Mahr, Michael A.

Purpose: The purpose of this study is to quantify cancer risk in patients with Fuchs endothelial corneal dystrophy (FECD). Methods: Using the 2014 to 2016 Medicare Limited 5% Data Sets—Carrier Line File, US Medicare fee-for-service beneficiaries (aged 65 years or older) with FECD and cancer were identified through International Classification of Diseases, ninth and 10th Revision diagnostic codes from January 1, 2014, to December 31, 2016. The main outcome measures were odds ratios (ORs) of cancer at various anatomic locations in patients with versus without FECD. Results: Of the 1,462,740 Medicare beneficiaries, 15,534 patients (1.1%) had an International Classification of Disease code for FECD. Compared with US Medicare beneficiaries without FECD, patients with FECD were at increased risk for the following malignancies: breast [OR: 1.32; 95% confidence interval (CI): 1.22–1.43; P < 0.001], cutaneous basal cell (OR: 1.42; 95% CI: 1.35–1.49; P < 0.001), cutaneous melanoma (OR: 1.20; 95% CI: 1.03–1.40; P = 0.02), cutaneous squamous cell (OR: 1.45; 95% CI: 1.38–1.53; P < 0.001), ovarian (OR: 1.84; 95% CI: 1.48–2.30; P < 0.001), and thyroid (OR: 1.32; 95% CI: 1.04–1.68; P = 0.02). By contrast, FECD cases were at lower odds of having lung (OR: 0.81; 95% CI: 0.71–0.93; P = 0.003) and prostate cancer diagnoses (OR: 0.88; 95% CI: 0.81–0.96; P = 0.002). Conclusions: Patients with FECD aged 65 years or older may be at increased risk for cancer at several anatomic locations. Follow-up studies are needed to further explore the association of FECD and malignancy, elucidate potential disease mechanisms, and identify genetic and/or environmental risk factors.

BACKGROUND: Previous studies of postoperative corneal injury rates relied on provider-initiated incident reports, which may underestimate the true incidence. Postoperative administration of proparacaine eye drops is used almost exclusively to diagnose corneal injury; therefore, identifying instances of administration may provide a better estimate of corneal injuries. We compared proparacaine administration versus provider-initiated reports to determine rates of corneal injury. In addition, potential associations between clinical variables and injury were assessed with a matched case–control study. METHODS: The health records of 132,511 sequential adult postanesthesia recovery room admissions (January 1, 2011 to June 30, 2017) were reviewed to identify postoperative proparacaine administration and incident reports of corneal injury. Patients with corneal injury were matched with control patients at a 1:2 ratio to assess factors associated with injury. RESULTS: Proparacaine drops were administered to 442 patients (425 patients received proparacaine for diagnosis and 17 patients received proparacaine for unrelated reasons). Incident reports identified 320 injuries, and the aggregate corneal injury count was 436 (incidence, 3.3 injuries [95% confidence interval {CI}, 3.0–3.6] per 1000 cases of general anesthesia). Proparacaine administration had a greater case ascertainment percentage than incident reporting (97.5% vs 73.4%; P < .001). The matched case–control analysis found greater risks associated with longer duration of anesthesia (odds ratio, 1.05 [95% CI, 1.03–1.07] per 10 minutes of anesthesia; P < .001) and nonsupine surgical position (odds ratio, 3.89 [95% CI, 2.17–6.98]; P < .001). Patients with injuries also had more evidence of sedation and agitation during anesthesia recovery. CONCLUSIONS: Calculation of incidence by using the administration of a medication (proparacaine eye drops) that is almost exclusively used to diagnose a specific injury (corneal injury) showed higher case ascertainment percentage than incident-reporting methods. Similar strategies could be used to monitor the rates of other adverse events.

Removing fish hooks is a common procedure performed by many emergency department providers. There are several techniques that are commonly employed to aid in successful removal. However, when a fish hook becomes embedded within the orbit, there are limited options as to avoid damaging vital surrounding structures. The authors report the removal of a fish hook within the anterior orbit using the string technique in a 25-year-old patient. The procedure was performed under general anesthesia with the aid of size 5 polyglactin suture wrapped around the hook. The procedure itself took less than 10 seconds and was successful in swiftly and safely removing the hook without damaging surrounding orbital structures. The patient recovered well without any permanent sequelae.

Purpose Endoxifen is a tamoxifen metabolite with potent antiestrogenic activity. Patients and Methods We performed a phase I study of oral Z-endoxifen to determine its toxicities, maximum tolerated dose (MTD), pharmacokinetics, and clinical activity. Eligibility included endocrine-refractory, estrogen receptor–positive metastatic breast cancer. An accelerated titration schedule was applied until moderate or dose-limiting toxicity occurred, followed by a 3+3 design and expansion at 40, 80, and 100 mg per day. Tumor DNA from serum (circulating cell free [cf); all patients] and biopsies [160 mg/day and expansion]) was sequenced. Results Of 41 enrolled patients, 38 were evaluable for MTD determination. Prior endocrine regimens during which progression occurred included aromatase inhibitor (n = 36), fulvestrant (n = 21), and tamoxifen (n = 15). Patients received endoxifen once daily at seven dose levels (20 to 160 mg). Dose escalation ceased at 160 mg per day given lack of MTD and endoxifen concentrations > 1,900 ng/mL. Endoxifen clearance was unaffected by CYP2D6 genotype. One patient (60 mg) had cycle 1 dose-limiting toxicity (pulmonary embolus). Overall clinical benefit rate (stable > 6 months [n = 7] or partial response by RECIST criteria [n = 3]) was 26.3% (95% CI, 13.4% to 43.1%) including prior tamoxifen progression (n = 3). cfDNA mutations were observed in 13 patients ( PIK3CA [n = 8], ESR1 [n = 5], TP53 [n = 4], and AKT [n = 1]) with shorter progression-free survival ( v those without cfDNA mutations; median, 61 v 132 days; log-rank P = .046). Clinical benefit was observed in those with ESR1 amplification (tumor; 80 mg/day) and ESR1 mutation (cfDNA; 160 mg/day). Comparing tumor biopsies and cfDNA, some mutations ( PIK3CA, TP53, and AKT) were undetected by cfDNA, whereas cfDNA mutations ( ESR1, TP53, and AKT) were undetected by biopsy. Conclusion In endocrine-refractory metastatic breast cancer, Z-endoxifen provides substantial drug exposure unaffected by CYP2D6 metabolism, acceptable toxicity, and promising antitumor activity.

Background The authors' department conducted a performance improvement initiative aimed to reduce the rate of perioperative corneal injuries. This study reports the effects of the initiative and examines the risk factors for corneal injury. Method The rate of corneal injuries during nonophthalmologic procedures under anesthesia was compared between the two time periods: preinitiative baseline (August 1, 2005-December 31, 2005) and initiative period (January 1, 2006-April 30, 2007). To examine the risk factors for corneal injury, a nested case-control study with a 2:1 matched-set design was separately performed and included cases between January 1, 2006 and July 31, 2008. Results During the baseline period, the corneal injury rate was 1.51 per 1,000, and it decreased to 0.79 per 1,000 during the performance initiative (P = 0.008). Independent risk factors were longer anesthetics (odds ratio = 1.2, 95% confidence interval (CI) 1.1-1.3 per 30 min), lower American Society of Anesthesiologists physical status (odds ratio 0.5, 95% CI 0.3-0.8 for American Society of Anesthesiologists physical status 3-4 vs. 1-2), and student nurse anesthetist as a primary anesthesia provider (odds ratio 2.6, 95% CI 1.3-5.0). Conclusion Corneal injury rate in our institution was significantly reduced and remains at low levels long after initiation of perioperative eye care improvement initiative. The higher rate of corneal injuries among student nurse anesthetists highlights the importance of standardizing education and supervision among all anesthesia providers. We believe that our model of performance improvement initiative can be used to improve other perioperative outcomes.