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acidosis metabolic [keywords]
- Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation. [JOURNAL ARTICLE]
- Br J Surg 2014 Oct 30.
The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting.Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111 mmol/l up to and including 154 mmol/l) or lower-chloride (concentration 111 mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling.The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1·64, 95 per cent c.i. 1·27 to 2·13; P < 0·001) and hyperchloraemia/metabolic acidosis (RR 2·87, 1·95 to 4·21; P < 0·001). High-chloride fluids were also associated with greater serum chloride (MD 3·70 (95 per cent c.i. 3·36 to 4·04) mmol/l; P < 0·001), blood transfusion volume (SMD 0·35, 0·07 to 0·63; P = 0·014) and mechanical ventilation time (SMD 0·15, 0·08 to 0·23; P < 0·001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time.A weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.
- Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD. [JOURNAL ARTICLE]
- Genet Med 2014 Nov 6.
Purpose:3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD.Methods:We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases.Results:We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD.Conclusion:Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes.Genet Med advance online publication 06 November 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.157.
- Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects. [Journal Article]
- Ann Clin Transl Neurol 2014 Jul; 1(7):462-70.
Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. PDHC deficiency is genetically heterogenous and most patients have defects in the X-linked E1-α gene but defects in the other components of the complex encoded by PDHB, PDHX, DLAT, DLD genes or in the regulatory enzyme encoded by PDP1 have also been found. Phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of pyruvate dehydrogenase kinases and thus, has potential for therapy of patients with PDHC deficiency. In the present study, we investigated response to phenylbutyrate of multiple cell lines harboring all known gene defects resulting in PDHC deficiency.Fibroblasts of patients with PDHC deficiency were studied for their enzyme activity at baseline and following phenylbutyrate incubation. Drug responses were correlated with genotypes and protein levels by Western blotting.Large deletions affecting PDHA1 that result in lack of detectable protein were unresponsive to phenylbutyrate, whereas increased PDHC activity was detected in most fibroblasts harboring PDHA1 missense mutations. Mutations affecting the R349-α residue were directed to proteasome degradation and were consistently unresponsive to short-time drug incubation but longer incubation resulted in increased levels of enzyme activity and protein that may be due to an additional effect of phenylbutyrate as a molecular chaperone.PDHC enzyme activity was enhanced by phenylbutyrate in cells harboring missense mutations in PDHB, PDHX, DLAT, DLD, and PDP1 genes. In the prospect of a clinical trial, the results of this study may allow prediction of in vivo response in patients with PDHC deficiency harboring a wide spectrum of molecular defects.
- A prospective cohort study of the morbidity associated with operative vaginal deliveries performed by day and at night. [Journal Article]
- BMJ Open 2014; 4(10):e006291.
To evaluate maternal and neonatal outcomes associated with operative vaginal deliveries (OVDs) performed by day and at night.Prospective cohort study.Urban maternity unit in Ireland with off-site consultant staff at night.All nulliparous women requiring an OVD with a term singleton fetus in a cephalic presentation from February to November 2013.Delivery outcomes were compared for women who delivered by day (08:00-19:59) or at night (20:00-07:59).The main outcomes included postpartum haemorrhage (PPH), anal sphincter tear and neonatal unit admission. Procedural factors included operator grade, sequential use of instruments and caesarean section.Of the 597 women who required an OVD, 296 (50%) delivered at night. Choice of instrument, place of delivery, sequential use of instruments and caesarean section did not differ significantly in relation to time of birth. Mid-grade operators performed less OVDs by day than at night, OR 0.60 (95% CI 0.43 to 0.83), and a consultant supervisor was more frequently present by day, OR 2.26 (95% CI 1.05 to 4.83). Shoulder dystocia occurred more commonly by day, OR 2.57 (95% CI 1.05 to 6.28). The incidence of PPH, anal sphincter tears, neonatal unit admission, fetal acidosis and neonatal trauma was similar by day and at night. The mean decision to delivery intervals were 12.0 and 12.6 min, respectively.There was no evidence of an association between time of OVD and adverse perinatal outcomes despite off-site consultant obstetric support at night.
- Prevalence of distal renal tubular acidosis in primary Sjögren's syndrome. [JOURNAL ARTICLE]
- Rheumatology (Oxford) 2014 Oct 29.
Our objectives were to analyse the prevalence of distal renal tubular acidosis (dRTA) in primary SS (pSS) and to compare a novel urinary acidification test with furosemide and fludrocortisone (FF) with the gold standard ammonium chloride (NH4Cl) to detect dRTA.Urinary acidification was assessed in 57 pSS patients using NH4Cl and FF. A urinary acidification defect was defined as an inability to reach a urinary pH of <5.3 after NH4Cl.The prevalence of complete dRTA (urinary acidification defect with acidosis) was 5% (3/57). All three patients had positive SSA/Ro and SSB/La autoantibodies and impaired kidney function. The prevalence of incomplete dRTA (urinary acidification defect without acidosis) was 25% (14/57). Compared with patients without dRTA, patients with incomplete dRTA had significantly lower venous pH and serum bicarbonate and higher urinary pH. SSB/La antibodies were more prevalent in the dRTA groups (P < 0.05). Compared with NH4Cl, the positive and negative predictive values of FF were 46% and 82%, respectively. Vomiting occurred more often during the urinary acidification test with NH4Cl than with FF (9 vs 0, P < 0.05).Incomplete dRTA is common in pSS and causes mild acidaemia and higher urinary pH, which may contribute to bone demineralization and kidney stone formation. FF cannot replace NH4Cl in testing urinary acidification in pSS, but may be considered as a screening tool, given its reasonable negative predictive value and better tolerability.
- Patterns of Growth after Kidney Transplantation among Children with ESRD. [JOURNAL ARTICLE]
- Clin J Am Soc Nephrol 2014 Oct 28.
Poor linear growth is a frequent complication of CKD. This study evaluated the effect of kidney transplantation on age-related growth of linear body segments in pediatric renal transplant recipients who were enrolled from May 1998 until August 2013 in the CKD Growth and Development observational cohort study.Linear growth (height, sitting height, arm and leg lengths) was prospectively investigated during 1639 annual visits in a cohort of 389 pediatric renal transplant recipients ages 2-18 years with a median follow-up of 3.4 years (interquartile range, 1.9-5.9 years). Linear mixed-effects models were used to assess age-related changes and predictors of linear body segments.During early childhood, patients showed lower mean SD scores (SDS) for height (-1.7) and a markedly elevated sitting height index (ratio of sitting height to total body height) compared with healthy children (1.6 SDS), indicating disproportionate stunting (each P<0.001). After early childhood a sustained increase in standardized leg length and a constant decrease in standardized sitting height were noted (each P<0.001), resulting in significant catch-up growth and almost complete normalization of sitting height index by adult age (0.4 SDS; P<0.01 versus age 2-4 years). Time after transplantation, congenital renal disease, bone maturation, steroid exposure, degree of metabolic acidosis and anemia, intrauterine growth restriction, and parental height were significant predictors of linear body dimensions and body proportions (each P<0.05).Children with ESRD present with disproportionate stunting. In pediatric renal transplant recipients, a sustained increase in standardized leg length and total body height is observed from preschool until adult age, resulting in restoration of body proportions in most patients. Reduction of steroid exposure and optimal metabolic control before and after transplantation are promising measures to further improve growth outcome.
- Fluid resuscitation in acute medicine: what is the current situation? [JOURNAL ARTICLE]
- J Intern Med 2014 Oct 28.
The administration of intravenous fluids for resuscitation is the most common intervention in acute medicine. There is increasing evidence that the type of fluid may directly affect patientcentred outcomes. There is a lack of evidence that colloids confer clinical benefit over crystalloids and they may be associated with harm. Hydroxyethyl starch preparations are associated with increased mortality and use of renal replacement therapy in critically ill patients, particularly those with sepsis; albumin is associated with increased mortality in patients with severe traumatic brain injury. Crystalloids, such as saline or balanced salt solutions, are increasingly recommended as first-line resuscitation fluids for the majority of patients with hypovolaemia. There is emerging evidence that saline may be associated with adverse outcomes due to the development of hyperchloraemic metabolic acidosis, although the safety of balanced salt solutions has not been established. Fluid requirements vary over the course of critical illness. The excessive use of fluids during the resuscitative period is associated with increased cumulative fluid balance and adverse outcomes in critically ill patients. The selection of fluid depends on the clinical context in which it is administered and requires careful consideration of the dose and potential for toxicity. There is an urgent need to conduct further high-quality randomised controlled trials of currently available fluid therapy in patients with critical illness. This article is protected by copyright. All rights reserved.
- On the evidence for intrapartum fetal monitoring with ECG-ST analysis. [JOURNAL ARTICLE]
- Acta Obstet Gynecol Scand 2014 Oct 28.
We appreciate the two commentaries by Øian and Blix (1,2) on our reviews of the evidence supporting the STAN concept as reflected in the randomized controlled trials (RCTs) (3), and the critical appraisal of the published meta-analyses of the STAN system (4). Øian and Blix state that the criteria used for quality assessment of the five RCTs are unclear (1). We respectfully disagree, as our review (3) explicitly identifies each element considered for such assessment: power calculations of outcome variables, pre-trial training, inclusion criteria, randomization and recruitment pace, management protocols during labor, intrapartum interventions, outcomes of metabolic acidosis, and neonatal intensive care admissions. This article is protected by copyright. All rights reserved.
- Clinical utility of third trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses. [JOURNAL ARTICLE]
- Ultrasound Obstet Gynecol 2014 Oct 27.
To evaluate the clinical value of uterine artery Doppler in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses.Uterine artery (UtA) Doppler, cerebroplacental ratio (CPR), and middle cerebral artery (MCA) pulsatility indices (PI) were weekly evaluated from diagnosis until 24 hrs before labor induction in a cohort of 327 SGA fetuses with normal umbilical artery PI (<95(th) centile) delivered above 37 weeks. Differences in the sequence of changes of CPR and MCA PI <5(th) centile between the group with normal and abnormal uterine artery Doppler at diagnosis were analyzed by survival analysis. In addition, the value of uterine artery Doppler, alone or in combination with brain Doppler before delivery, to predict cesarean delivery (CD), CD for nonreassuring fetal status (NRFS), neonatal acidosis (NA) and neonatal hospitalization was evaluated by logistic regression adjusted by gestational age at birth and birthweight percentile.Abnormal uterine artery at diagnosis was associated with a higher risk of developing abnormal brain Doppler before labor induction (62.7% vs. 34.6%, p < 0.01). Abnormal UtA Doppler was associated with a higher risk of intrapartum CD (52.2% vs. 37.3% with normal UtA Doppler, p = 0.03), CD for NRFS (35.8% vs. 23.1%, p = 0.03), NA (10.4% vs. 7.7%, p = 0.47) and neonatal hospitalization (23.9% vs. 16.5%, respectively, p = 0.16). Logistic regression analysis indicated that UtA Doppler had not significant association with adverse perinatal outcome independently of brain Doppler.Uterine artery Doppler predicts adverse outcome, but it does not help to improve the predictive value of brain Doppler. However, at the time of diagnosis it identifies the subgroup of fetuses at highest risk of progression to abnormal brain Doppler.
- Familial mixed nephrocalcinosis as a cause of chronic kidney failure: two case reports. [JOURNAL ARTICLE]
- J Med Case Rep 2014 Oct 27; 8(1):355.
Nephrocalcinosis consists of the deposition of calcium salts in the renal parenchyma and is considered the mixed form when it involves the renal cortex and medulla. The main etiological agents of this condition are primary hyperparathyroidism, renal tubular acidosis, medullary sponge kidney, hyperoxaluria and taking certain drugs. These factors can lead to hypercalcemia and/or hypercalciuria, which can give rise to nephrocalcinosis.Case presentations: Patient 1 was a 48-year-old Caucasian woman with a history of bilateral nephrocalcinosis causing chronic kidney failure. Imaging examinations (X-ray, ultrasound and computed tomography of the abdomen) revealed extensive calcium deposits in the renal parenchyma, indicating nephrocalcinosis as the causal factor of the disease. Patient 2 is the 45-year-old brother of patient 1. He exhibited an advanced stage of chronic kidney failure. As nephrocalcinosis is considered to have a genetic component, a family investigation revealed this condition in patient 2.Nephrocalcinosis may be detected incidentally through diagnostic imaging studies. Whenever possible, treatment should include the base disease that caused the appearance of the calcification, as the precise etiological determination is extremely important.