Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression.

Management of diabetic kidney disease (DKD) has evolved in parallel with our growing understanding of the multiple interrelated pathophysiological mechanisms that involve hemodynamic, metabolic, and inflammatory pathways. These pathways and others play a vital role in the initiation and progression of DKD. Since its initial discovery, the blockade of the renin-angiotensin system has remained a cornerstone of DKD management, leaving a large component of residual risk to be dealt with. The advent of sodium-glucose cotransporter 2 inhibitors followed by nonsteroidal mineralocorticoid receptor antagonists and, to some extent, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has ushered in a resounding paradigm shift that supports a pillared approach in maximizing treatment to reduce outcomes. This pillared approach is like that derived from the approach to heart failure treatment. The approach mandates that all agents that have been shown in clinical trials to reduce cardiovascular outcomes and/or mortality to a greater extent than a single drug class alone should be used in combination. In this way, each drug class focuses on a specific aspect of the disease's pathophysiology. Thus, in heart failure, ß-blockers, sacubitril/valsartan, a mineralocorticoid receptor antagonist, and a diuretic are used together. In this article, we review the evolution of the pillar concept of therapy as it applies to DKD and discuss how it should be used based on the outcome evidence. We also discuss the exciting possibility that GLP-1 RAs may be an additional pillar in the quest to further slow kidney disease progression in diabetes.

Obesity and Breast Cancer Risk: The Oncogenic Implications of Metabolic Dysregulation.

CONTEXT: Breast cancer is increasing in prevalence in parallel with rising rates of obesity worldwide. Obesity is recognized as a leading modifiable risk factor for the development of breast cancer; however, this association varies considerably by clinicopathologic features, and the underlying mechanisms are complex. EVIDENCE ACQUISITION: Pubmed literature search using combinations of "obesity," "breast cancer risk," "diet," "exercise," "weight gain," "weight loss," "adipose tissue inflammation," "crown-like structure," "immune markers," "metformin," "gliflozins," "SGLT-2i," "GLP1-RA," and related terms. EVIDENCE SYNTHESIS: Elevated body mass index and weight gain are associated with increased risk of postmenopausal, hormone receptor-positive breast cancer. Emerging evidence suggests that adverse measures of body composition in individuals of any weight can also confer increased breast cancer risk. Mechanistically, various factors including altered adipokine balance, dysfunctional adipose tissue, dysregulated insulin signaling, and chronic inflammation contribute to tumorigenesis. Weight loss and more specifically fat mass loss through lifestyle and pharmacologic interventions improve serum metabolic and inflammatory markers, sex hormone levels, and measures of breast density, suggesting a link to decreased breast cancer risk. CONCLUSION: Incorporating markers of metabolic health and body composition measures with body mass index can capture breast cancer risk more comprehensively. Further studies of interventions targeting body fat levels are needed to curb the growing prevalence of obesity-related cancer.

The evolving role of the Women's Health Specialist in cancer prevention and survivorship.

IMPORTANCE AND OBJECTIVE: This review provides a framework for primary care physicians, internists, family doctors, NP's, PA's, and oncologists caring for women-henceforth referred to as Women's Health Specialists-to identify and screen patients who may be at high risk for inherited cancer syndromes; an intervention referred to as previvorship care. For women who undergo risk-reducing oophorectomy, survivorship care is critical to optimizing quality of life thereafter. In this paper, we review management of the unique survivorship needs and management options for women at risk for or with a cancer diagnosis, highlighting the importance of interdisciplinary care. METHODS: To review the available previvorship and survivorship management strategies, a Pub Med search was performed using keywords "survivorship," "genetics," "cancer," "menopause," "hormone therapy," "screening" in addition to review of guidelines, position statements and expert, and committee opinions from the American College of OBGYN, the American Society of Clinical Oncology, The North American Menopause Society, the National Comprehensive Cancer Network , and the American Society for Reproductive Medicine. DISCUSSION AND CONCLUSION: Women's Health Specialists are in a unique position to identify and screen women who may be at risk for inherited cancer syndromes as well as provide necessary survivorship management following transition from their oncologists' care.

Denosumab Discontinuation in Patients Treated for Low Bone Density and Osteoporosis.

Denosumab (DMAB) is a potent antiresorptive treatment used for treatment of osteoporosis and low bone mineral density (BMD) in those at high risk for fracture. In postmenopausal women with osteoporosis, DMAB treatment for 10 years has been studied, with results showing continued gains in BMD, sustained fracture risk reduction, and low risk of adverse events. However, upon discontinuation of DMAB, there is a rapid reversal of effect, with increase in bone turnover, loss of BMD, and in a subset of patients, a greater risk for multiple vertebral fractures.

Chronic idiopathic urticaria: treatment with omalizumab.

Chronic idiopathic urticaria (CIU) is a common autoimmune skin condition characterized by spontaneously recurring hives for 6 weeks or longer. The new terminology used for CIU in most countries including Canada is chronic spontaneous urticaria (CSU). CSU is associated with significant psychosocial morbidity with a markedly negative impact on overall quality of life. Conventional approaches with antihistamines, even at high doses, is effective in about 50% of patients suffering from CSU. A new treatment option, omalizumab, a humanized monoclonal antibody against the Fc domain of IgE, has undergone the scrutiny of randomized research studies evaluating the efficacy in CSU. This editorial reviews mechanisms of action of omalizumab, efficacy, cost and potential side effect profile. Omalizumab has emerged as a very promising treatment option for patients with CSU. Future research is necessary to establish standardized protocols related to dosing as well as monitoring possible adverse effects of long-term treatment.

Status of psychological trials in breast cancer patients: a report of three meta-analyses.

This systematic review reports the results of three meta-analyses addressing the clinical efficacy of psychological interventions in breast cancer patients. Three outcome variables were examined: anxiety, depression and quality of life. Several moderator variables were found to both account for inter-trial heterogeneity and interact with treatment efficacy; methodological quality, prognosis, treatment type, orientation and duration. A clinically moderate treatment effect was found for anxiety (-0.40, 95% CI, -0.72 to -0.08, N = 1278). This was not robust to study quality, but remained stable for patients with more advanced disease. Short-term group therapy was more effective than longer term intervention and individual ones. A clinically moderate-to-strong effect was found in trials assessing depression (-1.01, 95% CI, -1.48 to -0.54, N = 1324). A more robust finding of -0.47 (95% -0.69 to -0.24) was based on methodologically more reliable studies treating patients with high psychological morbidity. Intervention was shown to have moderate effects on improving QOL (0.74, 95% CI, 0.12 to 1.37, N = 623), though it was not robust to study quality. Findings suggest that short-term treatments with a focus on coping may be more suitable for early breast cancer patients. Patients with advanced breast disease appear to benefit more from longer term interventions which emphasize support. Recommendations are also made for future clinical trials.

Coping with early breast cancer: couple adjustment processes and couple-based intervention.

Early breast cancer affects one in every nine women along with their families. Advances in screening and biomedical interventions have changed the face of breast cancer from a terminal condition to a chronic disease with biopsychosocial features. The present review surveyed the nature and extent of psychological morbidity experienced by the breast cancer survivor and her spouse during the post-treatment phase, with particular focus on the impact of disease on the marital relationship. Interpersonal processes shown to unfold in couples facing breast cancer, as well as risk factors associated with greater psychological morbidity, were reviewed. Moreover, interpersonal processes central to coping with chronic illness and adjustment were reconceptualized from the point of view of attachment theory. Attachment theory was also used as the grounding framework for an empirically supported couples-based intervention, Emotionally Focused Therapy, which is advanced as a potentially useful treatment option for couples experiencing unremitting psychological and relational distress following diagnosis and treatment for breast cancer.

Treating attachment injured couples with emotionally focused therapy: a case study approach.

This paper compared the attachment injury resolution process in two distressed couples undergoing ten sessions of Emotional Focused Therapy (EFT), a short-term empirically validated treatment for relational distress. An attachment injury is a newly coined clinical construct that denotes a specific type of betrayal within the couple's relationship. The incident is so potent that it calls into question assumptions about the safety of the relationship. The task analytic method was used to examine the pathways of change as related to attachment injury of each couple. Several outcome and process measures were employed in order to differentiate the therapeutic process between the resolved versus non-resolved couple. Results indicated that the couple who resolved their identified attachment injury at the outset of therapy adhered to the attachment injury resolution model, while the non-resolved couple showed marked deviations from the expected pathways of change. Findings suggest that the resolved couple tended to show more differentiation of interactional positions and greater levels of experiencing throughout the therapeutic process in relation to the non-resolved couple. It is recommended that further research is necessary to examine the clinical utility of the attachment injury resolution model in the context of a larger number of case studies.