bluuebunny/crossref_metadata_2025 huggingface dataset:
Provider-reported challenges and barriers to referring patients to neuro-oncology clinical trials: a report from the Society for Neuro-Oncology member survey
Authors: Rogers James L , Acquaye Alvina , Vera Elizabeth , Bates Amanda , Wen Patrick Y , Armstrong Terri S
Published: September 2019

Background

Whereas much information exists in general oncology regarding the barriers to clinical trial referral, those specific to neuro-oncology are not yet well known. Trial barriers lead to lower patient accrual, which can lead to less-efficient clinical trials and slower improvement of the standard of care, which may negatively effect patient outcomes. Thus, the aim of this study was to determine the clinical trial referral barriers that are specific to neuro-oncology to improve trial accrual rates.

Methods

An electronic survey was completed by 426 Society for Neuro-Oncology members, of whom 372 are included in this report. Descriptive statistics, including frequencies, means, and proportions, were used to characterize our survey sample.

Results

Only 22% of participants reported that their center tracks referrals to clinical trials inside as well as outside their own institution, with an estimate of less than 30% of patients referred. The most commonly reported provider-referral barrier was finding ongoing trials in the patient’s geographic area. Providers also perceived that while considering participation in a trial their patients may not qualify for any trials, and if they do, may be unable to travel to the study site for follow-up. Additionally, practice location and provider and institution type all influenced referral patterns.

Conclusion

Efforts should be made to broaden trial availability and eligibility criteria, improve trial referral tracking, and ensure patients and their caregivers understand the goals and importance of clinical trials to reduce barriers and improve trial participation.
The perspective of patients with early rheumatoid arthritis on the journey from symptom onset until referral to a rheumatologist
Authors: Diederik De Cock , Kristien Van der Elst , Veerle Stouten , Donna Peerboom , Johan Joly , Rene Westhovens , Patrick Verschueren
Published: September 2019

Objectives

Timely treatment of patients with Early Rheumatoid Arthritis (ERA) favors a beneficial disease outcome. However, individuals often delay their contact with a healthcare professional (HCP) after ERA-related symptom onset. This study investigates the patients’ perspective on the patient’s journey from RA symptom onset until referral to a specialist.

Methods

A subgroup of patients with ERA from the Care in ERA (CareRA) trial were retrospectively interviewed to discuss their initial ERA-related experiences preceding diagnosis, using a bespoke assessment form. The form’s first section focused on initial symptoms and patients’ help-seeking behavior. The second part probed the consulted HCPs’ actions. Additional notes derived from the patient stories were thematically analyzed.

Results

Among 94 patients, pain (97%), swelling (73%) and stiffness (52%), typically in multiple joints, were reported as initial ERA-symptoms. The general practitioner (GP) was generally the first contacted HCP (87%). Frequently reported reasons to visit a HCP were too intense pain (90.4%) and difficulties in performing daily activities (69%). In 44.1% of patients, the HCP suspected ERA at the first visit. Approximately 25% of patients needed >5 visits before ERA detection. GPs mainly referred patients to rheumatologists (71%). Thematic analysis uncovered that often multiple HCPs were involved in the journey to RA detection and referral.

Conclusion

Pain is the most commonly reported initial symptom of ERA and the main reason to visit a HCP, mostly a GP. These GPs play a pivotal role in early detection and correct referral. Furthermore, the patient’s journey seems complex with often multiple HCPs involved.
Occurrence and Extent of Boscalid Resistance in Populations of Alternaria alternata from California Pistachio Orchards
Authors: Avenot Hervé F. , Michailides Themis J.
Published: September 2019

Alternaria late blight (ALB) caused by Alternaria spp. is an annual disease problem in California pistachio and requires repeated applications of fungicides to prevent significant losses of pistachio foliage and nut quality. From 2003 onward, the succinate dehydrogenase inhibiting fungicide boscalid has played a key role in ALB management. The development of boscalid resistance in A. alternata populations was monitored from 2005 to 2012 in pistachio producing areas in California. A total of 1,765 single-spore isolates, collected from commercial and experimental pistachio orchards with or without a history of boscalid exposure, were tested in a radial growth assay in agar media amended with the discriminatory dose of 10 µg/ml of boscalid. The frequency of boscalid-resistant isolates in 2005 was 12% but increased significantly and remained stable toward the end of the survey period. Most of the resistant isolates exhibited a high level of resistance (R) to boscalid with percent of mycelial growth inhibition (PGI) values between 0 and 50%, whereas significantly fewer isolates had an intermediate level (IR) of resistance (50 < PGI < 75%). The frequency of sensitive (S) isolates (75 < PGI < 100%) was generally the highest in orchards with no history of boscalid usage, whereas mean incidences of boscalid-resistant populations of Alternaria were 81, 92.4, 80.2, and 98%, in 2006, 2007, 2011, and 2012, respectively, in orchards that received a high number (at least three per season) of boscalid spray applications. In comparison, none to relatively low frequencies (0 to 12%) of resistance were observed in populations with no or limited exposure to Pristine, suggesting an air-movement of resistant spores through wind from treated to nontreated areas. In 2012, boscalid-resistant isolates were found practically in every sampled location in all counties, with the orchards in Fresno, Madera, Tulare, and King Counties being the locations with the highest frequencies of resistance (100%). Monitoring of A. alternata AaSDHB, AaSDHC, and AaSDHD mutations in 286 boscalid-resistant phenotypes identified 11 mutations, leading to amino acid substitutions in AaSDHB (seven mutations: H277Y/R/L, P230A/R, N235D/T), AaSDHC (one mutation: H134R), and AaSDHD (three mutations: D123E, H133R/P), with AaSDHB mutations being the most prevalent (80%) ones throughout the survey period. The majority of isolates carrying these mutations exhibited the R phenotype toward boscalid. The increased prevalence of boscalid resistance in populations of A. alternata is a likely contributing factor to the inability of pistachio farmers to successfully control ALB with Pristine. Other factors implicated in the rapid and widespread occurrence of A. alternata boscalid-resistant populations in California pistachios are further discussed.
Assessing the Role of Temperature, Inoculum Density, and Wounding on Disease Progression of the Fungal Pathogen Ceratocystis fimbriata Causing Black Rot in Sweetpotato
Authors: Stahr M. , Quesada-Ocampo L. M.
Published: September 2019

In 2014, Ceratocystis fimbriata, causal agent of black rot in sweetpotato, reemerged and inflicted large financial losses on growers in the United States. Black rot continues to damage sweetpotatoes and has become a priority to the industry since then. In contrast, little is known about the biology of C. fimbriata and the epidemiology of sweetpotato black rot. In this study, effects of environmental factors such as inoculum density, RH, and temperature on sweetpotato black rot were determined. Cured sweetpotatoes were wounded with a toothpick to simulate puncture wounds, inoculated with different spore suspensions (inoculum density) (104, 105, or 106 spores/ml), and incubated under different RH (85.53, 94.09, or 97.01%) and temperature (13, 18, 23, 29, or 35°C) for 21 days. In a separate experiment, five root wounding types (cuts, punctures, abrasions, end breaks, and macerating bruises) were compared. All wounded roots were subsequently soaked in a 103 spores/ml suspension and incubated at 100% RH and 23°C for 21 days. This study found 29 and 23°C to be the optimal temperature for black rot disease development and sporulation, respectively. No pathogen growth was observed at 13 and 35°C. Increased inoculum density significantly (P < 0.0001) increased disease incidence, but increasing RH had an effect only on sporulation area. All wound types resulted in increased disease incidence and sporulation as early as 7 days postinoculation. Our results highlight the importance of characterizing factors that affect disease development for achieving successful disease management strategies. Findings from this study will be used to improve disease management for sweetpotato black rot by suggesting tighter regulation of curing and storage conditions and better postharvest handling of sweetpotato roots to avoid unnecessary wounding.
Unraveling the Complexity of Coffee Leaf Rust Behavior and Development in Different Coffea arabica Agroecosystems
Authors: Merle Isabelle , Pico Jimmy , Granados Eduardo , Boudrot Audrey , Tixier Philippe , Virginio Filho Elías de Melo , Cilas Christian , Avelino Jacques
Published: September 2019

Crop health management systems can be designed according to practices that help to reduce crop losses by restricting pathogen development and promoting host plant growth. A good understanding of pathogen and host dynamics, which are interdependent, is therefore needed. In this article, we used a holistic approach to explain the behavior of coffee leaf rust (CLR), a major coffee disease. We monitored coffee plant and CLR dynamics simultaneously in plots under different disease management and agroforestry systems. Diseased leaves were also collected to characterize inoculum stock and rust life stages (latent rust area, area with uredospores, necrosis due to rust) through picture analysis. We used structural equation modeling to obtain an overview of CLR pathosystem functioning on a plant scale. This overview integrates processes such as disease dilution by host leaf renewal, direct and indirect effects of fruit load on CLR development, antagonistic effects of shading depending on rust life stages, the tonic effect of copper-based fungicides on leaf retention, and effects on rust life stages depending on fungicide types. From our results, we also deduced that the inoculum stock could be calculated in unsprayed plots from the rust area with uredospores, with uredospores at 58 × 103 cm−2, on average.
Mutations in the Membrane-Anchored SdhC Subunit Affect Fitness and Sensitivity to Succinate Dehydrogenase Inhibitors in Botrytis cinerea Populations from Multiple Hosts
Authors: Amiri Achour , Zuniga Adrian I. , Peres Natalia A.
Published: September 2019

Succinate dehydrogenase inhibitors (SDHIs) are an essential group of fungicides for managing gray mold, caused by Botrytis cinerea, in numerous crops. Resistance to boscalid, an early-generation SDHI, is widespread worldwide and was linked to mutations in the iron-sulfur protein encoding the SdhB subunit of the SDH complex. Herein, we report on four simultaneous dependent mutations at codons 85 (G85A), 93 (I93V), 158 (M158V), and 168 (V168I) of the membrane-anchored SdhC subunit of B. cinerea. Isolates without and with mutations in SdhC were referred to as C− and C+ genotypes, respectively. The C+ genotype was found in all the five surveyed hosts from different U.S. regions but its frequency was higher, 25 to 40%, in the tree fruit isolates compared with 12 to 25% in the small fruit populations. The four SdhC mutations were found in isolates without mutations in SdhB or with mutations known to confer resistance to the SDHIs in SdhB. However, the frequency of C+ isolates was significantly higher in the SdhB wild-type isolates, which suggests that SDHI sprays may have played a role in selecting for the C− over the C+ genotype. Field C+ isolates exhibited reduced sensitivity to fluopyram and increased sensitivity to boscalid and penthiopyrad in vitro and on detached fruit. Homology modeling confirmed the positioning of the four mutations in the ubiquinone-binding pocket. The SdhCG85A is found in the proximal ubiquinone binding site and SdhCM158V is positioned in the iron sulfur protein interface next to the [3Fe-4S] cluster, whereas SdhCI93V is positioned next to the heme b with vital functions in the SDH enzyme. Beside the differential sensitivity to the SDHIs, these mutations caused a significant fitness cost in the C+ isolates including sporulation and increased sensitivity to reactive oxygen species. The presence of Botrytis populations differentially sensitive to the SDHIs suggests increased risks for resistance development but also opens up new perspective for future gray mold management using different SDHI fungicides.
Nicotine exposure during pregnancy programs osteopenia in male offspring rats via α4β2‐nAChR–p300‐ACE pathway
Authors: Xiao Hao , Wen Yinxian , Pan Zhengqi , Shangguan Yangfan , Magdalou Jacques , Wang Hui , Chen Liaobin
Published: September 2019

Prenatal nicotine exposure (PNE) induces developmental toxicity in offspring. However, the long‐term harmful effects on bone development and the intrauterine programming mechanism attributed to PNE remain unclear. In the present research, pregnant Wistar rats were injected subcutaneously with nicotine (2 mg/kg/d) to obtain and analyze bone samples from the fetal and adult offspring. Bone marrow mesenchymal stem cells (BMSCs) were treated with nicotine during osteogenic differentiation to clarify the related molecular mechanisms. The results indicated that PNE led to bone dysplasia in the fetuses and reduced bone mass in the adult offspring, which was mediated by the sustained activation of the local bone renin angiotensin system (RAS) and suppressed osteogenic differentiation before and after birth. In vitro, nicotine suppressed BMSCs' osteogenic function through promoting angiotensin‐converting enzyme (ACE) expression and activating RAS. Furthermore, nicotine induced histone acetylase p300 into the nuclei of the BMSCs by acting on the α4β2‐nicotinic acetylcholine receptor (α4β2‐nAChR), leading to the increased histone 3 lysine 9 acetylation level of ACE and RAS activation. Taken together, the sustained activation of local bone RAS mediated prenatal nicotine‐induced osteopenia in adult offspring via the α4β2‐nAChR–p300‐ACE pathway.—Xiao, H., Wen, Y., Pan, Z., Shangguan, Y., Magdalou, J., Wang, H., Chen, L. Nicotine exposure during pregnancy programs osteopenia in male offspring rats via α4β2‐nAChR–p300‐ACE pathway. FASEB J. 33, 12972–12982 (2019). www.fasebj.org
Procedural sedation in ambulatory anaesthesia: what's new?
Authors: Raeder Johan
Published: September 2019

Purpose of review

Although sedation traditionally has been regarded as an easy, straight forward and simple variety of general anaesthesia; the trends are to make sedation more sophisticated and dedicated. Also to have a critical look at old dogmas, as they are usually derived from the practice of general anaesthesia. Safety always has to be first priority, especially as the practice grows out of traditional theatres and frequently are being practiced by nonanaesthetic personnel.

Recent findings

Safety comes from learning of rare cases with severe problems as well as better guidelines and rules of accreditation. Further, there is a growing quest for evidence on pragmatic, high-quality, cost-effective practice; in terms of logistics, monitoring, choice of drugs and quality assurance. The traditional drugs, such as propofol, midazolam and remifentanil, are still defending their dominant position but are being challenged by ketamine and etomidate. Remimazolam and dexmedetomidine are new promising drugs in this area, whereas metoxyflurane may have a revival in some situations. Further, there is growing evidence into specific protocols, practice for special procedures and for patients with special challenges.

Procedural sedation deserves to have high degree of attention for further developments, both from a scientific and pragmatic point of view, as the practice is very diversified and growing.
Proper Surgical Dressing Removal Technique in Obstetrics and Gynecology
Authors: Cherry Steven B. , Vasko Michelle
Published: September 2019

BACKGROUND:

Medical adhesive–related skin injury is often caused by improper technique in removing surgical dressings and may lead to pain, infection, delayed healing, and litigation. It is rare for obstetrics and gynecology residents and staff to receive any training regarding the proper technique for removing surgical dressings.

TECHNIQUE:

The proper technique for the removal of adhesive dressings is discussed, minimizing patient discomfort and lessening the risk of skin injury. A video is included.

EXPERIENCE:

By using a slow rate of removal, the proper angle of traction, counter-traction with an index finger, and adhesive solvents when necessary, patients experience much less pain with dressing removal, and skin injury can be avoided.

CONCLUSION:

Using proper technique when removing adhesive dressings can reduce the incidence of skin injury. Obstetrician–gynecologists should be cognizant of the risk of iatrogenic medical adhesive–related skin injury.
Exploring Inflammatory Mediators in Fetal and Maternal Compartments During Human Parturition
Authors: Menon Ramkumar , Taylor Brandie D.
Published: September 2019

OBJECTIVE:

To examine inflammatory mediators in three fetomaternal biological compartments to inform theory related to the fetal and maternal inflammatory contributions to parturition at term and preterm.

METHODS:

We conducted a cross-sectional study of amniotic fluid, cord blood, and maternal plasma from women with singleton pregnancies. Women had one of four conditions: term labor (n=11), term not in labor (n=13), spontaneous preterm birth with intact membranes (preterm birth; n=13), or preterm prelabor rupture of membranes (PROM; n=8). We measured two damage-associated molecular pattern markers (high-mobility group box-1 [HMGB1] and uric acid) and two acute phase response markers (interleukin [IL]-6 and C-reactive protein [CRP]) using enzyme-linked immunosorbent assay. The distribution of each analyte within amniotic fluid, cord blood, and maternal plasma across the four conditions (term not in labor, term labor, preterm birth, and preterm PROM) were calculated. To explore whether there were distributional differences in each analyte across each of the four labor conditions, we used a nonparametric Kruskal-Wallis test. For analytes that differed across groups, we further compared distributions by labor group (term labor vs term not in labor, and preterm PROM vs preterm birth).

RESULTS:

Fetal compartments (amniotic fluid and cord blood) showed higher HMGB1 in term labor vs term not in labor and preterm PROM vs preterm birth. Amniotic fluid IL-6, cord blood CRP and cord blood uric acid were higher in term vs term not in labor. Cord blood uric acid was higher in preterm PROM vs preterm birth. Only maternal plasma IL-6 was higher in term labor vs term not in labor.

CONCLUSION:

Accumulation of HMGB1 and an overall increase in inflammation observed on the fetal side, but not the maternal side, may be signals of parturition. Understanding fetal-derived proparturition inflammatory signals at term and preterm, especially in preterm PROM, might provide fetal-specific biomarkers and identify underlying mechanisms and targets for interventions to reduce the risk of preterm birth and preterm PROM.
A National Survey of Profiles of Clerkship Directors in Obstetrics and Gynecology
Authors: Morgan Helen Kang , Graziano Scott C. , Craig LaTasha B. , Everett Elise N. , Forstein David A. , Hampton Brittany S. , Hopkins Laura , McKenzie Margaret L. , Pradhan Archana , Royce Celeste , Madani-Sims Shireen , Morosky Christopher M. ,   for the Undergraduate Medical Education Committee, Association of Professors of Gynecology and Obstetrics
Published: September 2019

OBJECTIVE:

To monitor demographics and factors associated with quality of life among obstetrics and gynecology clerkship directors. A secondary goal was to compare current demographics and survey responses to a 1994 survey of clerkship directors.

METHODS:

A 36-item electronic survey was developed and distributed to the 182 U.S. clerkship directors with active memberships with the Association of Professors of Gynecology and Obstetrics. Items queried respondents on demographics, attitudes about being a clerkship director, quality of life, and burnout.

RESULTS:

A total of 113 of the 182 (62%) clerkship directors responded to the survey. The mean full-time time equivalent allocated for clerkship director responsibilities was 25%. When compared with clerkship directors from 1994, current clerkship directors are younger, work fewer total hours per week, spend more time on patient care, and less time on research. Notably, 78% (87) of respondents were female compared with 21% (31) of respondents in 1994. Overall, most current clerkship directors responded optimistically to quality of life and burnout measures, with 25% (28) reporting symptoms of high emotional exhaustion and 17% (19) reporting symptoms of depersonalization. Clerkship directors' perception of support from their medical school was significantly correlated with increased personal fulfilment and positive quality of life, as well as decreased burnout and emotional exhaustion measures.

CONCLUSION:

The gender demographics of obstetrics and gynecology undergraduate medical education leadership have dramatically shifted over the past 25 years; however, many of the changes are not correlated with quality of life and burnout. The association between perceived support from the medical school and multiple quality of life measures point to the vital importance of support for our medical educators.
What Is New in Recovery After Gynecologic Surgery for Benign Indications?
Authors: Whiteside James L.
Published: September 2019

This month we focus on current research in recovery after gynecologic surgery for benign indications. Dr. Whiteside discusses four recent publications, which are concluded with a “bottom line” that is the take-home message. A complete reference for each can be found on Box 1 on this page along with direct links to the abstracts.
Reproductive Health in Xeroderma Pigmentosum
Authors: Merideth Melissa , Tamura Deborah , Angra Divya , Khan Sikandar G. , Ferrell Joyln , Goldstein Alisa M. , DiGiovanna John J. , Kraemer Kenneth H.
Published: September 2019

OBJECTIVE:

To assess the age at menarche and menopause of women with xeroderma pigmentosum, a DNA repair disease with premature aging, in a longitudinal natural history study.

METHODS:

We conducted a natural history study that reviewed medical records for gynecologic and reproductive health of all female patients with xeroderma pigmentosum aged older than 9 years examined at the National Institutes of Health (NIH). We performed gynecologic and laboratory examinations on a subset of the patients. Women in a second subset, who could not be examined, were interviewed using a questionnaire. Women who were deceased or lost to follow-up formed a third subset.

RESULTS:

Sixty females with xeroderma pigmentosum aged older than 9 years (median 29 years, range 10–61 years) were evaluated at the NIH from 1971 to 2018. Of these 60, 31 had history, questionnaire, record review, and gynecologic evaluation; 14 had record review and questionnaire interview by telephone; and 15 had only NIH record review. Menarche in females with xeroderma pigmentosum occurred at a median age of 12.0 years (range 9–17 years), which was comparable with the U.S. general population. Among the 18 patients with menopause, the median age at menopause of 29.5 years (range 18–49.5 years) was more than 20 years younger than in the U.S. general population (52.9 years). Premature menopause (before age 40 years) occurred in 14 of the 45 (31%) women aged 18 years or older, and primary ovarian insufficiency was documented in nine of them. There were 32 live births among 21 of the women, five of whom subsequently developed premature menopause.

CONCLUSION:

Females with xeroderma pigmentosum in our study had a normal age at menarche and were fertile but had increased incidence of premature menopause. Premature menopause, a symptom of premature aging, should be considered for gynecologic and reproductive health as well as implicating DNA repair in maintaining normal ovarian function.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT00001813.
Performance of Two-Stage Cervical Cancer Screening With Primary High-Risk Human Papillomavirus Testing in Women Living With Human Immunodeficiency Virus
Authors: Luckett Rebecca , Mogowa Neo , Li Howard J. , Erlinger Adrienne , Hacker Michele R. , Esselen Katharine , Feldman Sarah , Shapiro Roger , Morroni Chelsea , Ramogola-Masire Doreen
Published: September 2019

OBJECTIVE:

To evaluate the performance of cervical cancer screening algorithms for women living with human immunodeficiency virus (HIV), using primary high-risk human papillomavirus (HPV) testing followed by cytology, visual inspection with acetic acid, or colposcopy.

METHODS:

We conducted a prospective cohort study of women living with HIV in Botswana. All participants underwent high-risk HPV testing. Participants with positive high-risk HPV test results underwent cytology, visual inspection with acetic acid, colposcopy, and biopsy. Participants with negative high-risk HPV test results also underwent cytology. Histopathology was the reference standard for determination of preinvasive cervical disease and cervical cancer. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and likelihood ratios (LR) of high-risk HPV-based two-stage screening algorithms were calculated.

RESULTS:

Among 300 women screened, 88 (29%) had a positive high-risk HPV test result, and 29 of the 88 (35%) women who tested positive for high-risk HPV had CIN 2 or higher on histopathology. High-risk HPV followed by colposcopy resulted in a sensitivity of 83%, specificity of 49%, PPV of 47%, LR+ of +1.6, and LR− of −0.4. High-risk HPV followed by visual inspection with acetic acid resulted in a reduced sensitivity of 59%, specificity of 49%, PPV of 39%, LR+ of +1.2, and LR− of −0.8. High-risk HPV testing followed by cytology also resulted in a reduced sensitivity of 62%, specificity of 77%, PPV of 60%, LR+ of +2.7, and LR− of −0.5. Stratification by HPV 16/18/45 did not improve performance of the algorithms.

CONCLUSION:

In a high-risk population with HIV, high-risk HPV testing followed by colposcopy demonstrated the highest sensitivity and PPV in detecting high-grade cervical dysplasia. Allocating resources to colposcopy in resource-limited settings may be more effective than other screening strategies.
Effect of bar length on foot abduction and ankle dorsiflexion in Steenbeek foot abduction brace
Authors: Agarwal Anil , Barik Sitanshu
Published: September 2019

We investigated the impact of changes in bar length of Steenbeek foot abduction brace on foot and ankle range of motion in 150 children. The ankle dorsiflexion and foot abduction was measured without brace, with standard brace size (0) as depicted in Steenbeek manual and after variations in bar length (−2˝ to +2˝). The bar length (0) was also compared with shoulder width for Indian population. The Steenbeek foot abduction brace bar length in current use (11.53±1.2˝) was longer than shoulder size (8.14±1.18˝) with no true correlation. Steenbeek foot abduction brace usefulness was evident for foot abduction (46°) but not for dorsiflexion. The varied bar lengths tested did not significantly altered available dorsiflexion or abduction. The currently used Steenbeek foot abduction brace were larger than shoulder widths. The Steenbeek foot abduction brace was dynamic but required prefabrication for its effectiveness. The changes in bar length did not significantly alter foot dynamics occurring with brace.
The Effect of Preoperative Symptom Duration on Postoperative Outcomes After Minimally Invasive Transforaminal Lumbar Interbody Fusion
Authors: Yoo Joon S. , Patel Dillon S. , Hrynewycz Nadia M. , Brundage Thomas S. , Mogilevsky Franchesca A. , Singh Kern
Published: September 2019

Study Design:

Retrospective.

Object:

This study aims to examine whether the time spanning from symptom onset to surgical intervention has an effect on postoperative clinical improvement in patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF).

Summary of Background Data:

Evidence is limited regarding the influence of preoperative symptom duration on patient-reported outcomes (PROs).

Methods:

Patients undergoing a primary, single-level minimally invasive transforaminal lumbar interbody fusion were retrospectively reviewed and stratified according to preoperative symptom duration (<12 mo and ≥12 mo). Differences in PROs, including Oswestry Disability Index (ODI), 12-Item Short-Form Physical Component Score (SF-12 PCS), Visual Analogue Scale (VAS) back pain, and VAS leg pain, at each postoperative timepoint and were compared between duration of symptoms (DOS) cohorts using linear regression. Achievement of minimal clinically important difference (MCID) for PROs was compared using χ2 analysis.

Results:

A total of 248 patients were included: 96 had a DOS <12 months and 152 had a DOS >12 months. When comparing PROs preoperatively, the shorter DOS cohort had significantly worse ODI, VAS leg pain, and SF-12 PCS compared with patients with longer DOS. However, there was no preoperative difference in VAS back pain between cohorts. Postoperatively, there were no significant differences in improvement of PROs throughout the 12-month timepoint. The shorter DOS cohort had a comparable number of patients achieving MCID for ODI, VAS back pain, VAS leg pain, and SF-12 PCS relative to the longer DOS cohort.

Conclusions:

In our study, patients with DOS <12 months exhibited significantly worse ODI and VAS leg pain scores at the time of surgery compared with patients with longer DOS. However, these patients demonstrated similar clinical improvement postoperatively regardless of preoperative symptom duration. These findings suggest that delayed surgical intervention may not lead to impaired functional recovery in patients with degenerative lumbar disease.
Management of leptomeningeal carcinomatosis and challenges of trial design
Authors: Gill Corey M. , Brastianos Priscilla K.
Published: September 2019

Purpose of review

Highlight recent data in lung and breast cancer leptomeningeal disease and address clinical trials that are open for patients.

Recent findings

Patients with lung and breast cancer leptomeningeal disease have survival outcomes of less than 1 year, despite advances in treatment strategy. Efforts to develop liquid biopsy biomarkers of disease progression from cerebrospinal fluid and plasma are underway. There are over 10 clinical trials open for patients with leptomeningeal disease, half of which use immunotherapy.

Consortium-based, multicenter clinical trials for patients with leptomeningeal disease are urgently needed to expand the treatment armamentarium.
Systematic Literature Review and Meta-Analysis of Response to First-Line Therapies for Advanced/Metastatic Urothelial Cancer Patients Who Are Cisplatin Ineligible
Authors: Freshwater Tomoko , Li Haojie , Valiathan Chandni , Li Mengyao , Perini Rodolfo , Bracco Oswaldo L. , Frenkl Tara , Keefe Stephen
Published: September 2019

Objective:

The purpose of this systematic literature review (SLR) and meta-analysis was to compile the response of historic treatment options in first-line settings for patient populations who are cisplatin ineligible.

Materials and Methods:

SLR was conducted to compile objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of historic therapies for this population based on stringent criteria. Clinical trials published in English from January 1991 to June 2016 were identified by searching the PubMed (Medline), Cochrane, and Embase databases.

Results:

Eighteen studies (21 arms; N=810) were identified and used for this meta-analysis. For all treatments included in these studies, the pooled ORR was 0.36 (95% confidence interval [CI], 0.30-0.42). The ORR for the carboplatin+gemcitabine arms (6 arms; N=259), which is the National Comprehensive Cancer Network’s recommended first-line treatment (before approval of atezolizumab and pembrolizumab) for this population was 0.36 (95% CI, 0.30-0.42), the median DOR (4 arms) was 7.00 months (95% CI, 4.34-11.29), and the median OS was 8.39 months (95% CI, 7.05-9.98).

Conclusions:

The results of this SLR clearly demonstrate the paucity of clinical studies that assess therapeutic intervention in truly cisplatin-ineligible advanced/metastatic urothelial carcinoma subjects and highlight the development of novel therapies that can create real improvement in long-term outcomes. The recent approval of 2 checkpoint inhibitors, atezolizumab and pembrolizumab, were added in the National Comprehensive Cancer Network guidance as recommended first-line treatment for cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma and has provided alternatives for this patient population.
Evaluation of Genetic Variants in MIR3142HG in Susceptibility to and Prognosis of Glioma
Authors: Guo Xiaoye , Zhang Ming , Li Qi , Zhao Junjie , Wang Bo , Wang Jia , Mao Ping , Song Jinning
Published: September 2019

Objectives:

Studies have demonstrated that genetic variants in the miRNA-coding genes might be associated with cancer susceptibility and survival. Here, we aimed to investigate the influence of MIR3142HG single-nucleotide polymorphisms on the individual’s susceptibility to and patients’ prognosis of glioma.

Materials and Methods:

Six variants were genotyped by Agena MassARRAY iPLEX Gold assay among 529 glioma patients and 502 healthy controls. Association of MIR3142HG polymorphisms with the risk for and prognosis of glioma was analyzed by logistic regression analysis and Cox proportional hazards model, respectively.

Results:

In the risk analysis, rs17057846 (odds ratio [OR]=1.93, P=0.047), rs2961920 (OR=1.53, P=0.019), and rs58747524 (OR=1.23, P=0.046) polymorphisms were associated with increased glioma risk, while rs7727115 (OR=0.76, P=0.030) and rs1582417 (female individuals, OR=0.49, P=0.017) variants were associated with decreased risk. In the survival analysis, rs1582417 polymorphism (hazard ratio=1.26, P=0.017) contributed to poorer prognosis overall. Rs17057846, rs1582417, and rs2431689 polymorphisms were associated with prognosis of astrocytoma, and rs1582417, rs17057846, and rs58747524 variants were associated with the survival rate in patients with low-grade glioma (I to II).

Conclusion:

Our study provided the first evidence for the impact of rs1582417, rs17057846, rs2431689, rs2961920, rs58747524, and rs7727115 polymorphisms in MIR3142HG on the susceptibility to and/or prognosis of glioma in the Chinese Han population.
Intraoperative Three-dimensional Virtual Reality and Computed Tomographic Guidance in Temporomandibular Joint Arthroplasty of Syndromic Craniofacial Dysostoses
Authors: Bradley Daniel , Willson Thomas , Chang Jessica B. , Gandolfi Brad , Zhu Tian Ran , Bradley James P. , Lee Justine C.
Published: September 2019

Bony ankylosis of the temporomandibular joints (TMJ) occurs in up to 28% of patients with syndromic mandibular dysostoses. Release of complete osseous ankylosis is particularly challenging due to the lack of tissue planes separating the mandible from the skull base and the presence of congenital skeletal abnormalities. One recent advance in surgical imaging technology is three-dimensional virtual reality (3D VR), now in common use in neurosurgical resections. In this study, we describe the usage of 3D VR in TMJ arthroplasty and compare 3D VR to traditional computed tomographic (CT) guidance. Pediatric patients with syndromic mandibular micrognathia including Treacher Collins, Nager, and cerebrocostomandibular syndrome were retrospectively evaluated between 2008 and 2016. Patient characteristics, complications, inpatient times, and operative times were recorded. Of the 29 children with syndromic mandibular micrognathia treated between 2008 and 2016, 7 were diagnosed with TMJ ankyloses. Four consecutive pediatric patients (mean 8.7 years) undergoing interpositional TMJ arthroplasty with Matthews device placement were retrospectively evaluated. Two patients underwent traditional CT-guided versus 3D VR-guided temporomandibular joint arthroplasty (TMJA). No statistically significant differences were found among the age, complications, or inpatient hospitalization times. The average operative time in the traditional CT guidance group was 300 minute versus 134 minutes in the 3D VR group. Three-dimensional VR is a useful preoperative planning and intraoperative guidance tool. The major difference between VR and older technologies is the improved imaging in 3 dimensions for guidance, thereby potentially decreasing operative times.
The association between 24-h blood pressure patterns and left ventricular mechanics
Authors: Tadic Marijana , Cuspidi Cesare , Majstorovic Anka , Pencic Biljana , Mancia Giuseppe , Bombelli Michele , Grassi Guido , Kocijancic Vesna , Djukic Vladimir , Celic Vera
Published: September 2019

Objective:

We sought to investigate left ventricular (LV) mechanics in the recently diagnosed hypertensive patients with different 24-h blood pressure (BP) patterns (dipping, nondipping, extreme dipping and reverse dipping).

Methods:

The current cross-sectional study included 209 hypertensive patients who underwent 24-h ambulatory BP monitoring and comprehensive two-dimensional echocardiographic examination including multilayer strain analysis.

Results:

There was no difference in 24-h and daytime BP values between four groups. Night-time BP significantly and gradually increased from extreme dippers, across dippers and nondippers, to reverse dippers. LV global longitudinal and circumferential strains were greater in dippers and extreme dippers than in nondippers and reverse dippers. This was also found for endocardial and epicardial LV longitudinal and circumferential strains. Multivariate logistic regression analysis demonstrated that nondipping and reverse dipping patterns were associated with reduced LV longitudinal strain [odds ratio (OR) 1.71 (95% confidence interval (CI): 1.10–5.61) and OR 2.50 (95% CI: 1.31–6.82), respectively] independently of age, sex, 24-h SBP, LV mass index and E/è. Only the reverse dipping BP pattern was independently of clinical and echocardiographic parameters related with reduced LV circumferential strain [OR 1.90 (95% CI: 1.10–4.80)].

Conclusion:

Nondipping and reverse dipping BP patterns had stronger impact on LV mechanics compared with patients with dipping and extreme dipping BP patterns in hypertensive population. LV functional and mechanical remodeling deteriorated from extreme dippers and dippers, to nondippers and reverse dippers.
Additive Effect of Topical Nepafenac on Mydriasis in Patients With Diabetes Mellitus
Authors: Kiziltoprak Hasan , Koc Mustafa , Yetkin Esat , Tekin Kemal , Inanc Merve , Ozulken Kemal
Published: September 2019

Objectives:

To evaluate the additive effect of topical nepafenac on pupil diameter (PD) in patients with diabetes mellitus (DM) and cataract.

Methods:

This prospective comparative study included the patients having cataract surgery with and without DM. Two consecutive PD measurements were taken using an automatic quantitative pupillometry system (MonPack One, Metrovision). A baseline measurement was taken, then one drop of nepafenac % 0.1 (Nevanac; Alcon, Fort Worth, TX) was instilled only to the eye that will be operated on (study eye). Cyclopentolate 1.0% (Sikloplejin; Abdi İbrahim, İstanbul, Turkey) was instilled to both eyes (study eye/fellow eye) 5 minutes later. The second measurement was taken at 1 hour after this application.

Results:

The DM group consisted of 43 patients, and the control group consisted of 39 participants. The baseline PDs of both eyes were similar in the DM group (P=0.070) and the control group (P=0.345). The change in pupil size from baseline to mydriasis was statistically significantly greater in the study eyes (2.69±0.53) than fellow eyes (2.54±0.61) in the DM group (P=0.009), but there was no statistically significant difference in the control group (2.94±0.63 vs. 2.86±0.58). When the groups were compared, the PD changes were similar in the study eyes between groups (P=0.065), while the PD changes in the fellow eyes were lower in the DM group (P=0.017).

Conclusions:

Nepafenac has been shown additive effect on pupil dilation in diabetic patients before cataract surgery.
Pourfour du Petit Syndrome: A Rare Association With Cluster Headache
Authors: Nadal Jeremy , Daien Vincent , Audemard Didier , Jeanjean Luc
Published: September 2019

Pourfour du Petit syndrome is an uncommon cause of eyelid retraction, associated with unilateral mydriasis and hemifacial hyperhidrosis. This syndrome is caused by hyperactivity of the ipsilateral oculosympathetic pathway and needs to be recognized because it has an opposite clinical presentation but the same topographic and diagnostic value as Horner syndrome. The authors report a rare case of Pourfour du Petit syndrome associated with cluster headache and discuss pathophysiological hypotheses, clinical presentation, complementary exams, pharmacologic testing, treatment options, and prognosis. Early detection of these symptoms may lead to swift diagnosis and treatment.
Complex Bony Congenital Nasolacrimal Duct Obstruction Caused by an Adjacent Canine Tooth Bud
Authors: Fayet Bruno , Racy Emmanuel , Bordonné Corinne , Katowitz William R. , Katowitz James , Brémond-Gignac Dominique
Published: September 2019

The authors report the case of a 7-year old child with failed probing with stent intubation, who was found to have an unusual curvature of the nasolacrimal duct on the symptomatic side. CT imaging revealed a permanent maxillary canine tooth adjacent to the duct. It appeared that the relationship of the tooth bud to the curved nasolacrimal duct was most likely responsible for the symptoms of epiphora on this anomalous side.
Life After Trauma: A Survey of Level 1 Trauma Centers Regarding Posttraumatic Stress Disorder and Acute Stress Disorder
Authors: Guess Katherine E. , Fifolt Matthew , Adams Raeanna C. , Ford Eric W. , McCormick Lisa C.
Published: September 2019

Patients admitted to Level 1 trauma centers in the United States are rarely assessed for or educated about the potentially devastating effects of acute stress disorder (ASD) or posttraumatic stress disorder (PTSD). This descriptive research was conducted to describe current levels of assessment and education of ASD and PTSD in Level 1 trauma centers in the United States. The aims of this article are to (1) determine the extent to which Level 1 trauma centers in the United States assess and educate patients and providers about ASD and PTSD and (2) identify clinical staff who administer assessments and provide educational resources. A web-based survey was distributed to the trauma program managers and trauma medical directors of 209 adult and 70 pediatric Level 1 trauma centers in the United States. For PTSD, 26 (25.00%) adult and 17 (36.17%) pediatric centers had an assessment protocol for use with trauma patients. For ASD, 13 (12.50%) adult and 13 (27.66%) pediatric centers utilized an assessment protocol for use with trauma patients. For PTSD, 12 (12.37%) adult and 8 (20.00%) pediatric centers offered educational protocols for use with trauma patients. Seven (7.22%) adult and 7 (17.50%) pediatric centers maintain educational protocols for ASD in trauma patients. Fewer centers had assessment or educational protocols targeting formal and informal caregivers. This study was limited to Level 1 trauma centers in the United States. Results indicate that trauma patients are rarely assessed for or educated about the potential effects of PTSD or ASD. Formal and informal caregivers are also assessed and educated at low rates. Assessment, education, and incidence of PTSD and ASD should be included as universally measured health outcomes across trauma centers.
Acute kidney injury in interstitial nephritis
Authors: Caravaca-Fontán Fernando , Fernández-Juárez Gema , Praga Manuel
Published: September 2019

Purpose of review

The purpose of this review is to describe the most common causes of acute interstitial nephritis (AIN), the diagnostic work-up and the therapeutic management.

Recent findings

Several case series and registries have found an increasing incidence of AIN, especially among older patients. Drug-induced AIN still represents the most common cause. Early withdrawal of the culprit drug together with corticosteroid therapy remain the mainstay of treatment, although recent studies have shown that prolonged treatment beyond 8 weeks does not further improve kidney function recovery.

AIN is a common cause of acute kidney injury, and therefore, physicians should suspect this entity especially in patients exposed to multiple medications. While immune-allergic reaction to numerous drugs is the most common cause of AIN, other underlying systemic diseases may also be involved, and therefore, every patient should undergo a complete diagnostic evaluation. Kidney biopsy provides the definitive diagnosis of AIN, and certain histologic features may help to identify the underlying condition. In drug-induced AIN, an early discontinuation of the culprit drug is the mainstay of therapy, and unless a rapid recovery of kidney function is observed, a course of glucocorticoid therapy should be initiated.
Trauma-associated acute kidney injury
Authors: Perkins Zane B. , Haines Ryan W. , Prowle John R.
Published: September 2019

Purpose of review

A summary of recent research into the epidemiology, cause, management and outcomes of trauma-associated acute kidney injury (AKI). There is an increasing focus on subtypes of AKI to better target clinical management and future research.

Recent findings

AKI associated with trauma occurs in 20–24% of patients admitted to ICU. On the basis of creatinine and/or urine output, AKI occurs in the first few days of traumatic illness. Although various associations have been identified, shock and high-volume blood transfusion are the most consistent risks for development of trauma-associated AKI. Short-term outcomes appear worse for patients with AKI, but extent of longer term kidney function recovery remains unknown. Recent research in the general critical care population is beginning to better inform AKI management; however, currently, preventive and supportive strategies remain the mainstay of AKI management after trauma.

Well-designed, prospective research is required to better understand the phenotype, pathophysiology and recovery trajectory of trauma-associated AKI. Only then can potentially unique therapeutic targets be developed for this common subtype of AKI.
Celiac Disease
Authors: Therrien Amelie , Kelly Ciaran P. , Silvester Jocelyn A.
Published: September 2019

Celiac disease is a common form of enteropathy with frequent extraintestinal manifestations (EIM). Misrecognition of these presentations may lead to significant delays in diagnosis. Any organ may be involved, either through an immune/inflammatory phenomenon, or nutritional deficiencies. Some EIM, such as gluten ataxia, may be irreversible if left untreated, but most will improve with a gluten-free diet. Knowledge of the various EIM, as well as the associated conditions which do not improve on a gluten-free diet, will avoid delays in the diagnosis and management of celiac disease and associated manifestations.