Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.     

Intramedullary nailing of humeral diaphyseal fractures. Is distal locking really necessary?

Purpose:

Distal interlocking is regarded as an inherent part of the antegrade humeral nailing technique, but it exposes both the patient and surgeon to radiation, is time consuming, and has a potential risk of damaging neurovascular structures. We have presented our technique of diaphyseal humeral nailing without any distal interlocking in this paper.

Materials and Methods:

We have presented a series of 64 consecutive patients (33 male and 31 female, mean age: 41.5 years) with humeral shaft fractures treated with antegrade rigid intramedullary nailing without distal interlocking following a strict intra and postoperative protocol. According to the AO classification, there were 36 type A fractures, 22 type B, and 6 type C. Nails were inserted unreamed or by using limited proximal reaming and they were fitted as snuggly as possible into the medullary canal. After impaction of the nail into the fossa, we carefully tested rotational stability of fixation by checking any potential external rotation when the arm was slightly turned externally and left to the gravity forces. We were ready to add distal screws, but that was not required in these cases. Follow-up assessment included fracture union, complications and failures, and the final clinical outcome at minimum 2-year follow-up using the parameters of the constant score.

Results:

All fractures, except two, united between the 4^th and 5^th postoperative month. In one case, nail was exchanged with plate, and, in another, a larger nail was used at a second surgery. Shoulder function according to constant score, at a minimum of 2-year follow-up, was excellent or very good in 93.7% of the patients.

Conclusions:

Provided that some technical issues are followed, the method reduces intraoperative time and radiation exposure and avoids potential damage to neurovascular structures.     

Nephrostomy in percutaneous nephrolithotomy (PCNL): does nephrostomy tube size matter? Results from The Global PCNL Study from The Clinical Research Office Endourology Society

Purpose

To explore the relationships between nephrostomy tube (NT) size and outcome of percutaneous nephrolithotomy (PCNL).

Methods

The Clinical Research Office of the Endourological Society (CROES) prospectively collected data from consecutive patients treated with PCNL over a 1-year period at 96 participating centers worldwide. This report focuses on the 3,968 patients who received a NT of known size. Preoperative, surgical procedure and outcome data were analyzed according to NT size, dividing patients into two groups, namely small-bore (SB; nephrostomy size ≤ 18 Fr) and large-bore (LB; nephrostomy size > 18 Fr) NT.

Results

Patients who received a LB NT had a significantly lower rate of hemoglobin reduction (3.0 vs. 4.3 g/dL; P < 0.001), overall complications (15.8 vs. 21.4 %; P < 0.001) and a trend toward a lower rate of fever (9.1 vs. 10.7 %). Patients receiving a LB NT conversely had a statistically, though not clinically significant, longer postoperative hospital stay (4.4 vs. 4.2 days; P = 0.027). There were no differences in urinary leakage (0.9 vs. 1.3 %, P = 0.215) or stone-free rates (79.5 vs. 78.1 %, P = 0.281) between the two groups.

Conclusions

LB NTs seem to reduce bleeding and overall complication rate. These findings would suggest that if a NT has to be placed, it should better be a LB one.     

Bacterial prostatitis

Objectives

The prostatitis syndrome is classified into bacterial prostatitis (acute and chronic), chronic pelvic pain syndrome and asymptomatic prostatitis. The aim of this report is to review current management standards for bacterial prostatitis.

Methods

A research was performed on literature dealing with acute and chronic bacterial prostatitis.

Results

There is a consensus on diagnostic management of bacterial prostatitis comprising microbiological sampling of midstream urine in acute bacterial prostatitis and performance of a bacterial localisation test in chronic bacterial prostatitis. Approximately 10 % of acute bacterial prostatitis cases eventually develop into chronic bacterial prostatitis and further 10 % into chronic pelvic pain syndrome. Bacterial isolates causing acute bacterial prostatitis are highly virulent strains comprising an array of different virulence factors. Presumably, the additional ability of isolates to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis. Therapy for infectious prostatitis is standardised with antibiotics as the primary agents, empirically administered in acute prostatitis and after susceptibility testing in chronic bacterial prostatitis. Fluoroquinolones exhibit more favourable pharmacological properties; therefore, fluoroquinolones have been recommended as first-line agents in the treatment for chronic bacterial prostatitis. Antibiotic resistance to fluoroquinolones, however, is increasing and is posing significant clinical problems. Further studies on alternative antibiotics active within the prostate are therefore needed both for prophylaxis in transrectal prostate biopsy, for example, and for therapy of chronic bacterial prostatitis.

Conclusions

Bacterial prostatitis has developed into well-managed entities with increasing antimicrobial resistance being the most severe drawback of yielding therapeutic success.     

Pudendal nerve block in HDR-brachytherapy patients: do we really need general or regional anesthesia?

Purpose

In male patients, the pudendal block was applied only in rare cases as a therapy of neuralgia of the pudendal nerve. We compared pudendal nerve block (NPB) and combined spinal-epidural anesthesia (CSE) in order to perform a pain-free high-dose-rate (HDR) brachytherapy in a former pilot study in 2010. Regarding this background, in the present study, we only performed the bilateral perineal infiltration of the pudendal nerve.

Methods

In 25 patients (71.8 ± 4.18 years) suffering from a high-risk prostate carcinoma, we performed the HDR-brachytherapy with the NPB. The perioperative compatibility, the subjective feeling (German school marks principle 1–6), subjective pain (VAS 1–10) and the early postoperative course (mobility, complications) were examined.

Results

All patients preferred the NPB. There was no change of anesthesia form necessary. The expense time of NPB was 10.68 ± 2.34 min. The hollow needles (mean 24, range 13–27) for the HDR-brachytherapy remained on average 79.92 ± 12.41 min. During and postoperative, pain feeling was between 1.4 ± 1.08 and 1.08 ± 1.00. A transurethral 22 French Foley catheter was left in place for 6 h. All patients felt the bladder catheter as annoying, but they considered postoperative mobility as more important as complete lack of pain. The subjective feeling was described as 2.28 ± 0.74. Any side effects or complications did not appear.

Conclusions

Bilateral NPB is a safe and effective analgesic option in HDR-brachytherapy and can replace CSE. It offers the advantage of almost no impaired mobility of the patient and can be performed by the urologist himself. Using transrectal ultrasound guidance, the method can be learned quickly.     

Local cooling reduces regional bone blood flow

Local cooling is very common after bone and joint surgery. Therefore the knowledge of bone blood flow during local cooling is of substantial interest. Previous studies revealed that hypothermia leads to vasoconstriction followed by decreased blood flow levels. The aim of this study was to characterize if local cooling is capable of inducing reduced blood flow in bone tissue using a stepwise‐reduced temperature protocol in experimental rabbits. To examine bone blood flow we utilized the fluorescent microsphere (FM) method. In New Zealand white rabbits one randomly chosen hind limb was cooled stepwise from 32 to 2°C, whereas the contra lateral hind limb served as control. Injection of microspheres was performed after stabilization of bone and muscle temperature at each temperature level. Bones were removed, dissected and fluorescence intensity was determined to calculate blood flow values. We found that blood flow of all cooled regions decreased relative to the applied external temperature. At maximum cooling blood flow was almost completely disrupted, indicating local cooling as powerful regulatory mechanism for regional bone blood flow (RBBF). Postoperative cooling therefore may lead to strongly decreased bone blood flow values. As a result external cooling has capacity to both diminish bone healing and reduce bleeding complications. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1820–1827, 2013     

Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: An immunohistochemical and functional analysis

Chordomas are rare malignancies of the axial skeleton. Therapy is mainly restricted to surgery. This study investigates histone deacetylase (HDAC) inhibitors as potential therapeutics for chordomas. Immunohistochemistry (IHC) was performed using the HDAC 1–6 antibodies on 50 chordoma samples (34 primary tumors, 16 recurrences) from 44 patients (27 male, 17 female). Pan‐HDAC‐inhibitors Vorinostat (SAHA), Panobinostat (LBH‐589), and Belinostat (PXD101) were tested for their efficacy in the chordoma cell line MUG‐Chor1 via Western blot, cell cycle analysis, caspase 3/7 activity (MUG‐Chor1, UCh‐1), cleaved caspase‐3, and PARP cleavage. p‐Values below 0.05 were considered significant. IHC was negative for HDAC1, positive for HDAC2 in most (n = 36; 72%), and for HDACs 3–6 in all specimens available (n = 43; 86%). HDAC6 expression was strongest. SAHA and LBH‐589, but not PXD101 caused a significant increase of G2/M phase cells and of cleaved caspase‐3 (p = 0.0003, and p = 0.0014 after 72 h, respectively), and a peak of caspase 3/7 activity. PARP cleavage confirmed apoptosis. The presented chordoma series expressed HDACs 2–6 with strongest expression of HDAC6. SAHA and LBH‐589 significantly increased apoptosis and changed cell cycle distribution in vitro. HDAC‐inhibitors should be further evaluated as therapeutic options for chordoma. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1999–2005, 2013     

PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Purpose

To evaluate the effect of vardenafil on renal function after renal ischemia–reperfusion (IR) injury (IRI) in a rat model.

Materials and methods

Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3–6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.

Results

Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.

Conclusions

Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.