The Seventh Prototype of the Mini‐Spindle‐Pump: Does It Fulfill the Expectations of a Short‐Term Pump?

According to recent trends to develop implantable nonpulsatile blood pumps for different function modes and times, our intention was and still is to build a Mini-Spindle-Pump for a pumping duration of about 14 days. Initial conception for this plan was the premise that the device in a mock circuit should move 4 L of water/min at a speed of 12,000 to 15,000 rpm against a pressure difference of 90 mm Hg between pump inlet and outlet. Despite the development of 6 different prototypes, this project was not realized. Under the above-mentioned conditions, the main problem of this type of blood pump, the blood trauma, could not be reduced to an adequate level, i.e., the Mini-Spindle-Pump is not a high speed pump. Therefore, a revision of the conception was necessary. The device in a mock circuit should transport 5 L of water/min at a speed of about 9,000 rpm against a pressure difference of 90 mm Hg between its inlet and outlet. Considering the implantability of the blood pump, the following measurements for its components were arrived at. The U-shaped blockformed plexiglas housing was enlarged to 120 x 40 x 40 mm (length of blood chamber 86 mm, inner diameter 27 mm), and the rotor with 5 windings was redesigned at a length of 64 mm (outer diameter 25 mm, inner diameter 6.7 mm). In a mock circuit, this 7th prototype transported with a speed of 9,000 rpm about 10 L of water/min at an afterload of 80 mm Hg. In acute animal experiments with calves up to 15 h of pumping duration, the device showed the expected efficiency. Experiments with a longer pumping duration are necessary to confirm that this prototype will fulfill the criteria of a short-term pump according to Dr. Y. Nosé's advice.     

Do pre‐irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible?

BACKGROUND: This study was done to determine if pre-radiotherapy (pre-RT) dental extractions reduce the risk of osteoradionecrosis (ORN). METHODS: Between 1987 and 2004, 413 patients with oropharyngeal carcinomas were treated with definitive RT at the University of Florida. Dentate patients underwent pretreatment dental evaluation. Teeth in the RT field were usually extracted if thought to have poor long-term prognosis from dental disease. The endpoint was > or = grade 2 ORN using a modified staging system. Patients were excluded for local recurrence, additional RT above the clavicles, or head and neck surgery besides neck dissection. RESULTS: ORN rates were as follows: edentulous, <1%; teeth in-field with pre-RT extractions, 15%; and teeth in-field without pre-RT extractions, 9%. Patients with poor in-field teeth and pre-RT extractions had a higher 5-year incidence of ORN than those who did not have pre-RT extractions (16% vs 6%, p = .48). Likewise, for those with in-field teeth in good condition and pre-RT extractions, the 5-year ORN incidence was higher than for those who did not undergo extractions (15% vs 2%, p = .42). Multivariate analysis revealed increased ORN risk with doses of >70 Gy, once-daily fractionation, or brachytherapy. CONCLUSION: Pre-RT extractions do not appear to reduce the risk of ORN.     

Should the non‐operative management of appendicitis be the new standard of care?

Appendicitis is one of the most commonly encountered emergency presentations to the general surgical services. The operative management of this condition is associated with significant financial costs and represents a significant workload on the emergency surgical services. Negative appendicectomy rates remain high (20–25%) despite advancements in laboratory testing and imaging techniques. Recent data from randomized controlled trials suggests that non‐operative management in patients presenting with uncomplicated or non‐perforated acute appendicitis is a viable alternative, with only 23% of patients requiring an appendicectomy at 1 year and an overall reduction in complications. In view of this, the traditional teaching of mandatory appendicectomy for all patients with acute appendicitis should be challenged. This article briefly reviews the evidence that supports the use of diagnostic tests to reduce the negative appendicectomy rate and examines the potential selection criteria for non‐operative management. The data raises the questions: can a 20–25% negative appendicectomy rate be defended as best practice and can the traditional dogma of early appendicectomy to prevent perforation be supported?     

Does DCD Donor Time‐to‐Death Affect Recipient Outcomes? Implications of Time‐to‐Death at a High‐Volume Center in the United States

For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single‐center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0–1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1–2 h. Five‐year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5‐year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait‐time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually.     

Short‐term administration of prulifloxacin in patients with nonmuscle‐invasive bladder cancer: an effective option for the prevention of bacillus Calmette‐Guérin‐induced toxicity?

OBJECTIVE

To determine whether the new fluoroquinolone prulifloxacin might improve tolerance to Bacillus Calmette‐Guérin (BCG) intravesical therapy in patients with bladder cancer.

PATIENTS AND METHODS

A series of 72 patients with intermediate‐ or high‐risk nonmuscle‐invasive bladder cancer were enrolled in this prospective, randomized, open‐label, controlled clinical trial performed at a single tertiary care institution. After complete transurethral resection, patients were randomized to receive induction treatment with BCG and three capsules of prulifloxacin 600 mg or no prophylactic treatment (control group). Adverse events (AEs) were self‐recorded by the patients after each instillation and classified by the investigator according to a classification grid considering account duration and intensity. Cystoscopy findings at 3 and 6 months were also recorded.

RESULTS

There was no significant difference in baseline symptoms between the groups. Overall, there was a significant decrease in the percentage of patients with at least one AE between instillations in prulifloxacin‐treated group. The proportion of patients with moderate to severe AEs after the fourth instillation was significantly less in the prulifloxacin‐treated group. There was a significant effect of prulifloxacin on the need for anti‐tuberculosis treatment. More patients in the control group stopped or delayed the full induction course of BCG instillations (34% vs 19%, P = 0.04). Recurrence rates were not affected by prulifloxacin treatment.

CONCLUSION

Prulifloxacin reduces the incidence of moderate to severe AEs from BCG intravesical therapy in patients with nonmuscle‐invasive bladder cancer, improving compliance to the induction BCG course. These preliminary findings warrant further clinical research.     

Are anti‐endothelial cell antibodies a pre‐requisite for the acute vascular rejection of xenografts?

Dorling A. Are anti‐endothelial cell antibodies a pre‐requisite for the acute vascular rejection of xenografts? Xenotransplantation 2003; 10: 16–23. © Blackwell Munkgaard, 2003 Background: Vascular rejection occurring within the first few weeks after transplantation is still the major immunological barrier to the long term survival of xenografts. Currently there is no consensus about what to call this type of rejection (acute vascular rejection, delayed xenograft rejection or acute humoral xenograft rejection), nor about how to prevent or treat it. Methods: A review of published evidence to define the heterogeneity of this phase of rejection and examine the role of antibodies, complement and graft‐infiltrating inflammatory cells. Results: i) antibodies are always involved in acute vascular rejection; ii) this antibody‐mediated rejection may be complement‐dependent or ‐independent; iii) inflammatory cells may mediate an antibody‐ and complement‐independent phase of rejection in some small animal models (which, in its pure form cannot be called ‘vascular rejection’) iv) there remain significant questions about the relevance of ‘accommodation’ and the importance of coagulation abnormalities. Conclusions: Without doubt, future research would be helped by distinguishing between these different forms of delayed xenograft rejection, using terminology to reflect the involvement of specific pathophysiological mechanisms. An updated classification of the stages of xenograft rejection is proposed here.     

Does loading influence the severity of cartilage degeneration in the canine Groove‐model of OA?

Many animal models are used to study osteoarthritis (OA). In these models the role of joint loading in the development of OA is not fully understood. We studied the effect of loading on the development of OA in the canine Groove‐model. In ten female beagle dogs OA was induced in one knee according to the Groove‐model. The animals were divided in groups with and without forced‐loading. Forced‐loading was achieved by fixing the contra‐lateral limb to the trunk 3 times a week for 4 hours. After 20 weeks joint tissues of all dogs were evaluated. Subjective evaluation revealed less movement with more loading in the forced‐loading‐group compared to the group without forced‐loading. In both groups induction of OA resulted in macroscopical and microscopical OA changes as well as alterations in cartilage metabolism characteristics for OA. Although differences were small, for some parameters they were statistically significant for the forced‐loading‐group. There were no differences between the contra‐lateral healthy joints of both groups. The present study demonstrates that in the Groove‐model intensified loading is not a prerequisite for the development of OA, although it adds to some extent to the severity of the OA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1332–1338, 2009     

Can thrombin‐activated platelet releasate compensate the age‐induced decrease in cell proliferation of MSC?

Mesenchymal progenitor cells (MSCs) are promising for cell‐based regeneration therapies. In elderly patients a reduced proliferation of MSCs has been described. Platelet‐rich plasma (PRP) contains important factors necessary for osteogenic regeneration. The aim of this study was to find out whether the age‐induced decrease in cell proliferation can be compensated by the use of supernatant of centrifuged, activated PRP (tPR). MSCs of donors of three age groups (A: young, 14–16 years, B: middle age, 36–46 years, C: older, 74–83 years) were expanded with 20% FCS alone or supplemented with thrombin‐activated platelet releasate (tPR) (1%, 2.5%, and 5%) or platelet‐poor plasma (PPP 5%). Cell proliferation and differentiation was measured on days 0, 3, and 7. Proliferation increased significantly in groups A and B with tPR, and non‐significantly in group C. The generation times of MSCs of elderly patients were significantly increased in group C compared to groups A and B. Addition of 1% or 2.5% tPR significantly reduced population doubling times of all age groups. Adding tPR stimulates the proliferation rate of MSCs independent of donor age. For juvenile and middle‐aged patients this influence was significant. Cells differentiation into osteoblasts was not influenced by addition of tPR. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1786–1795, 2013     

What is the role of risk‐adjusted funnel plots in the analysis of radical cystectomy volume–outcome relationships?

Study Type – Therapy (outcomes research) Level of Evidence 2b What’s known on the subject? and What does the study add? The use of funnel plots has helped to overcome the limitations and risks of ranking surgical performance. The case for a more widespread application of funnel plots in assessing and reporting performance in surgery has been made. No study has previously published a funnel plot analysis of outcomes for radical cystectomy in England. No Trust, using the final complex model for risk‐adjustment, can be confidently said to have a performance worse than the national average for both mortality and re‐intervention rates following radical cystectomy. Funnel plots act as a complementary method of validating volume‐outcome data by displaying disaggregated outcomes at a provider level and reduce the opportunity for spurious labelling of outliers.

OBJECTIVE

? To explore whether risk‐adjusted funnel plots are a useful adjunct to analyse volume–outcome data and to further facilitate our understanding of institutional performance data by combining funnel‐plot methodology with an incremental statistical modelling approach.

PATIENTS AND METHODS

? Risk‐adjusted funnel plots were generated for mortality and re‐intervention rates after elective radical cystectomy using administrative data from NHS Hospital Trusts between 2000/01 and 2006/07. Trusts were divided into volume tertiles based on their average annual cystectomy rate. ? A funnel plot was produced for each of the following four incremental statistical models: model one (no adjustment), model two (adjusted for patient case mix variables), model three (case mix and ‘clustering’ of patients) and model four (additional adjustment for institutional structural and process‐of‐care variables).

RESULTS

? In the final complex model (model four), no Trusts had abnormally high mortality or re‐intervention rates. ? Comparison of the funnel plots showed the importance of adjusting for certain confounding factors, such as the surgeon, at the institutional level, before they could be labelled as having truly outlying performance.

CONCLUSION

? Risk‐adjusted funnel plots have a useful role to play as a component of a methodological framework for investigating the volume–outcome relationship at the institutional level. They can act as a complementary method of validating data by displaying disaggregated outcomes at provider level and account for unmeasured confounders, so reducing the opportunity for spurious labelling of outliers.     

Does photodynamic transurethral resection of bladder tumour improve the outcome of initial T1 high‐grade bladder cancer? A long‐term follow‐up of a randomized study

OBJECTIVE

To evaluate, in a long‐term follow‐up of T1 high‐grade bladder cancer treated in a prospective, randomized trial, whether fluorescence diagnosis (FD) increases recurrence‐free survival (RFS) or reduces progression to muscle‐invasive stages.

PATIENTS AND METHODS

In all, 191 patients with suspected superficial bladder cancer were treated with transurethral resection under white light (WL) or with FD; 46 presented with initial T1 high‐grade BC (WL, 25; FD, 21). There were no differences in multifocality of tumours, concomitant carcinoma in situ or tumour size in either group.

RESULTS

Patients were followed for a median of 7.3 (WL) and 7.5 (FD) years to evaluate RFS. In the WL group there were 11, and in the FD group three, recurrent tumours of the same stage and grade. The RFS at 4 and 8 years was 69% and 52% in the WL, and 91% and 80% in FD group, respectively. With FD, the RFS was significantly longer according to Kaplan‐Meier analysis (P = 0.025). In the WL group, three (12%), and in the FD group four (19%) patients progressed to muscle‐invasive stages (≥ T2).

CONCLUSION

In initial T1 high‐grade bladder cancer, FD is significantly better than conventional WL transurethral resection for RFS. However, the progression rate to muscle‐invasive disease was not reduced by FD. Thus the clinical course (progression) of T1 high‐grade bladder cancer remains unaffected by FD.     

Can we improve the definition of high‐risk,hormone naïve,non‐metastatic prostate cancer?

• To identify criteria beyond Tumour‐Node‐Metastasis (TMN)‐, prostate‐specific antigen (PSA)‐ and Gleason score‐based standard classifications to enhance the stratification of non‐metastatic high‐risk prostate cancer.
• A detailed search of the literature was performed using PubMed.
• The authors reviewed the literature and used a modified Delphi approach to identify relevant approaches to enhance standard classifications.
• Specific criteria for high‐risk prostate cancer vary across guidelines and clinical trials, reflecting the differing perspectives concerning the definition of ‘risk’ between different specialities within the urology/radiation oncology community.
• In addition to the present classifications, evidence exists that the measure of cancer volume can provide additional prognostic value.
• More accurate imaging, especially multiparametric magnetic resonance imaging can also provide information concerning staging and cancer volume, and thus may assist in the identification of patients with high‐risk prostate cancer.
• A refined definition of non‐metastatic high‐risk prostate cancer is proposed.
• Within this high‐risk cohort, patients with multiple high‐risk criteria are especially at risk of prostate cancer‐specific mortality.

     

Liver transplant from Anti‐HBc‐positive,HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature

Avelino‐Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti‐HBc‐positive, HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature.
Clin Transplant 2010: 24: 735–746. © 2010 John Wiley & Sons A/S. Abstract: Introduction: After liver transplant (LT) from Anti‐HBc+/HBsAg? donors into HBsAg? recipients, transmission of hepatitis B virus (HBV) may occur (de novo HBV infection). This study analyzes the incidence of de novo HBV infection in HBsAg? recipients of Anti‐HBc+/HBsAg? LT with respect to: (i) the recipients’ HBV serology and (ii) the type of preventive therapy adopted. Methods: A systematic review of the literature using the electronic database Medline. Results: Five hundred and fifty‐two LT in 36 articles were selected. Lamivudine, Hepatitis B immune globulin (HBIG), revaccination, and combined therapies were employed in multiple strategies as preventive interventions. Naïve recipients had a high risk of de novo HBV infection, with smaller incidences when HBIG and lamivudine were used, either alone or in association. Vaccinated recipients or those with isolated hepatitis B core antibodies (Anti‐HBc) and previous HBV infection had lower risks of viral transmission, additionally reduced by any prophylaxis adoption. Discussion: LT from Anti‐HBc+/HBsAg? donors into HBsAg? recipients is apparently safe, as long as the recipient is vaccinated or presents an isolated Anti‐HBc or previous HBV infection and some prophylaxis is employed. Currently lamivudine seems the best alternative; other nucleoside analogs and revaccination strategies should be considered in future studies. Follow‐up and preventive therapies should be maintained for five yr or preferably throughout the recipients’ life span.     

Is β‐endorphin significant in the control of the male sexual response?

It has been assumed that β‐endorphin, belonging to the family of opiodergic neuropeptides, might facilitate the inhibition of the male sexual response; however, its role in the control of the penile erectile tissue remains to be elucidated. This study aimed to evaluate in healthy men the course of β‐endorphin in the systemic and cavernous blood through different stages of sexual arousal. Thirty‐four (34) men were exposed to erotic stimuli to induce penile tumescence and rigidity. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Plasma levels of β‐endorphin were determined by means of radioimmunometric methods. The effects of β‐endorphin on isolated human penile erectile tissue were investigated in vitro. β‐endorphin did not induce a contractile response of the cavernous tissue or reverse the contraction induced by noradrenaline. β‐endorphin decreased in the systemic blood when the penis became tumescent and rigid and increased during detumescence. In the cavernous blood, no alterations in β‐endorphin concentrations were observed. The drop in β‐endorphin observed during tumescence and rigidity seems likely to reflect the inhibition of the opioidergic input with the beginning of sexual arousal.