Systematic Review and Meta-Analysis: Risk of Hospitalization in Patients with Ulcerative Colitis and Crohn's Disease in Population-Based Cohort Studies.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) lead to high morbidity and unplanned healthcare utilization. We conducted a systematic review with meta-analysis to estimate the cumulative incidence of IBD-related (and all-cause) hospitalization in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Through a systematic review to September 3, 2019, we identified population-based inception cohort studies in patients with IBD that reported patient-level cumulative incidence of hospitalization at 1, 3 and 5 years after diagnosis. Hospitalization risk was pooled using random effects meta-analysis, and risk factors analyzed through mixed-effects meta-regression and qualitative synthesis. RESULTS: In patients with UC (6 cohorts), 1-, 3- and 5-year risk of UC-related hospitalization was 10.4% (95% CI 8.2-13.2), 17.0% (95% CI 14.0-20.4) and 21.5% (95% CI 18.0-25.4), respectively, with considerable heterogeneity. In patients with CD (6 cohorts), 1-, 3- and 5-year risk of CD-related hospitalization was 29.3% (95% CI 20.0-40.8), 38.5% (95% CI 26.8-51.7) and 44.3% (95% CI 32.7-56.5), respectively, with considerable heterogeneity. On meta-regression, steady decline in risk of hospitalization was observed in patients diagnosed in a more contemporary era. Younger age at onset (both UC and CD), extensive colitis (UC), ileal-dominant CD, perianal CD and penetrating and/or stricturing behavior (CD) and early need for corticosteroids and immunosuppressive therapy (both UC and CD) were associated with increased risk of hospitalization. CONCLUSION: Approximately one in five and one in two patients with UC and CD are hospitalized within 5 years of diagnosis, respectively. Population health management strategies are required to mitigate unplanned healthcare utilization.

Epidemiology and Natural History of Perianal Crohn's Disease: A Systematic Review and Meta-Analysis of Population-Based Cohorts.

BACKGROUND AND AIMS: Perianal Crohn's disease (pCD) is a potentially severe phenotype of CD. We conducted a systematic review with meta-analysis to estimate cumulative incidence, risk factors, and outcomes of pCD in population-based cohort studies. METHODS: Through a systematic literature review through March 1, 2021, we identified population-based inception cohort studies reporting cumulative incidence of perianal disease (primarily abscess and/or fistula) in patients with CD. We estimated the cumulative incidence of pCD at presentation and 1-, 5-, and 10-year follow-up, and risk factors for perianal disease and outcomes including risk of major (bowel resection, proctectomy, ostomy) and minor perianal (incision and drainage, seton placement, etc.) surgery. RESULTS: In 12 population-based studies, prevalence of pCD was 18.7% (95% confidence interval [CI], 12.5%-27.0%) with 1-, 5-, and 10-year risk of perianal disease being 14.3% (95% CI, 7.9%-24.6%), 17.6% (95% CI, 11.3%-26.5%), and 18.9% (95% CI, 15.0%-23.4%), respectively. Approximately 11.5% of patients (95% CI, 6.7%-19.0%) had perianal disease at or before CD diagnosis. Colonic disease location and rectal involvement were associated with higher risk of pCD. Overall, 63.3% of patients (95% CI, 53.3-72.3) required minor perianal surgery and 6.4% of patients (95% CI, 1.8%-20.6%) required major abdominal surgery for pCD. Use of biologic therapy for pCD is common and has steadily increased throughout the years. CONCLUSIONS: Approximately 1 in 5 patients with CD develops perianal disease within 10 years of CD diagnosis, including 11.5% who have perianal disease at presentation. Approximately two-thirds of patients require perianal surgery, with a smaller fraction requiring major abdominal surgery.

In a systematic review and meta-analysis of 12 population-based cohort studies, we observed that approximately 1 in 5 patients develops perianal disease within 10 years of Crohn's disease diagnosis. Of these, two-thirds require perianal surgery and 6% require major abdominal surgery.

Contemporary Risk of Surgery in Patients With Ulcerative Colitis and Crohn's Disease: A Meta-Analysis of Population-Based Cohorts.

BACKGROUND & AIMS: We conducted a systematic review with meta-analysis to estimate rates and trends of colectomy in patients with ulcerative colitis (UC), and of primary and re-resection in patients with Crohn's disease (CD), focusing on contemporary risks. METHODS: Through a systematic review until September 3, 2019, we identified population-based cohort studies that reported patient-level cumulative risk of surgery in patients with UC and CD. We evaluated overall and contemporary risk (after 2000) of surgery and analyzed time trends through mixed-effects meta-regression. RESULTS: In patients with UC (26 studies), the overall 1-, 5-, and 10-year risks of colectomy was 4.0% (95% CI, 3.3-5.0), 8.8% (95% CI, 7.7-10.0), and 13.3% (95% CI, 11.3-15.5), respectively, with a decrease in risk over time (P < .001). Corresponding contemporary risks were 2.8% (95% CI, 2.0-3.9), 7.0% (95% CI, 5.7-8.6), and 9.6% (95% CI, 6.3-14.2), respectively. In patients with CD (22 studies), the overall 1-, 5-, and 10-year risk of surgery was 18.7% (95% CI, 15.0-23.0), 28.0% (95% CI, 24.0-32.4), and 39.5% (95% CI, 33.3-46.2), respectively, with a decrease in risk over time (P < .001). Corresponding contemporary risks were 12.3% (95% CI, 10.8-14.0), 18.0% (95% CI, 15.4-21.0), and 26.2% (95% CI, 23.4-29.4), respectively. In a meta-analysis of 8 studies in patients with CD with prior resection, the cumulative risk of a second resection at 5 and 10 years after the first resection was 17.7% (95% CI, 13.5-22.9) and 31.3% (95% CI, 24.1-39.6), respectively. CONCLUSIONS: Patient-level risks of surgery have decreased significantly over time, with a 5-year cumulative risk of surgery of 7.0% in UC and 18.0% in CD in contemporary cohorts. This decrease may be related to early detection and/or better treatment.

Femtosecond Laser-Assisted In Situ Keratomileusis Treatment of Residual Refractive Error following Femtosecond Laser-Enabled Keratoplasty.

PURPOSE: To evaluate the safety and effectiveness of femtosecond laser-assisted in situ keratomileusis (LASIK) in the treatment of residual myopia and astigmatism following femtosecond laser-enabled keratoplasty (FLEK). DESIGN: Retrospective case review. METHODS: Chart review of all patients with prior FLEK who subsequently underwent femto-LASIK surgery after full suture removal was performed at the Gavin Herbert Eye Institute at the University of California, Irvine. A total of 14 eyes in 13 patients met this criterion, and their comprehensive examinations performed at standard intervals were reviewed. Main outcome measures include uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) expressed as the logarithm of the minimum angle of resolution (logMAR), manifest refractive astigmatism, and spherical equivalent. RESULTS: From the preoperative visit to the 3 month visit, all 14 eyes significantly improved in UDVA (logMAR, 0.93 ± 0.23 to 0.44 ± 0.32, P = 0.002) with no loss of CDVA (logMAR, 0.26 ± 0.19 to 0.18 ± 0.23, P = 0.50). All 14 eyes showed significant improvement in manifest refractive astigmatism (4.71 ± 1.77 to 2.18 ± 1.45 diopters (D), P = 0.003) and spherical equivalent (-2.57 ± 2.45 to -0.48 ± 0.83 D, P = 0.0007). There were no flap or graft complications as a result of femto-LASIK. CONCLUSIONS: Our findings suggest that femto-LASIK on eyes with prior FLEK is safe and effective in improving visual acuity and reducing residual astigmatism.

Diversity in the American Society of Ophthalmic Plastic and Reconstructive Surgery.

PURPOSE: To assess the epidemiology of women and underrepresented minorities (URMs; Hispanic, African American, and Native American) in the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS). METHODS: An observational retrospective study of living ASOPRS members was identified through the ASOPRS member directory, search engine-driven informatics, and direct communication. Members were profiled for gender, race, geographic location, and academic rank (or not). The percentage of women and URMs in the society over time was also assessed. RESULTS: The authors identified 617 living ASOPRS members as of June 2017. Of these, 109 (17.7%) were female and 58 (9.4%) were URMs. Surgeons completed fellowships from 1961 (male) or 1973 (female) until 2015. Women members significantly increased from 7 (4.9% of the total) before 1986 to 24 (30.4%) between 2011 and 2015 (last 5 years). URMs significantly increased over time, with 0 female and 5 (3.4%) male minorities before 1985 to 5 (6.3%) females and 13 (16.5%) males within the last 5 years (p < 0.05). With only 1 female and 3 male members, African American representation was sparse. ASOPRS members were not found in 5 states and were most represented in California, New York, Florida, and Texas. Among ASOPRS members in full-time academic positions, women tended to have lower rank compared to men; however, after controlling for number of years post-fellowship, this finding was narrowly not statistically significant (p = 0.0624). There were no academic differences with URMs and nonminority groups. CONCLUSIONS: Women and URMs have increased steadily in ASOPRS, especially in recent years. Similar to the rest of ophthalmology and general medicine, there remain opportunities for ASOPRS to increase diversity.

Thrombosis of Inferior Vena Cava Diagnosed Using Point-of-Care Ultrasound After Pediatric Near-Syncope.

BACKGROUND: Venous thromboembolism (VTE) is extremely rare but under recognized in the pediatric population. Although the literature on the use of ultrasound to detect VTEs in adults is plentiful, little has been documented on its use in the pediatric population. CASE REPORT: We present a case of a healthy 16-year-old female who presented to our emergency department with 3 months of dyspnea on exertion and one episode of near-syncope. Point-of-care cardiac ultrasound identified an inferior vena cava thrombosis. Subsequent computed tomography angiography diagnosed concurrent bilateral pulmonary emboli (PE). The patient's identical twin sister presented with similar symptoms shortly thereafter and was also diagnosed with VTE and bilateral PE. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case demonstrates an instance of VTE and pulmonary embolism in twin adolescent girls. Physical examination findings, electrocardiogram, chest x-ray study, and several previous evaluations did not reveal the diagnosis. Point of care ultrasound was used to correctly diagnosis VTE and for heightened concern for a pulmonary embolism.

Withaferin a alters intermediate filament organization, cell shape and behavior.

Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects.