bluuebunny/crossref_metadata_2025 huggingface dataset:
PI-1 Age-specific HPV prevalence among adolescent girls in Jos, North-Central Nigeria
Authors: Dashe Nanma , Nimzing Lohya , Egah Daniel , Adebamowo Sally , Adebamowo Clement
Published: April 2019

Background:

Knowledge of the age-specific prevalence of HPV types among adolescent girls in SSA is essential to determine the best age for introduction of HPV vaccination, monitoring of vaccine efficacy and provision of insight into persistent infection.

Methods:

We randomly selected 205 girls, age 9–20 years living in Jos, Nigeria. Informed consent and assent were obtained prior to training on self-collection of vulvo-vaginal samples using sterile swab stick and first void urine. HPV detection was carried out using HPV SPF10-DEIA/LiPA25. Data analysis was done using STATA14.

Results:

The mean (SD) age of the girls was 14.9 (2.3) years. AnyHPV was detected in 29.3% of participants. The earliest age at which anyHPV and high-risk HPV (hrHPV) infections were detected in either urine or vulvo-vaginal samples were 10 and 11 years of age respectively. The prevalence of anyHPV, hrHPV, lrHPV and multiple hrHPV peaked at 16 years of age. The prevalence of hrHPV infection was 3.4% among the 9–12 years age group, 7.8% among 13–16 years and 5.4% among 17–20 year old. The commonest hrHPV types detected were 52 (10.2%), 18 (6.3%) and 51 (4.4%).

Conclusions:

While a larger study is warranted, our findings suggest that in this population, HPV vaccination starting at 9 years of age would cover the at-risk population.
PI-3 Single molecule fluorescence approaches to probe the binding of soluble-CD4 to native-like HIV-1 SOSIP trimers
Authors: Agrawal Parul , DeVico Anthony , Lewis George , Pazgier Marzena , Ray Krishanu
Published: April 2019

Several lines of evidence suggest that HIV-1 envelope (Env) on virions transition through a series of conformations in solution as well as when they engage CD4 molecules during viral attachment. Moreover, the flexibility and antigenicity of trimers changes as they progressively become saturated with CD4 molecules. HIV-1 Env can potentially engage up to 3 independent CD4 molecules for efficient Env triggering in the virial fusion. However, it is still unknown if one, 2 or 3 CD4 receptor molecules are required for this process. To date, the ensemble techniques and indirect biological assays have been unable to address this question quantitatively. Here, we employed a unique approach utilizing the single molecule detection (SMD) analyses to determine quantitatively the number of sCD4 molecules bound to HIV-1 Env and capture the intermediate interaction states that may be missed by the ensemble methods. A key step in direct counting of single molecules is to ensure single fluorophore labeling of the target molecule. For this purpose, we constructed a C-terminus SNAP-tagged human sCD4 fusion protein and fluorescently labeled it with a single Alexa 488 fluorophore (sCD4-SNAP-A488). This approach was devoid of any genetic or external perturbation to the SOSIP.664 trimers.

Our results by SMD confirm that up to 3 sCD4-SNAP-A488 molecules bind a single SOSIP trimer and provide insight into trimer occupancy shifts over time. The experimental data reveals that Env is intrinsically dynamic, transitioning between 3 distinct stoichiometries (1-, 2- and 3-sCD4 bound states). Real-time single molecule association kinetic experiments divulge different states of trimer triggering and stoichiometry of the complexes. We have developed an algorithm for automated analyses of our data to infer the stoichiometry in real-time. Importantly, our single-molecule based association kinetic analysis indicates that assemblies of trimer with 1 or 3 sCD4 molecules are more stable whereas binding of 2 sCD4s seems transitional. Our findings are consistent with structural information available for conformations of HIV-1 Env in its ligand-free, prefusion state and in the CD4-bound states and provide new critical insights into the sCD4 interaction with the Env for better understanding of the complex biology of HIV-1 entry into cells.
PI-5 Regulating Innate immune signaling using single immunoglobulin interleukin-1 regulated receptor protein
Authors: Ferandes Mercedes , Carr Jahid , Crnkovich Joseph , Alanezis Shouq , Wang Yajing , Brown Lindsey , Snyder Greg
Published: April 2019

The Single Immunoglobulin Interleukin-1- related receptor protein (SIGIRR) has been observed to be a negative regulator of the IL-1 (IL-1R) and Toll-like receptor (TLR) signaling pathways. Negative regulation of TLR and IL-1R signaling by SIGIRR is important for innate immune signaling. SIGIRR has been implicated in diseases involving chronic and acute inflammation, including but not limited to asthma, allergies, autoimmunity, and cancer. Based on SIGIRR's ability to negatively regulate IL-1R and TLR signaling, we hypothesize that SIGIRR could be developed as an IL-1 specific therapeutic for IL-1R and TLR receptor antagonism. Using biochemical, biophysical and functional studies, we will determine the molecular mechanism of SIGIRR's negative regulation of IL-1R and Toll-like receptor signaling. Specifically, we will characterize the structure-function relationship of SIGIRR-IL1R and TLR interactions using X-ray crystallography. In support of these studies we have successfully expressed, purified and crystallized a SIGIRR fusion protein. SIGIRR fusion crystals diffract to 2.8 angstrom at the National Synchrotron Light Source II AMX beamline in Brookhaven National Laboratory. We are currently collecting more X-ray diffraction data for determining the structure of the crystallized SIGIRR fusion protein. Future studies include structure determination of SIGIRR protein with IL-1 and Toll-like receptor and development of an IL-1R -SIGIRR based signaling assay. Molecular studies of SIGIRR's negative regulation of IL-1R will aid in our molecular understanding and development effective therapeutic treatment options for regulating IL-1 based inflammation and disease.
PI-6 Construction and analysis of V3 glycopeptide antigens for HIV-1 vaccine design
Authors: Zhang Roushu , Cai Hui , Orwenyo Jared , Giddens John , Yang Qiang , LaBranche Celia C. , Montefiori David C. , Wang Lai-Xi
Published: April 2019

The heavy glycosylation on HIV-1 envelope protein (Env) plays an important role in viral evasion and is critical for the viral plasticity and diversity in the circulating strains. The discovery of a new class of broadly neutralizing antibodies (bnAbs), including PG9, PGT128, PGT121, and 10-1074, that recognize conserved glycopeptide epitopes from the V1V2 and V3 domains provide a valuable template for vaccine design. Structural and mutational studies have provided basic information on the nature and structure of the glycopeptide epitopes of these antibodies. Nevertheless, due to the tremendous heterogeneity of envelope glycosylation, the fine glycan specificity of these antibodies remains to be fully characterized. Moreover, it remains a challenging task to reconstruct glycosylation-well defined antigenic structures even when the glycan specificity is defined. To address these problems, we have launched a chemical biology program aiming to reconstitute a library of structurally well-defined glycopeptides and glycoproteins to probe the glycan specificity of these glycan-reactive broadly neutralizing antibodies. Through the chemoenzymatic synthesis and antibody-binding studies of a library of V3 glycopeptides, we found that the PGT128 requires a high-mannose N-glycan on V3 domain with promiscuous site of glycosylation at either N332, N301, orN295); the PGT121 shows binding specificity towards a sialylated N-glycan at N301 site; and the 10-1074 prefers a high-mannose type glycan at N332 site. From the mapping of the epitopes, we designed glycopeptide-based immunogens derived from the V3 domain through chemical and biological approaches. The synthetic glycopeptide immunogens obtained by chemoenzymatic synthesis and the glycosylation-defined V3 glycopeptide-Fc fusion proteins obtained through mammalian cell expression both showed potent binding towards multiple V3-targeting bnAbs. Rabbit immunization experiments revealed that the synthetic V3 glycopeptide could elicit glycan-dependent antibody responses. These results together suggested that our glycosylation-defined V3 glycopeptide immunogens could serve as a valuable vaccine component in the combination with other vaccine candidates for further immunization studies.
Opioid-prescribing Patterns for Pediatric Patients in the United States
Authors: Groenewald Cornelius B.
Published: April 2019

Background and Objectives:

The opioid crisis in America affects both adults and children. However, knowledge about the epidemiology of the opioid crisis, opioid prescribing patterns, and the link between opioid prescribing and problematic opioid behaviors remain limited. Thus, children are often excluded from health care policies and guidelines aimed at curbing the opioid crises. The primary aim of this topical review is to provide a brief overview of the opioid crises affecting children, followed by a synopsis of recent research on opioid prescribing patterns and data on the links between legitimate opioid use and risk for problematic opioid use behaviors.

Methods:

This is a narrative review.

Results:

Opioid misuse is a public health crisis facing children and adolescents in the United States and serves as a key antecedent for other problematic opioid behaviors, including opioid use disorder, heroin use, and opioid overdose. Furthermore, the United States experienced a significant increase in opioid prescribing to children and adolescents as compared with prescribing rates before the year 2000. Yet, data on the associations between opioid prescribing patterns and risk for problematic opioid use remains limited.

Discussion:

There exist an urgent need to identify adolescents at increased risk for problematic opioid use behaviors following a receipt of medically prescribed opioids. The article closes with some general guidelines that providers may follow to reduce the risk of opioids in pediatric patients.
Opioid Use Disorder in Children and Adolescents
Authors: Eisdorfer Seth , Galinkin Jeffrey
Published: April 2019

Opioid medications are an important tool in the management of pain and have been used in clinical practice for centuries. However, due to the highly addictive nature of this class of medications coupled with the life-threatening side effect of respiratory depression, opioid misuse has become a significant public health crisis worldwide. Children and adolescents are at risk for opioid misuse, and early detection is imperative to facilitate treatment and improve outcomes. This review will address the current state of opioid misuse and treatment in children and adolescents in the United States.
Presurgical Comorbidities as Risk Factors For Chronic Postsurgical Pain Following Total Knee Replacement
Authors: Skrejborg Peter , Petersen Kristian K. , Kold Søren , Kappel Andreas , Pedersen Christian , Østgaard Svend E. , Simonsen Ole , Arendt-Nielsen Lars
Published: April 2019

Objectives:

Chronic postsurgical knee pain (CPSP) is a burden for ∼20% of the patients following total knee replacement (TKR). Presurgical pain intensities have consistently been found associated with CPSP, and it is suggested that comorbidities are likewise important for the development of CPSP. This study aimed to identify presurgical risk factors for the development of CPSP 5 years after TKR on the basis of medical records containing information with regard to comorbidities.

Materials and Methods:

Patients undergoing primary TKR surgery were contacted 5 years after TKR. Presurgical Knee Society Score and comorbidities were evaluated. Postsurgical knee pain at 5 years of follow-up was assessed on a Numeric Rating Scale (NRS, 0 to 10). Logistic regression models were utilized to identify patients with moderate-to-severe (NRS≥3) and mild-to-no (NRS<3) CPSP at 5-year follow-up. Odds ratio (OR) for significant factors was calculated.

Results:

A total of 604 patients were contacted, 493 patients responded, 352 patients provided a completed questionnaire. A total of 107 patients reported NRS≥3 at follow-up. Significant presurgical factors associated with CPSP were fibromyalgia (OR=20.66; P=0.024), chronic pain in body parts other than the knee (OR=6.70; P=0.033), previous diagnosis of cancer (OR=3.06; P=0.001), knee instability (OR=2.16; P=0.021), younger age (OR=2.15; P=0.007), and presurgical knee pain (OR=1.61; P=0.044). Regression analysis identified 36 of 107 (33.6%) patients with CPSP on the basis of presurgical factors, and 231 patients (94.3%) without CPSP were classified correctly.

Discussion:

The current study found that a variety of presurgical clinical factors can correctly classify 33.6% of patients at risk for developing CPSP 5 years following TKR.
The Association Between Patient Reported Outcomes of Spinal Surgery and Societal Costs
Authors: Hansson-Hedblom Amanda , Jonsson Emma , Fritzell Peter , Hägg Olle , Borgström Fredrik
Published: April 2019

Study Design.

Retrospective register-based study using Swedish registers and data prospectively collected in quality register Swespine.

Objective.

Analyze the association of societal costs and spine surgery outcome in low back pain (LBP) patients based on patient reported outcome measures (PROMs).

Summary of Background Data.

Studies show that LBP has a substantial impact on societal cost. There are indications that the burden diverges over different patient groups, but little is known about cost patterns in relation to PROMs of LBP surgery.

Methods.

We utilized a database with data from six registers. All lumbar spine surgery patients registered in Swespine 2000 to 2012 were identified. Swespine collects PROMs Global Assessment of pain improvement (GA), Oswestry Disability Index (ODI), Visual Analog Scale (VAS), and EuroQol five-dimension scale (EQ-5D). A literature search was conducted to identify threshold changes in ODI, VAS, and EQ-5D representing a significant improvement or deterioration as defined by the minimal clinically important difference (MCID). We categorized patients into groups by their GA response at 2-year follow-up and estimated mean changes in ODI, VAS, and EQ-5D for each group. These changes were compared with the MCID thresholds to determine a GA-anchored classification of surgical outcomes. Costs consisted of out/inpatient care, sick leave, early retirement, and pharmaceuticals.

Results.

In total, 12,350 patients were included. GA 1–2 (“pain has disappeared”/“pain is much improved”) were labeled successful surgery outcomes (67%), GA 3 (“pain somewhat improved”), undetermined (16%), and GA 4–5 (“no change in pain”/“pain has worsened”) unsuccessful (17%). Costs of the unsuccessful and undetermined were higher than of the successful during the entire study period, with differences increasing markedly post-surgery. For the successful, a downward cost trend was observed; costs almost returned to the level observed 3 years pre-surgery. No such trend was observed in the other groups.

Conclusion.

Identifying patients with higher probability of responding to surgery could lead to improved health and substantial societal cost savings.

Level of Evidence: 3
Fluid Intake But Not Fluid Balance Is Associated With Poor Outcome in Nontraumatic Subarachnoid Hemorrhage Patients
Authors: Rass Verena , Gaasch Max , Kofler Mario , Schiefecker Alois Josef , Ianosi Bogdan-Andrei , Steinkohl Fabian , Beer Ronny , Pfausler Bettina , Gizewski Elke R. , Thomé Claudius , Schmutzhard Erich , Helbok Raimund
Published: April 2019

Objectives:

Optimal fluid management is important in patients with acute brain injury, including subarachnoid hemorrhage. We aimed to examine the relationship between daily fluid intake and fluid balance with hospital complications and functional outcome.

Design:

Retrospective observational cohort study.

Setting:

Neurocritical care unit at a tertiary academic medical center.

Patients:

Two-hundred thirty-seven consecutive nontraumatic subarachnoid hemorrhage patients admitted to the neurologic ICU between 2010 and 2016.

Interventions:

Total daily amount of fluids and fluid balance were calculated over 15 days. Using multivariate generalized estimating equation models the association of daily fluid intake and fluid balance with disease severity, hospital complications and poor functional outcome (3-mo modified Rankin Score ≥ 3) was investigated. Additionally, we described the composition of fluids given.

Measurements and Main Results:

Patients presented with a median admission Hunt and Hess grade of 3 (interquartile range, 1–5) and were 57 years old (interquartile range, 47–67 yr old). A higher daily fluid intake was associated with higher admission Hunt and Hess grade (odds ratio, 1.61; 95% CI, 1.47–1.76; p < 0.001), increased pulmonary fluid accumulation (adjusted odds ratio, 1.11; 95% CI, 1.01–1.21; p = 0.033), prolonged mechanical ventilation (Wald statistic = 20.08; degrees of freedom = 1; p < 0.001), higher daily Subarachnoid hemorrhage Early Brain Edema Score (adjusted odds ratio, 1.11; 95% CI, 1.01–1.22; p = 0.034), occurrence of anemia (adjusted odds ratio, 1.36; 95% CI, 1.20–1.54; p < 0.001), delayed cerebral ischemia (adjusted odds ratio, 1.31; 95% CI, 1.14–1.51; p < 0.001), and poor functional outcome (adjusted odds ratio, 1.25; 95% CI, 1.10–1.41; p < 0.001). Daily fluid balance was associated with higher admission Hunt and Hess grade (odds ratio, 1.09; 95% CI, 1.05–1.13; p < 0.001) and anemia (adjusted odds ratio, 1.17; 95% CI, 1.03–1.33; p = 0.019). The main contributors to fluids were nutritional compounds (31%), IV drugs (30%), and volume substitution (17%).

Conclusions:

Our study demonstrates a significant association of fluid intake but not fluid balance with hospital complications and poor functional outcome in subarachnoid hemorrhage patients. A larger prospective study is needed to confirm our results.
Three Different Anesthesia Approaches in Blepharoptosis Surgery
Authors: Guo Ziyi , Park David Dae Hwan , Park Kisoo , Guo Naiqiang
Published: April 2019

Background:

Despite the many methods of anesthesia for blepharoptosis, there is little documentation in the literature. When using the Müller aponeurosis composite flap advancement approach, one of the 3 anesthesia methods is chosen: general, local, and sedative anesthesia. On the other hand, the choice of anesthesia method is controversial.

Methods:

A total of 101 patients (48 female and 53 male) admitted to hospital for treatment were selected: 38 (37.6%) patients (49 eyes) with local anesthesia, 34 (33.7%) patients (60 eyes) with general anesthesia, and 29 (28.7%) patients (42 eyes) with sedative anesthesia.

Results:

The preoperative average marginal reflex distance (MRD1) in the local, general, and sedative anesthesia groups was 0.90, 0.35, and 0.47 mm, respectively. The corneal exposure area (CEA) in the local, general, and sedative approach groups was 63.2%, 57.8%, and 55.9%, respectively. The postoperative average distance for the MRD1 was significantly different among the 3 anesthesia approaches. The postoperative MRD1 in the local approach group was 3.28 mm and the CEA improved to 75.4%. In the general anesthesia approach group, the MRD1 was 3.01 mm and the CEA was 73.4%. In the sedative anesthesia approach group, the MRD1 and CEA were 3.62 mm and 74.0%, respectively. The MRD1 in the general, local, and sedative groups was 2.65 ± 1.48, 2.39 ± 1.65, and 3.17 ± 1.77, respectively; the difference was not significant (P > 0.05).

Conclusions:

The general, local, and sedative anesthesia approaches are all effective in the correction of blepharoptosis; the results were similar regardless of the anesthesia approach. On the other hand, the patients felt more comfortable and surgeons could control the process more easily using the sedative approach.
Does Long-Term Rigid Contact Lens Wear Lead to Acquired Blepharoptosis in Chinese Eyes?
Authors: Yang Bi , Liu Longqian , Cho Pauline
Published: April 2019

Objectives:

To determine whether long-term rigid contact lens wear leads to acquired blepharoptosis and whether its development is affected by lens removal methods.

Methods:

Ninety rigid contact lens wearers (45 rigid gas permeable [RGP] [15–19 years old] and 45 ortho-k [15–40 years old]) who had worn lenses for at least 2 years and 45 spectacle-wearing controls (15–19 years old) were recruited. Margin reflex distance (MRD) and palpebral fissure height (PFH) were measured both subjectively and objectively, but levator function (LF) could only be measured subjectively. For RGP subjects, measurements were made before and 5 min after lens removal. Measurements were compared among the groups and, for rigid lens wearers, between two different lens removal techniques: using a suction holder or by finger-lid manipulation.

Results:

No significant differences in MRD, PFH, and LF were found between different lens removal techniques in the rigid lens groups (P>0.05). No significant correlations were found between the parameters of interest and duration of lens wear (P>0.05). For the RGP group, MRD, PFH, and LF were significantly greater after than before lens removal (P<0.05), and after lens removal, MRD was significantly smaller than that of the ortho-k and spectacle groups (P<0.001, P=0.01, respectively) and PFH was significantly smaller than that of the ortho-k group (P=0.001). However, after lens removal, according to the definition (amount) for ptosis, no subject was diagnosed as having ptosis.

Conclusions:

Long-term rigid contact lens wear did not lead to acquired blepharoptosis in Chinese eyes. Margin reflex distance, PFH, and LF were not affected by different lens removal techniques.
Implementation of a Quality Index for Improvement of Quantification of Corneal Nerves in Corneal Confocal Microscopy Images: A Multicenter Study
Authors: Sturm Dietrich , Vollert Jan , Greiner Tineke , Rice Andrew S. C. , Kemp Harriet , Treede Rolf-Detlef , Schuh-Hofer Sigrid , Nielsen Stine E. , Eitner Lynn , Tegenthoff Martin , Petropoulos Ioannis N. , Malik Rayaz A. , Maier Christoph , Schmidt-Wilcke Tobias , Schargus Marc
Published: April 2019

Purpose:

Corneal confocal microscopy (CCM) is an imaging method to detect loss of nerve fibers in the cornea. The impact of image quality on the CCM parameters has not been investigated. We developed a quality index (QI) with 3 stages for CCM images and compared the influence of the image quality on the quantification of corneal nerve parameters using 2 modes of analysis in healthy volunteers and patients with known peripheral neuropathy.

Methods:

Images of 75 participants were a posteriori analyzed, including 25 each in 3 image quality groups (QI 1–QI 3). Corneal nerve fiber length (CNFL) was analyzed using automated and semiautomated software, and corneal nerve fiber density and corneal nerve branch density were quantified using automated image analysis. Three masked raters assessed CCM image quality (QI) independently and categorized images into groups QI 1–QI 3. In addition, statistical analysis was used to compare interrater reliability. Analysis of variance was used for analysis between the groups. Interrater reliability analysis between the image ratings was performed by calculating Fleiss' kappa and its 95% confidence interval.

Results:

CNFL, corneal nerve fiber density, and corneal nerve branch density increased significantly with QI (P < 0.001, all post hoc tests P < 0.05). CNFL was higher using semiautomated compared with automated nerve analysis, independent of QI. Fleiss kappa coefficient for interrater reliability of QI was 0.72.

Conclusions:

The quantification of corneal nerve parameters depends on image quality, and poorer quality images are associated with lower values for corneal nerve parameters. We propose the QI as a tool to reduce variability in quantification of corneal nerve parameters.
Predictors of Severe Bleeding During Endobronchial Biopsy
Authors: Muthu Valliappan , Ram Babu , Sehgal Inderpaul S. , Dhooria Sahajal , Prasad Kuruswamy T. , Bal Amanjit , Aggarwal Ashutosh N. , Agarwal Ritesh
Published: April 2019

Background:

Endobronchial biopsy (EBB) remains the standard procedure for evaluating endobronchial lesions visualized during flexible bronchoscopy. However, the predictors of bleeding and its impact on the diagnostic yield of EBB remains unknown.

Methods:

This was a retrospective study of subjects who underwent EBB for suspected neoplastic endobronchial lesion. We noted the demographic details, radiology, bronchoscopy findings (vascularity and location of the lesion), and the procedural details. Immediately after EBB, the bronchoscopist recorded the severity of bleed as none, mild, moderate, or severe (requiring instillation of cold saline/topical adrenaline or tamponade to control bleed). We assessed the diagnostic yield of EBB, the incidence and predictors of severe bleeding.

Results:

A total of 537 subjects with a mean age of 59.7 years (84.2% males) were included. On histopathology, malignancy was confirmed in 429 (85.8%) subjects. Severe bleeding occurred in 45 (8%) subjects. On a multivariate logistic regression analysis, bronchoscopic appearance of increased vascularity [odds ratio (95% confidence interval), 2.68 (1.38-5.19)] and the central location of the tumor [odds ratio (95% confidence interval), 3.01 (1.52-5.96)] were independent predictors of severe bleeding during EBB. Severe bleeding led to significantly lesser median number of biopsies (4 vs. 6, P=0.001) obtained, and a higher proportion of nondiagnostic biopsies (20% vs. 7.1%, P=0.004).

Conclusion:

Severe bleeding during EBB was associated with a decrease in the number of biopsies obtained and a lower diagnostic yield. A centrally located and vascular-appearing lesion on bronchoscopy predicted severe bleeding.
Practical and ethical issues for delivery of advanced ENT services in the Indian subcontinent: efforts to ‘Bridge the Gap’
Authors: Kumar Raghu Nandhan Sampath , Kameswaran Mohan
Published: April 2019

Purpose of review

The Indian healthcare industry, one of the largest in the world, caters for 1.3 billion people. The modern middle class addresses its needs by visiting private hospitals, which provide comprehensive services but at a high cost. The low socioeconomic individuals visit government hospitals where all basic services are available, but there is a struggle to provide advanced healthcare. In order to rectify this dichotomous approach, new initiatives are being implemented to provide uniform healthcare across the society.

Recent findings

Technological advancements have been rapid and modern methods have reached the shores of India at the same pace as in the western world. In otolaryngology, advanced services especially for restoration of hearing loss and multimodality treatments for head and neck cancers have been two areas where practical and ethical dilemmas have existed to provide the most optimal treatment at subsidized costs. This article explores these two areas as examples to understand the specific problems encountered in delivering advanced ENT care in a low-resource setting in a large populous country.

Introduction of government health insurance schemes have helped the poor to make use of advanced healthcare. The highlight of this scheme has been the inclusion of expensive interventions like cochlear and auditory brainstem implantation, whereby cost of the device, surgery and habilitation have all been delivered cost free for eligible children.
Relationship Between Time to Left Atrial Decompression and Outcomes in Patients Receiving Venoarterial Extracorporeal Membrane Oxygenation Support: A Multicenter Pediatric Interventional Cardiology Early-Career Society Study*
Authors: Zampi Jeffrey D. , Alghanem Fares , Yu Sunkyung , Callahan Ryan , Curzon Christopher L. , Delaney Jeffrey W. , Gray Robert G. , Herbert Carrie E. , Leahy Ryan A. , Lowery Ray , Pasquali Sara K. , Patel Priti M. , Porras Diego , Shahanavaz Shabana , Thiagarajan Ravi R. , Trucco Sara M. , Turner Mariel E. , Veeram Reddy Surendranath R. , West Shawn C. , Whiteside Wendy , Goldstein Bryan H.
Published: April 2019

Objectives:

To assess the variation in timing of left atrial decompression and its association with clinical outcomes in pediatric patients supported with venoarterial extracorporeal membrane oxygenation across a multicenter cohort.

Design:

Multicenter retrospective study.

Setting:

Eleven pediatric hospitals within the United States.

Patients:

Patients less than 18 years on venoarterial extracorporeal membrane oxygenation who underwent left atrial decompression from 2004 to 2016.

Interventions:

None.

Measurements and Main Results:

A total of 137 patients (median age, 4.7 yr) were included. Cardiomyopathy was the most common diagnosis (47%). Cardiac arrest (39%) and low cardiac output (50%) were the most common extracorporeal membrane oxygenation indications. Median time to left atrial decompression was 6.2 hours (interquartile range, 3.8–17.2 hr) with the optimal cut-point of greater than or equal to 18 hours for late decompression determined by receiver operating characteristic curve. In univariate analysis, late decompression was associated with longer extracorporeal membrane oxygenation duration (median 8.5 vs 5 d; p = 0.02). In multivariable analysis taking into account clinical confounder and center effects, late decompression remained significantly associated with prolonged extracorporeal membrane oxygenation duration (adjusted odds ratio, 4.4; p = 0.002). Late decompression was also associated with longer duration of mechanical ventilation (adjusted odds ratio, 4.8; p = 0.002). Timing of decompression was not associated with in-hospital survival (p = 0.36) or overall survival (p = 0.42) with median follow-up of 3.2 years.

Conclusions:

In this multicenter study of pediatric patients receiving venoarterial extracorporeal membrane oxygenation, late left atrial decompression (≥ 18 hr) was associated with longer duration of extracorporeal membrane oxygenation support and mechanical ventilation. Although no survival benefit was demonstrated, the known morbidities associated with prolonged extracorporeal membrane oxygenation use may justify a recommendation for early left atrial decompression.
Predictors of Disengagement in Care for Individuals Receiving Pre-exposure Prophylaxis (PrEP)
Authors: Zucker Jason , Carnevale Caroline , Richards Paul , Slowikowski Jacek , Borsa Alexander , Gottlieb Felix , Vakkur Isabella , Hyden Christel , Olender Susan , Cohall Alwyn , Gordon Peter , Sobieszczyk Magdalena E.
Published: April 2019

Background:

HIV pre-exposure prophylaxis (PrEP) reduces incident HIV infections, but efficacy depends on adherence and retention, among other factors. Substance use disorders, unmet mental health needs, and demographic factors are associated with nonadherence in HIV-infected patients; we studied whether these affect PrEP retention in care.

Methods:

To investigate potential risk factors disengagement in a comprehensive HIV prevention program, we conducted a retrospective cohort analysis of individuals starting tenofovir–emtricitabine between January 1, 2015, and November 30, 2017. The primary outcome was adherence to the initial 3-visit schedule after PrEP initiation.

Results:

The cohort was predominantly African American (23%) and Hispanic (46%). Race, ethnicity, substance use, patient health questionnaire 9 score, insurance, and housing status were not associated with retention at the third follow-up visit. Age <30, PrEP initiation in 2017, PrEP initiation in the sexual health clinic, and PrEP same-day start were associated with lower retention; male gender at birth, transition from post‐exposure prophylaxis (PEP) to PrEP, feeling that they could benefit from, or participating in mental health services were associated with increased retention. Overall, retention in HIV preventative care at the first follow-up visit (68%) and third follow-up visit (35%) after PrEP initiation was low.

Conclusion:

Clinic services and ancillary services (such as mental health) may facilitate retention in care. In this study, select social and behavioral determinants of health were not found to be linked to retention. Focused investigation of reasons for dropout may elucidate the challenges to maintaining individuals in PrEP care and direct resource allocation to those in greatest need.
Differences Between Groups of Pre-exposure Prophylaxis (PrEP) Using Couples in HIV-Negative/Unknown Relationships
Authors: John Steven A. , Robles Gabriel , Starks Tyrel J. , Rendina H. Jonathon
Published: April 2019

Background:

Epidemiology research is limited on the characteristics of HIV pre-exposure prophylaxis (PrEP) using couples.

Setting:

US nationwide sample recruited online in 2017.

Methods:

HIV negative/unknown gay, bisexual, and other men who have sex with men with HIV negative/unknown partners (n = 3140) were asked about individual and main partner PrEP uptake. Men were coded into the following 5 groups: (1) neither participant nor partner on PrEP, (2) partner only on PrEP, (3) participant only on PrEP, (4) both on PrEP, and (5) unknown partner PrEP use. We examined associations of demographics, relationship factors, condomless anal sex (CAS) with main and causal partners, bacterial sexually transmitted infection diagnoses, and sexual positioning with reported dyadic PrEP use using fully adjusted multinomial logistic regressions.

Results:

PrEP use was 3.2% for the partner only, 5.7% for the participant only, and 4.9% for both the participant and partner; 5.6% reported not knowing their partner's PrEP use status. Men who reported any CAS with their main partner or any CAS with male casual partners were both more likely to be classified in the dyadic PrEP use group compared with the neither on PrEP group. Compared with monogamous, men in open arrangements were more likely to be classified in each of the 3 PrEP groups compared with the neither on PrEP group. Six-month bacterial sexually transmitted infection prevalence was 2.8%, 8.1%, 8.3%, 15.6%, and 4.0% for the 5 groups, respectively.

Conclusions:

PrEP use occurred during times of higher risk behavior engagement, but further efforts are needed to expand PrEP use to more partnered gay, bisexual, and other men who have sex with men.
Osteoporosis Circumscripta on 68Ga-DOTATATE PET CT
Authors: Gandy Nemi , Ordidge Katherine Louise , Arshad Mubarik , Win Zarni
Published: April 2019

Incidental findings on PET CT studies are common. The distribution of 68Ga-DOTATATE is dependent on cell surface expression of somatostatin receptors, which may be pathologic or physiologic. Osteoporosis circumscripta is the early lytic phase of Paget disease associated with well-defined osteopenia, most commonly seen within the skull on imaging. The appearance has been well demonstrated on 99mTc HDP/MDP bone scans. Here, we present the case of a 76-year-old man with a small bowel carcinoid tumor who underwent staging imaging with 68Ga-DOTATATE PET CT with the incidental finding of osteoporosis circumscripta.
Gated Tomographic Radionuclide Angiography Using CZT Gamma Camera in Patients Receiving Cardiotoxic Chemotherapy
Authors: Bailly Matthieu , Le Rouzic Gilles , Metrard Gilles
Published: April 2019

Tomographic radionuclide angiography (TRNA) can monitor cardiac function in patients receiving cardiotoxic chemotherapy. Gamma cameras using CZT detectors enable dose reduction and quicker acquisitions. We report 80 patients who underwent a 7-minute TRNA acquisition after injection of 550-MBq 99mTc–labeled human serum albumin. Data were analyzed full and half. Image quality was not visually decreased. There was no significant difference in left ventricular systolic and diastolic volumes and in left and right ventricular ejection fractions between full and half data acquisitions (P < 0.0001). When injecting half activity, effective dose could be reduced to 1.92 mSv.
Triple Ectopic Thyroid Detected on SPECT/CT
Authors: Agrawal Kanhaiyalal , Patro P. Sai Sradha , Pradhan Pradeep
Published: April 2019

Ectopic thyroid tissue is a rare entity of embryological aberration along the tract of descend of thyroid gland. Accurate localization and characterization are required for deciding management based on clinical features and symptoms. Ectopic thyroid in the absence of normal thyroid gland is uncommon. However, triple ectopic thyroid with absence of normal thyroid gland is very rare, with only a few cases reported previously. We present a case of triple ectopic thyroid, which appeared as single on planar 99mTc-sodium pertechnetate image, but was evident on SPECT/CT images.
Incidental Primary Breast Lymphoma on 99mTc-Sestamibi Myocardial Perfusion Imaging With SPECT/CT
Authors: Deng Zilong , Dong Aisheng , Zhao Min , Tang Youhong , Liu Yutao
Published: April 2019

We present a 53-year-old woman who had shortness of breath and atypical chest pain and underwent 99mTc-sestamibi myocardial perfusion imaging to detect coronary artery disease. The raw data in cine format showed an incidental focus close to the heart, and SPECT/CT fused images revealed a focus of intense uptake in the left breast. The subsequent histopathologic findings and 18F-FDG PET/CT imaging confirmed the diagnosis as primary breast lymphoma. After 3 cycles of chemotherapy, previously visualized abnormal uptake in the left breast disappeared on the follow-up PET/CT.
Ureteral Stone Mimicking Abnormal Sacral Uptake on 99mTc MDP Bone Scintigraphy
Authors: Wang Renjie , Zhao Gege , Chen Bin , Ji Bin
Published: April 2019

Bone tracer uptake related to ureteral stones has been reported several times before. We present a right ureteral stone mimicking abnormal focal sacral uptake on planar scan in a patient with rectal cancer. This case highlights the necessity of performing SPECT/CT to ascertain the origin of abnormal focal sacral uptake on planar scan, especially in patients with a history of kidney stones.
An Unusual False-Positive Uptake of Radioiodine Caused by Metallic Implants
Authors: Liu Lina , Chen Yu , Tian Tian , Huang Rui , Liu Bin
Published: April 2019

A 36-year-old woman with a history of papillary thyroid cancer underwent radioiodine remnant ablation using 131I. Postablation whole body 131I scintigraphy revealed increased activity not only in the thyroid bed but also in the right upper thigh. SPECT/CT images localized the activity to the metallic implants of the right femur, implanted 3 years earlier after the right femoral cyst resection.
Incidental Detection of a Radiation-Induced Soft-Tissue Sarcoma on 68Ga-PSMA PET/CT in a Patient Previously Treated for Prostate Cancer
Authors: Plouznikoff Nicolas , Woff Erwin , Artigas Carlos , Alexiou Jean , Flamen Patrick
Published: April 2019

Radiation-induced sarcoma is a rare complication of radiation therapy. We describe the incidental detection of a radiation-induced undifferentiated soft-tissue sarcoma with increased uptake on 68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT in a prostate cancer patient previously treated with surgery and external-beam radiotherapy. Results were confirmed by histological analysis. 68Ga-PSMA is known to bind not only to PSMA-expressing prostate cancer cells but also to the neovasculature of various other solid tumors. A careful 68Ga-PSMA PET/CT review of previously irradiated areas is warranted so as not to miss radiation-induced sarcoma in prostate cancer patients.
Use of Static Imaging as a Substitute for Conventional Dynamic Imaging for Salivagrams in Children
Authors: Wu Ha , Zhao Ruifang , Zhao Xiaofei
Published: April 2019

Objective

Salivagrams are commonly used for detecting pulmonary aspiration. However, conventional dynamic imaging is relatively time-consuming and could be difficult to perform in children with poor compliance. We analyzed the characteristics of conventional dynamic imaging to obtain a simple protocol suitable for use in children.

Methods

We conducted a retrospective analysis of salivagram data from 1163 patients (783 males, 380 females; age, 1 month to 9.0 years; mean age, 5.7 months) obtained in the past 4.5 years (January 2014 to June 2018). The various timepoint images were used for diagnosis. The positivity rate, missed diagnosis rate, and sensitivity were calculated and compared.

Results

Dynamic imaging revealed 353 cases of pulmonary aspiration (248 males, 105 females; age, 1 month to 4.5 years; mean age, 6.2 months). The positivity rate was 30.4% (353/1163), and 95.8% (338/353) of patients presented with continuous positive images after pulmonary aspiration. Only 4.2% (15/353) of positive cases showed clearance of pulmonary aspiration. The positivity rates were 11.8%, 18.2%, 21.9%, 25.0%, 27.0%, and 29.2% at 5, 10, 15, 20, 25, and 30 minutes, respectively. About 4.2% (15/353) of positive cases on earlier images showed clearance of pulmonary aspiration on later images, which indicate both early 15-minute and later 30-minute images were necessary.

Conclusions

Two static images acquired at 15 and 30 minutes might be an effective alternative to conventional salivagram, which mandates dynamic imaging.
Tumor Volume Analysis as a Predictive Marker for Prolonged Survival in Anaplastic Lymphoma Kinase–rearranged Advanced Non–Small Cell Lung Cancer Patients Treated With Crizotinib
Authors: Hida Tomoyuki , Dahlberg Suzanne E. , Lydon Christine A. , Hatabu Hiroto , Johnson Bruce E. , Awad Mark M. , Nishino Mizuki
Published: April 2019

Purpose:

Targeted inhibition of anaplastic lymphoma kinase (ALK) has been widely used for the treatment of advanced non–small cell lung cancer (NSCLC) with ALK rearrangements. We performed tumor volume analysis of ALK-rearranged advanced NSCLC treated with crizotinib to identify an early predictive marker for prolonged survival.

Materials and Methods:

Cases of 42 patients with ALK-rearranged advanced NSCLC (16 men, 26 women; median age: 55.7 y) treated with crizotinib as their first ALK-directed therapy were retrospectively studied. Tumor volume measurements of dominant lung lesions were performed on baseline computed tomography and follow-up computed tomography at 8 weeks of therapy. The relationships between the 8-week volume change (%) and overall survival (OS) were investigated.

Results:

The 8-week tumor volume change ranged from −99.3% to 117.5% (median: −57.7%). Using the 25th percentile of the 8-week volume change of −74%, 11 patients with >74% volume decrease at 8 weeks had a significantly longer OS compared with 31 patients with ≤74% decrease (median OS: 92.0 vs. 22.8 mo; P=0.0048). In multivariable analyses using Cox proportional hazards models, the 8-week volume decrease of >74% was significantly associated with longer OS (hazard ratio=0.14, 95% confidence interval: 0.03-0.59; Cox P=0.008) after adjusting for tumor stage (stage IV vs. recurrent NSCLC, hazard ratio=5.6, 95% confidence interval: 1.29-24.3; P=0.02).

Conclusions:

The 8-week tumor volume decrease of >74% is significantly associated with longer OS in patients with ALK-rearranged NSCLC treated with crizotinib.
Automatic proximal airway volume segmentation using optical coherence tomography for assessment of inhalation injury
Authors: Miao Yusi , Choi Jae Hyek , Chou Li-Dek , Desai Vineet , Roberts Teryn R. , Beely Brendan M. , Wendorff Daniel S. , Espinoza Mark , Sieck Kyle , Cancio Leopoldo C. , Brenner Matthew , Batchinsky Andriy I. , Chen Zhongping
Published: April 2019

BACKGROUND

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with a mortality rate of up to 40%. Early management of ARDS has been difficult due to the lack of sensitive imaging tools and robust analysis software. We previously designed an optical coherence tomography (OCT) system to evaluate mucosa thickness (MT) after smoke inhalation, but the analysis relied on manual segmentation. The aim of this study is to assess in vivo proximal airway volume (PAV) after inhalation injury using automated OCT segmentation and correlate the PAV to lung function for rapid indication of ARDS.

METHODS

Anesthetized female Yorkshire pigs (n = 14) received smoke inhalation injury (SII) and 40% total body surface area thermal burns. Measurements of PaO2-to-FiO2 ratio (PFR), peak inspiratory pressure (PIP), dynamic compliance, airway resistance, and OCT bronchoscopy were performed at baseline, postinjury, 24 hours, 48 hours, 72 hours after injury. A tissue segmentation algorithm based on graph theory was used to reconstruct a three-dimensional (3D) model of lower respiratory tract and estimate PAV. Proximal airway volume was correlated with PFR, PIP, compliance, resistance, and MT measurement using a linear regression model.

RESULTS

Proximal airway volume decreased after the SII: the group mean of proximal airway volume at baseline, postinjury, 24 hours, 48 hours, 72 hours were 20.86 cm3 (±1.39 cm3), 17.61 cm3 (±0.99 cm3), 14.83 cm3 (±1.20 cm3), 14.88 cm3 (±1.21 cm3), and 13.11 cm3 (±1.59 cm3), respectively. The decrease in the PAV was more prominent in the animals that developed ARDS after 24 hours after the injury. PAV was significantly correlated with PIP (r = 0.48, p < 0.001), compliance (r = 0.55, p < 0.001), resistance (r = 0.35, p < 0.01), MT (r = 0.60, p < 0.001), and PFR (r = 0.34, p < 0.01).

CONCLUSION

Optical coherence tomography is a useful tool to quantify changes in MT and PAV after SII and burns, which can be used as predictors of developing ARDS at an early stage.

LEVEL OF EVIDENCE

Prognostic, level III.
Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation
Authors: Williams Aaron M. , Bhatti Umar F. , Biesterveld Ben E. , Graham Nathan J. , Chtraklin Kiril , Zhou Jing , Dennahy Isabel S. , Kathawate Ranganath G. , Vercruysse Claire A. , Russo Rachel M. , Li Yongqing , Alam Hasan B.
Published: April 2019

BACKGROUND

Although damage control resuscitation (DCR) is routinely performed for short durations, prolonged DCR may be required in military conflicts as a component of prolonged field care. Valproic acid (VPA) has been shown to have beneficial properties in lethal hemorrhage/trauma models. We sought to investigate whether the addition of a single dose of VPA to a 72-hour prolonged DCR protocol would improve clinical outcomes.

METHODS

Fifteen Yorkshire swine (40–45 kg) were subjected to lethal (50% estimated total blood volume) hemorrhagic shock (HS) and randomized to three groups: (1) HS, (2) HS-DCR, (3) HS-DCR-VPA (150 mg/kg over 3 hours) (n = 5/cohort). In groups assigned to receive DCR, Tactical Combat Casualty Care guidelines were applied (1 hour into the shock period), targeting a systolic blood pressure of 80 mm Hg. At 72 hours, surviving animals were given transfusion of packed red blood cells, simulating evacuation to higher echelons of care. Survival rates, physiologic parameters, resuscitative fluid requirements, and laboratory profiles were used to compare the clinical outcomes.

RESULTS

This model was 100% lethal in the untreated animals. DCR improved survival to 20%, although this was not statistically significant. The addition of VPA to DCR significantly improved survival to 80% (p < 0.01). The VPA-treated animals also had significantly (p < 0.05) higher systolic blood pressures, lower fluid resuscitation requirements, higher hemoglobin levels, and lower creatinine and potassium levels.

CONCLUSION

VPA administration improves survival, decreases resuscitation requirements, and improves hemodynamic and laboratory parameters when added to prolonged DCR in a lethal hemorrhage model.