bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inherited and acquired clinical phenotypes associated with neuroendocrine tumors
Authors: Nicholaides Rory E. , de la Morena M. Teresa 
Published: October 2017

Purpose of reviewOverview of neuroendocrine neoplasms in the context of their associations with primary and secondary immunodeficiency states.Recent findingsMalignancies of neuroendocrine origin are well known to be associated with hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel–Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other immunocompromised states. Of all primary immune deficiency diseases, NETs appear to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor, and the mechanism behind this association remains unclear. In secondary immune deficiency states, NET occurrences were primarily in patients with HIV or AIDS, the autoimmune disease systemic lupus erythematosus and solid organ transplant recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients, whereas nongastroenteropancreatic–NETs, like Merkel cell carcinoma and small-cell lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature of these associations are discussed, including chronic infections and inflammation, and CD40–CD40L interactions. Many questions remain, and further studies are needed to clarify the predisposition of patients with XHIGM to the development of NETs. Given that many of these patients present late in their disease state and have poor outcomes, it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Regular monitoring with laboratory or imaging studies, including tumor markers, may be warranted, for which further studies are needed.SummaryOf all primary immunodeficiency diseases, NETs appear to be unique to XHIGM, and the mechanism behind this association remains unclear. Outcome for XHIGM patients with NETs is poor, and it is imperative to keep a high index of suspicion at the advent of early signs and symptoms.
The complexities of fibromyalgia and its comorbidities
Authors: Lichtenstein Adi , Tiosano Shmuel , Amital Howard 
Published: October 2017

Purpose of review
Fibromyalgia syndrome (FMS) is defined as chronic, widespread musculoskeletal pain and tenderness with concomitant mood and cognitive dysfunction. Several comorbidities have been reported to be associated with FMS. We reviewed the literature concerning the most noteworthy chronic conditions associated with FMS.

Recent findings
There is mounting evidence displaying the concurrence of fibromyalgia and coexisting medical and psychiatric conditions. Such comorbidities may blur the classical clinical presentations and erroneously lead to misinterpretation of disease activity. The recognition of this fact should be underlined, as misrecognition may lead to excessive therapy and avoidable side-effects of medications on the one hand and to a better handling of FMS on the other hand, leading to improved clinical outcomes.

Summary
A greater proportion of psychiatric and rheumatologic disorders are associated with FMS patients than the population. Consequently, physicians treating patients with either condition should keep in mind that these patients may have such comorbidities and should be treated accordingly.
In Vitro Effect of Vancomycin on the Viability of Articular Chondrocytes
Authors: Shaw K. Aaron , Eichinger Josef K. , Nadig Nischal , Parada Stephen A. 
Published: October 2017

Objectives:
To characterize the in vitro toxicity of vancomycin on articular cartilage.

Methods:
Osteochondral samples extracted from fresh, juvenile porcine stifle (knee) joints were exposed to vancomycin saline concentrations of 2, 5, and 10 mg/mL and compared with a saline and nonsaline treated control. Comparison of chondrocyte viability was assessed with histology examination of chondrocyte degeneration using the Mankin criteria and a live/dead staining using ethidium homodimer-2 and calcien acetoxymethylester stain and confocal laser scanning microscopy.

Results:
A comparison of chondrocyte viability in the control sample and 2 mg/mL group showed no statistical difference (P = 0.38). The chondrocyte toxicity was statistically significantly higher in both the 5 mg/mL (P = 0.003) and 10 mg/mL (P < 0.001) experimental groups in comparison to the control sample. Chondrocyte death increased in a statistically significant dose-dependent fashion. Histologically, the Mankin scores were higher for the saline-treated group in comparison to the untreated control group.

Conclusions:
Vancomycin is toxic to articular chondrocytes in concentrations of 5 mg/mL and greater. Strategies for controlling concentration must be developed before routine application of topical antibiotics around synovial joints is performed.
Sex Differences in Vascular Reactivity to Angiotensin II During the Evolution of Myocardial Infarction
Authors: Flores-Monroy Jazmin , Ramirez-Hernández Diana , Samano-Hernández Citali , Lezama-Martínez Diego , Sampieri-Cabrera Raul , Martínez-Aguilar Luisa 
Published: October 2017

Abstract:
The influence of sex on the vascular response during the progression of myocardial infarction (MI) has not been extensively studied. In this work, we analyzed the differences of the vasoconstriction induced by angiotensin II (Ang II) in the absence and presence of valsartan (200 nM) on the aortic rings of male and female Wistar rats at 2, 4, 24, and 48 hours and 1, 2, 3, and 4 weeks after induction of MI. In the aortic rings of males, an increase was observed in the contractile response that lasts up to 4 weeks; on females, this effect is diminished since 48 hours until reaching sham group values at 2 weeks of coronary occlusion. The incubation of valsartan generated greater reduction on vasoconstriction in males than females. In relation to the determination of infarct areas, we found them between 30% and 40% in all experimental groups. In addition, the index of hypertrophy was determined and no significant changes were observed in female rats, while in males we reported an increase at 2, 3, and 4 weeks. In conclusion, we found differences in vascular reactivity due to sex, as well as on the response of Ang II via AT1 during the evolution of MI.
TESTOSTERONE SUPPLEMENTATION AND RETINAL VASCULAR DISEASE
Authors: Dedania Vaidehi S. , Zacks David N. , Pan Wei , VanderBeek Brian L. 
Published: October 2017

Purpose:
To determine whether testosterone supplementation is associated with retinal artery occlusion (RAO) or retinal vein occlusion (RVO).

Methods:
Retrospective matched cohort study using data from a large national U.S. insurance database. The testosterone cohort consisted of all male patients who filled a prescription for testosterone from 2000 to 2013. Five controls were matched on age (±3 years), sex, race, and similar time in plan (±3 months) for every exposed patient. Exclusion occurred for <2 years in the plan, <1 eye care visit, medications known to affect androgen levels, and systemic diseases associated with occlusions or increased testosterone. Cox proportional hazard regression assessed the hazard of a new diagnosis of RAO or RVO while controlling for age, race, diabetes mellitus, and hypertension.

Results:
A total of 35,784 incident testosterone users were compared with 178,860 matched controls. Ninety-three (0.3%) RAOs and 50 (0.1%) RVOs were found in the testosterone cohort and contrasted with 316 (0.2%) RAOs and 232 (0.1%) RVOs in the control group. After multivariate analysis, testosterone supplementation significantly increased the hazard of RAO (hazard ratio: 1.43, 95% confidence interval: 1.12–1.81, P = 0.004), but not of RVO (hazard ratio: 1.03, 95% confidence interval: 0.74–1.42, P = 0.86).

Conclusion:
Although the incidence of RAO and RVO is low in users of testosterone, supplementation therapy is associated with an increased hazard of RAO, but apparently not of RVO.
Outcomes and Rationale of Excision and Mucous Membrane Grafting in Palpebral Vernal Keratoconjunctivitis
Authors: Iyer Geetha , Agarwal Shweta , Srinivasan Bhaskar 
Published: October 2017

Purpose:
To report outcomes of mucous membrane grafting (MMG) for refractory giant papillae in vernal keratoconjunctivitis.

Methods:
Eleven eyes of 6 patients having giant papillae and recurrent shield ulcers refractory to topical medications, cryotherapy, and supratarsal steroid injections and shave excision of papillae underwent surgical resection of the giant papillae with MMG. Average occurrence of shield ulcers was twice per eye per year before the procedure with 50% of eyes having steroid-induced cataract and glaucoma.

Results:
No recurrence of the shield ulcer in any eye was observed over a mean follow-up period of 38.2 (range 9–106) months. The papillae recurred beyond the graft junction in one eye.

Conclusions:
Surgical excision of refractory giant papillae followed by MMG does have its advantages in reducing their corneal complications, and it should be considered early in the management of exuberant refractory giant papillae.
Factors Limiting the Visual Outcome After Descemet Stripping Automated Endothelial Keratoplasty: Comprehensive Analysis Including the Graft Position and Irregularity
Authors: Iwama Yasuaki , Soma Takeshi , Maeda Naoyuki , Sasamoto Yuzuru , Oie Yoshinori , Koh Shizuka , Nishida Kohji 
Published: October 2017

Purpose:
To investigate factors affecting best postoperative corrected distance visual acuity (CDVA) in patients who have undergone Descemet stripping automated endothelial keratoplasty (DSAEK).

Methods:
Forty-two eyes of 42 patients with predominantly non-Fuchs endothelial corneal dystrophy after DSAEK were retrospectively evaluated. All patients were examined using anterior segment optical coherence tomography when their best postoperative CDVA had been achieved. We analyzed the relationship between best postoperative CDVA and preoperative, intraoperative, and postoperative factors, including corneal higher-order aberrations (HOAs), corneal backward scattering, graft irregularity, and graft decentration. Variables with P < 0.2 in univariate analysis were entered into a multivariate linear regression model to determine the factors affecting best postoperative CDVA.

Results:
Mean CDVA improved from 1.16 ± 0.46 preoperatively to 0.22 ± 0.19 logarithm of the minimum angle of resolution equivalents postoperatively (P < 0.0001). Best postoperative CDVA was achieved 11.6 ± 7.7 months after DSAEK. Multivariate analysis showed that anterior corneal coma-like HOAs and venting incisions inside the pupil area were significantly correlated with best postoperative CDVA (t = 2.90, P = 0.006; t = 2.62, P = 0.01, respectively). No significant relationship was found between the visual outcome and any other factor, including posterior corneal HOAs, corneal backward scattering, graft decentration, and graft irregularity.

Conclusions:
Irregularity of the anterior corneal surface and venting incisions inside the pupil area are important factors that impair best postoperative CDVA in patients who have undergone DSAEK. In contrast, our results indicate that the graft position and irregularity might not have a strong influence on the visual outcome after DSAEK.
Test Conditions in Macular Visual Field Testing in Glaucoma
Authors: Eura Mariko , Matsumoto Chota , Hashimoto Shigeki , Okuyama Sachiko , Takada Sonoko , Nomoto Hiroki , Tanabe Fumi , Shimomura Yoshikazu 
Published: October 2017

Purpose:
The purpose of this study is to evaluate the suitable visual field (VF) test conditions (target size, test type, and eccentricity) for the macular region, we investigated the correlations between the ganglion cell layer (GCL) thickness and 6 VF test results.

Methods:
We tested 32 eyes of patients (61.1±9.2 y) with preperimetric (6), early-stage (16), and moderate-stage (10) glaucoma. The VF tests included 3 SAP (the 10-2 HFA using SITA with target size III [HFA SITA (III)], full threshold with size III [HFA FULL (III)] and size I [HFA FULL (I)]) and 3 visual function-specific perimetry tests (the 10-2 SWAP, 10-2 flicker, and 10-2 Humphrey Matrix). The GCL and inner plexiform layer (GCL+IPL) thickness was measured by Spectral Domain Optical Coherence Tomography (SD-OCT) with a macular 7×7 mm2 cube scan (3D OCT-2000, Topcon). The coefficient of determination (r
2) for the correlation between visual sensitivity and the GCL+IPL thickness was calculated for each test at eccentricities 0 to 5 degrees, 5 to 7 degrees, and 7 to 10 degrees using linear and quadratic regressions.

Results:
All 6 tests showed the strongest correlation with the GCL+IPL thickness at 5 to 7 degrees. The respective r
2 (linear) and R
2 (quadratic) for HFA SITA (III), HFA FULL (III), HFA FULL (I), SWAP, Flicker, and Matrix were (0.40, 0.50), (0.43, 0.53), (0.44, 0.46), (0.51, 0.51), (0.33, 0.34), and (0.52, 0.52).

Conclusions:
As compared with the frequently-used SAP with a size III, SAP with size I and the function-specific perimetry tests (especially the Matrix) could be more suitable for testing the macular region.
Reversible Venting Stitch for Fenestrating Valve-less Glaucoma Shunts
Authors: Akil Handan , Vu Priscilla Q. , Nguyen Anhtuan H. , Nugent Alexander , Chopra Vikas , Francis Brian A. , Tan James C. 
Published: October 2017

Purpose:
The purpose of this is to describe a venting stitch modification for valveless glaucoma aqueous shunts and characterize early postoperative intraocular pressure (IOP) and glaucoma medication use following the modification.

Materials and Methods:
Retrospective chart review of 61 sequential patients undergoing Baerveldt glaucoma implant (BGI)-350 implantation at the Doheny Eye Institute. Twenty-four patients received a glaucoma shunt with venting stitch modification (modified BGI) and 37 patients received an unmodified shunt (BGI-only). IOP, number of glaucoma medications, and number of hypotony cases (intraocular pressure ≤5 mm Hg) were compared between the groups. T-tests were used for statistical analysis.

Results:
At postoperative-day 1, mean IOP was significantly lower compared with preoperatively in the modified BGI group (14 mm Hg; reduced by 51%; P<0.0001) but not the BGI-only group (27 mm Hg; P=0.06). IOP difference between groups persisted till immediately before tube opening (P=0.005) and fewer IOP-lowering medications needed in the modified BGI group (P<0.0001). One case (4.2%) of postoperative hypotony was encountered with BGI modification, which resolved after the stitch was removed in clinic.

Conclusions:
The venting stitch valveless shunt modification allows for effective, reliable, and safe control of early postoperative IOP.
Choice of Endoscopic Procedure in Children With Clinically Suspected Gastrointestinal Graft‐versus‐host Disease
Authors: Mårtensson Thomas , Szakos Attila , Mellgren Karin , Toporski Jacek , Arvidson Johan , Casswall Thomas H. , Gustafsson Britt 
Published: October 2017

ABSTRACTObjectives:Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a potentially life‐threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI‐GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. Optimal extent of endoscopy in children is, however, presently unknown. Therefore, we aimed to evaluate whether biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI‐GVHD and relevant differential diagnoses.Methods:Retrospective multicenter study based on histopathological re‐evaluation of biopsies and hospital record data, collected from children with suspected GI‐GVHD.Results:Forty‐four children with 51 endoscopic occasions (81 procedures) were included. Thirty‐nine of 51 (76.5%) were diagnosed as GI‐GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity, that is, simultaneous detection of a differential diagnosis and GI‐GVHD, was observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and esophagogastroduodenal areas. Sensitivity for detection of GI‐GVHD in biopsies collected from rectosigmoid‐ileocolonic‐, rectosigmoid‐, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter 2 were merged. The difference, nondetected GI‐GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (P = 0.03).Conclusions:Biopsies collected from the rectosigmoid area solely were not optimal for detection of pediatric GI‐GVHD. When biopsy sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity for GI‐GVHD was, however, equally high as for ileocolonoscopy or full upper and lower endoscopy.
Awareness and Implementation of the 2014 ESPGHAN/NASPGHAN Guideline for Childhood Functional Constipation
Authors: Koppen Ilan J.N. , Vriesman Mana H. , Tabbers Merit M. , Di Lorenzo Carlo , Benninga Marc A. 
Published: October 2017

ABSTRACTObjective:The aim of the study was to assess whether physicians approach children with functional constipation according to the 2014 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)/North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guideline.Methods:We invited pediatricians and pediatric gastroenterologists in the Netherlands and the United States to participate in this anonymous survey using a self‐developed questionnaire containing 19 multiple choice questions concerning evaluation and treatment of children with constipation.Results:We included 328 physicians (67% from the United States, 34% from the Netherlands). The majority of US responders (53%) worked in primary care, whereas all Dutch responders worked in a hospital. In total, 31% of responders were not familiar with the guideline (38% US responders vs 16% Dutch responders, P < 0.001). Perianal inspection was frequently (“often” or “always” on a 5‐point Likert scale) conducted by 78% of responders. Digital rectal examination was frequently done by 42%. Inquiry about sexual abuse was made by 18%. Commonly reported reasons for omitting these items were perceived patient or parental discomfort. Most frequently implemented initial nonpharmacological interventions included a toilet training program (89%), optimizing fluid and fiber intake (86% and 81%), a defecation diary (62%), and a reward system (60%). Polyethylene glycol was the most prescribed medication for disimpaction (68%) and maintenance treatment (57% for infants, 97% for children ≥1 year).Conclusions:Many responders were not familiar with the ESPGHAN/NASPGHAN guideline for functional constipation. Nonetheless, therapeutic decisions correlated fairly well with recommendations from the guideline, especially for children 1 year of age or older. Guideline awareness and adherence remain to be improved. Future studies should focus on exploring strategies to improve guideline implementation through the development of digital learning tools.
Impaired IL‐10 Receptor‐mediated Suppression in Monocyte From Patients With Crohn Disease
Authors: Nunberg Moran Y. , Werner Lael , Kopylov Uri , Haberman Yael , Lahad Avishay , Weiss Batia , Shouval Dror S. 
Published: October 2017

ABSTRACTObjectives:Interleukin‐10 (IL‐10) is an immunoregulatory cytokine that has a central role in suppressing proinflammatory responses. Patients with deleterious mutations in interleukin (IL)‐10 or IL‐10 receptor (IL‐10R) genes develop severe colitis and perianal disease in the first months of life. Whether IL‐10R expression and signaling in pediatric‐ or adult‐onset Crohn disease (CD) are altered is unknown. The objective of this study was to characterize IL‐10R expression and IL‐10R‐mediated suppression in patients with CD.Methods:Monocytes were sorted from peripheral blood mononuclear cells of patients with CD and control subjects. IL‐10R expression was determined by flow cytometry. Monocytes were stimulated with lipopolysaccharide (LPS) for 3 hours in the presence of different concentrations of IL‐10 to determine IL‐10‐mediated suppression of tumor necrosis factor α production. Signaling through the IL‐10R was evaluated by quantifying STAT3 phosphorylation in response to IL‐10 stimulation.Results:Forty‐two subjects were enrolled in this study: 19 with CD and 23 controls. Stimulation of monocytes with LPS markedly increased IL‐10R expression in both groups but to a much lower extent in patients with CD. In addition, IL‐10‐mediated suppression of TNFα production upon LPS stimulation and IL‐10‐induced STAT3 phosphorylation were attenuated in patients with CD versus controls. Finally, LPS‐stimulated monocytes from patients with CD secreted significantly lower quantities of IL‐10, compared with control monocytes.Conclusions:IL‐10R expression and signaling are decreased in monocytes from patients with CD. Additional studies are required to assess whether similar patterns occur in other innate immune cells, especially in the gut, and whether disease activity, medical therapy, and genetic factors modulate these findings.