Dengue has a benign presentation in renal transplant patients: a case series

AIM: Dengue fever and its complications are a poorly described entity in the renal transplant population. Previous reports in renal transplant patients suggest a high mortality rate. METHODS: We undertook a retrospective study of six cases of dengue fever in renal transplant patients during a dengue outbreak in Singapore in 2005 which involved a total of 1400 cases in the city state. RESULTS: Mean thrombocytopenia was 130,000/microL on presentation and 80,000/microL at deffervescence. No dengue haemorrhagic fever, dengue shock syndrome, deaths or abnormal graft function were observed. Mean hospital stay was 8.6 days. Four of six patients also had simultaneous CMV reactivation. CONCLUSION: In common with the majority of adults, dengue fever follows a benign course in the renal transplant population and dengue haemorrhagic fever is rare. This may be related to the relative immunosuppression reducing the risk for antibody-enhanced complications.     

Postconditioning protects human atrial muscle through the activation of the RISK pathway

Ischemic postconditioning (IPost) has been demonstrated to reduce myocardial injury in patients undergoing primary coronary angioplasty for an acute myocardial infarction.Pre-clinical animal studies suggest that pro-survival protein kinases of the Reperfusion Injury Salvage Kinase (RISK) pathway such as Akt and Erk1/2 mediate the cardioprotective effect of IPost.Whether IPost can protect human myocardial tissue ex vivo and whether it recruits the RISK pathway in human myocardium are both not known. To investigate this, atrial appendages were harvested from patients undergoing cardiac surgery. From these samples atrial trabeculae were isolated and mounted on a superperfusion apparatus and subjected to 90 min of hypoxia followed by 120 min of reoxygenation at the end of which function expressed as a percentage of the recovery of baseline contractile function was determined.Atrial trabeculae were randomized to control, hypoxic preconditioning (HPre), hypoxic postconditioning comprising either four 30-s (HPost-30) or 60-s (HPost-60) episodes of alternating hypoxia and reoxygenation, and HPost in the presence or absence of UO126 (a MEK1/2 inhibitor) or LY294002 (a PI3K inhibitor).HPre and HPost-60 improved the recovery of baseline contractile function (45.4±3.2% with HPre and 45.2±2.2% with HPost-60 vs 26.7±2.1 % in control: N≥ 6/group: P<0.05), whereas HPost-30 failed to cardioprotect (28.3±3.4% with HPost-30 vs 26.7±2.1 % in control: N≥ 6/group: P>0.05). The cardioprotective effect of HPost-60 was abolished in the presence of either LY (28.1±2.5% with HPost-60+LY vs 45.2±2.2% with HPost-60: N≥ 6/group: P<0.05) or UO (32.7±1.8% with HPost-60+UO vs 45.2±2.2% with HPost-60:N=7/group: P<0.05). The kinase inhibitors alone had no effect on functional recovery (28.2±3.6% with LY and 30.1±4.8% with UO vs 26.7±2.1 % in control: N≥ 5/group: P>0.05). In conclusion, we demonstrate for the first time that postconditioning protects human myocardium ex vivo and that this effect is dependent on the activation of the RISK pathway.     

Cardiac pathology of permanent pacemaker implementation

The cardiac findings in five cases of permanent pacemaker implantation seen at autopsy in a three-year period is reported. Implantation was done for complete heart block in four patients and sick sinus syndrome in one. The periods of implantation ranged from seven days to four years. The common findings were right sided valvar and mural bland thrombus formation. Additional findings included superior vena caval thrombosis, endocardial 'tunnel' formation for the pacing wires, perforation of the tricuspid leaflet and a gross morphology similar to that seen in right sided endomyocardial fibrosis.     

Platelet-Rich Plasma (PRP) Injection in Sports Injuries

BackgroundSports injuries are very common, and the management demands high degrees of skills and best techniques for an early return to play. The use of Platelet Rich Plasma (PRP) injections in the treatment of tendon, muscle and ligament injuries has become popular. This study observes the outcomes of PRP injections in sports injuries.MethodsForty-eight athletes (mean age 29.93 ± 8.48, Male: 37, Female: 11) presenting to a sports medicine centre with different sports injuries with symptom duration (2.81 ± 1.94) months were given PRP injections (single or multiple) four weeks apart with maximum number of injections up to three depending upon the clinical condition, Pre and Post VAS scores. Specific rehabilitation program was administered and compliance was graded by Sports Injury Rehabilitation Adherence Scale (SIRAS). A 1 year follow-up of cases was done for assessing player satisfaction and return to play.ResultsPre-procedure (7.25 ± 0.70) and post-procedure (2.42 ± 0.74) VAS score for all athletes showed significant difference with a p value at 0.0001. The average number of injections was 1.35 ± 1.41 with 72.91% requiring only one injection while 18.75% and 8.33% required two and three injections, respectively.ConclusionAthletes who required a single injection for acute injuries of lower grade returned to sports activity earlier than those who required multiple injections for chronic injuries. PRP injection has optimal effects on sports injuries not responding to conservative management     

Sunitinib in urothelial cancer: clinical, pharmacokinetic, and immunohistochemical study of predictors of response

Background

Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond.

Objective

To identify predictors of response to sunitinib.

Design, setting, and participants

Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution. Blood pressure (BP), immunohistochemistry (IHC), and pharmacokinetic (PK) results were correlated with response to sunitinib.

Measurements

BP was assessed on day 1 and 28 of each cycle and on day 14 of cycle 1. IHC was performed on 55 samples from 38 cases using mammalian target of rapamycin and hypoxia-inducible factor (HIF) pathway marker antibodies. Blood samples for PK analysis were collected from 15 patients at three time points. Response was assessed using Response Evaluation Criteria in Solid Tumors criteria.

Results and limitations

Sunitinib-induced hypertension predicted improved response when hypertension was categorized as a discrete (p = 0.02) or continuous variable (p = 0.005 [systolic BP] and p = 0.007 [diastolic BP]). The odds ratio of response was 12.5 (95% confidence interval, 1.95-246.8) for grade 3/4 hypertension compared with grade 0. Response was associated with low HIF-1α expression in primary (p = 0.07) tissue. A nonstatistically significant trend was seen for an association between greater drug concentration and best response. A correlation between expression markers within the same pathways was identified, phosphorylated-4EBP1 and phosphorylated-S6 (p = 6.5 × 10⁻⁹), and vascular endothelial growth factor receptor 2 and HIF-1α (p = 0.008). Results are limited by small numbers.

Conclusions

Clinical and molecular biomarkers of response to sunitinib may have clinical relevance and require prospective validation. There is an urgent need for predictive biomarkers to guide the management of UC.     

Repair of spondylolysis using compression with a modular link and screws

We describe the results of a prospective case series of patients with spondylolysis, evaluating a technique of direct stabilisation of the pars interarticularis with a construct that consists of a pair of pedicle screws connected by a U-shaped modular link passing beneath the spinous process. Tightening the link to the screws compresses bone graft in the defect in the pars, providing rigid intrasegmental fixation. We have carried out this procedure on 20 patients aged between nine and 21 years with a defect of the pars at L5, confirmed on CT. The mean age of the patients was 13.9 years (9 to 21). They had a grade I or less spondylolisthesis and no evidence of intervertebral degeneration on MRI. The mean follow-up was four years (2.3 to 7.3). The patients were assessed by the Oswestry Disability Index (ODI) and a visual analogue scale (VAS). At the latest follow-up, 18 patients had an excellent clinical outcome, with a significant (p < 0.001) improvement in their ODI and VAS scores. The mean ODI score at final follow-up was 8%. Assessment of the defect by CT showed a rate of union of 80%. There were no complications involving the internal fixation. The strength of the construct removes the need for post-operative immobilisation.     

Learning curve of minimally invasive radical prostatectomy: Comprehensive evaluation and cumulative summation analysis of oncological outcomes

Background and objective

The primary objective was to evaluate the learning curve of minimally invasive radical prostatectomy (MIRP) in our institution and analyze the salient learning curve transition points regarding oncological outcomes.