bluuebunny/crossref_metadata_2025 huggingface dataset:
Attitudes About Consumer Strategies Among Americans in High-deductible Health Plans
Authors: Cliff Betsy Q. , Krenz Christopher , West Brady T. , Levy Helen , Fendrick A. Mark , Winkelman Tyler N.A. , So Jonathan , Fagerlin Angela , Kullgren Jeffrey T.
Published: January 2019

Background:

More than 70 million Americans are enrolled in a high-deductible health plan (HDHP), with high upfront cost-sharing to encourage strategies such as price shopping to mitigate out-of-pocket spending. Recent research suggests HDHP enrollees are reluctant to engage in these consumer strategies, but there is little information on why.

Objectives:

To describe associations between HDHP enrollees’ attitudes about and intent to engage in consumer strategies.

Research Design:

We conducted a nationally representative web survey of 1637 HDHP enrollees that included 2 hypothetical scenarios amenable to consumer strategies. For each scenario, we asked participants whether they would compare price or quality information, discuss cost with a provider, or try to negotiate a service price. We measured participants’ ratings of the difficulty of each strategy, its effectiveness at reducing cost or increasing the likelihood of getting care, and how likely participants would be to actually engage in each strategy.

Results:

Fewer than half of HDHP enrollees intended to engage in any of the surveyed strategies. Enrollees who viewed a consumer strategy as helpful were more likely to engage in that strategy; no associations were found with perceived difficulty of a strategy and intent to engage in it.

Conclusions:

HDHP enrollees may not pursue consumer strategies because they believe they are not helpful for getting care or lowering costs. Providers and payers should ensure these strategies are actually helpful to HDHP enrollees and that enrollees understand how they could use these strategies to reduce their out-of-pocket costs.
Measuring and Analyzing Length of Stay in Critical Care Trials
Authors: Harhay Michael O. , Ratcliffe Sarah J. , Small Dylan S. , Suttner Leah H. , Crowther Michael J. , Halpern Scott D.
Published: January 2019

Background:

In randomized clinical trials among critically ill patients, it is uncertain how choices regarding the measurement and analysis of nonmortal outcomes measured in terms of duration, such as intensive care unit (ICU) length of stay (LOS), affect studies’ conclusions.

Objectives:

Assess the definitions and analytic methods used for ICU LOS analyses in published randomized clinical trials.

Research Design:

This is a systematic review and statistical simulation study.

Results:

Among the 80 of 150 trials providing sufficient information regarding the chosen definition of ICU LOS, 3 different start times (ICU admission, trial enrollment/randomization, receipt of intervention) and 2 end times (discharge readiness, actual discharge) were used. In roughly three quarters of these studies, ICU LOS was compared using approaches that did not explicitly account for death, either by ignoring it entirely or stratifying the analyses by survival status. The remaining studies used time-to-event (discharge) models censoring at death or applied a fixed LOS value to patients who died. In statistical simulations, we showed that each analytic approach tested a different question regarding ICU LOS, and that approaches that do not explicitly account for death often produce misleading or ambiguous conclusions when treatments produce small effects on mortality, even if those are not detected as significant in the trial.

Conclusions:

There is considerable variability in how ICU LOS is measured and analyzed which impairs the ability to compare results across trials and can produce spurious conclusions. Analyses of duration-based outcomes such as LOS should jointly assess the impact of the intervention on mortality to yield correct interpretations.
Pathways of smooth muscle foam cell formation in atherosclerosis
Authors: Pryma Collin S. , Ortega Carleena , Dubland Joshua A. , Francis Gordon A.
Published: January 2019

Purpose of review

Smooth muscle cells (SMCs) are the major cell type in human atherosclerosis-prone arteries and take up excess lipids, thereby contributing to luminal occlusion. Here we provide a focused review on pathways by which smooth muscle cells (SMCs) can become foam cells in atherosclerosis.

Recent findings

A synthesis of recent and older investigations provides key mechanistic insights into SMC foam cell formation. LDL and other apoB-containing lipoproteins are modified by a diverse array of oxidative, enzymatic, and nonenzymatic processes present in the arterial intima. These modifications of LDL all promote the aggregation of LDL (agLDL), a key finding from analysis of arterial lesion particles. Scavenger receptor and phagocytic capacity of SMCs can vary greatly, perhaps related to differences in SMC phenotype or in-vitro cell culture environments, and can be increased with exposure to cytokines, growth factors, and cholesterol. Macrophages promote the formation of SMC foam cells in direct or indirect co-culture models.

SMCs contribute significantly to the foam cell population in atherosclerosis. Further investigation and identification of key mechanisms of SMC foam cell formation will help drive new therapeutics to reduce cardiovascular disease.
Progress in finding pathogenic DNA copy number variations in dyslipidemia
Authors: Iacocca Michael A. , Dron Jacqueline S. , Hegele Robert A.
Published: January 2019

Purpose of review

DNA copy number variations (CNVs) are large-scale mutations that include deletions and duplications larger than 50 bp in size. In the era when single-nucleotide variations were the major focus of genetic technology and research, CNVs were largely overlooked. However, CNVs clearly underlie a substantial proportion of clinical disorders. Here, we update recent progress in identifying CNVs in dyslipidemias.

Recent findings

Until last year, only the LDLR and LPA genes were appreciated as loci within which clinically relevant CNVs contributed to familial hypercholesterolemia and variation in Lp(a) levels, respectively. Since 2017, next-generation sequencing panels have identified pathogenic CNVs in at least five more genes underlying dyslipidemias, including a PCSK9 whole-gene duplication in familial hypercholesterolemia; LPL, GPIHBP1, and APOC2 deletions in hypertriglyceridemia; and ABCA1 deletions in hypoalphalipoproteinemia.

CNVs are an important class of mutation that contribute to the molecular genetic heterogeneity underlying dyslipidemias. Clinical applications of next-generation sequencing technologies need to consider CNVs concurrently with familiar small-scale genetic variation, given the likely implications for improved diagnosis and treatment.
Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism
Authors: Joris Benjamin R. , Gloor Gregory B.
Published: January 2019

Purpose of review

Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations.

Recent findings

Byproducts of microbial metabolism are associated with health and disease: Trimethylamine N oxide is associated with atherosclerosis; whereas short-chain fatty acids are associated with decreased inflammation and increased energy expenditure. More broadly, a large number of association studies have been conducted to explore the connections between bacterial taxa and metabolic syndrome. In contrast, the relationship between the microbiome and triglycerides levels remains poorly understood.

We suggest that deeper understanding of the molecular mechanisms that drive linkages between the microbiome and disease can be determined by replacing 16S rRNA gene sequencing with shotgun metagenomic sequencing or other functional approaches. Furthermore, to ensure translatability and reproducibility of research findings, a combination of multiple different complementary ‘-omic’ approaches should be employed.
Management of the marginal mandibular nerve during and after neck dissection
Authors: Murthy Samskruthi P. , Paderno Alberto , Balasubramanian Deepak
Published: January 2019

Purpose of review

Marginal mandibular nerve palsy (MMNP) is often an understated complication after neck dissection. This article reviews literature regarding anatomic landmarks that help define marginal mandibular nerve (MMN) during neck dissection, oncologic safety of surgical maneuvers, implications of MMNP, and reconstructive options.

Recent findings

A thorough knowledge of anatomy of the nerve can aid in its preservation. Course, branching pattern and communications of MMN are extremely variable. The Hayes Martin method classically described to preserve the nerve may not be oncologically safe in patients with prefacial nodal involvement. MMNP significantly affects quality of life after neck dissection. Cause, timing, and degree of neural damage play an important role in determining diagnostic and therapeutic options to correct the deformity resulting from MMNP. Owing to treatment-related factors, functionality of local structures may be compromised, which limits available reconstructive options for the surgeon. This should favor a shift of management option toward more conservative procedures in patients treated for head and neck cancer.

When oncologically safe, the MMN must always be preserved. The patient perceived deformity resulting from MMNP is significantly higher than clinician-detected rate. In select patients who are affected by significant smile asymmetry, multiple dynamic and static corrective procedures can be offered.
Arguments for routine administration of probiotics for NEC prevention
Authors: Underwood Mark A.
Published: January 2019

Purpose of review

Probiotic administration to premature infants for the purpose of prevention of necrotizing enterocolitis is common in many parts of the world but uncommon in the United States. The present review will emphasize recent findings in support of routine administration of probiotics to this highly vulnerable population.

Recent findings

Additional evidence from animal models describing mechanisms of protection of probiotics in the immature gut and updated meta-analyses of randomized placebo-controlled trials and observational cohorts are presented (now including more than 40 000 premature infants from countries across the globe).

The preponderance of evidence suggests that probiotic administration to premature infants is well tolerated and decreases the risk of death, necrotizing enterocolitis, and sepsis. Further comparisons of probiotic administration to placebo are not likely to alter these conclusions. Rather, future work should focus on assurance of high-quality products with demonstrated purity and viability of probiotic microbes, and future clinical trials should focus on comparisons between high-quality products and doses.
Use of earth observations for temperature exposure assessment in epidemiological studies
Authors: Kloog Itai
Published: January 2019

Purpose of review

Low, high, extreme, and variable temperatures have been linked to multiple adverse health outcomes, particularly among the elderly and children. Recent models incorporating satellite remote sensing data have mitigated several limitations of previous studies, improving exposure assessment. This review focuses on these new temperature exposure models and their application in epidemiological studies.

Recent findings

Satellite observations of land surface temperature have been used to model air temperature across large spatial areas at high spatiotemporal resolutions. These models enable exposure assessment of entire populations and have been shown to reduce error in exposure estimates, thus mitigating downward bias in health effect estimates.

Satellite-based models improve our understanding of spatiotemporal variation in temperature and the associated health effects. Further research should focus on improving the resolution of these models, especially in urban areas, and increasing their use in epidemiological studies of direct temperature exposure and vector-borne diseases.
Insights Into Pediatric Autoimmune Gastritis
Authors: Moreira‐Silva Helena , Silva Gisela , Costa Emília , Guerra Isabel , Santos‐Silva Ermelinda , Tavares Marta , Cleto Esmeralda , Lima Rosa
Published: January 2019

Objectives:

Autoimmune gastritis (AIG) is a chronic inflammatory condition of the gastric mucosa, mainly described in adults presenting with pernicious anemia. It results from antibody‐mediated destruction of parietal cells, but the precise initiating event is unknown. The pathogenicity of Helicobacter pylori (H pylori) has been suggested but not established. This study aimed to better characterize AIG in pediatric patients and to address the possible role of H pylori infection.

Methods:

Descriptive single‐center study, retrospectively describing 20 patients with a diagnosis of AIG based on positivity for anti‐parietal cell autoantibodies, in addition to analytical and/or histological findings of oxyntic mucosa atrophy.

Results:

In the majority (18/20), AIG diagnosis was suggested during investigation of refractory iron‐deficient anemia. One patient had dyspepsia and none of the others had gastrointestinal symptoms. Fifty‐five percent (11/20) were H pylori positive, but there were no significant differences regarding mean hemoglobin values at presentation (10.6 ± 2.5 vs 9.5 ± 1.0 g/dL, P > 0.05), analytical indicators of gastric atrophy (gastrin, 564.4 ± 184 vs 721.2 ± 220.6 pg/mL, P > 0.05), or in the presence or the grade of oxyntic mucosa atrophy.

Conclusions:

Our findings highlight that AIG may have an age‐dependent presentation; thus, we can consider a pediatric phenotype that in contrast to adults, is manifested by refractory iron‐deficient anemia and associated with parietal cell autoantibody positivity, but not intrinsic factor autoantibodies. A correlation between H pylori and AIG was not evident in the current study and it is still unclear whether H pylori is a trigger for AIG.
Minimal Residual Disease–guided Risk Restratification and Therapy Improves the Survival of Childhood Acute Lymphoblastic Leukemia: Experience From a Tertiary Children’s Hospital in China
Authors: Liao Chan , Xu Xiaojun , Shen Diying , Song Hua , Xu Weiqun , Zhao Fenying , Yang Shilong , Shi Shuwen , Liang Juan , Li Sisi , Tang Yongmin
Published: January 2019

The minimal residual disease (MRD) has been shown to be very important to evaluate the prognostic significance in childhood acute lymphoblastic leukemia (ALL), but the impact under the current treatment protocol in China has not been fully elucidated. The aim of this study was to investigate the efficacy of MRD-guided risk restratification of ALL. A total of 676 children with ALL were enrolled. In the predictive study group, 476 patients were enrolled with 5-year cumulative incidence of relapse rates of the low-risk (LR), intermediate-risk (IR), and high-risk groups being 11.0%±2.3%, 12.6%±3.3%, and 32.7%±4.9%, respectively. In the intervention study group, 19/200 patients enrolled were reclassified into risk groups according to the MRD levels. The 3-year event-free survival and overall survival were 85.2%±2.9% and 90.6%±2.1%, respectively, which were higher than those of the predictive study group (79.1%±1.9% and 84.7%±1.7%, respectively; P<0.05). The 3-year cumulative incidence of relapse in the LR and IR groups of the intervention study group were 4.2%±3.1% and 6.4%±3.1%, respectively, which were significantly lower than those in the predictive study group (7.2%±1.8% and 11.8%±3.2%, respectively; P<0.05). We conclude that the risk of relapse in the LR and IR groups can be significantly reduced after MRD-guided risk restratification.
Impact of IgG Monitoring and IVIG Supplementation on the Frequency of Febrile Illnesses in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Maintenance Chemotherapy
Authors: Holmes Emily A. , Friedman Debra L. , Connelly James A. , Dulek Daniel E. , Zhao Zhiguo , Esbenshade Adam J.
Published: January 2019

Monitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as “ever IgG monitored” if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.
Conclusiveness of Cochrane Reviews in physiotherapy: a systematic search and analytical review
Authors: Momosaki Ryo , Tsuboi Marika , Yasufuku Yuichi , Furudate Ken , Kamo Tomohiko , Uda Kazuaki , Tanaka Yuu , Abo Masahiro
Published: January 2019

Numerous Cochrane Reviews (CRs) in the field of physiotherapy have been published, but their conclusiveness has not been investigated. The purpose of this study was to provide an overview and describe the conclusiveness of evidence from CRs regarding physiotherapy. We conducted a systematic search using the Cochrane Database of Systematic Reviews in the Cochrane Library from 2008 through 2017 in the field of physiotherapy, the Physical Rehabilitation Evidence Database, and the CRs list on the Cochrane Rehabilitation website. Reviewers extracted the following data: year of publication, editorial group, number of articles meeting the criteria, number of patients enrolled, conclusiveness, and need for additional studies. Linear regression was used to determine whether the percentage of conclusive reviews was affected by the year of publication. Reviewers found 283 CRs in the field of physiotherapy, and only 16 (5.7%) of which were conclusive. The number of trials and participants enrolled in conclusive reviews were significantly higher than those in inconclusive reviews (P < 0.001). The percentage of conclusive reviews was significantly correlated with year of publication (P = 0.03). Almost all reviews recognized the need for additional studies. Most CRs in physiotherapy are inconclusive, and most emphasize the need for further research. The ability of a Cochrane Review to reach a conclusion is affected by the cumulative patient sample size and number of trials included in the analysis.
Racial Disparities in Cervical Cancer Screening: Implications for Relieving Cervical Cancer Burden in Asian American Pacific Islander Women
Authors: Lee Hee Yun , Beltran Raiza , Kim Nam Keol , Lee Do Kyung
Published: January 2019

Background

While cervical cancer is considered preventable and the overall Papanicolaou (Pap) test utilization rate has gradually increased in the United States, certain Asian American Pacific Islander (AAPI) women consistently rate lower in Pap test receipt compared with non-Latina whites (NLWs), leading to a higher cervical cancer mortality rate for various AAPI women. Few studies, however, have focused on female AAPI college students' cervical cancer screening behavior in comparison with NLW students.

Objective

This study aimed to investigate cervical cancer screening behaviors among college-aged females by (1) determining AAPIs' and NLWs' screening rates, (2) assessing their knowledge about Pap tests, and (3) discovering factors associated with Pap test receipt. Andersen's Health Behavioral Model was used as a theoretical framework.

Methods

Using a simple random sampling strategy, 2270 female students (15% AAPIs, 85% NLWs) completed an online health survey.

Results

Results indicate AAPI students had significantly lower Pap test knowledge and Pap test receipt rate compared with NLW students. Age, nativity, human papillomavirus vaccination completion, frequency of obstetrician/gynecologist (OB/GYN) visits, and the number of sexual partners were associated with AAPI students' lower rate of Pap test receipt, whereas the Pap test receipt rate for NLW students was influenced by the same factors with the addition of having increased prior knowledge about Pap tests.

Conclusion

Results show the importance of OB/GYN visits in obtaining Pap tests for AAPI and NLW students.

Implication for Practice

Health practitioners should pay attention to students' race/ethnicity in their practice and provide corresponding ethnic group–specific preventive care.
Interdisciplinary Rounds on a Hospitalist Service
Authors: Smith Catherine V. , Maduro Ralitsa S. , Morgan Merri K. , Ver Schneider Patricia , Rutledge Carolyn M. , Zimbro Kathie S.
Published: January 2019

Background:

Despite growth in service availability, palliative care (PC) referrals are often underutilized or delayed, which may compromise patient outcomes.

Local Problem:

Underutilized or delayed PC referrals among hospitalized adults prompted this project aimed at improving PC measures, quality, and utilization outcomes.

Methods:

Data extracted from the electronic medical record were used to identify needed improvements in PC.

Intervention:

Interdisciplinary rounds (IDRs) were implemented on the hospitalist service in a nonintensive care setting.

Results:

Following implementation, median time to PC referral decreased by 2 days. Length of stay (LOS), direct cost, and 30-day mortality also decreased. Postintervention patients were more likely to transition home compared with another facility.

Conclusions:

Results support IDRs as a mechanism to improve time to PC referral, decrease LOS, direct cost, and 30-day mortality among hospitalized adults. A more objective method of identifying patients with unmet PC needs may be warranted.
Bacteria on the Soles of Patient-Issued Nonskid Slipper Socks
Authors: Welle Mary K. , Bliha Madeline , DeLuca Jenna , Frauhiger Alayna , Lamichhane-Khadka Reena
Published: January 2019

BACKGROUND:

This is the first study to determine whether nonskid slipper socks in contact with the hospital floor and worn into bed contaminate bed linen.

PURPOSE:

The main purpose of the study was to determine whether contamination of hospital linen occurred with bacteria transferred from the soles of nonskid slipper socks that have touched the floor.

METHODS:

This study mimicked real patients walking on a hospital floor wearing slipper socks and getting back into bed with the slipper socks on. Swab samples were collected from the surfaces of the hospital floor, nonskid slipper sock bottoms, and bed linen in 2 Midwestern hospitals. From the samples, bacterial isolates were identified and tested for antibiotic resistance.

RESULTS:

Isolates obtained from the samples were identified on all 3 surfaces at both hospitals, indicating spread of the bacteria from floor to the bed linen via the nonskid slipper socks. Antibiotic sensitivity test revealed that a significant number of isolates collected were resistant to at least 2 antibiotics tested.

CONCLUSION:

This study demonstrates cross-contamination of bed linen with potentially pathogenic bacteria present on the hospital floor via contact with patient-worn nonskid slipper socks. A simple practice change regarding the wearing of slipper socks could play an important role in preventing pathogen transfer to the bed linen. Awareness of the likelihood of hand contamination after touching the sock bottoms that have come in contact with the hospital floor should also be considered.
A Descriptive and Geospatial Analysis of Environmental Factors Attributing to Sudden Unexpected Infant Death
Authors: Drake Stacy A. , Wolf Dwayne A. , Yang Yijiong , Harper Sherhonda , Ross Jennifer , Reynolds Thomas , Giardino Eileen R.
Published: January 2019

This study examined medicolegal death investigation records and autopsy reports of a medical examiner's office to identify the circumstances surrounding sudden unexpected infant deaths (SUID) and geospatial analyses to pinpoint areas of infant death concentration. Analysis of 732 records of SUID deaths occurring in a 10-year span resulted in the conclusion that environmental factors associated with the sudden death were to some extent modifiable. Co-sleeping (sharing a sleeping surface, or bed-sharing) on various surfaces (mattress, pallet, couch) occurred in 53.4% of the infant deaths. Geographic areas where the largest number of deaths occurred were characterized as areas of high poverty level. The inclusion of additional information at the time of investigation (eg, alcohol and tobacco use of co-sleepers, illness of others in household, exceptions to normal sleep routine of infant) may aid in identifying modifiable circumstances to reduce infant mortality attributable to sudden infant death.
Rapid Streptococcus Pneumonia Antigen Detection on Postmortem Urine in a Death Due to Pneumococcal Meningitis
Authors: Hensby-Bennett Sarah , Garland Jack , Philcox Winston , McCarthy Sinead , Playle Veronica , Kesha Kilak , Stables Simon , Tse Rexson
Published: January 2019

Streptococcus pneumoniae is the leading cause of adult bacterial meningitis. Differing from Neisseria meningitidis (the second most common cause of acute bacterial meningitis), contact tracing and chemoprophylaxis are not required. At postmortem, the differentiation between S. pneumoniae and N. meningitidis is traditionally done by culture and polymerase chain reaction performed on blood or cerebrospinal fluid, but may take hours, if not days, to analyze. We present a death from bacterial meningitis in a 73-year-old woman in which a rapid urinary pneumococcal antigen testing was able to identify S. pneumoniae as the causative organism within 1 hour. This was confirmed by subsequent brain swab culture. The rapid urinary pneumococcal antigen test in the case prevented the need for contact tracing and chemoprophylaxis. This case highlights the potential use of this test to rapidly identify the culprit organism at postmortem examination when acute bacterial meningitis is detected.
Annexin A10 and HES-1 Immunohistochemistry in Right-sided Traditional Serrated Adenomas Suggests an Origin From Sessile Serrated Adenoma
Authors: Nourbakhsh Mahra , Minoo Parham
Published: January 2019

There is increasing body of evidence to suggest that some colonic serrated polyps do not fit morphologically with any of the proposed categories for serrated polyps recommended by the World Health Organization. Most of these polyps have morphologic features of traditional serrated adenoma (TSA) admixed with areas resembling sessile serrated adenoma (SSA) or hyperplastic polyp (HP). Based on these findings it has been suggested that at least some TSAs may arise in association with precursor HP or SSA lesions, particularly those that develop in right colon. To further evaluate this hypothesis, 39 serrated polyps from right side of the colon (cecum, ascending, and transverse colon) with mixed features of TSA and SSA were evaluated by 2 immunostains previously shown to represent markers of SSA. One is Annexin A10 which shows upregulated expression in SSA and the other is Hes-1 which is shown to be down regulated in SSA. The expression patterns of these markers were evaluated in SSA and TSA components of hybrid polyps and compared with control groups (pure SSAs and TSAs of right colon). SSA component in hybrid polyps did not show any significant difference in staining pattern compared with that seen in TSA component of hybrid polyps or in pure TSA polyps. These findings further support the hypothesis that recognizes SSA as a precursor lesion for TSA in the right colon.
NordiQC Assessments of Chromogranin A Immunoassays
Authors: Røge Rasmus , Kristoffersen Heidi L. , Bzorek Michael , Nielsen Ole , Vyberg Mogens
Published: January 2019

This paper is number 6 in a series developed through a partnership between ISIMM and Nordic IHC Quality Control with the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.
Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules
Authors: Bose Shikha , Sacks Wendy , Walts Ann E.
Published: January 2019

Fine needle aspiration biopsy (FNAB) and ultrasonography are the most common modalities for the diagnosis and follow up of thyroid nodules. FNAB is able to distinguish benign from malignant nodules with high sensitivity and specificity; however, 20% to 30% of nodules are diagnosed as indeterminate with a risk of malignancy varying from 10% to 75% based on the 2017 revision of the Bethesda System for Reporting Thyroid Cytopathology. Molecular tests are being increasingly used to triage this group of nodules. Several molecular tests are commercially available and newer upgrades are being developed to either “rule in” or “rule out” malignancy with greater accuracy. The Afirma gene expression classifier and its recent upgrade (the Afirma gene sequencing classifier), Thryoseq v2, a next generation sequencing test and its recent upgrade (the v3), RosettaGX Reveal based on microRNA alterations, and ThyGenX/ThyraMIR, a combination test, are currently on the market. Familiarity with these tests, their performance, and postvalidation publications will enable appropriate test selection and improve triage of patients for appropriate therapy. The underlying rate of malignancy at different institutions and the interobserver variability in cytologic and histologic diagnosis of thyroid lesions are important factors that impact the performance of the various molecular tests.
Activating Structural Alterations in MAPK Genes Are Distinct Genetic Drivers in a Unique Subgroup Of Spitzoid Neoplasms
Authors: Quan Victor L. , Zhang Bin , Mohan Lauren S. , Shi Katherine , Isales Maria C. , Panah Elnaz , Taxter Timothy J. , Beaubier Nike , White Kevin , Gerami Pedram
Published: January 2019

Recent studies have described kinase fusions as the most common initiating genomic events in Spitzoid neoplasms. Each rearrangement generates a chimeric protein with constitutive activation of the tyrosine kinase domain, resulting in the development of a Spitzoid neoplasm. Identifying key initiating genomic events and drivers may assist in diagnosis, prognostication, and management. Retrospective, consecutive search of our database between 2009 and 2018 for Spitzoid neoplasms identified 86 cases. Whole transcriptome mRNA and DNA sequencing (1714 genes) detected 9% of cases (8/86) with structural rearrangements in MAPK genes other than BRAF and 47% (40/86) with kinase fusions previously described in Spitzoid neoplasms. We identified in-frame fusions of MAP3K8-DIPC2, MAP3K8-PCDH7, MAP3K8-UBL3, MAP3K8-SVIL (n=6), and ATP2A2-MAP3K3 (n=1) as well as a p.I103_K104 in-frame deletion of MAP2K1 (n=1), in the absence of well-recognized drivers of melanocytic neoplasia. Fluorescence in situ hybridization validated all cases (n=7) with available tissue. Cases occurred in younger patients (median age 18 y). Morphologically, cases were predominantly epithelioid (P=0.0032), often with some melanin pigment (P=0.0047), and high-grade nuclear atypia (P=0.012). A significant proportion were thought to be Spitzoid melanomas (3/8). Average follow-up time was 11 months. One MAP3K8-DIP2C Spitzoid melanoma involved 4/5 sentinel lymph nodes and led to a complete lymph node dissection with unremarkable follow-up at 9 months. One MAP3K8-DIPC2 atypical Spitz tumor raised concern for recurrence at 10 months and was reexcised. We present a distinct subtype of Spitzoid neoplasm characterized by structural alterations in MAPK genes, which are important to recognize given the potential for treatment with MAPK inhibitors in metastatic cases.
Intrasinusoidal Spread of Hepatic Epithelioid Hemangioendothelioma
Authors: Agostini-Vulaj Diana , Pehlivanoglu Burcin , Weiss Sharon W. , Krasinskas Alyssa , Feely Michael M. , Hornick Jason L. , Cates Justin M.M. , Bentley Karen L. de Mesy , Adsay Nazmi Volkan , Gonzalez Raul S.
Published: January 2019

Epithelioid hemangioendothelioma (EHE) is an angiocentric tumor that, when arising in liver, is centered around hepatic/portal veins. However, EHE cells can also track along sinusoids, which is not well recognized or studied. We identified 18 cases of hepatic EHE and 6 nonhepatic EHEs. For all cases, we recorded EHE multifocality and maximum size. When tumor cells were identified apart from the main mass, we recorded their location, maximum distance from the main tumor, density per high-power field, and cytomorphology. Immunohistochemical staining for CAMTA1, ERG, and CAM5.2 was performed on all cases. Lesional cells were present apart from the main mass in 17 of 18 (94%) liver cases, always within sinusoids and occasionally (4/17, 24%) in central veins. They appeared intensely hyperchromatic with vaguely cerebriform nuclei and multinucleation in 6 (35%) of cases. CAMTA1 and ERG positivity was seen in all 17 cases. Two cases (12%) demonstrated focal CAM5.2 positivity. Sinusoidal EHE cells ranged from 0.1 to 0.8 cm away from the main tumor. There were no statistically significant associations between histologic findings and patient outcome. In the 6 nonhepatic cases, tumor cells did not extend beyond the main EHE. Lesional cells in hepatic EHE often extend beyond the main lesion into sinusoids, where they demonstrate an unusual, somewhat distinctive morphology. Care should be taken to identify such cells in limited biopsies; immunohistochemistry for CAMTA1, a specific and sensitive marker for EHE, can be confirmatory.
Association of Fluid Overload With Clinical Outcomes in Critically Ill Children With Bronchiolitis: Bronquiolitis en la Unidad de Cuidados Intensivos Pediátricos (BRUCIP) Study*
Authors: Flores-González Jose C. , Valladares Cristina Montero , Yun Castilla Cristina , Mayordomo-Colunga Juan , Quesada Sonia Pérez , Martín Delgado Carmen María , Goñi-Orayen Concha , Fernández Carrión Francisco , Veiga Alicia Miras , Olmedilla-Jodar Marta , Alcaraz Romero Andrés J. , Eizmendi-Bereciartua Miren , Gutierrez Carmen Santiago , Luján Esther Aleo , Navarro-Mingorance Álvaro , Jordán Iolanda
Published: January 2019

Objectives:

Increasing evidence supports the association of fluid overload with adverse outcomes in different diseases. To our knowledge, few studies have examined the impact of fluid balance on clinical outcome in severe bronchiolitis. Our aim was to determine whether fluid overload was associated with adverse clinical outcomes in critically ill children with severe bronchiolitis.

Design:

Descriptive, prospective, multicenter study.

Setting:

Sixteen Spanish PICUs.

Patients:

Severe acute bronchiolitis who required admission from October 2014 to May 2015 were included.

Interventions:

None.

Measurements and Main Results:

Total fluid intake and output were prospectively recorded during PICU assistance. Fluid balance was measured at 24, 48, and 72 hours after PICU admission. A total of 262 patients were enrolled; 54.6% were male. Median age was 1 month (interquartile range, 1–3 mo). Patients had a positive fluid balance during the first 4 days of PICU admission, reaching a neutral balance on day 4. A positive balance at 24 hours in patients admitted to the PICU with severe bronchiolitis was related with longer stay in PICU (p < 0.001), longer hospital stay (p < 0.001), longer duration of mechanical ventilation (p = 0.016), and longer duration of noninvasive ventilation (p = 0.0029).

Conclusions:

Critically ill patients with severe acute bronchiolitis who present a positive balance in the first 24 hours of PICU admission have poorer clinical outcomes with longer PICU and hospital length of stay and duration of invasive and noninvasive mechanical ventilation.
Association Between Tidal Volumes Adjusted for Ideal Body Weight and Outcomes in Pediatric Acute Respiratory Distress Syndrome*
Authors: Imber David A. , Thomas Neal J. , Yehya Nadir
Published: January 2019

Objectives:

The impact of tidal volume on outcomes in mechanically ventilated children with pediatric acute respiratory distress syndrome remains unclear. To date, observational investigations have failed to calculate tidal volume based on standardized corrections of weight. We investigated the impact of tidal volume on mortality and probability of extubation in pediatric acute respiratory distress syndrome using ideal body weight–adjusted tidal volume.

Design:

Retrospective analysis of an ongoing prospective cohort of pediatric acute respiratory distress syndrome patients. Tidal volume was calculated based on actual body weight and two different formulations of ideal body weight.

Setting:

PICU at a large, tertiary care children’s hospital.

Patients:

Pediatric acute respiratory distress syndrome patients on conventional ventilation with a documented height or length.

Interventions:

None.

Measurements and Main Results:

There were 483 patients with a measured height or length at pediatric acute respiratory distress syndrome onset included in the final analysis, with 73 nonsurvivors (15%). At 24 hours, there remained 400 patients on conventional ventilation. When calculating tidal volume based on ideal body weight by either method, volumes were larger both at onset and at 24 hours compared with tidal volume based on actual body weight (all p < 0.001), and the proportion of patients being ventilated with tidal volumes greater than 10 mL/kg based on ideal body weight was larger both at onset (12.4% and 15.5%) and 24 hours (10.3% and 11.5%) compared with actual body weight at onset (3.5%) and 24 hours (4.0%) (all p < 0.001). Tidal volume, based on both actual body weight and ideal body weight, was not associated with either increased mortality or decreased probability of extubation after adjusting for oxygenation index in the whole cohort, whereas associations between higher tidal volume and poor outcomes were seen in subgroup analyses in overweight children and in severe pediatric acute respiratory distress syndrome.

Conclusions:

Our retrospective analysis of a cohort of pediatric acute respiratory distress syndrome patients did not find a consistent association between tidal volume adjusted for ideal body weight and outcomes, although an association may exist in certain subgroups. Although it remains to be shown in a prospective trial whether high volumes or pressures are injurious in pediatric acute respiratory distress syndrome, tidal volume is likely an imprecise parameter for titrating lung-protective ventilation.
Effectiveness of a Ventilator Care Bundle to Prevent Ventilator-Associated Pneumonia at the PICU: A Systematic Review and Meta-Analysis
Authors: de Neef Marjorie , Bakker Leo , Dijkstra Sandra , Raymakers-Janssen Paulien , Vileito Alicija , Ista Erwin
Published: January 2019

Objectives:

Ventilator-associated pneumonia is one of the most frequent hospital-acquired infections in mechanically ventilated children. We reviewed the literature on the effectiveness of ventilator care bundles in critically ill children.

Data Sources:

Embase, Medline OvidSP, Web-of-Science, Cochrane Library, and PubMed were searched from January 1990 until April 2017.

Study Selection:

Studies were included if they met the following criteria: 1) implementation of a ventilator care bundle in PICU setting; 2) quality improvement or multicomponent approach with the (primary) objective to lower the ventilator-associated pneumonia rate (expressed as ventilator-associated pneumonia episodes/1,000 ventilator days); and 3) made a comparison, for example, with or without ventilator care bundle, using an experimental randomized or nonrandomized study design, or an interrupted-times series. Exclusion criteria were (systematic) reviews, guidelines, descriptive studies, editorials, or poster publications.

Data Extraction:

The following data were collected from each study: design, setting, patient characteristics (if available), number of ventilator-associated pneumonia per 1,000 ventilator days, ventilator-associated pneumonia definitions used, elements of the ventilator care bundle, and implementation strategy. Ambiguities about data extraction were resolved after discussion and consulting a third reviewer (M.N., E.I.) when necessary. We quantitatively pooled the results of individual studies, where suitable. The primary outcome, reduction in ventilator-associated pneumonia per 1,000 ventilator days, was expressed as an incidence risk ratio with a 95% CI. All data for meta-analysis were pooled by using a DerSimonian and Laird random effect model.

Data Synthesis:

Eleven articles were included. The median ventilator-associated pneumonia incidence decreased from 9.8 (interquartile range, 5.8–18.5) per 1,000 ventilator days to 4.6 (interquartile range, 1.2–8.6) per 1,000 ventilator days after implementation of a ventilator care bundle. The meta-analysis showed that the implementation of a ventilator care bundle resulted in significantly reduced ventilator-associated pneumonia incidences (incidence risk ratio = 0.45; 95% CI, 0.33–0.60; p < 0.0001; I
2 = 55%).

Conclusions:

Implementation of a ventilator-associated pneumonia bundle has the potential to reduce the prevalence of ventilator-associated pneumonia in mechanically ventilated children.
Comparison of International Pediatric Sepsis Consensus Conference Versus Sepsis-3 Definitions for Children Presenting With Septic Shock to a Tertiary Care Center in India: A Retrospective Study*
Authors: Sankar Jhuma , Dhochak Nitin , Kumar Kiran , Singh Man , Sankar M. Jeeva , Lodha Rakesh
Published: January 2019

Objectives:

To evaluate the proportion of children fulfilling “Sepsis-3” definition and International Pediatric Sepsis Consensus Conference definition among children diagnosed to have septic shock and compare the mortality risk between the two groups.

Design:

Retrospective chart review.

Setting:

PICU of a tertiary care teaching hospital from 2014 to 2017.

Patients:

Children (≤ 17 yr old) with a diagnosis of septic shock at admission or during PICU stay.

Interventions:

None.

Measurements and Main Results:

We applied both International Pediatric Sepsis Consensus Conference and the new “Sepsis-3” definition (sepsis with hypotension requiring vasopressors and a lactate value of ≥ 2 mmol/L) to identify cases of septic shock by these definitions. Key outcomes such as mortality, proportion attaining shock reversal at 24 hours and organ dysfunction were compared between those fulfilling “Sepsis-3” definitions (“Sepsis-3” group) and those fulfilling “International Pediatric Sepsis Consensus Conference” definition (“International Pediatric Sepsis Consensus Conference” group). A total of 216 patients fulfilled International Pediatric Sepsis Consensus Conference definitions of septic shock. Of these, only 104 (48%; 95% CI, 42–55) fulfilled “Sepsis-3” definition. Children fulfilling “Sepsis-3 plus International Pediatric Sepsis Consensus Conference definitions” (“Sepsis-3 and International Pediatric Sepsis Consensus Conference” group) had lower proportion with shock resolution (61% vs 82%; relative risk, 0.73; 95% CI, 0.62–0.88) and higher risk of multiple organ dysfunction (85% vs 68%; 1.24; 1.07–1.45) at 24 hours. The mortality was 48.5% in “Sepsis-3 and International Pediatric Sepsis Consensus Conference” group as compared with 37.5% in the “International Pediatric Sepsis Consensus Conference only” group (relative risk, 1.3; 95% CI, 0.94–1.75).

Conclusions:

Less than half of children with septic shock identified by International Pediatric Sepsis Consensus Conference definitions were observed to fulfill the criteria for shock as per “Sepsis-3” definitions. Lack of difference in the risk of mortality between children who fulfilled “Sepsis-3” definition and those who did not fulfill the definition raises questions on the appropriateness of using this definition for diagnosis of septic shock in children.
Modified Lung Ultrasound Examinations in Assessment and Monitoring of Positive End-Expiratory Pressure-Induced Lung Reaeration in Young Children With Congenital Heart Disease Under General Anesthesia*
Authors: Wu Lei , Hou Qiaoru , Bai Jie , Zhang Jianwei , Sun Liping , Tan Ruizhen , Zhang Mazhong , Zheng Jijian
Published: January 2019

Objectives:

Lung ultrasound can reliably diagnose pulmonary atelectasis. The object of this study is to determine the most efficient region to assess changes in atelectasis in children with congenital heart disease under general anesthesia.

Design:

Randomized controlled trial.

Setting:

Operating room at university-affiliated children’s hospital.

Patients:

Children between 3 months and 3 years old, scheduled for elective congenital heart disease surgery under general anesthesia.

Interventions:

Forty children with congenital heart disease were randomly allocated to either a 5 cm H2O positive end-expiratory pressure group or a standard therapy control group.

Measurements and Main Results:

Preoperative lung ultrasound was performed twice in each patient—after 1 and 15 minutes of mechanical ventilation. Atelectatic areas and B-lines were compared between two examinations. Different ultrasound regions were evaluated using Bland-Altman plots. The occurrence rate of atelectasis was much higher in inferoposterior lung regions (Scans 4–6) than in anterior and lateral regions (Scans 1–3). The median (interquartile range) lung ultrasound scores were lower in the positive end-expiratory pressure group than in the control group after treatment: 8 (3.3–9.8) versus 13 (8.3–17.5; p < 0.001). The atelectatic area was significantly decreased after treatment in the positive end-expiratory pressure group: 128 mm2 (34.5.5–213.3 mm2) versus 49.5 mm2 (5.3–75.5 mm2; p < 0.001). Bland-Altman plots revealed concordance between measurements in Scans 1–6 and those in Scans 4–6. In the posterior axillary line regions, changes in atelectatic area were significantly larger in the positive end-expiratory pressure group than in the control group (p = 0.03, 0.007, and 0.018).

Conclusions:

Lung ultrasound in inferoposterior lung regions may be more likely to reflect changes in atelectasis and save examination time; 5 cm H2O positive end-expiratory pressure may be useful in lung reaeration and can reduce, but not eliminate, atelectasis in children with congenital heart disease.