Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation

Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This report provides a review of all hand transplants performed to date. From September 1998 to February 2006 eighteen male patients underwent 24 hand/forearm/digit transplantations (eleven unilateral and four bilateral hand transplantations, two bilateral forearm transplantations, one thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. Patient average age was 32. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 34 to 85 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date occurred and were caused by severe inflammation and progressive rejection in a non-compliant patient. In addition, 6 hands were lost due to a rejection process as the Chinese recipients did not take their immunosuppressive treatment. These failures were communicated in January 2006. Acute rejection episodes occurred in 12 patients within the first year. Rejection was completely reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. As it would have been very difficult to analyse transplantation functional results in a standardized way, the Registry has performed a functional score system. All patients had achieved protective sensation and in 17 of them also discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities and 90% of the recipients returned to work, and improved manual skills allowed them not only to resume their previous jobs but also, in some cases, to find more suitable employment. Fifteen recipients reported an improvement of their quality of life and we evaluated as a very important point as patient satisfaction and well-being are mandatory goals of hand transplantation.     

Cerebrospinal fluid biomarkers versus glasgow coma scale and glasgow outcome scale in pediatric traumatic brain injury: the role of young age and inflicted injury

The Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) are widely used clinical scoring systems to measure the severity of neurologic injury after traumatic brain injury (TBI), but have recognized limitations in infants and small children. Cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE) and S100B show promise as markers of brain injury. We hypothesized that the initial GCS and 6-month GOS scores would be inversely associated with CSF NSE and/or S100B concentrations after severe pediatric TBI. Using banked CSF obtained during ongoing studies of pediatric TBI, NSE and S100B were determined in CSF collected within 24 h of trauma from 88 infants and children with severe TBI (GCS < or = 8) versus 20 non-injured controls. Victims of inflicted (iTBI) and non-inflicted TBI (nTBI) showed similar (>10-fold) increases in both NSE and S100B versus control. Both markers showed overall significant, inverse correlation with GCS and GOS scores. In subgroup analysis, both markers correlated significantly with GCS and GOS scores only in older (>4 years) victims of nTBI; no correlation was found for patients < or =4 years old or victims of iTBI. While confirming the overall correlations between GCS/GOS score and CSF NSE and S100B seen in prior studies, we conclude that these clinical and CSF biomarkers of brain injury do not correlate in children < or =4 years of age and/or victims of iTBI. Although further, prospective study is warranted, these findings suggest important limitations in our current ability to assess injury severity in this important population.     

The map kinase ERK regulates renal activity of cyclin-dependent kinase 2 in experimental glomerulonephritis.

BACKGROUND: In vitro, the extracellular signal-regulated kinase (ERK) is an intracellular convergence point of multiple stimuli, which affect the cell cycle. However, the role of ERK in cell cycle regulation in vivo is unknown. METHODS: To address this issue, ERK activity was blocked both in vitro in mesangial cells (MC) and in vivo in experimental glomerulonephritis (GN) by a pharmacological inhibitor (U0126) of the ERK-activating kinase. RESULTS: In stimulated MC, inhibition of ERK reduced cyclin-dependent kinase 2 (CDK2) phosphorylation, CDK2 activity and cyclin E/A expression, whereas downregulation of CDK inhibitor p27(Kip1) expression was inhibited. In vivo, U0126 was given to rats in the acute phase of anti-Thy 1.1 GN. We previously showed that glomerular cell proliferation was reduced by 67% upon treatment with the inhibitor compared to nephritic controls. Now, we detected a significant increase in renal CDK2-activity/phosphorylation in the nephritic controls, that was significantly and dose-dependently reduced by ERK inhibition. CDK2 activation was accompanied by an increase in renal expression of cyclins E/A and the enhanced binding of these cyclins to CDK2 in the nephritic controls. These changes were blunted by U0126 treatment. Finally, we noted an increased expression and CDK2-binding of p27(KIP1) protein in the nephritic controls which was decreased in U0126 treated rats. CONCLUSIONS: Our observations provide the first evidence that ERK is an intracellular regulator of renal CDK2 activity in vivo in a glomerulonephritis model.     

Laparoscopic extended pelvic lymph node dissection for prostate cancer: description of the surgical technique and initial results

OBJECTIVE: In patients with prostate cancer, extended pelvic lymph node dissection (ePLND) yields a higher number of lymph node metastases (LNM) than standard pelvic lymph node dissection (PLND) of the obturator fossa only. We describe our laparoscopic technique of extended lymph node dissection and provide the number and locations of positive lymph nodes from our experience. METHODS: In a total of 35 selected patients with clinically localized prostate cancer, laparoscopic ePLND was performed prior to laparoscopic radical prostatectomy. The template included the genitofemoral nerve up to the bifurcation of the common iliac artery and down to the epigastric artery. In the "split and roll" technique the internal and external iliac arteries including the bifurcation and the external iliac vein were completely mobilized. After freeing the obturator nerve, the entire lymph node package was released from the pelvic side wall. RESULTS: Mean operative time was 90min/patient. The complications were two temporary and reversible neurapraxias (ischiatic nerve and obturator nerve), one deep vein thrombosis, and two lymphoceles. One lymphocele healed conservatively; the second was marsupialized laparoscopically. Eleven (31.4%) patients had lymph node metastases; their mean prostate-specific antigen (PSA) level was 20.3+/-7.0 ng/ml (range: 5.2-39.7 ng/ml) and their median Gleason sum in biopsy was 7 (range: 6-8). Mean size of the LNM was 3.1+/-1.0 mm (range: 0.2-8). In 5 of the 11 patients with LNM these were detected exclusively outside the obturator fossa. LNM were in the obturator fossa only in two (one bilateral), around the external iliac artery only in two, around the internal iliac artery only in two, and around the external iliac artery and internal iliac only in one patient. CONCLUSIONS: Laparoscopic ePLND can be combined with laparoscopic radical prostatectomy. Standardization of the technique facilitates surgery to a great extent. e-PLND detects LNM in a significant number of patients. The majority of LNM are outside the obturator fossa. The transperitoneal approach allows a wide exposure and is the most important factor to enable successful ePLND.     

Symptoms suggestive of chronic pelvic pain syndrome in an urban population: prevalence and associations with lower urinary tract symptoms and erectile function

PURPOSE: We determined the prevalence of symptoms suggestive of chronic pelvic pain syndrome in an urban population and assessed associations with lower urinary tract symptoms and erectile dysfunction. MATERIALS AND METHODS: Men participating in a voluntary health examination free of charge that was organized by the Department of Preventive Health of the City of Vienna were analyzed. All participants completed 3 validated questionnaires on chronic pelvic pain syndrome (National Institutes of Health-Chronic Prostatitis Symptom Index), lower urinary tract symptoms (International Prostate Symptom Score) and erectile dysfunction (International Index of Erectile Function-5). RESULTS: A total of 1,765 men with a mean +/- SD age of 46.3 +/- 0.3 years (range 20 to 79) entered this study. The mean National Institutes of Health-Chronic Prostatitis Symptom Index score increased from 4.0 +/- 0.3 in the youngest age group of 20 to 29-year-old men to 6.3 +/- 0.6 in those 70 to 79 years old. The overall prevalence of symptoms suggestive of chronic pelvic pain syndrome, defined by a pain score of 4 or greater and perineal/ejaculatory pain, was 2.7% and it revealed no age dependence, such as the pain score. In contrast, urinary symptom and quality of life scores increased with age. International Index of Erectile Function-5 score was 20.6 +/- 0.3 for men without chronic pelvic pain symptoms vs 18.3 +/- 0.7 for men with mild symptoms and 16.5 +/- 1.1 for men with moderate/severe symptoms. A National Institutes of Health-Chronic Prostatitis Symptom Index score in the upper quartile was associated with 8.3-fold increased odds of erectile dysfunction. CONCLUSIONS: The prevalence of symptoms suggestive of chronic pelvic pain syndrome in this large cohort of men participating in a health screening project was 2.7% and it revealed no age dependence. Our study suggests that chronic pelvic pain syndrome has a negative impact on erectile function.     

Arthroskopische Schulterstabilisierung mittels Fadenankern unter besonderer Berücksichtigung des tiefen anterior-inferioren Zugangs (5:30 Uhr)

OBJECTIVE: Arthroscopic (re)stabilization of the unstable shoulder by anatomic refixation of the detached capsulolabral complex with suture anchors or reduction of excessive capsule volume by capsule plication. INDICATIONS: Any type of shoulder instability (anterior, posterior, inferior, or multidirectional instability). Revision stabilization (even after primary open stabilization). Bone defects affecting < 25% of the glenoid surface. Lesions of the superior biceps tendon anchor complex (SLAP lesion). CONTRAINDICATIONS: Preexisting bone defects of the glenoid affecting > 25% of the glenoid surface. "Engaging" Hill-Sachs defects: osseous defects of the humeral head that engage with the anterior glenoid rim in extreme external rotation/abduction and consequently lead to shoulder dislocation. Bone-related etiology, e. g., clearly increased glenoid retroversion/anteversion or glenoid dysplasias (e. g., inverse pear shape). Voluntary shoulder dislocation in young patients until the end of the growth period. SURGICAL TECHNIQUE: Diagnostic arthroscopy and additional procedures based on clinical and intraoperative findings. For anterior-inferior instability, an anterior-superior approach is made with mobilization of the labrum and decortication of the glenoid. Creation of deep anterior-inferior portal and insertion of the anchors in 5.30, 4.30 and 3.00 o'clock position. The sutures are pulled through the capsulolabral complex and tied arthroscopically. Reconstruction of the inferior glenohumeral ligament is especially important. Lesions of the superior biceps tendon anchor and/or posterior labrum detachment can be treated by the same technique. Capsule plication with PDS sutures can be performed to decrease a large rotator interval or excessive capsule volume. The range of motion at the shoulder is limited for 6 weeks postoperatively (depending on the initial direction of the instability). RESULTS: At the authors' hospital over 600 arthroscopic shoulder stabilizations using the deep anterior-inferior portal have been completed so far. The redislocation rate for the first 147 patients (average follow-up of 3 years) treated with the technique described here is 6.1% and is slightly higher for arthroscopic revision stabilizations (n=43; of these, redislocation n=3 and reinstability n=3). There were no instances of axillary nerve lesion.     

Erectile dysfunction, discrepancy between high prevalence and low utilization of treatment options: results from the 'Cottbus Survey' with 10 000 men

OBJECTIVE: To investigate the age-stratified prevalence of erectile dysfunction (ED) and its comorbidities, and to assess the population's knowledge, utilization, and general attitude towards the treatment for ED. SUBJECTS AND METHODS: In all, 10 000 men received a 35-item questionnaire including the International Index of Erectile Function (IIEF) and sociodemographic questions regarding life style, comorbidities, quality of sexual life and knowledge or experience of ED therapy. In all, 3124 responses were included (31.2%), 2499 men lived in well established partnerships and were assessed as the basic study group. RESULTS: In the entire population the prevalence rate of ED was 40.1%. However, although known, medical treatment for ED is used only by a minority of affected men. The prevalence of ED was independently associated with age, peripheral arterial occlusive disease, hypertension, ischaemic heart disease, diabetes mellitus, and liver diseases. Correlations between sexual quality of life (QoL) and ED were statistically significant (P < 0.01) and moderate to strong (absolute values: Spearman's rho 0.35-0.76). Although 96% of the study population knew at least one phosphodiesterase type 5 (PDE5) inhibitor by name, only 53% considered taking the medication and only 9% of the men with ED had had experience with available PDE5 inhibitors. CONCLUSIONS: The sexual QoL was significantly reduced by ED. Despite high levels of awareness and general acceptance of oral medication for ED, experience with PDE5 inhibitors was low. Further investigation is required to evaluate the general impact of ED on sexual QoL and the need or wish for treatment.     

Factors associated with improved survival among young adult melanoma patients despite a greater incidence of sentinel lymph node metastasis

INTRODUCTION: We sought to evaluate the factors that affect sentinel lymph node (SLN) metastasis and survival among young melanoma patients (< or =30 y). METHODS: The Sunbelt Melanoma Trial is a multi-institutional prospective randomized trial of patients aged 18 to 70 y. Statistical analyses were performed to determine if patients < or =30 y of age had a significantly different outcome in terms of SLN metastasis, disease-free survival (DFS), and overall survival (OS) compared to older patients. RESULTS: The median age of the 3031 patients in this study was 50 y (range 18 to 77 y); the 315 patients (10.4%) < or =30 y old were compared with those >30 y old. Of the 1944 patients with follow-up, the median follow-up was 48 mo. On univariate analysis, younger patients were more often female (54.7% versus 40.9%, P < 0.0005), with tumors <4 mm thick (94.9% versus 89.4%, P = 0.001) without ulceration (80.3% versus 70.9%, P < 0.0005) or evidence of regression (93.8% versus 87.8%, P = 0.003), and were less likely to have lentigo maligna (0.0% versus 2.6%) or acral lentiginous (0.4% versus 3.1%, P < 0.0005) subtype. Patient age < or =30 was associated with SLN metastasis on univariate (24.6% versus 19.7%, P = 0.05) and multivariate (OR = 1.77, 95% CI = 1.26-2.49, P = 0.001) analyses. With a median follow-up of 48 mo, younger patients had a significantly improved 5-y DFS (86.2% versus 79.1%, P = 0.036) and OS (89.9% versus 80.1%, P = 0.010). On multivariable Cox regression analysis, however, age group was not a significant independent prognostic factor affecting DFS or OS. CONCLUSION: Despite a higher rate of SLN metastasis, patients < or =30 y old do not have a worse survival attributable to a more favorable clinicopathologic profile.     

Quantitative analysis of EBV-specific CD4/CD8 T cell numbers, absolute CD4/CD8 T cell numbers and EBV load in solid organ transplant recipients with PLTD

Post transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients is assumed to be the result of impaired Epstein-Barr Virus (EBV)-specific cellular immunity. We analyzed the absolute CD4 and CD8 T cell counts as well as the EBV-specific CD4 and CD8 T cell responses in relation to EBV load in SOT recipients with PTLD. A prospective, single center study was initiated and 10 immunosuppressed patients with diagnosis of PTLD were analyzed and compared to 3 patients without PTLD (2 SOT recipients with EBV-reactivation, 1 patient with Infectious Mononucleosis) and 6 healthy EBV positive controls. EBV-specific CD8 T cells were enumerated using HLA class I tetramers and the IFN-gamma cytokine secretion assay. EBNA1-specific CD4 T cells were analyzed after protein stimulation and EBV load was quantified by real-time PCR. Absolute CD8 T cell counts were highly variable in all 19 cases analyzed. In contrast, the absolute EBV-specific CD8 T cell count was found to be low in 7/9 patients with PTLD (<5/microl whole blood). These frequencies were similar to absolute EBV-specific CD8 T cell numbers observed in healthy EBV positive donors, but much lower compared to patients with EBV reactivation but no PTLD. Absolute CD4 T cell counts were significantly lower in PTLD patients (mean: 336/microl+/-161 vs. controls 1008/microl+/-424, p=0.0001), with EBNA1-specific CD4 T cell responses being also low, but highly variable. Moreover, low absolute CD4 T cell counts (<230/microl) were associated with an elevated EBV load (>1000 copies/microg DNA). We conclude that SOT recipients with PTLD have an inadequate functional EBV-specific T cell response. Our data suggest that the frequency and function of circulating EBV-specific CD8 T cells are dependent on absolute CD4 T cell counts. Further studies are needed to verify if a low absolute CD4 T cell count presents a risk factor for the development of PTLD in SOT recipients.