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1.
J Clin Transl Endocrinol ; 30: 100307, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36217440

ABSTRACT

Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis that is associated with worse outcomes and higher mortality rates. CF transmembrane conductance regulator gene (CFTR) modulators have shown favorable effects on lung function, pulmonary exacerbations, and nutrition status. However, data regarding effects of CFTR modulators on glycemic control among those with CFRD is lacking. In this retrospective study, CGM data was analyzed to determine effect of elexacaftortezacaftor- ivacaftor therapy (ETI), a CFTR modulator, on glucose control among patients with CFRD. No difference was seen in glucose patterns after 3- and 6- months of starting ETI.

2.
J Clin Densitom ; 25(4): 615-621, 2022.
Article in English | MEDLINE | ID: mdl-35525792

ABSTRACT

Transgender and gender non-conforming (TGNC) individuals face numerous barriers to healthcare, which contribute to many health disparities. TGNC persons may choose gender-affirming therapies with surgery and/or hormone replacement therapy (HRT) to manage gender incongruence. Despite the expanding use of HRT, the long-term outcomes on bone health and metabolism, are still relatively unknown in the TGNC population. In 2019, the International Society of Clinical Densitometry (ISCD) released an official position statement on the appropriate use of dual energy x-ray absorptiometry (DXA) to measure bone density in the TGNC population. In this study, we reviewed which "sex" is currently utilized among providers when performing DXA scans to calculate T- and Z-scores for TGNC persons and how this compares to the positions published by the ISCD. A retrospective analysis was performed utilizing HERON queries and subsequent chart review. HERON is a type of Informatics for Integrating Biology and the Bedside software that was utilized to find sets of patients of interest from electronic medical record data while preserving patient privacy through a query interface tool. Project specific sets including patient demographics, medications, gonadectomy, and DXA scan information was created in HERON to make this highly detailed data of specific patients available to the investigators on the platform, as reviewed and retrieved by the Institutional Review Board. The qualitative DXA data obtained from chart review was determined as "correct" or "incorrect" based on positions provided from the ISCD. 10 DXA scans that met inclusion criteria were obtained between 9 TGNC patients. In total, 18 T-scores and Z-scores of the 10 DXAs were reviewed and scored. Based on ISCD positions, 67% of the T-score and Z-scores were calculated incorrectly; using the erroneous "sex" based standard to compare scores. Like DXA scans, many current healthcare standards and protocols are based on a patient's sex or gender, which may cause confusion amongst healthcare personnel who have not received proper training regarding the TGNC population. In this study, 67% of T-scores and Z-scores were calculated incorrectly based on ISCD recommendations. An additional prospective research design is required to determine the consequences of incorrectly calculated DXA scans for TGNC patients. Furthermore, future research is needed to determine HRT's effects on bone mineral density in the TGNC population in the United States.


Subject(s)
Transgender Persons , Humans , Absorptiometry, Photon , Retrospective Studies , Prospective Studies , Bone Density
3.
Am J Med Sci ; 364(4): 461-465, 2022 10.
Article in English | MEDLINE | ID: mdl-35469767

ABSTRACT

Bone disease is a known complication of cystic fibrosis (CF). To date, there have been no reports on the effectiveness of romosozumab, monoclonal antibody to sclerostin, to treat CF-related bone disease. We report a case of a 46-year-old premenopausal female with CF-related bone disease and multiple fractures who was treated with romosozumab. After one year of therapy with romosozumab, the patient tolerated therapy and bone mineral density (BMD) significantly improved. Of the currently available anti-resorptive or anabolic osteoporosis medications, only bisphosphonates have been studied in individuals with CF. This report highlights that romosozumab may be an effective alternative treatment modality in selected patients with CF at high risk for fractures. Further studies are warranted to evaluate the efficacy and safety profile of romosozumab in people with CF.


Subject(s)
Bone Density Conservation Agents , Cystic Fibrosis , Osteoporosis , Antibodies, Monoclonal/therapeutic use , Bone Density , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Diphosphonates/therapeutic use , Female , Humans , Middle Aged , Osteoporosis/drug therapy , Osteoporosis/etiology
4.
Cancer Med ; 6(12): 2998-3013, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29047224

ABSTRACT

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors.


Subject(s)
Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , ral GTP-Binding Proteins/metabolism , Animals , Humans , Mutation , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/therapy , Neoplastic Stem Cells/pathology , Oncolytic Virotherapy , Oncolytic Viruses/metabolism , Protein Conformation , Signal Transduction , Structure-Activity Relationship , ral GTP-Binding Proteins/chemistry , ral GTP-Binding Proteins/genetics
5.
Clin Interv Aging ; 11: 1111-6, 2016.
Article in English | MEDLINE | ID: mdl-27578967

ABSTRACT

BACKGROUND: Fractures in older patients are common, morbid, and associated with increased risk of subsequent fractures. Inpatient and outpatient management and treatment of fractures can be costly. With more emphasis placed on quality care for Medicare beneficiaries, we studied if patients were receiving proper screening for osteoporosis and treatment after diagnosis of fracture. This study aims to determine if adequate screening and treatment for osteoporosis occurs in the postfracture period. METHODS: A retrospective analysis of Medicare beneficiaries aged 67 years or older was gathered from a single institution in both inpatient and outpatient visits. Based on International Classification of Diseases ninth revision codes, primary diagnosis of fractures of neck and trunk, upper limb, and lower limb were obtained in addition to current procedural terminology codes for fracture procedures. We studied patients who had been screened for osteoporosis with a bone mineral study or received osteoporosis treatment after their fracture. RESULTS: Medicare beneficiaries totaling 1,375 patients were determined to have an inclusion fracture between June 1, 2013 and November 30, 2014. At the time of our analysis on December 1, 2014, 1,219 patients were living and included in the analysis. Of these patients, 256 (21.0%) either received osteoporosis testing with bone mineral density or received treatment for osteoporosis. On sex breakdown, 208/820 (25.4%) females received proper evaluation or treatment of osteoporosis in comparison to 48/399 (12.0%) males. This is in comparison to the Centers for Medicare and Medicaid Services' national average of 19.1% for osteoporosis management in females. CONCLUSION: A minority of studied patients received evaluation or treatment for osteoporosis after their fracture. Postfracture investigation and treatment for osteoporosis in Medicare beneficiaries is inadequate. If improved, Medicare costs could be reduced by prevention of future fractures. Future studies could determine how best to ensure this intervention occurs.


Subject(s)
Bone Density , Fractures, Bone/complications , Osteoporosis/diagnosis , Absorptiometry, Photon , Aged , Aged, 80 and over , Bone Density Conservation Agents/therapeutic use , Female , Fractures, Bone/prevention & control , Humans , Male , Mass Screening , Medicare , Osteoporosis/drug therapy , Quality of Health Care , Retrospective Studies , United States
7.
Eur J Pharmacol ; 691(1-3): 292-6, 2012 Sep 15.
Article in English | MEDLINE | ID: mdl-22819704

ABSTRACT

Exenatide or Exendin-4 is a 39-amino acid agonist of the glucagon like peptide (GLP-1) receptor approved for the adjunctive treatment for type 2 diabetes. Recent reports suggest that GLP-1 agonists may also have distant effects including C-cell thyroid hyperplasia. The aim of this study was to evaluate the effect of exendin-4 on the thyroid and parathyroid cells in a rat model. Rat thyroids were stained for calcitonin, H&E and for carcinoembryonic antigen (CEA). Thyroid C-cell hyperplasia was graded on H&E stained slides using cell size and secretory granule numbers, morphological features of the parathyroid glands and the serum calcium concentrations of the rats were also evaluated. Counts of stained cells/high power field and intensity of staining were recorded by two pathologists. Data were analyzed by ANOVA/post-tests. C cell hypertrophy was elevated in exenatide-treated vs. untreated animals (22.5 ± 8.7 vs. 10.5 ± 2.7 cells/HPF). CEA staining failed to show effects by exendin. Calcitonin staining was significantly elevated in exenatide treated controls (P<0.001). Parathyroid glands were histologically normal in both groups, and serum calcium levels were within normal range in all animals. In summary, exenatide was associated with C cell hyperplasia and increased calcitonin staining of thyroids, but was unrelated to CEA levels. These data raise important concerns about the effects of exenatide which, given its wide clinical use, should be clarified with urgency.


Subject(s)
Parathyroid Glands/drug effects , Parathyroid Glands/metabolism , Peptides/pharmacology , Receptors, Glucagon/agonists , Thyroid Gland/drug effects , Thyroid Gland/metabolism , Venoms/pharmacology , Animals , Calcitonin/metabolism , Calcium/blood , Carcinoembryonic Antigen/metabolism , Exenatide , Glucagon-Like Peptide-1 Receptor , Male , Rats , Rats, Sprague-Dawley
8.
Nutr Metab (Lond) ; 9: 24, 2012 Mar 27.
Article in English | MEDLINE | ID: mdl-22452897

ABSTRACT

Calcium is one of the most abundant minerals in the body and its metabolism is one of the basic biologic processes in humans. Although historically linked primarily to bone structural development and maintenance, calcium is now recognized as a key component of many physiologic pathways necessary for optimum health including cardiovascular, neurological, endocrine, renal, and gastrointestinal systems. A recent meta-analysis published in August 2011 showed a potential increase in cardiovascular events related to calcium supplementation. The possible mechanism of action of this correlation has not been well elucidated. This topic has generated intense interest due to the widespread use of calcium supplements, particularly among the middle aged and elderly who are at the most risk from cardiac events. Prior studies did not control for potential confounding factors such as the use of statins, aspirin or other medications. These controversial results warrant additional well-designed studies to investigate the relationship between calcium supplementation and cardiovascular outcomes. The purpose of this review is to highlight the current literature in regards to calcium supplementation and cardiovascular health; and to identify areas of future research.

9.
Clin Transplant ; 26(3): 447-53, 2012.
Article in English | MEDLINE | ID: mdl-22003964

ABSTRACT

Osteopenia and osteoporosis are well-known consequences of allogeneic stem cell transplantation (allo-SCT). The role of prophylactic zoledronic acid on bone turnover following allo-SCT has not been well characterized. We prospectively studied the role of prophylactic use of zoledronic acid on bone metabolism in 17 patients with acute myeloid leukemia (AML) undergoing allo-SCT over a period of three yr (2006-2009). We measured bone mineral density using dual energy X-ray absorptiometry (DXA) scanning and the markers of bone turnover by urinary N-terminal telopeptide (uNTX) and serum osteocalcin levels prior to and serially following transplantation. All patients received 4 mg of zoledronic acid (Zometa, Novartis Pharmaceuticals Corp., Basel, Switzerland) intravenously prior to starting conditioning regimen and at six months after SCT. DXA scores did not change significantly in any patient over time (p > 0.05). uNTX progressively decreased over time (p < 0.001) and serum osteocalcin stabilized after six months. No patient developed osteonecrosis of the jaw. In conclusion, in this prospective pilot study, prophylactic use of zoledronic acid to prevent early bone loss was found to be safe and feasible in patients with AML undergoing allo-SCT during the immediate post-transplantation period.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Resorption/drug therapy , Diphosphonates/therapeutic use , Graft vs Host Disease/drug therapy , Imidazoles/therapeutic use , Leukemia, Myeloid, Acute/complications , Postoperative Complications , Stem Cell Transplantation/adverse effects , Absorptiometry, Photon , Adult , Bone Density/drug effects , Bone Resorption/etiology , Bone Resorption/mortality , Feasibility Studies , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Osteoporosis/etiology , Osteoporosis/mortality , Osteoporosis/prevention & control , Pilot Projects , Prognosis , Prospective Studies , Survival Rate , Transplantation, Homologous , Young Adult , Zoledronic Acid
11.
South Med J ; 96(8): 824-7, 2003 Aug.
Article in English | MEDLINE | ID: mdl-14515930

ABSTRACT

Hypothyroidism is a common condition. Rarely, it may occur in combination with autoimmune failure of other endocrine glands (autoimmune polyendocrinopathy syndrome type 2, previously known as Schmidt's syndrome). In such cases, restoring normal thyroid function may precipitate adrenal failure. Clinicians should have a high index of suspicion for this condition in patients with Addison's disease, those with a family history of autoimmune endocrine gland failure, patients with one autoimmune endocrine disease who develop nonspecific or serious illness, and patients with type 1 diabetes mellitus whose insulin requirements drop without obvious explanation.


Subject(s)
Addison Disease/etiology , Hormone Replacement Therapy/adverse effects , Hypothyroidism/complications , Hypothyroidism/drug therapy , Iodide Peroxidase , Iron-Binding Proteins , Polyendocrinopathies, Autoimmune/complications , Polyendocrinopathies, Autoimmune/drug therapy , Thyroxine/adverse effects , Addison Disease/diagnosis , Addison Disease/drug therapy , Adrenocorticotropic Hormone , Adult , Autoantibodies/blood , Autoantigens/immunology , B-Lymphocytes/immunology , Diagnosis, Differential , Drug Monitoring , Female , Hormone Replacement Therapy/methods , Humans , Hydrocortisone/blood , Hypothyroidism/diagnosis , Hypothyroidism/immunology , Male , Polyendocrinopathies, Autoimmune/diagnosis , Polyendocrinopathies, Autoimmune/immunology , Precipitating Factors , T-Lymphocytes/immunology , Thyrotropin/blood , Thyroxine/blood , Weight Loss
12.
Osteoporos Int ; 14(8): 665-71, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12879218

ABSTRACT

The objective of this study was to determine if hospitalist consultation during admission for hip fracture results in improved treatment for osteoporosis. This was a retrospective chart review, carried out in a university-based academic hospital. Administrative discharge data was used to identify patients discharged between 1 September 1999 and 1 September 2001, discharged with the diagnosis of hip fracture. Eighty-two patient charts were reviewed after exclusion for traumatic and pathologic fractures. Treatment for osteoporosis consisted of medications recommended by the National Osteoporosis Foundation (NOF), including calcium (+/-vitamin D), estrogen, raloxifene, calcitonin, alendronate and risedronate. Osteoporosis treatment improvement was defined as the addition of a medication for osteoporosis that strengthened treatment. Twenty-nine percent of patients in our study received treatment for osteoporosis at the time of discharge from the hospitalization for hip fracture. While 20% received calcium, only 7% received a bisphosphonate. Twelve percent received improvement in osteoporosis treatment from admission to discharge. Those that received hospitalist consultation did not have a significant improvement in osteoporosis treatment (P=0.314), but had significantly more co-morbid illnesses and were significantly older than those receiving no consultation (P<0.05). Identification of osteoporosis as a medical problem was significantly associated with osteoporosis treatment (P<0.05). Potential barriers to hospitalist consultation's effect on osteoporosis treatment included patient age and co-morbidities. Further research is needed to identify and overcome barriers to effective osteoporosis treatment in patients with fractures.


Subject(s)
Hip Fractures/etiology , Hospitalists , Osteoporosis/complications , Osteoporosis/drug therapy , Aged , Calcium/therapeutic use , Drug Utilization , Female , Hospitalization , Humans , Kansas , Male , Middle Aged , Osteoporosis/diagnosis , Referral and Consultation , Retrospective Studies , Risk Factors
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