Non-Interventional Weight Changes Are Associated with Alterations in Serum Uric Acid Levels.

Background/Objectives: Serum uric acid is an established cardiovascular risk factor. Higher serum uric acid levels are associated with overweight and obesity. We assessed whether non-interventional weight changes affect serum uric acid levels. Methods: We performed a retrospective analysis of 19,193 participants referred to annual medical screening. Body mass index (BMI) and serum uric acid were measured annually. Subjects were divided into five groups according to changes in BMI between visits: large reduction (reduction of more than 5% in BMI), moderate reduction (reduction of more than 2.5% and 5% or less in BMI), unchanged (up to 2.5% change in BMI), moderate increase (increase of more than 2.5% and 5% or less in BMI), and large increase (increase of more than 5% in BMI). The primary outcome was serum uric acid level changes between visits. Results: A decrease in serum uric acid levels was evident as BMI decreased and an increase in serum uric acid levels was associated with an increase in BMI. The proportion of patients whose serum uric acid levels were increased by at least 10% between visits increased with the relative increase in BMI, while the proportion of patients whose serum uric acid levels were reduced by at least 10% decreased with the relative decrease in BMI. Conclusions: Non-interventional weight changes, even modest, are associated with significant alterations in serum uric acid levels. Our findings may aid in better risk stratification and the primary prevention of cardiovascular morbidity and mortality.

A 120-Minute Saline Infusion Test for the Confirmation of Primary Aldosteronism: A Pilot Study.

BACKGROUND: The saline infusion test (SIT) to confirm primary aldosteronism requires infusing 2 L of normal saline over 240 minutes. Previous studies raised concerns regarding increased blood pressure and worsening hypokalemia during SIT. We aimed to evaluate the diagnostic applicability of a SIT that requires 1 L of saline infusion over 120 minutes. METHODS: A cross-sectional study, including all patients in a large medical center who underwent SIT from 1 January 2015 to 30 April 2023. Blood samples were drawn for baseline renin and aldosterone (t = 0) after 2 hours (t = 120 min) and after 4 hours (t = 240 min) of saline infusion. We used ROC analysis to evaluate the sensitivity and specificity of various aldosterone cut-off values at t = 120 to confirm primary aldosteronism. RESULTS: The final analysis included 62 patients. A ROC analysis yielded 97% specificity and 90% sensitivity for a plasma aldosterone concentration (PAC) of 397 pmol/L (14 ng/dL) at t = 120 to confirm primary aldosteronism, and an area under the curve of 0.97 (95% CI [0.93, 1.00], P < 0.001). Almost half (44%) of the patients did not suppress PAC below 397 pmol/L (14 ng/dL) at t = 120. Of them, only one (4%) patient suppressed PAC below 276 pmol/L (10 ng/dL) at t = 240. Mean systolic blood pressure increased from 140.1 ±â€…21.3 mm Hg at t = 0 to 147.6 ±â€…14.5 mm Hg at t = 240 (P = 0.011). CONCLUSIONS: A PAC of 397 pmol/L (14 ng/dL) at t = 120 has high sensitivity and specificity for primary aldosteronism confirmation.

Nsaids Linked to IgA-Mediated Hypersensitivity Vasculitis and Purpura Fulminans-Like Eruption.

Background: IgA vasculitis and hypersensitivity reactions following exposure to non-steroidal anti-inflammatory drugs (NSAIDs) are very rarely associated with purpura fulminans (PF). The latter is a coagulation event characterised by decreased levels of protein C and a rapidly progressive purpuric rash, often leading to ischaemia, amputations and death. Case summary: A previously healthy 66-year-old man presented with a vasculitic rash and abdominal pain following exposure to naproxen (NSAID), which quickly deteriorated to purpura fulminans-like eruption and skin necrosis, mainly involving the face and hands. The presence of IgA sediments on skin biopsy and decreased levels of complement as well as protein C pointed to an immune-mediated inflammatory process. Dramatic clinical escalation with immediate risk to organs and life required an aggressive and broad-spectrum therapeutic approach in an intensive care setting. Clinical improvement and complete reconstitution of protein C were achieved following plasma exchange with fresh frozen plasma (FFP) and immunosuppression with glucocorticoids with no persistent organ damage. Conclusions: This rare case illustrates the catastrophic cross links between NSAIDs, IgA-mediated hypersensitivity vasculitis and purpura fulminans-like syndrome. A high index of suspicion is required for the evaluation of environmental exposures such as drugs and infections in patients with vasculitis and/or purpura. A rapid and comprehensive therapeutic approach should be implemented to avoid multi-organ damage, amputations and death. Complete avoidance of the offending agent is key for future prevention of recurrence. LEARNING POINTS: This case illustrates a rare cross link between a commonly used drug (NSAIDs) and severe, life-threatening hypersensitivity reactions (IgA vasculitis and purpura fulminans-like eruption).These events require a high index of suspicion and emphasise the importance of considering environmental exposures such as drugs in the immediate diagnosis of both conditions.In addition to long-term drug avoidance, early and aggressive interventions are required to avoid organ damage, amputations or death.

The association between adrenal adenoma size, autonomous cortisol secretion and metabolic derangements.

OBJECTIVE: Autonomous cortisol secretion (ACS) is common in patients with adrenal incidentalomas (AI). ACS is associated with increased cardiovascular morbidity and mortality. Data regarding the association between radiological characteristics of adrenal adenomas, their hormonal functionality and metabolic outcomes, are scarce and inconclusive. In this study, we aim to delineate the association between radiological characteristics of AI, ACS and metabolic status. METHODS: A cross-sectional study of 77 patients with AI who underwent a comprehensive hormonal evaluation. Radiological assessments were performed by an independent radiologist blinded to the clinical and hormonal phenotype of each case. Linear regression models were used to evaluate the association between post dexamethasone suppression test (DST) cortisol levels, metabolic indices and radiological measurements. RESULTS: Mean maximal adenoma diameter was greater in patients with versus without ACS (20.35 ± 6 vs. 27.09 ± 9.3 mm, respectively, p < .01). Maximal adenoma diameter was found to be positively and linearly correlated with post-DST morning cortisol levels across their entire range (R = .474, p < .01). Linear correlations between maximal adenoma diameter and indices of glycemic control showed a correlation coefficient (R) of .481 and .463 for fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c), respectively, p < .01. When analysis included only patients with ACS, an R = .584 and R = .565 was observed for FPG and HbA1c, respectively (p < .01 for both). The association between maximal adenoma diameter and both FPG and post-DST morning cortisol intensified in patients with metabolic syndrome. CONCLUSION: There is a quantitative positive mild correlation between AI size and both cortisol autonomy and metabolic parameters.

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019.

We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.

Evaluation of warm season annual forages for forage yield and quality in the north-central United States.

Grazing-based dairy operations require productive, high-quality forages capable of supporting the nutritional needs of mid-lactation dairy cows. Our objectives were to evaluate primary and regrowth harvests of two cultivars of sudangrass (SU), sorghum-sudangrass (S×SU), and pearl millet (PM) forages for growth and nutritive characteristics within the specific context of suitability for grazing by dairy cows. Three harvest cycles, including primary and regrowth cycles in 2016, and a single harvest cycle of primary growth in 2017, were evaluated at two locations (Prairie du Sac and Marshfield, WI). Within each cycle, sampling was initiated when canopy height was about 41 cm and continued thereafter on weekly intervals for 5 weeks, resulting in six equally spaced sampling dates per harvest cycle. Data were analyzed as a split-plot design with cultivars (6) as whole-plots arranged in randomized complete blocks and weekly harvest dates (6) as subplots. Yields of dry matter (DM) were less consistent at the more northern location (Marshfield), which is known for its heavier, poorly drained soils. Despite locational differences, the taller-growing cultivar within each forage type frequently exhibited yield advantages over dwarf or shorter-growing cultivars; this occurred for 7 of 9 intra-forage-type comparisons (P ≤ 0.021) across three harvest cycles at Prairie du Sac, and for 6 of 9 similar comparisons (P ≤ 0.032) at Marshfield. In 2016, shorter-growing cultivars had greater percentages of leaf in 4 of 6 intra-forage-type comparisons at both locations (P ≤ 0.004), which is especially relevant for grazing. Similarly, PM cultivars exhibited shorter canopy heights (P ≤ 0.002), but greater percentages of leaf (P < 0.001), than all other cultivars during all harvest cycles at both locations. However, the greater leaf percentages exhibited by PM cultivars did not translate into reduced percentages of structural plant fiber (asNDFom) on a whole-plant basis during any harvest cycle at either location; furthermore, asNDFom concentrations for PM cultivars were greater (P ≤ 0.047) than observed for other cultivars within 3 of 6 harvest cycles across both locations. Ruminal in-situ degradation of asNDFom for whole-plant forages based on a 48-h incubation was significantly greater (P ≤ 0.006) for PM compared with other cultivars in 4 of 6 harvest cycles. Pearl millet cultivars generally exhibited more suitable characteristics for grazing livestock than SU or S×SU cultivars.

The Quantitative Relationship Between Autonomous Cortisol Secretion, Dysglycemia and the Metabolic Syndrome.

OBJECTIVE: Autonomous cortisol secretion (ACS) is the most common endocrine abnormality in the evaluation of adrenal incidentalomas. The categorization of ACS is derived from a 1 mg dexamethasone suppression test (DST). Impaired DST is associated with several metabolic derangements. In this study we analyzed the association between post-DST cortisol level, analyzed as a continuous parameter, and indices of glycemic metabolism. METHODS: We prospectively collected data of 1,976 patients evaluated for adrenal incidentalomas in a large tertiary medical center between December 1, 2017, and August 31, 2019. Seventy-three patients completed the evaluation process. Post-DST cortisol levels were analyzed for correlation with various metabolic parameters, including fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) among the general cohort and for subgroups stratified by the number of metabolic syndrome (MS) criteria. RESULTS: Post-DST cortisol demonstrated a linear association with FPG and HbA1c across its entire cortisol range (R = 0.51 and 0.41, respectively; P≤.01). The association between post-DST cortisol and FPG was strengthened with an increased number of metabolic syndrome criteria. Patients with 4 MS criteria show a stronger association (R = 0.92) compared to patients with only a single criterion (R = 0.509). Furthermore, mean post-DST cortisol levels increased as the number of MS criteria accumulated. CONCLUSION: Post-DST cortisol should be viewed as a continuous parameter in risk stratification algorithms for the development of MS and particularly dysglycemia.

Common Laboratory Parameters for Differentiating Between Community-Acquired and Healthcare-Associated Pneumonia.

BACKGROUND AND OBJECTIVES: The correct diagnosis of healthcare-associated pneumonia (HCAP) as opposed to community-acquired pneumonia is essential for the selection of a correct empirical antimicrobial approach, reserving the broad-spectrum or highly potent antimicrobial therapies for resistant strains most commonly present in HCAP, whereas treating the less resistant strains, most commonly associated with community and long-term care facility-acquired infections, with a more targeted empirical approach. The standard approach today is to differentiate between the two based on the medical history of the past 90 days prior to admission. Measurable, quantitative assessment may be able to assist in this decision. The objective of this study is to find a measurable method of differentiating between community-acquired and healthcare-associated pneumonias. MATERIALS AND METHODS: The records of 126 patients admitted with a diagnosis of pneumonia were divided into two groups based on the probable cause of their disease, in accordance with common practice. The routine laboratory work taken upon admittance was analyzed using logistical regression and Student's t-test. RESULTS: We have found that the red blood cell distribution width and the neutrophil-to-lymphocyte ratio, both routine parameters obtained in a simple blood count, can each assist in differentiating between community-acquired and healthcare-associated pneumonias. CONCLUSION: We have found two statistically significant parameters that may be used as adjuncts to the medical history, chest radiography and other parameters in forming an immediate clinical impression of a patient presenting with pneumonia.

Centrobin regulates centrosome function in interphase cells by limiting pericentriolar matrix recruitment.

The amount of pericentriolar matrix at the centrosome is tightly linked to both microtubule nucleation and centriole duplication, although the exact mechanism by which pericentriolar matrix levels are regulated is unclear. Here we show that Centrobin, a centrosomal protein, is involved in regulating these levels. Interphase microtubule arrays in Centrobin-depleted cells are more focused around the centrosome and are less stable than the arrays in control cells. Centrobin-depleted cells initiate microtubule nucleation more rapidly than control cells and exhibit an increase in the number of growing microtubule ends emanating from the centrosome, while the parameters of microtubule plus end dynamics around the centrosome are not significantly altered. Finally, we show that Centrobin depletion results in the increased recruitment of pericentriolar matrix proteins to the centrosome, including γ-tubulin, AKAP450, Kendrin and PCM-1. We propose that Centrobin might regulate microtubule nucleation and organization by controlling the amount of pericentriolar matrix.

Traumatic events, other operational stressors and physical and mental health reported by Australian Defence Force personnel following peacekeeping and war-like deployments.

BACKGROUND: The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. METHODS: Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n = 1704) and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n = 1333). A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. RESULTS: The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled 'separation', 'different culture', 'other people' and 'work frustration'. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. CONCLUSION: Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations.

Risk of adverse health outcomes associated with frequency and duration of deployment with the Australian Defence Force.

The operational tempo of the Australian Defence Force has increased over the last two decades. We examine the relationship between health of personnel and the frequency and duration of their deployment. Self-reported health measures (number of symptoms, Kessler Psychological Distress Scale, and Post Traumatic Stress Disorder Checklist) were compared for people who had never deployed to those who had deployed only once and for those who had deployed at least twice with at least one deployment to East Timor and one deployment to Afghanistan or Iraq. Comparisons were also made between people who had deployed for at least one month and those who had deployed for longer periods. Frequency of deployment but not duration of deployment was associated with poorer health.

Living Well with Diabetes: a randomized controlled trial of a telephone-delivered intervention for maintenance of weight loss, physical activity and glycaemic control in adults with type 2 diabetes.

BACKGROUND: By 2025, it is estimated that approximately 1.8 million Australian adults (approximately 8.4% of the adult population) will have diabetes, with the majority having type 2 diabetes. Weight management via improved physical activity and diet is the cornerstone of type 2 diabetes management. However, the majority of weight loss trials in diabetes have evaluated short-term, intensive clinic-based interventions that, while producing short-term outcomes, have failed to address issues of maintenance and broad population reach. Telephone-delivered interventions have the potential to address these gaps. METHODS/DESIGN: Using a two-arm randomised controlled design, this study will evaluate an 18-month, telephone-delivered, behavioural weight loss intervention focussing on physical activity, diet and behavioural therapy, versus usual care, with follow-up at 24 months. Three-hundred adult participants, aged 20-75 years, with type 2 diabetes, will be recruited from 10 general practices via electronic medical records search. The Social-Cognitive Theory driven intervention involves a six-month intensive phase (4 weekly calls and 11 fortnightly calls) and a 12-month maintenance phase (one call per month). Primary outcomes, assessed at 6, 18 and 24 months, are: weight loss, physical activity, and glycaemic control (HbA1c), with weight loss and physical activity also measured at 12 months. Incremental cost-effectiveness will also be examined. Study recruitment began in February 2009, with final data collection expected by February 2013. DISCUSSION: This is the first study to evaluate the telephone as the primary method of delivering a behavioural weight loss intervention in type 2 diabetes. The evaluation of maintenance outcomes (6 months following the end of intervention), the use of accelerometers to objectively measure physical activity, and the inclusion of a cost-effectiveness analysis will advance the science of broad reach approaches to weight control and health behaviour change, and will build the evidence base needed to advocate for the translation of this work into population health practice. TRIAL REGISTRATION: ACTRN12608000203358.