Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

<p>Abstract</p> <p>Background</p> <p>The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.</p> <p>Methods</p> <p>Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.</p> <p>Results</p> <p>At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).</p> <p>Conclusions</p> <p>Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.</p

The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.

Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the position that resistance is nearly inevitable, we undertook a study to identify and exploit targetable vulnerabilities that were manifest in endocrine therapy-resistant disease. Using cellular and mouse models of endocrine therapy-sensitive and endocrine therapy-resistant breast cancer, together with contemporary discovery platforms, we identified a targetable pathway that is composed of the transcription factors FOXA1 and GRHL2, a coregulated target gene, the membrane receptor LYPD3, and the LYPD3 ligand, AGR2. Inhibition of the activity of this pathway using blocking antibodies directed against LYPD3 or AGR2 inhibits the growth of endocrine therapy-resistant tumors in mice, providing the rationale for near-term clinical development of humanized antibodies directed against these proteins

Stereoacuity after small aperture corneal inlay implantation

Steven H Linn,1 David F Skanchy,2 Tyler S Quist,3 Jordan D Desautels,4 Majid Moshirfar1,5 1Department of Clinical Research, HDR Research Center, Hoopes Vision, Draper, UT, 2McGovern Medical School, The University of Texas Health Science Center at Houston, TX, 3University of Utah School of Medicine, Salt Lake City, UT, 4Tufts University School of Medicine, Boston, MA, 5John A Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA Purpose: The aim of this study was to compare stereoacuity before and after KAMRA corneal inlay implantation for the correction of presbyopia.Patients and methods: This is a prospective study of 60 patients who underwent KAMRA inlay implantation. Patients were examined before and 6 months after surgery for stereoacuity, uncorrected distance visual acuity (UDVA), and uncorrected near visual acuity (UNVA).Results: The mean stereoacuity before surgery was 29.5&plusmn;28.1 arcsec (range: 20&ndash;200) and at 6 months was 29.8&plusmn;26.4 arcsec (range: 20&ndash;200). The decline in stereoacuity was not statistically significant. At 6 months follow-up, UDVA was 20/25 or better in all 60 patients and UNVA was J2 (20/25) or better in 51 (85%) patients.Conclusion: There is no significant change in stereoacuity following KAMRA inlay implantation. The KAMRA inlay is a good treatment option for improving near vision in presbyopic patients while preserving stereoacuity and distance vision. Keywords: KAMRA, corneal inlay, AcuFocus, stereoacuity, presbyopia&nbsp

Rainbow glare after laser-assisted in situ keratomileusis: a review of literature

Majid Moshirfar,1,2 Jordan D Desautels,3 Tyler S Quist,4 David F Skanchy,5 Mark T Williams,6 Ryan T Wallace7 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, 2HDR Research Center, Hoopes Vision, Draper, UT, 3Tufts University School of Medicine, Boston, MA, 4University of Utah School of Medicine, Salt Lake City, UT, 5McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 6University of California, San Francisco School of Medicine, San Francisco, CA, 7Brigham Young University, Provo, UT, USA Abstract: This article reviews the current literature pertaining to rainbow glare (RG), including incidence rate, clinical presentation, etiology, prognosis, and management. RG is a rare optical complication of femtosecond laser-assisted in situ keratomileusis that results in patients seeing an array of spectral bands surrounding point sources of light under mesopic and scotopic conditions. The mechanism is thought to be a consequence of the formation of a transmissive diffraction grating on the posterior surface of the corneal flap created by the FS laser. RG has a good prognosis and is usually self-limiting. Persistent RG with concomitant residual refractive error may warrant lifting the flap and photoablating the posterior surface of the flap. Patients with persistent RG and no residual refractive error should be considered candidates for phototherapeutic keratectomy on the posterior flap surface. Keywords: rainbow glare, femtosecond, LASIK, keratomileusis, phototherapeutic keratectom

Ectasia following small-incision lenticule extraction (SMILE): a review of the literature

Majid Moshirfar,1,2 Julio C Albarracin,3 Jordan D Desautels,1,4 Orry C Birdsong,1 Steven H Linn,1 Phillip C Hoopes Sr1 1HDR Research Center, Hoopes Vision, Draper, 2John A Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, Salt Lake City, UT, 3Department of Ophthalmology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 4Department of Ophthalmology, Warren Alpert Medical School of Brown University, Providence, RI, USA Purpose: Four cases of corneal ectasia after small-incision lenticule extraction (SMILE) have been reported. In this review, we provide an overview of the published literature on corneal ectasia after SMILE and risk factors associated with this complication.Methods: Case reports were identified by a search of seven electronic databases for pertinent heading terms between 2011 and July 2017. We identified patient characteristics and surgical details including preoperative topography, central corneal thickness, and anterior keratometry (Km). Residual stromal bed (RSB) values not reported were computed using VisuMax ReLEx SMILE software Version 2.10.10. Preoperative ectasia risk was measured using the Randleman Ectasia Risk Score System (ERSS). Percent tissue alteration was calculated for each patient as described by Santhiago et al.Results: Seven eyes of four patients developed corneal ectasia post SMILE. Two patients had abnormal topography in both eyes. One patient had abnormal topography in one eye. Only one patient was noted to have normal topography in both eyes and later developed ectasia in one eye in the absence of any known risk factors. The mean Randleman ectasia risk score was 4&plusmn;3 (range: 1&ndash;8). The mean calculated percent tissue altered (PTA) was 38%&plusmn;6% (range: 30%&ndash;47%).Conclusion: A majority of reported ectasia cases occurred in patients with subclinical keratoconus. These conditions may be exacerbated by SMILE and should be considered absolute contraindications to the procedure. Three patients were identified to have high risk based on the ERSS, and one patient exhibited a PTA &ge;40%. We formulated a modification to the current calculation of PTA that takes into account the differences in tissue altered between SMILE and laser in situ keratomileusis (LASIK). More studies are needed to fully quantify the risk of ectasia. For now, we propose adopting the same exclusion criteria used for LASIK in the SMILE procedure until more specific metrics have been validated. Keywords: SMILE, small-incision lenticule extraction, ectasia, keratoconus, percent tissue altered, Ectasia Risk Score Syste

Short-term visual result after simultaneous photorefractive keratectomy and small-aperture cornea inlay implantation

Majid Moshirfar,1,2 Ryan T Wallace,3 David F Skanchy,4 Jordan D Desautels,5 Steven H Linn,1 Phillip C Hoopes Jr,1 Daniel S Durrie1,6 1Hoopes, Durrie, Rivera, Research Center, Hoopes Vision, Draper, UT, 2Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, 3Brigham Young University, Provo, UT, 4McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 5Tufts University School of Medicine, Boston, MA, 6Durrie Vision, Overland Park, KS, USA Purpose: To report the short-term results of simultaneous photorefractive keratectomy (PRK) and small-aperture cornea inlay implantation (KAMRA) surgery in treating presbyopia. Methods: Simultaneous PRK and KAMRA inlay surgery was performed on 21 patients from July 2015 to March 2016. Follow-up exams were conducted at 1, 3, and 6&nbsp;months postoperatively. Our patients were also divided preoperatively into three categories: myopic, hyperopic, and emmetropic. Over the 6-month period, the main outcome measures were uncorrected near visual acuity (UNVA), changes in best-corrected distance visual acuity, and mean spherical equivalent refraction. Results: At 6-month follow-up, 83% (10/12) of patients had a monocular UNVA of 20/40 or better, and 75% had a binocular UNVA of 20/40 (J5) or better. At 6&nbsp;months, the overall mean refractive spherical equivalent (MRSE) was -0.60&nbsp;D (&plusmn;0.42 standard deviation [SD], range:&nbsp;-1.38 to -0.13) with a mean change of -0.43&nbsp;D (&plusmn;1.19 SD, range: -1.5 to 2.63) compared to preoperative&nbsp;data. Overall, 91% (10/11) of patients were within a &plusmn;0.5&nbsp;D range of our target&nbsp;-0.75&nbsp;D for KAMRA use. One-hundred percent (5/5) of the hyperopes, 50% (1/2) of emmetropes, and 100% (4/4) of myopes met the targeted range. At 6&nbsp;months, the MRSE for the hyperopic subgroup (n=5) was 0.33&nbsp;D (&plusmn;0.20 SD), the MRSE for the emmetropic subgroup (n=2) was -1.19&nbsp;D (&plusmn;0.19&nbsp;SD), and the MRSE for the myopic subgroup (n=4) was -0.66&nbsp;D (&plusmn;0.36 SD). Conclusion: Based on preliminary results and a small sample size, it seems that simultaneous PRK and KAMRA is effective and predictable. There are multiple advantages in performing simultaneous PRK and KAMRA including a shorter recovery time and less steroid use than the two surgeries performed separately. Keywords: KAMRA, PRKamra, PRK, femptosecond, corneal, presbyopi

Long-term changes in keratometry and refraction after small aperture corneal inlay implantation

Majid Moshirfar,1,2 Jordan D Desautels,1,3 Brian D Walker,4 Orry C Birdsong,1 David F Skanchy,4 Tyler S Quist,5 Michael S Murri,6 Steve H Linn,1 Phillip C Hoopes Jr,1,2 Phillip C Hoopes1,2 1Hoopes, Durrie, Rivera Research Center, Hoopes Vision, Draper, UT, USA; 2John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, School of Medicine, University of Utah, Salt Lake City, UT, USA; 3The Warren Alpert Medical School, Brown University, Providence, RI, USA; 4McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; 5Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA; 6Baylor College of Medicine, Houston, TX, USA Purpose: To assess longitudinal refractive, keratometric, and topographic changes following KAMRA small-aperture inlay implantation.Design and setting: Prospective study at a single site refractive surgery center.Methods: Fifty patients underwent KAMRA small-aperture corneal inlay implantation for the correction of presbyopia. Uncorrected near visual acuity (UNVA), uncorrected distance visual acuity, manifest refractive spherical equivalent (MRSE), mean keratometry (Km), corneal topography, and surgically induced astigmatism vector analysis assessments were performed preoperatively and at 1, 3, 6, 12, 24, and 36 months postoperatively.Results: The study comprises 50 eyes. An average shift of 0.15&plusmn;0.63 D (range -1.63 to 2.00 D) occurred between preoperative baseline and 36 months. At 36 months, 54% of patients had hyperopic MRSE and 40% had myopic MRSE compared with baseline. Km was significantly elevated at all postoperative measurements compared with baseline, with the largest Km measured at 12 months. Eighty-six percent of patients had UNVA of 20/32 or better and 88% uncorrected distance visual acuity of 20/25 or better at 36 months. Longitudinal corneal topography revealed a pattern of corneal steepening over the body of the inlay and flattening over the aperture, correlating with a hyperopic shift. There was no significant surgically induced astigmatism.Conclusion: KAMRA inlay may cause an increase in Km compared with baseline. Corneal steepening may occur in a specific pattern with steepening over the inlay and flattening over the aperture. This topographic pattern causes a hyperopic shift, which may be relevant for subsequent procedures, such as cataract extraction. Keywords: presbyopia, KAMRA, wound healing, IOL calculatio

ImmunoChip Study Implicates Antigen Presentation to T Cells in Narcolepsy

Contains fulltext : 118596.pdf (publisher's version ) (Open Access)Recent advances in the identification of susceptibility genes and environmental exposures provide broad support for a post-infectious autoimmune basis for narcolepsy/hypocretin (orexin) deficiency. We genotyped loci associated with other autoimmune and inflammatory diseases in 1,886 individuals with hypocretin-deficient narcolepsy and 10,421 controls, all of European ancestry, using a custom genotyping array (ImmunoChip). Three loci located outside the Human Leukocyte Antigen (HLA) region on chromosome 6 were significantly associated with disease risk. In addition to a strong signal in the T cell receptor alpha (TRA@), variants in two additional narcolepsy loci, Cathepsin H () and Tumor necrosis factor (ligand) superfamily member 4 (, also called ), attained genome-wide significance. These findings underline the importance of antigen presentation by HLA Class II to T cells in the pathophysiology of this autoimmune disease

Development of obesity in transgenic mice after genetic ablation of brown adipose tissue.

Brown adipose tissue, because of its capacity for uncoupled mitochondrial respiration, has been implicated as an important site of facultative energy expenditure. This has led to speculation that this tissue normally functions to prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically have been uninformative because it exists in diffuse depots and has substantial capacity for regeneration and hypertrophy. Here we have used a transgenic toxigene approach to create two lines of transgenic mice with primary deficiency of brown adipose tissue. At 16 days, both lines have decreased brown fat and obesity. In one line, brown fat subsequently regenerates and obesity resolves. In the other line, the deficiency persists and obesity, with its morbid complications, advances. Obesity develops in the absence of hyperphagia, indicating that brown fat deficient mice have increased metabolic efficiency. As obesity progresses, transgenic animals develop hyperphagia. This study supports a critical role for brown adipose tissue in the nutritional homeostasis of mice