ONSET-1 Phase 2b Randomized Trial to Evaluate the Safety and Efficacy of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease.

PURPOSE: The purpose of this trial was to evaluate the safety and efficacy of OC-01 (varenicline solution), a nicotinic acetylcholine receptor agonist nasal spray, on signs and symptoms of dry eye disease. METHODS: A phase 2b, multicenter, randomized, double-masked, vehicle-controlled trial (ONSET-1; NCT03636061) was performed. Patients were aged 22 years or older with a physician's diagnosis of dry eye disease and previous use of artificial tears were randomized 1:1:1:1 to control (vehicle nasal spray twice daily [BID]), OC-01 0.006 mg BID, OC-01 0.03 mg BID, and OC-01 0.06 mg BID. The primary end point was the change in the anesthetized Schirmer test score from baseline to day 28 in the study eye. The secondary end points included the change in the eye dryness score from baseline to day 28. RESULTS: One hundred eighty-two patients were randomized. After 28 days, patients who received OC-01 0.03 or 0.06 mg showed a statistically significant improvement in tear film production relative to vehicle, with least squares mean differences from vehicle of 7.7 mm [95% confidence interval, 3.8-11.7; P < 0.001] with OC-01 0.03 mg and 7.5 mm (95% confidence interval, 3.4-11.6; P < 0.001) with OC-01 0.06 mg. Patients receiving OC-01 0.03 mg showed a significant reduction in the eye dryness score by day 28 versus vehicle (P = 0.021); those receiving the OC-01 0.06 mg dose showed a nonsignificant reduction versus vehicle. OC-01 administration was associated with sneezing (62%-84%) and cough (9%-25%); these were transient and predominantly mild in severity. CONCLUSIONS: OC-01 nasal spray administered BID at 0.03 and 0.06 mg resulted in significant improvements in signs and symptoms of dry eye disease, was well tolerated, and warrants further clinical investigation.

Cancer-Selective Treatment of Cancerous and Non-Cancerous Human Cervical Cell Models by a Non-Thermally Operated Electrosurgical Argon Plasma Device.

Cold atmospheric plasma (CAP) treatment is developing as a promising option for local anti-neoplastic treatment of dysplastic lesions and early intraepithelial cancer. Currently, high-frequency electrosurgical argon plasma sources are available and well established for clinical use. In this study, we investigated the effects of treatment with a non-thermally operated electrosurgical argon plasma source, a Martin Argon Plasma Beamer System (MABS), on cell proliferation and metabolism of a tissue panel of human cervical cancer cell lines as well as on non-cancerous primary cells of the cervix uteri. Similar to conventional CAP sources, we were able to show that MABS was capable of causing antiproliferative and cytotoxic effects on cervical squamous cell and adenocarcinoma as well as on non-neoplastic cervical tissue cells due to the generation of reactive species. Notably, neoplastic cells were more sensitive to the MABS treatment, suggesting a promising new and non-invasive application for in vivo treatment of precancerous and cancerous cervical lesions with non-thermally operated electrosurgical argon plasma sources.

Recent Developments in Catheter-Based Cardiac Procedures.

New developments in transcatheter valve technologies including aortic valve replacement and mitral valve and tricuspid valve interventions are described. Recent studies evaluating the success rate, patient outcomes, and anesthesiologic management of the procedures are discussed.

Dose-Dependent Tissue-Level Characterization of a Medical Atmospheric Pressure Argon Plasma Jet.

Nonthermal treatment with cold atmospheric plasma (CAP) is a promising option for local treatment of chronic-inflammatory and precancerous lesions as well as various mucosal cancer diseases, besides its primary indication for wound healing and antiseptics. Atmospheric pressure plasma jets (APPJs) are versatile plasma sources, some of which are well-characterized and medically approved. The characterization of APPJs, however, is often based on the treatment of simple solutions or even studies on the plasma effluent itself. To better assess the in vivo effects of CAP treatment, this study aims to recapitulate and study the physicochemical tissue-level effects of APPJ treatment on human primary mucosal tissue and tissue models. High resolution on-tissue infrared (IR) thermography and a first-time-performed spatially resolved optical emission spectroscopy (OES) of the APPJ emissions did not identify potentially tissue-harming effects. In this study, electron-spin-resonance (ESR) spectroscopy on human tissue samples, treated with different CAP doses, enabled the measurement and the distribution of CAP-derived radicals in the tissues. The results correlate plasma dosage and the generation of radical species with cell viability and cell proliferation of primary human fibroblasts while demonstrating apoptosis-independent antiproliferative cell effects. Moreover, a dose-dependent increase of cells in the G1 phase of the cell cycle was observed, stressing the likely important role of cell cycle regulation for antiproliferative CAP mechanisms. This study introduces suitable methods for CAP monitoring on tissues and contributes to a better understanding of tissue-derived plasma effects of APPJs.

Agreement of tricuspid annular systolic excursion measurement between transthoracic and transesophageal echocardiography in the perioperative setting.

OBJECTIVE: The aim of our study was to evaluate the level of agreement between tricuspid annular plane systolic excursion (TAPSE) measured by transthoracic echocardiography (TTE) and TAPSE measured using transesophageal echocardiography (TEE) in anesthetized patients. MATERIALS AND METHODS: Thirty patients scheduled for elective cardiac surgery were prospectively studied. Shortly after induction of anesthesia before the operation, TAPSE was measured by TTE using M-mode in apical 4chamber view (4CH) and by TEE in six different views: using 2D echocardiography in midesophageal (ME) 4CH view, using M-mode in deep transgastric right ventricle (dTG RV) view at 0° and dTG RV longaxis view (LAX) as well as using anatomical M-mode (AM-mode) in ME 4CH, dTG RV at 0° and dTG RV LAX views. RESULTS: Bland-Altman analysis showed a good agreement for TAPSE measured using M-mode in TTE and using AM-mode in TEE in the ME 4CH and dTG RV at 0° views (-2.5 ± 18 and -2.2 ± 14% respectively). The agreement between TAPSE measured in TTE and TEE using 2D in ME 4CH, using M-mode in dT GRV 0° and using M-mode and AM-mode in dTG RV LAX view showed a significant systematic underestimation of the measurements (-8.8 ± 21, -8.8 ± 24, -17.8 ± 28 and -6.4 ± 20%). CONCLUSION: Our study showed that the right ventricular function can be accurately and precisely estimated using TAPSE measurement by TEE in the midesophageal four chamber and deep transgastric right ventricle view at 0° using anatomical M-mode.

The ponticulus posticus: implications for screw insertion into the first cervical lateral mass.

BACKGROUND: The arcuate foramen is an important osseous anomaly of the first cervical vertebra (the atlas) that must be taken into consideration during placement of lateral mass screws into the atlas. METHODS: The prevalence of this anomaly in our patient population was determined through a retrospective review of 464 lateral radiographs of the neck. The anatomy of the arcuate foramen was identified in a study of cadavers. RESULTS: Seventy-two arcuate foramina, complete or incomplete, were identified on the 464 lateral radiographs of the neck; thus, the prevalence was 15.5% in our patient population. CONCLUSIONS: Although the arcuate foramen is a common anomaly, it is often not recognized. Proper identification of this anomaly on preoperative lateral radiographs should alert the surgeon to avoid using the ponticulus posticus as a starting point for a lateral mass screw in order to not injure the vertebral artery.

Changes in plant species richness induce functional shifts in soil nematode communities in experimental grassland.

BACKGROUND: Changes in plant diversity may induce distinct changes in soil food web structure and accompanying soil feedbacks to plants. However, knowledge of the long-term consequences of plant community simplification for soil animal food webs and functioning is scarce. Nematodes, the most abundant and diverse soil Metazoa, represent the complexity of soil food webs as they comprise all major trophic groups and allow calculation of a number of functional indices. METHODOLOGY/PRINCIPAL FINDINGS: We studied the functional composition of nematode communities three and five years after establishment of a grassland plant diversity experiment (Jena Experiment). In response to plant community simplification common nematode species disappeared and pronounced functional shifts in community structure occurred. The relevance of the fungal energy channel was higher in spring 2007 than in autumn 2005, particularly in species-rich plant assemblages. This resulted in a significant positive relationship between plant species richness and the ratio of fungal-to-bacterial feeders. Moreover, the density of predators increased significantly with plant diversity after five years, pointing to increased soil food web complexity in species-rich plant assemblages. Remarkably, in complex plant communities the nematode community shifted in favour of microbivores and predators, thereby reducing the relative abundance of plant feeders after five years. CONCLUSIONS/SIGNIFICANCE: The results suggest that species-poor plant assemblages may suffer from nematode communities detrimental to plants, whereas species-rich plant assemblages support a higher proportion of microbivorous nematodes stimulating nutrient cycling and hence plant performance; i.e. effects of nematodes on plants may switch from negative to positive. Overall, food web complexity is likely to decrease in response to plant community simplification and results of this study suggest that this results mainly from the loss of common species which likely alter plant-nematode interactions.