Haematopoietic stem cell transplantation in Switzerland. Report from the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) Registry 1997-2003

In 1997, the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) initiated a mandatory national registry for all haematopoietic stem cell transplants (HSCT) in Switzerland. As of 2003, information was collected of 2010 patients with a first HSCT (577 allogeneic (29%) and 1433 autologous (71%) HSCT) and 616 additional re-transplants. This included 1167 male and 843 female patients with a median age of 42.4 years (range 0.2-76.6 years). Main indications were leukaemias (592; 29%) lymphoproliferative disorders (1,061; 53%), solid tumours (295; 15%) and non-malignant disorders (62; 3%). At the time of analysis 1,263 patients were alive (63%), 747 had died (37%). Probability of survival, transplant related mortality or relapse at 5 years was 52%, 21%, 36% for allogeneic and 54%, 5%, 60% for autologous HSCT. Outcome depended on indication, donor type, stem cell source and age of patient. HSCT is an established therapy in Switzerland. These data describe current practice and outcome.

Prevalence, incidence and distribution of erosion

There is some evidence that the presence of erosion is growing steadily. Because of different scoring systems, samples and examiners, it is difficult to compare and judge the outcome of the studies. Preschool children aged between 2 and 5 years showed erosion on deciduous teeth in 6-50% of the subjects. Young schoolchildren (aged 5-9) already had erosive lesions on permanent teeth in 14% of the cases. In the adolescent group (aged between 9 and 17) 11-100% of the young people examined showed signs of erosion. Incidence data (= increase of subjects with erosion) evaluated in three of these studies were 12% over 2 years, 18% over 5 years and 27% over 1.5 years. In adults (aged between 18 and 88), prevalence data ranged between 4 and 82%. Incidence data are scarce; only one study was found and this showed an incidence of 5% for the younger and 18% for the older examined group (= increase of tooth surfaces with erosion). Prevalence data indicated that males had somewhat more erosive tooth wear than females. The distribution of erosion showed a predominance of occlusal surfaces (especially mandibular first molars), followed by facial surfaces (anterior maxillary teeth). Oral erosion was frequently found on maxillary incisors and canines. Overall, prevalence data are not homogeneous. Nevertheless, there is already a trend for more pronounced rate of erosion in younger age groups. Therefore, it is important to detect at-risk patients early to initiate adequate preventive measures.

Liver transplantation for patients with metastatic endocrine tumors: single-center experience with 15 patients

In contrast to other secondary liver malignancy, orthotopic liver transplantation (OLT) is considered as a treatment modality for nonresectable endocrine liver metastases in selected patients. However, only few series have assessed patient selection criteria and long-term results, and no reports have focused on the impact of new technologies in this regard. Between 1992 and 2004, 28 patients with malignant endocrine tumors underwent evaluation for OLT according to our protocol. Data were entered into a prospective database. During pretransplant evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67 labeling results. One patient was excluded from further evaluation due to severe carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years, were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor liver transplantations, and 1 cluster transplantation). Four patients died during the hospital treatment. The median follow-up of the discharged patients was 60.8 months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%, and 48.3%, respectively. Two patients underwent surgery for isolated tumor recurrence. In 2 patients, peptide receptor radiotherapy was carried out because of multilocular recurrent disease. In conclusion, liver transplantation is a realistic therapeutic option for highly selected patients with hepatic metastases of endocrine tumors. Our strategy, which implements strict pretransplant selection and aggressive surgical approach, in case of disease recurrence, in addition to systemic radiopeptide treatment, led to an excellent long-term survival cure, however, is unlikely to be achieved.

Clinical evaluation of root filled teeth restored with or without post-and-core systems in a specialist practice setting

AIM: To assess survival rates and complications of root-filled teeth restored with or without post-and-core systems over a mean observation period of >or=4 years. METHODOLOGY: A total of 325 single- and multirooted teeth in 183 subjects treated in a private practice were root filled and restored with either a cast post-and-core or with a prefabricated titanium post and composite core. Root-filled teeth without post-retained restorations served as controls. The restored teeth served as abutments for single unit metal-ceramic or composite crowns or fixed bridges. Teeth supporting cantilever bridges, overdentures or telescopic crowns were excluded. RESULTS: Seventeen teeth in 17 subjects were lost to follow-up (17/325: 5.2%). The mean observation period was 5.2 +/- 1.8 (SD) years for restorations with titanium posts, 6.2 +/- 2.0 (SD) years for cast post-and-cores and 4.4 +/- 1.7 (SD) years for teeth without posts. Overall, 54% of build-ups included the incorporation of a titanium post and 26.5% the cementation of a cast post-and-core. The remaining 19.5% of the teeth were restored without intraradicular retention. The adjusted 5-year tooth survival rate amounted to 92.5% for teeth restored with titanium posts, to 97.1% for teeth restored with cast post-and-cores and to 94.3% for teeth without post restorations, respectively. The most frequent complications included root fracture (6.2%), recurrent caries (1.9%), post-treatment periradicular disease (1.6%) and loss of retention (1.3%). CONCLUSION: Provided that high-quality root canal treatment and restorative protocols are implemented, high survival and low complication rates of single- and multirooted root-filled teeth used as abutments for fixed restorations can be expected after a mean observation period of >or=4 years.

Evaluation of reparative cartilage after autologous chondrocyte implantation for osteochondritis dissecans: histology, biochemistry, and MR imaging

BACKGROUND: The aim of this study was to investigate the biochemical properties, histological and immunohistochemical appearance, and magnetic resonance (MR) imaging findings of reparative cartilage after autologous chondrocyte implantation (ACI) for osteochondritis dissecans (OCD). METHODS: Six patients (mean age 20.2 +/- 8.8 years; 13-35 years) who underwent ACI for full-thickness cartilage defects of the femoral condyle were studied. One year after the procedure, a second-look arthroscopic operation was performed with biopsy of reparative tissue. The International Cartilage Repair Society (ICRS) visual histological assessment scale was used for histological assessment. Biopsied tissue was immunohistochemically analyzed with the use of monoclonal antihuman collagen type I and monoclonal antihuman collagen type II primary antibodies. Glycosaminoglycan (GAG) concentrations in biopsied reparative cartilage samples were measured by high performance liquid chromatography (HPLC). MR imaging was performed with T1- and T2-weighted imaging and three-dimensional spoiled gradient-recalled (3D-SPGR) MR imaging. RESULTS: Four tissue samples were graded as having a mixed morphology of hyaline and fibrocartilage while the other two were graded as fibrocartilage. Average ICRS scores for each criterion were (I) 1.0 +/- 1.5; (II) 1.7 +/- 0.5; (III) 0.6 +/- 1.0; (IV) 3.0 +/- 0.0; (V) 1.8 +/- 1.5; and (VI) 2.5 +/- 1.2. Average total score was 10.7 +/- 2.8. On immunohistochemical analysis, the matrix from deep and middle layers of reparative cartilage stained positive for type II collagen; however, the surface layer did not stain well. The average GAG concentration in reparative cartilage was 76.6 +/- 4.2 microg/mg whereas that in normal cartilage was 108 +/- 11.2 microg/mg. Common complications observed on 3D-SPGR MR imaging were hypertrophy of grafted periosteum, edema-like signal in bone marrow, and incomplete repair of subchondral bone at the surgical site. Clinically, patients had significant improvements in Lysholm scores. CONCLUSIONS: In spite of a good clinical course, reparative cartilage after ACI had less GAG concentration and was inferior to healthy hyaline cartilage in histological and immunohistochemical appearance and on MRI findings.

Effects of high-yield thrombocytapheresis on the quality of platelet products

BACKGROUND: The steadily increasing demands for single-donor apheresis platelet (PLT) concentrates (APCs) are a challenge to the PLT supply system. Therefore, efforts to improve plateletpheresis yield, allowing apheresis products to be split into 2 or more units, are valuable strategies. No data to demonstrate in vivo transfusion efficacy of these high-yield split-APCs are currently available, however. STUDY DESIGN AND METHODS: The transfusion efficacy of APCs produced by two apheresis methods involving different harvest and storing procedures and varying PLT yields was investigated. Efficacy measures were the 1-hour percent PLT recovery (PPR(1h)) and the 1-hour corrected count increment (CCI(1h)). In total, 400 APCs, produced with either an Amicus device (Baxter) and stored in PLT additive solution (T-Sol; Amicus method [AM], n = 107) or a Trima device (Gambro) and stored in plasma (Trima method [TM], n = 293), were transfused to 55 children (31 girls; median age, 9.5 years; range, 0.2-18.5 years) with thrombocytopenia due to chemotherapy or aplastic anemia (median, 4 APCs per child; range, 1-68). RESULTS: Transfusion efficacy was significantly lower for AM-APCs than for TM-APCs (median PPR(1h), 17 and 33%; median CCI(1h), 7.9 and 15.6, respectively; p < 0.001). Reduced transfusion efficacy correlated in a yield-dependent manner with high apheresis PLT yields (>/=6 x 10(11)) for AM-APCs (p < 0.001). CONCLUSION: Although in vitro validation of AM- and TM-APCs has been performed, only by evaluating transfusion efficacy in vivo did the AM turn out to be not suitable for high-yield thrombocytapheresis. This study recommends the implementation of in vivo transfusion efficacy studies for high-yield APC apheresis donations.

Female patients with atherosclerotic lesions of the lower limbs. Not all are alike

BACKGROUND: Data on female patients with atherosclerotic peripheral arterial disease (PAD) are scarce, and limited primarily to the elderly population with multilevel disease. In this longitudinal observational study we compare female patients below 60 years of age with isolated lesions at the aortic bifurcation or focal superficial femoral artery disease. PATIENTS AND METHODS: Analysis is based on consecutive series of 43 female patients with PAD limited to the aortoiliac bifurcation (n = 28, group I) or an isolated femoral segment at the adductor channel (n = 15, group II) seen in a tertiary referral center between 1998 and 2000. The first assessment provided baseline data, with follow up data obtained at this study. Traditional risk factors, carotid artery disease and clinical outcome (mortality, cardiovascular events, vascular re-intervention rate, PAD progression) were evaluated over an interval of 5 (2 to 8) years. RESULTS: Female patients with aortic disease [group I] were younger (51.8 +/- 7.7 vs. 56.7 +/- 7.6 years in group II; p = 0.048), presented a more masculine phenotype, and smoked significantly more often (82% vs. 40%; p = 0.007). Arterial hypertension and diabetes mellitus were more common in group II, though it missed statistical significance (p = 0.068 and p = 0.085). Cardiovascular and limb outcome were comparable in both groups of female patients, while carotid artery disease was more severe in group I (i.e., carotid plaques in 71 vs. 53%). CONCLUSION: Our data support previous findings that cigarette smoking is a stronger risk factor for aortic disease as compared to femoral disease in younger female patients, with the strongest effect of smoking on a localized region of the aortic bifurcation.

Catch-up growth in autosomal dominant isolated growth hormone deficiency (IGHD type II)

OBJECTIVE: Data on the GH-induced catch-up growth of severely GH-deficient children affected by monogenetic defects are missing. PATIENTS: Catch-up growth of 21 prepubertal children (6 females, 15 males) affected with IGHD type II was analyzed in a retrospective chart review. At start of therapy, mean age was 6.2 years (range, 1.6-15.0), mean height SDS was -4.7 (-7.6 to -2.2), mean IGF-I SDS was -6.2 (-10.1 to -2.2). GH was substituted using a mean dose of 30.5microg/kg*d. RESULTS: Catch-up growth was characterized by a mean height gain of +0.92, +0.82, and +0.61 SDS after 1, 2, and 3 years of GH therapy, respectively. Mean height velocities were 10.7, 9.2 and 7.7cm/year during the first three years. Mean duration of complete catch-up growth was 6 years (3-9). Mean height SDS reached was -0.97 (-2.3 to +1.1), which was within the range of the estimated target height of -0.60 SDS (-1.20 to -0.15). The younger and shorter the children were at start of therapy the better they grew during the first year independent of the dose. Mean bone age was delayed at start by 2.1 years and progressed by 2.5 years during the first two years of therapy. Incomplete catch-up growth was caused by late initiation or irregular administration of GH in four cases. CONCLUSIONS: Our data suggest that GH-treated children with severe IGHD show a sustained catch-up growth over 6 years (mean) and reach their target height range. This response to GH is considered to be characteristic for young children with severe growth retardation due to IGHD.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.

Treatment of femoro-acetabular impingement: preliminary results of labral refixation. Surgical technique

BACKGROUND: Recent advances in the understanding of the anatomy and function of the acetabular labrum suggest that it is important for normal joint function. We found no available data regarding whether labral refixation after treatment of femoro-acetabular impingement affects the clinical and radiographic results. METHODS: We retrospectively reviewed the clinical and radiographic results of fifty-two patients (sixty hips) with femoro-acetabular impingement who underwent arthrotomy and surgical dislocation of the hip to allow trimming of the acetabular rim and femoral osteochondroplasty. In the first twenty-five hips, the torn labrum was resected (Group 1); in the next thirty-five hips, the intact portion of the labrum was reattached to the acetabular rim (Group 2). At one and two years postoperatively, the Merle d'Aubigné clinical score and the Tönnis arthrosis classification system were used to compare the two groups. RESULTS: At one year postoperatively, both groups showed a significant improvement in their clinical scores (mainly pain reduction) compared with their preoperative values (p = 0.0003 for Group 1 and p < 0.0001 for Group 2). At two years postoperatively, 28% of the hips in Group 1 (labral resection) had an excellent result, 48% had a good result, 20% had a moderate result, and 4% had a poor result. In contrast, in Group 2 (labral reattachment), 80% of the hips had an excellent result, 14% had a good result, and 6% had a moderate result. Comparison of the clinical scores between the two groups revealed significantly better outcomes for Group 2 at one year (p = 0.0001) and at two years (p = 0.01). Radiographic signs of osteoarthritis were significantly more prevalent in Group 1 than in Group 2 at one year (p = 0.02) and at two years (p = 0.009). CONCLUSIONS: Patients treated with labral refixation recovered earlier and had superior clinical and radiographic results when compared with patients who had undergone resection of a torn labrum. Although the results must be considered preliminary, we now recommend refixation of the intact portion of the labrum after trimming of the acetabular rim during surgical treatment of femoro-acetabular impingement.

CD4+ T-cell count increase in HIV-1-infected patients with suppressed viral load within 1 year after start of antiretroviral therapy

BACKGROUND: CD4+ T-cell recovery in patients with continuous suppression of plasma HIV-1 viral load (VL) is highly variable. This study aimed to identify predictive factors for long-term CD4+ T-cell increase in treatment-naive patients starting combination antiretroviral therapy (cART). METHODS: Treatment-naive patients in the Swiss HIV Cohort Study reaching two VL measurements <50 copies/ml >3 months apart during the 1st year of cART were included (n=1816 patients). We studied CD4+ T-cell dynamics until the end of suppression or up to 5 years, subdivided into three periods: 1st year, years 2-3 and years 4-5 of suppression. Multiple median regression adjusted for repeated CD4+ T-cell measurements was used to study the dependence of CD4+ T-cell slopes on clinical covariates and drug classes. RESULTS: Median CD4+ T-cell increases following VL suppression were 87, 52 and 19 cells/microl per year in the three periods. In the multiple regression model, median CD4+ T-cell increases over all three periods were significantly higher for female gender, lower age, higher VL at cART start, CD4+ T-cell <650 cells/microl at start of the period and low CD4+ T-cell increase in the previous period. Patients on tenofovir showed significantly lower CD4+ T-cell increases compared with stavudine. CONCLUSIONS: In our observational study, long-term CD4+ T-cell increase in drug-naive patients with suppressed VL was higher in regimens without tenofovir. The clinical relevance of these findings must be confirmed in, ideally, clinical trials or large, collaborative cohort projects but could influence treatment of older patients and those starting cART at low CD4+ T-cell levels.

Time required to obtain endobronchial biopsies in children during fiberoptic bronchoscopy

BACKGROUND: Endobronchial biopsies are an important tool for the study of airway remodeling in children. We aimed to evaluate the impact of performing endobronchial biopsies as a part of fiberoptic bronchoscopy on the length of the procedure. METHODS: Clinically indicated fiberoptic bronchoscopy at which endobronchial biopsy was attempted as a part of a research protocol was performed in 40 children (median age 6 years, range 2 months-16 years). Time needed for airway inspection, bronchoalveolar lavage (BAL) with three aliquots of 1 ml/kg of 0.9% saline, sampling of three macroscopically adequate biopsies, teaching, and other interventions (e.g., removal of plugs) was recorded. The bronchoscopist was not aware that the procedure was being timed. RESULTS: Median (range) duration (min) was 2.5 (1.0-8.2) for airway inspection, 2.8 (1.7-9.4) for BAL, 5.3 (2.5-16.6) for biopsy sampling, 2.4 (1.5-6.6) for teaching and 4.1 (0.8-18.5) for other interventions. Three adequate biopsies were obtained in 33 (83%) children. Use of 2.0 mm biopsy forceps (via 4.0 and 4.9 mm bronchoscopes) rather than 1.0 mm (via 2.8 and 3.6 mm bronchoscopes) significantly reduced biopsy time (4.6 min vs. 8.4 min, P < 0.001). CONCLUSIONS: It takes a median of just over 5 min to obtain three endobronchial biopsies in children, which we consider an acceptable increase in the duration of fiberoptic bronchoscopy for the purpose of research.

Effects of verum acupuncture compared to placebo acupuncture on quantitative EEG and heart rate variability in healthy volunteers

OBJECTIVES: The aim of this single-blind randomized crossover study was to evaluate specific effects of manual acupuncture on central and vegetative nervous system activity measured by quantitative electroencephalography (qEEG) and heart rate variability (HRV). DESIGN: Twenty (20) healthy volunteers (mean: 25.2 +/- 3.6 years) were monitored simultaneously using a qEEG system and a 12-channel electrocardiogram recorder during verum acupuncture (VA) at acupuncture point Large Intestine 4 (Hegu) (LI4) or placebo acupuncture (PA) at a sham point. RESULTS: In the EEG conduction of the occipital area, needle stimulation in VA increased alpha1-frequency significantly, and the ratio alpha1/theta was shifted to the benefit of alpha1 over all electrodes. The HRV parameters showed a significant increase of the low frequency/high frequency (HF) ratio during the first minute of stimulation in VA, indicating an initial increase of sympathetic activation. However, an increase of HF power in the minute after stimulation followed by a decrease in heart rate suggests delayed vagal activation. De qi (a sensation that is typical of acupuncture needling) occurred in 16 subjects during VA and in 9 volunteers during PA (80% versus 45%). CONCLUSIONS: Manual stimulation on LI4 seems to lead to specific changes in alpha EEG-frequency and in HRV parameters. A linear relationship between the HRV parameters and the alpha EEG band might point to a specific modulation of cerebral function by vegetative effects during acupuncture.

Primary reconstruction of open depressed skull fractures with titanium mesh

Open skull fractures have been traditionally managed in 2 stages: urgent craniotomy and elevation of the fracture with removal of contaminated bone, debridement, and delayed cranioplasty. Primary, single-stage repair of these injures has been said to entail risks such as infections. Recent experience, however, disproved these concerns.We used a primary single-stage reconstruction for patients presenting with open depressed skull fractures. All patients received antibiotic prophylaxis. The patients underwent elevation of the compound fracture and craniotomy if necessary. Debridement was performed, followed by skull reconstruction using a 0.6-mm titanium mesh.We present 5 consecutive male patients (age, 32.2 +/- 15.6 years) who underwent primary reconstruction of open depressed skull fractures. Clinical and radiologic follow-up was performed 2 months after surgery. The duration of the surgery was 2 +/- 1.6 hours. The size of the implanted mesh was 13 +/- 13.1 cm. No infection was detected in our series, with a follow-up period of 22 +/- 6.5 months (range, 16-29 months). The cosmetic result was defined in 4 patients as "excellent" and in 1 patient as "good."Primary reconstruction of open skull fractures with titanium mesh is feasible, safe, and cosmetically preferable than the conventional staged approach. The introduction into clinical practice can be warranted.

Blood pressure and vessel recanalization in the first hours after ischemic stroke

BACKGROUND AND PURPOSE: Transient elevation of arterial blood pressure (BP) is frequent in acute ischemic stroke and may help to increase perfusion of tissue jeopardized by ischemia. If this is true, recanalization may eliminate the need for this BP elevation. METHODS: We analyzed BP in 149 patients with acute ischemic stroke on admission to the hospital and 1 and 12 hours after intraarterial thrombolysis. BP values of patients with adequate recanalization were compared with BP values of patients with inadequate recanalization. Recanalization was determined on cerebral arteriography after thrombolysis using thrombolysis in myocardial infarction grades. RESULTS: Systolic, mean, and diastolic arterial BP decreased significantly from admission to 12 hours after thrombolysis in all patients (P<0.001). Before thrombolysis, patients with adequate and inadequate recanalization showed equal systolic (147.4 and 148.0 mm Hg), mean (102.1 and 104.1 mm Hg), and diastolic (79.5 and 82.1 mm Hg) BP values. Twelve hours after thrombolysis, patients with adequate recanalization had lower values than those with inadequate recanalization (systolic BP, 130 versus 139.9 mm Hg; mean BP, 86.8 versus 92.2 mm Hg; and diastolic, BP 65.2 versus 68.3 mm Hg). Two-way repeated ANOVA analysis showed a significant group x time interaction for systolic BP, indicating a larger systolic BP decrease when recanalization succeeded (P=0.019). CONCLUSIONS: The course of elevated systolic but not diastolic BP after acute ischemic stroke was found to be inversely associated with the degree of vessel recanalization. When recanalization failed, systolic BP remained elevated longer than when it succeeded.