243A>G mutation, from genetics to phenotype and the relationship between them, as well as the related influencing factors and potential strategies for preventing disease. These perceptions will provide clarity for clinicians providing genetic counseling to m.3243A>G patients.

Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer.

BACKGROUND: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. METHODS: Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours. RESULTS: We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. CONCLUSION: Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.

The value of prognostic ultrasound features of breast cancer in different molecular subtypes with a focus on triple negative disease.

The ultrasound (US) features of breast cancer have recently been shown to have prognostic significance. We aim to assess these features according to molecular subtype. 1140 consecutive US visible invasive breast cancers had US size and mean stiffness by shearwave elastography (SWE) recorded prospectively. Skin thickening (> 2.5 mm) overlying the cancer on US and the presence of posterior echo enhancement were assessed retrospectively while blinded to outcomes. Cancers were classified as luminal, triple negative (TN) or HER2 + ve based on immunohistochemistry and florescent in-situ hybridization. The relationship between US parameters and breast cancer specific survival (BCSS) was ascertained using Kaplan-Meier survival curves and ROC analysis. At median follow-up 6.3 year, there were 117 breast cancer (10%) and 132 non-breast deaths (12%). US size was significantly associated with BCSS all groups (area under the curve (AUC) 0.74 in luminal cancers, 0.64 for TN and 0.65 for HER2 + ve cancers). US skin thickening was associated most strongly with poor prognosis in TN cancers (53% vs. 80% 6 year survival, p = 0.0004). Posterior echo enhancement was associated with a poor BCSS in TN cancers (63% vs. 82% 6 year survival, p = 0.02). Mean stiffness at SWE was prognostic in the luminal and HER2 positive groups (AUC 0.69 and 0.63, respectively). In the subgroup of patients with TN cancers receiving neo-adjuvant chemotherapy posterior enhancement and skin thickening were not associated with response. US skin thickening is a poor prognostic indicator is all 3 subtypes studied, while posterior enhancement was associated with poor outcome in TN cancers.

A pre-operative prognostic model predicting all cause and cause specific mortality for women presenting with invasive breast cancer.

PURPOSE: The aim of this study is to develop a pre-operative prognostic model based on known pre-operative factors. METHODS: A database of ultrasound (US) lesions undergoing biopsy documented US lesion size, stiffness, and patient source prospectively. Women with invasive cancer presenting between 2010 and 2015 were the study group. Breast and axillary core results and ER, PR and HER receptor status were collected prospectively. Assessment of US skin thickening, US distal enhancement and presence of chronic kidney disease (CKD) was performed retrospectively. Patient survival and cause of death were ascertained from computer records. Predictive models for (i) all-cause mortality (ACM) and (ii) breast cancer death (BCD) were built and then validated using bootstrap k-fold cross-validation. A comparison of predictive performance was made between a full cause-specific Cox model, a sub cause-specific Cox model, and a full Fine-Gray sub-distribution hazard model. RESULTS: 1136 patients were included in the study. The median follow-up time was 6.2 years. 125 (11%) women died from breast cancer and 155 (14%) died from other causes. For the prediction of BCD, the cause-specific Cox sub-model performed the best. The time dependent AUC begins above 0.91 in year one to 3 reducing to 0.83 in year 6. The factors included in the Cox sub model were tumour size, skin thickening, source of detection, tumour grade, ER status, pre-operative nodal metastasis and CKD. CONCLUSION: We have shown that a model based on preoperative factors can predict BCD. Such prediction if externally validated and incorporating treatment data could be useful for treatment planning and patient counselling.

Preimplantation genetic diagnosis for a carrier with m.3697G > A mitochondrial DNA mutation.

OBJECTIVE: To explore inheritance of the m.3697G > A mitochondrial DNA (mtDNA) mutation and the effectiveness of preimplantation genetic diagnosis (PGD) for the carrier. METHODS: The study encompassed a pedigree of m.3697G > A mtDNA mutation, including one asymptomatic patient who pursued for PGD treatment. Twelve cumulus oocyte complexes (COCs) were collected in the first PGD cycle and 11 COCs in the second cycle. The efficiency of cumulus cells, polar bodies, and trophectoderm (TE) in predicting the m.3697G > A heteroplasmy of embryos was analyzed. RESULTS: From 23 COCs, 20 oocytes were fertilized successfully. On day 5 and 6 post-fertilization, 15 blastocysts were biopsied. The m.3697G > A mutation load of TE biopsies ranged from 15.2 to 100%. In the first cycle, a blastocyst with mutation load of 31.7% and chromosomal mosaicism was transferred, but failed to yield a clinical pregnancy. In the second cycle, a euploid blastocyst with mutation load of 53.9% was transferred, which gave rise to a clinical pregnancy. However, the pregnancy was terminated due to fetal cleft lip and palate. The mutation loads of different tissues (47.7 ± 1.8%) from the induced fetus were comparable to that of the biopsied TE and amniotic fluid cell (49.7%). The mutation load of neither cumulus cells (R2 = 0.02, p = 0.58) nor polar bodies (R2 = 0.33, p = 0.13) correlated with TE mutation load which was regarded as a gold standard. CONCLUSIONS: The m.3697G > A mutation showed a random pattern of inheritance. PGD could be used to reduce the risk of inheritance of a high mutation load. Cumulus cells are not a suitable predictor of blastocyst mutation load.

Erratum: Ribosomal RNA 2' O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer.

[This corrects the article DOI: 10.1093/narcan/zcaa036.].

Are baseline mammographic and ultrasound features associated with metastasis free survival in women receiving neoadjuvant chemotherapy for invasive breast cancer?

OBJECTIVES: To identify associations between baseline ultrasound (US) and mammographic features and metastasis free survival (MFS) in women receiving neo-adjuvant chemotherapy (NACT) for breast cancer. METHODS: The data were collected as part of an ethically approved prospective study. Women with invasive breast cancer receiving NACT who were metastasis free at diagnosis were included. Baseline US and mammography were performed. Imaging was assessed by an experienced breast radiologist who was blinded to outcomes. US imaging features documented included posterior effect, skin thickening, size and stiffness using shear wave elastography (SWE). The mammographic features documented were spiculation and microcalcification. The development of metastatic disease was ascertained from computer records. Statistical analysis was performed using Kaplan Meier survival curves and Receiver Operator Characteristic (ROC) analysis. RESULTS: 171 women with 172 cancers were included in the study and 55 developed metastatic disease. Mean follow-up was 6.0 years. Women with mammographic calcification had significantly poorer metastasis free survival (MFS) compared to women without calcification (p = 0.043, 6 yr MFS 50 % vs 69 %). Women bearing cancer with distal shadowing had poorer MFS than women without shadowing (p = 0.025, 6 yr MFS 47 % vs. 73 %). Women with US skin thickening had poorer MFS compared to women without skin thickening (p = 0.032, 6 yr MFS 52 % vs. 68 %). Mammographic spiculation, US size and stiffness at SWE had no significant association with MFS. CONCLUSION: We have identified mammographic and US features associated with MFS in women receiving NACT. Such information may be useful when counselling patients about the benefits and risks of NACT.

The combined action of monocytic myeloid-derived suppressor cells and mucosal-associated invariant T cells promotes the progression of cervical cancer.

One of the most common promoters of the initiation and growth of the tumor is an immune disturbance. Numerous immune cells and inflammatory factors play a role in the tumor-immune microenvironment. However, few studies have investigated the correlation between these immunological events and clinical consequences in cervical cancer. We measured the levels of numerous inflammatory mediators and frequencies of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and mucosal-associated invariant T (MAIT) cells in peripheral blood (PB) of cervical cancer patients. Cervical cancer patients showed elevated production of interleukin (IL)-18 and plasma C-C chemokine ligand (CCL) 3/5. Meanwhile, an accumulation of C-C chemokine receptor 5 (CCR5) monocytic (Mo)-MDSCs and Tregs was observed. The cervical cancer group displayed increased frequencies of CD8+ , CD4+ and highly activated CD38+ CD8+ MAIT cells, and reduction of double-negative (DN) and PD1(CD279+ ) DN MAIT cells. Importantly, it was demonstrated that MAIT cells were positively related to Mo-MDSCs. Furthermore, an elevated concentration of PD1(CD279+ ) DN MAIT cells was significantly related to increased progression-free survival of patients with cervical cancer. In conclusion, our study suggests that the combined action of Mo-MDSCs and MAIT cells might be associated with the progression of cervical cancer, and the frequency of DN MAIT cells in the peripheral blood mononuclear cells was associated with the survival benefit of patients.

Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP.

Our cluster analysis of the Cancer Genome Atlas for co-expression of HSP27 and CRYAB in breast cancer patients identified three patient groups based on their expression level combination (high HSP27 + low CRYAB; low HSP27 + high CRYAB; similar HSP27 + CRYAB). Our analyses also suggest that there is a statistically significant inverse relationship between HSP27 and CRYAB and known clinicopathological markers in breast cancer. Screening an unbiased 248 breast cancer patient tissue microarray (TMA) for the protein expression of HSP27 and phosphorylated HSP27 (HSP27-82pS) with CRYAB also identified three patient groups based on HSP27 and CRYAB expression levels. TMA24 also had recorded clinical-pathological parameters, such as ER and PR receptor status, patient survival, and TP53 mutation status. High HSP27 protein levels were significant with ER and PR expression. HSP27-82pS associated with the best patient survival (Log Rank test). High CRYAB expression in combination with wild-type TP53 was significant for patient survival, but a different patient outcome was observed when mutant TP53 was combined with high CRYAB expression. Our data suggest that HSP27 and CRYAB have different epichaperome influences in breast cancer, but more importantly evidence the value of a cluster analysis that considers their coexpression. Our approach can deliver convergence for archival datasets as well as those from recent treatment and patient cohorts and can align HSP27 and CRYAB expression to important clinical-pathological features of breast cancer.

Association between mitochondrial DNA D-loop region polymorphisms and endometriosis in a Chinese population.

OBJECTIVE: To investigate the correlation between endometriosis and mitochondrial DNA (mtDNA) D-loop single nucleotide polymorphisms (SNPs) and haplotype, as well as the predictive power of certain SNPs in reproductive outcomes in a Chinese Han population. METHODS: A case-control study was conducted in which 125 endometriosis patients and 124 controls were recruited from an academic fertility center. The entire 1124-bp D-loop region of mtDNA of whole blood samples from all subjects was amplified, sequenced, and compared with the revised Cambridge Reference Sequence (rCRS) to identify SNPs and haplotypes. The association between D-loop SNPs and embryo quality and clinical outcome following in vitro fertilization (IVF) was also assessed. RESULTS: A total of 321 polymorphisms were identified by sequencing, allowing comparison of the D-loop between endometriosis patients and controls. The frequency of the AC523-524 del, T16172C, and C16290T variants were significantly higher, while the frequency of polymorphisms T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins were lower, in the endometriosis group compared with the control group (p < 0.05). Within the endometriosis group, the high-quality blastocyst rate in the 16,290T subgroup was significantly lower than that in the 16290C subgroup (p < 0.05). In the control group, 16519C carriers showed a lower rate of high-quality blastocyst development compared with 16519T (p < 0.05). In endometriosis patients clinical pregnancy rate was significantly lower in the 150T subgroup compared with the 150C subgroup (p < 0.05). DISCUSSION: Data confirms a correlation between D-loop polymorphisms and endometriosis. The polymorphisms AC523-524 del, T16172C, and C16290T are associated with increased risk of endometriosis, while T195C, 573XCins, 16036Gins, 16049Gins, T16140C, A16183C, T16189C, and 16193Cins are associated with decreased risk of endometriosis. In addition, C16290T and T16519C can be associated with poor quality blastocyst development in population with and without endometriosis, respectively and C150T can be a predictor of poor IVF outcome.

Ribosomal RNA 2'O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer.

Recent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2'O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2'O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2'O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2'O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2'O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2'O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2'O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer.

∆Np63/p40 correlates with the location and phenotype of basal/mesenchymal cancer stem-like cells in human ER+ and HER2+ breast cancers.

ΔNp63, also known as p40, regulates stemness of normal mammary gland epithelium and provides stem cell characteristics in basal and HER2-driven murine breast cancer models. Whilst ΔNp63/p40 is a characteristic feature of normal basal cells and basal-type triple-negative breast cancer, some receptor-positive breast cancers express ΔNp63/p40 and its overexpression imparts cancer stem cell-like properties in ER+ cell lines. However, the incidence of ER+ and HER2+ tumours that express ΔNp63/p40 is unclear and the phenotype of ΔNp63/p40+ cells in these tumours remains uncertain. Using immunohistochemistry with p63 isoform-specific antibodies, we identified a ΔNp63/p40+ tumour cell subpopulation in 100 of 173 (58%) non-triple negative breast cancers and the presence of this population associated with improved survival in patients with ER- /HER2+ tumours (p = 0.006). Furthermore, 41% of ER+ /PR+ and/or HER2+ locally metastatic breast cancers expressed ΔNp63/p40, and these cells commonly accounted for <1% of the metastatic tumour cell population that localised to the tumour/stroma interface, exhibited an undifferentiated phenotype and were CD44+ /ALDH- . In vitro studies revealed that MCF7 and T47D (ER+ ) and BT-474 (HER2+ ) breast cancer cell lines similarly contained a small subpopulation of ΔNp63/p40+ cells that increased in mammospheres. In vivo, MCF7 xenografts contained ΔNp63/p40+ cells with a similar phenotype to primary ER+ cancers. Consistent with tumour samples, these cells also showed a distinct location at the tumour/stroma interface, suggesting a role for paracrine factors in the induction or maintenance of ΔNp63/p40. Thus, ΔNp63/p40 is commonly present in a small population of tumour cells with a distinct phenotype and location in ER+ and/or HER2+ human breast cancers.

User-Driven Comments on a Facebook Advertisement Recruiting Canadian Parents in a Study on Immunization: Content Analysis.

BACKGROUND: More people are searching for immunization information online and potentially being exposed to misinformation and antivaccination sentiment in content and discussions on social media platforms. As vaccination coverage rates remain suboptimal in several developed countries, and outbreaks of vaccine-preventable diseases become more prevalent, it is important that we build on previous research by analyzing themes in online vaccination discussions, including those that individuals may see without actively searching for information on immunization. OBJECTIVE: The study aimed to explore the sentiments and themes behind an unsolicited debate on immunization in order to better inform public health interventions countering antivaccination sentiment. METHODS: We analyzed and quantified 117 user-driven open-ended comments on immunization posted in the Comments section of a Facebook advertisement that targeted Canadian parents for recruitment into a larger study on immunization. Then, 2 raters coded all comments using content analysis. RESULTS: Of 117 comments, 85 were posted by unique commentators, with most being female (65/85, 77%). The largest proportion of the immunization comments were positive (51/117, 43.6%), followed by negative (41/117, 35.0%), ambiguous (20/117, 17.1%), and hesitant (5/117, 4.3%). Inaccurate knowledge (27/130, 20.8%) and misperceptions of risk (23/130, 17.7%) were most prevalent in the 130 nonpositive comments. Other claims included distrust of pharmaceutical companies or government agencies (18/130, 13.8%), distrust of the health care system or providers (15/130, 11.5%), past negative experiences with vaccination or beliefs (10/130, 7.7%), and attitudes about health and prevention (10/130, 7.7%). Almost 40% (29/74, 39%) of the positive comments communicated the risks of not vaccinating, followed by judgments on the knowledge level of nonvaccinators (13/74, 18%). A total of 10 positive comments (10/74, 14%) specifically refuted the link between autism and vaccination. CONCLUSIONS: The presence of more than 100 unsolicited user-driven comments on a platform not intended for discussion, nor providing any information on immunization, illustrates the strong sentiments associated with immunization and the arbitrariness of the online platforms used for immunization debates. Health authorities should be more proactive in finding mechanisms to refute misinformation and misperceptions that are propagating uncontested online. Online debates and communications on immunization need to be identified by continuous monitoring in order for health authorities to understand the current themes and trends, and to engage in the discussion.

A comparison of the imaging features of pleomorphic and classical invasive lobular carcinoma.

PURPOSE: Pleomorphic invasive lobular carcinoma (pILC) is a distinct morphological variant of ILC with a poorer prognosis than classical ILC (cILC). The aim of this study was to ascertain whether the conventional imaging appearances of the two entities differ. METHODS: A single-center retrospective review of conventional imaging was undertaken in 150 consecutive patients with histopathologically confirmed ILC (38 pILC; 112 cILC) between April 2010 and July 2015. Mammographic and sonographic findings were evaluated using the BI-RADS lexicon by a radiologist blinded to pathology, and the findings in the two groups were compared. The degree of discrepancy between imaging and pathological sizing in the two groups was evaluated. RESULTS: Lesions were mammographically occult in 11% of pILC and 14% of cILC (p = 0.56). On mammography, skin or trabecular thickening and microcalcification were commoner in pILC than cILC (13% vs. 1%, p < 0.01; 25% vs. 5%, p < 0.01). Architectural distortion was more frequent in cILC than pILC (26% vs. 9%, p = 0.01). On ultrasound, pILC more frequently exhibited mixed echogenicity (28% vs. 13%; p = 0.04), skin thickening, subcutaneous or parenchymal edema (8% vs. 0%; p = 0.02), echogenic surrounding fat (33% vs. 9%; p < 0.01), and posterior acoustic enhancement (10% vs. 1%; p = 0.02) than cILC. CILC was more frequently manifested as a focal area of altered echogenicity (24% vs. 8%; p = 0.04). Mean elastography stiffness was higher for pILC (174.8 vs. 124.6 kPa; p = 0.02). Imaging-pathological size disparity was similar for both subtypes. CONCLUSION: There are differences in the imaging features between pILC and cILC which reflect the more aggressive nature of pILC.