Mid-term surgical success after transscleral ab interno glaucoma gel stent implantation.

PURPOSE: To investigate the surgical success and efficacy of XEN45 implantation (XEN45 µm, AbbVie Inc., USA) with and without combined cataract surgery up to the first 5 years. METHODS: In a prospective observational monocentric trial, 192 eyes of 157 patients with open-angle glaucoma received either XEN45 implants only (solo surgery group) or combined surgery/cataract surgeries (combined surgery group). Surgical success (qualified and full success; IOP-limit: ≤12, 15, 18, 21 mmHg), time to secondary IOP-lowering procedure, IOP and number of IOP-lowering medications were analysed for 1, 2, 3, 4 and 5 years. RESULTS: Compared to baseline, IOP (24.1 ± 8.1 to 12.6 ± 2.8 mmHg, -48%, p < 0.001) and the number of IOP-lowering medications (3.0 ± 1.0 to 1.5 ± 1.2, -50%, p < 0.001) decreased significantly at 5 years. Although no differences between IOP and the number of IOP-lowering medication courses between the groups were detected at 5 years (p > 0.11), the combined procedure (63%, 37%) showed better success rates compared to the solo procedure (36%, 13%) in the definition IOP ≤18 and ≤12 mmHg (p = 0.035, 0.028). Solo XEN45 procedures had a higher rate of secondary IOP-lowering procedures compared to combined XEN45 cataract procedures (hazard ratio: 2.02, 95%CI: 1.03-3.97, p = 0.04). Twenty per cent of the eyes, including both procedures, required a secondary IOP-lowering procedure within 5 years. CONCLUSIONS: The XEN45 implant is effective in lowering IOP and the number of IOP-lowering medications in patients with open-angle glaucoma in the mid-term. Comparing XEN45 implant results with the results of trabeculectomy available in current literature, we speculate that there might be a higher surgical success rate without medications in favour of trabeculectomy.

Five-year follow-up of corneal endothelial cell density after transscleral ab interno glaucoma gel stent implantation.

PURPOSE: This study investigates the course of the endothelial cell density over a period of 5 years after XEN45 implantation (XEN45µm, Allergan Plc., USA) with or without combined cataract surgery. METHODS: This is a prospective, cross-sectional, monocentric, non-randomized clinical trial with the intention to treat a population of the University Eye Clinic Glaucoma Service Salzburg. One hundred and fifty-five eyes with preoperative central corneal endothelial cell counts were subjected to XEN45 implantation with (combined surgery group) or without (solo surgery group) combined cataract surgery. Endothelial cell density was measured at 3 corneal positions. XEN45 location parameters were determined with anterior segment OCT and gonioscopy. RESULTS: In the combined surgery group, a significant reduction of central endothelial cell count was found at years 2 and 4 when compared to baseline (p = 0.001 and p = 0.02, n = 86), whereas at years 1, 3, and 5, no change was detected (all p > 0.09). The median reduction of endothelial cell count was - 79 (95% CI: - 183 to - 9) and - 93 (95% CI: - 220 to 23) cells at years 2 and 4, respectively. In the solo surgery group (n = 69), no significant change in endothelial cell counts was detected at any time during the 5-year evaluation period (all p > 0.07). Explorative data analyses revealed that XEN45 location parameters did not significantly influence the course of endothelial cell count over time. CONCLUSIONS: Endothelial cell loss after XEN45 implantation seems to be low. The present data suggest no impact on the position of the implant with regard to central endothelial cell counts in this study.

Two-year efficacy after first transscleral controlled cyclophotocoagulation in patients with and without pseudoexfoliation.

PURPOSE: Transscleral controlled cyclophotocoagulation (COCO) is a transscleral 810-nm diode laser cyclophotocoagulation that automatically adjusts the applied laser energy utilizing an optical feedback loop. The present study investigates the influence of pseudoexfoliation (PEX) on the efficacy of COCO in a Caucasian study population. METHODS: Retrospective data from 130 consecutive eyes were analyzed during a 2-year follow-up. Baseline characteristics, intraocular pressure (IOP), number of IOP-lowering medications, visual field, best-corrected visual acuity (BCVA), and secondary surgical interventions (SSI) were analyzed. The primary endpoint was IOP reduction at M24 compared to baseline, and the secondary endpoints were IOP course, reduction of IOP-lowering medications, surgical success, and IOP-lowering SSIs stratified by PEX and baseline IOP. RESULTS: IOP reductions of -35, -39, -25, -25, -23, -34, and -36% could be achieved from baseline to D1, W1, M1, M3, M6, M12, and M24 (all p < 0.001), respectively, while there was a significant overall reduction over time (p < 0.001) in the number of topical IOP-lowering medications postoperatively. The proportion of eyes requiring additional systemic IOP-lowering medication reduced from 31 to 0% at M24 (p = 0.025). Eyes without PEX and IOP < 30 mmHg at baseline had the lowest risk for IOP-lowering SSIs (p < 0.03). BCVA dropped at M12 (0.25 [95% CI: 0.12-0.38]), and the drop persisted during the following 12 months. CONCLUSION: The present study demonstrates a midterm IOP-lowering effect after COCO while reducing the burden for topical and systemic IOP-lowering medications. Patients without PEX and IOP < 30 mmHg have a lower risk of SSI. The procedure per se cannot be excluded as causative for the decreased postoperative BCVA. Further prospective investigations are suggested.

Horsepower of Doctors' Cars Correlates with Cardiovascular Risk and Sedentary Lifestyle but Not with Sexual Dysfunction or Sexual Satisfaction.

Background: The horsepower not only of doctors' cars correlates with personal income and social status. However, no clear relationship has previously been described between the horsepower of doctors' cars and cardiovascular health or sexual dysfunction and/or satisfaction. Objective: Cross-sectional online survey to evaluate associations between self-reported horsepower of physicians' cars and health aspects. Methods: Of 1877 physicians from the two University-Hospitals in Austria that were asked to participate in the study, 363 (37.7 ± 8.0 years, 208 (57.3%) men) were included into the final analysis. Results: Physicians that own a car with a stronger engine were significantly older, were more often male, had more often a leading position, had a higher monthly income (all p < 0.001), had a higher scientific output (p = 0.030), and had hypercholesteremia more often (p = 0.009). They also tended to have a higher body mass index (p = 0.088), reported a higher maximum weight in previous years (p = 0.004) and less often reported regular healthy commuting to and from work (p = 0.010). No significant associations were found for self-reported physical fitness, smoking status, and arterial hypertension. In addition, sexual satisfaction and sexual dysfunction were also not related to horsepower in the whole population and the male subgroup. The findings essentially persisted after controlling for age. Conclusion: The horsepower of Austrian physicians' cars correlates with senior position and increased cardiovascular risk. However, our data shows no relationship between sexual dysfunction or lack of sexual satisfaction and the horsepower of doctors' cars.

Detection of Candida albicans by mass spectrometric fingerprinting.

Candida albicans is one of the most frequent causes of fungal infections in humans. Significant correlation between candiduria and invasive candidiasis has previously been described. The existing diagnostic methods are often time-consuming, cost-intensive and lack in sensitivity and specificity. In this study, the profile of low-molecular weight volatile compounds in the headspace of C. albicans-urine suspensions of four different fungal cell concentrations compared to nutrient media and urine without C. albicans was determined using proton-transfer reaction mass spectrometry (PTR-MS). At fungal counts of ≥1.5 × 10(5) colony forming units (CFU)/ml signals at 45, 47 and 73 atomic mass units (amu) highly significantly increased. At fungal counts of <1.5 × 10(5) CFU/ml signals at 47 and 73 amu also increased, but only at 45 amu a statistically significant increase was seen. Time course alterations of signal intensities dependent on different cell concentrations and after addition of Sabouraud nutrient solution were analysed. Recommendations for measurement conditions are given. Our study is the first to describe headspace profiling of C. albicans-urine suspensions of different fungal cell concentrations. PTR-MS represents a promising approach to rapid, highly sensitive and non-invasive clinical diagnostics allowing qualitative and quantitative analysis.

Oxygen utilization in newborns at delivery.

AIMS: To evaluate the arteriovenous (AV) pH difference in cord blood as a possible indicator of fetal O(2)-utilization at delivery. Furthermore to examine which maternal, fetal and obstetrical factors lead to elevated O(2)-utilization. METHODS: In this retrospective study all singleton live births, delivered within a four-month period at the University Hospital in Innsbruck, Austria, were analyzed. In total 491 deliveries were evaluated. Arterial and venous cord blood samples were collected at birth and analyzed by using a Radiometer ABL 510. RESULTS: Spontaneous deliveries showed a highly significant elevation in AV-difference (pH 0.10) as compared to cesarean sections (pH 0.05). In spontaneous births, the AV-difference was high in the case of low arterial cord blood pH (P<0.01), as well as in nuchal cord (P<0.01), high parity (P<0.01), very short labor (P<0.05) and elevated birth size and weight (P<0.05). CONCLUSIONS: As a result of increased fetal stress at birth, spontaneous delivery leads to higher O(2)-utilization than cesarean section, which is detectable in an elevated AV-difference. The AV-difference in combination with absolute pH-values can be used for the objective evaluation of fetal O(2)-utilization and consecutively the fetal stress at birth.

Scientific activity and working hours of physicians in university hospitals: results from the Innsbruck and Salzburg physician lifestyle assessment (TISPLA).

OBJECTIVE: Controllable lifestyle has become an important factor influencing career decision-making among physicians. In academic medicine, doctors are required to combine both patient care and research in their daily routine. Insufficient release of clinicians for research during contracted work hours may lead to increased weekly working hours in academic medical centers and deter medical graduates from academia. We tested for an association between numbers of scientific publications and an increased hourly workload among physicians. METHODS: This was a cross-sectional online survey among all salaried physicians working in the university hospitals of Innsbruck and Salzburg, Austria. The main outcome measures were the self-reported total number of scientific papers published in peer-reviewed medical journals over the past two years and self-reported working hours. RESULTS: Of 590 returned surveys, 393 were fully completed and included in the study. The sample was stratified into three groups according to scientific output in the past two years: Group A, >/= 6 publications; Group B, 1-5 publications; Group C, no publications. Men were more likely than women to have a scientific publication: in Group A there was a male predominance of 75%, whereas in Group C only 48% were men (P = 0.0034). A total of 59% (n = 232) of all participants had not published a scientific article in the past two years (Group C) and worked a mean of 58.3 +/- 12 h/week. Physicians in Group B (n = 113) had published 2.4 +/- 1.4 papers and worked 62.8 +/- 12.9 h/week; those in Group A (n = 48) had published 11.5 +/- 6.6 papers and worked 73 +/- 13.1 h/week (P < 0.0001). In Group A, research accounted for only 13.3% of total work time but for 60% of overtime hours, reflecting the fact that research was mainly performed during overtime. CONCLUSION: Research activity among clinicians in academic medical centers is associated with significantly increased overtime hours. Measures need to be taken to allow medical graduates an academic career at reasonable impairment of personal lifestyle.

In vitro, inhibition of mitogen-activated protein kinase pathways protects against bupivacaine- and ropivacaine-induced neurotoxicity.

BACKGROUND: Animal models show us that specific activation of the p38 mitogen-activated protein kinase (MAPK) may be a pivotal step in lidocaine neurotoxicity, but this has not been investigated in the case of two very widely used local anesthetics, bupivacaine and ropivacaine. We investigated the hypotheses that these drugs (A) are less neurotoxic than the prototype local anesthetic, lidocaine (B) are selectively toxic for subcategories of dorsal root ganglion neurons and (C) induce activation of either p38 MAPK or related enzymes, such as the c-jun terminal N-kinase (JNK) and extracellular signal-regulated kinase (ERK). METHODS: We incubated primary sensory neuron cultures with doses of lidocaine, bupivacaine, and ropivacaine equipotent at blocking sodium currents. Next, we sought to determine potential selectivity of bupivacaine and ropivacaine toxicity on neuron categories defined by immunohistochemical staining, or size. Subsequently, the involvement of p38 MAPK, JNK, and ERK was tested using enzyme-linked immunosorbent assays. Finally, the relevance of MAPK pathways in bupivacaine- and ropivacaine-induced neurotoxicity was determined by selectively inhibiting activity of p38 MAPK, JNK, and ERK. RESULTS: We found that the neurotoxic potency of bupivacaine and ropivacaine is dose-dependent and similar in vitro, but is not selective for any of the investigated subgroups of neurons. Neurotoxicity of bupivacaine and ropivacaine was mediated, at least in part, by MAPKs. Specifically, we demonstrated the relevance of both p38 MAPK and JNK pathways for the neurotoxicity of bupivacaine and characterized the involvement of the p38 MAPK pathway in the neurotoxicity of ropivacaine. CONCLUSIONS: Given equipotent doses, the neurotoxic potential of lidocaine does not appear to be significantly different from that of bupivacaine and ropivacaine in vitro. Moreover, bupivacaine and ropivacaine do not exert their neurotoxicity differently on specific subsets of dorsal root ganglion neurons. Their neurotoxic effects are brought about through the activation of specific MAPKs; the specific pharmacologic inhibition of these kinases attenuates toxicity in vitro.

In vitro, lidocaine-induced axonal injury is prevented by peripheral inhibition of the p38 mitogen-activated protein kinase, but not by inhibiting caspase activity.

BACKGROUND: All local anesthetics (LAs) are, to some extent, neurotoxic. Toxicity studies have been performed in dissociated neuron cultures, immersing both axon and soma in LA. This approach, however, does not accurately reflect the in vivo situation for peripheral nerve blockade, where LA is applied to the axon alone. METHODS: We investigated lidocaine neurotoxicity in compartmental sensory neuron cultures, which are composed of one central compartment containing neuronal cell bodies and a peripheral compartment containing their axons, allowing for selective incubation. We applied lidocaine +/- neuroprotective drugs to neuronal somata or axons, and assessed neuron survival and axonal outgrowth. RESULTS: Lidocaine applied to the peripheral compartment led to a decreased number of axons (to 59% +/- 9%), without affecting survival of cell bodies. During axonal incubation with lidocaine, the p38 mitogen-activated protein kinase inhibitor SB203580 (10 microM) attenuated axonal injury when applied to the axon (insignificant reduction of maximal axonal distance to 93% +/- 9%), but not when applied to the cell body (deterioration of maximal axonal length to 48% +/- 6%). Axonal co-incubation of lidocaine with the caspase inhibitor z-vad-fmk (20 microM) was not protective. CONCLUSIONS: Whereas inhibition of either p38 mitogen-activated protein kinase or caspase activity promote neuronal survival after LA treatment of dissociated neuronal cultures, axonal degeneration induced by lidocain (40 mM) is prevented by p38 MAP kinase but not by caspase inhibition. We conclude that processes leading to LA-induced neurotoxicity in dissociated neuronal culture may be different from those observed after purely axonal application.

Phase 1A safety assessment of intravenous amitriptyline.

UNLABELLED: The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain. Among its many actions, amitriptyline blocks Na+ channels and nerves in several animal and human models. As perioperative intravenous lidocaine has been suggested to decrease postoperative pain, amitriptyline, because of its longer half-life time, might be more useful than lidocaine. However, the use of intravenous amitriptyline is not approved by the US Food and Drug Administration. We therefore investigated the adverse effects of preoperative intravenous amitriptyline in a typical phase 1A trial. After obtaining written Food and Drug Administration and institutional review board approval, we obtained written consent for preoperative infusion of amitriptyline in an open-label, dose-escalating design (25, 50, and 100 mg, n=5 per group). Plasma levels of amitriptyline/nortriptyline were determined, and adverse effects were recorded in a predetermined symptom list. Infusion of 25 and 50 mg amitriptyline appears to be well tolerated; however, the study was terminated when 1 subject in the 100-mg group developed severe bradycardia. Intravenous infusion of amitriptyline (25 to 50 mg over 1 hour) did not create side effects beyond dry mouth and drowsiness, or dizziness, in 2 of our 10 otherwise healthy participants receiving the 25- to 50-mg dose. An appropriately powered future trial is necessary to determine a potential role of amitriptyline in decreasing postoperative pain. PERSPECTIVE: Amitriptyline potently blocks the persistently open Na+ channels, which are known to be instrumental in various pain states. As this occurs at very low plasma concentrations, a single preoperative intravenous infusion of amitriptyline could provide long-lasting pain relief and decrease the incidence of chronic pain.

Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline.

BACKGROUND: Cervical and high thoracic epidural anesthesia and analgesia have gained increasing importance in the treatment of painful conditions and as components of anesthetics for cardiac and breast surgery. In contrast to the hanging-drop technique, the loss-of-resistance technique is thought to rely on the penetration of the ligamentum flavum. However, the exact morphology of the ligamentum flavum at different vertebral levels remains controversial. Therefore, the aim of this study was to investigate the incidence and morphology of cervical and high thoracic ligamentum flavum mid-line gaps in embalmed cadavers. METHODS: Vertebral column specimens were obtained from 52 human cadavers. On each dissected level, ligamentum flavum mid-line gaps were recorded and evaluated with respect to shape and size. RESULTS: The following variations were encountered: complete fusion in the mid-line, mid-line fusion with a gap in the caudal part, mid-line gap, and mid-line gap with widened caudal end. The incidence of mid-line gaps at the following levels was: C3-C4: 66%, C4-C5: 58%, C5-C6: 74%, C6-C7: 64%, C7-T1: 51%, Th1-Th2: 21%, Th2-Th3: 11%, Th3-Th4: 4%, Th4-Th5: 2%, and Th5-Th6: 2%. The mean width of mid-line gaps was 1.0 +/- 0.3 mm. CONCLUSIONS: In conclusion, the present study shows that gaps in the ligamenta flava are frequent at cervical and high thoracic levels but become rare at the T3/T4 level and below, such that one cannot always rely on the ligamentum flavum as a perceptible barrier to epidural needle placement at these levels.