Healthcare Challenges in the Management of Primary Aldosteronism in Southeast Asia.

OBJECTIVE: While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited healthcare access. Hence, we aimed to assess the availability and affordability of healthcare resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries. DESIGN: We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment. Population and income status data were taken from the national census and registries. RESULTS: Nine ASEAN country members (48 respondents) participated. While screening with aldosterone-renin-ratio is performed in all countries, confirmatory testing is routinely performed in only six countries due to lack of facilities and local assays, and cost constraint. Assays are only locally available in four countries, and some centers have a test turnaround time exceeding three weeks. In seven countries (combined population of 442 million), adrenal vein sampling (AVS) is not routinely performed due to insufficient radiological facilities or trained personnel, and cost constraint. Most patients have access to adrenalectomy and medications. In six countries, the cost of AVS and adrenalectomy combined is >30% of its annual gross domestic product per capita. While most patients had access to spironolactone, it was not universally affordable. CONCLUSION: Large populations currently do not have access to the healthcare resources required for the optimal management of PA. Greater efforts are required to improve healthcare access and affordability. Future guideline revisions for PA may need to consider these limitations.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

CONTEXT: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). OBJECTIVE: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. METHODS: Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. RESULTS: Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. CONCLUSION: In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Passive permeability controls synthesis for the allelochemical sorgoleone in sorghum root exudate.

Competition for soil nutrients and water with other plants foster competition within the biosphere for access to these limited resources. The roots for the common grain sorghum produce multiple small molecules that are released via root exudates into the soil to compete with other plants. Sorgoleone is one such compound, which suppresses weed growth near sorghum by acting as a quinone analog and interferes with photosynthesis. Since sorghum also grows photosynthetically, and may be susceptible to sorgoleone action if present in tissues above ground, it is essential to exude sorgoleone efficiently. However, since the P450 enzymes that synthesize sorgoleone are intracellular, the release mechanism for sorgoleone remain unclear. In this study, we conducted an in silico assessment for sorgoleone and its precursors to passively permeate biological membranes. To facilitate accurate simulation, CHARMM parameters were newly optimized for sorgoleone and its precursors. These parameters were used to conduct 1 µs of unbiased molecular dynamics simulations to compare the permeability of sorgoleone with its precursors molecules. We find that interleaflet transfer is maximized for sorgoleone, suggesting that the precursor molecules may remain in the same leaflet for access by biosynthetic P450 enzymes. Since no sorgoleone was extracted during unbiased simulations, we compute a permeability coefficient using the inhomogeneous solubility diffusion model. The requisite free energy and diffusivity profiles for sorgoleone through a sorghum membrane model were determined through Replica Exchange Umbrella Sampling (REUS) simulations. The REUS calculations highlight that any soluble sorgoleone would quickly insert into a lipid bilayer, and would readily transit. When sorgoleone forms aggregates in root exudate as indicated by our equilibrium simulations, aggregate formation would lower the effective concentration in aqueous solution, creating a concentration gradient that would facilitate passive transport. This suggests that sorgoleone synthesis occurs within sorghum root cells and that sorgoleone is exuded by permeating through the cell membrane without the need for a transport protein once the extracellular sorgoleone aggregate is formed.

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

INTRODUCTION: Primary Aldosteronism (PA) is a common cause of hypertension. However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with hypertension is characteristic of PA, and is an indication for screening. We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. METHODS: Our study included all PA patients with hypokalemia diagnosed between 2001 to 2022. Delayed diagnosis was defined as duration of hypokalemia of >1 year from first occurrence, to first evaluation by a PA specialist. Patients were reassessed post-adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. RESULTS: Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 (2.4-7.5) years. Patients with delayed diagnosis were older, had longer duration of hypertension, higher pill burden, lower renal function and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidaemia, and less severe hypokalemia (serum potassium >3.0mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%), P<0.05. Sixty of 118 (50.8%) non-delayed, and 39 of 122 (32.0%) patients with delayed diagnosis underwent surgery. CONCLUSION: Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in hypertension guidelines, and efforts to improve awareness of PA amongst primary care physicians are urgently needed.

Proton-pump inhibitor use amongst patients with severe hypomagnesemia.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.

Treatment of Primary Aldosteronism and Reversal of Renin Suppression Improves Left Ventricular Systolic Function.

Introduction: Primary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA. Methods: We prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment. Results: At baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by -2.3, 95% CI: -3.9 to -0.6, P = 0.010, and post-medications by -1.3, 95% CI: -2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e' (P = 0.006), whereas it was not statistically significant in patients treated with medications. Conclusion: Treatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03174847.

11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial.

OBJECTIVE: Adrenal vein sampling (AVS) is recommended to subtype primary aldosteronism, but it is technically challenging. We compared 11C-Metomidate-PET-computed tomography (PET-CT) and AVS for subtyping of primary aldosteronism. METHODS: Patients with confirmed primary aldosteronism underwent both AVS and 11C-Metomidate PET-CT (post-dexamethasone). All results were reviewed at a multidisciplinary meeting to decide on final subtype diagnosis. Primary outcome was accuracy of PET versus AVS to diagnosis of unilateral primary aldosteronism based on post-surgical biochemical cure. Secondary outcome was accuracy of both tests to final subtype diagnosis. RESULTS: All 25 patients recruited underwent PET and successful AVS (100%). Final diagnosis was unilateral in 22 patients, bilateral in two and indeterminate in one due to discordant lateralization. Twenty patients with unilateral primary aldosteronism underwent surgery, with 100% complete biochemical success, and 75% complete/partial clinical success. For the primary outcome, sensitivity of PET was 80% [95% confidence interval (95% CI): 56.3-94.3] and AVS was 75% (95% CI: 50.9-91.3). For the secondary outcome, sensitivity and specificity of PET was 81.9% (95% CI: 59.7-94.8) and 100% (95% CI: 15.8-100), and AVS was 68.2% (95% CI: 45.1-86.1) and 100% (95% CI: 15.8-100), respectively. Twelve out of 20 (60%) patients had both PET and AVS lateralization, four (20%) PET-only, three (15%) AVS-only, while one patient did not lateralize on PET or AVS. Post-surgery outcomes did not differ between patients identified by either test. CONCLUSION: In our pilot study, 11C-Metomidate PET-CT performed comparably to AVS, and this should be validated in larger studies. PET identified patients with unilateral primary aldosteronism missed on AVS, and these tests could be used together to identify more patients with unilateral primary aldosteronism. VIDEO ABSTRACT: http://links.lww.com/HJH/B918.

Acute Flaccid Tetraparesis after COVID-19 Infection: Think of the Thyroid.

A previously well 32-year-old Chinese male presented with acute bilateral upper and lower limb paralysis upon waking, ten days after the onset of COVID-19 infection. Examination revealed areflexia over all four limbs, associated with reduced muscle strength, but no sensory or cranial nerve deficit. Initial concern was Guillain-Barre syndrome given the acute flaccid paralysis following COVID-19 infection. However, investigations revealed severe hypokalaemia (1.7 mmol/L) and primary hyperthyroidism. He was treated for thyrotoxic periodic paralysis (TPP) with ß-blockers, antithyroid medications, and intravenous potassium chloride (KCl). Despite frequent monitoring of potassium, rebound hyperkalaemia occurred with prompt resolution of paralysis.

Primary Aldosteronism More Prevalent in Patients With Cardioembolic Stroke and Atrial Fibrillation.

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension, and patients are at an increased risk of atrial fibrillation (AF) and stroke. We assessed the prevalence of PA in patients with recent stroke. Methods: We recruited 300 patients admitted to an acute stroke unit with diagnosis of cerebrovascular accident (haemorrhagic/ischaemic) or transient ischaemic attack. Three months post-stroke, plasma renin and aldosterone were measured. Patients with an elevated aldosterone-renin ratio proceeded to the confirmatory saline loading test. Results: Twenty-six of 192 (14%) patients had an elevated aldosterone-renin ratio. Three of 14 patients who proceeded to saline loading were confirmed with PA (post-saline aldosterone >138 pmol/l). Another three patients were classified as confirmed/likely PA based on the markedly elevated aldosterone-renin ratio and clinical characteristics. The overall prevalence of PA amongst stroke patients with hypertension was 4.0% (95% confidence interval (CI): 0.9%-7.1%). Prevalence of PA was higher amongst patients with cardioembolic stroke, 11% (95% CI: 1.3%-33%), resistant hypertension, 11% (95% CI: 0.3%-48%), and hypertension and AF, 30% (95%CI: 6.7%-65%). If only young patients or those with hypokalaemia were screened for PA, half of our patients with PA would not have been diagnosed. Our decision tree identified that stroke patients with AF and diastolic blood pressure ≥83mmHg were most likely to have PA. Conclusion: We found that amongst hypertensive patients with stroke, PA was more prevalent in those with AF, or cardioembolic stroke. Screening for PA should be considered for all patients with stroke.

Tolerability and Efficacy of Long-Term Medical Therapy in Primary Aldosteronism.

INTRODUCTION: Patients with primary aldosteronism (PA) have increased cardiovascular risk, and there are concerns about the efficacy of medical therapy. OBJECTIVE: We aimed to assess long-term tolerability and efficacy of medical therapy in PA patients. METHODS: We conducted a retrospective study on 201 PA patients treated with medical therapy (spironolactone, eplerenone, or amiloride) from 2000 to 2020 at 2 tertiary centers. Clinical and biochemical control and side effects were assessed. RESULTS: Among 155 patients on long-term medications, 57.4% achieved blood pressure (BP) <140/90 mmHg, 90.1% achieved normokalemia (48.0% potassium ≥4.3 mmol/L), and 63.2% achieved renin >1 ng/mL/h. Concordance of biochemical control using potassium and renin levels was 49.1%. Side effects were experienced by 52.3% of patients, with 10.3% switching, 22.6% decreasing dose, and 11.0% stopping medications. Risk factors for side effects were spironolactone use, dose ≥ 50 mg, treatment duration ≥1 year, male gender, and unilateral PA. Patients with unilateral PA used higher spironolactone doses vs bilateral (57 vs 50 mg, P < 0.001) and had more side effects (63.2% vs 41.8%, P = 0.008). Forty-six unilateral PA patients who underwent surgery after initial medical therapy experienced improved BP (systolic from 141 to 135 mmHg, P = 0.045; diastolic from 85 to 79 mmHg, P = 0.002). CONCLUSION: Dose-dependent side effects limit efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. For unilateral PA, surgery remains preferable, yielding better control with less long-term side effects.

Measurement Properties of Patient-Reported Outcome Measures for Diabetes: Systematic Review.

BACKGROUND: The management of diabetes is complex. There is growing recognition of the use of patient-reported outcome measures (PROMs) as a standardized method of obtaining an outlook on patients' functional status and well-being. However, no systematic reviews have summarized the studies that investigate the measurement properties of diabetes PROMs. OBJECTIVE: Our aims were to conduct a systematic review of studies investigating the measurement properties of diabetes PROMs by evaluating the methodological quality and overall level of evidence of these PROMs and to categorize them based on the outcome measures assessed. METHODS: This study was guided by the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Relevant articles were retrieved from the Embase, PubMed, and PsychINFO databases. The PROMs were evaluated with the COSMIN (COnsensus-based Standards for the selection of health Measurement Instruments) guidelines. RESULTS: A total of 363 articles evaluating the measurement properties of PROMs for diabetes in the adult population were identified, of which 238 unique PROMs from 248 studies reported in 209 articles were validated in the type 2 diabetes population. PROMs with at least a moderate level of evidence for ≥5 of 9 measurement properties include the Chinese version of the Personal Diabetes Questionnaire (C-PDQ), Diabetes Self-Management Instrument Short Form (DSMI-20), and Insulin Treatment Appraisal Scale in Hong Kong primary care patients (C-ITAS-HK), of which the C-PDQ has a "sufficient (+)" rating for >4 measurement properties. A total of 43 PROMs meet the COSMIN guidelines for recommendation for use. CONCLUSIONS: This study identified and synthesized evidence for the measurement properties of 238 unique PROMs for patients with type 2 diabetes and categorized the PROMs according to their outcome measures. These findings may assist clinicians and researchers in selecting appropriate high-quality PROMs for clinical practice and research. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020180978; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020180978.

Special Operations Medics Test the Novel iView Video Laryngoscope: A Prospective, Randomized, Crossover Trial.

BACKGROUND: Airway compromise is the second leading cause of preventable death on the battlefield. Special operations medic comprise the majority of medics trained to perform endotracheal intubation (ETI), mostly by way of direct laryngoscopy (DL). The iView is a disposable, low-cost video laryngoscopy (VL) device, enabling its distribution to prehospital medical providers. We seek to compare time to intubation between DL and iView VL among special operations combat medics (SOCM). METHODS: We conducted a prospective, randomized, crossover trial. We enrolled special operations medics assigned to Joint Base Lewis McChord, WA. We randomized subjects to first performing VL or DL. Subjects performed a total of 10 ETI, 5 by VL and 5 by DL, on adult airway manikins. The primary outcome was time (in seconds) for ETI completion. RESULTS: A total of 32 medics completed 160 with DL ETIs and 160 VL ETIs. A total of 10 of 32 (31.3%) medics reported no previous experience with VL devices. We found a significant difference in time to intubation between VL and DL (20.4 (95% CI 20.6 - 26.1) seconds versus 23.4 (95% CI 18.7 - 22.2) seconds; p = 0.03) in favor of VL. All VL attempts were successful while 96.9% of DL were successful (p = 0.10). With respect to end-user appraisal of devices, a significant number of medics preferred the iView VL over DL (23 versus 9; p is less than 0.00001). Additionally, medics considered iView VL easier to use (5 [5-6] versus 5 [4-5]; p=0.0004) and easier to learn, remember, and perform by combat medics (5 [5-5] versus 4 [4-5]; p=0.008). CONCLUSIONS: Special operations medics naïve to VL rapidly learned how to effectively utilize iView VL, as evidenced by a significant difference in time to intubation in favor of iView VL. Additionally, most medics favored iView VL and considered it easy to use, learn, and remember.

Re-evaluating absent clinical success after adrenalectomy in unilateral primary aldosteronism.

BACKGROUND: Adrenalectomy cures unilateral primary aldosteronism, and it improves or cures hypertension. However, a significant proportion of patients are classified with absent clinical success postsurgery, suggesting that surgery was ineffective. METHODS: We assessed all patients 6 to 12 months post-surgery for clinical outcomes using Primary Aldosteronism Surgical Outcomes (PASO), AVIS-2, and CONNsortium criteria. We estimated blood pressure changes after adjustment for changes in defined daily dosages of antihypertensive medications. We also reassessed all patients using PASO at their recent clinical visit. RESULTS: A total of 104 patients with unilateral primary aldosteronism underwent adrenalectomy at 2 tertiary centers from 2000 to 2019; 24 (23%), 31 (30%), and 54 (52%) patients were classified with absent clinical success using PASO, AVIS-2, and CONNsortium criteria, respectively. Among 24 patients with absent clinical success using PASO criteria, 10 had complete biochemical cure, 3 partial, 2 absent, and 9 had resolution of hypokalemia. On multivariable analysis, absent clinical success was associated with presence of hyperlipidemia, diabetes mellitus, and lower defined daily dosages at baseline. After adjustment for changes in defined daily dosages, 7 of 24 patients showed blood pressure improvement ≥20/10 mm Hg post-surgery. After a follow-up of mean 5.6 years, 12 of 24 patients showed partial or complete clinical success when reassessed using PASO criteria. Only 6 of 104 (5.8%) patients failed to show clinical improvement post-surgery using any of the 3 mentioned criteria or using PASO criteria at their recent clinical visit. CONCLUSION: Although some patients may be classified with absent clinical success post-surgery, the assessment of clinical outcomes remains subject to many variables. In patients with unilateral primary aldosteronism, evidenced by lateralization on AVS, unilateral adrenalectomy should remain the recommended treatment.

Outcomes in unilateral primary aldosteronism after surgical or medical therapy.

CONTEXT: Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. OBJECTIVE: To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. DESIGN: Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. PATIENTS: 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. MEASUREMENTS: Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. RESULTS: Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32-2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0-2.0) versus 2.6 (IQR 0.8-4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery. CONCLUSION: In patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.

Relationships of Bone Mineral Density to Whole Body Mass, Fat Mass and Fat-free Mass in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood.

Body size influences bone mineral density (BMD) in health. Relationships of BMD with body mass index, fat mass (FM), fat-free mass, and appendicular lean mass were explored in acute lymphoblastic leukemia (ALL) survivors (n=75; 41 males; 45 standard risk ALL) >10 years from diagnosis. Dual energy radiograph absorptiometry performed body composition analysis. Relationships were assessed by regression analyses and Pearson correlation coefficients (r). Twenty subjects (26.3%) were osteopenic; lumbar spine (LS) BMD Z score <-1.00. Age at diagnosis, sex, ALL risk-category, type of post-induction steroid or cranial radiation did not correlate with LS or whole body (WB) BMD. Body mass index correlated significantly with LS BMD (r=0.333, P=0.004) and WB BMD (r=0.271, P=0.033). FM index (FM/height²) Z score showed no significant correlation with LS or WB BMD. Fat-free mass index Z score correlated strongly with LS BMD (r=0.386, P=0.013) and WB BMD (r=0.605, P<0.001) in males but not in females. The appendicular lean mass index, a surrogate for skeletal muscle mass, correlated significantly with LS BMD (r=0.367, P=0.018) and WB BMD (r=0.604, P<0.001) in males but not in females. Future studies to evaluate interventions to enhance BMD focused on improving body composition particularly skeletal muscle mass are warranted.

COVID-19 and Undiagnosed Pre-diabetes or Diabetes Mellitus Among International Migrant Workers in Singapore.

Objective: Migrant workers, a marginalized and under-resourced population, are vulnerable to coronavirus disease 2019 (COVID-19) due to limited healthcare access. Moreover, metabolic diseases-such as diabetes mellitus (DM), hypertension, and hyperlipidemia-predispose to severe complications and mortality from COVID-19. We investigate the prevalence and consequences of undiagnosed metabolic illnesses, particularly DM and pre-diabetes, in international migrant workers with COVID-19. Methods: In this retrospective analysis, we analyzed the medical records of international migrant workers with laboratory-confirmed COVID-19 hospitalized at a tertiary hospital in Singapore from April 21 to June 1, 2020. We determined the prevalence of DM and pre-diabetes, and analyzed the risk of developing complications, such as pneumonia and electrolyte abnormalities, based on age and diagnosis of DM, and pre-diabetes. Results: Two hundred and fouty male migrant workers, with mean age of 44.2 years [standard deviation (SD), 8.5years], were included. Twenty one patients (8.8%) were diagnosed with pre-diabetes, and 19 (7.9%) with DM. DM was poorly controlled with a mean HbA1c of 9.9% (SD, 2.4%). 73.7% of the patients with DM and all the patients with pre-diabetes were previously undiagnosed. Pre-diabetes was associated with higher risk of pneumonia [odds ratio (OR), 10.8, 95% confidence interval (CI), 3.65-32.1; P < 0.0001], hyponatremia (OR, 8.83; 95% CI, 1.17-66.6; P = 0.0342), and hypokalemia (OR, 4.58; 95% CI, 1.52-13.82; P = 0.0069). Moreover, patients with DM or pre-diabetes developed COVID-19 infection with lower viral RNA levels. Conclusions: The high prevalence of undiagnosed pre-diabetes among international migrant workers increases their risk of pneumonia and electrolyte abnormalities from COVID-19.

Bilateral Aldosterone Suppression in Patients With Right Unilateral Primary Aldosteronism and Review of the Literature.

INTRODUCTION: Adrenal vein sampling (AVS) identifies unilateral primary aldosteronism but may occasionally show paradoxically low aldosterone-cortisol ratios bilaterally. Postulated reasons include venous anomalies, fluctuating aldosterone secretion, or superselective cannulation. We report our findings in patients who underwent repeat AVS and reviewed the current literature. METHODS: We performed a retrospective observational study of patients undergoing AVS in an experienced high-volume tertiary center over a 5-year period. RESULTS: From 2015 to 2019, 61 patients underwent sequential cosyntropin-stimulated AVS and all had bilateral successful cannulation (100%). Four of 61 (6.6%) patients had bilaterally low aldosterone-cortisol ratios. Three patients underwent repeat AVS, with all 3 cases demonstrating right-sided lateralization and cure of disease postadrenalectomy. Right-sided disease was also more common in other reports. This may be due to inadvertent superselective cannulation of the short right adrenal vein, resulting in sampling of the adjacent normal gland. Cortisol results cannot detect this problem. In 1 patient, computed tomography venography excluded any accessory right adrenal veins. In another patient, repeat bilateral simultaneous unstimulated AVS was done, and measurements of metanephrines aided in accurately identifying right-sided lateralization. CONCLUSION: In addition to technical difficulties in cannulating the right adrenal vein, we also have to avoid performing superselective cannulation inadvertently. In cases of inconclusive AVS, repeat sampling may identify patients with potentially curable unilateral primary aldosteronism. The role of corticotropin stimulation and metanephrines measurements during repeat AVS requires further study.

Understanding contemporary forms of exploitation: Attributions of passion serve to legitimize the poor treatment of workers.

The pursuit of passion in one's work is touted in contemporary discourse. Although passion may indeed be beneficial in many ways, we suggest that the modern cultural emphasis may also serve to facilitate the legitimization of unfair and demeaning management practices-a phenomenon we term the legitimization of passion exploitation. Across 7 studies and a meta-analysis, we show that people do in fact deem poor worker treatment (e.g., asking employees to do demeaning tasks that are irrelevant to their job description, asking employees to work extra hours without pay) as more legitimate when workers are presumed to be "passionate" about their work. Of importance, we demonstrate 2 mediating mechanisms by which this process of legitimization occurs: (a) assumptions that passionate workers would have volunteered for this work if given the chance (Studies 1, 3, 5, 6, and 8), and (b) beliefs that, for passionate workers, work itself is its own reward (Studies 3, 4, 5, 6, and 8). We also find support for the reverse direction of the legitimization process, in which people attribute passion to an exploited (vs. nonexploited) worker (Study 7). Finally, and consistent with the notion that this process is connected to justice motives, a test of moderated mediation shows this is most pronounced for participants high in belief in a just world (Study 8). Taken together, these studies suggest that although passion may seem like a positive attribute to assume in others, it can also license poor and exploitative worker treatment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aldosterone-potassium ratio predicts primary aldosteronism subtype.

OBJECTIVE: Prediction models have been developed to predict either unilateral or bilateral primary aldosteronism, and these have not been validated externally. We aimed to develop a simplified score to predict both subtypes and validate this externally. METHODS: Our development cohort was taken from 165 patients who underwent adrenal vein sampling (AVS) in two Asian tertiary centres. Unilateral disease was determined using both AVS and postoperative outcome. Multivariable analysis was used to construct prediction models. We validated our tool in a European cohort of 97 patients enrolled in the SPARTACUS trial who underwent AVS. Previously published prediction models were also tested in our cohorts. RESULTS: Backward stepwise logistic regression analysis yielded a final tool using baseline aldosterone-to-lowest-potassium ratio (APR, ng/dl/mmol/l), with an area under receiver-operating characteristic curve of 0.80 (95% CI 0.70-0.89). In the Asian development cohort, probability of bilateral disease was 90.0% (with APR <5) and probability of unilateral disease was 91.4% (with APR >15). Similar results were seen in the European validation cohort. Combining both cohorts, probability of bilateral disease was 76.7% (with APR <5), and probability for unilateral was 91.7% (with APR >15). Other models had similar predictive ability but required more variables, and were less sensitive for identifying bilateral PA. CONCLUSION: The novel aldosterone-to-lowest-potassium ratio is a convenient score to guide clinicians and patients of various ethnicities on the probability of primary aldosteronism subtype. Using APR to identify patients more likely to benefit from AVS may be a cost-effective strategy to manage this common condition.