Anti-inflammatory medication use after cataract surgery: online survey of practice patterns.

PURPOSE: To determine current prescribing patterns for topical or intraocular/periocular anti-inflammatory medications (AIMs) after routine cataract surgery. SETTING: kera-net online members. DESIGN: Cross-sectional survey. METHODS: An online survey was distributed to subscribers of kera-net, a global online platform sponsored by the Cornea Society. Questions were asked regarding the use of topical or intraocular/periocular AIM after cataract surgery and types of medications prescribed. RESULTS: Of 217 surgeon respondents (23% response rate), 171 (79%) practiced in the United States and 171 (79%) were cornea subspecialists. Most of the respondents (n = 196, 97%) prescribed topical corticosteroids after routine cataract surgery. The most frequently prescribed were prednisolone acetate (n = 162, 83%), followed by dexamethasone (n = 26, 13%), difluprednate (n = 24, 12%), and loteprednol etabonate (n = 13, 7%). Corticosteroids comprised (n = 40, 32%) of total intraocular/periocular injections, with triamcinolone acetonide 10 or 40 mg (n = 19, 47.5%) most commonly used. 23 surgeons (58%) who utilized intraocular/periocular corticosteroids also prescribed topical corticosteroids. Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 148 surgeons (73%). CONCLUSIONS: Most surgeons prescribed topical AIM after routine cataract surgery. Many surgeons injected intraocular or periocular AIM while prescribing topical AIM. The diversity of practice patterns may reflect the lack of clear evidence-based guidelines.

Presenting Features of Giant Cell Arteritis with Active Versus Healed Arteritis on Biopsy.

Giant cell arteritis (GCA) is often categorised as "active" or "healed" on temporal artery biopsy (TAB). The purpose of this study was to compare the initial clinical presentation of patients with GCA according to active versus healed arteritis on TAB. A retrospective chart review was performed for patients with biopsy-proven GCA (BP-GCA) at a single academic medical institution from a previously reported cohort. The arteritis on TAB was categorised as "active" or "healed" based on the pathological reports. Demographic information, clinical presentation, past medical history, and test results were collected from the date of TAB. These baseline characteristics were entered into the GCA Risk Calculator. Of 85 patients with BP-GCA, 80% had active and 20% had healed disease according to histopathology. A higher percentage of those with active arteritis had ischaemic optic neuropathy (ION) (36% versus 6%, p = .03), elevated erythrocyte sedimentation rates (92% versus 63%, p = .01), elevated C-reactive protein levels (79% versus 46%, p = .049), GCA risk score > 7.5% (99% sensitivity, 100% versus 71%, p < .001), higher mean GCA risk calculator scores (neural network p = .001; logistic regression p = .002). Patients with healed arteritis were less likely to have visual manifestations than the active arteritis group (38% versus 71%, p = .04). Patients with active vasculitis on biopsy had higher rates of ION and elevated inflammatory markers, as well as higher predictive scores from the GCA risk calculator. Further research is needed regarding correlation of biopsy findings and risk of complications or relapses.

Baseline Characteristics and Clinical Presentation of Biopsy-Proven Giant Cell Arteritis in White Compared with Black Patients.

BACKGROUND: Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in the elderly and can lead to permanent vision loss if left untreated. Most earlier studies have evaluated GCA in primarily white populations, and GCA was traditionally thought to occur at nearly negligible frequency in black populations. Our previous study showed that GCA may occur at similar rates in white and black patients, but little is known about the presentation of GCA in black patients. The purpose of this study is to examine baseline presentation of biopsy-proven GCA (BP-GCA) in a tertiary care center-based population with a sizeable proportion of black patients. METHODS: Retrospective study from a single academic institution of a previously described cohort of BP-GCA. Presenting symptoms, laboratory findings, and GCA Calculator Risk score were compared in black and white patients with BP-GCA. RESULTS: Among 85 patients with biopsy-proven GCA, 71 (84%) were white and 12 (14%) were black. White patients had higher rates of elevated platelet count (34% vs 0%, P = 0.04), whereas black patients had higher rates of diabetes mellitus (67% vs 12%, P < 0.001). There were no statistically significant differences in age, gender, biopsy classification (active vs healed arteritis), cranial symptoms, visual symptoms/ophthalmic findings, rates of abnormal erythrocyte sedimentation rate or C-reactive protein, unintentional weight loss, polymyalgia rheumatica, or GCA risk calculator score. CONCLUSIONS: Presenting features of GCA were similar between white and black patients in our cohort, except for rates of abnormal platelet level and diabetes. Physicians should feel comfortable relying on the usual clinical features for the diagnosis of GCA independent of race.

Ophthalmology Resident Oculofacial Surgery Case Exposure: An ACGME Case Log Analysis.

PURPOSE: The authors quantified trends in resident oculofacial surgery exposure between 2009 and 2018, reviewed specific procedure volume, and correlated procedure volume with program characteristics. METHODS: The authors requested de-identified case logs of residents graduating US ophthalmology residency programs in 2018 from all 118 programs. Current Procedural Terminology codes of all oculofacial procedures were analyzed. Current Procedural Terminology codes were grouped into 25 unique categories that the authors created in addition to the 11 Accreditation Council for Graduate Medical Education categories. RESULTS: One hundred and sixty-six of 488 (34%) US ophthalmology residents graduating in 2018 provided case logs (32.2% of programs). According to Accreditation Council for Graduate Medical Education case logs, residents graduating in 2018 completed significantly fewer eye removal/implant procedures, lacrimal surgeries, "other orbital" procedures, entropion/ectropion repairs, and temporal artery biopsies as primary surgeon than residents graduating in 2009, yet significantly more eyelid laceration repairs, chalazion excisions, tarsorrhaphies, ptosis repairs, and blepharoplasty/reconstruction procedures ( p < 0.05). No difference was found between the total number of oculofacial cases between 2009 and 2018 ( p = 0.051). The most frequently logged procedure per resident in the sample was blepharoplasty/reconstruction (17.2 ± 15) followed by "other oculoplastic" (12.7 ± 10.6). The least commonly performed procedures included temporal artery biopsy (1.5 ± 2.2) and "other orbital" (1.9 ± 3.1). Program size, location, and presence of oculofacial fellowship program all impacted case volume. CONCLUSIONS: Oculofacial surgery has the second highest case number requirement for residents per Accreditation Council for Graduate Medical Education guidelines. However, resident exposure to oculofacial surgery cases greatly varies in each ophthalmology residency program.

Ghost and Honorary Authorship in Ophthalmology: A Cross-Sectional Survey.

PURPOSE: To evaluate the rates of ghost and honorary authorship in ophthalmology and to determine risk factors associated with ghost and honorary authorship. DESIGN: Cross-sectional survey. METHODS: Corresponding authors of articles published in Ophthalmology, JAMA Ophthalmology, and the American Journal of Ophthalmology from June 2019 to December 2020 were emailed an electronic survey. The rates of ghost and honorary authorship, demographic characteristics of the corresponding authors with and without ghost and honorary authorship, and risk factors for ghost and honorary authorship were evaluated. RESULTS: Corresponding authors (n = 830) were emailed a survey and 278 total responses (34.1%) were received; 227 responses (27.9%) were complete and included for analysis. Most respondents (n = 206, 90.7%) believed that the International Committee of Medical Journal Editors (ICMJE) guidelines for authorship adequately address criteria for authorship. Twenty-seven corresponding authors (11.9%) reported characteristics of their articles that indicated the presence of both ghost and honorary authorship (95% CI, 7.7%-16.1%). One hundred fifteen (50.7%) reported honorary authorship (44.2%-57.2%), and 37 (16.3%) indicated ghost authorship (11.5%-21.1%). Being a resident or fellow corresponding author increased the risk of honorary authorship (OR 11.75; 1.91-231.57; P = .03). There were no factors that predicted articles having ghost authors. CONCLUSIONS: While many authors believe the ICMJE guidelines for authorship comprehensively delineate fair authorship practices, listing authors on scientific publications honorarily and excluding authors who qualify for authorship are relatively common practices in ophthalmological research. Further investigation into the drivers of honorary and ghost authorship practices in ophthalmology, and the effectiveness of preventive measures are needed to ensure fair authorship attributions.

Rural melanoma patients in Maryland do not present with more advanced disease than urban patients.

PURPOSE: Rural populations have higher poverty rates, lower educational attainment, higher smoking rates, lower rates of health insurance, higher proportions of elderly individuals, decreased access to health services including dermatology, higher all-cause mortality, and higher mortality from melanoma. Despite these disparities, rural patients have not been adequately studied within the dermatologic literature, particularly at geographic units smaller than the county level. METHODS: We used zip codes and Rural Urban Commuting Area (RUCA) codes to conduct a cross-sectional study on the prevalence and severity of melanoma among 31,750 rural versus urban patients treated by the Johns Hopkins Department of Dermatology from January, 2016 to June, 2017. RESULTS: Compared to urban patients, rural patients had a 2.6 times higher melanoma prevalence (P<0.0001), travelled much greater distances for treatment (101.8 miles versus 17.7 miles, P<0.0001), and lived in zip codes with median household incomes $18,188 lower ($58,718 versus $76,906; P=0.0040). However, there were no significant differences in Breslow depth or clinical stage between rural and urban patients. CONCLUSIONS: Despite having a higher prevalence of melanoma and travelling much greater distances to receive care, rural patients did not present with more advanced disease than their urban counterparts.

Clinical Outcomes of Secondary Scleral-Sutured Foldable Hydrophilic Acrylic Intraocular Lens Placement by Trainees: A Single-Site Analysis.

PURPOSE: To evaluate the outcomes of a 4-point scleral-fixated foldable Akreos AO60 intraocular lens (IOL) insertion using Gore-Tex suture performed by trainees under supervision of a single attending surgeon. METHODS: Retrospective chart review for 53 eyes of 50 patients whose surgery was performed by trainees under supervision of a single surgeon between 2015 and 2018 at a tertiary care hospital (Johns Hopkins Wilmer Eye Institute, Baltimore, MD). Indications for surgery, preoperative risk factors, and intraoperative techniques were analyzed. Outcome measures included final best-corrected visual acuity (BCVA), change in BCVA, difference between expected and final spherical equivalent (SE), and postoperative complications. RESULTS: Mean patient age was 62.8 years (range 26.9 to 88.4). The most common indication for surgery was IOL dislocation (59.6%) due to trauma in 21 cases (40.4%) and pseudoexfoliation in 6 (11.5%). Combined pars plana vitrectomy was performed simultaneously in 46 cases (88.5%). Mean BCVA improved from 20/100 to 20/40 (p < 0.001). The difference between expected and final SE was within 1.0 D in 28 cases (53.8%). Postoperative hypotony occurred in 12 eyes (21.2%) on day 1; all were resolved at last follow-up. Postoperative cystoid macular edema (CME) occurred in 20 cases (38.5%); 11 (21.2%) persisted through last follow-up. CONCLUSION: Scleral-fixation of Akreos AO60 IOL in absence of capsular support can be performed by trainees under supervision and results in effective visual rehabilitation. Postoperative CME occurred at a higher rate than previously reported in the literature. Future studies should assess the rates of postoperative complications amongst different techniques of secondary IOL fixation performed by trainees to determine which is the safest.

Screening for posttraumatic stress disorder in ARDS survivors: validation of the Impact of Event Scale-6 (IES-6).

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms are common in acute respiratory distress syndrome (ARDS) survivors. Brief screening instruments are needed for clinical and research purposes. We evaluated internal consistency, external construct, and criterion validity of the Impact of Event Scale-6 (IES-6; 6 items) compared to the original Impact of Event Scale-Revised (IES-R; 22 items) and to the Clinician Administered PTSD Scale (CAPS) reference standard evaluation in ARDS survivors. METHODS: This study is a secondary analysis from two independent multi-site, prospective studies of ARDS survivors. Measures of internal consistency, and external construct and criterion validity were evaluated. RESULTS: A total of 1001 ARDS survivors (51% female, 76% white, mean (SD) age 49 (14) years) were evaluated. The IES-6 demonstrated internal consistency over multiple time points up to 5 years after ARDS (Cronbach's alpha = 0.86 to 0.91) and high correlation with the IES-R (0.96; 95% confidence interval (CI): 0.94 to 0.97). The IES-6 demonstrated stronger correlations with related constructs (e.g., anxiety and depression; |r| = 0.32 to 0.52) and weaker correlations with unrelated constructs (e.g., physical function and healthcare utilization measures (|r| = 0.02 to 0.27). Criterion validity evaluation with the CAPS diagnosis of PTSD in a subsample of 60 participants yielded an area under receiver operating characteristic curve (95% CI) of 0.93 (0.86, 1.00), with an IES-6 cutoff score of 1.75 yielding 0.88 sensitivity and 0.85 specificity. CONCLUSIONS: The IES-6 is reliable and valid for screening for PTSD in ARDS survivors and may be useful in clinical and research settings.

Contemporary Rates of Preoperative Cardiac Testing Prior to Inpatient Hip Fracture Surgery.

Hip fracture is a common reason for urgent inpatient surgery. In the past few years, several professional societies have identified preoperative echocardiography and stress testing for noncardiac surgeries as low-value diagnostics. We utilized data on hospitalizations with a primary diagnosis of hip fracture surgery between 2011 and 2015 from the State Inpatient Databases (SID) of Maryland, New Jersey, and Washington, combined with data on hospital characteristics from the American Hospital Association (AHA). We found that the rate of preoperative ischemic testing is surprisingly but encouragingly low (stress tests 1.1% and cardiac catheterizations 0.5%), which is consistent with studies evaluating the outpatient utilization of these tests for low-and intermediate-risk surgeries. The rate of echocardiograms was 12.6%, which was higher than other published reports. Our findings emphasize the importance of ensuring that quality improvement efforts are directed toward areas where quality improvement is, in fact, needed.

Synthesized Mammography: The New Standard of Care When Screening for Breast Cancer with Digital Breast Tomosynthesis?

RATIONALE AND OBJECTIVES: This study aims to evaluate the screening performance of digital breast tomosynthesis (DBT) combined with synthesized mammography (SM) vs combined with full-field digital mammography (FFDM). MATERIALS AND METHODS: We retrospectively reviewed all screening studies utilizing FFDM + DBT (n = 7845) and SM + DBT (n = 14,776) between April 1, 2013, and February 15, 2016. Recall rate, biopsy rate, positive predictive value 1 (PPV1), positive predictive value 3 (PPV3), and cancer detection rate (CDR) were compared between the two groups. A generalized linear mixed model specifying the reading radiologist as the random effect and controlling for age was used to compare clinical outcomes between the two groups. RESULTS: The overall recall rate was significantly lower in the SM + DBT cohort compared to the FFDM + DBT cohort (7.06% vs 7.63%, P = .04). There was no difference in biopsy rate, PPV1, PPV3, or CDR between the two groups. CONCLUSIONS: When DBT is performed for screening, the use of SM rather than acquiring an additional FFDM has no significant effect on biopsy rate, PPV1, PPV3, or CDR. We found a decrease in recall rate in the SM + DBT group, which may be related to the learning curve of interpreting DBT. These findings support the use of SM for patients undergoing screening with DBT.

Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi.

Background: Stunting affects ∼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood.Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting.Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted.Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure.Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for ß-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation.

BACKGROUND: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. METHODS: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test. FINDINGS: 80.7% of children had EED. Of 677 serum metabolites measured, 21 were negatively associated and 56 were positively associated with gut permeability, using a false discovery rate approach (q<0.05, p<0.0095). Increased gut permeability was associated with elevated acylcarnitines, deoxycarnitine, fatty acid ß-oxidation intermediates, fatty acid ω-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate. INTERPRETATION: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

Response and Defense Mechanisms of Taxus chinensis Leaves Under UV-A Radiation are Revealed Using Comparative Proteomics and Metabolomics Analyses.

Taxus chinensis var. mairei is a species endemic to south-eastern China and one of the natural sources for the anticancer medicine paclitaxel. To investigate the molecular response and defense mechanisms of T. chinensis leaves to enhanced ultraviolet-A (UV-A) radiation, gel-free/label-free and gel-based proteomics and gas chromatography-mass spectrometry (GC-MS) analyses were performed. The transmission electron microscopy results indicated damage to the chloroplast under UV-A radiation. Proteomics analyses in leaves and chloroplasts showed that photosynthesis-, glycolysis-, secondary metabolism-, stress-, and protein synthesis-, degradation- and activation-related systems were mainly changed under UV-A radiation. Forty-seven PSII proteins and six PSI proteins were identified as being changed in leaves and chloroplasts under UV-A treatment. This indicated that PSII was more sensitive to UV-A than PSI as the target of UV-A light. Enhanced glycolysis, with four glycolysis-related key enzymes increased, provided precursors for secondary metabolism. The 1-deoxy-d-xylulose-5-phosphate reductoisomerase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were identified as being significantly increased during UV-A radiation, which resulted in paclitaxel enhancement. Additionally, mRNA expression levels of genes involved in the paclitaxel biosynthetic pathway indicated a down-regulation under UV-A irradiation and up-regulation in dark incubation. These results reveal that a short-term high dose of UV-A radiation could stimulate the plant stress defense system and paclitaxel production.

Characterisation of polyphenol constituents of Linderae aggregate leaves using HPLC fingerprint analysis and their antioxidant activities.

The leaves of Linderae aggregate (LAL) has been used as a type of tea in China and other Southeast Asian countries. In this study, 11 polyphenols in LAL were clarified for the first time using multiple high-performance liquid chromatographic techniques. An optimal extracting method was developed through the comparison of the amount of quercetin-3-O-α-L-rhamnoside using a uniform design method. From the fingerprint liquid chromatography data, 11 common peaks in the 8 samples collected from April to November were semi-determined. The antioxidant capacities were examined using the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay and the ferric reducing/antioxidant power assay. All 8 samples contained the same 11 polyphenols in similar ratios. Three samples, S2, S5 and S6 contained higher amount of quercetin-3-O-α-L-rhamnoside and were demonstrated to have stronger antioxidant capacities in both antioxidant assays. These results are critical in optimising harvest time and quality control of LAL.

Proteomics analysis of Mahonia bealei leaves with induction of alkaloids via combinatorial peptide ligand libraries.

Alkaloids are one of the most attractive sources for obtaining active natural products. However, alkaloids exist in the plants as the secondary metabolites with tracing amount, and there is an enormous demand for a large production. In the present study, we aimed to profile the modification of benzylisoquinoline alkaloids in Mahonia bealei seedlings under the binary stress of ultraviolet-B irradiation and dark incubation. Comparative proteomics analysis was carried out to address the underlying proteome variations that accounted for the alkaloid induction under treatment. Thirteen differential proteins were identified in the leaves under binary stress. Of note, the abundance of S-adenosyl-L-methionine synthetase was highly increased to sustain a high concentration of S-adenosyl-L-methionine for the enhanced biosynthesis of alkaloids. Additionally, we presented the application of CPLL to M. bealei leaf proteins. Three new secondary metabolism proteins and 12 additional differential proteins were identified only after CPLL treatment. Six genes in the benzylisoquinoline alkaloid biosynthesis pathway were selected to verify their variable expression using quantitative real time polymerase chain reaction. The results suggest that the benzylisoquinoline alkaloids in M. bealei leaf were increased to eliminate the adverse effect of UV-B exposure. The suppression of photosynthesis and respiratory rate may save an extra energy for the secondary metabolites, and the enhanced N-metabolism may supply sufficient primary metabolite precursors. To our best knowledge, this is the first work aimed at the secondary metabolism proteomic characterization of M. bealei using the CPLL technique. It also presented an effective and innovative process to improve the contents of alkaloids in medicinal plants for industrial production. BIOLOGICAL SIGNIFICANCE: Besides the effective and innovative process to improve the contents of alkaloids in M. bealei leaves for industrial production, the presented combinatorial hexapeptide ligand library technology was applied for the study of low-abundance protein in medicinal plant. It may be an available tool for the analysis of the secondary proteins.

Enantioselective synthesis of lobeline via nonenzymatic desymmetrization.

Lobeline has been prepared in enantiopure form via desymmetrization of lobelanidine with use of BTM, a nonenzymatic enantioselective acyl transfer catalyst.