Learning and implementation of TransREctus sheath PrePeritoneal procedure for inguinal hernia repair.

PURPOSE: The TransREctus sheath PrePeritoneal procedure (TREPP) was introduced as an alternative open and preperitoneal technique for inguinal hernia mesh repair, demonstrating safety and efficacy in retro- and prospective studies. However, little is known about the technique's inherent learning curve. In this study, we aimed to determine TREPP learning curve effects after its implementation in high-volume surgical practice. METHODS: All primary, unilateral TREPP procedures performed in the first three years after implementation (between January 2016 and December 2018) were included out of a large preconstructed regional inguinal hernia database. Data were analyzed on outcome (i.e., surgical complications, hernia recurrences, postoperative pain). Learning curve effects were analyzed by assessing outcome in relation to surgeon experience. RESULTS: In total, 422 primary, unilateral TREPP procedures were performed in 419 patients. In three patients a unilateral TREPP procedure was performed on both sides separated in time. A total of 99 surgical complications were registered in 83 procedures (19.6% of all procedures), most commonly inguinal postoperative pain (8%) and bleeding complications (7%). Hernia recurrences were observed in 17 patients (4%). No statistically significant differences on outcome were found between different surgeon experience (< 40 procedures, 40-80 procedures, > 80 procedures). CONCLUSION: Implementation of TREPP seems not to be associated with a notable increase of adverse events. We were not able to detect a clear learning curve limit, potentially suggesting a relatively short learning curve among already experienced hernia surgeons compared to other guideline techniques.

Observed to expected lung area to head circumference ratio (O/E LHR) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT): assessment and evaluation as predictive factor for acute postnatal outcome-a single center study.

Introduction: To assess the observed to expected lung area to head circumference ratio (O/E LHR) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) and to explore its value as a potential predictive factor for postnatal outcome. Methods: A retrospective single-center study was conducted on pregnancies complicated by CAKUT between 2007 and 2018. The lung-to-head ratio (LHR) was calculated for each fetus by two independent observers. Correlations between O/E LHR and various perinatal outcome factors were assessed with Spearman's rank correlation. Furthermore, nominal logistic regression was performed to assess O/E LHR as predictive factor for respiratory distress in newborn. Results: Of 64 pregnancies complicated by CAKUT, 23 were terminated. In the 41 cases of continuation of pregnancy, newborn presenting respiratory distress with need for respiratory support in the delivery room showed earlier gestational age at onset of amniotic fluid abnormalities and at birth. Although median O/E LHR and median single deepest pocket (SDP) of amniotic fluid were significantly smaller in newborn that did develop respiratory distress with need of respiratory support in the delivery room, neither O/E LHR nor SDP were accurate predictors for the development of respiratory distress. Conclusions: Our data show that O/E LHR alone cannot serve as a predictive marker for fetal outcome in pregnancies complicated by CAKUT, though it might still be a helpful parameter together with detailed renal ultrasound evaluation, onset of amniotic fluid abnormality and SDP, particularly in its extreme values.

Role of umbilicocerebral and cerebroplacental ratios in prediction of perinatal outcome in FGR pregnancies.

PURPOSE: Aim of our study was to compare the prognostic value of the Umbilical-to-Cerebral ratio (UCR) directly to the Cerebroplacental ratio (CPR) in the prediction of poor perinatal outcomes in pregnancies complicated by Fetal Growth Restriction (FGR). METHODS: A retrospective study was carried out on pregnant women with either a small-for-gestational age (SGA) fetus or that were diagnosed with FGR. Doppler measurements of the two subgroups were assessed and the correlation between CPR, UCR and relevant outcome parameters was evaluated by performing linear regression analysis, binary logistic analysis and receiver operator characteristic (ROC) curves. Outcomes of interest were mode of delivery, acidosis, preterm delivery, gestational age at birth as well as birthweight and centiles. RESULTS: Boxplots and Scatterplots illustrated the different distribution of CPR and UCR leading to deviant correlational relationships with adverse outcome parameters. In almost all parameters examined, UCR showed a higher independent association with preterm delivery (OR: 5.85, CI 2.23-15.34), APGAR score < 7 (OR: 3.52; CI 1.58-7.85) as well as weight under 10th centile (OR: 2.04; CI 0.97-4.28) in binary logistic regression compared to CPR which was only associated with preterm delivery (OR: 0.38; CI 0.22-0.66) and APGAR score < 7 (OR: 0.27; CI 0.06-1.13). When combined with different ultrasound parameters in order to differentiate between SGA and FGR during pregnancy, odds ratios for UCR were highly significant compared to odds ratios for CPR (OR: 0.065, 0.168-0.901; p = 0.027; OR: 0.810, 0.369-1.781; p = 0.601). ROC curves plotted for CPR and UCR showed almost identical moderate prediction performance. CONCLUSION: Since UCR is a better discriminator of Doppler values in abnormal range it presents a viable option to Doppler parameters and ratios that are used in clinical practice. UCR and CPR showed equal prognostic accuracy conserning sensitivity and specificity for adverse perinatal outcome, while adding UA PI and GA_scan increased prognostic accuracy regarding negative outcomes.

Transrectus sheath pre-peritoneal (TREPP) procedure versus totally extraperitoneal (TEP) procedure and Lichtenstein technique: a propensity-score-matched analysis in Dutch high-volume regional hospitals.

PURPOSE: Results of the most commonly used inguinal hernia repair techniques often originate from expert centers or from randomized controlled studies. In this study, we portray daily-practice results of a high-volume, regional surgical group in the Netherlands, comparing TREPP (open (posterior) transrectus sheath pre-peritoneal) with Lichtenstein (open anterior) and TEP (endoscopic (posterior) totally extraperitoneal). We hypothesize that the TREPP shows more favorable outcome compared to the current gold standard procedures: TEP and Lichtenstein. METHODS: Between January 2016 and December 2018, 3285 consecutive patients underwent surgical treatment and were included for analysis. The outcome measures were postoperative pain, recurrence rate and other surgical complications. Propensity-score matching was used to address potential selection bias. RESULTS: After propensity-score matching, there was no statistically significant difference in postoperative pain in the TREPP group compared to the Lichtenstein group (TREPP 7.3% versus Lichtenstein 6.3%; p = 0.67) nor in TREPP compared to TEP (TREPP 7.4% versus TEP 4.1%; p = 0.064). There was no statistically significant difference in recurrences in the TREPP group compared to Lichtenstein (3.8% vs 2.5%; p = 0.42), nor in the TREPP versus TEP comparison (3.9% vs 2.8%; p = 0.55) CONCLUSION: This study compares TREPP with Lichtenstein and TEP in the presence of postoperative pain, recurrences and other adverse outcomes. After propensity-score matching, no statistically significant difference in postoperative pain or recurrences remained between either TREPP compared to Lichtenstein, or TREPP compared to TEP. Based on these results, TREPP, Lichtenstein and TEP showed comparable results in postoperative pain, recurrences and other surgical site complications.

Wave intensity analysis of maternal arterial stiffness: augmentation index and pulse wave velocity in pregnancies complicated by diabetes or hypertension.

PURPOSE: The aim of our study was to compare the maternal arterial stiffness in pregnant women with diabetic disease, hypertension and those with normal pregnancies. METHODS: A cross-sectional study was performed involving 65 pregnant women with diabetic disease (DD group), 26 pregnant women with hypertension (RR group) and 448 women with normal pregnancies (control group). The augmentation index (AIx) and the pulse wave velocity (PWV) of the right carotid artery were assessed using non-invasive sonographic wave intensity analysis. Furthermore, the reliability of the measurements was evaluated in 21 healthy women. RESULTS: Compared with the controls, the AIx and PWV were increased in the DD group [11.0 (interquartile range, IQR 7.3, 15.2) vs. 5.7 (IQR 2.4, 9.3), P < 0.001; 5.7 (IQR 5.1, 6.4) vs. 5.2 (IQR 4.6, 6.1), P = 0.001; respectively] and the RR group [9.3 (IQR 6.6, 11.5) vs. 5.7 (IQR 2.4, 9.3), P < 0.001; 7.1 (6.3, 7.9) vs. 5.2 (IQR 4.6, 6.1), P < 0.001; respectively]. The intraclass and interclass correlation coefficients were good to excellent for the AIx (ICC: 0.91, P < 0.001 and 0.74, P < 0.002; respectively) and PWV measurements (ICC: 0.71, P < 0.004 and 0.70, P < 0.005; respectively). CONCLUSION: Pregnancies complicated by diabetic disease or hypertension are associated with increased maternal arterial stiffness. The importance of wave intensity analysis needs to be verified and larger studies are needed to establish both normal and cutoff values that may be relevant for clinical decisions.

Outcome of fetuses with gastroschisis after modification of prenatal management strategies : Prenatal management and outcome of gastroschisis.

PURPOSE: To improve the outcome of fetuses with gastrochisis several studies evaluated prenatal predictors. But there are different guidelines established and therefore the prenatal care is not standardized. With our study we wanted to evaluate the outcome of fetuses with gastroschisis after modification of prenatal management strategies at the Department of Obstetrics and Gynecology of the University Hospital Münster. METHODS: In this explorative retrospective study of 39 fetuses with gastroschisis, we compare the clinical outcome between two management groups. In the first group (group 1, n = 14) prenatal indication for delivery was confirmed by a subjective evaluation of the small bowel diameter and the wall thickness without established cut-off values for these parameters. In the second group (group 2, n = 25) certain limits for the small bowel diameter (25 mm) and the wall thickness (2.5 mm) were used for fetal surveillance. RESULTS: Noticeable differences between the two groups regarding birth weight, weight centile, arterial pH, small bowel diameter, wall thickness, adverse bowel condition and re-operations could not be observed. In group 2, delivery was earlier (p = 0.011), and a lower rate of prenatal complications was observed (p = 0.016). CONCLUSION: To avoid adverse prenatal complications we recommend the observation of fetuses with gastroschisis by sonographic monitoring of the small bowel diameter and the wall thickness.

Importance of Transvaginal Elastography in the Diagnosis of Uterine Fibroids and Adenomyosis.

PURPOSE: To evaluate normal uterine tissue with special regard to age and the presence of uterine fibroids and adenomyosis with transvaginal elastography. MATERIALS AND METHODS: In a prospective study elastographic data of the uterus were obtained in 206 unselected women with transvaginal ultrasound. Women who presented without any uterine pathology in ultrasonography were included in a control group, women with uterine fibroids in a uterine fibroid group, and women with adenomyosis in an adenomyosis group. In the control group strain values were measured at two regions of interest (ROIs) placed one upon the other in the anterior inferior uterine segment during a cycle of compression. The maximum strain ratio (ROI1 / ROI2) was stored as the "age index". In all groups strain values were measured at two ROIs placed side by side in a uterine fibroid (uterine fibroid group) or adenomyosis (adenomyosis group) or healthy homogeneous tissue (control group) and adjacent healthy tissue. Maximum strain ratios (ROI3 / ROI4) were stored as the "lesion index". RESULTS: The "age index" was significantly negatively correlated with the age of the women (r = -0.49, p < 0.001). The median "lesion indices" were significantly (p < 0.001) different between the uterine fibroid, adenomyosis and control groups. Median "lesion indices" were 2.65, 0.44 and 1.19, respectively. CONCLUSION: The "age index" shows that normal uterine tissue has a certain age-dependent stiffness that increases with age. The "lesion index" allows for the assessment of the presence of a uterine fibroid or adenomyosis and helps to differentiate between both focal findings. Thus the use of elastography in addition to conventional ultrasound could help to diagnose uterine focal lesions and may be useful in preoperative planning.

Disinfection of transvaginal ultrasound probes in a clinical setting: comparative performance of automated and manual reprocessing methods.

OBJECTIVES: Transvaginal and intracavitary ultrasound probes are a possible source of cross-contamination with microorganisms and thus a risk to patients' health. Therefore appropriate methods for reprocessing are needed. This study was designed to compare the standard disinfection method for transvaginal ultrasound probes in Germany with an automated disinfection method in a clinical setting. METHODS: This was a prospective randomized controlled clinical study of two groups. In each group, 120 microbial samples were collected from ultrasound transducers before and after disinfection with either an automated method (Trophon EPR®) or a manual method (Mikrozid Sensitive® wipes). Samples were then analyzed for microbial growth and isolates were identified to species level. RESULTS: Automated disinfection had a statistically significantly higher success rate of 91.4% (106/116) compared with 78.8% (89/113) for manual disinfection (P = 0.009). The risk of contamination was increased by 2.9-fold when disinfection was performed manually (odds ratio, 2.9 (95% CI, 1.3-6.3)). Before disinfection, bacterial contamination was observed on 98.8% of probes. Microbial analysis revealed 36 different species of bacteria, including skin and environmental bacteria as well as pathogenic bacteria such as Staphylococcus aureus, enterobacteriaceae and Pseudomonas spp. CONCLUSIONS: Considering the high number of contaminated probes and bacterial species found, disinfection of the ultrasound probe's body and handle should be performed after each use to decrease the risk of cross-contamination. This study favored automated disinfection owing to its significantly higher efficacy compared with a manual method. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Quantitative elastography of the uterine cervix as a predictor of preterm delivery.

OBJECTIVE: To evaluate the correlation between preterm delivery before 37 weeks of gestation and ultrasound elastography strain measurement of cervical stiffness. STUDY DESIGN: In this prospective study, 182 pregnant women were examined vaginally by ultrasound elastography from a mid-sagittal plane. Cervical length was measured and strain was calculated in four regions of interest on the anterior cervical lip. First, the software was validated by intraobserver variability. Second, strain and strain ratios were calculated with adjusted software presets and correlated to the outcome of spontaneous preterm delivery (sPTD). RESULT: A total of 8928 regions of interest (ROIs) and 6696 ratios were evaluated. The median gestational age at examination was 26 ± 6.1 weeks. A median maternal age of 33 ± 5.6 and a medial parity of 1 ± 0.9 were observed. Intra-Class-Correlation values in validation phase ranged from 0.893 to 0.967. The prevalence of sPTD was 11.9%. Strain ratio Rselective was identified as the best predictor of preterm delivery. Rselective values >0.89 were associated with preterm delivery with a sensitivity of 0.59 and a specificity of 0.86 (odds ratio=1.474 for an increase of 0.1 in Rselective; P=0.002). CONCLUSION: Ultrasound elastography strain measurement of cervical stiffness is correlated with the predictability of preterm delivery.

[Hemiarthroplasty for femoral neck fracture in the elderly--an operation suitable for teaching?]. / Ist die Versorgung der Schenkelhalsfraktur mittels Duokopfprothese beim alten Menschen ein geeigneter Ausbildungseingriff?

BACKGROUND: Hemiarthroplasty is a common procedure for treating femoral neck fractures in orthogeriatrics. For training purposes the operation may also be performed by supervised residents. Our study aims at evaluating the rates of early surgical complications after hemiarthroplasty in different age groups, comparing operations performed by consultants and residents. METHODS: All patients treated with hemiarthroplasty between December 2006 and July 2011 at our municipal, maximum-care-providing hospital were included in a retrospective cohort. The Excia® stem with a self-centering bipolar head (Aesculap, Tuttlingen) was used in all patients. Educational level of the operator (consultant vs. resident) and operation time were noted as well as early complications including luxation, infection, haematoma, seroma, and early periprosthetic fractures (e.g., intraoperative lesions of the greater trochanter). The complication rates were evaluated and compared by the chi-square test. RESULTS: 241 of 729 hemiarthroplasties were performed by supervised residents. Neither the overall complication rate nor the rates of specific complications differed significantly between the patients operated by consultants and those operated by residents. The result was still true if comparing the different age groups. On average operation time was 8 minutes longer in teaching operations. CONCLUSIONS: Focusing on early surgical complications, the teaching of hemiarthroplasty does not seem to increase the risk to patients of any age. We conclude that the hemiarthroplasty procedure is suitable for teaching younger colleagues in orthogeriatrics. As age is just one of several potential risk factors, additional studies on this topic should be undertaken.

Prevalence, incidence and persistence of genital HPV infections in a large cohort of sexually active young women in the Netherlands.

BACKGROUND: We assessed age- and type-specific HPV prevalence, incidence and persistence and their associated risk factors in young women prior to vaccination, to enable monitoring of the impact of introduction of HPV vaccination in the years before participation in the cervical screening program. METHODS: The HPV status was assessed in 3282 women aged 16-29 who participated in a Chlamydia trachomatis screening implementation program, of which 2014 women (61%) participated in two rounds (one year apart). Self-collected vaginal swab were analyzed by SPF(10) LiPA on the presence of HPV DNA. Risk factors for prevalent, incident and persistent HPV infections were calculated using generalized estimating equation. RESULTS: The prevalence of any HPV in the first round amounted to 54%, while 34% of the women who participated in the second round had a persistent infection and 45% an incident infection. The five most common HPV types found in this study were HPV16, -51, -52, -31 and -53. HPV16 and/or HPV18 prevalence, incidence and persistence in the second round were 15%, 8% and 9%, respectively and for HPV6 and/or HPV11 6%, 4% and 2%, respectively. Relatively to other HPV genotypes, hrHPV types were found more often as a persistent infection than as an incident infection. Furthermore, there is an age-dependent increase within this age range for persistent infections but not for incident infections. CONCLUSION: The HPV prevalence (54%), incidence (45%) and persistence (34%) is high among sexually active young women in the Netherlands. The different HPV type distribution and risk factors for prevalent, incident and persistent infections, as well as the observed age-trends should be taken into account in interpreting data obtained after vaccine introduction. Repeating measurements post-immunization are particularly relevant until the age when screening starts (i.e. 30 years in the Netherlands).

Prevalence of genital HPV infections and HPV serology in adolescent girls, prior to vaccination.

INTRODUCTION: Monitoring the prevalence of type-specific HPV-DNA infections before and shortly after introduction of routine HPV vaccination offers the opportunity to evaluate early effects of the vaccination program. With this aim a cohort study was set up of 14- to 16-year-old girls eligible for HPV vaccination in the Netherlands. Annually, HPV-DNA and antibody status in vaginal self-samples and in serum respectively, will be studied among vaccinated (58%) and unvaccinated girls (42%). Here we present baseline data on vaginal HPV-DNA status in relation to serum antibodies. METHODS: The 1800 enrolled girls filled out an internet-based questionnaire and provided a vaginal self-sample for genotype specific HPV-DNA detection using SPF(10) PCR amplification and reverse line probe hybridization. Furthermore, 64% of the girls provided a blood sample for HPV antibody analysis. IgG antibodies against virus-like particles were determined for 7 HPV genotypes. RESULTS: At baseline, type-specific HPV-DNA was detected in 4.4% (n = 79) of the 1800 girls: 2.7% (n = 49) concerned a high risk HPV type (hrHPV-DNA). The three most common types were HPV type 16, 18 and 51 (40%). Out of the hrHPV-DNA positive girls, 32% was seropositive vs. 12% in HPV-DNA negative girls (p<0.001). Risk factors independently associated with hrHPV-DNA infection among the sexually active girls were age >15 years vs. 14-15 years (OR = 2.6 (1.2-5.9)), age of sexual debut <14 vs. above 14 years (OR = 3.0 (1.1-8.2)), total number of lifetime partners above two vs. less than two partners (OR = 3.2 (1.3-8.0)) and age of partner >17 vs. under 17 years (OR = 4.2 (1.5-13.0)). CONCLUSION: A low hrHPV-DNA prevalence was found in the adolescent girls. The observed vs. expected age-related increase in HPV-DNA prevalence in this cohort in the coming years (with increased sexual activity) will provide understanding of the effect of HPV vaccination. Furthermore, this cohort study will offer the opportunity to improve knowledge of antibody responses following natural infection and vaccination.

Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease.

In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I-123]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p<0.01). Contralateral putamen and caudate nucleus FP-CIT uptake correlated significantly with severity of rigidity (p<0.01) and hypokinesia (p<0.01) but not with severity of resting or postural tremor (p>0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor.

Intracranial arteriovenous fistula caused by endovascular stent-grafting and dilatation.

A 58-year-old man developed a self-occluding arteriovenous fistula following stent-grafting of the right internal carotid artery (ICA). Due to prolonged ischaemic neurological deficits carotid angiography had been performed 3 weeks previously. It revealed marked atherosclerotic lesions predominantly narrowing the distal right carotid siphon. MRI confirmed ischaemic lesions and massive deficits of perfusion in the right ICA cerebral territory. Stent-grafting was performed successfully, but subsequent angiography revealed a new arteriovenous fistula adjacent to the stent, between the right carotid siphon and the cavernous sinus. On angiography 10 days later, the fistula no longer was present, and flow MRI were normal; the patient was by then asymptomatic. Arteriovenous fistula can thus complicate following endovascular stenting.

Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry. METHODS: Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease. RESULTS: Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells. CONCLUSIONS: Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.

Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: an EORTC double-blind placebo-controlled phase III study.

BACKGROUND: CDE (cyclophosphamide, doxorubicin, etoposide) is one of the standard chemotherapy regimens in the treatment of small-cell lung cancer (SCLC), with myelosuppression as dose-limiting toxicity. In this trial the impact of prophylactic antibiotics on incidence of febrile leucopenia (FL) during chemotherapy for SCLC was evaluated. PATIENTS AND METHODS: Patients with chemo-naïve SCLC were randomized to standard-dose CDE (C 1,000 mg/m2 day 1, D 45 mg/m2 day 1, E 100 mg/m2 days 1-3. i.v., q 3 weeks, x5) or to intensified CDE chemotherapy (125% dose, q 2 weeks, x4, with filgrastim 5 microg/kg/day days 4-13) to assess the impact on survival (n = 240 patients). Patients were also randomized to prophylactic antibiotics (ciprofloxacin 750 mg plus roxithromycin 150 mg, bid. days 4-13) or to placebo in a 2 x 2 factorial design (first 163 patients). This manuscript focuses on the antibiotics question. RESULTS: The incidence of FL during the first cycle was 25% of patients in the placebo and 11% in the antibiotics arm (P = 0.010; 1-sided), with an overall incidence through all cycles of 43% vs. 24% respectively (P = 0.007; 1-sided). There were less Gram-positive (12 vs. 4), Gram-negative (20 vs. 5) and clinically documented (38 vs. 15) infections in the antibiotics arm. The use of therapeutic antibiotics was reduced (P = 0.013; 1-sided), with less hospitalizations due to FL (31 vs. 17 patients, P = 0.013: 1-sided). However, the overall number of days of hospitalization was not reduced (P = 0.05; 1-sided). The number of infectious deaths was nil in the antibiotics vs. five (6%) in the placebo arm (P = 0.022; 2-sided). CONCLUSIONS: Prophylactic ciprofloxacin plus roxithromycin during CDE chemotherapy reduced the incidence of FL, the number of infections, the use of therapeutic antibiotics and hospitalizations due to FL by approximately 50%, with reduced number of infectious deaths. For patients with similar risk for FL, the prophylactic use of antibiotics should be considered.

The effect of high-dose fluticasone propionate and budesonide on lung function and asthma exacerbations in patients with severe asthma.

The purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate (FP) and inhaled budesonide (BUD) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid. This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP (2000 micrograms daily via a Diskhaler inhaler; Glaxo Wellcome, Evreux, France) and BUD (2000 micrograms daily via a Turbuhaler inhaler; Astra Pharmaceuticals, Rijswijka, Netherlands) on lung function and asthma exacerbations in 395 patients with asthma. FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days (P = 0.02), the incidence of days free from rescue bronchodilator usage (P = 0.02) and the distribution of change in peak expiratory flow (PEF) expressed as a percentage of the predicted PEF (P = 0.04). During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec (FEV1) at 8, 16 and 24 weeks, change in the median daytime symptom score during weeks 5-16, for incidence of symptom-free days and incidence of days free from rescue bronchodilator usage during weeks 17-24. There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation (33.8 and 28.4% of patients, respectively). There was, however, evidence that the exacerbations were clinically less severe in patients treated with FP, in that the time to resolution was quicker (11.0 vs. 14.7 days; P = 0.035), mean duration of all exacerbations (for an individual patient) tended to be shorter (18.5 vs. 23.6 days; P = 0.12), the time off work was reduced (4.2 vs. 7.6 days; P = 0.012) and the lowest PEF recorded during the exacerbation was higher (301 vs. 263 l min-1; P = 0.07). There were no clinically relevant differences in the safety (serum cortisol levels, markers of bone turnover, adverse events) of FP and BUD at these microgram equivalent doses. The patients recruited into this study, in retrospect, probably had no need for such high doses of inhaled corticosteroid but, irrespective of this, FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect.

[Arterial vascular lesions after total hip joint replacement]. / Arterielle Gefässläsionen nach totalem Hüftgelenkersatz.

We report on three arterial thromboses of the external iliac artery following total hip replacement. As a result of implanted cement/spongiosa or protrusion of the acetabular component, the iliac vessels were compressed. Furthermore, we report about one intraoperative arterial vessel lesion in a 65-year-old patient during a revision operation. We recommend that in case of acute ischemic syndromes of lower limbs following total hip replacement, an angiography should be performed in order to exclude an extravascular cause of thrombosis. For therapy in those cases extra-anatomic bypasses should be preferred to thrombectomies.

Nitric oxide and proteoglycan turnover in rabbit articular cartilage.

Articular chondrocytes are known to synthesize large amounts of nitric oxide in response to exposure to interleukin-1, but the role of this radical in proteoglycan turnover remains controversial. In this study, we used two different inhibitors of nitric oxide synthase, NG-methyl-L-arginine and thiocitrulline, to study the effects of nitric oxide on the synthesis and breakdown of proteoglycan in rabbit articular cartilage. Synthesis of nitric oxide by cartilage slices in response to treatment with interleukin-1 and a partially purified mixture of synovial cytokines known as chondrocyte-activating factors peaked during the first 2 days of culture and then fell to low levels, despite daily replenishment with fresh medium and cytokines to the cultures. The production of nitric oxide was completely inhibited by NG-methyl-L-arginine and thiocitrulline. Interleukin-1 and the chondrocyte-activating factors inhibited proteoglycan synthesis and accelerated proteoglycan breakdown in the slices of cartilage. Both nitric oxide synthase inhibitors substantially counteracted the suppression of proteoglycan synthesis but exacerbated proteoglycan catabolism occurring in response to interleukin-1 and the chondrocyte-activating factors. The accelerated catabolism was associated with increased levels of matrix metalloproteinases in the conditioned medium. This dual effect of nitric oxide complicates decision making with regard to the possible clinical applications of nitric oxide agonists or antagonists in diseases of cartilage.

[Outcome of management of femoral neck fractures with cemented bipolar endoprostheses]. / Ergebnisse der Versorgung von Schenkelhalsfrakturen mit zementierten bipolaren Endoprothesen.

In our hospital 334 patients were treated with a bipolar prosthesis for medial femoral neck fracture in the years 1990 and 1991. After an average of 54 months (minimum 48 months) informations about function could be obtained by examination and x-ray from 19 patients (5.7%), from 42 patients (12.6%) a questionnaire was analyzed. No function of the hip was described as poor, 2/3 of the patients had no pain, nearly 50% walked without crutches or other tools. No protrusio acetabuli or acetabular erosion was seen. Together with further follow-up examinations from another 230 patients out of 1365 patients treated with a bipolar prosthesis up to now, these results support the statement that bipolar prostheses play an important role in treatment of medial femoral neck fractures in the elderly.