Appropriateness and long-term discontinuation rate of biological therapies in ulcerative colitis

BACKGROUND Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome. METHODS We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents. Appropriateness of the first-line anti-TNFα treatment was assessed using detailed criteria developed during the European Panel on the Appropriateness of Therapy for UC. Treatment discontinuation as an outcome was assessed for categories of appropriateness. RESULTS Appropriateness of the first-line biological treatment was determined in 186 UC patients. For 64% of them, this treatment was considered appropriate. During follow-up, 37% of all patients discontinued biological treatment, 17% specifically because of failure. Time-to-failure of treatment was significantly different among patients on an appropriate biological treatment compared to those for whom the treatment was considered not appropriate (p=0.0007). Discontinuation rate after 2years was 26% compared to 54% between those two groups. Patients on inappropriate biological treatment were more likely to have severe disease, concomitant steroids and/or immunomodulators. They were also consistently more likely to suffer a failure of efficacy and to stop therapy during follow-up. CONCLUSION Appropriateness of first-line anti-TNFα therapy results in a greater likelihood of continuing with the therapy. In situations where biological treatment is uncertain or inappropriate, physicians should consider other options instead of prescribing anti-TNFα agents.

Does Full Wound Rupture following Median Pilonidal Closure Alter Long-Term Recurrence Rate?

OBJECTIVE The purpose of this study was to examine the recurrence rate of wound rupture in primary pilonidal sinus disease (PSD) after median closure. SUBJECTS AND METHODS A total of 583 patients from the German military cohort were interviewed. We compared the choice of surgical therapy, wound dehiscence (if present) and long-term recurrence-free survival for patients with primary open treatment, marsupialization and primary median treatment (closed vs. secondary open, respectively). Actuarial recurrence rate was determined using the Kaplan-Meier calculation with a follow-up of up to 20 years after primary PSD surgery. RESULTS Patients with excision followed by primary open wound treatment showed a significantly lower 5- than 10-year recurrence rate (8.3 vs. 11.2%) compared to the patients with primary midline closure (17.4 vs. 20.5%, p = 0.03). The 20-year recurrence rate was 28% in primary open wound treatment versus 44% in primary midline closure without wound rupture. In contrast to these findings, long-term recurrence rates following secondary open wound treatment (12.2% at 5 years vs. 17.1% at 10 years) tended to be higher (although not significantly, p = 0.57) compared to primary open treatment (8.3% at 5 years vs. 11.2% at 10 years). There was no statistical difference in long-term recurrence rates between secondary open and primary midline closure (p = 0.7). Hence, despite only a short wound closure time experienced before wound rupture, the patient does not fully benefit from an open wound treatment in terms of recurrence rate. CONCLUSION The postoperative pilonidal sinus wound rupture of primary midline closures did not significantly increase the 5- and 10-year long-term recurrence rates compared to uneventfully healing primary midline closures.

Recurrence-free survival, but not surgical therapy per se, determines 583 patients' long-term satisfaction following primary pilonidal sinus surgery.

PURPOSE With pilonidal sinus disease (PSD) incidence increasing and patients freely choosing their surgeon, patients' interest issues have been brought forward estimating patient satisfaction following pilonidal sinus surgery. The influence of wound healing time and long-term recurrence rate on patient satisfaction in primary PSD surgery has not been investigated yet. METHODS Five hundred eighty-three patients (German military cohort) were interviewed, compiling wound healing time, aesthetic satisfaction, long-term recurrence-free survival and patient satisfaction having undergone primary open (PO) treatment, marsupialization (MARS) or primary midline closure (PMC) treatment. Recurrence rate was determined by Kaplan-Meier calculation following up to 20 years after primary PSD surgery. RESULTS Patient satisfaction ranking from 1 to 10 (10 = max. satisfied) showed an average satisfaction of 8.2 (range 0-10; 95% confidence interval (CI) 7891-8250). In-hospital stay time was significantly longer in primary open (PO) and marsupialization (MARS) group as compared to primary midline closure (PMC; p < 0.0001, Kruskal-Wallis test). Satisfaction was comparable between treatment groups, and was neither linked to in-hospital stay time nor to longer outpatient wound care period or total treatment time. Recurrence-free survival, as seen in the PO and PMC treatment group, revealed a highly significant difference for all patients. Improvement in MARS patients with versus without recurrence was low, as satisfaction with primary treatment was lower as the other groups. CONCLUSIONS Neither choice of surgical treatment nor treatment duration within hospital or after hospital influences patient satisfaction, as long as recurrence-free survival can be provided. Marsupialization was ranked lower in both groups (with or without recurrence), and should be abandoned, as patients are significantly less satisfied with either results, independent of recurrence.

Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in the rabbit microsurgical venous pouch bifurcation model

In experimental aneurysm models, long-term patency without spontaneous thrombosis is the most important precondition for analyses of embolization devices. We recently reported the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, low mortality, and high short-term aneurysm patency. In order to further evaluate our model, we examined the long-term patency rate.

[Long-term follow up after antithyroid drug treatment in Graves' disease]

In Europe antithyroid drug (ATD) therapy is the preferred initial treatment for patients with a first episode of Graves' disease. Results of long-term recurrence rates following ATD therapy are conflicting. The main goal was to assess long-term recurrence rate after ATD treatment. Secondarily we tried to verify chemical and clinical findings (thyrotropin receptor antibodies (TRAb), duration of primary treatment, age and goitre size) as predictive factors.

Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.

AIMS The purpose of this study was to identify novel genetic variants influencing circulating asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and to evaluate whether they have a prognostic value on cardiovascular mortality. METHODS AND RESULTS We conducted a genome-wide association study on the methylarginine traits and investigated the predictive value of the new discovered variants on mortality. Our meta-analyses replicated the previously known locus for ADMA levels in DDAH1 (rs997251; P = 1.4 × 10(-40)), identified two non-synomyous polymorphisms for SDMA levels in AGXT2 (rs37369; P = 1.4 × 10(-40) and rs16899974; P = 1.5 × 10(-38)) and one in SLC25A45 (rs34400381; P = 2.5 × 10(-10)). We also fine-mapped the AGXT2 locus for further independent association signals. The two non-synonymous AGXT2 variants independently associated with SDMA levels were also significantly related with short-term heart rate variability (HRV) indices in young adults. The major allele (C) of the novel non-synonymous rs16899974 (V498L) variant associated with decreased SDMA levels and an increase in the ratio between the low- and high-frequency spectral components of HRV (P = 0.00047). Furthermore, the SDMA decreasing allele (G) of the non-synomyous SLC25A45 (R285C) variant was associated with a lower resting mean heart rate during the HRV measurements (P = 0.0046), but not with the HRV indices. None of the studied genome-wide significant variants had any major effect on cardiovascular or total mortality in patients referred for coronary angiography. CONCLUSIONS AGXT2 has an important role in SDMA metabolism in humans. AGXT2 may additionally have an unanticipated role in the autonomic nervous system regulation of cardiac function.

Initial clinical experience with the 4-F self-expanding XPERT stent system for infrapopliteal treatment of patients with severe claudication and critical limb ischemia

PURPOSE: To evaluate the primary success and short-term patency associated with a new 4-F sheath-compatible self-expanding nitinol stent after failed conventional angioplasty of distal popliteal and infrapopliteal lesions in severe lifestyle-limiting claudication (LLC) and chronic critical limb ischemia (CLI). MATERIALS AND METHODS: Between May 2003 and July 2005, 35 patients with Rutherford category 3-5 disease (16 patients with CLI, 19 patients with LLC) underwent percutaneous transluminal angioplasty (PTA) and stent implantation. Indications for stent placement were residual stenosis, flow-limiting dissections, or elastic recoil after PTA. Before and after the intervention and during the 6-month follow-up, clinical investigation, color-flow and duplex Doppler ultrasonography, and digital subtraction angiography were performed. Technical success, primary patency at 6 months, clinical improvement as defined by Rutherford with clinical and hemodynamic measures, and complications were evaluated. RESULTS: A total of 22 patients underwent distal popliteal artery stent placement and 13 underwent tibioperoneal artery stent placement. Stent implantation was successfully performed in all patients. After stent placement, the primary cumulative patency rate for the study group at 6 months was 82%. The mean resting ankle-brachial index at baseline was 0.50 +/- 0.16 and significantly increased to 0.90 +/- 0.17 at 12-24 hours after intervention and 0.82 +/- 0.24 at latest follow-up (P < .001 for both). The sustained clinical improvement rate was 80% at the 6-month follow-up. The 6-month limb salvage rate regarding major amputation was 100%. The rate of major complications was 17%. CONCLUSIONS: Infrapopliteal application of the new nitinol stent is a safe, feasible, and effective method with good short-term patency rate in the treatment of severe LLC and chronic CLI.

Trigger activity more than three years after left atrial linear ablation without pulmonary vein isolation in patients with atrial fibrillation.

OBJECTIVES The aim of this study was to analyze trigger activity in the long-term follow-up after left atrial (LA) linear ablation. BACKGROUND Interventional strategies for curative treatment of atrial fibrillation (AF) are targeted at the triggers and/or the maintaining substrate. After substrate modification using nonisolating linear lesions, the activity of triggers is unknown. METHODS With the LA linear lesion concept, 129 patients were treated using intraoperative ablation with minimal invasive surgical techniques. Contiguous radiofrequency energy-induced lesion lines involving the mitral annulus and the orifices of the pulmonary veins without isolation were placed under direct vision. RESULTS After a mean follow-up of 3.6 +/- 0.4 years, atrial ectopy, atrial runs, and reoccurrence of AF episodes were analyzed by digital 7-day electrocardiograms in 30 patients. Atrial ectopy was present in all patients. Atrial runs were present in 25 of 30 patients (83%), with a median number of 9 runs per patient/week (range 1 to 321) and a median duration of 1.2 s/run (range 0.7 to 25), without a significant difference in atrial ectopy and atrial runs between patients with former paroxysmal (n = 17) or persistent AF (n = 13). Overall, 87% of all patients were completely free from AF without antiarrhythmic drugs. CONCLUSIONS A detailed rhythm analysis late after specific LA linear lesion ablation shows that trigger activity remains relatively frequent but short and does not induce AF episodes in most patients. The long-term success rate of this concept is high in patients with paroxysmal or persistent AF.

Catheter ablation of persistent and long-standing persistent atrial fibrillation. Strategies and results

Catheter ablation for paroxysmal atrial fibrillation is a meanwhile established therapy option, which is most frequently performed using radiofrequency ablation. Mid-term success rate of 70 % are achievable with a single ablation procedure. However, the mechanistics of persistent atrial fibrillation are less well understood and catheter ablation is a far more challenging procedure. Different ablation approaches are being performed to treat persistent atrial fibrillation ranging from sole pulmonary vein isolation to additional ablation of fractionated electrograms aiming for termination of atrial fibrillation. Thus far, it has not been investigated which strategy is most successful in treating persistent atrial fibrillation. After extended ablation of atrial fibrillation, occurrence of organized atrial arrhythmias is not uncommon and can be successfully ablated. These consecutive arrhythmias can be considered as a next step towards stable sinus rhythm after repeat ablation. Improvement of mapping methods as well as a better understanding of mechanisms of atrial fibrillation may increase success rate of catheter ablation of persistent atrial fibrillation and may also help to improve success rate of these complex procedures.

Range-based Weighted-likelihood Particle Filter for RSS-based Indoor Tracking

Attractive business cases in various application fields contribute to the sustained long-term interest in indoor localization and tracking by the research community. Location tracking is generally treated as a dynamic state estimation problem, consisting of two steps: (i) location estimation through measurement, and (ii) location prediction. For the estimation step, one of the most efficient and low-cost solutions is Received Signal Strength (RSS)-based ranging. However, various challenges - unrealistic propagation model, non-line of sight (NLOS), and multipath propagation - are yet to be addressed. Particle filters are a popular choice for dealing with the inherent non-linearities in both location measurements and motion dynamics. While such filters have been successfully applied to accurate, time-based ranging measurements, dealing with the more error-prone RSS based ranging is still challenging. In this work, we address the above issues with a novel, weighted likelihood, bootstrap particle filter for tracking via RSS-based ranging. Our filter weights the individual likelihoods from different anchor nodes exponentially, according to the ranging estimation. We also employ an improved propagation model for more accurate RSS-based ranging, which we suggested in recent work. We implemented and tested our algorithm in a passive localization system with IEEE 802.15.4 signals, showing that our proposed solution largely outperforms a traditional bootstrap particle filter.

Hysteroscopic outpatient metroplasty to expand dysmorphic uteri (HOME-DU technique): a pilot study.

The new classification system of uterine anomalies from the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy defines T-shaped and tubular-shaped infantilis uteri as 'dysmorphic'. Such malformations have been proven to be associated with poor reproductive performance. A prospective observational study was conducted with 30 infertile women with dysmorphic uterus who underwent the novel Hysteroscopic Outpatient Metroplasty to Expand Dysmorphic Uteri (HOME-DU ) technique. Incisions are made on the uterine walls with a 5 Fr bipolar electrode. The procedure was conducted in outpatients under conscious sedation, using a 5-mm office hysteroscope. The technique was successful in all cases without complications. A net increase of uterine volume was found, as measured at hysteroscopy and three-dimensional transvaginal ultrasound (P < 0.001). Uterine morphology improved in all patients but one. At mean follow-up of 15 months, clinical pregnancy rate was 57% and term delivery rate 65%. These early data support HOME-DU as safe and effective in expanding the volume and normalizing the appearance of the uterine cavity of dysmorphic uteri. Although the cohort was small, pregnancy and live births outcomes were favourable in this poor-prognosis group, implying desirable benefits, which should be compared with other techniques.

Patterns of landscape form in the upper Rhône basin, Central Swiss Alps, predominantly show lithologic controls despite multiple glaciations and variations in rock uplift rates

The development of topography depends mainly on the interplay between uplift and erosion. These processes are controlled by various factors including climate, glaciers, lithology, seismic activity and short-term variables, such as anthropogenic impact. Many studies in orogens all over the world have shown how these controlling variables may affect the landscape's topography. In particular, it has been hypothesized that lithology exerts a dominant control on erosion rates and landscape morphology. However, clear demonstrations of this influence are rare and difficult to disentangle from the overprint of other signals such as climate or tectonics. In this study we focus on the upper Rhône Basin situated in the Central Swiss Alps in order to explore the relation between topography, possible controlling variables and lithology in particular. The Rhône Basin has been affected by spatially variable uplift, high orographically driven rainfalls and multiple glaciations. Furthermore, lithology and erodibility vary substantially within the basin. Thanks to high-resolution geological, climatic and topographic data, the Rhône Basin is a suitable laboratory to explore these complexities. Elevation, relief, slope and hypsometric data as well as river profile information from digital elevation models are used to characterize the landscape's topography of around 50 tributary basins. Additionally, uplift over different timescales, glacial inheritance, precipitation patterns and erodibility of the underlying bedrock are quantified for each basin. Results show that the chosen topographic and controlling variables vary remarkably between different tributary basins. We investigate the link between observed topographic differences and the possible controlling variables through statistical analyses. Variations of elevation, slope and relief seem to be linked to differences in long-term uplift rate, whereas elevation distributions (hypsometry) and river profile shapes may be related to glacial imprint. This confirms that the landscape of the Rhône Basin has been highly preconditioned by (past) uplift and glaciation. Linear discriminant analyses (LDAs), however, suggest a stronger link between observed topographic variations and differences in erodibility. We therefore conclude that despite evident glacial and tectonic conditioning, a lithologic control is still preserved and measurable in the landscape of the Rhône tributary basins.