RESUMO
INTRODUCTION: Temozolomide is an oral alkylating agent used as first line treatment of glioblastoma multiforme (GBM). It has also been used in the treatment of certain solid tumors such as metastatic melanoma. Commonly reported adverse effects include nausea and vomiting, constipation, headache, fatigue and myelosuppression. Cutaneous hypersensitivity reactions are rare and include an urticarial hypersensitivity reaction, alopecia, and Stevens-Johnson syndrome. To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. CASE REPORT: We present a 54-year-old man with glioblastoma multiforme who presented with a fever, diarrhea and progressively worsening rash 6 weeks after starting temozolomide. MANAGEMENT & OUTCOME: The patient was diagnosed recurrent DRESS syndrome and restarted on a gradual prednisone taper with resolution over the following weeks. Unfortunately, the patient was unable to be followed long-term due to relocation to a different state. DISCUSSION: To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. The diagnosis can be life-threatening, which makes management of patients with GBM and no alternative treatment option challenging. The use of de-sensitization therapy to temozolomide has been proposed for the management of severe adverse cutaneous reactions.
Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Exantema , Glioblastoma , Melanoma , Glioblastoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Temozolomida/efeitos adversosRESUMO
OBJECTIVE: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial. METHODS: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index [BMI], 36.5 ± 3.6 kg/m2) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% [78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed. RESULTS: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB ( P<.001) and 61.1 ± 90% in SG ( P<.001) compared to 29.8 ± 93% in IMT ( P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB ( P<.001) and 71 ± 69% in SG ( P<.001) compared to 43.8 ± 121.1% in IMT ( P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients ( P<.001). Increase in CTX correlated with decreased BMI in SG patients ( P = .039). CONCLUSION: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients. ABBREVIATIONS: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione.
Assuntos
Cirurgia Bariátrica , Remodelação Óssea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Adulto , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Resultado do TratamentoAssuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Difosfonatos/uso terapêutico , Remodelação Óssea , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea , Osteoporose Pós-Menopausa/tratamento farmacológico , Biomarcadores , Administração Oral , Adesão à MedicaçãoRESUMO
Background/Objective: Teriparatide, an osteoanabolic agent similar to parathyroid hormone in properties, is used to manage severe osteoporosis. Aortic valve stenosis is a common valve condition observed in the elderly. Its natural history includes gradual progression toward severity. We present a case of a patient who had rapidly progressive aortic stenosis after teriparatide initiation. Case Report: An 84-year-old woman who was diagnosed with osteoporosis was treated with oral bisphosphonates. When she had spinal compression fractures, she was found to have primary hyperparathyroidism. She underwent parathyroidectomy and was treated with denosumab infusions every 6 months. However, after she experienced bilateral atypical femoral fractures, she was switched to teriparatide daily injections. Her laboratory test results showed a calcium level of 10 mg/dL (reference range, 8.5-10.2 mg/dL), 25-hydroxyvitamin D level of 38.2 ng/mL (reference range, 31.0-80.0 ng/mL), and phosphorus level of 3.3 mg/dL (reference, range, 2.7-4.8 mg/dL). On reviewing echocardiograms before and after teriparatide initiation, we found a rapid progression of her aortic stenosis from moderate to severe based on the mean gradients (23 to 40 mm Hg) and peak velocities (3.09 to 4 m/s), over a span of 10 months. She eventually required valve replacement. Discussion: Natural progression of mild to severe aortic stenosis typically occurs at the rate of 3 to 7 mm Hg per year over several years. Chronic exposure of human valvular endothelial cells to parathyroid hormone can trigger endothelial dysfunction and valvular calcification. Conclusion: In patients with preexisting aortic stenosis, coordination of care with cardiology and echocardiographic monitoring while on therapy may be considered.
RESUMO
Currently, no published cases report concomitant X-linked hypophosphatemia (XLH) and adult hypophosphatasia (HPP). Both diseases share clinical phenotypes that are almost indistinguishable. The correct diagnosis may be missed without a standardized laboratory and genetic testing approach. Pathogenic variants in the phosphate regulating endopeptidases homolog X-linked gene (PHEX) and the tissue-nonspecific alkaline phosphatase gene (ALPL) are genes that cause XLH and HPP, respectively. We describe a concomitant yet undescribed genetic pathogenic variant in a family. A 61-year-old woman was referred by orthopedic surgery for the presence of bilateral leg bowing and short stature during the assessment of knee surgery. The patient had a biochemical workup relevant for low serum phosphorus and 1,25-dihydroxy vitamin D and normal alkaline phosphatase (ALP). Genetic analysis revealed pathogenic variants in PHEX and ALPL. Her 42-year-old daughter shared identical symptoms and genetic variants with her mother. Both patients started conventional treatment for XLH with phosphorus and vitamin D, and the daughter later switched to burosumab-twza. Adult XLH and HPP may have similarities in clinical presentation but differ in some essential laboratory findings. Normal ALP levels helped direct our diagnosis toward XLH. However, the diagnosis was challenging due to the presence of concurrent variants in the genes involved. These variants illustrate the significant heterogeneity of the clinical expression.
RESUMO
Vitamin A, like many things in life, should be consumed in appropriate amounts. Excessive intake of preformed vitamin A, such as that found in supplements and animal sources (animal liver, fish liver oil, dairy, and eggs), is associated with multisystem effects that can include bone resorption and hypercalcemia. Hence, vitamin A toxicity should be explored in unexplained cases of parathyroid hormone-independent hypercalcemia. Serum retinol levels can be helpful in the diagnosis, but the results must be interpreted with caution since they do not always reflect total body levels. Treatment involves supportive care and withdrawal of vitamin A sources, especially preformed ones. Given the long half-life of retinol, normalization of serum levels can take several months.
Assuntos
Hipercalcemia , Vitaminas , Animais , Suplementos Nutricionais/efeitos adversos , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hormônio Paratireóideo , Vitamina A/uso terapêutico , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
Dual-energy x-ray absorptiometry (DXA) can detect bone mineral density loss before it can be identified on usual skeletal radiography, making it possible to diagnose osteoporosis in postmenopausal women and older men before clinical fractures arise. However, when DXA is used outside these populations or if the clinical picture does not match the reported T-scores, mistakes can arise in interpreting results and determining the need for pharmaceutical therapy.
Assuntos
Densidade Óssea , Osteoporose , Absorciometria de Fóton , Idoso , Feminino , Humanos , Masculino , Osteoporose/diagnóstico por imagem , Atenção Primária à Saúde , Medição de RiscoRESUMO
Disease registries are a searchable list of all patients with a particular chronic condition that often interface with an electronic medical record. The well-designed registry links all members of the patient's health team and provides key information for patients and physicians. The critical impact of a registry is that it can allow timely identification of high-risk subpopulations permitting the health care team to intensify treatment. Diabetes is a data-driven disease that lends itself well to registry use. This review will examine some current registry uses and highlight some of the respective challenges and benefits. This review compares key examples of registries in different health settings. These include a municipal registry (New York City), academic health centers (Penn State Milton S. Hershey Medical Center), third-party payers (Kaiser Permanente), the Veterans Affairs Health System, and international registries (the DIABCARE Q-NET in Europe and the National Diabetes Surveillance System in Canada). Different aspects are compared and contrasted such as the institutional plan for each and whether care in the "here and now" is impacted.
Assuntos
Diabetes Mellitus/epidemiologia , Sistema de Registros , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Complicações do Diabetes/classificação , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/reabilitação , Diabetes Mellitus/reabilitação , Equipamentos e Provisões Elétricas , Hemoglobinas Glicadas/metabolismo , Humanos , Cooperação Internacional , Prontuários Médicos , Cidade de Nova Iorque/epidemiologia , Pennsylvania , Autocuidado , Estados Unidos/epidemiologia , United States Department of Veterans Affairs/estatística & dados numéricosRESUMO
GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the alpha 5 beta 1 integrin, but not to laminin through the alpha 2 beta 1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-kappa B transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-kappa B through a signaling pathway requiring Ras, phosphatidylinositol 3-kinase, and Rho family proteins, whereas adhesion to laminin has a limited effect. Retroviral transfer of the superrepressor of NF-kappa B, I kappa B-2A, blocks basic fibroblast growth factor-induced angiogenesis in vivo. These results suggest that engagement of the alpha 5 beta 1 integrin promotes an NF-kappa B-dependent program of gene expression that coordinately regulates angiogenesis and inflammation.
Assuntos
Adesão Celular/fisiologia , Regulação da Expressão Gênica , Proteínas I-kappa B , Inflamação/fisiopatologia , NF-kappa B/metabolismo , Neovascularização Fisiológica/fisiologia , Receptores de Fibronectina/metabolismo , Animais , Materiais Biocompatíveis , Células Cultivadas , Colágeno , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Combinação de Medicamentos , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibronectinas/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Laminina , Camundongos , Camundongos Nus , Inibidor de NF-kappaB alfa , Fosfatidilinositol 3-Quinases/metabolismo , Proteoglicanas , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais/fisiologia , Proteínas ras/metabolismo , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
Numerous studies indicate a gap between evidence-based recommendations for care and clinical outcomes. Barriers reported by physicians include inefficiencies in data gathering. Information technology provides a potent solution to this problem. Diabetes registries are increasingly being utilized as a critical feature for population-based disease management. As an increasing number of organizations realize the need to choose among a plethora of different diabetes registry systems, we seek to identify important features in successful programs and address several of the critical features essential to an effective diabetes registry. A diabetes registry can be used to target high-risk patients, send reminders to patients, and provide physicians with feedback on their care, all important aspects of an optimal diabetes registry that can lead to significant improvements in clinical outcomes. As the healthcare system moves toward wider adoption of diabetes registries, key features of diabetes registry use are discussed.
Assuntos
Diabetes Mellitus , Sistema de Registros , Adolescente , Adulto , Idoso , Diabetes Mellitus/terapia , Humanos , Internet , Pessoa de Meia-Idade , Software , Resultado do TratamentoRESUMO
To find the rational intervals for bone mineral density screening, Gourlay et al (N Engl J Med 2012; 366:225-233) used T scores to calculate the time required for women age 67 and older with normal bone mineral density or osteopenia to progress to osteoporosis. They estimated that the screening interval for women with normal bone mineral density or mild osteopenia (T score -1.49 or higher) could be as long as 15 years. However, the investigators focused mainly on T scores and when these scores reached -2.5. In our opinion, the testing interval should be guided by an assessment of clinical risk factors and not just baseline T scores.
Assuntos
Programas de Rastreamento/métodos , Osteoporose Pós-Menopausa/diagnóstico , Absorciometria de Fóton , Idoso , Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico , Progressão da Doença , Feminino , Fraturas Ósseas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Fatores de Risco , Fatores de TempoRESUMO
Parathyroid hormone-related protein (PTHrP)(1-36) increases lumbar spine (LS) bone mineral density (BMD), acting as an anabolic agent when injected intermittently, but it has not been directly compared with parathyroid hormone (PTH)(1-34). We performed a 3-month randomized, prospective study in 105 postmenopausal women with low bone density or osteoporosis, comparing daily subcutaneous injections of PTHrP(1-36) to PTH(1-34). Thirty-five women were randomized to each of three groups: PTHrP(1-36) 400 µg/day; PTHrP(1-36) 600 µg/day; and PTH(1-34) 20 µg/day. The primary outcome measures were changes in amino-terminal telopeptides of procollagen 1 (PINP) and carboxy-terminal telopeptides of collagen 1 (CTX). Secondary measures included safety parameters, 1,25(OH)2 vitamin D, and BMD. The increase in bone resorption (CTX) by PTH(1-34) (92%) (p < 0.005) was greater than for PTHrP(1-36) (30%) (p < 0.05). PTH(1-34) also increased bone formation (PINP) (171%) (p < 0.0005) more than either dose of PTHrP(1-36) (46% and 87%). The increase in PINP was earlier (day 15) and greater than the increase in CTX for all three groups. LS BMD increased equivalently in each group (p < 0.05 for all). Total hip (TH) and femoral neck (FN) BMD increased equivalently in each group but were only significant for the two doses of PTHrP(1-36) (p < 0.05) at the TH and for PTHrP(1-36) 400 (p < 0.05) at the FN. PTHrP(1-36) 400 induced mild, transient (day 15) hypercalcemia. PTHrP(1-36) 600 required a dose reduction for hypercalcemia in three subjects. PTH(1-34) was not associated with hypercalcemia. Each peptide induced a marked biphasic increase in 1,25(OH)2 D. Adverse events (AE) were similar among the three groups. This study demonstrates that PTHrP(1-36) and PTH(1-34) cause similar increases in LS BMD. PTHrP(1-36) also increased hip BMD. PTH(1-34) induced greater changes in bone turnover than PTHrP(1-36). PTHrP(1-36) was associated with mild transient hypercalcemia. Longer-term studies using lower doses of PTHrP(1-36) are needed to define both the optimal dose and full clinical benefits of PTHrP. © 2013 American Society for Bone and Mineral Research.