Hemodialysis vascular access modifies the association between dialysis modality and survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.     

Value of an objective assessment tool in the operating room

Background

Concerns about the achievement of surgical proficiency during residency are increasing. To objectify surgical skills, the Objective Structured Assessment of Technical Skills (OSATS) was developed and proven valid, feasible and reliable for use in laboratory settings. This study aimed to evaluate the value of this tool for intra-operative use.

Methods

Residents were assessed with an OSATS after every procedure they performed as the primary surgeon during a 3-month clinical rotation in gynecological surgery. We mapped individual learning curves (OSATS scores plotted against experience) and established the average procedure-specific learning curve. We used linear mixed models to assess the relation between performance and experience.

Results

Nine residents were recruited and 319 OSATS analyzed. Individual learning curves revealed progression beyond 24 of 30 OSATS points for 7 residents. Performance on the average procedure improved with experience, and the OSATS score increased by an average of 1.10 points per assessed procedure (p = 0.008, 95%confidence interval 0.44–1.77). Median OSATS scores ranged from 18 to 30 among the 21 assessors.

Conclusion

Intraoperative implementation of OSATS seems to offer important advantages: structured feedback is facilitated, and learning curves enable insight into individual progression. However, doubts have been raised about the objectivity of the tool. Therefore, caution is warranted in using it for graduation and certification.     

Dobutamine stress thallium-201 single-photon emission tomography versus echocardiography for evaluation of the extent and location of coronary artery disease late after myocardial infarction

Dobutamine stress echocardiography and thallium-201 myocardial perfusion scintigraphy are clinically useful methods for the evaluation of coronary artery disease (CAD). However, the relative merits of these imaging modalities in the evaluation of the extent of CAD after myocardial infarction have not been well studied. The aim of this study was to compare the accuracy of dobutamine stress echocardiography and simultaneous ²⁰¹Tl single-photon emission tomography (SPET) imaging for the diagnosis and localization of CAD late after acute myocardial infarction. Dobutamine (up to 40 μg kg^–1 min^–1)-atropine (up to 1 mg) stress echocardiography in conjunction with stress-reinjection ²⁰¹Tl SPET was performed for the evaluation of myocardial ischaemia in 90 patients with previous myocardial infarction who underwent coronary angiography. Significant CAD was predicted on bases of myocardial ischemia (new or worsening wall motion abnormalities on echocardiography and reversible perfusion defects on ²⁰¹Tl SPET). Significant CAD (≥ 50% luminal diameter stenosis) was detected in 73 (81%) patients. The sensitivity, specificity and accuracy of echocardiography in detecting remote ischaemia for the diagnosis of remote CAD (present in 53 patients) were, respectively, 79% (CI 70%–88%), 85% (CI 77%–93%) and 81% (CI 73%–90%), while the corresponding figures for ²⁰¹Tl SPET were 75% (CI 66%–85%), 78% (CI 69%–87%) and 76% (CI 67%–86%) respectively (P = NS vs echocardiography). The sensitivity, specificity and accuracy of echocardiography in detecting peri-infarction ischaemia for the diagnosis of infarct-related artery stenosis (present in 70 patients) were, rspectively, 77% (CI 68%–86%), 85% (CI 78%–92%) and 79% (CI 70%–87%) while the corresponding figures for ²⁰¹Tl SPET were 73% (CI 64%–82%), 85% (CI 78%–92%) and 76% (CI 67%–84%) respectively (P = NS vs echocardiography). The agreement between the two methods for the diagnosis of peri-infarction and remote ischaemia was 70% (kappa = 0.37) and 80% (kappa = 0.59) respectively. It is concluded that dobutamine stress echocardiography and ²⁰¹Tl SPET have comparable accuracy for the diagnosis of infarct related and remote CAD in patients with previous myocardial infarction. The agreement between the methods is higher for the diagnosis of remote CAD than for that of peri-infarction ischaemia. Received 17 October 1998 and in revised form 5 January 1999     

Contrast in the efficacy of hDAF mouse hearts between ex vivo perfusion and transplantation into primates

Abstract: In recent experiments, in which we compared hDAF transgenic rat hearts perfused with 15% human serum in the Langendorff device and hDAF rat hearts transplanted into cynomolgus monkeys, we demonstrated that in the ex vivo heart perfusion model both homozygous and heterozygous hDAF hearts survived longer as nontransgenic controls. Surprisingly, we found that only homozygous hDAF hearts were protected against hyperacute rejection in vivo. The first aim of this study was to determine whether perfusion of mouse hearts with higher human serum concentrations or human blood might explain some of the differences found in survival time of the recently performed experiments with rat heart xenografts. Secondly, we investigated whether the observed differences in survival times of rat xenografts between in vivo and ex vivo transplantation would also hold for mouse hearts transgenic for hDAF. An ex vivo model was used to perfuse hDAF mouse hearts and controls with human serum or blood, and hDAF transgenic hearts and controls were transplanted into cynomolgus monkeys. hDAF transgenic mouse hearts survived significantly longer than their controls when perfused with 15% human serum, but no difference was found when 30% human serum was used, or when these hearts were transplanted into cynomolgus monkeys. However, in both the in vivo and ex vivo models the amount of PMNs adhering to the vascular endothelium was significantly lower in hDAF transgenes as compared with their controls. In conclusion, in the ex vivo situation, the efficacy of hDAF transgenesis in preventing HAR is limited by serum complement concentration.     

State of the art of where we are at using stem cells for stress urinary incontinence

AIMS: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors. METHODS: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory. RESULTS: In anatomical and functional studies of human and animal urethra, the middle urethra containing rhabdosphincter, is critical for maintaining continence. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as MDSCs and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. Not all cellular therapies are the same, as demonstrated by the differences in safety and efficacy from muscle-sourced MDSCs versus myoblasts versus fibroblasts. CONCLUSIONS: Transplanted stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. The dawn of a new paradigm in the treatment of SUI may be near.     

Comparison between the C-leg microprocessor-controlled prosthetic knee and non-microprocessor control prosthetic knees: a preliminary study of energy expenditure, obstacle course performance, and quality of life survey

This study investigated energy expenditure and obstacle course negotiation between the C-leg and various non-microprocessor control (NMC) prosthetic knees and compared a quality of life survey (SF-36v2) of use of the C-leg to national norms. Thirteen subjects with unilateral limb loss (12 with trans-femoral and one with a knee disarticulation amputation) participated in the study. The mean age was 46 years, range 30-75. Energy expenditure using both the NMC and C-leg prostheses was measured at self-selected typical and fast walking paces on a motorized treadmill. Subjects were also asked to walk through a standardized walking obstacle course carrying a 4.5 kg (10 lb) basket and with hands free. Finally, the SF-36v2 was completed for subjects while using the C-leg. Statistically significant differences were found in oxygen consumption between prostheses at both typical and fast paces with the C-leg showing decreased values. Use of the C-leg resulted in a statistically significant decrease in the number of steps and time to complete the obstacle course. Scores on a quality of life index for subjects using the C-leg were above the mean for norms for limitation in the use of an arm or leg, equal to the mean for the general United States population for the physical component score and were above this mean for the mental component score. Based on oxygen consumption and obstacle course findings, the C-leg when compared to the NMC prostheses may provide increased functional mobility and ease of performance in the home and community environment. Questionnaire results suggest a minimal quality of life impairment when using a C-leg for this cohort of individuals with amputation.     

A ten-year experience with laparoscopic treatment of splenic cysts.

BACKGROUND AND OBJECTIVES: The management of symptomatic splenic cysts lacks clear, evidence-based guidelines due to its low incidence. Recently, laparoscopic treatment has been described. We present our experience with the laparoscopic management of solitary splenic cysts with a review of the existing literature, and recommendations for therapy. METHODS: All patients who underwent laparoscopic treatment of splenic cysts over a 10-year period were identified. The medical records of these 9 patients were reviewed. RESULTS: All surgeries were performed laparoscopically, with no conversions. Two patients underwent cyst decapsulation, and 7 patients underwent cyst unroofing. No major complications occurred. Recurrence occurred in 33.3% of patients; unroofing had a recurrence rate of 42.9% compared with 0% after decapsulation. Pseudocysts were found in 66.7% of patients and true cysts on final pathology were found in 33.3%. CONCLUSIONS: Laparoscopic decapsulation and unroofing of splenic cysts are safe procedures that confer the advantages of both splenic preservation and minimally invasive surgery. Cyst unroofing has a high recurrence and should be selectively used. Laparoscopic cyst decapsulation is associated with longer operative time, but should be considered as first-line therapy.     

Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies promotes long-term survival and function of neonatal porcine islet xenografts in spontaneously diabetic NOD mice

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic islet beta-cells, which are required for the production of insulin. Islet transplantation has been shown to be an effective treatment option for TIDM; however, the current shortage of human islet donors limits the application of this treatment to patients with brittle T1DM. Xenotransplantation of pig islets is a potential solution to the shortage of human donor islets provided xenograft rejection is prevented. We demonstrated that a short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) was highly effective in preventing rejection of neonatal porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune-prone nonobese diabetic (NOD) mice is not known. Given that the current application of islet transplantation is for the treatment of T1DM, we set out to determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote long-term survival of NPI xenografts in NOD mice. Short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in preventing rejection of NPI xenografts in B6 mice, failed to promote long-term survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted in xenograft function in 9/12 animals and long-term graft (>100 days) survival in 2/12 mice. Immunohistochemical analysis of islet grafts from these mice identified numerous insulin-producing beta-cells. Moreover, the anti-porcine antibody as well as autoreactive antibody responses in these mice was reduced similar to those observed in naive nontransplanted mice. These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice.     

As time goes by: temporal constraints on emotional activation of inferior medial prefrontal cortex

To investigate the influence of stimulus duration on emotional processing, we measured changes of regional cerebral blood flow (rCBF) in 14 healthy subjects who viewed neutral or emotional images presented for 3 or 6 s. Presentation for 3 s reproduced the previous result of higher rCBF in inferior medial prefrontal cortex (IMPC) during neutral than emotional stimulation. Six-second presentation reverted this relationship, with activity in IMPC being higher during emotional stimulation. Prolonged stimulus presentation attenuated the rise of rCBF associated with emotions in left parietal cortex and cerebellar hemisphere. We speculate that the different rCBF during neutral and emotional stimulation for 6 s is a consequence of attention divided between the emotional stimuli and their associations. Thus, prefrontal activity rises when a cognitive task accompanies emotional stimulation because several cognitive processes compete for attention. The IMPC may serve the mechanism of attention underlying the concept of a default mode of brain function, selecting among competitive inputs from multiple brain regions rather than just processing emotions. The results emphasize the importance of implicit cognitive processing during emotional activation, however, unintended.