The Impact of Medicaid Expansion Under the Affordable Care Act on the Gap Between American Indians and Whites in Breast Cancer Management and Prognosis.

BACKGROUND: Breast cancer (BC) death rates in the USA have not significantly declined for American Indians (AIs) in comparison to Whites. Our objective was to determine whether Medicaid Expansion as part of the Affordable Care Act led to improved BC outcomes for AIs relative to Whites. PATIENTS AND METHODS: Using the National Cancer Database, we conducted a retrospective cohort study. Included were BC patients who were AI and White; 40 to 64 years of age; diagnosed in 2009 to 2016; lived in states that expanded Medicaid in January 2014, and states that did not expand Medicaid. Our outcomes were stage at diagnosis, insurance status, timely treatment, and 3-year mortality. RESULTS: There were 359,484 newly diagnosed BC patients, 99.49% White, 0.51% AI. Uninsured rates declined more in the expansion states than in the nonexpansion states (OR = 0.44, 95% CI: 0.15-0.97, P < 0.001). Lower rates of Stage I BC diagnosis was found in AIs compared to Whites (46.58% vs. 55.33%, P < .001); these differential rates did not change after Medicaid expansion. Rates of definitive treatment initiation within 30 days of diagnosis declined after Medicaid expansion (P < .001); there was a smaller decline in the expansion states (OR 1.118, 95% CI: 1.09, 1.15, P < .001). Three year mortality was not different between expansion and nonexpansion states post Medicaid expansion. CONCLUSIONS: In newly diagnosed BCs, uninsured rates declined more in the states that expanded Medicaid in January 2014. Timely treatment post Medicaid expansion declined less in states that expanded Medicaid. There was no differential benefit of Medicaid expansion in the 2 races.

Differences in Breast Cancers Among American Indian/Alaska Native and non-Hispanic Whites in the USA.

IMPORTANCE: Breast cancer (BC) death rates have not improved for American Indian/Alaska Native (AI/AN) women, whereas, it has significantly decreased for non-Hispanic White (White) women. OBJECTIVE: Delineate the differences in patient and tumor characteristics among AI/AN and Whites with BC, and its impact on age and stage at diagnosis as well as overall survival (OS). METHODS: Hospital-based, cohort study using the National Cancer Database to identify female AI/AN and Whites diagnosed with BC between the years 2004 and 2016. RESULTS: BC in 6866 AI/AN (0.3%) and 1,987,324 Whites (99.7%) were studied. The median age at diagnosis was 58 for AI/AN and 62 for Whites. AI BC patients traveled double the distance for treatment, lived in lower median income zip codes, had a higher percentage of uninsured, higher comorbidities, lower percentage of Stage 0/I, larger tumor size, greater number of positive lymph nodes, higher proportion of triple negative and HER2-positive BC than Whites. All the above comparisons were significant, p<0.001. Association between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AI/AN and Whites. Unadjusted OS was worse for AI/AN as compared to Whites (HR=1.07, 95% CI=1.01-1.14, p=0.023). After adjustment of all covariates, OS was not different (HR=1.038, 95%CI=0.902-1.195, p=0.601). CONCLUSION: There were significant differences in patient/tumor characteristics among AI/AN and White BC which adversely impacted OS in AI/AN. However, when adjusted for various covariates, the survival was similar, suggesting that the worse survival in AI/AN is mostly the impact of known biological, socio-economic, and environmental determinants of health.

Association Between Race and Usage of Pain Medications in Children With Long Bone Fractures in US Emergency Departments, 2011-2019.

OBJECTIVES: The purpose of this study was to determine the association between race and analgesic administration for children with long bone fracture (LBF) in US emergency departments. Previous studies have shown conflicting results regarding association between race and analgesic administration for pediatric LBFs. METHODS: We conducted a retrospective analysis of pediatric emergency department visits for LBF using the 2011-2019 National Hospital Ambulatory Medical Care Survey-Emergency Department. We investigated the diagnostic workup and analgesic prescription rate among White, Black, and other pediatric emergency department visits for LBF. RESULTS: Of the estimated 292 million pediatric visits to US emergency departments from 2011 to 2019, 3.1% were LBFs. Black children were less likely to be seen for a LBF than White or other children (1.8% vs 3.6% and 3.1%, P < 0.001). There was no association between race and subjective pain scale ( P = 0.998), triage severity ( P = 0.980), imaging (x-ray, P = 0.612; computed tomography scan, P = 0.291), or analgesic administration (opioids, P = 0.068; nonsteroidal antiinflammatory drugs/acetaminophen, P = 0.750). Trend analysis showed a significant decrease in opioid administration for pediatric LBF from 2011 to 2019 ( P < 0.001), with 33.0% receiving opioids. CONCLUSIONS: There was no association between race and analgesic administration, including opioids, or diagnostic workup in pediatric LBF. In addition, there was a significant downtrend in opioid administration for pediatric LBF from 2011 to 2019.

Integrated secure messaging to enhance medical education: a mixed methods study.

BACKGROUND: Instant messaging applications and texting are useful for educating and communicating with medical students; however, they present patient privacy concerns and do not address the challenge of student inclusion in patient care communication. EMR-integrated secure messaging offers an opportunity to include students on team communication, enhance their medical education, and ensure patient privacy. METHODS: Between July 2019 through March 2020, we performed a mixed method study to evaluate use of EPIC® Secure Chat as a means of enhancing student education and team communication. We promoted use of secure messaging in orientation, performed a pre- and post-rotation survey to assess perceptions of Secure Chat effect on communication, and directly reviewed and categorized messages. RESULTS: Twenty-four 3rd and 4th year students completed the pre-rotation survey, and 22 completed the post-rotation survey. Twelve (50%) students reported the quality of communication with faculty was either good or very good prior to internal medicine rotation, while 20 (91%) reported this post-rotation (p-value 0.001). There was a similar improvement in communication with ancillary staff. Nineteen (86%) students felt that secure messaging improved their communication with faculty. On message review, threads were frequently logistical, but also often included discussions of patient management. CONCLUSIONS: Students viewed Secure Chat as having a favorable effect on their communication with team members and reported communication on internal medicine to be improved compared to prior rotations. Messages included students on important patient care conversations. Secure messaging offers a novel medium to improve team communication, enhance student education, and maintain patient privacy.

Trends and risk factors in the antibiotic management of skin and soft tissue infections in the United States.

OBJECTIVE: The aim of this study was to examine the trends and risk factors of antibiotic treatment for skin and soft tissue infections (SSTIs), in the United States. METHODS: We conducted a retrospective analysis of SSTIs visits utilizing the 2011-2016 National Ambulatory Medical Care Survey. RESULTS: There were over 43 million visits for SSTIs in the US. We found no association between antibiotic treatment and gender, age, race, insurance, region, and metropolitan statistical area. Methicillin-resistant Staphylococcus aureus (MRSA) antibiotics were prescribed at 34.8% of SSTI visits, methicillin-sensitive Staphylococcus aureus (MSSA) antibiotics at 27.5%, and other antibiotics at 21.7%. Among visits treated with an antibiotic, 40.4% (n = 378) received an antibiotic with MSSA coverage, while 59.6% (n = 558) received an antibiotic with MRSA coverage. Region where the visit occurred was associated with the use of MSSA versus MRSA antibiotics (p = .013). Mean age of visits receiving MSSA antibiotics was significantly older than visits receiving MRSA antibiotics, 53.8 ± 1.2 vs. 50.9 ± 0.9 (p = .045). CONCLUSIONS: This study found that providers more frequently utilize antibiotics with MRSA coverage for SSTIs. Antibiotic class chosen was associated with region, with MRSA coverage antibiotics more likely to be prescribed in the South. Additionally, individuals receiving antibiotics with MSSA coverage were older than those receiving antibiotics with MRSA coverage.

The efficacy of low dose short-term prednisone therapy for remission induction in newly diagnosed rheumatoid arthritis patients.

BACKGROUND: The ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients' flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients. METHODS: A retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients' medical charts. Patients treated with (< 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria. RESULTS: Data on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5-10; SD = 1.2) and the mean treatment duration was 42.2 days (12-177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission. CONCLUSION: Short-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.

A cross-sectional analysis of infant-driven and traditional feeding outcomes for neonatal intensive care unit infants.

OBJECTIVE: The goal of this study was to assess the impact of infant-driven feeding (IDF) compared to traditional feeding protocols in promoting earlier successful feeding outcomes. STUDY DESIGN: We performed a cross-sectional analysis of infants admitted to a level three neonatal intensive care unit (NICU) over a 2-year period. We compared infants fed with the traditional protocol to those under the IDF protocol. RESULTS: Infants in the IDF group were younger at first feed (p < 0.001). There was no difference in age at nasogastric (NG) tube removal or at discharge, length of stay, or percentage breastfeeding at discharge. There were no differences in outcomes within two subgroups born at <35 and <32 weeks gestation, respectively. CONCLUSION: The IDF program led to earlier initiation of oral feeding. However, this did not lead to earlier NG tube removal or discharge, a shorter length of stay, or increase in the rates of breastfeeding.

Antibiotic utilization for adult acute respiratory tract infections in United States Emergency Departments.

BACKGROUND: Antibiotic stewardship programs have been a major focus in recent years to curtail antibiotic resistance. The purpose of this study was to evaluate antibiotic utilization for acute respiratory tract infections (ARTI) in the Emergency Department (ED) setting. MATERIAL AND METHODS: A retrospective analysis of adult ARTI visits to EDs utilizing 2011-2017 National Hospital Ambulatory Medical Care Survey- Emergency Department (NHAMCS-ED) datasets was conducted. Included were all visits of adults (≥18 years) diagnosed with ARTI. Antibiotics were determined based upon NHAMCS-ED use of the Multum Lexicon Drug Database coding system. All significance tests were two-sided, P-value <0.05 for significance. RESULTS: A total of 4632 unweighted ED visits, which represented more than 28 million US ED visits from 2011 to 2017, with 57.2% receiving a prescription for antibiotics. Antibiotic prescriptions for ARTI significantly declined from 65.8% in 2011 to 54.3% in 2017 (P = 0.046). Among all visits, patients were more likely to receive an antibiotic if they were over age 45 (33.0% vs 27.6%, P = 0.005), male (36.7% vs. 32.3%, P = 0.039), and presenting in a non-MSA ED (21.4% vs. 14.5%, P = 0.002). No association was found between antibiotic prescription and race (P = 0.076) insurance (P = 0.488), CBC (P = 0.148), x-ray (P = 0.278), and blood cultures (P = 0.182). CONCLUSION: We found a significant reduction in the utilization of antibiotics among adult ARTI visits to U.S. EDs from 2011 to 2017. This is an improvement from previous studies which showed no change, suggesting that antimicrobial stewardship efforts may be impacting overall antibiotic use and should continue to be practiced.

The efficacy of low dose short-term prednisone therapy for remission induction in newly diagnosed rheumatoid arthritis patients

Abstract Background: The ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients' flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients. Methods: A retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients' medical charts. Patients treated with (≤ 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria. Results: Data on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5-10; SD = 1.2) and the mean treatment duration was 42.2 days (12-177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission. Conclusion: Short-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.

DAS28-CRP Cutoffs for High Disease Activity and Remission Are Lower Than DAS28-ESR in Rheumatoid Arthritis.

OBJECTIVE: Guidelines do not specify how cutoffs for high disease activity differ between the Disease Activity Score 28-joint count indices DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP). Studies that compare DAS28-CRP and DAS28-ESR depend on data from clinical trials, registries, or practices with multiple providers. Existing studies use data from patients who received immunosuppressive therapy. This study compared the DAS28-ESR and DAS28-CRP values from immunosuppressive treatment-naïve patients in a single physician practice. METHODS: A retrospective electronic medical chart review was conducted for new diagnoses of rheumatoid arthritis (RA; International Classification of Diseases [ICD]-9 714), based on the American College of Rheumatology/European League against Rheumatology 2010 RA classification criteria. The number of patients with high disease activity (>5.1) was compared using ESR and CRP data to calculate the proportion of discordance. A receiver operator curve and Youden index was used to calculate the DAS28-CRP high disease activity cutoff estimation that corresponds with DAS28-ESR of more than 5.1. RESULTS: There were 171 patients included in this study. The baseline mean DAS28-ESR was higher than the baseline mean DAS-28 CRP: 5.1 ± 1.2 versus 4.1 ± 1.0 (P < 0.001); 48.5% of patients met criteria for high disease activity (score >5.1) compared with only 14.6% when measured by DAS28-CRP. Discordance was 33.9%. κ coefficient was only .307. Receiver operator curve and Youden index analysis suggested that the cutoff point for high disease activity of DAS28-CRP greater than 4.1, which corresponds to DAS28-ESR greater than 5.1. Similarly, DAS28-ESR posttreatment scores were significantly higher than DAS28-CRP. When measured by DAS28-ESR, patients in remission had higher scores as measured by DAS28-ESR (1.81) than DAS28-CRP (1.45). CONCLUSION: There is a difference between DAS28-ESR and DAS28-CRP, even when calculated for immunosuppressive treatment-naïve patients. DAS28-CRP is significantly lower than DAS28-ESR.

Differences in Clinical Management and Outcomes of American Indian and White Women Diagnosed With Endometriosis.

Objective: Endometriosis is a chronic, painful disease that can be disabling. There is a scarcity of research on the clinical management and outcomes of endometriosis in American Indian (AI) women. The aim of this study was to determine whether there are discrepancies between AI and White women in symptoms at presentation, initial diagnosis methods, clinical management, and long-term outcomes of endometriosis, in a rural state. Materials and methods: This retrospective study described and compared the clinical management and long-term outcomes of AI and White women diagnosed with endometriosis. All statistical tests were two-tailed with p-value < .05 considered to be significant. Results: 110 women diagnosed with endometriosis were included in the study, with 50% (n = 55) AI and 50% (n = 55) White. White women were more likely to have private insurance (80% vs. 42%; p < 0.001). AI women were more likely than White women to report abdominal pain at diagnosis (20.3% vs. 9%; p = 0.010), and be diagnosed with mild endometriosis symptoms at the initial visit, (44.4% vs. 10%; p = 0.051). White women were more likely to report a reduction or cessation of pain compared to AI women (63.3% vs. 34%; p = 0.004). Conclusion: We found the majority of women continue to report pain long after endometriosis diagnosis. AI women were less likely to report a reduction or cessation of pain. Future research should investigate why pain is more persistent in AI women.

The Association Between Patient Visit Demographics and Opioid Analgesic Received in the Emergency Department.

INTRODUCTION: Minimal research has been conducted on the prescribing patterns of emergency room physicians. The opioid epidemic is a well-known public health crisis and increased knowledge of providers' tendencies to prescribe opioids over other analgesia may help to update guidelines, improve patient safety, and lower the amount of opioid diversion and death from overdose. The purpose of this study was to determine the association between patient visit demographics and prescribed opiate analgesics. METHODS: We conducted a retrospective study analyzing adult patient visits that were seen in the emergency setting for acute pain including chest pain, back pain, abdominal pain, headache, face/tooth/ear, or musculoskeletal pain, utilizing the 2011-2016 National Hospital Ambulatory Medical Care Survey Emergency Department Patient Record dataset. We analyzed the relationship between various patient visit characteristics and whether opiate analgesics were given or prescribed.  Results: Our study included 73,983 visits for pain, representing an estimated 407 million weighted visits over the study period. We found that those who received opiates were more likely to be female, 62.9% vs. 60.2% and more likely to be white, 74.2% vs. 71.3 %. Furthermore, visits that received opiates were more likely to be younger, have private insurance, and be in increased pain (all P-values = 0.000).  Conclusion: We found that certain patient visit characteristics - including being female, white, younger, and private insurance - were given opiates more in the emergency department. Females have been found to report more pain, the elderly have special considerations regarding pain medications (including the risk of delirium and drug-drug interactions), while insurance status may be confounded by age (Medicare being a large portion of government insurance). However, explanations for differences in prescription rates by race could not be easily discerned.

Race and Length of Time Pursuing Pregnancy Among Women Who Utilized Medical Help to Get Pregnant.

Objective: The evaluation of racial disparities in access to and use of infertility services in the U.S. has been documented. The aims of this study were to: 1) investigate racial differences in length of time women report attempting to become pregnant until seeking medical help; and 2) determine the predictors of seeking medical help to achieve pregnancy. Materials and methods: The National Survey of Family Growth 2011-2015 was used to analyze the duration women attempted to get pregnant among those who sought medical help. Results: 563 women reported seeking medical help to achieve pregnancy. The majority 422 (81%) were white. Multiple linear regression showed that age (ß = .93; p = .00), having less than high school education (ß = 14.64; p = .01), and higher body mass index (ß = .59; p = .00) are significantly associated with an increased length of time for seeking medical help to get pregnant. Religions other than Catholic or Protestant (ß = -8.63; p = .04) is significantly associated with a decreased length of time for seeking medical help to get pregnant. Race was not associated with a significant difference in the length of time attempting to become pregnant (ß = -1.80; p = .44). Conclusion: Age, education attainment, religious affiliation, and body mass index are significantly associated with the length of time pursuing pregnancy. Once women have utilized medical resources, racial differences in the length of time pursuing pregnancy are not apparent.

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells.

Cholesterol has been shown to promote cell proliferation/migration in many cells; however the mechanism(s) have not yet been fully identified. Here we demonstrate that cholesterol increases Ca(2+) entry via the TRPM7 channel, which promoted proliferation of prostate cells by inducing the activation of the AKT and/or the ERK pathway. Additionally, cholesterol mediated Ca(2+) entry induced calpain activity that showed a decrease in E-cadherin expression, which together could lead to migration of prostate cancer cells. An overexpression of TRPM7 significantly facilitated cholesterol dependent Ca(2+) entry, cell proliferation and tumor growth. Whereas, TRPM7 silencing or inhibition of cholesterol synthesis by statin showed a significant decrease in cholesterol-mediated activation of TRPM7, cell proliferation, and migration of prostate cancer cells. Consistent with these results, statin intake was inversely correlated with prostate cancer patients and increase in TRPM7 expression was observed in samples obtained from prostate cancer patients. Altogether, we provide evidence that cholesterol-mediated activation of TRPM7 is important for prostate cancer and have identified that TRPM7 could be essential for initiation and/or progression of prostate cancer.

Ovarian cancer incidence in the United States in relation to manufacturing industry.

OBJECTIVE: Ovarian cancer is primarily a disease of the industrialized world. However, few factors associated with industrialization that contribute to the etiology of ovarian cancer have been identified. We sought to explore factors potentially associated with ovarian cancer by correlating ovarian cancer incidence rates in US states with the distribution of US manufacturing. METHODS: Data on age-adjusted incidence rates for ovarian cancer per state in the United States and manufacturing rates per state were analyzed using multiple linear regression controlling for access to ovarian cancer care, fertility rate, and other potential confounders. RESULTS: In univariate analyses, ovarian cancer incidence rates were positively correlated with the extent of manufacturing, with dairy production, and with the manufacturing of pulp and paper. Using multiple linear regression, only the correlation of ovarian cancer with pulp and paper manufacturing industry was significant. The correlation of ovarian cancer with pulp and paper manufacturing industry remained significant after adjusting for access to ovarian cancer care, fertility rates, and other potential confounders (P < 0.05). CONCLUSIONS: Pulp and paper mills are associated with exposures to known ovarian carcinogens. Further epidemiological study of exposures involved in the manufacturing of pulp and paper in relation to risk of ovarian cancer is warranted.

Are open abdominal procedures a thing of the past? An analysis of graduating general surgery residents' case logs from 2000 to 2011.

INTRODUCTION: Since the introduction of laparoscopic surgery for cholecystectomy in 1989, the growth of minimally invasive surgery (MIS) has increased significantly in the United States. There is a growing concern that the pendulum has now shifted too far toward MIS and that current general surgery residents' exposure to open abdominal procedures is lacking. OBJECTIVE: We sought to analyze trends in open vs MIS intra-abdominal procedures performed by residents graduating from US general surgery residency programs over the past twelve years. METHODS: We conducted a retrospective analysis of the data from the ACGME national resident case log reports for graduating US general surgery residents from 2000 to 2011. We analyzed the average number of cases per graduating chief resident for the following surgical procedures: appendectomy, inguinal/femoral hernia repair, gastrostomy, colectomy, antireflux procedures, and cholecystectomy. RESULTS: For all the procedures analyzed, except antireflux procedures, a statistically significant increase in the number of MIS cases was seen. The increases in MIS procedures were as follows: appendectomy, 8.5 to 46 (542%); inguinal/femoral hernia repair, 7.6 to 23.3 (265%); gastrostomy, 1.4 to 3 (114%); colectomy, 1.8 to 18.2 (1011%); and cholecystectomy, 84 to 105.7 (26%). The p value was set at <0.001 for all procedures. There has been a concomitant decrease in the number of open procedures. The numbers of open appendectomy decreased from 30.9 to 15.5 (p < 0.0001), open inguinal/femoral hernia repair from 52.1 to 48 (p = 0.0038), open gastrostomy from 7.7 to 4.9 (p = 0.0094), open colectomy from 48 to 40.7 (p < 0.0001), open cholecystectomy from 15.5 to 10.4 (p = 0.0005), and open antireflux procedures from 4.7 to 1.7 (p < 0.001). An analysis conducted over time reveals that the rates of increase in MIS procedures in 5 of the 6 categories continue to rise, whereas the rates of open appendectomy, open colectomy, and open antireflux procedures continue to decrease. However, the rates of decline of open hernia repairs and open gastrostomies seem to have plateaued. CONCLUSIONS: The performance of open procedures in general surgery residency has declined significantly in the past 12 years. The effect of the decline in open cases in surgical training and practice remains to be determined.

Increase in serum Ca2+/Mg2+ ratio promotes proliferation of prostate cancer cells by activating TRPM7 channels.

TRPM7 is a novel magnesium-nucleotide-regulated metal current (MagNuM) channel that is regulated by serum Mg(2+) concentrations. Changes in Mg(2+) concentration have been shown to alter cell proliferation in various cells; however, the mechanism and the ion channel(s) involved have not yet been identified. Here we demonstrate that TRPM7 is expressed in control and prostate cancer cells. Supplementation of intracellular Mg-ATP or addition of external 2-aminoethoxydiphenyl borate inhibited MagNuM currents. Furthermore, silencing of TRPM7 inhibited whereas overexpression of TRPM7 increased endogenous MagNuM currents, suggesting that these currents are dependent on TRPM7. Importantly, although an increase in the serum Ca(2+)/Mg(2+) ratio facilitated Ca(2+) influx in both control and prostate cancer cells, a significantly higher Ca(2+) influx was observed in prostate cancer cells. TRPM7 expression was also increased in cancer cells, but its expression was not dependent on the Ca(2+)/Mg(2+) ratio per se. Additionally, an increase in the extracellular Ca(2+)/Mg(2+) ratio led to a significant increase in cell proliferation of prostate cancer cells when compared with control cells. Consistent with these results, age-matched prostate cancer patients also showed a subsequent increase in the Ca(2+)/Mg(2+) ratio and TRPM7 expression. Altogether, we provide evidence that the TRPM7 channel has an important role in prostate cancer and have identified that the Ca(2+)/Mg(2+) ratio could be essential for the initiation/progression of prostate cancer.

Serum calcium levels, TRPM7, TRPC1, microcalcifications, and breast cancer using breast imaging reporting and data system scores.

BACKGROUND: An association between higher serum calcium (Ca2+) levels and breast cancer has been previously reported. However, little is known regarding the relationship between serum Ca2+ levels and the expression of Ca2+ channels in the presence of breast microcalcifications. METHODS: A retrospective analysis of women newly diagnosed with breast microcalcifications was performed based on the Breast Imaging Reporting and Data System (BI-RADS). The expression of TRPC1, TRPC3, and TRPM7 using normal biopsy without microcalcifications (controls) and infiltrating ductal carcinoma with microcalcifications was evaluated. RESULTS: Data on 138 women were analyzed. Seventy percent of women had a BI-RADS score (1-3) corresponding to benign disease. Seventy-six percent of women with a BI-RADS score (4 or 5) were diagnosed with breast cancer, 56% were cancers in situ, and 93% were infiltrating ductal carcinomas. No difference in the distribution of corrected serum Ca2+ levels between BI-RADS scores (1-3) and BI-RADS scores (4-5) (P = 0.82) was observed. Serum Ca2+ levels were similar in women without cancer and women diagnosed with breast cancer (P = 0.94). However, the expression of TRPM7 and TRPC1, but not TRPC3, Ca2+ channels were increased in infiltrating ductal carcinoma samples with microcalcifications when compared with age-matched controls without calcification or cancer. CONCLUSION: We observed an increase in the expression of TRPM7 and TRPC1 Ca2+ channels in infiltrating ductal carcinoma samples with microcalcifications, whereas no change in serum Ca2+ levels was observed. Together these data suggest that increased expression of these channels might lead to an increase in intracellular Ca2+ levels thereby restoring serum Ca2+ levels, but these can contribute to the breast microcalcifications. However, future studies exploring the intracellular Ca2+ levels as well as the role of TRPM7 and TRPC1 function according to BI-RADS scores are needed.

Prevalence of diagnosis and staging of chronic kidney disease by primary care providers in a rural state.

CONTEXT: The Kidney Disease Outcomes and Quality Initiative guidelines are the most widely disseminated guidelines regarding the clinical evaluation and management of chronic kidney disease (CKD). PURPOSE: Assess the prevalence of diagnosis and staging of CKD by primary care providers (PCPs). METHODS: For the purpose of this assessment, stage 3 CKD was defined as an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73 m(2) for at least 3 months. Eligible individuals were 1447 white, nondiabetic patients 40-74 years of age. RESULTS: Information on a random sample of 110 patients was analyzed. Chronic kidney disease was reported in 22% of the patients, whereas only 7% of patients had both CKD and stage 3 reported in their medical record. PCPs were significantly more likely to record CKD in male than in female patients (79% vs 34%; P < .001). Patients who had CKD recorded were significantly more likely to be referred to a nephrologist (46% vs 3%; P < .001). Even among patients who had a diagnosis of coronary artery disease, were older, or had lower eGFR, a diagnosis of CKD was less likely to be recorded. Only 22% had their serum phosphorus, 12% their parathyroid hormone, and 64% a urinalysis recorded. CONCLUSIONS: This study found that the prevalence of recording CKD and staging by PCPs was low. Primary care providers were more likely to record CKD in male than in female patients. Finally, testing for bone disease is underperformed. There is a need to identify mechanisms to improve evaluation and management of CKD by PCPs.

Does a higher ratio of serum calcium to magnesium increase the risk for postmenopausal breast cancer?

Breast cancer is the most commonly diagnosed cancer among United States (US) women. Established risk factors explain only about 13% of breast cancer incidence among women in the US. Thus, the cause of most cases of breast cancer remains unknown. In postmenopausal women, serum calcium (Ca) and serum magnesium (Mg) play an important role in skeletal health, cell proliferation and cancer. Mg is essential for DNA duplication and repair and Mg deficiency favors DNA mutations leading to carcinogenesis. Dietary intake of Mg in the US is less than the recommended amount, and the deficit is more pronounced in older individuals where gastrointestinal and renal mechanisms for Mg conservation are not as efficient. Furthermore, healthy postmenopausal women are frequently recommended to take supplemental Ca, but not Mg and vitamin D to maintain bone and overall health. Most women with hormone sensitive breast cancer are recommended to take aromatase inhibitors, which causes bone loss and thus are generally prescribed Ca and vitamin D, but not Mg. Although the association between serum Ca and breast cancer risk remains controversial, we hypothesize that this may be because Mg levels have not been accounted for. Mg level directly influences transient receptor potential melastatin 7 (TRPM7) related Ca influx, calcium-adenosine triphosphatase (Ca-ATP) levels, and cell proliferation, and thereby could lead to cancer. Thus a high serum Ca/Mg ratio is more appropriate and alterations in this ratio could lead to increased development of new and recurrent breast cancer.