Reference intervals for various measurements of canine left atrial size and function obtained using two-dimensional and three-dimensional echocardiography.

BACKGROUND: Many canine cardiac diseases are associated with left atrial (LA) remodeling and decreased function. For accurate assessment of LA indices, large-scale and prospectively determined reference intervals are necessary. OBJECTIVES: To generate reference intervals of LA size and function using two-dimensional and three-dimensional echocardiography. ANIMALS: Two hundred and one healthy adult dogs. METHODS: Left atrial volume was assessed in right parasternal long-axis, left apical four-chamber and two-chamber views using monoplane Simpson's method, two-dimensional and three-dimensional speckle tracking. Additionally, LA diameter was measured in right parasternal short-axis and long-axis views. Furthermore, LA function was determined by measuring strain and calculating LA fractional shortening and ejection fraction. All variables were tested for correlation to heart rate, age, and body weight. For LA diameter and volume, scaling exponents and prediction intervals were generated using allometric scaling. Reference intervals for LA function parameters were calculated using nonparametric methods. RESULTS: Left atrial diameter and volume showed a strong correlation with body weight. The scaling exponent for LA diameter was approximately 1/3 (0.34-0.40) and approximately one for volume measurements (0.97-1.26). Parameters of LA function showed no clinically relevant correlation with body weight, except for two variables, which showed a mild negative correlation. No clinically relevant correlations with age or heart rate were found. CONCLUSIONS: Reference intervals for linear, two-dimensional and three-dimensional measurements of LA size and function were established. The wide range of measurement methods offers the opportunity to select the appropriate reference values for LA evaluation depending on the available technical possibilities.

Systolic function in dogs with pulmonic stenosis of different severities and the effect of balloon valvuloplasty.

INTRODUCTION/OBJECTIVES: Pulmonic stenosis (PS) is one of the most common congenital heart diseases in dogs leading to right ventricular (RV) pressure overload, myocardial remodeling, and potential RV dysfunction. Our objectives were to investigate the extent of RV systolic dysfunction in canine PS and to examine the immediate influence of balloon valvuloplasty (BV) on systolic function. ANIMALS, MATERIALS AND METHODS: This prospective study evaluated 72 dogs with PS and 86 healthy dogs. Echocardiographic parameters of systolic function included normalized tricuspid annular plane systolic excursion (N-TAPSE), normalized systolic myocardial tissue Doppler velocity of the lateral tricuspid annulus (N-RVFW-S'), fractional area change, and speckle-tracking longitudinal endocardial RV strain. Forty-four dogs underwent BV and were re-examined after surgery. RESULTS: Systolic function at the basal segment of the RV was significantly lower in the PS group when compared to healthy dogs (mean N-TAPSE 4.29 ± standard deviation 1.18 mm/kg0.285 vs. 5.60 ± 1.29 mm/kg0.285; median N-RVFW-S' 5.28 [lower-upper 25% quantile 4.35-6.43 cm/s/kg0.186] vs. 7.82 [6.73-8.79 cm/s/kg0.186]; all P<0.001). Global longitudinal RV endocardial strain showed no significant difference between the two groups (-28.50 ± 6.23% vs. 28.61 ± 4.64%; P=0.886), but segmental strain analyses revealed basal hypo- and potential compensatory hyperkinesis of the apical RVFW. Furthermore, BV affected most parameters of systolic function, but not the segmental strain values and N-TAPSE. CONCLUSIONS: Right ventricular basal longitudinal systolic function is decreased in dogs with PS in comparison to a healthy cohort. Regional and global function does not necessarily coincide.

The role of atrial fibrillation as a prognostic factor in doberman pinschers with dilated cardiomyopathy and congestive heart failure.

Atrial fibrillation (AF) in congestive heart failure (CHF) is associated with a high risk of mortality and shorter survival times in human and veterinary medicine. A retrospective review of medical records was performed to evaluate the impact of AF on survival times in Doberman Pinschers with dilated cardiomyopathy (DCM). Time of first onset of CHF and its role as a prognostic factor were also determined, as were predictors of AF development. Forty-eight client-owned purebred Doberman Pinschers with DCM and CHF were included; 23 dogs presented with AF and 25 dogs did not develop AF until immediately before cardiac-related death. Dogs with AF survived for significantly shorter times than those without AF (P = 0.043). For dogs with AF, mean and median survival times were 88.2 days and 22 days, respectively (range, 42.1-134.4 days); mean and median survival times for dogs without AF were 150.7 days and 98 days, respectively (range, 98.5-203 days). AF increased the risk of cardiac-related death (hazard ratio [HR], 2.371; 95% confidence intervals [CI], 1.14-4.95; P = 0.021). Biventricular and right atrial dilation was only present in dogs with AF and right atrial enlargement was the only significant predictor of AF after multivariate analysis (P < 0.001). Dogs with AF had significantly higher mean heart rates than dogs without AF (201 beats per min [bpm] vs. 132 bpm; P < 0.001). In conclusion, AF in Doberman Pinschers with DCM and CHF increased the risk of cardiac-related death and reduced survival time.

A randomized controlled, non-inferiority trial of modified natural versus artificial cycle for cryo-thawed embryo transfer.

STUDY QUESTION: Are live birth rates (LBRs) after artificial cycle frozen-thawed embryo transfer (AC-FET) non-inferior to LBRs after modified natural cycle frozen-thawed embryo transfer (mNC-FET)? SUMMARY ANSWER: AC-FET is non-inferior to mNC-FET with regard to LBRs, clinical and ongoing pregnancy rates (OPRs) but AC-FET does result in higher cancellation rates. WHAT IS ALREADY KNOWN: Pooling prior retrospective studies of AC-FET and mNC-FET results in comparable pregnancy and LBRs. However, these results have not yet been confirmed by a prospective randomized trial. STUDY DESIGN, SIZE AND DURATION: In this non-inferiority prospective randomized controlled trial (acronym 'ANTARCTICA' trial), conducted from February 2009 to April 2014, 1032 patients were included of which 959 were available for analysis. The primary outcome of the study was live birth. Secondary outcomes were clinical and ongoing pregnancy, cycle cancellation and endometrium thickness. A cost-efficiency analysis was performed. PARTICIPANT/MATERIALS, SETTING, METHODS: This study was conducted in both secondary and tertiary fertility centres in the Netherlands. Patients included in this study had to be 18-40 years old, had to have a regular menstruation cycle between 26 and 35 days and frozen-thawed embryos to be transferred had to derive from one of the first three IVF or IVF-ICSI treatment cycles. Patients with a uterine anomaly, a contraindication for one of the prescribed medications in this study or patients undergoing a donor gamete procedure were excluded from participation. Patients were randomized based on a 1:1 allocation to either one cycle of mNC-FET or AC-FET. All embryos were cryopreserved using a slow-freeze technique. MAIN RESULTS AND THE ROLE OF CHANCE: LBR after mNC-FET was 11.5% (57/495) versus 8.8% in AC-FET (41/464) resulting in an absolute difference in LBR of -0.027 in favour of mNC-FET (95% confidence interval (CI) -0.065-0.012; P = 0.171). Clinical pregnancy occurred in 94/495 (19.0%) patients in mNC-FET versus 75/464 (16.0%) patients in AC-FET (odds ratio (OR) 0.8, 95% CI 0.6-1.1, P = 0.25). 57/495 (11.5%) mNC-FET resulted in ongoing pregnancy versus 45/464 (9.6%) AC-FET (OR 0.7, 95% CI 0.5-1.1, P = 0.15). χ(2) test confirmed the lack of superiority. Significantly more cycles were cancelled in AC-FET (124/464 versus 101/495, OR 1.4, 95% CI 1.1-1.9, P = 0.02). The costs of each of the endometrial preparation methods were comparable (€617.50 per cycle in NC-FET versus €625.73 per cycle in AC-FET, P = 0.54). LIMITATIONS, REASONS FOR CAUTION: The minimum of 1150 patients required for adequate statistical power was not achieved. Moreover, LBRs were lower than anticipated in the sample size calculation. WIDER IMPLICATIONS OF THE FINDINGS: LBRs after AC-FET were not inferior to those achieved by mNC-FET. No significant differences in clinical and OPR were observed. The costs of both treatment approaches were comparable. STUDY FUNDING/COMPETING INTERESTS: An educational grant was received during the conduct of this study. Merck Sharpe Dohme had no influence on the design, execution and analyses of this study. E.R.G. received an education grant by Merck Sharpe Dohme (MSD) during the conduct of the present study. B.J.C. reports grants from MSD during the conduct of the study. A.H. reports grants from MSD and Ferring BV the Netherlands and personal fees from MSD. Grants from ZonMW, the Dutch Organization for Health Research and Development. J.S.E.L. reports grants from Ferring, MSD, Organon, Merck Serono and Schering-Plough during the conduct of the study. F.J.M.B. receives monetary compensation as member of the external advisory board for Merck Serono, consultancy work for Gedeon Richter, educational activities for Ferring BV, research cooperation with Ansh Labs and a strategic cooperation with Roche on automated anti Mullerian hormone assay development. N.S.M. reports receiving monetary compensations for external advisory and speaking work for Ferring BV, MSD, Anecova and Merck Serono during the conduct of the study. All reported competing interests are outside the submitted work. No other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: Netherlands trial register, number NTR 1586. TRIAL REGISTRATION DATE: 13 January 2009. FIRST PATIENT INCLUDED: 20 April 2009.

Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? A randomized comparison.

STUDY QUESTION: What is the treatment success rate of systemic methotrexate (MTX) compared with expectant management in women with an ectopic pregnancy or a pregnancy of unknown location (PUL) with low and plateauing serum hCG concentrations? SUMMARY ANSWER: In women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations, expectant management is an alternative to medical treatment with single-dose systemic MTX. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: MTX is often used in asymptomatic women with an ectopic pregnancy or a PUL with low and plateauing serum hCG concentrations. These pregnancies may be self-limiting and watchful waiting is suggested as an alternative, but evidence from RCTs is lacking. The results of this RCT show that expectant management is an alternative to treatment with systemic MTX in a single-dose regimen in these women. STUDY DESIGN, SIZE, DURATION: A multicentre RCT women were assigned to systemic MTX (single dose) treatment or expectant management, using a web-based randomization program, block randomization with stratification for hospital and serum hCG concentration (<1000 versus 1000-2000 IU/l). The primary outcome measure was an uneventful decline of serum hCG to an undetectable level (<2 IU/l) by the initial intervention strategy. Secondary outcome measures included additional treatment, side effects and serum hCG clearance time. PARTICIPANTS, SETTING, METHODS: From April 2007 to January 2012, we performed a multicentre study in The Netherlands. All haemodynamically stable women >18 years old with both an ectopic pregnancy visible on transvaginal sonography and a plateauing serum hCG concentration <1500 IU/l or with a PUL and a plateauing serum hCG concentration <2000 IU/l were eligible for the trial. MAIN RESULTS: We included 73 women of whom 41 were allocated to single-dose MTX and 32 to expectant management. There was no difference in primary treatment success rate of single-dose MTX versus expectant management, 31/41 (76%) and 19/32 (59%), respectively [relative risk (RR) 1.3 95% confidence interval (CI) 0.9-1.8]. In nine women (22%), additional MTX injections were needed, compared with nine women (28%) in whom systemic MTX was administered after initial expectant management (RR 0.8; 95% CI 0.4-1.7). One woman (2%) from the MTX group underwent surgery compared with four women (13%) in the expectant management group (RR 0.2; 95% CI 0.02-1.7), all after experiencing abdominal pain within the first week of follow-up. In the MTX group, nine women reported side effects versus none in the expectant management group. No serious adverse events were reported. Single-dose systemic MTX does not have a larger treatment effect compared with expectant management in women with an ectopic pregnancy or a PUL and low and plateauing serum hCG concentrations. WIDER IMPLICATIONS OF THE FINDINGS: Sixty percent of women after expectant management had an uneventful clinical course with steadily declining serum hCG levels without any intervention, which means that MTX, a potentially harmful drug, can be withheld in these women. BIAS, LIMITATION AND GENERALISABILITY: A limitation of this RCT is that it was an open (not placebo controlled) trial. Nevertheless, introduction of bias was probably limited by the strict criteria to be fulfilled for treatment with MTX. STUDY FUNDING: This trial is supported by a grant of the Netherlands Organization for Health Research and Development (ZonMw Clinical fellow grant 90700154). TRIAL REGISTRATION: ISRCTN 48210491.

Anesthetic management of a massively morbidly obese patient.

BACKGROUND AND OBJECTIVES: A 408-kg patient presented for surgical resection of a lower extremity mass. METHODS: A specially designed bed and well-planned transport were used to deliver the patient to the operating room suite. The anesthetic technique included a continuous subarachnoid catheter with tetracaine and epinephrine. Intraoperative monitoring consisted of electrocardiography, pulse oximetry, intraarterial blood pressure, and mental status examinations. Massive intraoperative hemorrhage was treated with rapid volume infusions and vasopressors. RESULTS: Resection of a lower extremity mass was accomplished and the patient was eventually discharged from the hospital. CONCLUSIONS: The case report emphasizes that prior planning of all aspects of patient care is important in massively morbidly obese patients and that regional anesthesia is a valuable option in these patients.

Sodium nitroprusside: twenty years and counting.

SNP remains an effective, reliable, and commonly used drug for the rapid reduction of significant arterial hypertension regardless of the etiology, for afterload reduction in the face of low CO when blood volume is normal or increased, and for intraoperative induced hypotension. After establishing indwelling arterial monitoring, an initial infusion rate of 0.3-0.5 micrograms.kg-1.min-1 is begun with titration as needed up to 2.0 micrograms.kg-1.min-1. Higher rates for brief periods of time (10 min) are acceptable. The use of alternative drugs to reduce the dose or shorten the duration of infusion should be considered when the 2.0 micrograms.kg-1.min-1 range is exceeded (Table 1). SNP should not be used by individuals unfamiliar with its potency and metabolic pathways, as the many reports of adverse reactions testify. Careful attention to infusion rates, particularly in patients at risk for depleted thiosulfate stores, is mandatory, and the use of other drugs in conjunction with or instead of SNP should always be considered. As with many therapeutic interventions, SNP requires careful administration to appropriately selected patients by a clinician who knows its inherent hazards. Despite its toxicity, SNP is popular because it is often the most (in some cases, the only) effective drug in some difficult clinical circumstances.

The sensitivity of muscle force predictions to changes in physiologic cross-sectional area.

The mechanical effects of a muscle are related in part to the size of the muscle and to its location relative to the joint it crosses. For more than a century, researchers have expressed muscle size by its 'physiological cross-sectional area' (PCSA). Researchers mathematically calculating muscle and joint forces typically use some expression of a muscle's PCSA to constrain the solution to one which is reasonable (i.e. a solution in which small muscles may not have large forces, and large muscles have large forces when expected or when there is significant electromyographic activity). It is obvious that muscle mass (and therefore any expression of PCSA) varies significantly from person to person, even in individuals of similar weight and height. Since it is not practical to predict the PCSA of each muscle in a living subject's limb or trunk, it is important to generally understand the sensitivity of muscle force solutions to possible variations in PCSA. We used nonlinear optimization techniques to predict 47 muscle forces and hip contact forces in a living subject. The PCSA (volume/muscle fiber length) of each of 47 lower limb muscle elements from two cadaver specimens and the 47 PCSA's reported by pierrynowski were input into an optimization algorithm to create three solution sets. The three solutions were qualitatively similar but at times a predicted muscle force could vary as much as two to eight times. In contrast, the joint force solutions were within 11% of each other and, therefore, much less variable.(ABSTRACT TRUNCATED AT 250 WORDS)