Hemoglobin Yamagata [ß132(H10)Lys→Asn; (HBB: c.399A>T)]: a mosaic to be put together.

OBJECTIVES: Artifactually altered glycated hemoglobin (HbA1c) concentrations are frequently linked to hemoglobin (Hb) variants. Their expression and detection require in-depth analysis. METHODS: Cation exchange high performance liquid chromatography (HPLC) (Bio-Rad Variant™ II; Trinity Biotech Premier Hb9210 Resolution), capillary electrophoresis (CE) (Sebia Capillarys 2 Flex Piercing) and mass spectrometry (MS) (Waters) were used for variant detection; Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) were used for DNA analysis; HbA1c was measured with cation exchange HPLC (Bio-Rad Variant™ II; Arkray Adams HA-8180V; Tosoh HLC-723 G7), CE (Sebia Capillarys 2 Flex Piercing), boronate affinity HPLC (Trinity Biotech Hb9210 Premier), immunoassay (Cobas c501 Tina-quant HbA1c Gen. 3; Nihon Kohden CHM-4100 Celltac chemi HbA1c HA-411V) and enzymatic assay (Abbott Architect c 8000 HbA1c). RESULTS: Hb Yamagata [ß132(H10)Lys→Asn; (HBB: c.399A>T)] was identified in the proband by MS after the observation of an abnormal peak in HPLC and CE. A mosaic expression of this variant was detected by NGS (mutant: 8%; wild type: 92%), after negative results in Sanger sequencing. Hb Yamagata interfered with HbA1c measurements by cation exchange HPLC and CE whereas immuno and enzymatic assay values showed good agreement with boronate affinity HPLC measurement. CONCLUSIONS: A mosaicism of Hb Yamagata was found in a patient with altered HbA1c values. This rare gene variant was detected only by advanced technologies as MS and NGS. The variant interfered with common HbA1c determination methods.

Evaluation of renal function in the elderly, not as easy as it seems: a review.

In the elderly assessment of renal function by glomerular filtration rate estimation is crucial for diagnostic, therapeutic and prognostic purposes. Our aim is to illustrate the different formulas available and their respective advantages and disadvantages.

Fall prevention in the elderly.

Falls are frequent in the elderly and affect mortality, morbidity, loss of functional capacity and institutionalization. In the older patient the incidence of falls can sometimes be underestimated, even in the absence of a clear cognitive impairment, because it is often difficult to reconstruct the dynamics. It is quite common that forms due to syncope are associated with retrograde amnesia and in 40 to 60% of the cases falls happen in the absence of witnesses. The pathogenesis of falls is often multifactorial, due to physiological age-related changes or more properly pathological factors, or due to the environment. The identification of risk factors is essential in the planning of preventive measures. Syncope is one of major causes of falls. About 20% of cardiovascular syncope in patients older than 70 appears as a fall and more than 20% of older people with Carotid Sinus Syndrome complain of falls as well as syncope. These data clearly state that older patients with history of falls should undergo a cardiovascular and neuroautonomic assessment besides the survey of other risk factors. Multifactorial assessment requires a synergy of various specialists. The geriatrician coordinates the multidisciplinary intervention in order to make the most effective evaluation of the risk of falling, searching for all predisposing factors, aiming towards a program of prevention. In clear pathological conditions it is possible to enact a specific treatment. Particular attention must indeed be paid to the re-evaluation of drug therapy, with dose adjustments or withdrawal especially for antihypertensive, diuretics and benzodiazepines. The Guidelines of the American Geriatrics Society recommend modification of environmental hazards, training paths, hip protectors and appropriate use of support tools (sticks, walkers), which can be effective elements of a multifactorial intervention program. Balance exercises are also recommended. In conclusion, an initial assessment, supported by a comprehensive cardiovascular and neuroautonomic evaluation, allows for reaching a final diagnosis in most cases, demonstrating a key role in the real identification of the etiology of the fall and implementing the treatment measures.

Low Creatinine Potentially Overestimates Glomerular Filtration Rate in Older Fracture Patients: A Plea for an Extensive Use of Cystatin C?

AIM: Muscle mass is frequently reduced in older patients experiencing injurious falls and may further reduce during hospitalization for bone fracture. In these patients, renal function may be overestimated, because it is usually calculated using serum creatinine, which is strictly related to muscle mass. We evaluated if creatinine levels change during hospitalization in older patients with fracture. We also assessed the role of cystatin C as a more appropriate marker of renal function, comparing estimated glomerular filtration rate (eGFR) according to different formulas based on creatinine and/or cystatin C levels. METHODS: Patients aged 65+ years, consecutively hospitalized for fracture, were enrolled in a prospective cohort study. Creatinine and cystatin C levels were measured at baseline and in the post-operative period; eGFR was calculated using six equations based on creatinine and/or cystatin C. RESULTS: 425 patients were enrolled (mean age 84 years, mean creatinine 0.97 mg/dL, mean cystatin C 1.53 mg/L). Creatinine levels significantly decreased after surgery (p<0.001), while cystatin C remained stable. According to creatinine-based formulas, eGFR was < 60 mL/min/1.73 m2 in 29-30% at baseline and only in 17% participants in the post-operative period. Conversely, according to equations including cystatin C, eGFR was < 60 mL/min/1.73 m2 in half to three-quarters of the sample at all assessments. CONCLUSIONS: In older fractured patients, creatinine levels decline during hospital stay and may possibly overestimate renal function, whereas cystatin C remains stable. Whether cystatin C is a more reliable marker of renal function in this specific population should be further investigated.

Renal function and delirium in older fracture patients: different information from different formulas?

OBJECTIVES: the association between renal function and delirium has not been investigated in older fracture patients. Creatinine is frequently low in these subjects, which may influence the association between delirium and renal function as estimated with creatinine-based formulas. Cystatin C could be a more reliable filtration marker in these patients. AIM: to confirm the association between renal function and delirium in older fracture patients comparing creatinine- and cystatin-based estimated glomerular filtration rate (eGFR) METHODS: patients aged 65+ requiring surgery for traumatic bone fractures were included. Six equations were used to calculate eGFR, based on serum creatinine and/or cystatin C obtained within 24 h of admission: Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology (CKD-EPIcr, CKD-EPIcys, CKD-EPIcr-cys) and Berlin Initiative Study equations (BIS-1, BIS-2). Delirium was identified with a chart-based method. RESULTS: 571 patients (mean age 83) were enrolled. Delirium occurred in the 34% and was associated with a lower eGFR regardless of the equation used. In a multivariable model, the association between moderate renal impairment (eGFR 30-60 ml/min/1.73 m2) and delirium remained significant in patients aged 75-84 and only when estimated with cystatin-based or BIS-1 equations. Only dementia was significantly associated with delirium in subjects 85+. CONCLUSIONS: in older fracture patients, moderate renal impairment was independently associated with delirium only among subjects aged 75-84, when eGFR was estimated with cystatin-based or BIS 1 equations, and not with the most commonly used equations (MDRD, CKD-EPIcr).

Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials.

OBJECTIVE: Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists. DESIGN AND METHODS: MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events. RESULTS: Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50-1.08), P = .12 (0.85 (0.50-1.45), P = .55, and 0.69 (0.40-1.22), P = .20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25-0.83), P = .009, and 1.05 (0.63-1.76), P = .84, respectively. CONCLUSIONS: To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect.