Loss of PPARγ activity characterizes early protumorigenic stromal reprogramming and dictates the therapeutic window of opportunity.

Although robustly expressed in the disease-free (DF) breast stroma, CD36 is consistently absent from the stroma surrounding invasive breast cancers (IBCs). In this study, we primarily observed CD36 expression in adipocytes and intralobular capillaries within the DF breast. Larger vessels concentrated in interlobular regions lacked CD36 and were instead marked by the expression of CD31. When evaluated in perilesional capillaries surrounding ductal carcinoma in situ, a nonobligate IBC precursor, CD36 loss was more commonly observed in lesions associated with subsequent IBC. Peroxisome proliferator-activated receptor γ (PPARγ) governs the expression of CD36 and genes involved in differentiation, metabolism, angiogenesis, and inflammation. Coincident with CD36 loss, we observed a dramatic suppression of PPARγ and its target genes in capillary endothelial cells (ECs) and pericytes, which typically surround and support the stability of the capillary endothelium. Factors present in conditioned media from malignant cells repressed PPARγ and its target genes not only in cultured ECs and pericytes but also in adipocytes, which require PPARγ for proper differentiation. In addition, we identified a role for PPARγ in opposing the transition of pericytes toward a tumor-supportive myofibroblast phenotype. In mouse xenograft models, early intervention with rosiglitazone, a PPARγ agonist, demonstrated significant antitumor effects; however, following the development of a palpable tumor, the antitumor effects of rosiglitazone were negated by the repression of PPARγ in the mouse stroma. In summary, PPARγ activity in healthy tissues places several stromal cell types in an antitumorigenic state, directly inhibiting EC proliferation, maintaining adipocyte differentiation, and suppressing the transition of pericytes into tumor-supportive myofibroblasts.

High-dose tramadol conversion to buprenorphine-naloxone.

Buprenorphine-naloxone is a combination medication of an opioid partial agonist and opioid antagonist that is proven to be effective in outpatient management of opioid use disorder (OUD). Tramadol is a centrally acting analgesic. This commonly used pain medication inhibits serotonin and noradrenaline reuptake by acting as a selective agonist on opioid µ receptors. Transition and tapering high-dose tramadol to buprenorphine-naloxone is not well described in the literature. We report a case of a patient who was taking 1,000-1,250 mg of tramadol daily upon presentation to the clinic. She was originally prescribed 150 mg daily with escalation in dose and frequency over a 10-year period. The patient was converted to bupren-orphine-naloxone and has been successful in treatment of OUD for 1 year.

The correlation between food insecurity and infant mortality in North Carolina.

OBJECTIVE: Food insecurity (FI) affects approximately 11·1 % of US households and is related to worsened infant outcomes. Evidence in lower income countries links FI and infant mortality rates (IMR), but there are limited data in the USA. This study examines the relationship between FI and IMR in North Carolina (NC). DESIGN: NC county-level health data were used from the 2019 Robert Woods Johnson Foundation County Health Rankings. The dependent variable was county-level IMR. Eighteen county-level independent variables were selected and a multivariable linear regression was performed. The independent variable, FI, was based on the United States Department of Agriculture's Food Security Supplement to the Current Population Survey. SETTING: NC counties. PARTICIPANTS: Residents of NC, county-level data. RESULTS: The mean NC county-level IMR was 7·9 per 1000 live births compared with 5·8 nationally. The average percentage of county population reporting FI was 15·4 % in the state v. 11·8 % nationally. Three variables statistically significantly predicted county IMR: percent of county population reporting FI; county population and percent population with diabetes (P values, respectively, < 0·04; < 0·05; < 0·03). These variables explained 42·4 % of the variance of county-level IMR. With the largest standardised coefficient (0·247), FI was the strongest predictor of IMR. CONCLUSIONS: FI, low birth weight and diabetes are positively correlated with infant mortality. While correlation is not causation, addressing FI as part of multifaceted social determinants of health might improve county-level IMR in NC.

Launching a Medication-Assisted Treatment in an Outpatient Office-Based Practice.

Background: Opioid use and overdose are escalating in the United States. Primary care providers are in a strategic position to assess patients for medication-assisted treatment (MAT). Objectives: To describe the implementation of MAT in an integrated primary care residency clinic and assess provider comfort levels with evaluating patients for high-risk opioid use, conduct crucial conversations about MAT treatment options and referral to MAT for evaluation and treatment. Methods: As part of a Primary Care Training and Enhancement grant through Health Resources and Services Administration, we used an implementation process to allow for optimal clinic flow. The process included assessment of patient populations, identifying a provider champion, organizing multidisciplinary team, engaging a practice facilitator, designing clinic model and infrastructure, creating the electronic health record order sets along with provider and staff training. Providers responded to brief questions to evaluate comfort levels in 3 domains: identifying high-risk opioid use, conducting crucial conversations about treatment options and referral to MAT for evaluation and treatment. Discussion: Incorporating MAT within an integrated primary care clinic and residency program with waiver training for residents was a successful and innovative program. The availability of MAT provided a solution for patients that could benefit from this type of treatment. MAT presence gave providers the opportunity to refer these patients for treatment that had not previously been as accessible. Conclusion: An integrated primary care practice with an embedded MAT can be successful with an organized structure to optimize clinic flow.

Assessing the Need for a Structured Nutrition Curriculum in a Primary Care Residency Program.

Background: Given the epidemic of diet-related illnesses, medical training regarding nutrition counseling is not fully known. Historically, there is a lack of formalized nutrition training in both medical school and residency programs.Objective: This study surveyed a group of family medicine residents to elicit previous nutrition education and outlook on nutrition counseling. A measure of resident attitudes toward nutrition education and comfort with relaying nutrition education to patients was conducted.Design: A validated, self-administered questionnaire was administered. The survey was composed of 32 questions with yes/no or Likert scale response.Participants and setting: Participants were 30 family medicine residents in the final quarter of their individual postgraduate year of training (PGY1-3). A total of 23 residents electively responded.Results: The majority surveyed conveyed nutrition education in routine care is important in a physician-patient relationship. Except in diabetes, the overwhelming majority reported they were not adequately trained to give nutrition education in specific disease states. The group was not familiar with types of diets, the role of fatty acids, or the impact of specific vitamins on health.Conclusions: The data from this survey indicate a need for formalized nutrition education in primary care training. From the survey data results, the next steps include building a nutrition curriculum to be implemented in the residency program and potentially set a standard for nutrition education in the North Carolina region and beyond.

Knowledge and Perception of Breast Density, Screening Mammography, and Supplemental Screening: in Search of "Informed".

BACKGROUND: As of 2019, 37 US states have breast density notification laws. No qualitative study to date has examined women's perspectives about breast density in general or by states with and without notification laws. OBJECTIVE: Explore women's knowledge and perceptions of breast density and experiences of breast cancer screening across three states with and without notification laws. DESIGN: Qualitative research design using four focus groups conducted in 2017. PARTICIPANTS: Forty-seven women who had a recent normal mammogram and dense breasts in registry data obtained through the Breast Cancer Surveillance Consortium. APPROACH: Focus groups were 90 min, audio recorded, and transcribed for analysis. Data were analyzed using mixed deductive and inductive coding. KEY RESULTS: Women reported variable knowledge levels of personal breast density and breast density in general, even among women living in states with a notification law. A number of women were aware of the difficulty of detecting cancer with dense breasts, but only one knew that density increased breast cancer risk. Across all states, very few women reported receiving information about breast density during healthcare visits beyond being encouraged to get supplemental imaging or to pay for new mammography technology (i.e., breast tomosynthesis). Women offered more imaging or different technology held strong convictions that these were "better," even though knowledge of differences, effectiveness, or harms across technologies seemed limited. Women from all states expressed a strong desire for more information about breast density. CONCLUSIONS: More research needs to be done to understand how the medical community can best assist women in making informed decisions related to breast density, mammography, and supplemental screening. Options to explore include improved breast density notifications and education materials about breast density, continued development of personalized risk information tools, strategies for providers to discuss evidence and options based on risk stratification, and shared decision-making.

Extra-abdominal umbilical vein varix in a newborn.

Umbilical vein varices are rare fetal anomalies typically found intra-abdominally and identified on ultrasound prior to birth. Intra-abdominal umbilical vein varices account for approximately 4% of umbilical cord abnormalities and are thought to be a developmental abnormality rather than a congenital malformation. The umbilical vein varix anomaly been shown to be associated with a higher incidence of adverse perinatal outcomes and there is evidence of a relationship between this and chromosomal abnormalities. There have been few case reports of extra-abdominal varices. This case reviews a multiparous Hispanic female who delivered a baby with an extra-abdominal umbilical vein varix who was admitted to the neonatal intensive care unit but had an uncomplicated hospital course. The report reviews strategies for antenatal testing and surveillance of identified varices.

Glomangiomatosis of the sciatic nerve: a case report and review of the literature.

Glomus tumors are hamartomas, which tend to occur in sites rich in glomus bodies, such as the subungual regions of digits or the deep dermis of the palm, wrist, forearm, and foot. Very rarely, they may involve peripheral nerves. We describe a patient, who, following surgical resection of a solitary glomus tumor of the left distal sciatic nerve in his teens, had recurrence with development of multiple tumors in the course of the nerve over several years. To our knowledge, this is the only known case of glomangiomatosis involving a major peripheral nerve.

Burnout in Female Faculty Members.

Despite approximately equal numbers of male and female medical school graduates, women are entering academic medicine at a lower rate than their male colleagues. Of those who do assume a faculty position, female faculty members report higher levels of burnout, often attributable to gender-specific difficulties in clinical expectations and maintenance of work-life balance. Many of these struggles are attributable to issues that are amenable to supportive policies, but these policies are inconsistent in their availability and practice. This commentary presents evidence for inconsistencies in the day-to-day experience of female faculty members, and proposes solutions for the mitigation of the challenges experienced more often by female faculty members with the goal of diversifying and strengthening academic medicine.

Role of Statin Drugs for Polycystic Ovary Syndrome.

Objective: To review the potential role and specific impact of statin drugs in women with PCOS. The evidence for this use of statins in PCOS is limited and still under further investigation. Materials and methods: A search was conducted using PubMed, DynaMed and PubMedHealth databases through October 16, 2016 using the terms polycystic ovary syndrome, PCOS, hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA, statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. English-language trials evaluating statins in PCOS were obtained and incorporated if they provided relevant data for providers. Results: We summarize twelve trials involving statins in PCOS. The trials were predominantly 12 weeks to 3 months in length (8 of the 12 trials) and low to moderate dose of statin drugs were used. The majority (10 of 12) of the trials show that statins reduce testosterone levels or other androgen hormones (DHEA-S and androstenedione), half of the trials evaluating LH/FSH ratio show an improvement, and all had positive effects on lipid profiles. Conclusion: Statins show promising improvements in serum levels of androgens and LH/FSH ratios translating to improved cardiovascular risk factors above and beyond simply lowering LDL levels. More investigation is needed to determine if statins can clinically impact women with PCOS long term, particularly those who are young and are not yet candidates for traditional preventative treatment with a statin medication.

Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis.

Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus.

Calcific tendinitis of the prevertebral space: a case report.

Calcific prevertebral tendinitis is a self-limiting inflammatory condition of the prevertebral space that involves the insertion of the longus colli tendon. Understanding this condition and its characteristic imaging findings is essential for early diagnosis and differentiation of the disorder from other acute conditions. We describe a case of a 40-year-old patient who presented to the emergency department with severe odynophagia and exhibited the computed tomography findings necessary to confirm this disease.

Intraventricular ganglioglioma.

Gangliogliomas are mixed tumors consisting of both glial elements and differentiated neurons. Although any part of the central nervous system can be affected, little is known about intraventricular gangliogliomas. A patient with a ganglioglioma is presented in the previously unreported location of the anterior third ventricle at the foramen of Monro, mimicking a colloid cyst. We review all other reported cases of intraventricular ganglioglioma (n=6) to characterize this entity. Intraventricular gangliogliomas typically affect younger patients with female predominance (male:female, 2:5; median age 25 years). Symptoms occur secondary to obstruction of physiological cerebrospinal fluid circulation. Complete surgical resection with re-establishment of cerebrospinal fluid drainage is the goal of treatment.