Use Of Antimetabolites Research Articles

Effective Strategy to Prevent Acute Graft-Versus-Host Disease in Unrelated Donor Allogeneic Hematopoietic Cell Transplants By Using a Combination of Anti-Thymocyte Globulin (ATG), Post-Transplant Cyclophosphamide and Cyclosporine

Introduction:Acute Graft-versus-Host Disease (aGVHD) is a frequent complication of Allogeneic Hematopoietic cell transplants (allo-HCT); aGVHD, especially Grade III-IV, can be lethal with increased morbidity and mortality and can occur in upto 40-50% of allo-HCT. GVHD prophylaxis has been used for control of GVHD, with use of calcineurin inhibitors, anti-metabolites and anti T cell antibodies. Use of Post-transplant Cyclophosphamide (PTCy) has recently been used extensively in haplo-identical transplant setting with promising results. However, PtCy has mainly been used in patients with BM as the stem cell source. In those patients with PBSC as the stem cell source, alone PTCy has been associated with clinically significant acute and chronic GVHD. As most of our patients use PBSC as the graft source, we hypothesized to combine both ATG and PTCy to reduce incidence of both acute and chronic GVHD in our patient cohort. Here we present a small cohort data using a combination of all these agents to effectively reduce aGVHD in hematological malignancies..Methods:A total of 28 patients with hematological malignancies, who had an unrelated donor underwent allo-HCT at our center from 1 Oct 2015 to 31 Mar 2016. The characteristics of the patients are summarized in Table 1. The conditioning regimen was either myeloablative (MAC, namely FBT400) or Reduced Intensity (RIC, namely FBT200) in patients with age ≤ 60 and >60 years, respectively. After interim analysis when increased non-hematological toxicity was observed in the MAC arm, all patients subsequently received FBT 200 conditioning. Peripheral blood was used as the stem cell source in all patients. Filgrastim was used from day +7 onwards for 13 patients. Special emphasis was given to incidence of acute GVHD, infections, regimen related toxicities and engraftment.Results:Out of total of 28 patients, aGVHD was seen in only 6 (21.4%) patients, five of which had skin involvement (Grade I-II) and one suspected liver involvement (Grade III), all of which responded rapidly to steroids. However, we did observe increased toxicities such as sinusoidal obstruction syndrome (32%), bacterial infections (68%) and viral infections (46%; CMV reactivations in 64%). Primary disease relapse, secondary graft failure and EBV reactivations were seen in 10% of cases, with documented Post Transplant Lymphoproliferative Disorder (PTLD) in only 2 patients. The overall survival of the entire cohort was 67.8% with a median duration of 6 months (range; 3-8 months). In comparison to MAC, RIC regimen was found to be superior with no Gr III-IV aGVHD, less toxicity and improved survival (RIC-82% vs MAC-45%).Conclusions: Combination of ATG-PTCy-CsA is an effective strategy to reduce aGVHD in unrelated donor transplants, albeit with moderate increase in toxicities. RIC with this combination was associated with less organ damage and superior survival. However, a long term follow up is needed to assess relapse and cGVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Glaucoma Surgery Outcome in Rwanda.

To assess long-term intraocular pressure (IOP) outcome after adult trabeculectomy surgery in Central Africa. All adult glaucoma patients who underwent trabeculectomy surgery in the Kabgayi Eye Unit, Rwanda between August 2003 and March 2008 were invited for a follow-up visit. Surgical and clinical data were collected from medical records. At the study visit, best-corrected visual acuity was measured and Goldmann applanation tonometry and biomicroscopy were done. Good IOP outcome was defined as both an IOP<21 mm Hg and achieving ≥30% reduction from the preoperative IOP. Considering first operated eyes, univariate and multivariate logistic regression was used to investigate risk factors for failure. Of 163 individuals operated 3 had died, 118 (74%) participated. Preoperatively, the mean IOP was 31 mm Hg (SD=11; range, 12 to 60). At the time of the follow-up study visit the mean postoperative IOP was 13 mm Hg (SD=5; range, 4 to 35). Good IOP outcome was achieved in 132 eyes (84%). Univariate analysis suggested a protective effect against failure of use of antimetabolites [odds ratio (OR)=0.39; 95% confidence interval (CI), 0.14-1.11; P=0.07] and a decrease in success with length of follow-up (OR=3.57; 95% CI, 1.09-12.50; P=0.03). The latter remained borderline significant with multivariate analysis. Seven eyes went from previously better vision (at least hand movements) down to perception of light or no perception of light after trabeculectomy. Particularly a flat anterior chamber in the first postoperative week (OR=0.07; 95% CI, 0.01-0.49; P<0.001) and late hypotony (OR=0.04; 95% CI, 0.002-0.99; P=0.004) were significant risk factors for severe visual loss. Trabeculectomy with antimetabolites is one of the best available options for glaucoma management in Africa. However, the IOP control reduced at a follow-up duration beyond 2 years, highlighting the importance of regular long-term follow-up.

Secondary Epiretinal Membrane After Trabeculectomy.

To determine the frequency of epiretinal membranes (ERM) in eyes with primary open-angle glaucoma subjected to trabeculectomy. We conducted a retrospective study on patients subjected to trabeculectomy with at least a 6-month follow-up. Ophthalmologic examination and spectral-domain optical coherence tomography (SD-OCT) were analyzed. Eyes with previous surgical or laser treatments or other pathologies (other than glaucoma and ERM) were excluded. A total of 50 eyes (40 patients) were included in this study. The mean follow-up time after surgery was 27.8 months. After surgery, 9 eyes (18%) had preretinal macular fibrosis and 19 eyes (38%) had cellophane macular reflex. Of the 16 eyes with a preoperative macular SD-OCT, 3 (18.8%) developed ERM and 4 (25%) progressed from cellophane macular reflex to preretinal macular fibrosis, after surgery. The ERM frequency did not differ significantly between eyes subjected to trabeculectomy with or without the use of antimetabolites (P=0.08), or between eyes subjected to simple or combined surgery (phacotrabeculectomy) (P=0.09). Trabeculectomy may predispose one to the appearance and progression of ERM. Further studies are needed to clarify this intriguing relation.

Early Predictors of Long-term Outcomes of HCV-negative Liver Transplant Recipients Having Survived the First Postoperative Year.

The non-improvement in >1-year post-liver transplant (LT) survival and diminishing importance of hepatitis C (HCV) with modern antivirals justify identification of early factors predictive of long-term outcome post-LT in HCV-negative recipients. This nationwide study included all 631 HCV-negative adult patients transplanted in Finland 1982-2013 with at least 1-year graft survival (6311 person-year follow-up). We tested 37 variables, including immunosuppression, for their association with >1-year combined graft loss/mortality, late rejection, cancer, or infections. Significant multivariate predictors of graft loss/mortality were male gender (HR 2.40, P = 0.001), pretransplant hepatocellular (HR 2.92, P = 0.001) or biliary cancer (HR 12.7, P < 0.001), glomerular filtration rate (HR 0.89, P = 0.002), hypertension (HR 0.44, P < 0.001), early posttransplant infections (HR 1.52-1.67, P = 0.007-0.03), and alkaline phosphatase (ALP) (HR 1.05, P < 0.001). Elevated ALP at 1 year, affecting 30% of patients, predicted both graft loss and rejection, independent of immunologic stability, etiology, and immunosuppression type. Area under the curve of ALP in predicting graft loss from rejection was 0.81 (95% CI 0.71-0.90) and 0.85 (95% CI 0.72-0.98, P = 0.001) among patients under 50. Among immunologically stable patients who underwent transplantation after 2000, antimetabolite use at 1 year was associated with improved survival (P = 0.04), specifically in the subgroup with native-liver hepatocellular or biliary cancer (P = 0.02). Easily measurable, widely available, and noninvasive factors known at 1 year post-LT can help stratify patients according to their long-term risk of death or graft loss, and thus facilitate a personalization of long-term follow-up. ALP deserves routine monitoring, and the cause for an elevated ALP should be sought.

Pattern and outcome of conjunctival surgeries in jos university teaching hospital, Jos, Nigeria

Objective: To assess the output, pattern, and outcome of conjunctival surgeries in Jos University Teaching Hospital over a 7‑year period. Methodology: The minor ophthalmic surgical records of the hospital were retrospectively reviewed to obtain information on patients who had conjunctival surgery. These included patients’ demographics, diagnosis, indications and types of surgery, type of anesthesia, histology report, and outcome. The data were analyzed using Epi Info statistical software version 3.4, Atlanta, Georgia, USA. Results: A total of 155 patients and 187 eyes were operated upon; 73 (47.1%) males and a mean age of 39.9 years (standard deviation: 15). Pterygium excision accounting for 104 (55.6%), excisional biopsy 58 (31.0%), and conjunctival flap in 14 eyes (7.5%) were the most common procedures. There was an increase in the proportion of patients who had pterygium surgery with increasing age ( X 2 = 19.6, P < 0.001). Pterygium excision also remained the most common conjunctival surgery over the 7‑year period with an annual average of 55.1% ( X 2 = 8.4, P < 0.001). Most pterygium excision 91 (87.5%) were performed using the bare sclera technique with a 31.6% recurrence rate. The most common conjunctival neoplasia was squamous cell carcinoma 7 (58.3%) and squamous cell papilloma 3 (25%). Conclusion: Over half of conjunctival surgeries were pterygium excisions mostly performed using the bare sclera method with a significant recurrent rate; hence, the need for modifications which includes the use of antimetabolites and conjunctival autograft. Keywords: Conjunctiva, outcome, surgery

Prognostic factors for trabeculectomy failure in a Cuban population

ObjectiveTo identify the prognostic factors for mid-term trabeculectomy failure. MethodA prospective cohort study was conducted on 113 eyes (113 patients) that had undergone a trabeculectomy for primary open or closed angle, pigmentary, or juvenile glaucoma. Surgical failure was defined if intraocular pressure was equal or more than 18mmHg with medication (two or more drops), after 1–4 postoperative years. The relative risk was calculated and a logistic regression analysis was performed. ResultsPrevious trabeculectomy, preoperative intraocular pressure ≥31mmHg, black race, and advanced glaucoma increased the failure risk by 7.9 times (p=.036), 5.3 times (p=.011) and 4.7 times (p=.028, and p=.027), respectively. The addition of two or more factors increased the risk by 6.4 times (p<.001). It was not affected by age, sex, pre-operative drops, or surgical complication. ConclusionsPrevious trabeculectomy, pre-operative intraocular pressure ≥31mmHg, black race, and advanced glaucoma are prognostic factors for trabeculectomy failure, in decreasing order of their association with surgical failure. The addition of two or more factors increased the risk of failure. In those situations, the use of trans-operative anti-metabolites is suggested.

Eye Whitening Using Subconjunctival Injections

Introduction: Recent reports have alerted medical providers about the danger of certain eye whitening procedures that involve a combination of removing generous areas of conjunctiva, cautery, laser, and the later use of antimetabolites. This case report describes an alternative technique using subconjunctival injections. This novel procedure may avoid risks associated with previously described techniques. Materials and Methods: The subconjunctival space was entered and lidocaine 2% with epinephrine was injected. White tattoo ink was then injected into the subconjunctival space and spread throughout with external pressure. The patient was observed as to the appearance, longevity, and tolerance of the ink as well as possible side effects. Results: The ink could be spread easily throughout the eye in a homogeneous fashion and remained visibly apparent throughout the observation period. The patient reported mild transient tearing, light sensitivity, and seepage of ink during the first 5 days, but it quickly abated after that time period. Visual acuity, intraocular pressure, and corneal appearance were unchanged throughout the observation period. The appearance of the eyes postoperatively was consistent for 24 months. Conclusions: The technique of using subconjunctival injections as a means to whiten eye appearance is feasible and avoids the risks associated with previously used techniques.

Combined trabeculotomy-trabeculectomy with antimetabolite and releasable suture: outcome with primary congenital glaucoma in a north Indian population.

To determine the surgical outcomes of combined trabeculotomy- trabeculectomy with mitomycin-C and releasable suture in children with primary congenital glaucoma (PCG) in a North Indian population. Retrospective, interventional, consecutive, non-comparative case series. The medical records of 137 eyes of 77 patients who underwent combined trabeculotomy- trabeculectomy with 0.2 mg/ml mitomycin C (MMC) either bilaterally (49 patients) or unilaterally (28 patients) between January 2004 and March 2012 were reviewed retrospectively. The main outcome measures were postoperative intraocular pressures, corneal clarity and diameter, duration of follow-up, success rate and complications. The mean preoperative intraocular pressure reduced from 34 ± 7 mm Hg (range 15- 54 mm Hg) to 17 ± 7 mm Hg (range 5 - 32 mm Hg) with a mean reduction of 44 % (P less than 0.001). The mean follow-up period was 24.4 ± 10.3 months (range 6 - 48 months). Complete success defined as intraocular pressure less than 21 mm Hg without any medication and clinically stable glaucoma at last follow-up was achieved in 113 eyes (83 %) while a 'qualified success' of intraocular pressure less than 21 mm Hg with one medication was achieved in ten eyes (7 %). The Kaplan-Meier survival analysis revealed success rates (at 'n' months) of 90 % (6), 85 % (12), 82 % (24), 80 % (36) and 77 % (48). There were no significant intraoperative or postoperative complications. Primary combined trabeculotomy-trabeculectomy with mitomycin-C and releasable suture offers a viable surgical option in Northern Indian infants with primary congenital glaucoma. The use of 0.2 mg/ml mitomycin C for 2 minutes improves the overall success while the releasable suture decreases the risk of postoperative complications especially associated with the use of antimetabolites.

Mitomycin-C in dacryocystorhinostomy: From experimentation to implementation and the road ahead: A review.

Dacryocystorhinostomy (DCR) is the procedure of choice in patients with epiphora due to primary acquired nasolacrimal duct obstruction. The evolution of surgical tools, fiber-optic endoscopes, effective anesthesia techniques, and the adjunct use of antimetabolites intraoperatively; namely mitomycin-C (MMC) have significantly contributed to the advancement of DCR surgery. MMC is a systemic chemotherapeutic agent derived from Streptomyces caespitosus that inhibits the synthesis of DNA, cellular RNA, and protein by inhibiting the synthesis of collagen by fibroblasts. Even the cellular changes in the human nasal mucosal fibroblasts induced by MMC at an ultrastructural level have been documented. There, however, seems to be a lack of consensus regarding MMC: The dosage, the route of delivery/application, the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery. In this review, an attempt is made to objectively examine all the evidence regarding the role of MMC in DCR. MMC appears to improve the success rate of DCR.

Outcome of surgical treatment of primary and secondary glaucoma in young children.

To describe a paediatric cohort surgically treated for primary or secondary glaucoma (PG/SG), with regard to incidences, visual outcome and control of intraocular pressure (IOP). All children (n = 29, 42 eyes in total) surgically treated for PG or SG at the age of 4 years or younger between January 2002 and December 2010 at Sahlgrenska University Hospital in Mölndal were retrospectively studied through medical records. Median follow-up time after initial surgery was 5.9 years (range 2.4-11.2 years). The incidence of primary congenital glaucoma was 4.3 cases per 100 000 live births in the county of Västra Götaland. For glaucoma secondary to cataract surgery, the incidence was 13% with a median postoperative duration to diagnosis of glaucoma of 3.8 months (range 1.6 months to 4.3 years). Preoperative mean IOP was 31.5 (SD 8.1) mmHg, and mean IOP at last visit was 17.1 (SD 4.4) mmHg. For the entire cohort, 30% of the glaucoma eyes required more than two IOP-lowering surgical procedures during the study period. BCVA was ≥0.3 (decimal) in 45% of glaucomatous eyes at last follow-up with no statistically significant difference between PG and SG. Analysis of functional visual outcome, that is BCVA in the better eye, showed that 83% of all patients attained a BCVA of ≥0.5. The incidences and outcome of surgically treated paediatric glaucoma were in accordance with previous studies. Chamber angle surgery, and if necessary, tube implantation without the use of antimetabolites, is a favourable approach leaving most sites needed for future glaucoma surgery unaffected.

Novel Developments in the Use of Antimetabolites

Antimetabolites are the most widely used and most efficacious group of anticancer drugs. Antimetabolites are also the oldest rationally designed anticancer drugs, targeted against RNA and DNA, and can, therefore, be considered as the first generation of targeted drugs. Unfortunately, resistance often develops, leading to the design of new antimetabolites, which either have a novel mechanism of action, bypass resistance or in combination enhance the effect of other drugs, such as another antimetabolite, other DNA, or protein kinase targeted anticancer drugs. Several novel antimetabolites are in clinical development. The cytidine-analog fluorocyclopentenylcytosine (RX-3117) is active in gemcitabine-resistant tumors and is activated by uridine-cytidine-kinase, can be incorporated into RNA and DNA and can downregulate DNA-methyltransferase-1. TAS-114 is a new generation dUTPase inhibitor. dUTPase normally prevents incorporation of dUTP and of the 5FU-nucleotide FdUTP into DNA. However, inhibition of dUTPase will enhance their incorporation, thereby increasing thymine-less cell-death. The formulation TAS-102 (trifluorothymidine and thymidine-phosphorylase-inhibitor) acts by incorporation into DNA and has shown efficacy in tumors progressing on 5FU therapy. Gemcitabine and cytarabine prodrugs were tested in model systems and have entered clinical evaluation. The elaidic-acid prodrugs of gemcitabine (CP-4126, CO101) and cytarabine (elacytarabine) failed in randomized Phase III studies. Two other gemcitabine prodrugs LY2334737 (gemcitabine with a valproic acid at the 5′-position) and NUC1031 (a 5′-arylphosphoamidate prodrug, with a side-chain at the 5′-phosphate) are in early clinical development.In summary, several novel antimetabolites show promise in clinical development, either because of a novel mechanism of action, or clever combination or by innovative prodrug design.

Everolimus With Reduced Tacrolimus in Liver Transplantation

Everolimus With Reduced Tacrolimus in Liver Transplantation

Long-Term Outcomes of Lung Transplantation (LT) in Hepatitis C Positive (HCV+) Patients

Purpose Long term outcomes of LT in HCV + recipients is not known. We report our findings in this unique cohort of patients. Methods and Materials Retrospective chart review of all LT recipients from 1990 to 2011 was performed to identify HCV + prior to LT. Demographic data, HCV RNA load pre & post LT, liver biopsy, and hepatic malignancy, antimetabolite use, BOS and survival was collected. Results 11 patients were identified as having HCV + status out of 1165 patients. 8/11 (4 male) had a positive HCV qualitative RNA PCR, [Mean age±SD] 49.25±9.22; 2/8 patients received antiviral therapy pre LT. HCV Genotype was identified in 5/8 patients, HCV genotype 1 [n=3] & HCV genotype 2 [n=2]. CT scan of abdomen in all patients showed cirrhosis but no portal hypertension. All patients underwent a liver biopsy prior to LT. [Minimal periportal fibrosis – 7, no cirrhosis – 8, granulomatous hepatitis - 1]. The median duration from HCV diagnosis to transplantation was 4.25 years [range 0.6 – 12]. The pre LT median quantitative HCV RNA level was 50,000 IU/ml. Post LT median quantitative HCV RNA levels increased [34,950 to 2,755,000 IU/ml] without an associated increase in the liver function tests. The post LT immunosuppression included calcineurin inhibitor + prednisone but only 3 patients were on an antimetabolite. Median survival for this group was 4.5 years post LT with the longest survival 10 years post transplant. Causes of death included BOS, lung cancer, and sepsis but no patient died of progressive liver disease. The average survival at 1, 3, & 5 years post LT was 75%, 62.5%, and 50%. Conclusions HCV + patients can successfully undergo LT and achieve comparable survival to non HCV + status. Viral loads after transplant will increase but is not associated with worsening liver function or outcomes. BOS still remains the leading cause of death in this population long term.

Immunosuppressive treatment of idiopathic membranous nephropathy: the dilemma continues

Idiopathic membranous nephropathy(IMN) is one of the most common causes of nephrotic syndrome (NS) in adults and may progress to end-stage renal disease(ESRD). Given the variable course, it remains unclear who to treat with immunosuppression(IS) and with what regimen. Corticosteroids, alkylating agents, calcineurin inhibitors (CNIs), and antimetabolities have all been used in randomized controlled trials (RCTs). Previous meta-analyses of these trials were unable to demonstrate a benefit on death or progression to ESRD compared to no treatment or placebo. Since the last round of these analyses (in 2004) additional RCTs have been published. The Cochrane Central Register of Controlled Trials and Medline were searched from 2003 until February 2012 for new RCTs in the treatment of IMN to update the database. Twelve trials were found. Due to significant heterogeneity of patients and regimens, they are discussed qualitatively only and are integrated with prior RCTs and relevant observational data. In conclusion, patients with non-nephrotic proteinuria should not be offered IS therapy. Those with NS and declining renal function should be treated. The best evidence supports a combined steroid and alkylating agent regimen. Calcineurin inhibitors clearly produce short-term benefit (proteinuria reduction and remission) but their ability to favorably affect death or ESRD remains unproven. There is little support for antimetabolite use. Other agents (rituximab and adrenocorticotropin) require further study. For the large group of patients with NS but normal renal function it remains a dilemma who to treat and with regimen.

Vision‐related quality of life in patients with birdshot chorioretinopathy

Dear Editor, Birdshot chorioretinopathy (BSCR) is a potentially blinding chronic form of bilateral posterior uveitis. Despite intensive anti-inflammatory therapies, patients may exhibit a slow decline in visual functioning including the central visual acuity and contrast sensitivity (Shah et al. 2005). Here, we ascertain the vision-specific quality of life (QOL) in patients with BSCR and study the associations between QOL and treatment modalities. The study was performed in accordance with the Declaration of Helsinki and with the approval of the local institutional review board. We included 127 consecutive patients with BSCR from the department of ophthalmology of the University Medical Centre Utrecht and the Eye Hospital Rotterdam, the Netherlands. Diagnosis was based on research criteria established by an international consensus conference (Levinson et al. 2006) and included fluorescein angiography. All included patients were HLA-A29 positive. The Dutch translation of the NEI Visual Function Questionnaire (VFQ)-25 was sent to all subjects (Mangione et al. 2001). A total of 105 (83%) patients (median age 59.5; range 28–83 years) completed questionnaires, which were returned after obtaining informed consent. The reasons for not responding included death (n = 4) or no interest in participation (n = 18). Gender, age, duration of uveitis, previous treatment and best-corrected visual acuity (BCVA) were registered for all subjects (mean binocular visual acuity; LogMAR 0.82 ± 0.24; range 0.05–1.0). Previous treatment was divided into three groups: (i) no systemic treatment (26 patients, 25%), (ii) systemic corticosteroids, but no other immunosuppressive drugs (15 patients, 14%), and (iii) immunosuppressive drugs occasionally in combination with systemic corticosteroids (64 patients, 61%). A p-value of 0.0045 or less was accepted as indicating statistical significance, using Bonferroni correction. The median NEI VFQ-25 composite score for patients with BSCR was 75.9, and median subscale scores ranged from 60 for general health to 91.7 for social functioning and dependency (Table 1). There was no difference in NEI VFQ-25 composite or subscales scores between the various treatment categories (Kruskal–Wallis test, p = 0.473). The composite scores were related to BCVA (Spearman correlation, p = 0.003), but not related to age (p = 0.6) or duration of uveitis (p = 0.8). The BCVA was not different between the treatment categories (p = 0.289). All correlations between the NEI VFQ-25 subscale scores and BCVA were significant, except for ocular pain (p = 0.878). BSCR has a high impact on vision-related QOL. VFQ-25 scores were associated with visual acuity, but no difference in VFQ-25 scores or BCVA was observed among the different treatment regimens and between treated and not treated patients. Our NEI VFQ-25 subscale score results are in the same range of those found in a previous cohort of BSCR (Levinson et al. 2009) and a recent study of vision-related QOL in noninfectious ocular inflammatory disease (Qian et al. 2012). The authors of the latter study stated that low composite VFQ-25 score was a predictor of depression, which they found was associated with the use of corticosteroids and antimetabolites. In this study, we did not assess depression specifically; however, the median composite and mental health scores were lower in the group of patients treated with systemic corticosteroids compared with the other groups (Table 1). The design of our study does not allow the evaluation of specific treatment efficacy because the treatment regimens were not random. Future randomized studies on the effect of different immunosuppressive treatment regimes and visual outcomes in BSCR are warranted.

Decreasing Colectomy Rates for Ulcerative Colitis: A Population-Based Time Trend Study

Colectomy rates for ulcerative colitis (UC) have been inconsistently reported. We assessed temporal trends of colectomy rates for UC, stratified by emergent vs. elective colectomy indication. From 1997 to 2009, we identified adults hospitalized for a flare of UC. Medical charts were reviewed. Temporal changes were evaluated using linear regression models to estimate the average annual percent change (AAPC) in surgical rates. Logistic regression analysis compared: (i) UC patients responding to medical management in hospital to those who underwent colectomy; (ii) UC patients who underwent an emergent vs. elective colectomy; and (iii) temporal trends of drug utilization. From 1997 to 2009, colectomy rates significantly dropped for elective colectomies with an AAPC of -7.4% (95% confidence interval (CI): -10.8%, -3.9%). The rate of emergent colectomies remained stable with an AAPC of -1.4% (95% CI: -4.8%, 2.0%). Azathioprine/6-mercaptopurine prescriptions increased from 1997 to 2009 (odds ratio (OR)=1.15; 95% CI: 1.09-1.22) and infliximab use increased after 2005 (OR=1.68; 95% CI: 1.25-2.26). A 13% per year risk adjusted reduction in the odds of colectomy (OR=0.87; 95% CI: 0.83-0.92) was observed in UC patients responding to medical management compared with those who required colectomy. Emergent colectomy patients had a shorter duration of flare (<2 weeks vs. 2-8 weeks, OR=5.31; 95% CI: 1.58-17.81) and underwent colectomy early after diagnosis (<1 year vs. 1-3 years, OR=5.48; 95% CI: 2.18-13.79). From 1997 to 2009, use of purine anti-metabolites increased and elective colectomy rates in UC patients decreased significantly. In contrast, emergent colectomy rates were stable, which may have been due to rapid progression of disease activity.

Use of Antimetabolites in the Reconstruction of Severe Anophthalmic Socket Contraction

The use of antimetabolites is well established in ophthalmology with expanded uses still being defined. We describe our experience of antimetabolite use in the reconstruction of severe anophthalmic socket contraction. Nonrandomized, retrospective case series. The medical records and clinical photographs of 5 patients with severe socket contraction were reviewed. Either 5-Fluorouracil (5-FU) (50 mg/ml) or Mitomycin C (MMC) (0.4 mg/ml) was used during the course of the surgery via direct injection into the operative bed in the area of scarring. In addition, in 3 cases, 5-FU was also applied after surgery, in the clinic setting. Variables examined included: number of previous socket operations; preoperative ability to retain a prosthesis; type of socket reconstruction; type, amount, and location of antimetabolite injected; number of postoperative injections; average follow-up; and the postoperative ability to retain a prosthesis. All 5 patients had multiple operations previously. After surgery, all 5 were able to retain an ocular prosthesis. We did not observe any delay in wound healing, implant exposure, or extrusion, and no significant side effects were noted. The use of adjunct antimetabolite in severe anophthalmic socket reconstruction is an effective option that is well tolerated with minimal side effects.

Treatment of new‐onset ulcerative colitis and ulcerative proctitis: a retrospective study

Although guidelines recommend use of oral 5-aminosalicylates (5-ASAs) as first-line therapy in patients with mild to moderate ulcerative colitis (UC) and ulcerative proctitis (UP) and steroids with or without 5-ASAs in those more severely ill, little is known about how UC and UP are actually treated. To document treatment of new-onset UC and UP in routine clinical practice. Using a large US health insurance database, we identified all persons with new-onset UC or UP between 1 January 2005 and 31 December 2007, based on: (i) initial receipt of an oral 5-ASA, mesalazine (mesalamine) suppository, 5-ASA enema, steroid, antimetabolite, budesonide or TNF inhibitor; (ii) sigmoidoscopy/colonoscopy in prior 30days resulting in a new diagnosis of UC or UP and (iii) no prior encounters for Crohn's disease. We examined patterns of pharmacotherapy over 1year. We identified 1516 UC patients and 636 UP patients who met study entry criteria. In UC, initial therapies most frequently used were oral 5-ASAs (53% of patients), oral 5-ASAs and systemic steroids (12%), systemic steroids (8%) and mesalazine suppositories (6%); in UP, mesalazine suppositories (42%) and oral 5-ASAs (19%) were most often used, followed by combination therapy (14%), mesalazine enema(11%) and rectal steroids (10%). Few patients received maintenance therapy, and there was limited use of antimetabolites and biological agents. Oral 5-ASAs and systemic steroids are the mainstay of treatment in patients with new-onset ulcerative colitis; in those with new-onset ulcerative proctitis, it is mesalazine suppositories. Care of these patients appears consistent with treatment guidelines.

Prospective study of surgical outcomes and bleb morphology using indocyanine green as a surgical dye in trabeculectomy with mitomycin C

To investigate the effect of adding indocyanine green to mitomycin C in augmented trabeculectomy. A prospective, non-comparative interventional case series. A total of 37 eyes of 37 patients followed up for 1 year. A solution containing 12.5 mg/mL of indocyanine green was added to mitomycin C, resulting in an mitomycin C concentration of 0.2-0.4 mg/mL, which was applied to bare sclera and Tenon's capsule for 3 min during trabeculectomy. Visual acuity, intraocular pressure, bleb morphology, Moorfields Bleb Grading System scores and complications. Indocyanine green could be visualized on clinical examination for all eyes on the first postoperative day. Mean intraocular pressure decreased from 22.9 ± 6.2 mmHg to 12.1 ± 4.4 mmHg postoperatively (P < 0.001) at 1 year. Thirty-four eyes (91.9%) achieved an intraocular pressure of less than 21 mmHg at final visit without additional topical intraocular pressure-lowering medications. Three eyes (8.1%) developed bleb failure and required Baerveldt device implantation. There were no cases of blebitis or late bleb leak. No adverse effects attributable to indocyanine green could be identified postoperatively. The addition of indocyanine green during trabeculectomy improves the visibility of antimetabolites intraoperatively and allows for the estimation of antimetabolite treatment area intraoperatively and postoperatively. It appears to have no adverse effect on surgical outcomes and complication rates, while improving safety of antimetabolite use.

Prevention of Ocular Scarring Post Glaucoma Filtration Surgery Using the Inflammatory Cell and Platelet Binding Modulator Saratin in a Rabbit Model

Clinical RelevanceLate complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought.ObjectivesThe protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections.MethodsTwenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings.ResultsRabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity.ConclusionsTreatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective.