HUNK as a key regulator of tumor-associated macrophages in triple negative breast cancer.

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC tumors are not sensitive to endocrine therapy, and standardized TNBC treatment regimens are lacking. TNBC is a more immunogenic subtype of breast cancer, making it more responsive to immunotherapy intervention. Tumor-associated macrophages (TAMs) constitute one of the most abundant immune cell populations in TNBC tumors and contribute to cancer metastasis. This study examines the role of the protein kinase HUNK in tumor immunity. Gene expression analysis using NanoString's nCounter PanCancer Immune Profiling panel identified that targeting HUNK is associated with changes in the IL-4/IL-4 R cytokine signaling pathway. Experimental analysis shows that HUNK kinase activity regulates IL-4 production in mammary tumor cells, and this regulation is dependent on STAT3. In addition, HUNK-dependent regulation of IL-4 secreted from tumor cells induces polarization of macrophages into an M2-like phenotype associated with TAMs. In return, IL-4 induces cancer metastasis and macrophages to produce epidermal growth factor. These findings delineate a paracrine signaling exchange between tumor cells and TAMs regulated by HUNK and dependent on IL-4/IL-4 R. This highlights the potential of HUNK as a target for reducing TNBC metastasis through modulation of the TAM population.

TL1A priming induces a multi-cytokine Th9 cell phenotype that promotes robust allergic inflammation in murine models of asthma.

Multi-cytokine-producing Th9 cells secrete IL-9 and type 2 cytokines and mediate mouse and human allergic inflammation. However, the cytokines that promote a multi-cytokine secreting phenotype have not been defined. Tumor necrosis factor superfamily member TL1A signals through its receptor DR3 to increase IL-9. Here we demonstrate that TL1A increases expression of IL-9 and IL-13 co-expressing cells in murine Th9 cell cultures, inducing a multi-cytokine phenotype. Mechanistically, this is linked to histone modifications allowing for increased accessibility at the Il9 and Il13 loci. We further show that TL1A alters the transcription factor network underlying expression of IL-9 and IL-13 in Th9 cells and increases binding of transcription factors to Il9 and Il13 loci. TL1A-priming enhances the pathogenicity of Th9 cells in murine models of allergic airway disease through the increased expression of IL-9 and IL-13. Lastly, in both chronic and memory-recall models of allergic airway disease, blockade of TL1A signaling decreases the multi-cytokine Th9 cell population and attenuates the allergic phenotype. Taken together, these data demonstrate that TL1A promotes the development of multi-cytokine Th9 cells that drive allergic airway diseases and that targeting pathogenic T helper cell-promoting cytokines could be an effective approach for modifying disease.

The Dichotomy of Interleukin-9 Function in the Tumor Microenvironment.

Interleukin 9 (IL-9) is a cytokine with potent proinflammatory properties that plays a central role in pathologies such as allergic asthma, immunity to parasitic infection, and autoimmunity. More recently, IL-9 has garnered considerable attention in tumor immunity. Historically, IL-9 has been associated with a protumor function in hematological malignancies and an antitumor function in solid malignancies. However, recent discoveries of the dynamic role of IL-9 in cancer progression suggest that IL-9 can act as both a pro- or antitumor factor in various hematological and solid malignancies. This review summarizes IL-9-dependent control of tumor growth, regulation, and therapeutic applicability of IL-9 blockade and IL-9-producing cells in cancer.

Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation.

Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by immunoglobulin E-dependent mast cell (MC) activation. Interleukin-9 (IL-9) promotes MC expansion during allergic inflammation but precisely how IL-9 expands tissue MCs and promotes MC function is unclear. In this report, using multiple models of allergic airway inflammation, we show that both mature MCs (mMCs) and MC progenitors (MCp) express IL-9R and respond to IL-9 during allergic inflammation. IL-9 acts on MCp in the bone marrow and lungs to enhance proliferative capacity. Furthermore, IL-9 in the lung stimulates the mobilization of CCR2+ mMC from the bone marrow and recruitment to the allergic lung. Mixed bone marrow chimeras demonstrate that these are intrinsic effects in the MCp and mMC populations. IL-9-producing T cells are both necessary and sufficient to increase MC numbers in the lung in the context of allergic inflammation. Importantly, T cell IL-9-mediated MC expansion is required for the development of antigen-induced and MC-dependent airway hyperreactivity. Collectively, these data demonstrate that T cell IL-9 induces lung MC expansion and migration by direct effects on the proliferation of MCp and the migration of mMC to mediate airway hyperreactivity.

A Molecular Cloning and Sanger Sequencing-based Protocol for Detecting Site-specific DNA Methylation.

DNA methylation is a conserved chemical modification, by which methyl groups are added to the cytosine of DNA molecules. Methylation can influence gene expression without changing the sequence of a particular gene. This epigenetic effect is an intriguing phenomenon that has puzzled biologists for years. By probing the temporal and spatial patterns of DNA methylation in genomes, it is possible to learn about the biological role of cytosine methylation, as well as its involvement in gene regulation and transposon silencing. Advances in whole-genome sequencing have led to the widespread adoption of methods that examine genome-wide patterns of DNA methylation. Achieving sufficient sequencing depth in these types of experiments is costly, particularly for pilot studies in organisms with large genome sizes, or incomplete reference genomes. To overcome this issue, assays to determine site-specific DNA methylation can be used. Although often used, these assays are rarely described in detail. Here, we describe a pipeline that applies traditional TA cloning, Sanger sequencing, and online tools to examine DNA methylation. We provide an example of how to use this protocol to examine the pattern of DNA methylation at a specific transposable element in maize.

Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9.

Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the expansion of both CD11c+ and CD11c- interstitial macrophage populations in lung tumor models. Mechanistically, the IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r-/- mice promotes tumor growth. Moreover, targeting IL-9 signaling using macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor prognosis in lung cancer patients. Thus, our study suggests the IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer therapy.

Interplay between spirituality and religiosity on the physical and mental well-being of cancer survivors.

PURPOSE: This study explored the relationship of spirituality and religiosity as it affects the physical and mental quality of life (pQOL, mQOL) of cancer survivors. METHODS: This is a prospective observational study that included adults ≥ 19 years who received treatment for various types of cancer. Patients' QOL was obtained at baseline, 6, and 12 months. Cohorts were categorized according to spirituality/religiosity levels: low spirituality-low religiosity (LSLR), low spirituality-high religiosity (LSHR), high spirituality-low religiosity (HSLR), and high spirituality-high religiosity (HSHR). RESULTS: Of the 551 eligible, 248 (45%) had HSHR, 196 (36%) had LSHR, 75 (14%) had LSLR, and 32 (6%) had HSLR. The pQOL of LSLR were significantly lower than those with HSHR (p = 0.02). The differences in pQOL between LS and HS were observed among those who have HR (p < 0.0001). Among patients with LR, pQOL did not differ. The mQOL of patients with LSLR was significantly lower than those with HSHR (p < 0.0001). The mQOL of those with HS was significantly higher than those with LS in both cohorts having LR (p < 0.0001) or HR (p < 0.0001). pQOL decreased while mQOL increased over time regardless of spirituality or religiosity levels. CONCLUSION: Spirituality is important in the improvement of both pQOL and mQOL of cancer survivors, while religiosity may have some impact on pQOL. Clinicians' incorporation of spirituality into cancer treatment facilitates well-rounded care, which offers measurable improvements for patients with an illness, of which the treatment is often arduous, and uncertain.

Evaluation of the Short-Term Cost-Effectiveness of IDegLira Versus Basal Insulin and Basal-Bolus Therapy in Patients with Type 2 Diabetes Based on Attainment of Clinically Relevant Treatment Targets.

BACKGROUND: Effective glycemic control can reduce the risk of complications and their related costs in patients with type 2 diabetes (T2D). Many patients fail to reach hemoglobin A1c (HbA1c) ≤ 6.5% or < 7.0%, often due to adverse effects of treatment, such as hypoglycemia and weight gain. Glycemic targets should be individualized and consider multiple factors, including the risk of adverse events and the patient's characteristics and comorbid conditions. OBJECTIVE: To compare the odds and annual cost of achieving treatment targets, which incorporate HbA1c targets of < 7.5%, < 8.0%, and ≤ 9.0%, with insulin degludec/liraglutide (IDegLira) versus basal insulin and basal-bolus therapy. METHODS: This is a post hoc analysis of the DUAL V and DUAL VII 26-week trials, which randomized patients with T2D uncontrolled (HbA1c 7%-10%) on insulin glargine 100 units/mL (IGlar U100) and metformin to IDegLira or continued IGlar U100 titration (DUAL V) or IGlar U100 + insulin aspart (DUAL VII), all with metformin. Proportions of patients achieving HbA1c targets (< 7.5%, < 8.0%, and ≤ 9.0%) by the end of trial were assessed via 3 outcomes: alone, without either hypoglycemia or weight gain (double composite outcome), or without a combination of hypoglycemia and weight gain (triple composite outcome). The cost per patient achieving the triple composite outcome at each HbA1c target (< 7.5%, < 8.0%, and ≤ 9.0%) was calculated by dividing the annual cost of treatment by the proportion of patients achieving the target. This short-term (1-year) cost-effectiveness analysis was conducted from the perspective of a U.S. health care payer. RESULTS: More patients achieved HbA1c < 7.5% (P < 0.0001) and < 8.0% (P = 0.0003), and a similar percentage achieved HbA1c ≤ 9.0% with IDegLira versus IGlar U100 (DUAL V). Similar proportions of patients achieved all 3 HbA1c targets with IDegLira compared with basal-bolus therapy (DUAL VII). The odds of achieving double or triple composite outcomes were significantly higher for IDegLira versus IGlar U100 or basal-bolus for all 3 HbA1c targets (P < 0.0001 in each case) in both trials. For each $1 spent on IDegLira, the equivalent annual costs per patient to achieve HbA1c targets of < 7.5%, < 8.0%, or ≤ 9.0% without hypoglycemia and without weight gain were $2.43, $2.10, and $2.05, respectively, for IGlar U100 and $6.33, $5.80, and $6.06, respectively, for basal-bolus therapy. CONCLUSIONS: Based on data from DUAL V and DUAL VII, this analysis showed that a greater or similar proportion of patients with T2D reached HbA1c targets with IDegLira compared with IGlar U100/basal-bolus therapy. Odds of achieving double or triple composite outcomes of HbA1c reduction without hypoglycemia and/or without weight gain were greatest for IDegLira. Short-term cost analyses based on the triple composite outcomes suggest that IDegLira is a cost-effective treatment option in the United States compared with either uptitration of IGlar U100 or basal-bolus therapy. DISCLOSURES: This study was supported by Novo Nordisk A/S. The analysis was based on the DUAL V (NCT01952145) and DUAL VII (NCT02420262) trials, which were funded and conducted by Novo Nordisk. This post hoc analysis was conceived and interpreted by the authors and drafted with medical writing support that was funded by Novo Nordisk. Novo Nordisk also reviewed the manuscript for medical accuracy. Hunt and Malkin are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk during the conduct of this study and has received consulting fees from Novo Nordisk, unrelated to this study. Mocarski, Ranthe, and Schiffman are employees of Novo Nordisk and Novo Nordisk A/S. Cannon has received speaker fees/honoraria from Abbvie, Amgen, and Janssen; speaker fees from Novo Nordisk; and has stock ownership in Novo Nordisk. Bargiota has received speaker fees/honoraria from AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi, Boehringer Ingelheim, and Novartis. Billings has received personal fees from Novo Nordisk, Sanofi, and Dexcom, unrelated to this study. Leiter reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and GSK, unrelated to this study. Doshi has no relevant conflicts of interest to disclose. Parts of this study were presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Burden of Illness in Type 2 Diabetes Mellitus.

An estimated 30.2 million Americans have diabetes, and this number is expected to increase based on trends over recent decades and compounded by an aging U.S. POPULATION: As reviewed in this article, type 2 diabetes mellitus (T2DM) is associated with impaired health-related quality of life (HRQoL) and with a substantial socioeconomic burden. Compared with individuals without T2DM, those with T2DM have worse HRQoL, greater decrements in HRQoL over time, and possibly greater depressive symptomology. Diabetes-related complications and comorbidities (e.g., obesity and cardiovascular disease) are associated with worse HRQoL. Hypoglycemic episodes are associated with reduced HRQoL and greater levels of depression; they can also interfere with social and occupational activities. In turn, low HRQoL can be a driver for poor glycemic control. In 2012, the total estimated cost associated with diagnosed diabetes in the United States was $245 billion. Factors contributing to increased health care resource utilization and costs in patients with T2DM include medical comorbidities, diabetes-related complications, inadequate glycemic control, and hypoglycemic episodes. Readmission is a key driver of hospital-related costs and is more common among elderly patients with T2DM. Elderly patients with T2DM represent a particularly vulnerable population given that these patients may have varying degrees of physical and mental comorbidities that can increase their risk of hypoglycemia, falls, and depression. This review demonstrates that T2DM imposes a considerable burden on both the individual and society. Treatment strategies should consider the effects of treatment on HRQoL and on outcomes (e.g., complications and hypoglycemia) that affect both HRQoL and costs. Management strategies that maximize HRQoL while minimizing the risk of hypoglycemia and other treatment-related complications are particularly critical in the elderly. DISCLOSURES: This supplement was funded by Novo Nordisk. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance.

Glycemic Efficacy, Weight Effects, and Safety of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists.

This article provides an overview of the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic GLP-1 receptors, which increases insulin secretion, delays gastric emptying, and increases satiety. As a class, GLP-1 RAs lower A1c levels and have been associated with reductions in weight and blood pressure and reduced fluctuations in glucose levels, and they have a low risk of hypoglycemia. Exenatide extended release (ER) and dulaglutide monotherapy have shown similar or superior reductions in A1c and weight compared with various oral antidiabetic drugs (OADs). Semaglutide has been shown to reduce both A1c and body weight compared with placebo and, in head-to-head studies versus both exenatide ER and dulaglutide, showed greater reductions in A1c and body weight. Once-weekly GLP-1 RAs have also been evaluated as add-on therapy in the continuum of care for the treatment of T2DM in combination with a variety of background medications, including 1 or more OADs (metformin, sulfonylureas, and/or thiazolidinediones), basal insulin, and prandial insulin. Gastrointestinal adverse events (e.g., nausea, vomiting, and diarrhea) are the most common side effects with once-weekly GLP-1 RAs. Rates of hypoglycemia, and especially major/severe hypoglycemia, are low with once-weekly GLP-1 RAs but, as expected, are higher when used in combination with sulfonylureas or insulin. These once-weekly GLP-1 RAs provide a safe and effective treatment option for patients with T2DM and may offer improved convenience and possibly greater adherence compared with daily GLP-1 RAs. DISCLOSURES: This supplement was funded by Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Schneider reports advisory board fees from Intarcia, Lilly, and Novo Nordisk. Wyne has nothing to disclose.

Cardiovascular Outcomes with Once-Weekly GLP-1 RAs: Clinical and Economic Implications.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM. DISCLOSURES: This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.

Insulin/Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy for the Treatment of Type 2 Diabetes: Are Two Agents Better Than One?

IN BRIEF Given the progressive nature of type 2 diabetes, treatment intensification is usually necessary to maintain glycemic control. However, for a variety of reasons, treatment is often not intensified in a timely manner. The combined use of basal insulin and a glucagon-like peptide-1 receptor agonist is recognized to provide a complementary approach to the treatment of type 2 diabetes. This review evaluates the efficacy and safety of two co-formulation products, insulin degludec/liraglutide and insulin glargine/lixisenatide, for the treatment of type 2 diabetes inadequately controlled on either component agent alone. We consider the benefits and limitations of these medications based on data from randomized clinical trials and discuss how they may address barriers to treatment intensification.

Ethnic differences in psychological outcomes among people with diabetes: USA results from the second Diabetes Attitudes, Wishes, and Needs (DAWN2) study.

OBJECTIVE: To assess differences in psychological outcomes as well as risk and protective factors for these outcomes among several USA ethnic groups and identify correlates of these psychological outcomes among adults with diabetes in the second Diabetes Attitudes, Wishes and Needs (DAWN2 * ) study. RESEARCH DESIGN AND METHODS: The core USA DAWN2 sample was supplemented by independent samples of specific ethnic minority groups, yielding a total of 447 White non-Hispanics, 241 African Americans, 194 Hispanics, and 173 Chinese Americans (n = 1055). Multivariate analysis examined ethnic differences in psychological outcomes and risk/protective factors (disease, demographic and socioeconomic factors, health status and healthcare access/utilization, subjective burden of diabetes and social support/burden). Separate analyses were performed on each group to determine whether risk/protective factors differed across ethnic groups. MAIN OUTCOME MEASURES: Psychological outcomes include well-being, quality of life, impact of diabetes on life domains, diabetes distress, and diabetes empowerment. CLINICAL TRIAL REGISTRATION: NCT01507116. RESULTS: Ethnic minorities tended to have better psychological outcomes than White non-Hispanics, although their diabetes distress was higher. Levels of most risk and protective factors differed significantly across ethnic groups; adjustment for these factors reduced ethnic group differences in psychological outcomes. Health status and modifiable diabetes-specific risk/protective factors (healthcare access/utilization, subjective diabetes burden, social support/burden) had strong associations with psychological outcomes, especially diabetes distress and empowerment. Numerous interactions between ethnicity and other correlates of psychological outcomes suggest that ethnic groups are differentially sensitive to various risk/protective factors. Potential limitations are the sample sizes and representativeness. CONCLUSIONS: Ethnic groups differ in their psychological outcomes. The risk/protective factors for psychological outcomes differ across ethnic groups and different ethnic groups are more/less sensitive to their influence. These findings can aid the development of strategies to overcome the most prominent and influential psychosocial barriers to optimal diabetes care within each ethnic group.

Ovarian leydig cell hyperplasia: an unusual case of virilization in a postmenopausal woman.

Objective. To report an unusual case of ovarian Leydig cell hyperplasia resulting in virilization in a postmenopausal woman. Methods. Patient's medical history and pertinent literature were reviewed. Results. A 64-year-old woman presented with virilization with worsening hirsutism, deepening of her voice, male musculature, and male pattern alopecia. Her pertinent past medical history included type 1 diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history included hysterectomy due to fibroids. On further work-up, her serum total testosterone was 506 ng/dL (nl range: 2-45) and free testosterone was 40 pg/mL (nl range: 0.1-6.4). After ruling out adrenal causes, the patient underwent an empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology. Six weeks postoperatively, serum testosterone was undetectable with significant clinical improvement. Conclusion. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia of her ovaries, a rarely reported cause of virilization.

Insights on practice variations in the management of lymphoma and leukemia.

Clinical practice guidelines are systematically developed statements designed to assist practitioners in making decisions about appropriate healthcare for specific clinical circumstances. Their successful implementation should improve quality of care by decreasing inappropriate variation and expediting the application of effective advances to everyday practice. Despite wide promulgation, guidelines have had limited effect on changing physician behaviors. This two-part review article highlights variations in the current recommended management of lymphoma (Part I) and leukemia (Part II), with some focus on targeted therapies. Focus on variations that may be amenable to educational programs designed for physicians were also considered in the review. For the purpose of this report, "variation" is defined as any deviation in the treatment or management of a particular hematologic malignancy where practice guidelines exist. Specific studies that demonstrate factors that may cause variations in clinical outcomes of hematologic malignancies and may contribute to variations in practice are featured.

Spirituality, patients' worry, and follow-up health-care utilization among cancer survivors.

BACKGROUND: Spirituality may aid cancer survivors as they attempt to interpret the meaning of their experience. OBJECTIVE: We examined the relationship between spirituality, patient-rated worry, and health-care utilization among 551 cancer survivors with different malignancies, who were evaluated prospectively. METHODS: Baseline spirituality scores were categorized into low and high spirituality groups. Patient-rated worries regarding disease recurrence/progression, developing new cancer, and developing complications from treatment were collected at baseline and at 6 and 12 months. Follow-up health-care utilization was also examined at 6 and 12 months. RESULTS: Among the survivors, 271 (49%) reported low spirituality and 280 (51%) reported high spirituality. Of the cohort, 59% had some kind of worry regarding disease recurrence/progression, development of new cancers, and treatment complications. Highly spiritual survivors were less likely to have high levels of worries at both 6 and 12 months. Highly worried survivors were significantly more likely to place phone calls to their follow-up providers and had more frequent follow-up visits at 6 and 12 months. No interactions between spirituality and level of worry were noted to affect follow-up health-care utilization. CONCLUSION: Given spirituality's effect on anxiety, spirituality-based intervention may have a role in addressing cancer survivors' worries but may not improve health-care utilization.

Association of number of follow-up providers with outcomes in survivors of hematologic malignancies.

Studies examining follow-up care among cancer survivors have increased in number, and are mostly focused on who best provides care. It is not known whether having single or multiple physicians as follow-up providers has outcome implications. We prospectively studied the association between number of follow-up providers among survivors of hematologic malignancies and serious medical utilization (defined as emergency room visits or hospitalizations) within a 6-month period. Patients completing treatment (n = 314) were included. Patients seeing multiple follow-up providers were more likely to be younger, to reside farther away from the university hospital, to have prescription drug insurance, to have received prior cancer treatment, to have multiple myeloma, and to have undergone hematopoietic cell transplant as a part of cancer treatment. Multivariate analysis showed that the number of follow-up providers was not associated with serious medical utilization (odds ratio 1.29, 95% confidence interval 0.68–2.48, p = 0.44) after adjusting for patient factors. Our study showed that among survivors of hematologic malignancies, outcomes were not different for survivors who were seen by single or multiple follow-up providers.