Reference Interval for Serum Concentration of Small Dense LDL Cholesterol in the Healthy Japanese Population

Background: Small dense low-density lipoprotein (sdLDL), a smaller and denser subfraction among whole LDL particles, is known to be highly atherogenic. The reference interval (RI) is not strictly defined for serum concentration of sdLDL-cholesterol (sdLDL-C) in Japan. The purpose of this study is to set the RI for sdLDL-C in healthy subjects. Methods: The population of this cross-sectional study were consisted of 40,862 individuals who had annual health checkups, and healthy subjects were extracted based on exclusion criteria such as medical history, social history, and blood sampling test results. Their serum sdLDL-C values were statistically analyzed and the RIs were set in men, premenopausal women, and postmenopausal women separately. Results: The mean values of serum sdLDL-C in healthy subjects were 23.9 mg/dL in men, 20.0 mg/dL in premenopausal women and 23.7 mg/dL in postmenopausal women, and the RIs were 12.6-45.3 mg/dL in men, 11.4-35.1 mg/dL in premenopausal women and 14.6-38.6 mg/dL in postmenopausal women. Serum sdLDL-C values were significantly higher in men than in women. Besides, sdLDL-C values were significantly higher in postmenopausal women than in premenopausal women. In both genders, sdLDL-C values tended to increase with age. Conclusion: These results suggest that the RIs for sdLDL-C are recommended as follows: 13-45 mg/dL in men, 11-35 mg/dL in premenopausal women, and 15-39 mg/dL in postmenopausal women, respectively. Aside from these RIs, it is also necessary to define clinical cutoff values graded according to individual risk levels for atherosclerotic cardiovascular diseases.

Serum Antithyroglobulin Antibody Levels Are Associated with Diabetic Retinopathy among Euthyroid Type 2 Diabetes Patients: A Hospital-Based, Retrospective Study

Background. Previous studies have revealed that the variation of thyroid indicators may be associated with the risk of diabetic retinopathy (DR) among euthyroid type 2 diabetes (T2D) patients. But the specific conclusions are currently inconsistent. Methods. This is a hospital-based retrospective survey. We recruited 1,145 euthyroid T2D patients and checked the thyroid function and fundus photographs. The modified Airlie House classification system was used to categorize the stages of DR. The association between thyroid indicators and different stages of DR was analyzed. Results. We divided free triiodothyronine (FT3) into tertiles and found that the prevalence of mild nonproliferative DR (NPDR) was significantly higher in T2, compared with T1 (32.0% vs. 25.2%, p < 0.05 ). When FT3 was within the level of T2, FT3 could be an independent risk factor for mild NPDR (OR 1.426, 95% CI (1.031, 1.971), p < 0.05 ). In addition, the prevalence of severe NPDR and proliferative DR (PDR) was significantly higher in thyroglobulin antibody (TgAb) positive group (8.8% vs. 4.1%, p < 0.05 ) and vice versa (33.3% vs. 18.4%, p < 0.05 ). TgAb positivity was also an independent risk factor for severe NPDR and PDR (OR 2.212, 95% CI (1.244, 3.934), p < 0.05 ). Conclusions. We hardly observed a significant change in DR risk with the elevation or reduction of serum TSH or thyroid hormone within the reference interval. Although the slightly elevated FT3 may be associated to mild NPDR, the extensibility of this result remains to be seen. For T2D patients with euthyroid function, there may be a significant correlation between serum TgAb positivity and severe NPDR and PDR.

Resuscitation Patterns and Massive Transfusion for the Critical Bleeding Dog—A Multicentric Retrospective Study of 69 Cases (2007–2013)

Objective: To describe resuscitation patterns of critically bleeding dogs, including those receiving massive transfusion (MT).Design: Retrospective study from three universities (2007–2013).Animals: Critically bleeding dogs, defined as dogs who received ≥ 25 ml/kg of blood products for treatment of hemorrhagic shock caused by blood loss.Measurements and Main Results: Sixty-nine dogs were included. Sources of critical bleeding were trauma (26.1%), intra/perioperative surgical period (26.1%), miscellaneous (24.6%), and spontaneous hemoabdomen (23.1%). Median (range) age was 7 years (0.5–18). Median body weight was 20 kg (2.6–57). Median pre-transfusion hematocrit, total protein, systolic blood pressure, and lactate were 25% (10–63), 4.1 g/dl (2–7.1), 80 mm Hg (20–181), and 6.4 mmol/L (1.1–18.2), respectively. Median blood product volume administered was 44 ml/kg (25–137.4). Median plasma to red blood cell ratio was 0.8 (0–4), and median non-blood product resuscitation fluid to blood product ratio was 0.5 (0–3.6). MT was given to 47.8% of dogs. Survival rate was 40.6%. The estimated odds of survival were higher by a factor of 1.8 (95% CI: 1.174, 3.094) for a dog with 1 g/dl higher total protein above reference interval and were lower by a factor of 0.6 (95% CI: 0.340, 0.915) per 100% prolongation of partial thromboplastin time above the reference interval. No predictors of MT were identified.Conclusions: Critical bleeding in dogs was associated with a wide range of resuscitation patterns and carries a guarded to poor prognosis.

Homoarginine test for evaluation of metabolic renal dysfunction

Low plasma L-homoarginine (hArg) concentration is an independent predictor of adverse cardiovascular outcomes and overall mortality, as well as the progression of chronic kidney disease (CKD). The enzyme L-arginine:glycinamidinotransferase (AGAT, EC 2.1.4.1) acts in the mitochondrial membrane of the renal tubular epithelium, forming the precursor of creatine, guanidinoacetic acid, and additionnaly by-product hArg. As it was shown recently, there is a decreased level of hArg in the late stages of CKD, however, the the level of hArg in the early stages of CKD remained unexplored. The aim of this study was to determine the diagnostic threshold levels of hArg in the blood of patients with stages 1 and 2 of CKD. In patients with the initial stages of CKD (n = 44) at the age of 58 (45-67) years, compared with the group of donors of 55 (42-58) years (n = 30), a significant decrease of hArg level was found. In the subgroup with stage CKD 2, the cut-off point of 1.59 μM threshold was characterized by greater sensitivity and specificity than in the subgroup with stage CKD 1 with 1.66 μM threshold level of hArg. For the full group, the hArg cut-off threshold was 1.60 μM, which is about to 0.2 μM lower than the lower limit of the reference interval for healthy individuals. It can be assumed that even before the formation of symptoms of proteinuria and albuminuria, a significant part of individuals from population cohort develops a state of decreased AGAT activity, since the expression of this enzyme is associated with a certain regulatory feedback inhibition at the body level. As a result of the study, it can be noted that in patients with early stages of CKD in the age group 45-67 years, there is a disturbance of the kidneys metabolic function. These metabolic changes can be detected by testing the level of hArg.

Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease

(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological diseases (n = 70) and controls (33). We measured CSF neurogranin levels by a commercial ELISA kit. CSF RI of neurogranin was calculated by a robust method; (3) Results: AD patients showed increased levels of neurogranin. We also found that neurogranin was significantly correlated with T-tau, P-tau and mini mental state examination in AD patients. The lower and upper reference limits of the RI were 2.9 (90%CI 0.1–10.8) and 679 (90%CI 595–779), respectively; (4) Conclusion: This is the first study establishing the RI of CSF neurogranin.

Resolution of Severe Neurologic Signs Following Intravenous Lipid Emulsion Therapy in a Young Dog With a Portosystemic Shunt: Case Report

A 5-month-old male intact Great Pyrenees was presented for an acute onset of severe neurologic signs (stupor, absent menace, intermittent head turn to the left). The patient's history included possible naproxen ingestion with a maximum ingested dose of 59 mg/kg, exceeding the reported dose of &gt;50 mg/kg known to cause neurologic signs. Blood sampling for baseline bloodwork was performed, and intravenous lipid emulsion (ILE) was subsequently administered, for treatment of the suspected toxicosis. Due to severe and life-threatening neurologic signs, other methods of decontamination were contraindicated and unlikely to be effective; extracorporeal therapy was also unavailable. Complete resolution of neurologic signs occurred 30 min after completion of ILE therapy. At this time, the owners found the missing naproxen tablets after returning home and the bloodwork results returned revealing findings consistent with hepatic encephalopathy. The fasted blood ammonia concentration immediately prior to ILE administration was 702.1 μg/dL (reference interval, RI: 24–36 μg/dL) and decreased to 194.1 μg/dL 24 h later. In the first 24 h, the patient also received three doses of lactulose, N-acetylcysteine, and intravenous fluids. The patient was subsequently diagnosed with a single, large intrahepatic portosystemic shunt via computed tomography and underwent an endovascular coil embolization procedure. Given the rapid and dramatic improvement in severe neurologic signs after ILE therapy alone, it is strongly suspected that this treatment resulted in improvement of hepatic encephalopathy.

Controlled drainage under two climate change scenarios in a flat high-latitude field

This simulation study focused on the hydrological effects of climate change and controlled drainage operated with subsurface drains and an open collector ditch in an agricultural field. The objective was to understand the potential of controlled drainage and open ditch schemes for managing groundwater levels and field water balance in climate conditions projected to take place in Finland during the 21st century with representative concentration pathways 8.5 and 2.6. A methodological aim was to find ways to condense hourly hydrological results to understand future changes in field hydrology. During the historical reference interval (1970–2005), controlled drainage caused 17–36 cm higher mean groundwater levels and decreased the mean annual drain discharge by 11–23% compared to conventional subsurface drainage. Controlled drainage was projected to increase groundwater levels by additional 1–4 cm in the future compared to its effect on drainage during the reference interval. The effect on annual drain discharge did not change significantly. The open collector ditch lowered groundwater tables and diminished the effect of controlled drainage on groundwater levels in the vicinity of the ditch. Controlled drainage was shown to remain an effective method for countering early summer drought and reducing drain discharge.

Reference interval for urinary neutrophil gelatinase-associated lipocalin in healthy adults in Jiangsu region in Eastern China: a multicenter study

Aim: We explored the concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL) in healthy adults in the Jiangsu region in Eastern China and established a reference interval using latex-enhanced immunoturbidimetry to provide important guidelines for the interpretation and application of urinary NGAL in clinical practice. Methods: In total, 1970 eligible subjects from four regions were included in this study. The urinary NGAL levels were measured using an AU5800 automatic biochemical analyzer with its matched reagents. The urinary NGAL reference interval was established using the one-sided percentile method (95th percentile). Results: The urinary NGAL data were non-normally distributed. The urinary NGAL levels were not significantly different by sex or age. Therefore, the urinary NGAL reference interval in healthy adults in the Jiangsu region in Eastern China was <87.5 ng/ml (95th percentile of the upper limit). Conclusion: Urinary NGAL reference interval will play an important role in promoting the clinical value of urinary NGAL.

Acute kidney injury in paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is not associated with progression to chronic kidney disease

BackgroundPaediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a rare complication of SARS-CoV-2 associated with single or multiorgan dysfunction.ObjectiveWe aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors for kidney dysfunction in PIMS-TS, with reporting of 6-month renal follow-up data. We also evaluated renal involvement between first and second waves of the SARS-CoV-2 pandemic in the UK, the latter attributed to the Alpha variant.DesignA single-centre observational study was conducted through patient chart analysis.SettingData were collected from patients admitted to Great Ormond Street Hospital, London, UK, between April 2020 and March 2021.Patients110 patients <18 years of age.Main outcome measureAKI during hospitalisation. AKI classification was based on upper limit of reference interval (ULRI) serum creatinine (sCr) values.ResultsAKI occurred in 33 (30%) patients. Hypotension/hypoperfusion was associated with almost all cases. In univariate analysis, the AKI cohort had higher peak levels of triglycerides (OR, 1.27 (95% CI, 1.05 to 1.6) per 1 mmol/L increase) and C reactive protein (OR, 1.06 (95% CI, 1.02 to 1.12) per 10 mg/L increase), with higher requirement for mechanical ventilation (OR, 3.8 (95% CI, 1.46 to 10.4)) and inotropic support (OR, 15.4 (95% CI, 3.02 to 2.81)). In multivariate analysis, triglycerides were independently associated with AKI stages 2–3 (adjusted OR, 1.26 (95% CI, 1.04 to 1.6)). At follow-up, none had macroalbuminuria and all had sCr values <ULRI. No discrepancy in renal involvement between pandemic waves was found.ConclusionDespite a high incidence of AKI in PIMS-TS, renal recovery occurs rapidly with current therapies, and no patients developed chronic kidney disease.