The effect of two- and three-dimensional cell culture on the chondrogenic potential of human adipose-derived mesenchymal stem cells after subcutaneous transplantation with an injectable hydrogel

Articular cartilage is an avascular tissue composed of chondrocytes, a unique cell type responsible for abundant matrix synthesis and maintenance. When damaged, it never heals spontaneously under physiological circumstances. Therefore, the delivery of mesenchymal stem cells using hydrogel has been considered for cartilage repair. This study aims at investigating the influence of in vitro chondrogenic differentiation of human adipose tissue-derived stem cells (hATSCs) on in vivo cartilage formation when associated with a cellulose-based self-setting hydrogel (Si-HPMC). hATSCs were characterized for their proliferation, surface marker expression, and multipotency. The in vitro chondrogenic potential of hATSCs cultured within Si-HPMC in control or chondrogenic medium was evaluated by measuring COL2A1, ACAN, SOX9, and COMP expression by real-time PCR. Alcian blue and type II collagen staining were also performed. To determine whether in vitro chondrogenically differentiated hATSCs may give rise to cartilage in vivo, cells differentiated as a monolayer or in pellets were finally associated with Si-HPMC and implanted subcutaneously into nude mice. Cartilage formation was assessed histologically by alcian blue and type II collagen staining. Our data demonstrate that hATSCs exhibited proliferation and self-renewal. hATSCs also expressed typical stem cell surface markers and were able to differentiate towards the adipogenic, osteogenic, and chondrogenic lineages. Real-time PCR and histological analysis indicated that Si-HPMC enabled chondrogenic differentiation of hATSCs in inductive medium, as demonstrated by increased expression of chondrogenic markers. In addition, histological analysis of implants showed that chondrogenically differentiated hATSCs (monolayers or pellets) have the ability to form cartilaginous tissue, as indicated by the presence of sulphated glycosaminoglycans and type II collagen. This study therefore suggests that an in vitro induction of hATSCs in 2D was sufficient to obtain cartilaginous tissue formation in vivo. Si-HPMC associated with autologous hATSCs could thus be a significant tool for regenerative medicine in the context of cartilage damage.     

Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients

Ecochard M, Boillot O, Guillaud O, Roman S, Adham M, Mion F, Dumortier J. Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients.
Clin Transplant 2011: 25: 755–765. © 2010 John Wiley & Sons A/S. Abstract: Background: Allocation of graft in liver transplantation (LT) depends mainly on Model for End Stage Liver Disease (MELD) score. We studied the prognostic ability of three metabolic liver function tests in 560 cirrhotic patients listed for transplantation, in comparison with MELD and Child–Turcotte–Pugh (CTP) scores. Methods: Indocyanine green retention rate (ICG), aminopyrine breath test (ABT), and galactose elimination capacity were performed at the time of listing in addition to standard biological parameters. Seventy‐three patients died on waiting list, 438 were transplanted, and 73 died after LT. Cox regression analysis and receiver operating characteristic curves with c‐statistics were calculated after stratification according to CTP and MELD score. Results: For the mortality before transplantation, c‐statistics showed that ICG and ABT had a slightly better prognostic ability (0.73 and 0.68, respectively) than MELD score (0.66), and similar to CTP score (0.70). ABT’s prognostic ability remained significant once the MELD score (below and above 20) had already been taken into account. Only ICG had a prognostic ability to predict the survival after LT, even after stratification according to MELD and CTP score. Conclusions: Our results strongly support that ABT and ICG may be useful in the ranking of the patients in LT list, adding prognosis information in association with MELD score.     

Incidental Gallbladder Cancer by the AFC-GBC-2009 Study Group

Background  

Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry.     

Does the surgical technique for management of the distal ureter influence the outcome after nephroureterectomy?

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? The resection of the distal ureter and its orifice is an oncological principle during radical nephroureterectomy which is based on the fact that it represents a part of the urinary tract exposed to a considerable risk of recurrence. After removal of the proximal part it is hardly possible to image or approach it by endoscopy during follow‐up. Recent publications on survival after nephroureterectomy do not allow the conclusion that removal of distal ureter and bladder cuff are useless. Several techniques of distal ureter removal have been described but they are not equivalent in term of oncological safety. ? The standard treatment of upper urinary tract urothelial carcinomas (UUT‐UCs) must obey oncological principles, which consist of a complete en bloc resection of the kidney and the ureter, as well as excision of a bladder cuff to avoid tumour seeding. ? The open technique is the ‘gold standard’ of treatment to which all other techniques developed are necessarily compared, and various surgical procedures have been described. ? The laparoscopic stapling technique maintains a closed system but risks leaving behind the ureteric and bladder cuff segments. ? Transvesical laparoscopic detachment and ligation is a valid approach from an oncological stance but is technically difficult. The major inconvenience of the transurethral resection of the ureteric orifice and intussusception techniques is the potential for tumour seeding. ? Management of the distal ureter via the robot‐assisted laparoscopic method is technically feasible, but outcomes from these procedures are still preliminary. ? Therefore, prospective comparative studies with more thorough explorations of these techniques are needed to solve the dilemma of the management of the distal ureter during nephroureterectomy. However, bladder cuff excision should remain the standard of care irrespective of the stage of the disease.     

Postoperative analgesia after total hip arthroplasty: patient-controlled analgesia versus transdermal fentanyl patch

STUDY OBJECTIVE: To determine whether a new transdermal fentanyl patch (TFP) is a good choice for the postoperative pain management of patients undergoing primary total hip arthroplasty compared with patient-controlled analgesia (PCA). DESIGN: Randomized, prospective study. SETTING: University hospital. PATIENTS: 30 patients undergoing primary total hip arthroplasty. INTERVENTIONS: Patients received either a TFP (group T; Duragesic 50 microg/h, matrix fentanyl patch, Janssen-Cilag) applied approximately 10 hours before induction of general anesthesia and PCA programmed in the postanesthesia care unit (PACU), or PCA programmed in the PACU (group P). MEASUREMENTS: Intraoperative sufentanil and additional postoperative morphine administration were recorded, as well as visual analog scores and routine vital signs at predetermined intervals during the first 48 hours. MAIN RESULTS: Morphine consumption on arrival in the PACU was 3.5+/-3 mg in group T versus 13+/-5 mg in group P (P<0.0001). Visual analog scores on arrival in the PACU were 37+/-22 mm in group T versus 73+/-13 mm in group P (P<0.0001). Cumulative morphine consumption at the 24th hour was 43+/-16 mg in group P and 4+/-3 mg in group T (P<0.0001). Cumulative morphine consumption at the 48th hour was 54+/-26 mg in group P and 5+/-4 mg in group T (P<0.0001). Intraoperative sufentanil consumption was 38+/-15 microg in group T versus 30+/-5 microg in group P (not significant). The sedation score was 0 in both groups during the first 48 postoperative hours. CONCLUSIONS: Preoperative TFP application decreases pain scores and morphine consumption in the PACU and appears to have prolonged effects spanning the first 48 postoperative hours.     

Allosensitization in bridge to transplant Novacor left ventricular assist device patients: analysis of long-term outcomes with regard to acute rejection and chronic allograft vasculopathy

BACKGROUND: The true relevance of allosensitization in patients benefiting from left ventricular assist device (LVAD) as bridge to transplant (BTT) is still debated. Available registry data referred to numerous devices precluding LVAD-specific analysis. Therefore, we studied all patients with Novacor LVAD prior to transplantation. METHODS: From 1985 to 2006, 37 Novacor LVADs were implanted as BTT, with 30 patients surviving to transplantation (81%). Post-LVAD sensitization was determined for anti-HLA-class I and class II IgGs. Study endpoints were overall survival and/or graft loss, > or =3A cellular rejection and chronic allograft vasculopathy (CAV). The results from LVAD patients were compared to non-LVAD primary heart transplant recipients (n=318). RESULTS: After LVAD insertion, 5 out of 27 patients available for analysis developed anti-HLA antibodies (18.5%). The mean anti-HLA titer after Novacor LVAD implantation was 14% [SD 31]. Actuarial 5- and 10-year patient/graft survival for LVAD and non-LVAD transplant recipients were 73% and 55%, and 70% and 55%, respectively (p=NS). Overall prevalence of rejection > or =3A was 23.3 % (LVAD group) and 18.9% (non-LVAD group) (p=NS). At follow-up, the respective incidence of CAV was 8% (LVAD group) and 32.4% (non-LVAD group) (p<0.01). However, mean follow-up was significantly different for LVAD and non-LVAD patients, 46 vs 90 months (p<0.001). CONCLUSION: In this study, allosensitization occurred infrequently after Novacor LVAD implantation. Secondly, analysis of outcome variables shows that Novacor-LVAD BTT patients can anticipate similar survival to non-LVAD patients, thus minimizing the impact of allosensitization after LVAD implantation.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Myocardial and Coronary Effects of Propofol in Rabbits with Compensated Cardiac Hypertrophy

Background: Myocardial effects of propofol have been previously investigated but most studies have been performed in healthy hearts. This study compared the cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts.

Methods: The effects of propofol (10-1,000 [mu]m) on myocardial contractility, relaxation, coronary flow and oxygen consumption were investigated in hearts from rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM group, n = 10), using an isolated and erythrocyte-perfused heart model. In addition, to assess the myocardial and coronary effects of propofol in more severe LVH, hearts with a degree of hypertrophy greater than 140% were selected (severe LVH group, n = 7).

Results: The cardiac hypertrophy model induced significant left ventricular hypertrophy (136 +/- 21%, P < 0.05). The pressure-volume relation showed normal systolic function but an altered diastolic compliance in hypertrophic hearts. Propofol only decreased myocardial contractility and relaxation at supratherapeutic concentrations (>= 300 [mu]m) in SHAM and LVH groups. The decrease in myocardial performances was not significantly different in SHAM and LVH groups. Propofol induced a significant increase in coronary blood flow which was not significantly different between groups. In severe LVH group, the degree of hypertrophy reached to 157 +/- 23%. Similarly, the effects of concentrations of propofol were not significantly different from the SHAM group.     

Minimum Alveolar Concentration of Volatile Anesthetics in Rats during Postnatal Maturation

Background: Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown.

Methods: We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37[degrees]C).

Results: In adult rats, inspired MAC values corrected at 37[degrees]C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%).