Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients.

INTRODUCTION: Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes. METHODS: Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength. RESULTS: Out of 59 hemodialysis patients (65 ± 15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9 g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P < 0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P = 0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std ß: -0.34 [-0.59;-0.09];P = 0.009), lower vitality (std ß: -0.30 [-0.55;-0.05];P = 0.02), and more fatigue (std ß: 0.32 [0.07;0.57];P = 0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase. CONCLUSION: Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.

Applications of deep convolutional neural networks to predict length, circumference, and weight from mostly dewatered images of fish.

Simple biometric data of fish aid fishery management tasks such as monitoring the structure of fish populations and regulating recreational harvest. While these data are foundational to fishery research and management, the collection of length and weight data through physical handling of the fish is challenging as it is time consuming for personnel and can be stressful for the fish. Recent advances in imaging technology and machine learning now offer alternatives for capturing biometric data. To investigate the potential of deep convolutional neural networks to predict biometric data, several regressors were trained and evaluated on data stemming from the FishL™ Recognition System and manual measurements of length, girth, and weight. The dataset consisted of 694 fish from 22 different species common to Laurentian Great Lakes. Even with such a diverse dataset and variety of presentations by the fish, the regressors proved to be robust and achieved competitive mean percent errors in the range of 5.5 to 7.6% for length and girth on an evaluation dataset. Potential applications of this work could increase the efficiency and accuracy of routine survey work by fishery professionals and provide a means for longer-term automated collection of fish biometric data.

Pulmonary arterial hypertension screening practices in scleroderma patients among Canadian rheumatologists.

Background: Current international guidelines recommend annual screening for pulmonary arterial hypertension with transthoracic echocardiogram and pulmonary function testing in all patients with scleroderma (systemic sclerosis). Our objectives were to determine Canadian rheumatologists' screening practices for pulmonary arterial hypertension in patients with systemic sclerosis and identify reasons why current guideline recommendations may not be followed. Methods: A survey was emailed to all Canadian Rheumatology Association members. They self-identified as systemic sclerosis experts or non-experts and provided basic demographic data. Participants were asked how frequently they screened with transthoracic echocardiogram and pulmonary function testing and, if applicable, why they did not adhere to recommendations. Results: A total of 71 rheumatologists participated, of whom 43 identified as non-experts. Overall, 81.4% ordered annual transthoracic echocardiogram and 77.6% annual pulmonary function testing. Rates of annual transthoracic echocardiogram testing were similar between experts and non-experts, whereas experts ordered annual pulmonary function testing more often. Clinicians with a higher proportion of systemic sclerosis patients in their practice were more likely to follow guidelines. There was an inverse relationship between years in practice and adherence to screening guidelines. The most common reason for not following screening guidelines was disagreement with recommendations, followed by unfamiliarity with guidelines. Conclusions: Pulmonary arterial hypertension screening rates remain sub-optimal in Canada but have improved since 2012. Failure to adopt guidelines is due to rheumatologists disagreeing with or not knowing current recommendations. Future studies should examine why rheumatologists disagree with guidelines and how to improve awareness.

ANCA-associated pauci-immune glomerulonephritis in a patient with bacterial endocarditis: a challenging clinical dilemma.

PURPOSE: We report the case of a 59-year-old man with chronic hepatitis B and C infection presenting with acute kidney injury and enterococcus faecalis-infective endocarditis (IE). An elevated proteinase-3 (PR3)-ANCA and pauci-immune glomerulonephritis (GN) on renal biopsy were discovered, corresponding to ANCA-mediated GN. We conducted a literature review to assess the role of ANCA in IE and treatment implications. METHODS: On systematic review of the literature, we found five previous cases whereby IE caused by streptococcus and bartonella species were related to ANCA vasculitis-associated GN. RESULTS: Most reports of IE-related GN are mediated by immune complex deposition and resolve following microbial clearance. Of the 5 cases of ANCA GN in the setting of IE, all had markedly elevated levels of PR3-ANCA with either a subacute or chronic course of infection. Patients were treated with a combination of steroids and cyclophosphamide (2/5), steroids and antibiotics alone (1/5), or with valvular replacement (2/5). Renal function was recovered in 4/5 patients. CONCLUSION: Infection is a major etiologic player in the formation of ANCA; however, the role of PR3-ANCA in IE remains unclear. Kidney biopsy is essential in differentiating IE-related GN due to infection and immune complex deposition versus ANCA-associated vasculitis. A paucity of reports on the development of GN in IE-associated ANCA vasculitis exists, highlighting the rarity of our case and lack of clear therapeutic strategies in a patient with active infection requiring immunosuppression. In this case, the patient's chronic hepatitis B and C coinfection presented a unique challenge.

Agreement between automated and manual quantification of corneal nerve fiber length: Implications for diabetic neuropathy research.

AIMS: Quantification of corneal nerve fiber length (CNFL) by in vivo corneal confocal microscopy represents a promising diabetic neuropathy biomarker, but applicability is limited by resource-intensive image analysis. We aimed to evaluate, in cross-sectional analysis of non-diabetic controls and patients with type 1 and type 2 diabetes with and without neuropathy, the agreement between manual and automated analysis protocols. METHODS: Sixty-eight controls, 139 type 1 diabetes, and 249 type 2 diabetes participants underwent CNFL measurement (N=456). Neuropathy status was determined by clinical and electrophysiological criteria. CNFL was determined by manual (CNFLManual, reference standard) and automated (CNFLAuto) protocols, and results were compared for correlation and agreement using Spearman coefficients and the method of Bland and Altman (CNFLManual subtracted from CNFLAuto). RESULTS: Participants demonstrated broad variability in clinical characteristics associated with neuropathy. The mean age, diabetes duration, and HbA1c were 53±18years, 15.9±12.6years, and 7.4±1.7%, respectively, and 218 (56%) individuals with diabetes had neuropathy. Mean CNFLManual was 15.1±4.9mm/mm2, and mean CNFLAuto was 10.5±3.7mm/mm2 (CNFLAuto underestimation bias, -4.6±2.6mm/mm2 corresponding to -29±17%). Percent bias was similar across non-diabetic controls (-33±12%), type 1 (-30±20%), and type 2 diabetes (-28±16%) subgroups (ANOVA, p=0.068), and similarly in diabetes participants with and without neuropathy. Levels of CNFLAuto and CNFLManual were both inversely associated with neuropathy status. CONCLUSIONS: Although CNFLAuto substantially underestimated CNFLManual, its bias was non-differential between diverse patient groups and its relationship with neuropathy status was preserved. Determination of diagnostic thresholds specific to CNFLAuto should be pursued in diagnostic studies of diabetic neuropathy.

In vivo corneal confocal microscopy and prediction of future-incident neuropathy in type 1 diabetes: a preliminary longitudinal analysis.

OBJECTIVE: In vivo corneal confocal microscopy (IVCCM) has been established in cross-sectional studies as a valid measure for the identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine the predictive validity of a baseline IVCCM measure in identifying future DSP onset in patients with type 1 diabetes. METHODS: We followed 65 patients with type 1 diabetes without DSP at baseline. They were followed longitudinally for a mean of 3.5±0.9 years and underwent IVCCM, clinical and electrophysiologic examinations at baseline and follow up. At the end of follow up, participants were assigned as new-onset cases of DSP or as controls. Predictive validity was assessed using receiver operating characteristic curves. RESULTS: At baseline, participants were 34±15 years of age with mean diabetes duration of 18±12 years. The 11 (17%) new-onset cases of DSP were similar to the 54 (83%) controls in baseline age, diabetes duration, gender, glycated hemoglobin levels and electrophysiologic parameters (p≥0.20). However, cases of new onset had significantly lower baseline corneal nerve fibre length (CNFL) and branch density (p<0.05). For identification of new-onset cases, area under the receiver operating characteristic curve for CNFL was 0.78 with an optimal threshold of 14.9 mm/mm(2) (sensitivity=0.82, specificity=0.69). CONCLUSIONS: Despite similar clinical and electrophysiologic parameters, participants with type 1 diabetes at risk for future DSP had significantly lower baseline IVCCM measures. CNFL may have applicability in identifying high-risk patients for therapeutic intervention in clinical research and practice.

Blood glucose levels and performance in a sports cAMP for adolescents with type 1 diabetes mellitus: a field study.

Background. Acute hypo- and hyperglycemia causes cognitive and psychomotor impairment in individuals with type 1 diabetes mellitus (T1DM) that may affect sports performance. Objective. To quantify the effect of concurrent and antecedent blood glucose concentrations on sports skills and cognitive performance in youth with T1DM attending a sports camp. Design/Methods. 28 youth (ages 6-17 years) attending a sports camp carried out multiple skill-based tests (tennis, basketball, or soccer skills) with glucose monitoring over 4 days. Glucose levels at the time of testing were categorized as (a) hypoglycemic (<3.6 mM); (b) within an acceptable glycemic range (3.6-13.9 mM); or (c) hyperglycemic (>13.9 mM). Results. Overall, sports performance skill was approximately 20% lower when glucose concentrations were hypoglycemic compared to either acceptable or hyperglycemic at the time of skill testing (P < .05). During Stroop testing, "reading" and "color recognition" also degraded during hypoglycemia, while "interference" scores improved (P < .05). Nocturnal hypoglycemia was present in 66% of subjects, lasting an average of 84 minutes, but this did not affect sports skill performance the following day. Conclusions. Mild hypoglycemia markedly reduces sports skill performance and cognition in young athletes with T1DM.