bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurophysiological Effects of High Velocity and Low Amplitude Spinal Manipulation in Symptomatic and Asymptomatic Humans
Authors: Wirth Brigitte , Gassner Antonia , de Bruin Eling D. , Axén Iben , Swanenburg Jaap , Humphreys Barry Kim , Schweinhardt Petra 
Published: July 2019

Study Design.
Systematic review.

Objective.
To summarize the evidence of neurophysiological effects of spinal manipulative therapy (SMT) with a high velocity low amplitude thrust (HVLA-SMT) in asymptomatic and symptomatic humans.

Summary of Background Data.
HVLA-SMT is effective in reducing back pain, but its mode of action is not fully understood.

Methods.
A systematic literature search (until July 2018) was conducted by a professional librarian in seven databases (Medline (OvidSP), Premedline (PubMed), EMBASE, Cochrane, CINAHL, PEDro, and Scopus). Two authors selected the studies according to the a priori described criteria and scored study quality. Only controlled studies of at least moderate quality were included. Effects of HVLA-SMT on a particular outcome measure were defined as more than one study showing a significantly greater effect of HVLA-SMT compared with the control intervention.

Results.
From the 18 studies included (932 participants in total), there was evidence only for an association between HVLA-SMT and changes in the autonomic nervous system, reflected in changes in heart rate variability and skin conductance. Most studies focused on healthy volunteers and none related neurophysiologic changes to pain reduction.

Conclusion.
This systematic review points to HVLA-SMT affecting the autonomic nervous system. The effects seem to depend on the spinal level of HVLA-SMT application and might differ between healthy volunteers and pain patients. There is a need for high-quality studies that include patients, well characterized for pain duration and outcome measure baseline values, and address the relation between changes in neurophysiology and pain.

Level of Evidence: 2
Association Between Smoking and Survival Benefit of Immunotherapy in Advanced Malignancies
Authors: Wallis Christopher J.D. , Satkunasivam Raj , Butaney Mohit , Khan Usman A. , Goldberg Hanan A. , Freedland Stephen J. , Patel Sandip P. , Hamid Omid , Pal Sumanta K. , Klaassen Zachary 
Published: July 2019

Objectives:
Smoking is associated with an increased tumor mutational burden. As tumor mutational burden has been shown to correlate with response to immunotherapy (IO), we hypothesized that a history of smoking may be associated with better response to IO.

Methods:
We utilized a systematic review with stratified meta-analysis of randomized clinical trials of IO versus standard of care in patients with advanced solid organ malignancies.

Results:
Among 9 relevant studies, we found no significant difference in the benefit of IO, compared with other systemic therapies, between ever smokers (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.58-1.04; P=0.09) and never smokers (HR, 0.75; 95% CI, 0.67-0.86; P<0.0001) (test for difference P=0.83). We also observed no significant difference between current (HR, 0.92; 95% CI, 0.63-1.34; P=0.66; I
2=67%) and never smokers (HR, 0.74; 95% CI, 0.59-0.93; P=0.01; I
2=46%) (test for difference P=0.35).

Conclusions:
Stratified meta-analysis demonstrates that smoking status is not significantly associated with the response to IO in the treatment of advanced solid organ malignancies.
An Atypical Fibroxanthoma and Intradermal Nevus Collision Tumor—Potential for Misdiagnosis
Authors: Steel Andrea , Debbaneh Maya , Cassarino David 
Published: July 2019

Abstract:
Atypical fibroxanthomas (AFX) are rare cutaneous tumors, which typically present as a solitary ulcerated papule or nodule on sun-damaged skin. Despite malignant-appearing features on histology, AFX typically pursue a benign clinical course. In rare instances, AFX can form collision tumors with other lesions. However, to the best of our knowledge, AFX in collision with a nevus has never been previously reported. In this study, we describe such a lesion for its novelty and challenge in diagnosis, as this case was originally considered to be melanoma arising in a nevus. On histologic examination, there were 2 distinct populations of cells; one composed of markedly atypical and pleomorphic epithelioid and oval to spindled cells, consistent with AFX, and the other, a bland-appearing intradermal nevus with congenital features. The AFX population stained positive with smooth muscle actin, CD10, and CD68 and was negative for S100, SOX10, Melan-A, desmin, pancytokeratin, CK5/6, and p63. Deep to this was a second population of small, bland-appearing melanocytes in a broad, band-like distribution. This unusual collision tumor between AFX and an intradermal nevus highlights the important role immunohistochemistry plays in avoiding the misdiagnosis and potential overtreatment of benign or low-grade lesions, and in identifying potential mimickers.
DBP Evaluations in DBPNet Sites: Is Race/Ethnicity a Significant Factor in Care?
Authors: Augustyn Marilyn , Silver Ellen Johnson , Blum Nathan , High Pamela , Roizen Nancy , Stein Ruth E. K. 
Published: July 2019

ABSTRACT:

Objective:
To examine whether there are differences between non-Hispanic white (NHW) and nonwhite (NW) children in referral questions, evaluations, and diagnoses during developmental behavioral pediatrician (DBP) evaluations at academic medical centers and the potential role of socioeconomic factors in any disparities noted.

Design/Methods:
This observational study used survey data from 56 DBPs at 12 sites participating in DBPNet. Child race and ethnicity were obtained from DBP report. Mixed-model logistic and linear regression analyses controlling for site, provider, and socioeconomic proxy variables (insurance type, parent education, and language spoken at home) were used to compare groups on referral concerns, evaluation procedures, and diagnoses.

Results:
Among the patients evaluated, 349 were NHW, 406 were NW (187 Hispanic, 135 black, 58 Asian/Pacific Islander, and 26 other/mixed), and 29 were missing race/ethnicity data. The mean waiting time controlling for site and provider was 20.4 weeks for NHW children and 20.5 weeks for NW children. Reasons for referral were similar in the NWH and NW groups, with only sleep problem concerns being more frequent among NHW children (9.2% vs 3.4% NW, p = 0.01). Patients also had similar evaluations in the 2 groups; the only differences found were that more NHW than NW children had genetic testing (33.1% vs 19.3%, p = 0.02), ophthalmology evaluations (8.7% vs 3.4%, p = 0.03), and psychopharmacologic evaluations (19.1% vs 9.7%, p = 0.008). Numbers and types of diagnoses did not vary by race/ethnicity.

Conclusion:
This study suggests little inequality between NHW and NW children in wait time to care, reasons for referral, workup, or final diagnosis for initial DBP evaluation at these 12 academic DBP centers when socioeconomic factors are considered. Nevertheless, because differences in these related factors may be mechanisms through which racial/ethnic disparities can arise, it will be important to consider them in planning models and care protocols for underserved communities.
Air pollution-associated changes in biomarkers of diabetes risk
Authors: Holliday Katelyn M. , Lamichhane Archana P. , Gondalia Rahul , Stewart James D. , Madrigano Jaime , Shih Regina A. , Yanosky Jeff D. , Liao Duanping , Wellenius Gregory A. , Whitsel Eric A. 
Published: July 2019

Background:
Ambient particulate matter (PM) and nitrogen oxide (NOx) air pollution may be diabetogenic.

Objective:
To examine longitudinal associations of short- and longer-term mean PM ≤10 μm (PM10), PM ≤2.5 μm (PM2.5), and NOx concentrations with five biomarkers of diabetes risk.

Methods:
We studied a stratified, random minority oversample of nondiabetic Women’s Health Initiative clinical trials participants with biomarkers and geocoded participant address-specific mean air pollution concentrations available at repeated visits (years = 1993–2004; n = 3,915; mean age = 62.7 years; 84% white). We log-transformed the biomarkers, then used multi-level, mixed-effects, longitudinal models weighted for sampling design/attrition and adjusted for sociodemographic, clinical, and meteorological covariates to estimate their associations with air pollutants.

Results:
Biomarkers exhibited null to suggestively negative associations with short- and longer-term PM10 and NOx concentrations, e.g., −3.1% (−6.1%, 0.1%), lower homeostatic model assessment of insulin resistance per 10 μg/m3 increase in 12-month PM10. A statistically significant interaction by impaired fasting glucose (IFG) at baseline in this analysis indicated potentially adverse effects only among women with versus without IFG, i.e., 1.4% (−3.5%, 6.5%) versus −4.6% (−7.9%, −1.1%), P
interaction < 0.05. In contrast, longer-term PM2.5 concentrations were largely but not statistically significantly associated with higher biomarkers.

Conclusions:
Low-level short-term PM10 and NOx concentrations may have negligible adverse effects on biomarkers of diabetes risk. Although longer-term mean PM2.5 concentrations showed primarily null associations with these biomarkers, results suggestively indicated that PM2.5 exposure over the range of concentrations experienced in the United States may adversely affect biomarkers of diabetes risk at the population level, as may longer-term mean PM10 concentrations among women with IFG.
The NLRP3 Inflammasome as a Pharmacological Target
Authors: Marchetti Carlo 
Published: July 2019

Abstract:
NLRP3 is a cytosolic receptor member of the nucleotide-binding oligomerization domain NOD-like receptor family that surveys the intracellular environment for the presence of infection, pathogens, and metabolic alarms. Although the surveillance activity of NLRP3 is required to protect the host from several pathogens, uncontrolled activity can be detrimental to the host. Pharmacological and genetic strategies limiting NLRP3 inflammasome activation have been shown to be beneficial in a wide range of experimental models, from common pathologies such as arthritis, cardiovascular disease, and metabolic syndromes to rare genetic disorders such as cryopyrin-associated periodic syndrome. Thus, compounds that prevent NLRP3 inflammasome activation are of common interest with relevant therapeutic potential. The focus of this review is recent developments in NLRP3 inflammasome inhibitors.
FIRST FAILED MACULAR HOLE SURGERY OR REOPENING OF A PREVIOUSLY CLOSED HOLE
Authors: Reid Gerard A. , McDonagh Niamh , Wright David M. , Yek John T. O. , Essex Rohan W. , Lois Noemi 
Published: July 2019

Purpose:
To evaluate repeated surgery for idiopathic full-thickness macular hole that failed to close (FTC) after first surgery or reopened (RO) once originally closed.

Methods:
Systematic review and meta-analysis. Pubmed.gov and Cochrane Library were searched for studies in English presenting outcomes of idiopathic full-thickness macular hole that FTC or RO (case reports/series of <5 cases excluded).

Outcome Measures:
Anatomical closure, postoperative best-corrected visual acuity, intraoperative/postoperative complications, and patient-reported outcomes. Meta-analysis was performed on aggregate and available individual participant data sets using the metafor package in R.

Results:
Twenty-eight eligible studies were identified. After reoperation, pooled estimates for anatomical closure were 78% (95% confidence interval 71–84%) and 80% (95% confidence interval 66–89%) for FTC and RO groups, respectively. On average, best-corrected visual acuity improved in both groups. However, only 15% (28 of 189 eyes) of FTC eyes achieved best-corrected visual acuity of ≥6/12. The pooled estimated probability of ≥2-line best-corrected visual acuity improvement was 58% in the FTC group (95% confidence interval 45–71%); meta-analysis was not possible in the RO group. The most common complication was cataract.

Conclusion:
Reoperation for FTC or RO idiopathic full-thickness macular hole achieved a clinically meaningful visual acuity improvement in more than half of patients; high levels of vision (≥6/12), however, were uncommon.
SEVERE RECURRENT FIBROVASCULAR PROLIFERATION AFTER COMBINED INTRAVITREAL BEVACIZUMAB INJECTION AND LASER PHOTOCOAGULATION FOR AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY
Authors: Tanaka Shin , Yokoi Tadashi , Katagiri Satoshi , Yoshida Tomoyo , Nishina Sachiko , Azuma Noriyuki 
Published: July 2019

Purpose:
To describe the clinical features of severe recurrent fibrovascular proliferation after intravitreal bevacizumab injections and laser photocoagulation for aggressive posterior retinopathy of prematurity.

Methods:
This retrospective, nonrandomized case series reviewed the medical and ophthalmic records in the referral hospital and our hospital.

Patients:
Four patients (seven eyes) with aggressive posterior retinopathy of prematurity.

Results:
The patients were referred for vitrectomy with/without lensectomy for recurrent fibrovascular proliferation with a tractional retinal detachment after combined intravitreal bevacizumab injections and laser photocoagulation. Three patients were born at 22 weeks or 23 weeks' gestational age and one patient at 29 weeks' gestational age. Preoperatively, fluorescein angiography images showed all eyes had tractional retinal detachment from regrowth of fibrovascular proliferation 3 months to 5 months after the intravitreal bevacizumab injection and abnormal retinal vasculature; four eyes had a broad ischemic retina. Postoperatively, four eyes had retinal attachment and three eyes a total retinal detachment. Neovascular glaucoma developed in five of the seven eyes during the clinical course.

Conclusion:
Severe fibrovascular proliferation may recur due to widespread retinal ischemia with capillary dropout and abnormal vasculature after failed combined intravitreal bevacizumab and laser photocoagulation therapy as the initial treatment for aggressive posterior retinopathy of prematurity. Careful follow-up is important especially after anti–vascular endothelial growth factor treatment, with recognition that severe reactivation is possible.
Graft Survival After Penetrating and Endothelial Keratoplasty in Iridocorneal Endothelial Syndrome
Authors: Rotenberg Michael , Downward Lewis , Curnow Elinor , Larkin Daniel F. , Tuft Stephen J. ,   on behalf of the National Health Service Blood and Ocular Tissue Advisory Group and Contributing Ophthalmologists (OTAG Study 27)
Published: July 2019

Purpose:
To compare the survival of a first penetrating keratoplasty (PK) or endothelial keratoplasty (EK) for iridocorneal endothelial (ICE) syndrome with transplant survival in Fuchs endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK).

Methods:
We compared graft survival of PK and EK for ICE syndrome for 2 time periods. We then compared graft survival in ICE syndrome with graft survival in FED and PBK. Kaplan–Meier estimates of graft survival up to 5 years posttransplant were calculated with 95% confidence intervals (CI), whereas comparisons between the groups were performed using the log-rank test.

Results:
We included 86 first transplants for ICE syndrome. There was no difference in graft survival between the 58 PKs and the 28 EKs for up to 5 years after surgery (P = 0.717). For the period from 2009 to 2017, the 5-year graft survival rates for ICE syndrome were 64.3% (CI, 21.8%–88.0%) for the 16 PKs and 66.8% (CI, 41.8%–83.0%) for the 26 EKs (P = 0.469). Between 2009 and 2017, the 5-year survival rate for 42 grafts with ICE syndrome was 62.7% (CI, 39.6%–79.0%), which was lower than 75.9% (CI, 74.2%–77.4%) in 7058 transplants for FED but higher than 55.1% (CI, 52.0%–58.0%) in 3320 transplants for PBK, although the numbers of ICE transplants are too small to tell whether this difference was by chance.

Conclusions:
The results indicate no difference in graft survival between PK and EK for ICE syndrome. Graft survival in ICE syndrome is intermediate between that of FED and PBK.
Direct Visualization of Continuous Meibum Secretion From the Orifices of Meibomian Glands to the Tear Film
Authors: Cho Bum-Joo , Jee Dong Hyun , Kim Won Jun , Shin Min Chul , Kim Eun Chul , Kim Man Soo , Hwang Ho Sik 
Published: July 2019

Purpose:
To present a new method to directly visualize meibum secretion on the tear film from meibomian gland orifices and show that meibum is continuously secreted between blinking.

Methods:
Eighteen patients with dry eye syndrome and 17 healthy subjects were included in the study. We used the Lipiscanner to evaluate the tear film lipid layer. The lipid layer was classified into thick, normal, and thin lipid layer. The lipid layer on the lower tear meniscus of the right eye was observed after a drop of saline solution was applied to the eye. We recorded continuous meibum secretion onto the tear meniscus surface. We calculated the rate of continuous meibum secretion by analyzing videos. Noncontact meibography was performed for meibomian glands in the lower eyelid. The quality of meibum from the 5 orifices at the same area was then scored.

Results:
The mean continuous meibum secretion rate was 2.7 pL/s in the healthy group and 8.0 pL/s in the dry eye group. The rates were 1.3, 6.7, and 9.4 pL/s in the thin, normal, and thick tear film lipid layer group, respectively. They were 3.4, 3.4, 10.7, and 18.1 pL/s in grade 0, 1, 2, and 3 meibomian gland dropout groups, respectively. The rates were 0.00, 4.7, 10.1, 2.0, and 0.7 pL/s in the normal meibum, yellow without increased viscosity, yellow with increased viscosity, toothpaste, and no meibum groups, respectively.

Conclusions:
We showed how to visualize meibum being secreted into the tear film from the meibomian gland orifices, and we were able to observe the continuous secretion of meibum between blinks.
Sex Disparity in How Pain Sensitivity Influences Dry Eye Symptoms
Authors: Li Wing , Lin Meng C. 
Published: July 2019

Purpose:
Women have a higher dry eye disease prevalence compared with men, although only relatively minor differences in the ocular surface have been observed. Interestingly, a sex difference in pain sensitivity is known, and recent research suggests that pain sensitivity is associated with dry eye symptoms. This study attempts to discern whether the association between pain sensitivity and dry eye symptoms varies between women and men.

Methods:
In this prospective cross-sectional study, subjects were seen for one visit where they were asked to fill out a set of questionnaires consisting of the Pain Sensitivity Questionnaire, Ocular Surface Disease Index (OSDI), and other dry eye questionnaires. This was followed by an ocular surface assessment on both eyes.

Results:
Two hundred eighty-seven subjects (194 women, 93 men) completed the study. Intersex differences in the ocular surface were noted. Even after accounting for these differences, an interaction effect between sex and Pain Sensitivity Questionnaire-minor score on dry eye symptoms was observed, with only women noting increased symptoms on the OSDI (P < 0.005) and other dry eye questionnaires (P values ranging from 0.01 to <0.005) with greater pain sensitivity. After controlling for other variables, women with the highest pain sensitivity had a 17-point higher OSDI score and greater symptoms, as reported by all the other dry questionnaires compared with their male counterparts.

Conclusions:
The role of pain sensitivity on dry eye symptoms appears to vary between women and men. This difference provides insight into why women have a significantly higher dry eye disease prevalence than men.
Pediatric Microbial Keratitis in Queensland, Australia (2005 to 2015)
Authors: Green Matthew , Apel Andrew , Stapleton Fiona 
Published: July 2019

Purpose:
To estimate the incidence and define the demographic and microbiological profile of pediatric microbial keratitis (MK) in Queensland, Australia.

Methods:
This is a retrospective study based on the multicenter database of all patients with positive corneal scrapes in Queensland, Australia, between 2005 and 2015. Pathology organizations in Queensland were identified by online and local directory search and were requested to provide digital records of the corneal scrapes, including patient demographics and culture and antibiotic sensitivity results. Patient demographics, yearly incidence (based on state population data), cultured organisms, and antibiotic sensitivities in MK in patients 16 years old or younger with keratitis were reported and compared with adults.

Results:
Pediatric cases comprised 125 cases of a total 3182 (3.9%) included in the database. The yearly incidence of MK in children was estimated to be 0.11 cases per 10,000 people 16 years old or younger (95% confidence interval, 0.086–0.134), which was significantly lower than the estimated incidence in people older than 16 years (0.82 per 10,000 people; 95% confidence interval, 0.72–0.92; P < 0.0001). The average age of pediatric patients was 9.2 years (SD 5.5). Culture results showed Gram-positive organisms were the most common causative organisms (84%; 67.2%), Pseudomonas aeruginosa was the most common single organism (24%; 19.2%), and fungal recovery was low (4%; 3.2%). Cultures positive for Streptococcus pneumoniae (17%; 13.6%; P < 0.001) and bacteria sensitive to all recorded antibiotics (96.8%; P < 0.001) were significantly more common in children.

Conclusions:
MK in pediatric patients is less common than in adults. Although Streptococcus pneumoniae was more common in children, P. aeruginosa was the most common isolate.
Keratoconus Prevalence Among High School Students in New Zealand
Authors: Papali'i-Curtin Alistair T. , Cox Rachel , Ma Tiffany , Woods Lisa , Covello Albie , Hall R. C. 
Published: July 2019

Purpose:
To determine the prevalence of keratoconus among high school students in Wellington, New Zealand.

Method:
The Wellington Keratoconus Study was a population-based prospective cross-sectional study of 2 cohorts in Wellington: cohort 1 (year 9 students, mean age 13.9 years) and cohort 2 (year 11 students, mean age 15.5 years).

Results:
A total of 1916 students with a mean age of 14.6 years participated from 20 schools in the region. Keratoconus was found in 1:191 (0.52%) participants overall and in 1:45 (2.25%) Maori participants. Pentacam mean Kmax of 48.7 diopters (D) (cohort 1, 45.5 D; cohort 2, 49.9 D), thinnest pachymetry of 494.05 μm (cohort 1, 479.0 μm; cohort 2, 499.5 μm), posterior elevation at the thinnest point of 23.4 (cohort 1, 15.2; cohort 2, 26.6), Belin/Ambrosio enhanced ectasia display overall D value of 4.30 (cohort 1, 3.2; cohort 2, 4.7) were noted in participants with keratoconus. In those with keratoconus, 8 of 10 had visual impairment of 0.2 Logarithm of the Minimum Angle of Resolution (LogMAR) or worse in the better eye; 7 of 10 did not use visual aids; 7 of 10 had atopy; and 6 of 10 were from a low school decile. In those without keratoconus, 43.8% had atopy.

Conclusions:
Keratoconus may affect up to 1 in 191 New Zealand adolescents and 1 in 45 Maori adolescents. Keratoconus appeared to be associated with Maori ethnicity, atopy, lower school decile, visual impairment, and the underutilization of visual aids. Nationwide screening programs may have a role in reducing the burden of disease associated with keratoconus.