The Utility of Repeat Culture in Fungal Corneal Ulcer Management: A Secondary Analysis of the MUTT-I Randomized Clinical Trial.

PURPOSE: To determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I). DESIGN: Secondary analysis from a multicenter, double-masked, randomized clinical trial. METHODS: setting: Multiple hospital sites of the Aravind Eye Care System, India. STUDY POPULATION: Patients with culture-positive filamentous fungal ulcers and visual acuity of 20/40 to 20/400 reexamined 6 days after initiation of treatment. INTERVENTION: Corneal scraping and cultures were obtained from study participants at day 6 after enrollment. MAIN OUTCOME MEASURES: We assessed 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate/scar size, corneal perforation, and re-epithelialization rates stratified by culture positivity at day 6. RESULTS: Of the 323 patients with smear-positive ulcers enrolled in MUTT-I, 299 (92.6%) were scraped and cultured 6 days after enrollment. Repeat culture positivity was 31% (92/299). Among patients who tested positive at enrollment, those with positive 6-day cultures had significantly worse 3-month BSCVA (0.39 logMAR; 95% confidence interval [CI]: 0.24-0.44; P < .001), had larger 3-month scar size (0.39 mm; 95% CI: 0.06-0.73; P = .02), were more likely to perforate or require therapeutic penetrating keratoplasty (odds ratio: 6.27; 95% CI: 2.73-14.40; P < .001), and were slower to re-epithelialize (hazard ratio: 0.33; 95% CI: 0.21-0.50; P < .001) than those with a negative 6-day culture result. CONCLUSIONS: Early microbiological cure on culture is a predictor of clinical response to treatment.

The Efficacy of Residents as Teachers in an Ophthalmology Module.

OBJECTIVE: Resident physicians have reported spending upward of 25% of their time teaching fellow residents and medical students. Until relatively recently, there have not been formal requirements in residency programs to learn teaching skills. The first goal of this study was to develop a novel residents-as-teachers training program to educate Ophthalmology residents on facilitating group learning and emphasizing critical-thinking skills. The second goal was to educate residents on how to teach clinical reasoning skills. DESIGN: We designed a longitudinal residents-as-teachers program that consisted of a 2-hour workshop, voluntary observation of their teaching in the small group, and student feedback on their teaching. The focus of the workshop was to educate the residents on how to facilitate critical thinking and clinical reasoning in a small group format. Voluntary video recording of residents' teaching was offered, and feedback on their teaching was provided. SETTING: Yale University School of Medicine, Department of Ophthalmology and Visual Science. PARTICIPANTS: In total, ten second-year medical student groups consisting of approximately 7 to 11 students in each group were organized in this course and each group had one teacher: 4 senior Ophthalmology residents and 6 community faculty. RESULTS: This study found that the resident teachers who completed the residents-as-teachers program were equally as effective as community faculty teachers in building medical students' comprehension of ophthalmic principles during small group seminars according to the students' evaluation of teaching performance. We also found that all of the medical students' responses were overwhelmingly positive toward having residents as teachers. The medical students particularly noted residents' preparedness and effectiveness in facilitating a discussion during the small group seminars. CONCLUSIONS: Our novel program was effective at teaching residents how to teach critical-thinking skills and the resident teachers were well received by medical students in the classroom. Given the requirement that residents learn teaching skills during residency and our preliminary success, we plan to continue inviting residents to teach small group seminars in Ophthalmology, and we will continue to provide them with the residents-as-teachers program.

Bevacizumab salvage therapy following progression in high-grade glioma patients treated with VEGF receptor tyrosine kinase inhibitors.

Agents targeting the vascular endothelial growth factor (VEGF) pathway are being used with increasing frequency in patients with recurrent high-grade glioma. The effect of more than one antiangiogenic therapy given in succession has not been established. We reviewed the efficacy of bevacizumab, a VEGF-A monoclonal antibody, in patients who progressed following prior therapy with VEGF receptor tyrosine kinase inhibitors (R-TKi). Seventy-three patients with recurrent high-grade gliomas received VEGF R-TKi (cediranib, sorafenib, pazopanib, or sunitinib) as part of phase I or II clinical trials. Twenty-four of these patients with glioblastoma progressed and received bevacizumab-containing regimens immediately after R-TKi. Those who stopped R-TKi therapy for reasons other than disease progression, or received a treatment that did not include bevacizumab, were excluded from the analysis. The efficacy of bevacizumab-containing regimens in these 24 patients was evaluated. During R-TKi therapy, 6 of 24 patients (25%) had a partial response (PR) to treatment. The 6-month progression-free survival (APF6) was 16.7% and median time-to-progression (TTP) was 14.3 weeks. Grade III/IV toxicities were seen in 13 of 24 patients (54%). Subsequently with bevacizumab salvage therapy, 5 of 24 patients (21%) had a PR, the APF6 was 12.5%, and the median TTP was 8 weeks. Five of 24 patients had grade III/IV toxicities (21%). The median overall survival (OS) from the start of R-TKi therapy was 9.2 months (range: 2.8-34.1+), whereas the median OS after bevacizumab was 5.2 months (range: 1.3-28.9+). Bevacizumab retains modest activity in high-grade glioma patients who progress on R-TKi. However, the APF6 of 12.5% in this cohort of patients indicates that durable tumor control is not achieved for most patients.

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer.

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites.