Amelioration of Paget Disease of Bone After Denosumab for Osteopenia.

Background/Objective: Denosumab is a monoclonal antibody that inhibits bone resorption and is indicated for the treatment of osteoporosis, bone metastases, and giant cell tumor of bone. We describe a woman with symptomatic Paget disease of the skull whose headaches and monostotic disease of the skull improved after receiving denosumab for concomitant low bone density. Case Report: A 75-year-old woman presented with unremitting headache of 1 month. She had a medical history of polymyalgia rheumatica, osteopenia, hypothyroidism, and gastroesophageal reflux disease. She reported taking prednisone 1 to 20 mg daily for polymyalgia rheumatica for 1 year and received a dose of denosumab 60 mg for osteopenia 1 month before presentation. The calcium, alkaline phosphatase, and bone-specific alkaline phosphatase levels were 8.2 mg/dL (reference range [RR], 8.5-10.5 mg/dL), 132 U/L (RR, 40-129 U/L), and 17.8 µg/L (RR, 7-22.4 µg/L), respectively. Skull radiography revealed sclerosis/hyperostosis, lytic lesions, and expansion of bone, consistent with Paget disease of bone (PDB). Five months after the initial presentation, her headache resolved, and her calcium and alkaline phosphatase levels were 9.7 U/L and 96 U/L, respectively. Discussion: Denosumab neutralizes the receptor activator of nuclear factor-kappa B ligand. To date, there have been 2 case reports reported in the English literature of denosumab used successfully in patients with PDB who could not tolerate or were not eligible for bisphosphonates. This case report describes a patient with PDB treated with denosumab for osteopenia who experienced improvement in PDB-related symptoms. Conclusion: Although denosumab was originally approved for the treatment of osteoporosis, the inhibition of bone resorption via inhibition of the receptor activator of nuclear factor-kappa B ligand may be potentially effective in the treatment of PDB.

Tissue Dielectric Constant and Skin Stiffness Relationships in Lower Extremity Lymphedema.

Background: Lower extremity lymphedema or edema (LELE) may progressively transition from a state of excess tissue fluid to increased fat accumulation and collagen deposition, with tissue fibrosis and hardening. Such changes may lead to altered tissue water holding and thereby impact tissue dielectric constant (TDC). This study seeks to evaluate the relationship between TDC and tissue indentation force (TIF) in patients with LELE and assess the utility of the leg/arm TDC ratio (LAR) as an indicator of LELE. Methods and Results: Thirty females (49-91 years) with previously diagnosed LELE were evaluated during a scheduled session. TDC and TIF were measured 8 cm proximal to the medial malleolus on the medial and lateral aspects of both legs and on one forearm 8 cm distal to the antecubital fossa. The TDC-TIC relationship and the LAR were subsequently determined. Main results showed an absence of a significant correlation between TDC and TIF on medial or lateral leg sites but a positive correlation on the normal forearm site. Further, LAR values exceeded the published proposed threshold of 1.35 for 29/30 patients when using medial-side TDC values and 28/30 patients when using lateral-side TDC values. Conclusions: Findings suggest that for patients with LELE, TDC values are significantly elevated on medial and lateral standardized sites. The LAR determined using either medial or lateral sites that are similar to each other and have values consistent with a lymphedema threshold of 1.35. In edematous legs of the type evaluated herein, there is no apparent relationship between TDC values and indentation force.

Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study. / Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte.

BACKGROUND: Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. OBJECTIVE: We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. METHODS: This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. RESULTS: Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI -0.217 to -0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). CONCLUSION: Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

FUNDAMENTO: Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. OBJETIVO: Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. MÉTODOS: O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. RESULTADOS: A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). CONCLUSÃO: Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte / Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study

Resumo Fundamento Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. Objetivo Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. Métodos O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. Resultados A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). Conclusão Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Abstract Background Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. Objective We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. Methods This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. Results Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI −0.217 to −0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). Conclusion Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

Mechanisms and pharmacotherapy of hypertension associated with type 2 diabetes.

Type 2 diabetes is often complicated with hypertension, such that 73.6 % of patients ≥ 18 years with type 2 diabetes also have hypertension. With increasing age, the risk of developing these conditions rises significantly. Co-existence of type 2 diabetes and hypertension suggests that there are overlapping genetic, physiologic, and environmental factors at play. Research has shown several overlying metabolic abnormalities including sympathetic nervous system overactivation, insulin resistance, inflammatory and endothelial dysfunction, deleterious expression of microRNAs, and obstructive sleep apnea. Though diet and physical activity are the mainstays of treatment early in the disease course, they are generally not a viable long-term strategy. Treatment with novel hypoglycemic and anti-hypertensive medications can greatly assist in preventing long-term complications of these chronic conditions. Recognition of the common causes and consequences of type 2 diabetes and comorbid hypertension allows for a robust response towards being proactive regarding prevention and treatment of this unique patient population. Thus, the purpose of this current review is four-part: to (1) review the latest discoveries into the mechanisms of hypertension in the setting of type 2 diabetes, (2) discuss the latest treatments of hypertension with a brief discussion about novel hypoglycemic agents in patients with type 2 diabetes, (3) summarize blood pressure targets and (4) to address evidence gaps in treating patients with diabetes and resistant hypertension, and elderly individuals with both hypertension and diabetes.

Diuretic Resistance Associated With Heart Failure.

Fluid retention is common in patients with heart failure (HF) and diuretics are a major source of management and stabilization. Diuretic resistance (DR) is defined as a failure to achieve therapeutically desired congestion relief despite using an appropriate diuretic dose. In this study, the underlying mechanisms of DR in HF patients are described and several currently available evidence-based strategies to mitigate this condition are provided. Specific aims were to investigate how DR occurs in patients with HF, how HF medications interfere with diuretic treatment, and what alternative methods are available for patients with DR while undergoing treatment for HF. Results provide several rationales for novel strategies used to help reach a state of euvolemia where there is a proper amount of blood in the circulatory system. These include reducing sodium intake, changing the timing of drug administration, and modifying diuretic dose.

Highlights of mechanisms and treatment of obesity-related hypertension.

The prevalence of obesity has increased two to three times from 1975 to 2015. Large-scale epidemiological and longitudinal prospective studies link obesity with hypertension. Research suggests that excessive weight gain, particularly when associated with visceral adiposity, may account for as much as 65% to 75% of the risk of incident hypertension. Also, exercise and bariatric/metabolic surgery significantly lowers blood pressure, whereas weight gain increases blood pressure, thus establishing a firm link between these two factors. The mechanisms underpinning obesity-related hypertension are complex and multifaceted, and include, but are not limited to, renin-angiotensin-aldosterone system/sympathetic nervous system overactivation, overstimulation of adipokines, insulin resistance, immune dysfunction, structural/functional renal, cardiac, and adipocyte changes. Though weight loss is the mainstay of treatment for obesity-related hypertension, it is often not a feasible long-term solution. Therefore, it is recommended that aggressive treatment with multiple antihypertensive medications combined with diet and exercise be used to lower blood pressure and prevent complications. The research regarding the mechanisms and treatment of obesity-related hypertension has moved at a blistering pace over the past ten years. Therefore, the purpose of this expert review is two-fold: to discuss the pathophysiological mechanisms underlying obesity-related hypertension, and to revisit pharmacotherapies that have been shown to be efficacious in patients with obesity-related hypertension.

Contrast-Induced Nephropathy: A Review of Mechanisms and Risks.

Radiological procedures utilizing intravenous iodinated contrast agents are being widely utilized for both therapeutic and diagnostic purposes. This has resulted in an increasing incidence of procedure-related, contrast-induced nephropathy (CIN). CIN is commonly defined as a decline in kidney function occurring in a narrow time window after administration of iodinated contrast agents. Although self-limiting in most cases, CIN carries a risk of more permanent renal insufficiency, dialysis, and death. It remains a common and serious complication among at-risk patients after exposure of contrast agents. Therefore, it is important to identify patients who are at risk during early stages to implement preventative strategies to decrease the incidence of CIN. Minimizing the amount of contrast administered and providing adequate hydration are the cornerstones of an effective preventative approach. This review focuses on the basic concepts of CIN and summarizes the current understanding of its pathophysiology. In addition, it provides practical recommendations with respect to CIN prevention and management.

Finger skin blood perfusion during exposure of ulnar and median nerves to the static magnetic field of a rare-earth magnet: A randomized pilot study.

This pilot study's goal was to investigate the impacts of static magnetic fields (SMF) on finger skin blood perfusion (SBP) when exposing the ulnar artery and ulnar and medial nerves to a rare earth concentric magnet for 30 minutes. Control SBP was measured in 4th fingers of adults (n = 12, age 26.0 ± 1.4 years) for 15 minutes using laser-Doppler. Then, active-magnets were placed over one arm's ulnar and median nerves at the wrist and sham-magnets placed at corresponding sites on the other arm. Devices were randomly assigned and placed by an investigator "blinded" to device type. The maximum SMF perpendicular to skin was 0.28 T measured 2 mm from magnet surface. The tangential field at this distance was 0.20 T. SBP was analyzed and tested for differential effects attributable to magnets compared to shams in each of the 5-minute intervals over the full 45-minute experiment. Results showed no statistically significant difference between SBP measured on the magnet-treated side compared to the sham side. Magnet and sham side SBP values (mean ± SEM, arbitrary units) prior to device placement were 0.568 ± 0.128 vs. 0.644 ± 0.115, p = .859 and during device placement were 0.627 ± 0.135 vs. 0.645 ± 0.117, p = .857. In conclusion, these findings have failed to uncover any significant effects of the static magnetic field on skin blood perfusion in the young healthy adult population evaluated. Its potential for altering SBP in more mature persons or those with underlying conditions affecting blood flow has not been evaluated but represents the next target of research inquiry. ClinicalTrials.gov registration number is NCT04539704.

The Role of Pre-Hospital Telecardiology in Reducing the Coronary Reperfusion Time; a Brief Report.

INTRODUCTION: Telecardiology is defined as using telecommunication for remote treatment of cardiac patients. This study aimed to assess the role of pre-hospital triage via telecardiology on coronary reperfusion time of patients with ST segment elevation myocardial infarction (STEMI). METHODS: This cross-sectional study was conducted from September, 2015 to January, 2018 in six academic referral hospitals, Tehran, Iran. Studied patients were divided into two groups of percutaneous coronary intervention (PCI) following telecardiology or PCI following emergency department (ED) diagnosis of STEMI and time to reperfusion was compared between them. RESULTS: 1205 patients with the mean age of 58.99 ± 12.33 (19-95) years entered the study (82.7% male). 841 (69.8%) cases were transferred directly to the Cath-Lab following telecardiology and 364 (30.2%) cases were first admitted to the ED. There was no significant difference between the groups regarding mean age (p = 0.082) and gender (p = 0.882) of participants. Symptom-to-device interval time in patients who underwent PCI following telecardiology was significantly lower (p < 0.001); however, the difference was not significant in the first medical contact (FMC)-to-device interval time (p = 0.268). CONCLUSIONS: It is likely that the use of telecardiology in pre-hospital triage plays an important role in reducing time to PCI for patients with STEMI.

Imipenem resistance in clinical Escherichia coli from Qom, Iran.

OBJECTIVE: The emergence of metallo-ß-lactamase-producing Enterobacteriaceae is a worldwide health concern. In this study, the first evaluation of MBL genes, bla IMP and bla VIM , in Escherichia coli resistant to imipenem isolated from urine and blood specimens in Qom, Iran is described. Three hundred urine and blood specimens were analysed to detect the presence of E. coli. Resistance to imipenem and other antimicrobials was determined by disk diffusion and MIC. MBL production was screened using CDDT. PCR was also carried out to determine the presence of bla IMP and bla VIM genes in imipenem-resistant isolates. RESULTS: In total, 160 E. coli isolates were collected from March to May 2016. According to disk diffusion, high-level of resistance (20%) to cefotaxime was observed, whereas the lowest (1%) was detected for tetracycline. In addition, five isolates showed resistance to imipenem with a MIC ≥ 4 µg/mL. CDDT test confirmed that five isolates were MBL-producing strains, but no bla IMP and bla VIM genes were detected. Results of this study show a very low level of resistance to imipenem in our geographical area.