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Abstract Background Bronchoalveolar lavage (BAL) cytology results from 1 lung might not be representative of both lungs. Objectives To determine whether the lung site sampled would influence the horse's BAL cytology profile, and if a pooled BAL sample would be superior with regard to BAL cytology diagnosis in a cohort of healthy and subclinical asthmatic warmblood horses. Animals Fifty‐nine horses in 2021 and 70 horses in 2022, the follow‐up included 53 of the same in each year. Methods A cross‐sectional study with follow‐up included BAL cytology samples from individual lungs and from pooled BAL samples. The BAL samples were enumerated and differential cell count were applied to categorize the horses as control or with airway inflammation (AI). Results Bronchoalveolar lavage mast cell count was higher in left lung compared to right lung (2021; median 1.6 [range, 0.6‐3.3] vs 1.2 [0.7‐1.5] P = .009, 2022; median 3.1 [2.1‐4.2] vs 2.4 [1.7‐3.4], P

Abstract Two siblings were diagnosed with adult metachromatic leukodystrophy (MLD) and treated with hematopoietic stem cell transplantation (HSCT). While the older sibling was symptomatic at the time of diagnosis, her younger brother was diagnosed and transplanted at the presymptomatic state. We describe patients' clinical, biochemical, and genetic features, as well as neuropsychological and neurophysiological test results, and brain magnetic resonance imaging from pretransplantation and posttransplantation assessments. Both patients converted to complete donor chimerism and arylsulfatase A levels normalized 3 months posttransplantation. Twelve months posttransplantation, neurological and neuropsychological assessment for both patients showed stabilization, and they remained stable for the 38 months long observation period. To assess the effect of HSCT used as treatment for the rare, adult MLD subtype on survival and stabilization, we performed a systematic literature review and included 7 studies with a total of 26 cases. Of these 26 cases, 6 patients died of HSCT‐related complications and 2 patients had graft rejection. Of the remaining 18 patients, 2 patients improved after HSCT, 13 patients stabilized, and 3 patients progressed, suggesting that HSCT potentially benefits adult MLD patients. Larger studies focusing on this subtype are needed and recommendations on criteria for HSCT in adult MLD need to be evolved.

Objective. Adipose tissue (AT) macrophages are increased in obesity and associated with low grade inflammation. We aimed to characterize the phenotype of AT macrophages in humans in relation to obesity and insulin resistance. Design. Gene-expression levels of general macrophage markers (CD68 and CD14), proinflammatory markers/M1 (TNF-α, MCP-1, and IL-6), and anti-inflammatory markers/M2 (CD163, CD206, and IL-10) were determined by RT-PCR in subcutaneous AT samples from lean and obese subjects. Insulin resistance was determined by HOMA-IR. Results. All the macrophage markers were elevated in the AT from obese compared to lean subjects (P

Abstract Background Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age ≥ 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent. Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. Discussion For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

Abstract Seasonal changes affect the concentration of dust particles and aeroallergens in the equine stable environment and are hypothesized to change airway cytology in healthy stabled horses. The objective of the study was to evaluate if seasonal changes from May to November influenced the lower airway health cytological findings in clinically healthy stabled horses. Endoscopic examination, including tracheal aspiration (TA) and bronchoalveolar lavage (BAL) cytology was performed in November and May on 63 clinically healthy stabled Danish Warmblood geldings, aged 12.9 (±4.6) years. Tracheal aspiration and BAL cytology were evaluated via May-Grünwald-Giemsa stain after cytocentrifugation of samples. Five-hundred cells were identified microscopically as macrophages, lymphocytes, neutrophils, eosinophils, or mast cells. A significant difference in climatic conditions with lower temperatures (P <.001), fewer sunlight hours (P =.004), less precipitation (P =.006), and higher humidity (P <.001) was found in November compared to May. A significantly higher percentage of neutrophils (Median 6.10%, Quartiles 4.00–8.80, P <.001) and a higher tracheal mucus score (Median 3.50%, Quartiles 1.95–5.20, P =.010) were found during November compared to May period. Furthermore, a positive correlation between TA and BAL neutrophils was found for both sampling times. Mild winter weather conditions with lower temperatures, fewer minutes of sunlight, and a higher percent humidity were associated with significantly higher BAL neutrophil percentage and significantly higher mucus score in stabled clinical healthy horses. The clear seasonal influence on BAL neutrophilia and tracheal mucous findings in clinically normal horse needs to be included in the working diagnosis of asthma in horses. Highlights • Significant increase in tracheal mucus score in November compared to May • Significant increase in BAL neutrophils in November compared to May • Positive correlation between TA and BAL neutrophils • November sampling period had significant fewer hours of sun than May sampling period • November sampling period had significant higher humidity than May sampling period. [ABSTRACT FROM AUTHOR]

Background Fibroblast growth factor 21 (FGF21) is elevated in obesity. Objectives We investigated the circulating level of FGF21 and the expression of FGF21, beta-klotho (KLB), and FGF receptor 1 (FGFR1) in adipose tissue in relation to weight, fat distribution, and Roux-en-Y gastric bypass (RYGB)-induced weight loss. Setting The Department of Endocrinology at Aarhus University Hospital. Methods Thirty-one obese patients were enrolled. Visceral adipose tissue volume measured by magnetic resonance imaging, hepatic fat content measured by magnetic resonance spectroscopy, and body composition measured by dual-energy x-ray absorbtiometry were determined at baseline and 12 months after RYGB. Fasting blood samples and subcutaneous and visceral adipose tissue samples were obtained. Moreover, 25 lean controls were enrolled. Results FGF21 was significantly elevated in obese patients compared with lean patients (281±151 pg/mL versus 149±99 pg/mL, P <.05). RYGB-induced weight loss resulted in a smaller reduction in FGF21 ( P = .08). However, a significant reduction was seen in obese patients with initially high FGF21 levels (42% reduction, P <.001). A significant association was found between FGF21 and hepatic fat content at baseline (r = 0.40, P <.05). Moreover, ΔFGF21 was significantly associated with Δhepatic fat content after RYGB (r = 0.39, P <.05). FGF21 mRNA was not detectable in AT from either lean or obese patients. KLB and FGFR1 were upregulated in AT in relation to obesity, and both were further increased 12 months after RYGB. Conclusions FGF21 is reduced in relation to weight loss in patients with initial high levels of FGF21 and this reduction is significantly associated with a reduction in hepatic fat content. Thus, changes in FGF21 after RYGB-induced weight loss are closely related to changes in liver fat content. [ABSTRACT FROM AUTHOR]

• Evaluation of a new treatment option for mild equine asthma. • Included horses had bronchoalveolar lavage (BAL) cytological evidence of mild equine asthma. • A significant decrease in BAL neutrophils with treatment and controls was found. • A significant decrease in BAL mast cells with treatment and controls was found. Alternative treatment options to glucocorticoids for equine asthma is desirable due to withdrawal time. The objective was to evaluate if serum and Respiratory Gene Technology (RGT), a commercial kit to produce autologous conditioned serum, was effective in reducing bronchoalveolar lavage (BAL) neutrophils and mast cells in racehorses with cytological evidence of mild equine asthma. Thirty-six Standardbred trotters in active training were enrolled in this randomized clinical trial; a healthy control group (n=11), a RGT group (n=12) and a serum group (n=13). Endoscopy including tracheal wash (TW) and BAL was performed before (T0), after a 6-week treatment period including 12 intramuscular injections of RGT or serum (T6) and as a follow-up 10 weeks after treatment (T16). A significant decrease in BAL neutrophils for the RGT group was found between T0 and T6 (P =.002, d =-1.51, CI: -2.43;-0.59) and for the serum group between T0-T6 (P =.002, d =-1.36, CI: -2.26;-0.46). Further, a significant decrease in BAL mast cells between T0-T6 for the both the RGT group (P =.019, d =-1.23, CI: -1.22;-0.34) and the serum group (P =.004, d =-0.81, CI: -1.65;0.04), and further between T0-T16 (RGT P =.011, d =-1.55, CI: -2.62;-0.48; serum P =.044, d =-0.65, CI: -1.68;-0.37). No significant difference in TW cytology was found for any of the time-points. Pro- and anti-inflammatory cytokines were regulated according to treatment. The control group showed no cytological differences between any time-point. Study results showed that intramuscular treatment with both RGT and serum was effective associated with reduction of BAL neutrophils and mast cells in horses with cytological evidence of mild equine asthma. Further large-scale studies are necessary. [ABSTRACT FROM AUTHOR]

Flexion of the horse's head and neck during dressage riding reduces the pharyngeal lumen with the risk of increased upper airway resistance and upper airway obstructions. According to the Fédération Equestre Internationale, hyperflexion is achieved through force, whereas the position low–deep–round is nonforced. The objectives of this study were to evaluate (1) applied rein tension and (2) dynamic structural disorders in the upper airways in dressage horses in different gaits and different head–neck positions (HNPs). Overground endoscopy (OGE) and rein tension were evaluated in 13 clinically healthy and high-performance Warmblood dressage horses while being ridden in a standardized program comprised of four different gaits (halt, walk, trot, and canter) and in four HNPs (unrestrained, competition frame, hyperflexion, and low–deep–round). All included horses were able to achieve the desired HNPs. The HNP low–deep–round showed significantly lower rein tension than competition frame (P <.001) and hyperflexion (P <.001). An association was found between dynamic structural disorders in the upper airway tract evaluated by OGE and head–neck flexion, but this association was not linked to the degree of flexion. The HNP hyperflexion was neither associated with greater rein tension nor severe dynamic structural disorders than the HNP competition frame. This study confirms that low–deep–round is a nonforced position, in contrast to hyperflexion. Further studies are needed to evaluate whether dynamic structural disorders are a result of flexion or if the degree of flexion has an impact. • Rein tension does not differ between competition frame and hyperflexion. • Rein tension is lower in low–deep–round than in competition frame and hyperflexion. • Significant differences in rein tension were seen between gaits and riders. • Dynamic structural disorders were seen more often with head–neck flexion. [ABSTRACT FROM AUTHOR]

Objective: For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival., Design: Randomized controlled open-label trial., Setting: Nine multidisciplinary intensive care units across Denmark., Patients: A total of 1,200 critically ill patients were included after meeting the following eligibility requirements: expected intensive care unit stay of ≥ 24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive)., Interventions: : Patients were randomized either to the "standard-of-care-only arm," receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the "procalcitonin arm," in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements., Measurements and Main Results: The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval [CI] -4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0-6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15-1.27)., Conclusions: Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.

Background: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients., Methods: Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients., Discussion: For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

The effect of propranolol on renal haemodynamics was studied in nine patients with arterial hypertension and moderate to severe chronic renal failure. A reduction of the renal function in this type of patient might have clinical consequence. The patients, whose glomerular filtration rate (GFR) ranged between 17 ml/min/1.73 m2 and 71 ml/min/1.73 m2, were studied during three 4-week periods with alternately placebo, propranolol (40 mg b.i.d.) and placebo treatment. The GFR and the effective renal plasma flow (ERPF) were determined as the plasma clearance of 51Cr-EDTA and 125I-hippurane. The GFR fell on the average 7% (95% confidence limits: 1-12%) during propranolol treatment, and the fall was reversible. No changes were found in ERPF. In conclusion, propranolol treatment in this type of patient causes a modest and reversible fall of GFR.

In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

A method by which 51Cr-EDTA plasma clearance is determined from a single capillary blood sample (Clsc) was studied in 52 children less than 1 year old. The Clsc is calculated as the ratio between the injected dose and the total area under a transformed monoexponential function. The monoexponential curve is determined from the plasma activity 120 min after i.v. single injection of 51Cr-EDTA and a hypothetical initial activity calculated as the injected dose divided by the distribution space of 51Cr-EDTA. The distribution space was estimated from the body surface area. The rate constant of the monoexponential function is transformed by an empirically determined factor to make the area under the curve identical to the area under the true plasma disappearance curve. The Clsc was compared with 51Cr-EDTA plasma clearance (range 18-146 ml/min/1.73 m2) determined by a standard method from five capillary blood samples (Cl). The regression of Cl on Clsc did not differ from the line of identity, the SD being 5.9 ml/min/1.73 m2. In advanced renal failure the one-sample method is very sensitive to inaccuracies in the distribution space estimate and, accordingly, this method should be used only when the clearance value is predicted higher than 30 ml/min/1.73 m2.

Fourteen healthy women aged 21-41 years, who did not take oral contraceptives and who all had ovulatory cycles, were examined once in the follicular phase and once in the luteal phase of a single menstrual cycle. The glomerular filtration rate (51Cr-EDTA clearance) increased from the follicular to the luteal phase by a median of 7.0% (95% confidence interval: 0.7-10.3%). Endogenous overnight (22.00-08.00 hours) creatinine clearance increased by a median of 7.3% (95% confidence interval: 1.0-14.6%). The urinary creatinine excretion rate also increased with a median of 7.3% (95% confidence interval: 1.5-11.9%) whereas the serum concentrations of creatinine and beta 2-microglobulin, urine flow and urinary excretion rate of urea did not change. The results confirm previous observations of an increase in creatinine clearance in the luteal phase of the menstrual cycle and indicate that the increase in overnight creatinine clearance reflects a true change in glomerular filtration rate.