bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis
Authors: Mehra Varun , Rhone Elijah , Widya Stefani , Zuckerman Mark , Potter Victoria , Raj Kavita , Kulasekararaj Austin , McLornan Donal , de Lavallade Hugues , Benson-Quarm Nana , Lim Christina , Ware Sarah , Sudhanva Malur , Malik Omar , Nicholas Richard , Muraro Paolo A , Marsh Judith , Mufti Ghulam J , Silber Eli , Pagliuca Antonio , Kazmi Majid A
Published: January 2019

Introduction

Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG.

Methods

Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records.

Results

All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events.

Conclusion

Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.
Risk of Latent Tuberculosis Reactivation After Hematopoietic cell Transplantation
Authors: Cheng Matthew P , Kusztos Amanda E , Bold Tyler D , Ho Vincent T , Glotzbecker Brett E , Hsieh Candace , Baker Meghan A , Baden Lindsey R , Hammond Sarah P , Marty Francisco M
Published: January 2019

There were no cases of tuberculosis in a cohort of 2531 patients who underwent hematopoietic cell transplantation from 2010 to 2015 after 7323 person-years of follow up (95% confidence interval [CI], 0.0–0.05 cases/100 person-years), including 29 (1.15%) patients with untreated latent tuberculosis after 89 person-years of follow-up (95% CI, 0.0–4.06 cases/100 person-years).
A Moving Lemma for Algebraic Cycles With Modulus and Contravariance
Authors: Kai Wataru
Published: January 2019

We prove a moving lemma that implies the contravariance of Bloch–Esnault’s additive higher Chow group in smooth affine schemes and that of Binda–Saito’s higher Chow group (taken in the Nisnevich topology).
Gardnerella vaginalis and Prevotella bivia Trigger Distinct and Overlapping Phenotypes in a Mouse Model of Bacterial Vaginosis
Authors: Gilbert Nicole M , Lewis Warren G , Li Guocai , Sojka Dorothy K , Lubin Jean Bernard , Lewis Amanda L
Published: January 2019

Background

Bacterial vaginosis (BV) is a common imbalance of the vaginal microbiota characterized by overgrowth of diverse Actinobacteria, Firmicutes, and Gram-negative anaerobes. Women with BV are at increased risk of secondary reproductive tract infections and adverse pregnancy outcomes. However, which specific bacteria cause clinical features of BV is unclear.

Methods

We previously demonstrated that Gardnerella vaginalis could elicit many BV features in mice. In this study, we established a BV model in which we coinfected mice with G. vaginalis and another species commonly found in women with BV: Prevotella bivia.

Results

This coinfection model recapitulates several aspects of human BV, including vaginal sialidase activity (a diagnostic BV feature independently associated with adverse outcomes), epithelial exfoliation, and ascending infection. It is notable that G. vaginalis facilitated uterine infection by P. bivia.

Conclusions

Taken together, our model provides a framework for advancing our understanding of the role of individual or combinations of BV-associated bacteria in BV pathogenesis.
Infrequent Transmission of Monovalent Human Rotavirus Vaccine Virus to Household Contacts of Vaccinated Infants in Malawi
Authors: Bennett Aisleen , Pollock Louisa , Jere Khuzwayo C , Pitzer Virginia E , Lopman Benjamin , Parashar Umesh , Everett Dean , Heyderman Robert S , Bar-Zeev Naor , Cunliffe Nigel A , Iturriza-Gomara Miren
Published: January 2019

Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8–10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi.
Effects of time of feeding during gestation on sow’s performance1
Authors: Manu Hayford , Lee Su H , Ren Ping , Pangeni Devi , Yang Xiaojian , Baidoo Samuel K
Published: January 2019

The aim of this study was to investigate the effect of different feeding time regimes given similar energy intake per kilogram live BW0.75 during gestation on sow’s performance. One hundred and seventy-four sows [Topigs TN 70 (Landrace × Large White, Topigs USA); parity 3.81 ± 0.16; initial BW = 211.57 ± 3.34 kg; backfat (BF) 13.70 ± 0.42 mm] were blocked by parity, farrowing date, balanced for BW and randomly assigned to 1 of 3 treatments in a randomized complete block design. Treatments included sows fed corn-soybean meal-based diet once at [0730 (control, T1), 1130 (T2), or 1530 h (T3)], with daily feed quantity kept at 1.25× maintenance energy intake [100 × (BW)0.75] kcal ME/d. Sows received 6,758, 7,434, and 8,110 kcal ME/d from days 30 to 60, days 61 to 90, days 91 to 109 of gestation, respectively. The gestation diet was formulated to contain 3,379 kcal of ME/kg, 0.70% Ca, 0.61% total P, 0.58% SID Lys, 0.26% SID Met, 0.45% SID Thr, 0.12% SID Trp, and 0.48% SID Met+Cys. Body weight and BF were recorded on days 30, 60, 90, and 109 of gestation, 24 h after farrowing and at weaning. Results showed that feeding times evaluated did not alter BW changes from day 30 to day 109 of gestation (P = 0.81) or from day 30 to weaning (P = 0.87). Similarly, feeding sows daily at 1130 h did not influence BF gains and sow reproductive performance relative to the control sows (P > 0.10). Sows fed once daily at 1530 h gained more BF compared with the control (3.69 ± 0.47 vs. 2.12 ± 0.50 mm, P = 0.04) from day 30 to day 109 of gestation. From day 30 of gestation to weaning, treatments did not influence BF gain (P = 0.24). Feeding sows daily meal at 1530 h had propensity to increase (P = 0.09) the number of piglets weaned by 0.54 piglets compared with the control sows. In conclusion, the present study demonstrated that feeding pregnant sows at 1530 h altered energy and nutrient metabolism improving their BF gain and exhibited a potential to increase the number of weaned piglets compared with conventional feeding regime.
Development of Common Data Elements for Use in Chiari Malformation Type I Clinical Research: An NIH/NINDS Project
Authors: Luciano Mark G , Batzdorf Ulrich , Kula Roger W , Rocque Brandon G , Maher Cormac O , Heiss John , Martin Bryn A , Bolognese Paolo A , Ashley-Koch Allison , Limbrick David , Poppe Dorothy J , Esposito Kaitlyn M , Odenkirchen Joanne , Esterlitz Joy R , Ala’i Sherita , Joseph Kristen , Feldman Robin S , Riddle Robert ,   Chiari I Malformation Common Data Element Working Group
Published: January 2019

The management of Chiari I malformation (CMI) is controversial because treatment methods vary and treatment decisions rest on incomplete understanding of its complex symptom patterns, etiologies, and natural history. Validity of studies that attempt to compare treatment of CMI has been limited because of variable terminology and methods used to describe study subjects. The goal of this project was to standardize terminology and methods by developing a comprehensive set of Common Data Elements (CDEs), data definitions, case report forms (CRFs), and outcome measure recommendations for use in CMI clinical research, as part of the CDE project at the National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health. A working group, comprising over 30 experts, developed and identified CDEs, template CRFs, data dictionaries, and guidelines to aid investigators starting and conducting CMI clinical research studies. The recommendations were compiled, internally reviewed, and posted online for external public comment. In October 2016, version 1.0 of the CMI CDE recommendations became available on the NINDS CDE website. The recommendations span these domains: Core Demographics/Epidemiology; Presentation/Symptoms; Co-Morbidities/Genetics; Imaging; Treatment; and Outcome. Widespread use of CDEs could facilitate CMI clinical research trial design, data sharing, retrospective analyses, and consistent data sharing between CMI investigators around the world. Updating of CDEs will be necessary to keep them relevant and applicable to evolving research goals for understanding CMI and its treatment.
Conforming Choices: Peer Influence, Adoption, and Interpretation of the Islamic Headscarf in Indonesia
Authors: Brown Gustav
Published: January 2019

This article examines the role of peer influence in structuring adoption and interpretation of the Islamic headscarf among young Muslim women in Indonesia. I argue that approaches to the jilbab fall into two broad-based categories of practice, each of whose practitioners play distinct roles in the social process driving both adoption and interpretation of the headscarf. Proactively pious Muslims act as “influencers” who encourage adoption by morality signaling (i.e., signaling “virtue” and “correct-ness” to others) in the immediate social environment. The reactively pious adopt the practice in response to the internalized urge to conform to new expectations within a pietized field, but then transform the practice by treating it as a commodified element in broader repertoires of fashion and femininity. The result is both a pietized social field and one in which piety has been informalized.
The Identity of a Single Residue of the RNA-Dependent RNA Polymerase of Grapevine Fanleaf Virus Modulates Vein Clearing in Nicotiana benthamiana
Authors: Osterbaan Larissa J. , Choi Jiyeong , Kenney Jaimie , Flasco Madison , Vigne Emmanuelle , Schmitt-Keichinger Corinne , Rebelo Ana Rita , Heck Michelle , Fuchs Marc
Published: January 2019

The mechanisms underlying host plant symptom development upon infection by viruses of the genus Nepovirus in the family Secoviridae, including grapevine fanleaf virus (GFLV), are poorly understood. In the systemic host Nicotiana benthamiana, GFLV strain GHu produces characteristic symptoms of vein clearing in apical leaves, unlike other GFLV strains such as F13, which cause an asymptomatic infection. In this study, we expanded on earlier findings and used reverse genetics to identify residue 802 (lysine, K) of the GFLV-GHu RNA1-encoded RNA-dependent RNA polymerase (1EPol) as a modulator of vein-clearing symptom development in N. benthamiana. Mutations to this site abolished (K to G, A, or Q) or attenuated (K to N or P) symptom expression. Noteworthy, residue 802 is necessary but not sufficient for vein clearing, as GFLV-F13 RNA1 carrying K802 remained asymptomatic in N. benthamiana. No correlation was found between symptom expression and RNA1 accumulation, as shown by reverse transcription-quantitative polymerase chain reaction. Additionally, the involvement of RNA silencing of vein clearing was ruled out by virus-induced gene silencing experiments and structure predictions for protein 1EPol suggested that residue 802 is flanked by strongly predicted stable secondary structures, including a conserved motif of unknown function (805LLKT/AHLK/RT/ALR814). Together, these results reveal the protein nature of the GFLV-GHu symptom determinant in N. benthamiana and provide a solid basis for probing and determining the virus-host proteome network for symptoms of vein clearing.
Film-Forming Polymers and Surfactants Reduce Infection and Sporulation ofPhytophthora ramorumon Rhododendron
Authors: Peterson Ebba K. , Larson Eric R. , Parke Jennifer L.
Published: January 2019

Phytophthora ramorum, cause of sudden oak death and ramorum leaf blight, can persist undetected in infested nurseries. Many conventional fungicides are effective in reducing or delaying symptom expression but some may confound visual detection of infected plants. We tested film-forming polymers (FFPs) and surfactants for their ability to reduce infection and sporulation of P. ramorum on rhododendron. FFPs (Anti-Stress, Moisturin, Nature Shield, Nu-Film, and Vapor Gard) and surfactants (Tergitol, Zonix, and an unregistered AGAE product) were screened in detached-leaf assays. Anti-Stress, Nu-Film, Zonix, and a Nu-Film-Zonix mixture were additionally tested for durability, protection against exposure to infested water, and a reduction in sporulation. FFP effectiveness was retained for at least 3 weeks of exposure to overhead irrigation and rain. Relative to controls, foliar treatments protected rhododendron branches exposed to infested water. No treatments prevented symptom development when applied postinfection but leaves treated with Anti-Stress, Zonix, and the Nu-Film-Zonix mixture produced significantly fewer sporangia relative to controls. Application of FFPs and surfactants to quarantined, potentially infected plants offers a management tool for reducing infection and sporulation but not symptom expression, thereby limiting disease spread without interfering with disease detection.
Rasta Disease of Tomato in Ghana is Caused by the PospiviroidsPotato spindle tuber viroidandTomato apical stunt viroid
Authors: Batuman Ozgur , Çiftçi Ö. Cem , Osei Michael K. , Miller Sally A. , Rojas Maria R. , Gilbertson Robert L.
Published: January 2019

Rasta is a virus-like disease of unknown etiology affecting tomato (Solanum lycopersicum) plants in Ghana. Symptoms include stunting; epinasty, crumpling, and chlorosis of leaves; and necrosis of leaf veins, petioles, and stems. Leaf samples with rasta symptoms were collected from commercial tomato fields in Ghana in October 2012 and applied to FTA cards, and RNA extracts were prepared. Reverse-transcription polymerase chain reaction (RT-PCR) tests with primers for Columnea latent viroid, which causes rasta-like symptoms in tomato plants in Mali, were negative, whereas tests with degenerate viroid primer pairs were inconclusive. However, tomato seedlings (Early Pak 7) mechanically inoculated with RNA extracts of 10 of 13 samples developed rasta-like symptoms. In RT-PCR tests with RNA from leaves of the 10 symptomatic seedlings and primers for Potato spindle tuber viroid (PSTVd) or Tomato apical stunt viroid (TASVd), the expected size (approximately 360 bp) of DNA fragment was amplified from eight and two seedlings, respectively. Sequence analyses confirmed that these fragments were from PSTVd and TASVd isolates, and revealed a single PSTVd haplotype and two TASVd haplotypes. The PSTVd and TASVd isolates from Ghana had high nucleotide identities (>94%) with isolates from other geographic regions. In a host range study, PSTVd and TASVd isolates from Ghana induced rasta symptoms in the highly susceptible tomato cultivar Early Pak 7 and mild or no symptoms in Glamour, and symptomless infections in a number of other solanaceous species. PSTVd and TASVd isolates were seed associated and possibly seed transmitted.
Immediate Use of Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea Following Transsphenoidal Pituitary Surgery: A Case Series
Authors: Rieley William , Askari Ayda , Akagami Ryojo , Gooderham Peter A. , Swart Petrus A. , Flexman Alana M.
Published: January 2019

Background:

Patients who undergo transsphenoidal pituitary resection have an elevated risk of obstructive sleep apnea (OSA) yet their outcomes and the safety of continuous positive airway pressure (CPAP) remains unclear. Our study objective was to determine the incidence of complications related to the use of early positive airway pressure following pituitary resection.

Methods:

We retrospectively identified all patients who underwent endoscopic transsphenoidal pituitary tumor resection between January 1, 2005 and March 24, 2016 at our institution, including those with diagnosed or suspected OSA. We compared characteristics and postoperative complications of OSA patients who did and did not receive CPAP postoperatively.

Results:

In total, 427 patients underwent transsphenoidal pituitary resection. Of these, 64 (15%) had OSA. Acromegaly was more common in patients with OSA (42% vs. 10%; P<0.001) but not Cushing Disease (19% vs. 16%; P=0.54). Hypoxia was more common in patients with OSA as compared to those without (14% vs. 5%; P<0.001) and one patient with OSA was reintubated compared with none in the control group (P=0.017). Eight patients had CPAP applied in the immediate postoperative period and the incidence of postoperative cerebrospinal fluid (CSF) leak, infection, and pneumocephalus was similar between OSA patients with and without CPAP.

Discussion:

Our case series of patients with OSA who received CPAP immediately following transsphenoidal pituitary resection resulted in similar rates of surgical complications. Our results support further investigation to establish the safety of CPAP in this population.
30-Day Emergency Department Visits After Primary Lumbar Fusion
Authors: Jain Nikhil , Brock John L. , Phillips Frank M. , Weaver Tristan , Khan Safdar N.
Published: January 2019

Our objective was to describe the incidence, causes, risk factors, and costs associated with 30-day emergency department (ED) visits after primary lumbar fusion. A national insurance database was retrospectively analyzed to study patients with primary lumbar fusions performed for degenerative pathology of the spine between 2007 and Q3-2015. Risk factors for ED visits, and ED to hospital transfer were studied using multiple-variable logistic regression analysis. Our cohort included 37,559 patients with a mean age of 66.0±10.0 years. A total of 4806 (12.8%) patients had 10,281 ED visits within 30 days after surgery. Of these, 945 (19.9%) had multiple (≥3) visits, and 1466 (30.5%) were admitted to the hospital for management. Common causes for presentation in the ED were cardiorespiratory complaints (49.4%, n=2377), and back and/or leg pain (47.7%, n=2294). Risk factors for all ED visits, multiple ED visits, and hospital admission from the ED have been identified. The overall ED cost burden was nearly two-thirds as much as hospital readmissions within 30 days ($6,994,260 vs. $10,880,999). There is a sizable subset of patients that present to the ED for acute care but do not require hospitalization. Causes and risk factors for presentation in patients with multiple ED visits are somewhat different than patients requiring hospital readmission.
BRAF Inhibitor–Associated Granulomatous Dermatitis: A Report of 3 Cases
Authors: Hui Ong Eugene Liat , Sinha Rishika , Jmor Shilan , Fearfield Louise
Published: January 2019

Cutaneous toxicities associated with BRAF inhibitor treatment in patients with metastatic melanoma have been well described. We present a rare association of granulomatous dermatitis in association with the BRAF inhibitor vemurafenib. Three patients with metastatic melanoma all presented with asymptomatic papular eruptions 8–21 months into vemurafenib therapy. Skin biopsies confirmed the diagnosis of granulomatous dermatitis. Other causes of granulomatous dermatitis including infectious agents and sarcoid were excluded. Treatment with potent topical and oral steroids improved the eruptions, but only after the cessation of vemurafenib did all 3 cases of granulomatous dermatitis completely resolve within 2 weeks. It is important to recognize that this association, unlike most other BRAF inhibitor–related skin toxicities, can occur many months after commencement of therapy and that vemurafenib treatment can be continued without clinically significant adverse effects.
Familial Associations of Colon and Rectal Cancers With Other Cancers
Authors: Yu Hongyao , Hemminki Akseli , Sundquist Kristina , Hemminki Kari
Published: January 2019

BACKGROUND:

Many studies have indicated that colon and rectal cancers differ in etiology and histology.

OBJECTIVE:

The aim of this study was to investigate whether the associations of colon and rectal cancers with any other (discordant) cancer were site specific.

DESIGN:

A novel approach was implemented in which cancer risks were analyzed in families with increasing numbers of family members diagnosed with defined cancers. The novel assumption was that, for a true familial association, the risk should increase by the number of affected family members. In separate analyses, familial risks were calculated after the exclusion of putative families with hereditary nonpolyposis colorectal cancer.

SETTINGS:

The study was conducted using the Swedish Family-Cancer Database.

MAIN OUTCOME MEASURES:

The outcome measure was relative risk.

RESULTS:

Relative risks of colorectal cancer and colon cancer were higher when family members were diagnosed with colon cancer than when family members were diagnosed with rectal cancer (incidence rate ratio for colorectal: 1.82 (95% CI, 1.74–1.90) vs 1.61 (95% CI, 1.51–1.71); incidence rate ratio for colon: 1.92 (95% CI, 1.83–2.02) vs 1.56 (95% CI, 1.45–1.69)). Relative risks for 10 discordant cancers were increased in colon or rectal cancer families, whereas none of the relative risks differed significantly between colon and rectal cancers. After deleting hereditary nonpolyposis colorectal cancer families, the relative risks of endometrial and ovarian cancers were no longer significant.

LIMITATIONS:

Genetic data are unavailable in the database.

CONCLUSIONS:

Our results suggested that familial risks for colon cancer were higher than risks for rectal cancer in families of patients with colorectal cancer and colon cancer. The relationships of lung cancer and nervous system cancer with colorectal cancer were site specific. The associations of colon and rectal cancers with lung cancer, myeloma, and cancer of unknown primary appeared not to point out known syndromes and may suggest involvement of a novel predisposition. See Video Abstract at http://links.lww.com/DCR/A791.
Head-Mounted Mixed-Reality Technology During Robotic-Assisted Transanal Total Mesorectal Excision
Authors: Huber Tobias , Hadzijusufovic Edin , Hansen Christian , Paschold Markus , Lang Hauke , Kneist Werner
Published: January 2019

INTRODUCTION:

Head-mounted mixed-reality technologies may enable advanced intraoperative visualization during visceral surgery. In this technical note, we describe an innovative use of real-time mixed reality during robotic-assisted transanal total mesorectal excision.

TECHNIQUE:

Video signals from the robotic console and video endoscopic transanal approach were displayed on a virtual monitor using a head-up display. The surgeon, assistant, and a surgical trainee used this technique during abdominal and transanal robotic-assisted total mesorectal excision. We evaluated the feasibility and usability of this approach with the use of validated scales.

RESULTS:

The technical feasibility of the real-time visualization provided by the current setup was demonstrated for both the robotic and transanal parts of the surgery. The surgeon, assistant, and trainee each used the mixed-reality device for 15, 55, and 35 minutes. All participants handled the device intuitively and reported a high level of comfort during the surgery. The task load was easily manageable (task load index: <4/21), although the surgeon and assistant both noted a short delay in the real-time video.

CONCLUSION:

The implementation of head-mounted mixed-reality technology during robotic-assisted transanal total mesorectal excision can benefit the operating surgeon, assistant, and surgical trainee. Further improvements in display quality, connectivity, and systems integration are necessary.
ASYMPTOMATIC MULTIFOCAL PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH JUVENILE DERMATOMYOSITIS: OPTICAL COHERENCE ANGIOGRAPHY FINDINGS
Authors: Starr Matthew R. , Softing Hataye Alaina L. , Bakri Sophie J.
Published: January 2019

Purpose:

To describe a unique presentation of multifocal paracentral acute middle maculopathy in a young patient with juvenile dermatomyositis including optical coherence tomography angiography findings.

Methods:

Retrospective single case report.

Patient:

Seventeen-year-old male patient with a history of juvenile dermatomyositis presented for routine hydroxychloroquine screening.

Results:

Optical coherence tomography revealed undulations of the outer retinal layers and retinal thinning near the fovea in both eyes. Optical coherence tomography angiography revealed loss of flow void densities in the superficial and deep capillary plexi in both eyes. These findings were consistent with a diagnosis of paracentral acute middle maculopathy.

Conclusion:

To the authors' knowledge, this is the first report of the optical coherence tomography angiography findings in paracentral acute middle maculopathy associated with juvenile dermatomyositis. The defects were located in the superficial and deep capillary plexi and likely due to the known occlusive retinopathy associated with juvenile dermatomyositis.
Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency
Authors: Deng Sophie X. , Borderie Vincent , Chan Clara C. , Dana Reza , Figueiredo Francisco C. , Gomes José A. P. , Pellegrini Graziella , Shimmura Shigeto , Kruse Friedrich E. ,   and The International Limbal Stem Cell Deficiency Working Group
Published: January 2019

Purpose:

Despite extensive knowledge gained over the last 3 decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging, and classification system among treating physicians and research scientists working on this field. There is therefore an unmet need to obtain global consensus on the definition, classification, diagnosis, and staging of LSCD.

Methods:

A Limbal Stem Cell Working Group was first established by The Cornea Society in 2012. The Working Group was divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to obtain agreement on a strategic plan and methodology from all participants after a comprehensive literature search, and final agreement was reached on the definition, classification, diagnosis, and staging of LSCD. A writing group was formed to draft the current manuscript, which has been extensively revised to reflect the consensus of the Working Group.

Results:

A consensus was reached on the definition, classification, diagnosis, and staging of LSCD. The clinical presentation and diagnostic criteria of LSCD were clarified, and a staging system of LSCD based on clinical presentation was established.

Conclusions:

This global consensus provides a comprehensive framework for the definition, classification, diagnosis, and staging of LSCD. The newly established criteria will aid in the correct diagnosis and formulation of an appropriate treatment for different stages of LSCD, which will facilitate a better understanding of the condition and help with clinical management, research, and clinical trials in this area.
Intraoperative Optical Coherence Tomography–Guided Femtosecond Laser–Assisted Deep Anterior Lamellar Keratoplasty
Authors: Liu Yu-Chi , Wittwer Valéry V. , Yusoff Nur Zahirah Bte M. , Lwin Chan Nyein , Seah Xin Yi , Mehta Jodhbir S. , Seiler Theo
Published: January 2019

Purpose:

To describe the feasibility and outcomes of intraoperative optical coherence tomography (OCT)–guided, femtosecond laser–assisted deep anterior lamellar keratoplasty in which the lamellar and tunnel cuts were completed by laser.

Methods:

The Ziemer Z8 system was used to scan the corneas intraoperatively and guide the stromal lamellar and tunnel cuts created by the laser. Thirty porcine eyes and 3 human cadaver globes were used to evaluate the accuracy of laser-created intrastromal tunnels and the feasibility of achieving big-bubble pneumatic dissection. The tunnel distance above the Descemet membrane (D
t-dm) was set at 100 and 130 μm, and the accuracy of laser cut was assessed by anterior segment OCT and histological sections. Fourteen patients with keratoconus or corneal scars were then included to evaluate the clinical outcomes.

Results:

The deviation from the targeted D
t-dm was 5.5% to 8.6% and 0.7% to 9.8% for the 100 and 130 μm groups, respectively. The achieved thickness had a significantly and positively strong correlation with the targeted thickness (r = 0.86; P < 0.001). In all cases, the anterior stromal lamella was removed without difficulty, except in the patients with corneal scars in whom some remaining stromal fiber attachments were observed. A type 1 big bubble was successfully achieved in all patients.

Conclusions:

We present the accuracy and clinical outcomes of femtosecond laser–assisted, intraoperative OCT–guided deep anterior lamellar keratoplasty, in which controlled lamellar and tunnel cuts at desired depths were performed by laser in one step, and a successful big bubble was achieved.
Epidemiology of intrahepatic, perihilar, and distal cholangiocarcinoma in the French population
Authors: Al Mahjoub Aimen , Bouvier Véronique , Menahem Benjamin , Bazille Céline , Fohlen Audrey , Alves Arnaud , Mulliri Andrea , Launoy Guy , Lubrano Jean
Published: January 2019

Objectives

The objective of this study was to investigate the differences between cholangiocarcinoma (CC) subtypes in terms of incidence rate, clinical presentation, management and survival by applying a stable anatomical classification in a population-based study.

Patients and methods

Cancer data for the period 2000–2012 were obtained from a specialized digestive cancer registry in the Department of Calvados, France. Patients’ files were checked, and the diagnosis was verified by two hepatobiliary surgeons. This approach prevents classifying perihilar cholangiocarcinoma (PHCC) as intrahepatic cholangiocarcinoma (ICC), thereby allowing an accurate estimation of their respective epidemiological characteristics.

Results

A total of 320 patients with CC were included. ICC represented 41% (130), whereas PHCC and distal cholangiocarcinoma represented 36 (116) and 23% (74), respectively. The mean age at the time of diagnosis differed significantly between the three subtypes (P<0.05). ICC was discovered accidently more frequently than PHCC, which was associated significantly with clinical symptoms. No change in the incidence or survival rates of CC subtypes were noticed, except for PHCC, in which female individuals had a significantly shorter median and 5-year survival rate of 0% (P<0.05).

Conclusion

The frequency of PHCC is overestimated in the literature. The anatomical reclassification of CC subtypes shows the stability of their incidence and survival rates. Considering ICC and PHCC as two different entities implies the need to assign a specific topographic code for PHCC.
Comparison of transjugular intrahepatic portosystemic shunt for treatment of variceal bleeding in patients with cirrhosis with or without spontaneous portosystemic shunt
Authors: Leng Xiafei , Zhang Feng , Zhang Ming , Guo Huiwen , Yin Xiaochun , Xiao Jiangqiang , Wang Yi , Zou Xiaoping , Zhuge Yuzheng
Published: January 2019

Background and aims

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications in cirrhosis. Spontaneous portosystemic shunts (SPSSs) may increase the risk of post-TIPS complications and mortality. This study was done to evaluate the safety and efficacy of TIPS for treating variceal bleeding between patients with and without SPSSs.

Patients and methods

The clinical data of 467 consecutive patients with cirrhosis who received TIPS for variceal bleeding from January 2012 to January 2018 were screened. A total of 33 patients with coexisting SPSSs were included as the SPSS group, and 33 patients without SPSSs were randomly selected as control. The procedure-related complications and long-term outcomes were compared between the two groups.

Results

Both groups were successfully treated with TIPS. SPSSs were antegradely embolized before TIPS placement. In terms of safety, one patient in the SPSS group experienced an asymptomatic pulmonary embolism, and another patient experienced serious gastric ulcer bleeding. Overall, 23 (70.0%) patients in the SPSS group and 16 (51.5%) patients in the control group experienced different mild complications (P=0.131). During a median follow-up of more than 2 years, the rebleeding rates (7.1 vs. 3.7% at 1 year, P=0.508), overt hepatic encephalopathy occurrence rates (34.4 vs. 39.4% at 2 years, P=0.685), and orthotopic liver transplantation-free survival rates (73.2 vs. 70.7% at 2 years, P=0.557) were not significantly different between the two groups.

Conclusion

TIPS combined with antegrade embolization is safe, effective, and feasible for patients with SPSSs, with safety and long-term outcomes comparable to patients without SPSSs.
What are the most promising new agents in myelodysplastic syndromes?
Authors: Chandhok Namrata S. , Boddu Prajwal C. , Gore Steven D. , Prebet Thomas
Published: January 2019

Purpose of review

Myelodysplastic syndromes (MDS) are a diverse group of clonal disorders of hematopoietic stem or progenitor cells that represent the most common class of acquired bone marrow failure syndromes in adults. Despite significant improvement in the pathologic insight into this group of disorders, therapeutic options remain limited and allogeneic hematopoietic stem-cell transplantation is the only treatment that can induce long-term remission in patients with MDS. The goals of therapy for MDS are based on disease prognostication, with a focus of minimizing transfusion dependence and preserving quality of life in low-risk groups and preventing progression of disease to acute myeloid leukemia in high-risk groups. Given the dearth of approved treatment options, there is a marked need for novel therapies across the board, and there are several novel agents currently in the pipeline.

Recent findings

Among the promising agents with preclinical and early phase efficacy in higher risk MDS, apoptosis targeting with BCL-2 inhibitors have been a standout. There is also a keen interest in immunotherapy, and targeted agents (genetic, signaling pathways, bispecific antibodies, antibody-drug conjugates, and others described in this review).

In this review, we will highlight some of the promising new agents currently under investigation for the management of MDS.
Deliveries at extreme prematurity: outcomes, approaches, institutional variation, and uncertainty
Authors: Arzuaga Bonnie H. , Cummings Christy L.
Published: January 2019

Purpose of review

Medical decision making and practices surrounding extremely premature birth remains challenging for parents and care providers alike. Recently, concerns have been raised regarding wide practice variation, selection bias, and the limitations of outcomes data in this population. The purpose of this review is to summarize the recent literature relevant to deliveries at extreme prematurity with a focus on outcomes, approaches, and institutional variation.

Recent findings

Newer data suggest that evidence-based clinical guidelines and protocols for both pregnant women and infants at extreme prematurity are emerging and may improve care and outcomes at lower gestational ages. It has also been recently shown that wide practice variation, selection bias, and methodological limitations of outcomes data reporting with respect to deliveries at extreme prematurity exist.

Counseling at extreme prematurity should prioritize eliciting parental values and preferences with the goal of personalized shared decision-making. Providers should recognize limitations in counseling families at extreme prematurity, including selection bias, institutional variation, outcomes inaccuracies, prognostic uncertainty, and implicit biases. Standardized reporting of perinatal outcomes should be developed to help alleviate current outcomes misrepresentations and improve counseling at extreme prematurity. Education for providers in advanced communication skills is needed when counseling at extreme prematurity.
Barium Enema Revisited in the Workup for the Diagnosis of Hirschsprung's Disease
Authors: Lourenção Pedro Luiz Toledo de Arruda , Valerini Felipe Gilberto , Cataneo Antonio Jose Maria , Ortolan Erika Veruska Paiva , Silveira Guilherme Lopes da , Piva Mariana Floriano Luiza , Cucco Lucas da Matta , Rodrigues Maria Aparecida Marchesan
Published: January 2019

Objective:

To analyse the diagnostic capacity of barium enema (BE) in the diagnostic investigation for Hirschsprung's disease (HD) was analyzed for transition zone (TZ) identification and rectosigmoid index (RSI) ⩽1.0 determination.

Patients and Methods:

BE images were analyzed retrospectively by 2 examiners and the results were compared with the histopathology of rectal biopsies.

Results:

TZ identification and RSI ⩽1.0 were assessed separately and combined in 43 patients. Twelve (27.9%) patients had the diagnosis of HD based on rectal biopsies. TZ identification presented better diagnostic capacity for the 2 examiners than RSI ⩽1.0. However, interexaminer agreement was higher for RSI ⩽1.0 than for TZ identification. The combination of TZ identification and RSI ⩽1.0 increased the sensitivity (83.3%–92.3%) and the negative predictive value (90.4%–92.3%).

Conclusion:

Therefore, the high diagnostic sensitivity of TZ identification combined to RSI ⩽1.0 reinforces the usefulness of these BE parameters in the screening for Hirschsprung's disease.
Serum Calprotectin in Adolescents With Inflammatory Bowel Disease—A Pilot Investigation
Authors: Carlsen Katrine , Malham Mikkel , Hansen Lars Folmer , Petersen Jens Jakob Herrche , Paerregaard Anders , Houen Gunnar , Wewer Vibeke
Published: January 2019

Objectives:

Fecal calprotectin (FC) is a well‐integrated parameter in the monitoring of adolescent patients with inflammatory bowel disease (IBD). However, measurement of FC is limited by day‐to‐day‐variation and by the feces consistency. Furthermore, adolescents are often noncompliant to deliver fecal sampling leading to suboptimal monitoring. Consequently, we see the need of a substitute biomarker whenever measurement of FC fails and aimed to investigate serum calprotectin (SC) in adolescents with IBD.

Methods:

In cross sectional data from 19 ulcerative colitis (UC) patients <18 years old, a Spearman correlation was used to analyze the correlation between SC, FC, C‐reactive protein (CRP) and endoscopic and symptom scores. In longitudinal data collected from 20 UC and Crohn disease (CD) patients (10–17 years old), Mixed Effect Models (MEM) were used to analyze the association between SC, FC, CRP, and symptom scores.

Results:

We found positive correlations between SC (19 samples) and the endoscopic score, symptom score, and CRP (r = 0.56, P = 0.01; r = 0.64, P = 0.003; r = 0.97, P < 0.0001). We found no significant correlation between SC and FC. In 27 samples from UC patients, the association of SC with FC and CRP were positive and significant (P = 0.004, estimate = 0.32; P = 0.0001, estimate = 0.002). The association between SC and symptom score was insignificant. In 49 samples from CD patients, the association between SC and CRP was significant (P = 0.02, estimate = 0.002) whereas associations between SC and FC and symptom score were insignificant.

Conclusions:

In the current pilot study, we found a correlation between SC and the endoscopically assessed inflammation in UC. SC may have the potential to improve disease monitoring of adolescent patients.
Change in Prevalence of Family History During Long‐term Follow‐up of Patients With Pediatric‐onset Inflammatory Bowel Disease
Authors: Capone Kristin , Rosenberg Harry J. , Wroblewski Kristen , Gokhale Ranjana , Kirschner Barbara S.
Published: January 2019

Objectives:

The aim of the study was to prospectively study changes in prevalence of positive family history (FH+) in pediatric‐onset inflammatory bowel disease (IBD) in contrast to previously published cross‐sectional data.

Methods:

An observational cohort study was performed using a prospective pediatric‐onset IBD database including 485 patients with disease duration ≥10 years as of December 2016. Proband characteristics and FH+ were obtained at diagnosis and subsequently from the database, medical records, and follow‐up telephone interviews in 2006 and 2016.

Results:

Updated 2016 information was obtained from 322 (66%) patients and included in analysis with median follow‐up of 18 years (interquartile range 14, 26). Prevalence of FH+ increased from 13.7% at diagnosis to 26.6% at 20 years for first‐degree relatives and from 38.5% to 52.2% for all relatives. At 20‐year follow‐up, an additional 10.0% of probands had a sibling, 6.1% had a parent, 1.9% had a grandparent, and 4.5% had a cousin diagnosed with IBD. FH+ at diagnosis was associated with greater risk for additional FH+ at 20 years (43% vs 22%, P < 0.001). Non‐Jewish Caucasians had significantly lower risk of a FH+ compared to Jewish Caucasians (P = 0.002), but similar risk to African Americans (P = 0.55). FH+ at diagnosis was not associated with disease type (P = 0.33) or age at diagnosis (P = 0.24).

Conclusions:

This prospective study documents changes in family history of IBD in pediatric‐onset IBD patients over time. Prevalence of FH+ increased for first‐degree and all relatives at 20 years by 12.9% and 13.7%, respectively. FH+ at diagnosis was associated with a 2‐fold greater likelihood of subsequent FH+ at 20 years.
Congenital Portosystemic Shunts
Authors: McLin Valérie A. , Franchi Abella Stephanie , Debray Dominique , Guérin Florent , Beghetti Maurice , Savale Laurent , Wildhaber Barbara E. , Gonzales Emmanuel ,   Members of the International Registry of Congenital Porto‐Systemic Shunts
Published: January 2019

Congenital portosystemic shunts are increasingly recognized in several settings and at any age. The following are some of the most common presentations: prenatal ultrasound, neonatal cholestasis, incidental finding on abdominal imaging, or systemic complications such as unexplained cardiopulmonary or neurological disease, or the presence of liver nodules in a noncirrhotic liver. The purpose of the present review is to summarize clinical presentation and current recommendations for management, and highlight areas of future research. Illustrative examples from the veterinary literature complement our current lack of knowledge of this rare malformation often masquerading as a multisystem disease.
Adequate Infliximab Exposure During Induction Predicts Remission in Paediatric Patients With Inflammatory Bowel Disease
Authors: van Hoeve Karen , Dreesen Erwin , Hoffman Ilse , Van Assche Gert , Ferrante Marc , Gils Ann , Vermeire Séverine
Published: January 2019

Objectives:

Therapeutic drug monitoring has been proposed as a useful tool in the management of infliximab (IFX) treated patients with inflammatory bowel disease. The aim of this retrospective study was to determine whether IFX trough levels after induction therapy are predictive for outcome at week 52.

Methods:

All pediatric patients with inflammatory bowel disease receiving maintenance IFX at our centre, with IFX trough level available at their first maintenance infusion and a follow‐up of at least 52 weeks were included. IFX induction regimens could be intensified at the discretion of the treating physician. All children received proactive drug monitoring during maintenance with dose adaptation aiming to target a therapeutic window of 3 to 7 μg/mL.

Results:

We included 35 children (23 with Crohn disease and 12 with ulcerative colitis). Median IFX trough levels just before the first maintenance infusion were significantly higher in children achieving clinical (4.6 μg/mL [2.7–11.8] vs 1.5 μg/mL [0.9–3.0]), biological (4.6 μg/mL [2.5–10.3] vs 2.6 μg/mL [0.3–3.2]) and combined clinical/biological remission (6.0 μg/mL [3.2–12.0] vs 2.6 μg/mL [1.1–3.2]) at week 52 compared to children not meeting these criteria (all P ⩽ 0.002). Binary logistic regression identified these trough levels as the only predictor for the same outcomes with an odds ratio (95% confidence interval) of 2.083 (1.085–3.998), 2.203 (1.101–4.408), and 2.264 (1.096–4.680), respectively (all P < 0.05).

Conclusions:

Adequate IFX exposure during induction therapy is associated with better clinical and/or biological remission at week 52. Postinduction IFX trough levels were the only predictor for clinical and/or biological remission at week 52.
Impact of Race and Socioeconomic Status on Psychologic Outcomes in Childhood Cancer Patients and Caregivers
Authors: Ramsey Logan H. , Graves Patricia E. , Howard Sharp Katianne M. , Seals Samantha R. , Collier Anderson B. , Karlson Cynthia W.
Published: January 2019

Complex relationships between race and socioeconomic status have a poorly understood influence on psychologic outcomes in pediatric oncology. The Family Symptom Inventory was used to assess symptoms of depression and anxiety in pediatric patients with cancer and their caregivers. Separate hierarchical linear regression models examined the relationship between demographic variables, cancer characteristics, socioeconomic status, and access to care and patient or caregiver depression/anxiety. Participants included 196 pediatric patients with cancer (mean age, 11.21 y; 49% African American) and their caregivers. On average, caregivers reported low levels of depression/anxiety. Symptoms of depression and anxiety in patients were correlated with poorer mental health in caregivers (r=0.62; P<0.01). Self-reported financial difficulty (β=0.49; P<0.001) and brain cancer diagnosis for their child (β=0.42; P=0.008) were significantly associated with depression and anxiety in caregivers. Analysis did not reveal significant associations between race, household income, or access to care and patient or caregiver depression/anxiety. Perception of financial hardship can adversely impact mental health in caregivers of children with cancer. Psychosocial assessment and interventions may be especially important for caregivers of patients with brain tumors and caregivers who report feeling financial difficulty.