Pars plana vitrectomy and iris suture fixation of posteriorly dislocated intraocular lenses.

PURPOSE: To describe the outcomes of combined pars plana vitrectomy (PPV) and iris suture fixation of posteriorly dislocated intraocular lenses (IOLs). SETTING: Tertiary academic referral center. DESIGN: Retrospective noncomparative consecutive case series. METHODS: The included eyes had posteriorly dislocated IOLs and had combined PPV and iris suture fixation. The IOL dislocations amenable to surgical repair with an anterior approach were excluded. Outcome measures included improvement in corrected distance visual acuity (CDVA), induction of astigmatism, and complications. RESULTS: This study consisted of 27 consecutive cases. The mean follow-up was 6.61 months ± 8.1 (SD). The median postoperative CDVA was 20/30, and 16 of 27 eyes had stable or improved CDVA compared with baseline; 8 of the others had a shift from aphakic to pseudophakic correction. Overall, a significant myopic shift in spherical equivalent occurred after surgery, from 7.62 ± 4.38 diopters (D) to -1.33 ± 1.45 D (P < .001). Surgically induced astigmatism (SIA) assessed by comparing the difference in preoperative keratometry readings with the difference in postoperative manifest refraction cylinder adjusted to the corneal plane gave the following: 1.89 ± 1.09 D versus 1.13 ± 0.86 D, respectively (P < .001). All IOLs were stable and centered at the last follow-up; however, 1 was mildly tilted. One eye had a recurrent subluxation, and the IOL was resutured before the end of the study. No cases of endophthalmitis or retinal detachment occurred. CONCLUSION: Combined PPV and iris suture fixation of posteriorly dislocated IOLs led to stable fixation of the IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Outcomes Associated With Concurrent Iris-Sutured Intraocular Lens Placement and Subluxated Crystalline Lens Extraction.

IMPORTANCE: We have developed a novel surgical technique, to our knowledge, for the management of subluxated crystalline lenses involving preplacement of an iris-sutured posterior chamber intraocular lens (PCIOL) before pars plana vitrectomy and lensectomy. OBJECTIVE: To investigate the outcomes of eyes with subluxated crystalline lenses, predominantly a result of Marfan syndrome (14 eyes [58%]) or trauma (5 eyes [21%]), that underwent pars plana vitrectomy and lensectomy with placement of an iris-sutured PCIOL. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective, noncomparative case series of 24 eyes from 17 consecutive adult patients with surgically treated subluxated crystalline lenses presenting to the Wilmer Eye Institute at Johns Hopkins Hospital from October 6, 2006, through May 1, 2013. The mean (SD) postoperative follow-up was 24.4 (20.5) months for eyes with at least 6 months of follow-up (last date, October 13, 2014). We performed the analysis from January 21, 2014, through January 3, 2015. MAIN OUTCOMES AND MEASURES: Improvement in best-corrected visual acuity using an automated Snellen chart and induction of astigmatism for eyes with at least 6 months of follow-up (n = 18) and IOL stability during follow-up for all eyes (n = 24). RESULTS: The mean (SD) age at surgery was 49.4 (10.7 [range, 29-67]) years. We found an improvement in mean (SD [95% CI]) best-corrected visual acuity from 0.66 (0.71 [0.30-1.02]) logMAR preoperatively (Snellen equivalent, approximately 20/90; range, 20/30 to hand motions) to 0.07 (0.11 [95% CI, 0.01-0.12]) logMAR postoperatively (Snellen equivalent, approximately 20/23; range, 20/15 to 20/50). We found little change in astigmatism postoperatively (mean change, -0.1 [95% CI, -0.5 to 0.13] diopters). Postoperative complications included retinal detachment (1 eye [4%]), retained cortical fragment (1 [4%]), cystoid macular edema (2 [8%]), and IOL subluxation (3 [13%]) owing to haptic slippage within 3 months of the procedure. The overall probability of successfully achieving placement of a centered iris-sutured PCIOL in patients with follow-up of longer than 6 months (n = 18) was 100% (95% CI, 81.5%-100%). CONCLUSIONS AND RELEVANCE: Placement of iris-sutured PCIOLs at the time of subluxated lens extraction with a pars plana surgical approach yields favorable results in terms of postoperative visual outcomes and surgical complications. This technique offers an effective procedure for surgeons to use when treating clinically significant subluxated crystalline lenses.

Iris suture fixation of subluxated intraocular lenses.

PURPOSE: To assess the results of iris suture fixation of subluxated intraocular lenses. DESIGN: Retrospective study. METHODS: This was a nonrandomized chart review of eyes with subluxated intraocular lenses that underwent iris suture fixation at an academic institutional care center. Seventy-two eyes of 67 consecutive patients were included. The following cases were excluded: posterior dislocations necessitating pars plana vitrectomy; secondary implantations for aphakia; and iris suture fixation at primary cataract extraction. Main outcome measures included visual acuity improvement, surgically induced astigmatism, and postsurgical complications. RESULTS: The mean follow-up duration was 16.64 ± 24.37 months (median = 4.03 months). All patients had preoperative monocular diplopia or unstable vision attributable to the subluxated intraocular lenses, and 40.3% of them required aphakic correction. There was an overall improvement in best-corrected visual acuity from a mean preoperative logMAR 0.35 ± 0.32 (Snellen equivalent∼20/45) to logMAR 0.21 ± 0.25 (20/32, P = .001). There was no significant change in astigmatism secondary to the surgery. The mean difference in preoperative keratometry readings was 1.6 ± 1.07 diopter (D), whereas the mean postoperative manifest refraction astigmatic error (vertexed to the corneal surface) was 1.29 ± 0.92 D (P < .02). Re-subluxations occurred in 7 eyes during follow-up; the majority of these eyes underwent repeat fixation. Most (93.55%) intraocular lenses were stable and centered at the final follow-up. Glaucoma developed in 2 eyes postoperatively. CONCLUSIONS: Iris suture fixation of subluxated intraocular lenses was efficacious for the eyes included in this study, and it led to long-term stability of the intraocular lenses in 93.55% of cases.

A single institution's 26-year experience with nonfunctional pancreatic neuroendocrine tumors: a validation of current staging systems and a new prognostic nomogram.

OBJECTIVE: To validate the 2010 American Joint Committee on Cancer (AJCC) and 2006 European Neuroendocrine Tumor Society (ENETS) tumor staging systems for pancreatic neuroendocrine tumors (PanNETs) using the largest, single-institution series of surgically resected patients in the literature. BACKGROUND: The natural history and prognosis of PanNETs have been poorly defined because of the rarity and heterogeneity of these neoplasms. Currently, there are 2 main staging systems for PanNETs, which can complicate comparisons of reports in the literature and thereby hinder progress against this disease. METHODS: Univariate and multivariate analyses were conducted on the prognostic factors of survival using 326 sporadic, nonfunctional, surgically resected PanNET patients who were cared for at our institution between 1984 and 2011. Current and proposed models were tested for survival prognostication validity as measured by discrimination (Harrel's c-index, HCI) and calibration. RESULTS: Five-year overall-survival rates for AJCC stages I, II, and IV are 93% (88%-99%), 74% (65%-83%), and 56% (42%-73%), respectively, whereas ENETS stages I, II, III, and IV are 97% (92%-100%), 87% (80%-95%), 73% (63%-84%), and 56% (42%-73%), respectively. Each model has an HCI of 0.68, and they are no different in their ability to predict survival. We developed a simple prognostic tool just using grade, as measured by continuous Ki-67 labeling, sex, and binary age that has an HCI of 0.74. CONCLUSIONS: Both the AJCC and ENETS staging systems are valid and indistinguishable in their survival prognostication. A new, simpler prognostic tool can be used to predict survival and decrease interinstitutional mistakes and uncertainties regarding these neoplasms.

Improving immunization delivery using an electronic health record: the ImmProve project.

OBJECTIVE: Though an essential pediatric preventive service, immunizations are challenging to deliver reliably. Our objective was to measure the impact on pediatric immunization rates of providing clinicians with electronic health record-derived immunization prompting. METHODS: Operating in a large, urban, hospital-based pediatric primary care clinic, we evaluated 2 interventions to improve immunization delivery to children ages 2, 6, and 13 years: point-of-care, patient-specific electronic clinical decision support (CDS) when children overdue for immunizations presented for care, and provider-specific bulletins listing children overdue for immunizations. RESULTS: Overall, the proportion of children up to date for a composite of recommended immunizations at ages 2, 6, and 13 years was not different in the intervention (CDS active) and historical control (CDS not active) periods; historical immunization rates were high. The proportion of children receiving 2 doses of hepatitis A immunization before their second birthday was significantly improved during the intervention period. Human papillomavirus (HPV) immunization delivery was low during both control and intervention periods and was unchanged for 13-year-olds. For 14-year-olds, however, 4 of the 5 highest quarterly rates of complete HPV immunization occurred in the final year of the intervention. Provider-specific bulletins listing children overdue for immunizations increased the likelihood of identified children receiving catch-up hepatitis A immunizations (hazard ratio 1.32; 95% confidence interval 1.12-1.56); results for HPV and the composite of recommended immunizations were of a similar magnitude but not statistically significant. CONCLUSIONS: In our patient population, with high baseline uptake of recommended immunizations, electronic health record-derived immunization prompting had a limited effect on immunization delivery. Benefit was more clearly demonstrated for newer immunizations with lower baseline uptake.

Factors associated with pharyngoesophageal stricture in patients treated with concurrent chemotherapy and radiation therapy for oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to elucidate factors associated with pharyngoesophageal strictures after treatment for head and neck squamous cell carcinoma (SCC). METHODS: We conducted a retrospective review of patients receiving cisplatin and 5-fluorouracil chemotherapy combined with concurrent hyperfractionated radiation therapy for oropharyngeal squamous cell carcinoma. RESULTS: Strictures developed in 13 of 67 patients (19%). Strictures were associated with tumor location (tonsil vs base of tongue; p = .03), neck dissection after completion of therapy (p = .03), and the duration of treatment-induced mucositis (weeks with mucositis grade ≥2; National Cancer Institute (NCI) Common Toxicity Criteria; p < .001). Age, sex, race, tumor stage, nodal stage, American Joint Committee on Cancer (AJCC) stage, human papillomavirus (HPV) status, smoking, radiation dose, maximum severity of mucositis, amifostine use, and pretreatment swallow dysfunction were not significantly associated with stricture. In multivariate analysis, only duration of mucositis, after controlling for age, sex, and tumor location, remained highly significant (p < .01). CONCLUSION: The duration of treatment-related mucositis is an independent risk factor for stricture formation in patients with oropharyngeal SCC treated with concurrent chemotherapy and radiation therapy.

Comprehensive methylome map of lineage commitment from haematopoietic progenitors.

Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.

Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study.

Cytomegalovirus (CMV), a prevalent pathogen, causes severe disease in immunocompromised humans. However, present understanding is limited regarding the long-term clinical effect of persistent CMV infection in immunocompetent adults. The authors conducted a prospective observational cohort study (1992-2002) of 635 community-dwelling women in Baltimore, Maryland, aged 70-79 years in the Women's Health and Aging Studies to examine the effect of CMV infection on the risk of frailty, a common geriatric syndrome, and mortality in older women. The effect of baseline serum CMV antibody (immunoglobulin G) concentration on the risk of 3-year incident frailty, defined by using a 5-component measure, and 5-year mortality was examined with Cox proportional hazards models. Compared with those who were CMV seronegative, women in the highest quartile of CMV antibody concentration had a greater incidence of frailty (hazard ratio = 3.46, 95% confidence interval: 1.45, 8.27) and mortality (hazard ratio = 3.81, 95% confidence interval: 1.64, 8.83). After adjustment for potential confounders, CMV antibody concentration in the highest quartile independently increased the risk of 5-year mortality (hazard ratio = 2.79, 95% confidence interval: 1.22, 6.40). Better understanding of the long-term clinical consequences of CMV infection in immunocompetent humans is needed to guide public health efforts for this widely prevalent infection.

Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.

Induced pluripotent stem (iPS) cells are derived by epigenetic reprogramming, but their DNA methylation patterns have not yet been analyzed on a genome-wide scale. Here, we find substantial hypermethylation and hypomethylation of cytosine-phosphate-guanine (CpG) island shores in nine human iPS cell lines as compared to their parental fibroblasts. The differentially methylated regions (DMRs) in the reprogrammed cells (denoted R-DMRs) were significantly enriched in tissue-specific (T-DMRs; 2.6-fold, P < 10(-4)) and cancer-specific DMRs (C-DMRs; 3.6-fold, P < 10(-4)). Notably, even though the iPS cells are derived from fibroblasts, their R-DMRs can distinguish between normal brain, liver and spleen cells and between colon cancer and normal colon cells. Thus, many DMRs are broadly involved in tissue differentiation, epigenetic reprogramming and cancer. We observed colocalization of hypomethylated R-DMRs with hypermethylated C-DMRs and bivalent chromatin marks, and colocalization of hypermethylated R-DMRs with hypomethylated C-DMRs and the absence of bivalent marks, suggesting two mechanisms for epigenetic reprogramming in iPS cells and cancer.