bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with health related quality of life of patients with stroke in Sri Lankan context
Authors: Kariyawasam Pramudika Nirmani , Pathirana Kithsiri Dedduwa , Hewage Don Chandana
Published: May 2020

Background

Stroke is a major global health concern which affects the health related quality of life (HRQOL). As the prevalence of stroke is increasing especially in lower-middle income countries, it is vital to identify the factors associated with the HRQOL of affected individuals.

Available literature for post stroke HRQOL and the associated factors are mainly from high income countries. Therefore, we conducted this study to identify the factors associated with HRQOL of stroke survivors using a stroke specific measure.

Methods

A longitudinal study was conducted with the participation of 257 stroke survivors. Participants were followed up after 3 months at the neurology and medical clinics in the Teaching Hospital, Karapitiya, Sri Lanka.

Health related quality of life was assessed using the validated version of Stroke Aphasia Quality of Life (SAQOL)-39 generic scale. Pearson correlation, independent sample t-test, one-way ANOVA and regression analysis were used to identify the factors associated with quality of life.

Results

Mean age of the participants with stroke was 66.1 (SD 11.7) years. The mean overall HRQOL was 3.15 (SD 0.96) as measured by the SAQOL-39 g. The socio-demographic factors which had significant associations with HRQOL were; gender, level of education, marital status, occupation and monthly income (p < 0.05). The clinical factors which had significant associations with HRQOL were; level of dependence and disability, type of stroke, side of the lesion, type of aphasia, level of language impairment, receiving physiotherapy and speech therapy and follow up care (p < 0.05). The results of regression indicated six independent predictors [F (6,234) = 42.6,p < 0.05], with an R2of 0.52. The HRQOL was significantly predicted by the level of dependence (β = .43,p < .01), level of language impairment (β = .20,p < .01), age (β = −.23,p < .01), type of stroke (β = −.19,p < .01), side of the lesion (β = .17,p < .01) and the level of education (β = .12,p < .05).

Conclusion

Severe degree of dependence, severe level of language impairment, older age, hemorrhagic stroke, and lesions in the left side were associated with lower HRQOL. Higher education level was associated with higher HRQOL scores.
Hemoperitoneum due to bleeding from a vein overlying a subserous uterine myoma: a case report
Authors: Rokhgireh Samaneh , Kashi Abolfazl Mehdizadeh , Kermansaravi Mohammad , Tajbakhsh Banafsheh , Allahqoli Leila , Alkatout Ibrahim , Khodaverdi Sepideh
Published: May 2020

Background

Fibroids are the most common pelvic tumors in women; serious complications are rare but can be life-threatening.

Case presentation

We present a case report of a 38-year-old Persian woman with acute abdominal pain and a history of uterine fibroids. The patient refused to undergo a laparoscopic myomectomy. Her ultrasound examination revealed free fluid in the abdominal cavity, and her vital signs were indicative of vasogenic shock. A diagnostic laparoscopy was performed to identify and control the source of bleeding: 400 ml of blood and blood clots were removed. Active bleeding was seen from a vein overlying a subserosal myoma. A laparotomic myomectomy was performed, and the patient was discharged 3 days after surgery with no complications.

Conclusion

Surgeons should consider the possibility of this complication in women with acute abdominal pain and a history of uterine leiomyoma.
Physiologic perfusion monitoring methods during endovascular revascularization for atherosclerotic peripheral arterial disease: protocol for a systematic review
Authors: Rockley Mark , Jetty Prasad , Wells George
Published: May 2020

Background

Endovascular therapy is a fundamental treatment for peripheral arterial disease. However, the success rate of endovascular therapy remains poor, as a third of patients with critical limb ischemia ultimately require a major amputation for gangrene despite endovascular treatment. This failure rate has prompted investigation into methods of determining physiologic procedural success before and after treatment, before clinically apparent outcomes occur such as gangrene. The aim of this systematic review is to evaluate if in patients undergoing endovascular surgery for lower extremity atherosclerotic peripheral arterial disease, do changes in physiologic measures of perfusion during surgery correlate with clinical outcomes.

Methods

We registered and designed a study protocol for a systematic review. Literature searches will be conducted in MEDLINE, EMBASE, and CENTRAL (from January 1977 onwards). Grey literature will be identified through OpenGrey and clinical trial registries, and supplemented by citation searches. We will include randomized controlled trials, quasi-experimental trials, and observational (cohort, case-control) studies conducted in human adults (age 18 or older) who received elective arterial angioplasty for atherosclerotic peripheral vascular disease. The primary outcome of interest will be major adverse limb events. Two investigators will independently screen all citation, full-text articles, and abstract data. The study quality (risk of bias) will be appraised appropriate tools. Data analysis and synthesis will be qualitative; no meta-analysis is planned, as the anticipated homogeneity of measurement and outcome reporting standardization is low.

Discussion

The treatment of peripheral arterial disease is unique in that the tissue of the ischemic leg is easily accessible for direct monitoring during procedures. This is contrasted with cardiac and neurologic monitoring during cardiac and cerebral procedures, where indirect or invasive measures are required to monitor organ perfusion. Currently synthesized evidence describing limb perfusion focuses on static states of ischemia, and does not evaluate the value of change in perfusion measurement as an indicator of endovascular treatment success. These methods could potentially be applied to optimize procedural outcomes by guiding perfusion-based decision-making during surgery.

Systematic review registration

PROSPERO CRD42019138192
Logbooks alone are not enough: initial experience with implementing a logbook for medical students in a clinical internship in gynecology and obstetrics
Authors: Jud Sebastian M. , Cupisti Susanne , Frobenius Wolfgang , Benn Sigrid , Winkler Andrea , Antoniadis Sophia , Beckmann Matthias W. , Heindl Felix
Published: May 2020

Background

Logbooks are being increasingly widely used as a means of improving medical education and further training. They will in all probability continue to be mandatory in the Practical Year (PJ) in Germany even after the upcoming amendment of the Medical Licensing Regulations (ÄAppO). However, there are different approaches to their design and use, and these are also currently undergoing considerable change. This study for the first time examines and discusses the influence of logbooks on students’ evaluation of a gynecology internship.

Methods

The study was based on a well-established two-part 1-week internship course, with initially unstructured morning classes on wards and duty areas, along with precisely planned afternoon classes with skills training by peer teachers and seminars supervised by duty-exempted physicians. The postgraduate lecturers were prepared for the introduction of the logbook in a special course, and the aim was to optimize morning classes by introducing learning objectives adapted to the respective locations. The effects over 38 weeks of practical training were examined in evaluations by 235 prospectively group-randomized students with and without logbooks (n = 166 and n = 66, respectively; three datasets were not evaluable).

Results

In the cohort comparison, the logbook group responded significantly more positively toward the internship at the start of the course (P = 0.046). In the final evaluation, however, medical supervision during the entire internship was rated significantly more poorly (P = 0.007). The logbook cohort also considered that guidance based on learning objectives was significantly worse, as was the extent to which wards and duty areas were prepared for the students (P = 0.001 and P = 0.029).

Conclusions

Introducing a logbook to optimize clinical teaching in internships may raise expectations that cannot always be met. In addition to adapting the learning objectives to a general framework that is less favorable in comparison with the Practical Year, the least that is required appears to be simultaneous and continuous mentoring of the lecturers, as well as an increase in staffing resources.
A nonintrusive reduced order model for nonlinear transient thermal problems with nonparametrized variability
Authors: Casenave Fabien , Gariah Asven , Rey Christian , Feyel Frederic
Published: May 2020

In this work, we consider a transient thermal problem, with a nonlinear term coming from the radiation boundary condition and a nonparametrized variability in the form complex scenarios for the initial condition and the convection coefficients and external temperatures. We use a posteriori reduced order modeling by snapshot Proper Orthogonal Decomposition. To treat the nonlinearity, hyperreduction is required in our case, since precomputing the polynomial nonlinearities becomes too expensive for the radiation term. We applied the Empirical Cubature Method, originally proposed for nonlinear structural mechanics, to our particular problem. We apply the method to the design of high-pressure compressors for civilian aircraft engines, where a fast evaluation of the solution temperature is required when testing new configurations. We also illustrate that when using in the reduced solver the same model as the one from the high-fidelity code, the approximation is very accurate. However, when using a commercial code to generate the high-fidelity data, where the implementation of the model and solver is unknown, the reduced model is less accurate but still within engineering tolerances in our tests. Hence, the regularizing property of reduced order models, together with a nonintrusive approach, enables the use of commercial software to generate the data, even under some degree of uncertainty in the proprietary model or solver of the commercial software.
Analyzing the disaster response competency of the local government official and the elected representative in Nepal
Authors: Malla Shrijan Bahadur , Dahal Ranjan Kumar , Hasegawa Shuichi
Published: May 2020

Local authorities i.e. government officials working at the district level and below and elected representatives of municipalities are the steering body of local-level disaster response mechanism in Nepal. The effectiveness of response operation moreover depends on their competency. This paper investigates their disaster response knowledge, preparedness, and perception, and to identify gaps and suggest recommendations.

The prevailing competency of Nepalese local authorities doesn’t warrant an effective response during the time of disaster. They lack awareness and preparedness. Amidst their positive perception towards the need of disaster response capacity building, in the void of an effective mechanism, the government has failed to enhance their competency.

The national investment for disaster response competency building is meager in Nepal. The country heavily relies on foreign aid. The present capacity-building mechanism should be redressed from the newer dynamic.
Predictors of mental health and academic outcomes in first-year university students: Identifying prevention and early-intervention targets
Authors: Duffy A. , Keown-Stoneman C. , Goodday S. , Horrocks J. , Lowe M. , King N. , Pickett W. , McNevin S. H. , Cunningham S. , Rivera D. , Bisdounis L. , Bowie C. R. , Harkness K. , Saunders K. E. A.
Published: May 2020

Background

Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts.

Aims

To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes.

Method

Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders.

Results

In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being.

Conclusions

Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.
A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal Men
Authors: Swerdloff Ronald S , Wang Christina , White William B , Kaminetsky Jed , Gittelman Marc C , Longstreth James A , Dudley Robert E , Danoff Theodore M
Published: May 2020

Context

A novel formulation of oral testosterone (T) undecanoate (TU) was evaluated in a phase 3 clinical trial.

Objective

Determine efficacy, short-term safety, and alignment of new oral TU formulation with current US approval standards for T replacement therapy.

Design

Randomized, active-controlled, open-label study.

Setting and Patients

Academic and private clinical practice sites; enrolled patients were clinically hypogonadal men 18 to 65 years old.

Methods

Patients were randomized 3:1 to oral TU, as prescribed (JATENZO®; n = 166) or a topical T product once daily (Axiron®; n = 56) for 3 to 4 months. Dose titration was based on average T levels (Cavg) calculated from serial pharmacokinetic (PK) samples. T was assayed by liquid chromatography–mass spectrometry/mass spectrometry. Patients had 2 dose adjustment opportunities prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory blood pressure (BP).

Results

87% of patients in both groups achieved mean T Cavg in the eugonadal range. Sodium fluoride-ethylenediamine tetra-acetate plasma T Cavg (mean ± standard deviation) for the oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L); serum T equivalent, ~489 ± 155 ng/dL (17 ± 5 nmol/L); and topical T, 391 ± 140 ng/dL (~14 ± 5 nmol/L). Modeling/simulation of T PK data demonstrated that dose titration based on a single blood sample 4 to 6 h after oral TU dose yielded efficacy (93%) equivalent to Cavg-based titration (87%). Safety profiles were similar in both groups, but oral TU was associated with a mean increase in systolic BP of 3 to 5 mm Hg.

Conclusion

A new oral TU formulation effectively restored T to mid-eugonadal levels in hypogonadal patients.
SUN-366 Neonatal Severe Hyperparathyroidism: Extreme Hypercalcemia as a Robust Marker for Homozygous Dosage of Pathogenic CASR Variants
Authors: Marx Stephen J , Sinaii Ninet
Published: May 2020

Context: Neonatal severe hyperparathyroidism (NSHPT) is a rare and life-threatening emergency. It includes generalized hyperparathyroid bone disease and respiratory distress from combinations among a narrowed thorax, rib fractures, hypotonia, and biochemical disturbances. Successful therapy is compatible with long life and a healthy prognosis. However, neuromotor retardation may persist after otherwise successful therapy. The time and amplitude of hypercalcemia likely correlate with irreversible neuromotor retardation; thus, early intervention seems critical in many cases. NSHPT is usually caused by homozygous or heterozygous pathogenic variant(s) of the CASR; a heterozygous variant of this gene is also the usual cause of familial hypocalciuric hypercalcemia (FHH or FHH1). Homozygotes and heterozygotes with NSHPT are often not distinguished in the current literature. In theory, their management should differ. Optimum treatment in homozygotes is early total parathyroidectomy with induction of postoperative hypoparathyroidism. Optimal management of heterozygotes is more complex. It consists in temporizing measures and varies from careful observation without surgery, to bisphosphonates and/or calcimimetics, and to subtotal parathyroidectomy. The heterozygotes can then develop into healthy babies with asymptomatic FHH1.

Evidence Acquisition: Each case met strict criteria for “severe” and neonatal disease. We analyzed the core biochemical parameters of the maximal serum calcium and maximal PTH. To compare different immunoassays, PTH was analyzed as a ratio (thus without units) of the raw data divided by the upper limit of its normal range. Each case also required information about the allelic dosage of the pathogenic or likely pathogenic CASR variant(s).

Evidence Synthesis: There were 36 cases with homozygous pathogenic CASR variants and 21 cases with heterozygous pathogenic or likely pathogenic variants. Maximal serum calcium was far higher in homozygotes 5.8 +/- 1.5 versus 3.2 +/- 0.2 (P<.001) (normal 2.2–2.6 mM). Maximal serum PTH as a ratio was also far higher in homozygotes 17 +/- 12 versus 8 +/- 9 (P=.003) (normal ratio 0.3–1.0). We defined extreme hypercalcemia empirically as any calcium value above 4.5 mM. No heterozygote had a maximal calcium above 3.7 mM; however, 30 of 36 (81%) of the homozygotes had maximal calcium above 4.5 mM. Whenever tested early, this extreme hypercalcemia was usually recognized in the first week of life.

Conclusions: Extreme hypercalcemia greater than 4.5 mM was newly identified as a conservative cutoff that was 100% predictive of homozygosity for pathogenic CASR variants. Extreme hypercalcemia in NSHPT is an early, facile, rapid, and inexpensive determinant of homozygosity for pathogenic variants of the CASR. It should be sought and used to promote early and definitive total parathyroidectomy, whenever it is identified in NSHPT.
SAT-508 Oh My Thyrotoxic Heart! An Uncommon Presentation of High Output Heart Failure
Authors: Morales Maria Del Mar Felix , Nieves Rebeca Vazquez , Olan Jonathan Torrens , Maymi Lorianna Aleman , Bracero Xiomara Cruz , Carrero Quiñones Milton D
Published: May 2020

High output heart failure is an extremely rare manifestation of thyrotoxicosis in patients without heart disease. Thyroid hormone has a potent metabolic, vascular, positive chronotropic and inotropic effects. Thyrotoxicosis is accompanied by a reduction in systemic vascular resistance and an obligatory increase in cardiac output to compensate high metabolic state. Most of the patients had completed or near completed recovery of cardiac function after treatment to euthyroid status, if cut in time.

Case of 70 y/o female with past medical history of hypothyroidism, hypertension and chronic smoker, came to emergency room due to lightheadedness, weakness, shortness of breath, palpitations and acute bedridden for one week ago. Denied fever, nausea, vomiting or chest pain. On examination patient presented with 122bpm, 23rpm and normotensive. She was in acute respiratory distress requiring BiPAP. Lungs auscultation bilateral crackles, decrease sounds in the bases. Cardiac exam significant for tachycardia, lower extremity edema and JVD +. Laboratories significant for CKD stage 2, chronic anemia and hypoxemia. EKG no ST changes neither T depressions. CXR day #1 reported no cardiopulmonary disease. Basing in these she was admitted with Suspected Pulmonary Embolism. Well’s score was moderate risk; a Chest CTA and full anticoagulation were ordered. Later, venous duplex reported no DVT and D-dimer levels 1.65μg/ml. TSH levels significant decrease 0.0002mU/L and T4 1.800ng/dL. CXR Day#2 reported pulmonary edema and pleural effusion. ECHO2D moderate LVH and preserved systolic function. Patient referred her doctor recently increased thyroid medications from 50 to 100 mcg. Instead of presenting with pulmonary embolism, she has hyperthyroidal state causing cardiac failure. Levothyroxine, heparin and Chest CTA scan were cancelled. She was started in Atenolol and diuretics. Patient symptoms improved and was discharged home to be followed in the clinic. After one week, TSH levels were in 0.008mU/L and one month later in 3.032mU/L. She was started in Levothyroxine 50mcg, to maintain patient euthyroid state.

This case illustrates that sometimes tachycardia and tachypnea are symptoms which frequently presents as baffling diagnostic problems. The association of thyrotoxicosis and cardiovascular morbidity is well established. Thyrotoxicosis most common cardiac manifestation is high output heart failure. Patients presenting with heart failure may have thyrotoxicosis as the underlying cause. Treatment of the thyrotoxicosis can restore normal heart function. Hyperthyroidal state may be take into consideration as a differential of tachycardia and tachypnea even if it’s not one of the common causes. Awareness of this presentation may help identify patients with reversible dilated cardiomyopathy and other complications.
MON-272 Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients
Authors: Yamamoto Koichiro , Hanayama Yoshihisa , Hasegawa Kou , Yasuda Miho , Tokumasu Kazuki , Hagiya Hideharu , Ogawa Hiroko , Obika Mikako , Otsuka Fumio
Published: May 2020

PRL is a polypeptide hormone that is, in phylogeny, well conserved but elicits various species-dependent functions. PRL is related to the regulation of osmotic pressure in fish and amphibians, fat retention in reptiles and birds, and glucose-lipid metabolism, bone homeostasis and development of the mammary gland in mammals. In humans, PRL secretion is regulated in an inhibitory manner by dopaminergic neurons that project from the hypothalamus to PRL-producing cells in the anterior pituitary gland. Since dopaminergic actions are mainly mediated by D2R, various agents that bind D2R can affect serum PRL levels. In the clinical aspect, hyperprolactinemia is considered in cases with galactorrhea, infertility and sexual dysfunction. Other causes of hyperprolactinemia include hypothyroidism, chronic kidney disease and pregnancy. Also, PRL receptors have been considered as therapeutic targets for some cancers and autoimmune diseases. Given that several pathophysiological functions related to PRL have been recently uncovered, the utility of measuring serum PRL levels could be more widely applicable for a clinical setting. We therefore attempted to reveal the relevance of PRL levels to various clinical parameters in patients who visited a general medicine department. We reviewed medical records of 353 patients whose serum PRL levels were measured in our department during the period from 2016 to 2018. Patients lacking detailed clinical records (n=194) and patients taking medications that affect D2R (n=19) were excluded from this study. Data were analyzed for 140 patients (42 males, aged 49 ± 18 years; 98 females, 45 ± 19 years) in whom various pain and general fatigue were major symptoms at the first visit and in whom hypertension and dyslipidemia were frequently seen in past histories. Average PRL levels were significantly lower in males than in females. The median PRL level in males was 6.5 ng/ml (IQR: 4.2–10.3) ng/ml and that in females was 8.1 ng/ml (5.9–12.9). Patients were divided into two groups depending on whether PRL levels were higher than 10 ng/ml. The group of males with relatively high PRL levels (≥10 ng/ml) had significantly lower levels of serum albumin and higher levels of serum LDH. Of note, there were significant correlations of male PRL levels to erythrocyte sedimentation rate (ESR) (r=0.6), serum LDH (r=0.4) and albumin level (r=-0.5), and TSH/FT4 ratio (r=0.5). On the other hand, female PRL levels were negatively correlated to age (r=-0.2) and serum levels of FSH (r=-0.3) and positively correlated to serum levels of GH (r=0.3). Collectively, the results revealed that PRL levels had gender-specific relevance to various clinical factors. It is notable that PRL levels in males were related to inflammatory status shown by high ESR and low serum albumin and were also associated with a hypothyroid condition.
MON-668 The Content of Serum Clusterin in Patients with Diabetic Macular Edema Depending on the Kind of Glucose Lowering Therapy
Authors: Kyryliuk Mykhailo L , Suk Sviatoslav A
Published: May 2020

Relevance. Insight into the pathophysiology of diabetic macular edema (DME) has led to novel treatments, including anti-VEGF, corticosteroid-based treatment strategies and novel therapies, such as a clusterin blood retina barrier (BRB) cytoprotection. It has been shown the protective effect of clusterin on oxidative stress-induced cell death and its emerging roles in reduction of both BRB breakdown and neural retina damage. Goal. To assess the content of serum clusterin in patients with type 2 diabetes (T2D) and diabetic macular edema depending on the type of glucose lowering therapy. Material and methods. This study was conducted in 82 patients with T2D and DME. The average age of patients was 65.25 ± 10.85 years (±SD) [25; 84], the average duration of diabetes was 14.0 ± 7.05 years (±SD) [1; 35], the average level of HbA1c was 8.40 ± 1.58% (±SD). The criteria for inclusion in the open study was voluntary informed consent, age 18 years and more, the presence of T2DM. Non-inclusion criteria were the presence of endocrine diseases, which can lead to type 2 diabetes, T1D, acute infectious diseases, cancer, decompensation of comorbid pathology, mental disorders, antipsychotics, antidepressants, neurodegenerative diseases of the central nervous system, proteinuria, damage to the optic nerve, glaucoma and mature cataracts. 43 patients received oral glucose lowering drugs (OGLD: sulfonylureas, biguanides), 39 patients received insulin therapy. All patients had instrumental ophthalmological examinations. The concentration of serum clusterin was measured by «Human Clusterin ELISA» kits. Statistical analysis was performed by one-way ANOVA analysis. Results. A study of level variability of blood clusterin in patients with DME showed its dependence from the type of glucose lowering therapy. Comparison of mean values of strum clusterin in patients with DME and T2DM revealed the following statistically significant differences: OGLD 87,08 ± 3,15 mcg/ml [95% CI 82,63 - 91,54 mcg/ml]; insulin therapy 74,79±2,98 mcg/ml [95% CІ 70,58 - 78,99 mcg/ml] (р=0,006). Apparently, clusterin is involved in the pathogenesis of DME and may have a potential in reducing of the pathogenic effect of diabetes on the neurovascular unit. The data obtained make it possible to discuss the neuroprotective role of clusterin in DME with the use of voiced oral hypoglycemic drugs, which usually prescribe for patients with mild form of T2D or for the patients with moderate severity T2D (i. e. at the initial stages of development of diabetes). Conclusion. Against the background of glucose lowering drugs in patients with type 2 diabetes and diabetic macular edema statistically significant (р=0,006) increases the content of serum clusterin compared to insulin therapy.
MON-378 Efficacy and Safety of Romosozumab vs Alendronate Is Similar Across Different Levels of Renal Function Among Postmenopausal Women with Osteoporosis
Authors: Miller Paul , Cheung Angela M , Reid Ian , Rojeski Maria , Vanderkelen Mark , Yang Wenjing , Santiago Norma Ruiz , Oates Mary
Published: May 2020

Postmenopausal women with osteoporosis may also have renal insufficiency. We conducted a post hoc analysis of the ARCH study to determine the efficacy and safety of romosozumab (Romo) vs alendronate (ALN) among patients with different levels of baseline renal function.

In ARCH, 4,093 postmenopausal women, 55–90 years old, were randomized 1:1 to receive monthly subcutaneous Romo 210 mg or weekly oral ALN 70 mg for 12 months (double-blind phase [DBP]). Eligible patients had a bone mineral density (BMD) T score of ≤ –2.5 at the total hip (TH) or femoral neck (FN) and either ≥ 1 moderate/severe vertebral fracture (VFx) or ≥ 2 mild VFx; or a T score of ≤ –2.0 at the TH or FN and either ≥ 2 moderate/severe VFx or an Fx of the proximal femur sustained 3–24 months before randomization. Pts were excluded for significantly impaired renal function (eGFR < 35 mL/min/1.73 m2, calculated using the MDRD equation). For the current analysis, patients were categorized by baseline eGFR: normal renal function (eGFR ≥ 90), mild renal insufficiency (eGFR 60–89), or moderate renal insufficiency (eGFR 30–59). The least squares mean (LSM) % change from baseline in BMD at the lumbar spine (LS), TH, and FN; incidence of new VFx; incidence of adverse events (AEs); and changes in renal function were assessed for each eGFR category at month 12 of the DBP.

At baseline, 15% of patients had eGFR ≥ 90, 60% had eGFR 60–89, 24% had eGFR 30–59, and 0.3% had eGFR 15–29. In the overall patient population, LSM % change (95% CI) from baseline in BMD (Romo vs ALN) was 13.7% (13.4–14.0) vs 5.0% (4.7–5.2) for LS, 6.2% (5.9–6.4) vs 2.8% (2.7–3.0) for TH, and 4.9% (4.7–5.2) vs 1.7% (1.5–2.0) for FN (P < 0.001 at each site). Changes in BMD were similar irrespective of baseline eGFR. Among patients with eGFR ≥ 90, eGFR 60–89, and eGFR 30–59, the incidence of new VFx (Romo/ALN) was 3.3%/7.3% (relative risk reduction [RRR] = 57%; 95% CI: 1–81), 3.2%/3.9% (RRR = 19%; 95% CI: -28–49), and 3.4%/6.2% (RRR = 51%; 95% CI: 5–75), respectively. The incidences of AEs, serious AEs, and fatal AEs were similar in both treatment groups within each eGFR category as well as across eGFR categories; there was a higher incidence of positively adjudicated cardiovascular events in the Romo vs ALN group overall and across eGFR categories. One patient in the Romo group with eGFR 60–89 at baseline and 1 in the ALN group with eGFR ≥ 90 at baseline had an AE of mild hypocalcemia. Similar percentages of patients in the Romo and ALN groups had changes in renal function over 12 months of treatment.

In conclusion, the efficacy and safety of Romo vs ALN was similar across different levels of renal function.
SUN-191 The Creatinine, the Crib and the Manometer - Navigating the Labyrinth of Primary Aldosteronism
Authors: Hashmi Hiba , LaFave Laura
Published: May 2020

A 21-year-old Ethiopian female with a five-year history of hypertension presented to medicine clinic with headaches and fatigue for two weeks. She was hypertensive to 163/113 mmHg. She had recently moved to the US and no prior medical records were available. She had been taking an unknown antihypertensive until three weeks prior. She was found to have a creatinine of 3.49 mg/dL. Renal ultrasound revealed bilateral, small echogenic kidneys without any evidence of renal artery stenosis. An intrauterine pregnancy was also incidentally discovered. Her aldosterone level was elevated to 486 ng/dL and her renin activity was 1.3 ng/ml/hr, with a ratio of 373, diagnostic of primary aldosteronism. Due to the markedly high ratio, a saline suppression test was deemed unnecessary for confirmation. Her serum potassium was normal at 3.6 mEq, likely due to poor renal clearance. Given renal failure, a CT non-contrast of the adrenal glands was performed with normal findings. She elected to terminate the high-risk pregnancy.

Based upon her young age at presentation, family history of early onset hypertension, grossly elevated aldosterone: renin ratio and unrevealing workup for a primary tumor or hyperplastic adrenals, a diagnosis of familial hyperaldosteronism was considered. She failed a month-long trial of dexamethasone therapy, therefore glucocorticoid remediable aldosteronism was excluded. She was subsequently started on spironolactone with good response. Adrenal vein sampling was considered to find a surgical target for adrenalectomy but could not be performed given worsening kidney function. After discussion with Nephrology she opted for a pre-emptive renal transplant evaluation, rather than pursuing dialysis. Genetic testing for subclassification has been negative for mutations in KCNJ5 and CACNA1H with ongoing testing for novel mutations.

Primary aldosteronism (PA) usually presents with recalcitrant hypertension, hypokalemia and an elevated aldosterone: renin ratio. It is commonly attributed to adrenal adenomas or hyperplasia with familial hyperaldosteronism (FH) remaining a rare etiology. FH is sub-divided into glucocorticoid remediable, type I, and non- glucocorticoid remediable, types II – IV. The initial diagnosis of such a condition during pregnancy and in the setting of worsening kidney disease presents a diagnostic and management challenge as this precludes adrenal vein sampling and contrast imaging. Our case highlights the importance of early screening for PA and illustrates the need for updated guidelines on aldosteronism workup in the setting of ESRD and pregnancy.
SUN-200 Adrenal Cortical Neoplasm with Progression to Metastatic Adrenal Cortical Carcinoma One Year After Adrenalectomy
Authors: Sands Mollie , Zhang Jian , Tan Marilyn , Hoffman Andrew R
Published: May 2020

Background: Adrenal cortical carcinoma (ACC) is a rare and aggressive malignancy; diagnostic tools for a pathologic confirmation of ACC are currently limited to scoring systems such as the modified Weiss criteria, the Helsinki score, and criteria proposed by Bisceglia et al. There is lack of consensus on appropriate monitoring and therapeutic strategies for suspicious lesions that do not fulfill all criteria for malignancy or metastatic potential. This is a case of a previously resected localized adrenal neoplasm with progression to metastatic ACC 1 year later.

Clinical Case: A 63-year-old male with hypertension and type 2 diabetes was referred to Endocrinology due to fragility fractures, weight gain, and uncontrolled hypertension concerning for cortisol excess. Workup revealed a 24-hour urinary free cortisol of 283 μg [0–50 μg/24hr], a post-1 mg dexamethasone suppression cortisol of 24.6 μg/dL [<1.8 μg/dL], and a random ACTH of <1.1 pg/mL. CT adrenals revealed a left 3.3 cm nodule measuring 40 Hounsefield units and 27% washout. The patient underwent left adrenalectomy with clear margins. Pathology reported an oncocytic adrenal cortical neoplasm with a Ki-67 of 4.3%, an elevated mitotic activity of up to 12 mitoses per 50 high-power fields, and large nuclei with prominent nucleoli. There was no evidence of necrosis, capsular or vascular invasion. The final pathologic diagnosis was “adrenal cortical neoplasm with worrisome features”, and close follow-up was recommended. 1 year later, the patient presented with recurrent Cushing’s syndrome; he was found to have metastatic ACC with lesions in the adrenalectomy bed, liver, and lungs. Despite maximal medical therapy, the patient suffered severe sequelae of Cushing’s and transitioned to palliative measures.

Clinical Lessons: There are several pathologic scoring systems used to diagnose and predict prognosis in ACC. The challenge of this case is balancing fulfilling the highly-sensitive Bisceglia criteria for ACC [1 “major criterion” of high mitotic rate favors oncocytic ACC] with the other aspects that suggest a more positive outcome: clear surgical margins and a Helsinki score of 7.3 [≥8.5 favors metastatic potential]. His diagnosis fell into an intermediate area of “neoplasm with worrisome features”, and he did not receive adjunctive mitotane therapy. Current guidelines do not recommend adjuvant mitotane therapy for indeterminate lesions or for cases of confirmed ACC with Ki-67 <10% after complete resection, and there is limited guidance regarding monitoring of such lesions. Retrospectively, it is unclear if our patient would have had an improved outcome with adjunctive mitotane therapy or closer surveillance for recurrence.

Bisceglia M, Ludovico O, Di Mattia A, Ben-Dor D, Sandback J, Pasquinelli G, Lau SK, Weiss LM. Adrenocortical Oncocytic Tumors: Report of 10 Cases and Review of the Literature. Int J Surg Pathol. 2004 Jul; 12(3)231–43
OR31-02 Diagnostic Criteria for Polycystic Ovary Syndrome in Adolescents: Impact on Prevalence and Longitudinal Body Mass Index Trajectories
Authors: Tay Chau Thien , Teede Helena Jane , Hart Roger , Earnest Arul , Doherty Dorota , Hickey Martha , Moran Lisa J , Joham Anju Elizabeth
Published: May 2020

Background: Polycystic ovary syndrome (PCOS) is characterised by oligo-anovulation (OA), hyperandrogenism (HA) and polycystic ovary morphology (PCO). While the Rotterdam criteria (defined as 2 out of 3 features) are the most widely used criteria in adults, controversy remains for the diagnostic criteria in adolescents as many PCOS features overlap with normal pubertal physiological changes. The 2018 international evidence-based PCOS guideline recommends modified Rotterdam criteria (OA and HA) in adolescents based on expert consensus. We aimed to 1) compare the prevalence of PCOS using original and modified Rotterdam criteria in an unselected adolescent cohort and 2) explore the association between diagnostic phenotypes and long-term body mass index (BMI) trajectories. Methods: 227 adolescent females of the Western Australian Pregnancy Cohort (Raine) Study undertook detailed PCOS assessment at the mean age of 15.3 years (mean age of menarche 12.4 years). Detailed anthropometric measurements were collected from birth until age 22 years. T-test was used for group BMI comparisons and longitudinal BMI was analysed using Generalised Estimating Equations with PCOS by time and PCOS phenotypes by time as interaction terms. Results: PCOS was diagnosed in 66 (29.1%) participants using original Rotterdam criteria versus 37 (16.3%) participants using modified Rotterdam criteria. Using modified Rotterdam criteria, participants with PCOS had higher mean group BMI than participants without PCOS from age 5 years onwards. Significant interaction was detected between PCOS and time (p<0.001) on longitudinal BMI gain where higher BMI gain was observed in participants with PCOS from age 14 years onwards. Only the modified criteria phenotype was significantly associated wth long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories as participants without PCOS (p<0.001). Conclusions: Our findings validate the PCOS guideline recommendation as modified Rotterdam criteria reduce over-diagnosis of PCOS in adolescents and accurately identify the phenotype at risk of long-term weight gain. The BMI trajectories of females with and without PCOS diverge from early childhood suggesting that metabolic dysfunction in PCOS commences early in the pre-pubertal period. Disclosures: Nothing to disclose. Funding: PCOS CRE scholarship and Research Training Program Scholarship awarded to CT; NHMRC Medical Research Future fund awarded to HT; National Heart Foundation Future Leader Fellowship awarded to LM; NHMRC early career fellowship awarded to AJ.
MON-662 Diabetes Risk for Non-Obese Subjects in a Japanese Population
Authors: Tatsukawa Yoshimi , Kitamura Hiroko , Yamada Michiko , Ohishi Waka , Hida Ayumi , Yoneda Masayasu
Published: May 2020

[Background] Obesity is a major risk factor of developing diabetes and cardiovascular diseases, though not all obese people develop these conditions and diseases. Because Asian populations have a lower frequency of obesity in comparison with populations in the United States and Europe, it is important to detect risk factors for developing diabetes in non-obese Japanese populations. [Objectives] To examine risk factors for diabetes, and to consider countermeasures against diabetes development in Japanese populations, especially non-obese individuals. [Methods] This study examined 1,794 individuals (514 males and 1,280 females) who participated in both Adult Health Study health examinations on A-bomb survivors and their controls in Hiroshima and Nagasaki between 1994–1996 (baseline) and 2008–2011. They were aged 48–79 years and had not been diagnosed with diabetes at baseline or cancer. Obesity was defined as a BMI of 23 kg/m2 or greater based on the WHO recommendation for Asians. In accordance with AHA/NHLBI criteria for diagnosis of metabolic syndrome, we defined a diagnosis of metabolic abnormality as having at least two of the criteria other than abdominal obesity. The diagnostic criteria for diabetes were a fasting blood glucose ≥126 mg/dL, a non-fasting blood glucose ≥200mg/dL, a self-report of a diabetes diagnosis, or the initiation of medical treatment for diabetes during the follow-up period. We compared presences of fatty liver and metabolic abnormality, BMI at baseline, and changes of body weight from baseline between the group that developed diabetes and the group did not over a 15-year follow-up. [Results] During the follow-up period until 2001, 66 (7.0%) individuals and 127 individuals (14.8%) from the non-obese and obese groups, respectively, developed diabetes. BMI at baseline and presences of fatty liver and metabolic abnormality were associated with developing diabetes in both non-obese and obese groups. Changes in body weight from baseline were not a significant risk factor of diabetes in this study. Furthermore, we analyzed the association between diabetes risk and appendicular lean mass/height2 (ALM/H2) and handgrip strength based on the diagnostic criteria for sarcopenia among 676 subjects with information of these measurements at baseline. Occurrences of low ALM/H2 were associated with developing diabetes, but an association between low handgrip strength and developing diabetes was not observed. [Conclusion] Regardless of whether obesity was observed or not, presences of metabolic abnormality and fatty liver were significant risk factors. Increased risk of developing diabetes was observed among non-obese individuals with suspected sarcopenia. This study suggests that maintenance of muscle mass may be an effective countermeasure to reduce the risk of developing diabetes.
OR30-06 Assessment of Dulaglutide Safety in Older Patient Populations in Rewind
Authors: Konig Manige , Gerstein Hertzel C , Lakshmanan Mark C , Xavier Denis , Atisso Charles , Allen Sheryl , Cushman William C , Leiter Lawrence A , Raubenheimer Peter J , Franek Edward M
Published: May 2020

Background: Dulaglutide (DU) was superior to placebo (PL) in reducing the incidence of Major Adverse Cardiovascular Events in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND Study) broad patient population. The safety of DU treatment is also of interest to health care providers who treat an older patient population (≥65 years of age).

Aims: The primary objective of this post-hoc analysis was to evaluate DU safety in the REWIND patient subgroup populations categorized by age (≥ 65 and < 65 years) with regards to the occurrence of the composite safety outcome of overall mortality and severe hypoglycemia. One of the key secondary objectives was first occurrence of severe hypoglycemia.

Methods: Patients were grouped into two age groups: ≥65 and <65 years. Time-to-event for the composite safety endpoint as well as individual variables were analyzed using Cox proportional hazards regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for between group treatment differences were also calculated.

Results: Of the 9,901 patients randomized in REWIND, a total of 5,256 (DU, 2,619; PL, 2,637) were aged ≥65 years. The incidence of the composite safety outcome for patients aged ≥65 years was 399 of 2619 (15.2%) for DU-treated patients and 425 of 2,637 (16.1%) for PL-treated patients. The incidence of the composite safety outcome for those aged <65 years was 188 of 2,330 (8.1%) for DU-treated patients and 224 of 2,315 (9.7%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.94 (0.82, 1.08) for patients ≥65 years of age and 0.82 (0.68, 1.00) for patients <65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged ≥65 years was 46 of 2619 (1.8%) for DU-treated patients and 49 of 2,637 (1.9%) for PL-treated patients. The incidence of this outcome for patients <65 years was 18 of 2,330 (0.8%) for DU-treated patients and 25 of 2,315 (1.1%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.95 (0.63, 1.42) for patients ≥65 years of age and 0.71 (0.39, 1.31) for patients <65 years of age; interaction p-value = 0.443. The safety profile of DU was reviewed based upon the results of subgroup analysis of treatment emergent adverse events and serious adverse events by preferred terms for comparing PL and DU for age subgroups (≥65 years of age versus <65 years). None of the results indicated that DU has a different safety profile across the age subgroups evaluated in this post-hoc analysis.

Conclusions: Treatment with DU demonstrated similar safety in REWIND patients aged ≥65 years and those aged <65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.
MON-437 False Positive I-131 Uptake
Authors: Yadav Pavan Rajendra , Idea Raul J
Published: May 2020

Background

Iodine has high specificity for thyroid tissue hence it plays very important role is management for differentiated thyroid cancer. Despite its high specificity and sensitivity, false-positive I-131 uptake could be seen on whole body scan (WBS).

We are presenting a case of false positive intense uptake in lung due to bronchiectasis.

Clinical case

Patient is a 78-year-old Asian female who initially present with left sided 5.8 cm thyroid nodule. The fine needle aspiration was performed, and the cytology came back as Bethesda category III. Per our institute protocol a molecular mutation panel was sent, which came back with NRAS mutation.

She underwent total thyroidectomy and the histology showed 6.2 cm Follicular carcinoma with extensive angioinvasion, oncocyte type. She received adjuvant 165.2 mci of RAI. Per protocol she had a one-week I-131whole body scan.

There was intense abnormal uptake in left mid and upper chest. The stimulate thyroglobulin with a TSH of >100mcIU/ml was only 0.17 ng/dl with Tab negative.

Patient subsequently had a PET CT which showed a faint diffuse FDG activity noted in the cystic bronchiectasis predominantly in the left apex, lingula, and right middle lobe. Patient informed us that she has history of pulmonary tuberculosis in 1970’s for which she was successfully treated in her home country. We had 10-year-old chest X-ray which showed stable cystic bronchiectasis lesion in the region of intense uptake.

Discussion

Although I131 whole body scan has high specificity and sensitivity but physician should be aware of potential false positive uptake to avoid unnecessary intervention. In a retrospective evaluation i the most common non-thyroid conditions included were bronchiectasis, lung infection, subcutaneous injection into gluteal fatty tissue, aortic calcification, benign bone cyst, vertebral hemangioma, recent nonthyroidal surgical procedure site, rotator cuff injury, mature cystic teratoma and ovarian follicle cyst). The accumulation of the bronchial secretion is the proposed mechanism of the high false positive uptake in bronchiectasis.

Endnotes

i Mol Imaging Radionucl Ther 2018; 27:99–106 DOI:10.4274/mirt.37450