Noninvasive quantitation of blood flow turbulence in patients with aortic valve disease using online digital computer analysis of Doppler velocity data.

Previous experimental studies have demonstrated that aortic valve disease is associated with significant downstream turbulence (T). In this study, we developed a noninvasive method on the basis of Doppler velocity recording for quantitating aortic blood flow T in patients with aortic valve disease. The instantaneous blood velocity at a point in the aorta is equal to the sum of a mean periodic velocity component with a random or turbulent velocity component. According to the ensemble average method, time mean absolute T intensity is the root-mean-square value of turbulent velocity averaged over time and T is better quantitated by the relative T intensity (TIr), which is the ratio of absolute T intensity to the ensemble average velocity averaged over time. We computed TIr in 18 patients with mild to severe aortic stenosis and in 13 healthy volunteers from instantaneous modal velocities of 70 cycle length-matched heart beats recorded in the proximal part of the descending aorta by pulsed Doppler using an ultrasound system with an output port for online digital data transfer into a microcomputer. TIr was greater in patients with aortic valve disease (18.4 +/- 5.1%, range 11.2%-28.9%) than in control patients (7.9 +/- 1.9%, range 4.8%-9.8%; P =.0001). In patients with aortic valve disease, TIr was better linearly related to the ratio of postvalvular aorta to valvular orifice cross-sectional areas (r = 0.89, P =.0001) than to other parameters of valve restriction: transvalvular pressure gradient (r = 0.78, P =.0001); valve area (r = -0.56, P =.01); and valve resistance (r = 0.72, P =.0002). Thus, T that can be computed noninvasively from direct digital transfer of Doppler velocity data appears to be linearly related to indices of aortic valve restriction. Our data support the concept of the postvalvular aorta to valvular orifice cross-sectional areas ratio as a new important hemodynamic parameter in patients with aortic valve disease.     

The age-dependent vasodilatation and endothelial calcium influx induced by elastin peptides are modulated by extracellular glucose level.

Elastin peptides have been shown to produce many biological effects on various cell types, including an endothelium- and NO-dependent vasodilatation mediated by extracellular calcium influx and intracellular calcium elevation. Under normal concentration of extracellular glucose, the vasodilatory effect is observed in adult rats and is lost with age. Here, we have studied the consequences of extracellular glucose level changes on these effects triggered by elastin peptides (10(-4)-10(-3) mg ml(-1)), on 6- and 30-month-old rats, using the tension myography and the patch-clamp techniques. Our results show that low (0 mM) or high (33 mM) extracellular glucose concentrations abolish the extracellular calcium influx induced, under normal glucose level (11 mM), by the elastin peptides in cultured human endothelial cells. Also, low or high glucose abolish the vasodilatory action of elastin peptides observed on aorta rings from adult rats under normal glucose concentration. On the contrary, a dilation of aged rat aorta is observed in the presence of elastin peptides and high glucose, whereas such dilation is not observed when the elastin peptides are added in the presence of normal glucose concentration. In aging, a restoration by high glucose of the NO-dependent vasodilatation induced by elastin peptides could enhance the production of damaging peroxynitrite, potentially altering the structure and function of the blood vessels. These results could be of importance in the evaluation and treatment of aged patients with pathophysiological dysregulations of the circulating glucose level, such as in diabetes, age-related glucose intolerance, or low glucose levels caused by inappropriate glucose control treatments.     

We Offer Renal Replacement Therapy to Patients Who Are Not Benefitted by It

Nephrologists offer renal replacement therapy (RRT) to patients who are unlikely to benefit in part because of our discomfort discussing goals of care in the setting of an uncertain prognosis for a given individual. Permanent neurological impairment, terminal illness (life expectancy <6 months), medical conditions precluding the safe delivery of dialysis, elderly patients with poor prognosis, and those who begin “early” RRT are categories of patients for whom dialysis may not be beneficial. Successful use of time‐limited trials of dialysis may reduce the number of patients who are started on RRT without significant benefit. However, clear achievable milestones and goals need to be incorporated into plans for time‐limited trials to ensure that continuing RRT beyond the trial period is appropriate. The lack of information on outcomes and symptom management using a “palliative approach” to dialysis suggests this should not be a clinical option until additional study is done and efficacy data available. Clinical practice guidelines are available to assist nephrologists in the appropriate withholding of RRT.     

Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta‐analysis

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post‐transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate‐treated kidney transplant recipients through meta‐analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow‐up duration was more than 6 months. We performed random‐effects meta‐analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm², 95% CI 0.012–0.099 and 0.053 g/cm², 95% CI 0.032–0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.     

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10‐year postrandomization follow‐up study

Long‐term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post‐transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients’ survival was 100%, 94.2%, and 95.8% (P = 0.25), and death‐censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m², respectively (P = 0.16). The incidence of biopsy‐proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus‐associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody‐mediated rejection (n = 6). De novo donor‐specific antibodies were detected in 13% of AZA‐, 21% of MMF‐, and 14% of CsA‐treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well‐selected renal transplant recipient ( ClinicalTrials.gov number: 980654).     

Eight‐year results of the Spiesser study,a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation

We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death‐censored graft survival (log‐rank compared), de novo DSA appearance, risk of malignancy, post‐transplant diabetes mellitus (PTDM), and anemia. Intent‐to‐treat and on‐treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death‐censored graft survival (P = 0.858). In conditional intent‐to‐treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long‐term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.     

Is tibial cut navigation alone sufficient in medial unicompartmental knee arthroplasty? Continuous series of fifty nine procedures

Purpose

Our purpose was to assess medial unicompartmental knee arthroplasty with navigation alone for the tibial cut and limb alignment. We hypothesised that this technique could be used routinely in practice.

Methods

Outcome measures were tibial cut orientation and residual varus. Six-month post-operative radiographs of 59 knees were assessed.

Results

Tibial cut orientation was within 2° of planned in 70.2 and 76.3 % of knees in the coronal and sagittal planes, respectively (49.1 % in both), within 4° in 91.2 and 91.5 %, respectively (82.5 % in both). All coronal-plane errors were in varus. Excessive planed tibial slope was at risk of excessive varus of the tibial cut. The hip-knee-ankle angle was ≤179° in 81.4 % and the mechanical axis through Kennedy Zone 2 in 59.3 % of knees. Risk factors for inadequate varus were pre-operative hip-knee-ankle angle >176° and strictly articular varus.

Conclusions

Our results are not as good as previously reported with this technique, but taking into account the factors of failure identified, we could enhance the results.