Alcon (United Kingdom)

Abstract Aim Small bowel obstruction (SBO) is a common surgical emergency, typically caused by post-operative adhesions. In patients with a virgin abdomen—no prior abdominal surgery—the traditional approach has been operative management. However, emerging evidence supports non-operative treatment in selected cases. This study evaluates the management and outcomes of SBO in a virgin abdomen. Method We retrospectively reviewed all CT-confirmed SBO cases between 01/01/2019 and 08/07/2024. Inclusion criteria were a clear transition point and no history of abdominal surgery, radiotherapy, or intra-abdominal inflammatory disease. Patients with SBO due to hernia, malignancy, Crohn’s disease, strictures, or foreign bodies were excluded. Data included demographics, imaging, management strategy, time to surgery, complications, and readmissions. Results Thirty-seven patients were included (59% male; age range 26–96). Eleven (29.7%) underwent surgery, primarily for suspected ischaemia or internal hernia. Eight of these had laparoscopic procedures, and two required bowel resection. One patient experienced a Clavien-Dindo IIIa complication. Median time to surgery was 1 day. Twenty-six patients (70.3%) were managed non-operatively, of whom 10 received contrast and 20 had NG decompression. None required surgery during admission. Mean length of stay was comparable: 7.7 days (operative) vs. 7.2 days (non-operative). Three patients were readmitted within 30 days. Conclusions Non-operative management appears safe and effective for selected patients with SBO in a virgin abdomen. With 70% successfully managed without surgery, our findings support reconsidering the routine operative approach in this population.

To compare postenhancement visual acuity between patients who underwent postcataract laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK). A private, tertiary referral practice in Sioux Falls, South Dakota. 3-year, retrospective chart review. Patients who underwent postcataract extraction excimer laser enhancement surgery targeted for emmetropia (±0.50 diopter). Postenhancement uncorrected distance visual acuity (UDVA) and manifest refraction spherical equivalent (MRSE) was recorded for all available follow-ups and compared for both groups. 822 postcataract enhanced eyes (491 LASIK; 331 PRK). For patients with at least 6-month follow-up, mean UDVA was 0.05 ± 0.13 logMAR in LASIK-enhanced patients and 0.15 ± 0.20 in PRK-enhanced patients ( P < .001). Mean absolute value MRSE was 0.22 ± 0.36 and 0.48 ± 0.62 for LASIK-enhanced and PRK-enhanced patients at or beyond 6 months, respectively ( P < .001). 330 (67%) LASIK-enhanced patients achieved 20/20 or better postenhancement UDVA, compared with 142 (43%) PRK-enhanced patients ( P < .001). Controlling for pre-enhancement UDVA, LASIK-enhanced patients showed significantly better postenhancement UDVA than PRK-enhanced patients, except in those with pre-enhancement vision of 20/20 or better, or those worse than 20/50. LASIK-enhanced virgin corneas had mean postenhancement of 0.05 ± 0.14 UDVA compared with 0.13 ± 0.19 UDVA in PRK-enhanced virgin cornea patients ( P < .001). LASIK provides better and more predictable outcomes in UDVA than PRK in postcataract enhancement patients, even when controlling for pre-enhancement visual acuity and prior ocular procedures.

We thank Sandali et al. for their thoughtful comments. We are delighted to learn that their experience in regard to safety and visual recovery associated with 3D digital visualization and use of lower coaxial illumination levels during cataract surgery is also a positive one. Although we did not formally examine the relationship between lower coaxial illumination levels and patient impressions of reduced photophobia and improved operative tolerance during cataract surgery, we agree with Sandali et al. and have anecdotally found this to be the case as well. For example, one young man with keratoconus was only able to tolerate the procedure at a 5% (of maximum) light intensity level; the 3D digital visualization system allowed sufficient visualization at that illumination level for the procedure to be performed safely. In regard to the possible association between a faster visual recovery and use of 3D digital visualization and lower coaxial illumination levels, we find the observations of Sandali et al. most interesting and a direct correlation with our own results. Nevertheless, as they elaborate so well, the speed of visual recovery likely depends not only on intraoperative light intensity levels but also on preoperative macular integrity, as well as probably a host of other factors. In our study, all patients had no known history of retinal pathology, and all patients exhibited grossly normal preoperative macular ocular coherence tomography (Spectralis, Heidelberg Engineering) studies—with the exception of 1 patient in the 3D digital visualization group with evidence of moderate age-related macular degeneration. That said, an even more in-depth and extensive preoperative and postoperative analysis of macular anatomy and function, perhaps expanded to other relevant tests such as fundus autofluorescence, optical coherence tomography angiography, and focal electroretinograms, would be of great value, and we hope future studies incorporate this type of analysis. Sandali et al. also astutely point out that the presence of corneal edema on postoperative day 1 would affect the analysis of visual recovery times. We attempted in this study to control for this by selecting patients with only mild to moderate cataracts and no ocular comorbidities that would predispose to a postoperative complication such as corneal edema. And, in fact, no patient in either the 3D digital or the analog microscope visualization group was found to exhibit clinically apparent corneal edema postoperatively. That said, formal corneal thickness measurements offer an added level of precision, and we hope to see future studies incorporating this type of measurement. Again, we appreciate the superb and detailed insights offered by Sandali et al. In aggregate, the pilot studies from our group, as well as theirs, suggest that cataract surgery can be performed safely with greatly reduced illumination, and the putative benefits of reducing intraoperative light levels deserve our most careful characterization.

Abstract The calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.

In a subchronic (13-week) inhalation toxicity study with a terminal sacrifice (after 13 weeks inhalation) and several recovery period sacrifices (13, 26, 39, and 52 weeks), the effects of AEROSIL® 200 (pyrogenic synthetic amorphous silica (SAS)), AEROSIL® R 974 (surface-treated pyrogenic SAS), and SIPERNAT® 22 S (precipitated SAS) were tested in rats at multiple dose levels. The aforementioned materials are all SAS products. A comparative group of animals was exposed to quartz dust. This study attempts to reexamine the lung tissues originally evaluated in a study published by Reuzel et al. using the current standards. To reach a high level of credibility, the results of the reevaluation were subsequently examined by a pathology working group (PWG). In particular, the reevaluating pathologist and the PWG concluded that, even though quartz (crystalline silica) persisted, induced alterations in the lungs following 13 weeks of exposure to amorphous silicas were reversible following 52 weeks of recovery. A long-term adversity has not been established with SAS products. However, quartz dust damages lungs significantly by causing pulmonary fibrosis.

For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible. A key element necessary to ensure the transition towards successfully utilising both non-animal and refined safety testing is the better understanding of chemical exposure. This includes approaches such as measuring chemical concentrations within cell-based assays and during in vivo studies, understanding how predicted human exposures relate to levels tested, and using existing information on human exposures to aid in toxicity study design. Such approaches promise to increase the human relevance of safety assessment, and shift the focus from hazard-driven to risk-driven strategies similar to those used in the pharmaceutical sectors. Human exposure-based safety assessment offers scientific and 3Rs benefits across all sectors marketing chemical or medicinal products. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) convened an expert working group of scientists across the agrochemical, industrial chemical and pharmaceutical industries plus a contract research organisation (CRO) to discuss the current status of the utilisation of exposure-driven approaches, and the challenges and potential next steps for wider uptake and acceptance. This paper summarises these discussions, highlights the challenges - particularly those identified by industry - and proposes initial steps for moving the field forward.

Abstract This paper presents a study of 10 English chalk streams in the River Thames Basin historically affected by abstraction of groundwater. Using macroinvertebrates, macrophytes and river discharge records from across 76 monitoring sites, and spanning the period 1992–2009 we assess how the communities change over time. River discharge is seen to be the most influential variable in biological community composition, and is used to calculate the annual average river discharge (in m3/s) needed to sustain different biological assemblages at each study site, from the lowest to the highest expression of fluvial aquatic community development. This represents a bottom‐up or site‐specific approach to the determination of ecological flow thresholds, from which more empirical trends may be inferred at regional level. The approach also provides a useful understanding of the timescales involved in the recovery of communities from drought.

The need to improve reproducibility and reliability of animal experiments has led some journals to increase the stringency of the criteria that must be satisfied before manuscripts can be considered suitable for publication. In this article we give advice on experimental design, including minimum group sizes, calculating statistical power and avoiding pseudo-replication, which can improve reproducibility. We also give advice on normalisation, transformations, the gateway analysis of variance strategy and the use of p-values and confidence intervals. Applying all these statistical procedures correctly will strengthen the validity of the conclusions. We discuss how InVivoStat, a free-to-use statistical software package, which was designed for life scientists, especially animal researchers, can be used to help with these principles.