Background/aimsWith a paradigm shift in geographic atrophy (GA) treatments now available, establishing consensus on the identification and diagnosis of the disease along with considerations for ...management of patients with GA will assist eye care professionals (ECP) in their day-to-day practices, leading to improved patient outcomes.MethodsA modified Delphi panel process (Geographic Atrophy Management Consensus) consisting of three total surveys and one virtual live meeting held between survey 2 and survey 3. Data were collected from July to October 2022. Participants included expert members of the eye care community that have demonstrated outstanding leadership among peers: a steering committee with three ECPs and a 15-member panel divided between five optometrists, five comprehensive ophthalmologists and five retina specialists. Consensus on statements related to the management of patients with GA was calculated using the RAND/UCLA Appropriateness Method.ResultsAt the conclusion of the third survey, consensus was reached on 91% of the 77 statements. Critical consensus topics include: (1) optical coherence tomography as the favoured method to diagnose and monitor GA, (2) preferred practice patterns regarding referral of patients to retina specialists and (3) treatment criteria given the advent of emerging therapeutics for GA.ConclusionsGenerating awareness of early signs of disease development, progression and identifying the best tools to evaluate GA establishes ideal management and referral strategies. Given the paradigm shift in GA management driven by approved therapies, coupled with the fact that the disease is progressive resulting in devastating vision loss, these strategies are critical to ensure best overall outcomes.
To investigate the safety and tolerability of the multi-pressure dial with a continuous 8-hr duration in subjects with open-angle glaucoma.
Prospective, controlled open-label, randomized, single site ...study.
Twenty eyes of 10 subjects with open-angle glaucoma were fitted with a multi-pressure dial and randomized to negative pressure application of -10 mmHg in one eye for 8 (continuous) hours and ambient atmospheric pressure in the contralateral eye.
Main safety outcome measures include best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were administered both hourly during the 8-hr study period and immediately following the study period.
There were no statistically significant changes in IOP, BCVA or TBUT immediately following the 8-hr study period or at the 1-week follow-up visit. Patient-reported tolerability was favorable with a mean response of 1.8 ± 0.4 (scale → 1=best, 10 = worst). Subjects also reported positive interest in the MPD as a glaucoma therapy with a mean response of 1.8 ± 0.5 (scale → 1=best, 10 = worst). One adverse event was reported (headache) and resolved at conclusion of the Day 0 visit.
The MPD demonstrated favorable safety with key parameters remaining stable after an 8-hr wear with negative pressure. Negative pressure application through the MPD was well tolerated by subjects enrolled in the study. The favorable findings demonstrate the safety of sustained delivery of negative pressure over a continuous, uninterrupted 8-hr duration.
Controlling metal nanoparticle size and preserving metal dispersion at elevated temperature remain key challenges in designing new supported metal catalysts. Many methods have been proposed to ...stabilize metal nanoparticles for catalysis, but the use of specialized equipment or metal precursors can limit the application of these methods for scalable production. Here, we demonstrate a synthesis strategy to improve the dispersion and thermal stability of Pt nanoparticles on an oxide support. A thin SiO2 coat (<2 nm) was deposited on TiO2 through repeated condensation cycles of tetraethyl orthosilicate (TEOS) with or without an organic template on the surface. H2PtCl6 was deposited using wetness impregnation, and the samples were dried, calcined, and reduced. The as-synthesized Pt nanoparticles are 1–2 nm by TEM and maintain dispersion >45% by CO chemisorption even after prolonged heating at 500 °C, whereas Pt nanoparticles on unmodified TiO2 are less dispersed (∼33%) and their dispersion falls further upon prolonged heating. Ethylene hydrogenation demonstrates that the Pt nanoparticles on modified TiO2 preserve the catalytic activities of Pt on unmodified TiO2. The use of wet chemistry-based oxide modification and wetness impregnation makes this strategy a scalable and generalizable synthesis method to prepare other supported metal nanoparticles for catalysis applications.
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101
Background: Genetically engineered T-cell therapy has shown remarkable clinical activity in hematologic malignancies. It is not known if this type of treatment can be applied ...effectively to epithelial cancers, which account for 80% to 90% of human malignancies. Methods: We conducted a phase I clinical trial with a 3 + 3 dose escalation in which patients with metastatic HPV-16+ epithelial cancers were treated with a one-time infusion of genetically engineered T cells expressing a T-cell receptor targeting an HLA-A*02:01-restricted epitope of HPV-16 E7 (E7 TCR-T cells). A lymphocyte-depleting conditioning regimen was administered before cell infusion, and high-dose systemic aldesleukin was administered after cell infusion. Results: Twelve patients, previously treated with a median of 4 (range, 3 to 7) anticancer agents, were treated. The cell dose was not limited by toxicity. Six patients demonstrated objective clinical responses, which included regression of bulky tumors and complete elimination of some tumors. Responses occurred in patients with vulvar, anal, head and neck, and cervical cancer. Four patients who previously received PD-1-based therapy responded. Response duration ranged from 3 to 9 months. Sustained, high-level engraftment of E7 TCR-T cells in peripheral blood was observed (median after approximately 6 weeks, 66% of total T cells, range 1% to 88%) and correlated with cell dose but not with clinical response. Infused T cell characteristics did not correlate strongly with response. Of the 4 resistant tumors that were studied, 3 demonstrated genetic defects in HLA-A*02:01 or B2M (necessary components of the target complex) and 1 demonstrated copy loss with decreased expression of antigen presentation and interferon response molecules (i.e. TAP1, TAP2, IFNGR1, IFNGR2). Of the 3 sensitive tumors studied, 0 showed genetic defects in these molecules. Conclusions: E7 TCR-T cells demonstrated safety and clinical activity in the treatment of highly refractory metastatic HPV-16+ cancers. Treatment resistance was linked to definitive genetic defects in the targeted peptide-HLA complex and to manifold defects in antigen processing and interferon response. Clinical trial information: NCT02858310.
Controlling metal nanoparticle size and preserving metal dispersion at elevated temperature remain key challenges in designing new supported metal catalysts. Many methods have been proposed to ...stabilize metal nanoparticles for catalysis, but the use of specialized equipment or metal precursors can limit the application of these methods for scalable production. Here, we demonstrate a synthesis strategy to improve the dispersion and thermal stability of Pt nanoparticles on an oxide support. A thin SiO2 coat (<2 nm) was deposited on TiO2 through repeated condensation cycles of tetraethyl orthosilicate (TEOS) with or without an organic template on the surface. H2PtCl6 was deposited using wetness impregnation, and the samples were dried, calcined, and reduced. The as-synthesized Pt nanoparticles are 1–2 nm by TEM and maintain dispersion >45% by CO chemisorption even after prolonged heating at 500 °C, whereas Pt nanoparticles on unmodified TiO2 are less dispersed (~33%) and their dispersion falls further upon prolonged heating. Ethylene hydrogenation demonstrates that the Pt nanoparticles on modified TiO2 preserve the catalytic activities of Pt on unmodified TiO2. The use of wet chemistry-based oxide modification and wetness impregnation makes this strategy a scalable and generalizable synthesis method to prepare other supported metal nanoparticles for catalysis applications.
An unprecedented irruption of thousands of Razorbills Alca torda into Florida in winter 2012/13 was followed by a 'wreck' of Razorbills and Atlantic Puffins Fratercula arctica in outer Cape Cod, ...Massachusetts, in January-March 2013. We describe these events using citizen-science sources (eBird and beached-bird surveys) and band recoveries, then we discuss them in relation to extreme weather and oceanographic change. We explored effects on likely source populations using census and monitoring data, along with possible contributions from population increases, reduced food supply, and extreme weather. Winter 2012/13 followed a marine heatwave throughout the northwest Atlantic, whose effects included reduced availability of plankton. We attribute the irruption of Razorbills into Florida partly to delayed effects of Hurricane Sandy, which disrupted their coastal habitat sufficiently to cause starving birds to move south on the Labrador Current as far as Florida. Despite the continuation of anomalously warm ocean temperatures in subsequent years and a reduction in plankton communities in the Bay of Fundy and Gulf of Maine that continues to date, no comparable events have been recorded in subsequent winters; this supports our theory that the delayed effects of Hurricane Sandy contributed to these wrecks. We highlight the power of these datasets to detect and to investigate birds' responses to extreme and anomalous conditions, which in turn provides insight into the dynamics of rapidly changing ecological systems.
Background
The authors analyzed surgical factors and outcomes data in the largest single institutional study comparing endoscopic (ECS) and open component separation (OCS) in ventral hernia repairs ...(VHR).
Methods
A prospectively maintained database was reviewed, identifying 76 patients who underwent component separation for VHR with mesh from 2010 to 2013: 34 OCS and 42 ECS. Comparisons were made for demographics, surgical risk factors, and peri-operative outcomes. Wound complications and hernia occurrence post-operatively were reviewed. Risk analyses were performed to determine the association of pre-operative risk factors with surgical site occurrences.
Results
Twenty-five ECS patients underwent subsequent laparoscopic hernia repair, and 17 underwent open repair. Operative time for ECS was longer than OCS (334 vs. 239 min;
P
< 0.001); however, there was no difference in length of stay (4 days in both groups,
P
= 0.64) and estimated blood loss (ECS: 97 vs. OCS: 93 cc,
P
= 0.847). In a sub-analysis of ECS patients, those who underwent laparoscopic hernia repair had a 96 min shorter operative time (
P
< 0.001) and lower EBL (63 vs. 147 cc,
P
< 0.001) than open repair. Wound complications were 24 % in the ECS (
n
= 10) and 32 % in OCS group (
n
= 11). There was one midline hernia recurrence in the ECS group (mean follow-up of 8 months, range 0.5–34.5 months) and no hernia recurrences in the OCS group (mean follow-up 10 months, range 0.5–30 months). Three of the patients in the ECS group developed new lateral abdominal wall hernias post-operatively.
Conclusions
The ECS group had a significantly longer operative time than the OCS group. Post-operative wound complications were similar between ECS and OCS groups. Patients in the ECS group who underwent subsequent laparoscopic VHR had a shorter operative time and blood loss than open repair.
To evaluate the safety and efficacy of intravitreal administration of a steroid and antibiotics during cataract surgery compared with the typical postoperative topical regimen in preventing ...postoperative inflammation, pain, cystoid macular edema (CME), and endophthalmitis.
Private practice, Sioux Falls, South Dakota, USA.
Retrospective case series.
The study group included eyes that had an intravitreal injection of triamcinolone–moxifloxacin–vancomycin at the time of cataract surgery with concomitant trabecular microbypass stent insertion. The control eyes had the same procedure but were prescribed topical antibiotics, steroids, and nonsteroidal antiinflammatory drugs postoperatively. Data were recorded preoperatively and 1 day, 1 week, 1 month, and 3 months postoperatively. Primary outcomes included the number of glaucoma medications, intraocular pressure (IOP), and IOP spikes of at least 15 mm Hg from baseline.
There were 234 eyes in the study group and 249 eyes in the control group. The mean reduction in glaucoma medications was 0.24 drops in the study group and 0.80 drops in the control group 3 months postoperatively, whereas the mean IOP reduction was 2.59 mm Hg in the study group and 3.63 mm Hg in the control group. Pressure spikes were detected at 54 (5.7%) of 936 postoperative visits in the study group and at 37 (3.7%) of 996 visits in the control group. There were no cases of severe inflammation, CME, infection, or retinal detachments.
Both groups had similar postoperative pressure reductions and incidence of IOP spikes. The results indicate that intravitreal injections of a steroid and antibiotics might be a safe option for glaucomatous eyes having cataract surgery with trabecular microbypass stent insertion.
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