[Safety of treatment with tacrolimus ointment for anterior segment inflammatory diseases]

BACKGROUND: The off-label use of topical tacrolimus (Protopic) for inflammatory external eye diseases is gaining popularity. However, there are no reports on the safety profile of this new treatment option. PATIENTS AND METHODS: We treated six patients with different inflammatory eye diseases with topical tacrolimus (Protopic 0.03 %) as off-label use in addition to the conventional anti-inflammatory treatment. Patients were interviewed for side effects and serum drug concentrations were measured under steady state conditions one hour after topical application of tacrolimus ointment. RESULTS: Two patients reported a slight burning sensation immediately after application, in one patient we found a slight worsening of the dry eye problems. No patient abandoned the treatment due to side effects. Serum drug concentrations remained below the analytical threshold in all cases (< 1.5 ng/ml). CONCLUSIONS: Tacrolimus for the topical treatment of anterior segment inflammatory eye diseases is well tolerated without detectable systemic drug resorption.

USING AUTO- AND CROSS-CORRELATIONS FROM SEISMIC NOISE TO MONITOR VELOCITY CHANGES AT VILLARRICA VOLCANO, CHILE

We used the Green's functions from auto-correlations and cross-correlations of seismic ambient noise to monitor temporal velocity changes in the subsurface at Villarrica volcano in the Southern Andes of Chile. Campaigns were conducted from March to October 2010 and February to April 2011 with 8 broadband and 6 short-period stations, respectively. We prepared the data by removing the instrument response, normalizing with a root-mean-square method, whitening the spectra, and filtering from 1 to 10 Hz. This frequency band was chosen based on the relatively high background noise level in that range. Hour-long auto- and cross-correlations were computed and the Green's functions stacked by day and total time. To track the temporal velocity changes we stretched a 24 hour moving window of correlation functions from 90% to 110% of the original and cross correlated them with the total stack. All of the stations' auto-correlations detected what is interpreted as an increase in velocity in 2010, with an average increase of 0.13%. Cross-correlations from station V01, near the summit, to the other stations show comparable changes that are also interpreted as increases in velocity. We attribute this change to the closing of cracks in the subsurface due either to seasonal snow loading or regional tectonics. In addition to the common increase in velocity across the stations, there are excursions in velocity on the same order lasting several days. Amplitude decreases as the station's distance from the vent increases suggesting these excursions may be attributed to changes within the volcanic edifice. In at least two occurrences the amplitudes at stations V06 and V07, the stations farthest from the vent, are smaller. Similar short temporal excursions were seen in the auto-correlations from 2011, however, there was little to no increase in the overall velocity.

FOSSIL PLANTS AND PALYNOMORPHS FROM THE LATE PALEOZOIC CUTLER FORMATION, EASTERN PARADOX BASIN

The late Paleozoic Cutler Formation, where exposed near the modern-day town of Gateway, Colorado, has traditionally been interpreted as the product of alluvial fan deposition within the easternmost portion of the Paradox Basin. The Paradox Basin formed between the western margin of the Uncompahgre Uplift segment of the Ancestral Rocky Mountains and the western paleoshoreline of the North American portion of Pangea. The Paradox Basin region is commonly thought to have experienced semi-arid to arid conditions and warm temperatures during the Pennsylvanian and Permian. Evidence described in this paper support prior interpretations regarding paleoclimate conditions and the inferred depositional environment for the Cutler Formation near Gateway, Colorado. Plant fossils collected from the late Paleozoic Cutler Formation in The Palisade Wilderness Study Area (managed by the U.S. Department of the Interior, Bureau of Land Management) of western Colorado include Calamites, Walchia, Pecopteris, and many calamitean fragments. The flora collected is interpreted to have lived in an arid or semi-arid environment that included wet areas of limited areal extent located near the apex of an alluvial fan system. Palynological analysis of samples collected revealed the presence of the common Pennsylvanian palynomorphs Thymospora pseudothiessenii and Lophotriletes microsaetosus. These fossils suggest that warm and at least seasonally and locally wet conditions existed in the area during the time that the plants were growing. All evidence of late Paleozoic plant life collected during this study was found along the western margin of the Uncompahgre Uplift segment of the Ancestral Rocky Mountains. During the late Paleozoic, sediment was eroded from the Uncompahgre Uplift and deposited in the adjacent Paradox Basin. The preservation of plant fossils in the most proximal parts of the Paradox Basin is remarkable due to the fact that much of the proximal Cutler Formation consists of conglomerates and sandstones deposited as debris flow and by fluvial systems. The plants must have grown in a protected setting, possibly an abandoned channel on the alluvial fan, and been rapidly buried in the subsiding Paradox Basin. It is likely that there was abundant vegetation in and adjacent to low-lying wet areas at the time the Cutler Formation was deposited.

Surgical instrumentation for the in vivo determination of lumbar spinal segment stiffness and viscoelasticity

The definition of spinal instability is still controversial. For this reason, it is essential to better understand the difference in biomechanical behaviour between healthy and degenerated human spinal segments in vivo. A novel computer-assisted instrument was developed with the objective to characterize the biomechanical parameters of the spinal segment. Investigation of the viscoelastic properties as well as the dynamic spinal stiffness was performed during a minimally invasive procedure (microdiscectomy) on five patients. Measurements were performed intraoperatively and the protocol consisted of a dynamic part, where spinal stiffness was computed, and a static part, where force relaxation of the segment under constant elongation was studied. The repeatability of the measurement procedure was demonstrated with five replicated tests. The spinal segment tissues were found to have viscoelastic properties. Preliminary tests confirmed a decrease in stiffness after decompression surgery. Patients with non-relaxed muscles showed higher stiffness and relaxation rate compared to patients with relaxed muscles, which can be explained by the contraction and relaxation reflex of muscles under fast and then static elongation. The results show the usefulness of the biomechanical characterization of the human lumbar spinal segment to improve the understanding of the contribution of individual anatomical structures to spinal stability.

Non-selective cutaneous sensory neurectomy as an alternative treatment for auto-mutilation lesion following arthrodesis in three dogs

OBJECTIVE: To describe an alternative method for the treatment of non-responsive self-mutilation injuries in three dogs after carpal/tarsal arthrodesis. STUDY DESIGN: Case series ANIMALS: Two dogs with carpal injury and one dog with tarsal injury treated by arthrodesis METHODS: All dogs developed self-mutilation injuries due to licking and/or chewing of the toes within 21-52 days of surgery. Clinical signs did not resolve within one week after conservative treatment with wound debridement and protective bandages. Following general anaesthesia, a deep horseshoe-shaped skin incision, including the subdermal tissue, was performed proximal to the self-mutilation injury transecting the sensory cutaneous afferent nerves. The skin incision was closed with simple interrupted sutures. RESULTS: All wounds healed without complication. Self-mutilation resolved completely within 24 hours after surgery in all dogs. No recurrence was observed (5 months to 3 years). CONCLUSION: Non-selective cutaneous sensory neurectomy may lead to resolution of self-mutilation following arthrodesis in dogs. CLINICAL RELEVANCE: Failure of conservative treatment in self-mutilation injuries often leads to toe or limb amputation as a last resort. The technique described in this case series is a simple procedure that should be considered prior to amputation. The outcome of this procedure in dogs self-multilating due to neurological or behavioral disturbances unrelated to carpal or tarsal arthrodesis is not known.

Comparison of Newer-Generation Drug-Eluting With Bare-Metal Stents in Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pooled Analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) Trials

OBJECTIVES This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. METHODS Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. RESULTS Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Gender-related mortality trends among diabetic patients with ST-segment elevation myocardial infarction: insights from a nationwide registry 1997-2010

BACKGROUND Data on temporal trends in outcomes, gender differences, and adherence to evidence-based therapy (EBT) of diabetic patients with ST-segment elevation myocardial infarction (STEMI) are sparse. METHODS We performed a retrospective analysis of prospectively acquired data on 3565 diabetic (2412 males and 1153 females) STEMI patients enrolled in the Swiss AMIS Plus registry between 1997 and 2010 and compared in-hospital outcomes and adherence to EBT with the nondiabetic population (n=15,531). RESULTS In-hospital mortality dramatically decreased in diabetic patients, from 19.9% in 1997 to 9.0% in 2010 (p trend<0.001) with an age-adjusted decrease of 6% per year of admission. Similar trends were observed for age-adjusted reinfarction (OR 0.86, p<0.001), cardiogenic shock (OR 0.88, p<0.001), as well as death, reinfarction, or stroke (OR 0.92, p<0.001). However, the mortality benefit over time was observed in diabetic males (p trend=0.006) but not females (p trend=0.082). In addition, mortality remained twice as high in diabetic patients compared with nondiabetic ones (12.1 vs. 6.1%, p<0.001) and diabetes was identified as independent predictor of mortality (OR 1.23, p=0.022). Within the diabetic cohort, females had higher mortality than males (16.1 vs. 10.2%, p<0.001) and female gender independently predicted in-hospital mortality (OR 1.45, p=0.015). Adherence to EBT significantly improved over time in diabetic patients (p trend<0.001) but remained inferior - especially in women - to the one of nondiabetic individuals. CONCLUSIONS In-hospital mortality and morbidity of diabetic STEMI patients in Switzerland improved dramatically over time but, compared with nondiabetic counterparts, gaps in outcomes as well as EBT use persisted, especially in women.

Future treatment strategies in ST-segment elevation myocardial infarction

Over the past five decades, management of acute ST-segment elevation myocardial infarction (STEMI) has evolved substantially. Current treatment encompasses a systematic chain of network activation, antithrombotic drugs, and rapid instigation of mechanical reperfusion, although pharmacoinvasive strategies remain relevant. Secondary prevention with drugs and lifestyle modifications completes the contemporary management package. Despite a tangible improvement in outcomes, STEMI remains a frequent cause of morbidity and mortality, justifying the quest to find new therapeutic avenues. Ways to reduce delays in doing coronary angioplasty after STEMI onset include early recognition of symptoms by patients and prehospital diagnosis by paramedics so that the emergency room can be bypassed in favour of direct admission to the catheterisation laboratory. Mechanical reperfusion can be optimised by improvements to stent design, whereas visualisation of infarct size has been improved by developments in cardiac MRI. Novel treatments to modulate the inflammatory component of atherosclerosis and the vulnerable plaque include use of bioresorbable vascular scaffolds and anti-proliferative drugs. Translational efforts to improve patients' outcomes after STEMI in relation to cardioprotection, cardiac remodelling, and regeneration are also being realised. This is the third in a Series of three papers about ST-segment elevation myocardial infarction.