Flattening the Playing Field for Treatment of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) remains a major health care issue and is beset with significant racial and ethnic disparities in regard to its incidence, progression, and complication rate. An individual's health is influenced strongly by an array of societal-level factors commonly called the social determinants of health. Among these, DKD is influenced highly by structured resources and opportunities, as well as an individual's socioeconomic status, health insurance status, access to care, education, health literacy, nutrition, green space exposure, level of trust in the medical community, and more. Health equity is considered a state in which everyone has a fair and just opportunity to attain his or her highest level of health. Conversely, health inequities are a consequence of a structured discriminatory system of inequitable allocation of social determinants of health. When this discriminatory system is race-based it is referred to as structural racism, which eventually leads to racial and ethnic health disparities. The further downstream sequela of structural racism, consciously or unconsciously, impacts health systems, providers, and patients, and can lead to disparities in DKD development, progression, and complications. In this article, we explore potential interventions at the societal, health system, and provider levels that can help flatten the playing field and reduce racial and ethnic disparities in DKD.

Hemodialysis Disparities in African Americans: The Deeply Integrated Concept of Race in the Social Fabric of Our Society.

End-stage renal disease (ESRD) is one of the starkest examples of racial/ethnic disparities in health. Racial/ethnic minorities are 1.5 to nearly 4 times more likely than their non-Hispanic White counterparts to require renal replacement therapy (RRT), with African Americans suffering from the highest rates of ESRD. Despite improvements over the last 25 years, substantial racial differences are persistent in dialysis quality measures such as RRT modality options, dialysis adequacy, anemia, mineral and bone disease, vascular access, and pre-ESRD care. This report will outline the current status of racial disparities in key ESRD quality measures and explore the impact of race. While the term race represents a social construct, its association with health is more complex. Multiple individual and community level social determinants of health are defined by the social positioning of race in the U.S., while biologic differences may reflect distinct epigenetic changes and linkages to ancestral geographic origins. Together, these factors conspire to influence dialysis outcomes among African Americans with ESRD.

SHOULD FNA BE PERFORMED IN PATIENTS WITH A MULTINODULAR GOITER AND COMPRESSIVE SYMPTOMS?

OBJECTIVE: In this study, we aimed to determine whether preoperative thyroid fine-needle aspiration (FNA) in patients with multinodular goiter (MNG) and compressive symptoms influences the type of thyroid surgery performed, the incidence of recurrent thyroid cancer, or the need for successive surgery. METHODS: We retrospectively reviewed the charts of 431 patients who underwent thyroidectomy at our institution from 2008 to 2011. Patients who presented with compressive symptoms and no prior FNA at initial presentation were included in this study. RESULTS: Eighty patients met the criteria for our study, of which 46 (57.5%) underwent FNA prior to surgery and 34 (42.5%) were referred to surgery without FNA. The prevalence rates of malignancy (>1 cm) on surgical pathology in the FNA and non-FNA groups were 41% (n = 19) and 38% (n = 13), respectively. There was no statistically significant difference between the rate of total/subtotal thyroidectomies (71.7% in FNA vs. 79.4% in non-FNA, P = .31), lobectomies/partial thyroidectomies (28.3% in FNA vs. 20.5% in non-FNA, P = .43), neck lymph node dissections (P = .89) or subsequent surgeries (P = .72) between the 2 groups. CONCLUSION: Our findings show that preoperative FNA in patients with an MNG and compressive symptoms does not influence the type of surgery performed, short-term outcomes, or the need for subsequent surgeries. Further studies are needed to validate the need for preoperative FNA in such patients. ABBREVIATIONS: FNA = fine-needle aspiration MNG = multinodular goiter WHO = World Health Organization.

African Americans, hypertension and the renin angiotensin system.

African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system (RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.

Molecular diagnosis of a BRAF papillary thyroid carcinoma with multiple chromosome abnormalities and rare adrenal and hypothalamic metastases.

OBJECTIVE: Molecular characterization of thyroid tumors is rarely applied to patient management. Our aim was to demonstrate the application of molecular and cell biology to patient care. DESIGN: Clinical and molecular case study. MAIN OUTCOMES: A 57-year-old man with papillary thyroid carcinoma presented with adrenal and several other presumed metastases, pulmonary nodules, and mediastinal lymphadenopathy. Bronchial carcinoma was entertained for the pulmonary lesions because of a tobacco history. Mediastinal lymph node biopsy was nondiagnostic. Cells from the biopsy were grown in tissue culture and characterized by immunocytochemical (ICC), allele-specific polymerase chain reaction (PCR), reverse transcription (RT)-PCR, DNA sequencing, and cytogenetics. A panel of agents were tested the cells for tumoricidal activity. The cells expressed thyroid-specific markers [thyroid-stimulating hormone receptor (TSH-R), thyroglobulin (TG), sodium iodide symporter (NIS)] and markers [thyroid transcription factor-1 (TTF-1), cytokeratin-7, epidermal growth factor receptor (EGF-R)] present in the primary tumor and adrenal metastasis. The BRAF V600E mutation was detected. The karyotype was 44-48,XY, + der(1) t(1;9)(p13;p13),add(9)(p13),-17,-18, + 0-3mar[cp20]. Lovastatin, gefitinib, paclitaxel, depsipeptide, and 17-AAG inhibited the growth of the cultured cells. Combinations of two or three drugs produced additive or synergistic effects depending upon the combination. CONCLUSIONS: Unusual metastases may be associated with multiple molecular and cytogenetic abnormalities. Thus, molecular and cell-biological studies can allow otherwise difficult thyroid tumor diagnosis and may be used for targeted, individualized selection of potential treatments.

Spurious hypocalcemia after gadodiamide administration.

Severe hypocalcemia may require prompt intervention to avoid life-threatening consequences. We report a case in which a 78-year-old man had a critically low serum calcium level measured with use of standard colorimetric assay after gadodiamide administration during magnetic resonance angiography. Reanalysis of the same serum specimen using absorption spectroscopy revealed normal calcium values, confirming the diagnosis of spurious hypocalcemia. The increasing use of gadolinium chelates during magnetic resonance imaging and anglography will lead to a marked increase in reports of critically low serum calcium values. Increasing physicians' awareness of gadodiamide-induced spurious hypocalcemia may prevent unnecessary and potentially inappropriate therapeutic interventions.

Targeting the ERK pathway: novel therapeutics for thyroid cancer.

Over the past two decades significant progress has been made in elucidating the pathogenesis of thyroid cancer. The ongoing identification of mutations in cellular signaling pathways has revolutionized the field of thyroid cancer biology and has led to the development of novel new therapeutic agents. One of the signaling cascades implicated in the oncogenic process is the ERK pathway that normally functions to transmit mitogenic signals from the cell membrane to the nucleus. Genetic alterations of key components of this cascade, namely RET, Ras and Raf, are thought to result in constitutive activation of the pathway and subsequent thyroid tumorigenesis. Targeting of these components with pharmaceutical agents holds the potential of providing newer and more effective treatment modalities for thyroid cancer. Several such drugs are currently being developed to inhibit RET, Ras, Raf, as well as other factors impacted by the ERK pathway. These include a vast array of agents such as antisense compounds, small molecule inhibitors as well as inhibitors of farnesyl transferase, heat shock proteins, matrix metalloproteinases and histone deacetylases. Some of these drugs have already entered preclinical and clinical testing with promising anti-tumor effects. These as well as even newer agents may offer exciting possibilities for the future treatment of thyroid cancer.

Inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura.

We report an unusual case of a 51-year-old woman with inclusion body myositis associated with celiac sprue and idiopathic thrombocytopenic purpura. We propose that the presence of all three disorders together suggests that they may share an interrelated immune mechanism.