Pedro Alía

Postresection Parathyroid Hormone and Parathyroid Hormone Decline Accurately Predict Hypocalcemia After Thyroidectomy

Hypocalcemia is the most frequent complication after total thyroidectomy. Parathyroid hormone (PTH) measurement has been proposed as an early predictor of this condition. Total thyroidectomy was performed in 39 patients. Hypocalcemia was present in 15 cases (38%). Patients undergoing hemithyroidectomy (n = 13) were considered control subjects not developing hypocalcemia. PTH was measured before surgery and 10 minutes after resection of the gland using a rapid (15 minutes) chemiluminescent immunometric assay. Patients developing hypocalcemia had lower calcium and postresection PTH levels and higher PTH decline than patients not developing hypocalcemia (P < .0001). PTH decline (cutoff value, 62.5%) had the better sensitivity (93.3%) for predicting hypocalcemia, allowing for a fairly safe early discharge. However, the best overall results corresponded to the combination of postresection PTH level (< or = 18 pg/mL [< or = 1.9 pmol/L]) and PTH decline (>62.5%), with a sensitivity of 90% and a specificity of 97.9%. Perioperative PTH measures can accurately predict hypocalcemia after thyroidectomy, granting the laboratory a key role in the immediate decision about calcium supplementation for patients at risk.

Usefulness of an ACTH Test in the Diagnosis of Nonclassical 21-Hydroxylase Deficiency among Children Presenting with Premature Pubarche

Adrenal steroidogenic function was evaluated in 55 children with typical premature pubarche (PP) to investigate the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase (21-OH) deficiency and to evaluate the usefulness of routine ACTH testing in these patients. Four patients fulfilled criteria for LOCAH due to 21-OH deficiency. Of these, 3 had elevated baseline 17-OHP levels; in the remainder, basal 17-OHP was within normal limits. Mean basal and stimulated 17-OHP responses in children with PP, excluding those with an enzymatic defect, were very similar to those of controls (2.3 +/- 1.8 vs. 1.6 +/- 0.9 and 10.0 +/- 4.0 vs. 9.5 +/- 3.3 nmol/l, respectively). However, 5 patients had basal 17-OHP values exceeding the upper limit of controls and 8 patients, including 2 of those with elevated baseline levels, showed supranormal poststimulated 17-OHP values. Body mass indices, height standard deviation scores (SDS) and bone age SDS showed no correlation with the basal or incremental rises of any hormone. Four (7%) of our population of patients with typical PP had LOCAH due to 21-OH deficiency. Basal 17-OHP levels were helpful in detecting altered steroidogenesis in 3, thus suggesting that in some PP patients, LOCAH due to this enzymatic defect may remain undiagnosed if ACTH stimulation test is not routinely performed.

Interaction between APOA5 -1131T>C and APOE polymorphisms and their association with severe hypertriglyceridemia.

BACKGROUND Apolipoprotein A5 gene (APOA5) has been shown to modulate plasma triglyceride concentrations. The apolipoprotein E gene (APOE) has been implicated in cholesterol and triglyceride homeostasis in humans and plays an important role in atherogenesis. The aim of this study was to determine the genotypic distribution of the APOA5 -1131T>C and APOE polymorphisms and to identify the combined association of these variants between patients with and without severe hypertriglyceridemia (HTG). METHODS We genotyped 96 individuals who had reached plasma TG concentrations of more than 10 mmol/L and 225 ischemic patients without severe HTG. RESULTS Minor allele carriers were significantly more frequent in HTG group for all three polymorphisms (APOA5, APOE2 and APOE4). Adjusted individual risks for severe HTG were: APOA5 -1131C, OR=4.1 (95%CI:2.02-8.24); APOE2, OR=1.6 (95%CI:0.73-3.58); APOE4, OR=3.0 (95%CI:1.68-5.86). Adjusted risks for APOA5-APOE combinations were: APOA5 -1131C/APOE2, OR=45.2 (95%CI:4.92-415.5); APOA5 -1131C/APOE4, OR=6.4 (95%CI:2.28-18.01). CONCLUSIONS These data provide evidence that APOA5 -1131T>C polymorphism is associated with risk for severe HTG. Furthermore, this effect is strongly increased when -1131C variant is combined with APOE variants.

Angiotensin Converting Enzyme Genotype and Chronic Allograft Nephropathy in Protocol Biopsies

Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = -3.36 +/- 2.35 versus non-DD = -5.65 +/- 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.

APOLIPOPROTEIN E GENOTYPES IN NONAGENARIANS

intrusion of political correctness into our speech and an increasing burden of overpoliteness layered upon our communication with and about our patients. Nevertheless, the rejection of these terms by geriatricians reflects a growing awareness of the subtle and often undesired ways that such terms can influence our relationships with those we care for. Yet, despite this increasing awareness, the geriatric community continues to find acceptable what I find an even more problematic term: the term ‘‘demented’’ to describe patients with various forms of dementia, an acceptance reflected by the use of the word in several prior issues of this Journal. The term ‘‘demented’’ derives from the Latin ‘‘de,’’ to undo, plus ‘‘mens,’’ meaning mind. Thus, to say that a person has dementia is to say that she or he has a disease process that ‘‘undoes the mind,’’ whereas to say that a person is ‘‘demented’’ is tantamount to saying that he or she no longer has a mind. And although I may well be among the last to espouse the unquestionably more politically correct term ‘‘sanitation engineer’’ in lieu of ‘‘garbage collector,’’ I would wish to be among the first to publicly denounce the deeply entrenched, but no less politically incorrect, term ‘‘demented.’’ The problem with the term ‘‘demented’’ lies even beyond its etymologic roots. Despite the intentions of the speaker, the term ‘‘demented,’’ whether used as noun or as adjective, can subtly contribute to dehumanizing patient–doctor relationships with older people and their families; to say that so-andso is ‘‘demented,’’ or to speak of ‘‘the demented’’ in general, has the subtle linguistic effect of shifting significance from a condition that the patient possesses to an unwitting reduction of the patient to little more than the debilitated state itself in which the condition has left her or him. Although some may argue that that is precisely the point of the wordFto emphasize that there is no humanity left, only the physical remnants of itFsuch a position could only be defended, if at all, in patients with the most severe, end-stage dementia. It is one of our most sacred duties as physicians, in caring for those with dementia in particular, not only to recognize their humanity, but also to acknowledge and celebrate it in the way that we communicate with others. And as for what word to offer as an acceptable replacement for the pithy term in question so firmly ensconced in our medical parlance, how about the more mannerly, if somewhat less terse ‘‘cognitively disenfranchised’’ or the more descriptive, if perhaps formulaic ‘‘cholinergically challenged’’? Perhaps, however, we would do well to abandon altogether the goal of finding a suitable word to replace the term in much the way clinical speech is increasingly giving up the terms ‘‘schizophrenic’’ and ‘‘alcoholic’’ in favor of ‘‘man with schizophrenia’’ and ‘‘woman with alcoholism.’’ Although whatever epithet we end up choosing will invariably roll off the tongue with considerably less ease than ‘‘demented,’’ patients’ families, friends, and perhaps even many of our ‘‘patients with dementia’’ themselves will no doubt appreciate the effort invested in those few extra syllables.

Development and validation of a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of β-lactam antibiotic concentration in human plasma

BACKGROUND The administration of β-lactam antibiotics in continuous infusion could let optimize the pharmacokinetic/pharmacodynamic parameters, especially in the treatment of serious bacterial infections. In this context, and also due to variability in their plasmatic concentrations, therapeutic drug monitoring (TDM) may be useful to optimize dosing and, therefore, be useful for the clinicians. MATERIAL AND METHODS We developed and validated a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of amoxicillin, ampicillin, cloxacillin, piperacillin, cefepime, ceftazidime, cefuroxime, aztreonam and meropenem concentrations in plasma. The chromatographic separation was achieved using an Acquity®-UPLC® BEH™ (2.1×100mm id, 1.7μm) reverse-phase C18 column, with a water/acetonitrile linear gradient containing 0.1% formic acid at a 0.4mL/min flow rate. β-Lactam antibiotics and their internal standards were detected by electrospray ionization mass spectrometry in multiple reaction monitoring mode. RESULTS Chromatography run time was 7.0min and β-lactam antibiotics eluted at retention times ranging between 1.08 and 1.91min. The lower limits of quantification were between 0.50 and 1.00mg/L. Coefficients of variation and relative bias absolute values were <13.3% and 14.7%, respectively. Recovery values ranged from 55.7% to 84.8%. Evaluation of the matrix effect showed ion enhancement for all antibiotics. No interferences or carry-over were observed. CONCLUSIONS Our measurement procedure could be applied to daily clinical laboratory practice to measure the concentration of β-lactam antibiotics in plasma, for instance in patients with bone and joint infections and critically ill patients.

Gen de la apolipoproteína A5: asociación con el metabolismo de los triglicéridos y las enfermedades cardiovasculares☆

La hipertrigliceridemia constituye un factor de riesgo independiente para la enfermedad coronaria. El gen de la apolipoproteina A5 (ApoA5) es el miembro mas recientemente descubierto del complejo ApoA1/C3/A4/A5, y su producto, la apolipoproteina A5, influye en los trigliceridos por un mecanismo todavia no aclarado. En fechas recientes se han descrito las consecuencias clinicas y los efectos funcionales de mas de 10 variantes del gen ApoA5 asociadas con la arteriosclerosis. En estudios realizados en diferentes grupos etnicos se ha observado una gran variacion en la distribucion de los genotipos ApoA5 para los respectivos polimorfismos. Varios autores han descrito la asociacion de los polimorfismos del gen ApoA5 con concentraciones elevadas de trigliceridos y aumento del riesgo cardiovascular. En este contexto, el gen ApoA5 se presenta como un posible marcador bioquimico y genetico del aumento de la concentracion de trigliceridos y del riesgo de enfermedad coronaria en algunas poblaciones.

Serum Insulin-Like Growth Factor Levels Do Not Predict Functional Recovery after Hospitalization in Nonagenarian Patients

Aim: To analyze the insulin-like growth factor 1 (IGF-1) serum levels in nonagenarian patients and to investigate the predictive capacity of this measure to assess the functional recovery of this population following hospitalization. Methods: We performed a prospective study in 60 consecutive nonagenarian patients admitted for medical or surgical diseases. We assessed IGF-1 serum levels and nutritional status. The functional status was assessed using the Barthel index. Thirty-four patients were reinvestigated 3 months after discharge from hospital. Results: The mean levels of IGF-1 were lower in nonagenarians than in younger patients. No relationship was found between IGF-1 levels and nutritional status. The decline in Barthel index values 3 months after discharge from hospital did not correlate with serum levels of IGF-1 on admission. Conclusion: IGF-1 serum levels in nonagenarian patients do not predict functional recovery after hospitalization.

Analytical goals for rectilinear calibration functions

Analytical goals for rectilinearity based on within-subject biological variation have not yet been advocated. On the other hand, the statistical tests to evaluate rectilinearity may be too restrictive for clinical purposes. If rectilinearity of the least-squares regression is rejected by the statistical test used, we propose to compare the systematic error introduced using such a regression line as the calibration function, with the allowable total error. Since total error ideally should be less than the within-subject biological coefficient of variation (C.V.Bw) the goal for rectilinearity we propose is that the maximum allowable systematic relative error produced by the calibration function (LoRi) when a lack of rectilinearity really occurs is: LoRi < C.V.Bw -1.96 C.V.M, where C.V.M is the between-run metrological coefficient of variation of the measurement procedure, corresponding to the value of concentration under study.

Association of APOA5 and APOC3 Genetic Polymorphisms With Severity of Hypertriglyceridemia in Patients With Cutaneous T-Cell Lymphoma Treated With Bexarotene

Importance Hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives To analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants This case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures Primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results Among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.