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.

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.

Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease.

BACKGROUND: The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. METHODS: In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. RESULTS: A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. CONCLUSIONS: In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques.

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated.

Body composition in long-term survivors of acute lymphoblastic leukemia diagnosed in childhood and adolescence: A focus on sarcopenic obesity.

BACKGROUND: The late effects of treatment for acute lymphoblastic leukemia (ALL) include disordered body composition, especially obesity. Less attention has been focused on the loss of skeletal muscle mass (SMM) and the combined morbidity of sarcopenic obesity. METHODS: A cross-sectional study of body composition was undertaken via dual-energy x-ray absorptiometry in 75 long-term survivors of ALL (more than 10 years after the diagnosis). Measures were obtained of the fat mass (FM), fat-free mass (equivalent to the lean body mass [LBM]), and whole-body bone mineral content. Health-related quality of life (HRQL) was measured with the Health Utilities Index. RESULTS: The sum of the FM, LBM, and whole-body bone mineral content matched the total body weight measured directly (r = 0.998). The appendicular lean mass (ALM) was derived from the LBM in all 4 limbs and accounted for approximately 75% of the SMM. According to the fat mass index (FMI; ie, FM/height2 ), 12% of females and 18% of males were frankly obese by World Health Organization criteria. The median FMI z score was + 0.40, whereas the median z score for the appendicular lean mass index (ALMI; ie, ALM/height2 ) was -0.40. Sarcopenic obesity, defined as a positive FMI z score with a negative ALMI z score, was present in 32 subjects (43%). There were statistically significant and clinically important differences in overall HRQL between subjects with and without sarcopenic obesity. CONCLUSIONS: Sarcopenic obesity is prevalent in long-term survivors of ALL, and this places them in double jeopardy from excess body fat and inadequate SMM (eg, a combination of metabolic and frailty syndromes). It is associated with an adverse impact on overall HRQL. Cancer 2018;124:1225-31. © 2017 American Cancer Society.

AXIAL BMD IN DIABETIC AND NONDIABETIC SOUTHEAST ASIANS WITH HIP FRACTURES: DO RACE AND BODY MASS INDEX MATTER?

OBJECTIVE: Obesity is less prevalent in Asian subjects with type 2 diabetes mellitus (T2DM) in contrast to Caucasians. Whether higher axial bone mineral density (BMD) often reported in T2DM is independent of body mass index (BMI) has not been clearly shown. BMD characterization in T2DM patients with hip fractures has also not been performed. We compared the BMD of Asian diabetic and nondiabetic patients with new hip fractures and explored how BMD was influenced by BMI. METHODS: We included 255 diabetic and 148 nondiabetic patients. BMD adjusted for age; BMI; race; sex; renal function; and use of statins, proton pump inhibitors, steroids, anticonvulsants, and calcium and/or vitamin D supplements were compared between the groups. We were particularly interested in the BMD comparison between underweight diabetics and nondiabetics with hip fractures. RESULTS: The presence of T2DM was associated with higher BMD (g/cm(2)) at the femoral neck (0.527 ± 0.103 vs. 0.491 ± 0.102, P<.01) and lumbar spine [LS] (0.798 ± 0.147 vs. 0.723 ± 0.156, P<.01). This association persisted after adjustment for multiple confounding variables including BMI. The age-, BMI-, and sex-adjusted LS BMD was higher in underweight (BMI <18.5 kg/m(2)) diabetics compared to similar weight nondiabetics (0.733 ± 0.126 vs. 0.649 ± 0.131 g/cm(2), P = .014). CONCLUSION: T2DM is independently associated with higher axial BMD in patients with new hip fractures. The finding of higher BMD even in underweight diabetics with hip fractures compared to their nondiabetic counterparts suggests that higher BMD in subjects with T2DM is not due to higher BMI. ABBREVIATIONS: BMD = bone mineral density BMI = body mass index CV = coefficient of variation DXA = dual-energy X-ray absorptiometry HbA1c = glycated hemoglobin IGF-1 = insulin growth factor-1 LS = lumbar spine 25(OH)D = 25-hydroxyvitamin D T2DM = type 2 diabetes mellitus.

Dichloroacetate induces autophagy in colorectal cancer cells and tumours.

BACKGROUND: Dichloroacetate (DCA) has been found to have antitumour properties. METHODS: We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 Bax-ko), prostate carcinoma cells (PC3) and HT29 xenografts by flow cytometry, western blotting, electron microscopy, (1)H and hyperpolarised (13)C-magnetic resonance spectroscopy. RESULTS: Increased expression of the autophagy markers LC3B II was observed following DCA treatment both in vitro and in vivo. We observed increased production of reactive oxygen species (ROS) and mTOR inhibition (decreased pS6 ribosomal protein and p4E-BP1 expression) as well as increased expression of MCT1 following DCA treatment. Steady-state lactate excretion and the apparent hyperpolarised [1-(13)C] pyruvate-to-lactate exchange rate (k(PL)) were decreased in DCA-treated cells, along with increased NAD(+)/NADH ratios and NAD(+). Steady-state lactate excretion and k(PL) returned to, or exceeded, control levels in cells recovered from DCA treatment, accompanied by increased NAD(+) and NADH. Reduced k(PL) with DCA treatment was found in HT29 tumour xenografts in vivo. CONCLUSIONS: DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased NAD(+)/NADH ratio. The observed cellular and metabolic changes recover on cessation of treatment.

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.

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.

Health Care Challenges in the Management of Primary Aldosteronism in Southeast Asia.

CONTEXT: While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited health care access. OBJECTIVE: We aimed to assess the availability and affordability of health care resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries. METHODS: 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 6 countries due to lack of facilities and local assays, and cost constraint. Assays are locally available in only 4 countries, and some centers have a test turnaround time exceeding 3 weeks. In 7 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 6 countries, the cost of AVS and adrenalectomy combined is more than 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 health care resources required for the optimal management of PA. Greater efforts are required to improve health care access and affordability. Future guideline revisions for PA may need to consider these limitations.

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.

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.

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.

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.

Temozolomide for corticotroph pituitary adenomas refractory to standard therapy.

To highlight the potential of temozolomide (TMZ) to induce rapid tumor regression in patients with aggressive corticotroph adenomas (CA) that are refractory to surgery and radiation therapy and to review use of TMZ in other pituitary tumors. We present a case of a 56-year-old male with a 3 cm CA treated with transphenoidal surgery (TSS) and conventional radiotherapy in the same year. His hypercortisolemia recurred 11 years later with rapid tumor growth (to 4.2 × 2.5 cm) and he underwent a second TSS with good resection. The tumor recurred 6 months later with ophthalmoplegia. Over 16 months he underwent an additional three surgeries (two TSS, one craniotomy) and repeated conventional radiotherapy. Ki67 staining index on surgical specimens was 5-6%. Temozolomide is an oral alkylating agent approved for glioblastoma multiforme treatment that has only recently shown promise in treating some pituitary tumors. In this patient TMZ was started at 150 mg/m²/day, titrated to 200 mg/m²/day, taken 5 days per month. The only significant side effect was moderate nausea. After 10 weeks, the tumor showed a remarkable 60% regression with objective improvement in ophthalmoplegia. Treatment of aggressive CAs represents a therapeutic challenge and in some cases surgical debulking and radiotherapy are of limited success. Few reports of CAs responsive to TMZ have been reported in the literature. To our knowledge, this case represents the most rapid robust CA shrinkage response reported to date. Further randomized clinical trials of TMZ in the treatment of aggressive pituitary adenomas are warranted.

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.