bluuebunny/crossref_metadata_2025 huggingface dataset:
Priority Needs for Conducting Pandemic-relevant Clinical Research With Children in Europe
Authors: Gal Micaela , Gobat Nina , Francis Nicholas A. , Hood Kerenza , Butler Christopher C. , Bielicki Julia , Fraaij Pieter L. , Sharland Mike , Jarvis Jessica , van Rossum Annemarie M. C. , Heikkinen Terho , Martinon-Torres Federico , Herberg Jethro , Watkins Angela , Webb Steve A. R. , Moore Ronnie , Sukumar Prasanth , Nichol Alistair
Published: September 2018

Background:

Infectious disease (ID) pandemics pose a considerable global threat and can disproportionately affect vulnerable populations including children. Pediatric clinical research in pandemics is essential to improve children’s healthcare and minimize risks of harm by interventions that lack an adequate evidence base for this population. The unique features of ID pandemics require consideration of special processes to facilitate clinical research. We aimed to obtain consensus on pediatric clinician-researchers’ perceptions of the priorities to feasibly conduct clinical pediatric pandemic research in Europe.

Methods:

Mixed method study in 2 stages, recruiting pediatric clinician-researchers with experience of conducting pediatric ID research in clinical settings in Europe. Stage 1 was an expert stakeholder workshop and interviews. Discussions focused on participant’s experience of conducting pediatric ID research and processes to facilitate pandemic research. Information informed stage 2, an online consensus survey to identify pediatric inician-researchers priorities to enable ID pandemic research.

Results:

Twenty-three pediatric clinician-researchers attended the workshop and 39 completed the survey. Priorities were primarily focused on structural and operational requirements of research design and regulation: (1) clarity within the European Clinical Trials Directive for pediatric pandemic research; (2) simplified regulatory processes for research involving clinical samples and data; and (3) improved relationships between regulatory bodies and researchers.

Conclusions:

Results suggest that changes need to be made to the current regulatory environment to facilitate and improve pediatric research in the pandemic context. These findings can provide expert evidence to research policy decision-makers and regulators and to develop a strategy to lobby for change.
Physical Therapy for an Adult Male Presenting With Torsion Dystonia Postcardiac Arrest: Posture Is Key
Authors: Hodgdon Andrew
Published: September 2018

Introduction:

Patients suffering from cardiac arrest followed by anoxic brain injury have improved survival rates and often have debilitating neurologic and functional consequences. There is currently limited guidance in the literature for physical therapists treating adult patients in the acute care setting with presentations that can include dystonia.

Case Description:

This case report describes acute hospital physical therapy for a young adult after cardiac arrest. Physical therapy examination was initially limited secondary to severe torsion dystonia. A supported seating intervention was key in managing the dystonia and allowing for functional gains.

Outcomes:

Physical therapy treatments were successful in advancing the patient's functional status following investigation of historical treatment approaches, with subsequent application of an evidence-based intervention.

Discussion:

This case report highlights fundamental physical therapy requisite to establish a static sitting position when faced with opisthotonic posture as well as general torsion, postural distortions and dystonia. In addition, the study emphasizes the role of physical therapists as team members in the acute hospital setting.
Loading in an Upright Tilting Hospital Bed Elicits Minimal Muscle Activation in Healthy Adults
Authors: Mayer Kirby P. , Uhl Timothy L. , Morris Peter E. , Dupont-Versteegden Esther E.
Published: September 2018

Purpose:

Upright tilting hospital beds (THB) are used during early rehabilitation of critically ill patients. Tilting patients in a THB to achieve weight-bearing or loading is purported to mitigate the response of prolonged immobility associated with critical illness. The primary aim of this study is to determine the level of muscle activation during loading in a THB and secondarily to assess whether safety straps influence the level of muscle activation.

Methods:

Quasi-experimental design in a musculoskeletal laboratory. Nineteen healthy community-dwelling adults with no prior neuromuscular disorder were included. Two groups, 10 subjects with straps-on and 9 subjects with straps-off, were tilted in a THB through 9 intervals of 10° (0°-80°). Muscle activation was recorded using surface electromyography in tibialis anterior, rectus femoris, gluteus medius, and lumbar erector spinae muscles. Raw and electromyography-normalized data were analyzed across angles and conditions. Loading (weight-bearing) was recorded using the THB footplate scale.

Results:

Electromyographic activity in the tibialis anterior, rectus femoris, gluteus medius, and lumbar erector spinae muscles was minimal as the angle of tilt and loading increased. No statistically significant increases compared with supine rest were observed, except rectus femoris muscle activation at 60° in the groups without straps (P = .023). Similarly, only muscle activation in the rectus femoris was higher in the group without straps from angles 40° to 80° than in the group with straps.

Conclusion:

Relaxed, gravity-facilitated loading in a THB elicits minimal muscle activation in healthy subjects and, therefore, passive loading's usefulness for enhancing muscle strength is questioned. Removal of safety straps did lead to increased muscle activation in the rectus femoris; this concept should be explored further to understand whether location of the straps, tightness of the straps, and/or the angle of the hip and knee joints during loading could hamper muscle activation.
Acute Rehabilitation of a 27-Year-Old Man With Failure to Thrive
Authors: Terrill Joseph , Roos Jennifer , Zarrinkhameh Leslie
Published: September 2018

Background and Purpose:

Failure to thrive is a complex medical diagnosis that does not describe a single disease process, but rather a variety of symptoms associated with one or more possible underlying diseases or conditions. It is a diagnosis that is not well-documented outside pediatric or geriatric populations. The purpose of this case report is to present the physical therapy examination and treatment of a 27-year-old Hispanic man with a diagnosis of failure to thrive, a history of superior mesenteric artery syndrome, chronic malnutrition, type 1 diabetes mellitus, and osteopenia.

Case Description:

A 27-year-old Hispanic man, BMI of 12, admitted to the hospital for acute hypothermia, urinary tract infection, generalized weakness, hypotension, and failure to thrive. The complexity of his medical condition required nearly 2 weeks to stabilize general health prior to initiating physical therapy services. Personal and environmental factors contributed to progressive decline in physical activity prior to this hospital admission and led to increased dependence and support.

Outcomes:

Blood pressure increased by 18 mm Hg systolic and 20 mm Hg diastolic and stabilized within normal range; 5 repetitions in the 30-second sit-to-stand; functional balance composite score of 35 seconds; 20% reduction in subjective Numeric Pain Rating Scale; supervised bed mobility; maximum assistance stand-pivot transfer; and family to support caregiver needs upon return home. The patient was discharged home with recommendation for continued services through home health care referral.

Discussion:

Evidence-based literature regarding failure to thrive in the young adult or middle-aged adult population is limited. Therefore, the physical therapy plan of care necessitates the application of interventions shown to be effective in addressing the physical structure and function limitation upon examination generally applied to the geriatric and/or pediatric population. Clinical decision-making focused on improving physical activity and participation are imperative across clinical settings. Manual therapy interventions applied in this case may prove beneficial in the acute care setting to maximize muscle activation within available range of motion elicited through patterns of functional movements emphasizing existing abilities.
Expression of Psoriasin in Human Papillomavirus–Induced Cervical High-Grade Squamous Intraepithelial Lesions
Authors: Alvendal Cathrin , Kamolvit Witchuda , Wagner Siegfried , Brauner Annelie , Bohm-Starke Nina
Published: September 2018

Objectives

Persistent infection with human papillomavirus causes cervical high-grade squamous intraepithelial lesions (HSILs). The role of antimicrobial peptides (AMPs) in premalignant and malignant transformation is not fully understood. In this study, we examined the expression of human β-defensin 1 (HBD-1), HBD-2, HBD-3, LL37, psoriasin, and interleukin 8 (IL-8) in women with HSIL before and 6 months after surgery.

Materials and Methods

Biopsies and secretion samples from the cervical canal were collected from 19 patients with HSIL and 14 healthy controls. The mRNA expression of HBD-1, HBD-2, HBD-3, LL37, psoriasin, and IL-8 was analyzed before and 6 months after surgery excision using reverse transcriptase real time polymerase chain reaction. For protein analyses, ELISA and immunohistochemistry were used for psoriasin and ELISA for IL-8.

Results

The mRNA expression of psoriasin was lower in patients before treatment compared with healthy controls (p = .05). After surgery, when the infection was cleared, psoriasin increased on mRNA (p = .04) and protein (p = .03) levels compared with before treatment. Immunostaining for psoriasin after treatment was prominent and localized in the cytoplasm of the epithelial cells. After treatment, IL-8 mRNA was reduced compared with before treatment (p = .05), but not on the protein level. No changes in mRNA expression of the other AMPs analyzed were observed in pretreatment and posttreatment samples.

Conclusions

In this study of AMP expression in human papillomavirus–induced HSIL, we observed lower psoriasin levels before surgery compared with after treatment, when both mRNA and protein levels were similar to healthy controls. Interleukin 8, on the other hand, was increased before treatment, indicating an inflammatory response.
Individual and Geospatial Characteristics Associated With Use and Nonuse of the Fecal Immunochemical Test (FIT) for Colorectal Cancer Screening in an Urban Minority Population
Authors: Ramai Daryl , Etienne Denzil , Ayide Gloria , Fields Paul J. , Reddy Madhavi
Published: September 2018

Purpose:

Initiatives by the Centers for Disease Control and Prevention as well as the National Colorectal Cancer Roundtable aim to increase the rate of colorectal cancer (CRC) screening. We assess individual and geographic characteristics associated fecal immunochemical test (FIT) CRC screening over 3 years.

Methods:

This is a retrospective study of 1500 FIT kits which were mailed or opportunistically handed to eligible participants in Brooklyn, New York from January 2014 to December 2016. Eligibility criteria included increased risk for colon cancer, uninsured or underinsured, and a minimum age of 50 years to warrant CRC screening. We looked at the association of individual demographic characteristics and FIT screening by logistic regression using SPPS version 23 software. In addition, using ArcGIS, we coded patients address and layered census tract population information to find associations.

Results:

In total, 1367 Cancer Services Participants met our study criteria. The study sample was predominantly female (95.2%) and minority (46% African American, 24.7% Hispanic, 17.3% Caucasian, 11.4% Asian) and on average 59 years old (SD, 5.7). A large majority (73%) had household incomes below $20,000/year. Approximately half (49.9%) of all Cancer Services Participants returned their FIT kit. In participants who did not return their FIT kit, the majority were African American (41%), followed by Hispanics (26.5%), Caucasians (20.6%), and Asians (11.8%). Multivariable logistic regression showed that a screening history of prior colonoscopy or FIT, gender, ethnicity, and educational attainment were significantly associated with FIT CRC screening uptake (P<0.05). Geospatial mapping showed clusters of low screening uptake in areas of high poverty. Hot-spot analysis identified areas of significant vulnerability.

Conclusions:

FIT uptake remains suboptimal. Individual predictors as well as area poverty is associated with low screening uptake. Geospatial mapping is an effective tool for evaluating CRC screening uptake.
Randomized controlled trial of polyethylene glycol versus lactulose for the treatment of overt hepatic encephalopathy
Authors: Shehata Hala H. , Elfert Asem A. , Abdin Amany A. , Soliman Samah M. , Elkhouly Reham A. , Hawash Nehad I. , Soliman Hanan H.
Published: September 2018

Background

Overt hepatic encephalopathy (HE) is a frequent complication of cirrhosis and one of the most debilitating manifestations that necessitates hospitalization. Although many treatment modalities are being investigated, none of them are satisfactory. So, newer treatment modalities have to be tried.

Objective

To evaluate the safety and efficacy of polyethylene glycol (PEG) versus lactulose in the management of HE.

Patients and methods

This clinical trial included 100 patients with post-hepatitis C cirrhosis who were admitted with HE. Patients were randomized into two equal groups: group I patients received lactulose and group II patients received PEG. The clinico-epidemiological characteristics of patients, Child–Pugh score, and HE scoring algorithm were registered before and 24 h after administration of the drug. Moreover, any suspected adverse effects were recorded.

Results

All 100 patients received treatment. Three patients died within 24 h of admission and did not complete the follow-up period. According to intention-to-treat approach, they were considered as treatment failure. On analysis, 36/50 (72%) patients improved one grade or more in HE scoring algorithm score after 24 h of lactulose therapy versus 47/50 (94%) of those on PEG therapy (P<0.05). The time needed for resolution of HE and length of hospital stay were significantly lower in PEG group versus lactulose group (P<0.001). Both therapies were tolerated, and no significant adverse events were reported.

Conclusion

Both lactulose and PEG were safe and effective in the treatment of HE. PEG significantly decreased the time needed for resolution of HE and significantly shortened the hospital stay.
LI-RADS: a great opportunity not to be missed
Authors: Renzulli Matteo , Clemente Alfredo , Brocchi Stefano , Milandri Matteo , Lucidi Vincenzo , Vukotic Ranka , Cappabianca Salvatore , Golfieri Rita
Published: September 2018

The Liver Imaging Reporting and Data System (LI-RADS) is a widespread comprehensive system for standardising the reporting and data collection of liver imaging to standardise chronic liver disease evaluation. However, the LI-RADS, based on the identification of some categories of lesions by means of a conceptual and nonquantitative probability approach, has many limitations. In fact, recently, the European Association for the Study of the Liver Guidelines regarding the management of hepatocellular carcinoma did not accept the LI-RADS. The aim of this paper was to critically analyse the LI-RADS, focusing on some interesting issues such as the absence of a clear distinction between two different imaging modalities (computed tomography and MRI), the lack of validation of some major features, the assessment of its ancillary features and its complexity. Despite these limitations, the LI-RADS represents a great opportunity for the radiological community. We must not let it escape, but time and experience are necessary for its improvement.
Effects of Pain, Insomnia, and Depression on Psychoactive Medication Supply in Older Adults With Osteoarthritis
Authors: Liu Minhui , McCurry Susan M. , Belza Basia , Buchanan Diana T. , Dobra Adrian , Von Korff Michael , Vitiello Michael V.
Published: September 2018

Background:

Determinants of prescribing psychoactive medications for symptom management in older adults remain underexamined despite known risks and cautions concerning these medications.

Objective:

To examine independent and combined effects of pain, concurrent insomnia and depression symptoms on psychoactive medications supplied to older adults with osteoarthritis (OA).

Research Design:

Survey data on pain, insomnia, and depression obtained from OA patients screened for a randomized controlled trial were used to identify predictors of psychoactive medication supply [opioids, sedatives, tricyclic antidepressants (TCAs), and non-TCAs] over a 4-year period.

Subjects:

Group Health Cooperative patients with a diagnosis of OA (N=2976).

Measures:

Survey data on pain (Graded Chronic Pain Scale), insomnia (Insomnia Severity Index), and depression (Patient Health Questionnaire-8); and medications supply assessed from electronic medical records.

Results:

In negative binomial models, pain [incidence rate ratio (IRR), 2.8–3.5; P<0.001], insomnia (IRR, 2.0; P<0.001), and depression (IRR, 1.5; P<0.05) each independently predicted opioid supply. Insomnia (IRR, 3.2; P<0.001) and depression (IRR, 3.0; P<0.001) each independently predicted sedative supply. Pain (IRR, 2.1; P<0.05) and insomnia (IRR, 2.0; P<0.05) independently predicted TCA supply, whereas only depression (IRR, 2.2; P<0.001) independently predicted non-TCA supply. Combined effects of pain and insomnia/depression on these medications were additive and increased the rate of medication supply 1.5–7.5 times. Combined effects increased with insomnia or depression severity.

Conclusions:

Concurrent insomnia and depressive symptoms predicted increased supply of opioids, sedatives, and antidepressants after accounting for pain, indicating the importance of sleep and mood disorders as factors increasing supply of these medications.
The Relative Ability of Comorbidity Ascertainment Methodologies to Predict In-Hospital Mortality Among Hospitalized Community-acquired Pneumonia Patients
Authors: Weir Ronald E. , Lyttle Christopher S. , Meltzer David O. , Dong Tien S. , Ruhnke Gregory W.
Published: September 2018

Background:

Despite widespread use of comorbidities for population health descriptions and risk adjustment, the ideal method for ascertaining comorbidities is not known. We sought to compare the relative value of several methodologies by which comorbidities may be ascertained.

Methods:

This is an observational study of 1596 patients admitted to the University of Chicago for community-acquired pneumonia from 1998 to 2012. We collected data via chart abstraction, administrative data, and patient report, then performed logistic regression analyses, specifying comorbidities as independent variables and in-hospital mortality as the dependent variable. Finally, we compared area under the curve (AUC) statistics to determine the relative ability of each method of comorbidity ascertainment to predict in-hospital mortality.

Results:

Chart review (AUC, 0.72) and administrative data (Charlson AUC, 0.83; Elixhauser AUC, 0.84) predicted in-hospital mortality with greater fidelity than patient report (AUC, 0.61). However, multivariate logistic regression analyses demonstrated that individual comorbidity derivation via chart review had the strongest relationship with in-hospital mortality. This is consistent with prior literature suggesting that administrative data have inherent, paradoxical biases with important implications for risk adjustment based solely on administrative data.

Conclusions:

Although comorbidities derived through administrative data did produce an AUC greater than chart review, our analyses suggest a coding bias in several comorbidities with a paradoxically protective effect. Therefore, chart review, while labor and resource intensive, may be the ideal method for ascertainment of clinically relevant comorbidities.
The Impact of Public Performance Reporting on Market Share, Mortality, and Patient Mix Outcomes Associated With Coronary Artery Bypass Grafts and Percutaneous Coronary Interventions (2000–2016)
Authors: Dunt David , Prang Khic-Houy , Sabanovic Hana , Kelaher Margaret
Published: September 2018

Objective:

Public performance reporting (PPR) of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) outcomes aim to improve the quality of care in hospitals, surgeons and to inform consumer choice. Past CABG and PCI studies have showed mixed effects of PPR on quality and selection. The aim of this study was to undertake a systematic review and meta-analysis of the impact of PPR on market share, mortality, and patient mix outcomes associated with CABG and PCI.

Methods:

Six online databases and 8 previous reviews were searched for the period 2000–2016. Data extraction, quality assessment, systematic critical synthesis, and meta-analysis (where possible) were carried out on included studies.

Results:

In total, 22 relevant articles covering mortality (n=19), patient mix (n=14), and market share (n=6) outcomes were identified. Meta-analyses showed that PPR led to a near but not significant reduction in short-term mortality for both CABG and PCI. PPR on CABG showed a positive effect on market share for hospitals (3 of 6 studies) and low-performing surgeons (2 of 2 studies). Five of 6 PCI studies found that high-risk patients were less likely to be treated in States with PPR.

Conclusions:

There is some evidence that PPR reduces mortality rates in CABG/PCI-treated patients. The significance of there being no strong evidence, in the period 2000–2016, should be considered. There is need for both further development of PPR practice and further research into the intended and unintended consequences of PPR.
Transient Elastography Measurements of Spleen Stiffness as a Predictor of Clinically Significant Varices in Children
Authors: Sutton Harry , Fitzpatrick Emer , Davenport Mark , Burford Charlotte , Alexander Emma , Dhawan Anil , Grammatikopoulos Tassos
Published: September 2018

Objectives:

Investigate the use of spleen stiffness measurements (SSMs), measured by transient elastography (TE), for the prediction of clinically significant varices (CSV) in children with portal hypertension.

Methods:

This observational cohort study included children selected for endoscopy, as per department protocol, between September 2015 and June 2016. Those included underwent single TE FibroScan for liver stiffness measurements and SSM. Clinical and laboratory data were collected and variceal prediction scores were calculated at time of elastography.

Results:

In total 67 children (32 boys) underwent TE. Fifty‐two children (25 boys) had chronic liver disease (CLD), 15 (7 boys) portal vein thrombosis (PVT). In all children SSM was the best predictor of CSV+ve, with an optimal cut‐off value of 38.0 kPa (area under the receiver operator curve [AUROC] = 0.92, sensitivity = 89%, specificity = 82%, P < 0.01). In the CLD group SSM was also the best predictor, with an optimal cut‐off value of 38.05 kPa (AUROC = 0.90, sensitivity = 84%, specificity = 87%, P < 0.01). In the PVT group only SSM was predictive of CSV+ve, with an optimal cut‐off value of 16.8 kPa (AUROC = 1.00, sensitivity = 100%, specificity = 100%, P < 0.001). For the prediction of GI bleeding (n = 6), liver stiffness measurement performed the best, with an optimal cut‐off value of 34.3 kPa (AUROC = 0.84, sensitivity of 80%, specificity of 88%, P = 0.01).

Conclusions:

SSM was the greatest predictor of CSV+ve in the whole cohort, and individual CLD and PVT groups. SSM could be used as a noninvasive screening tool for children with portal hypertension to stratify the risk of having CSV.
Direct‐acting antiviral Therapy Is Safe and Effective in Pediatric Chronic Hepatitis C
Authors: Dhiman Radha K. , Grover Gagandeep S. , Premkumar Madhumita , Taneja Sunil , Duseja Ajay , Rathi Sahaj , Satsangi Sandeep
Published: September 2018

Objectives:

We assessed the efficacy of decentralized public health services and safety of direct‐acting antiviral agents (DAAs) in the treatment of pediatric chronic hepatitis C (CHC) in the Mukh‐Mantri Punjab Hepatitis C Relief Fund, a public‐health initiative for prevention and control of CHC in Punjab, India.

Methods:

Consecutive children with CHC [age ≥12 to <18 years; both treatment‐naïve (TN) and treatment‐experienced (TE)] were enrolled. Genotyping was not recommended for non‐cirrhotic patients and were treated with sofosbuvir (SOF)+ daclatasvir (DCV) for 12 weeks, while genotyping was recommended for patients with cirrhosis. Patients with cirrhosis and genotype (G2) were treated with SOF+DCV+ribavirin (RBV) for 12 weeks, G3 with SOF+DCV+RBV for 24 weeks and G1, 4, 5, and 6 patients were treated with SOF+ledipasvir (LDV)+RBV for 12 weeks. Treatment duration was increased to 24 weeks if RBV was not tolerated.

Results:

In the first 16 months (June 18, 2016–October 31, 2017), 88 children (mean age 15.8 years; 69.3.3% boys, 72.3% rural) were enrolled. The mean baseline hepatitis C virus RNA log10 IU/mL was 6.0 (range 4.2–7.5 log10 IU/mL), 65.5% with G3, and 2 (2.5%) with cirrhosis. Of 57 with completed treatment, sustained virological response (SVR) 12 was achieved in 56 (98.2%). Unsafe medical practices (55.5%), IV drug abuse (11.1%), and prior surgery (2.7%) were risk‐factors for transmission (n = 36). Comparable results were noted in G3 (SVR at 12 weeks [SVR12], 94.3%) versus non‐G3 (SVR12, 100%; P = 0.073). No serious adverse effects like anemia and decompensation were reported.

Conclusions:

The study demonstrates that the decentralized algorithm‐based public‐health program can ensure high efficacy (SVR12, 98.2%) and low‐cost DAA‐based treatment of pediatric patients with CHC.
There Is No Excuse for Mortality Due to Lack of Competency and Training of Paediatric Endoscopists in Gastrointestinal Bleeding Therapy in 2018
Authors: Thomson Mike
Published: September 2018

Acute upper gastrointestinal bleeding in children is possibly the last medical emergency which continues to lead to the death of a child due to the lack of competency/clinical judgement of the doctor, as opposed to the disease itself, leading to mortality despite optimum medical intervention. This is unacceptable in any circumstances in 2018. It occurs due to a number of conspiring factors including lack of appreciation of the clinical presentation requiring urgent endoscopic intervention; misapprehension of the urgency of timing required of such an intervention predicated on the severity of the gastrointestinal (GI) bleed; lack of application of a paediatric‐specific validated score predicting for such endoscopic intervention; lack of skill in endo‐haemostatic intervention techniques by paediatric endoscopists; poor training in such techniques among paediatric endoscopists; paucity of cases with lack of exposure of the paediatric endoscopist regularly to enable skills to be maintained, once acquired; reluctance of adult endoscopists in many centres to support paediatric GI bleeding services. In essence then the paediatric GI community urgently needs to identify centres of excellence to whom these children should be transferred. Transfer is safe in all but the most critical cases once stabilised with transfusion, octreotide/terlipressin and iv proton pump inhibitors. The resources are country‐dependent but this is really no excuse. We must not let this parlous state of affairs continue. Solutions are explored in this article and please let this serve as a call to action for all those involved in this continuing debacle in order to save “save‐able” lives.
Severe Deoxyguanosine Kinase Deficiency in Austria
Authors: Waich Stephanie , Roscher Anne , Brunner‐Krainz Michaela , Cortina Gerard , Köstl Gerhard , Feichtinger Rene G. , Entenmann Andreas , Müller Thomas , Knisely A.S. , Mayr Johannes A. , Janecke Andreas R. , Vodopiutz Julia
Published: September 2018

Mutations in the nuclear gene DGUOK, encoding deoxyguanosine kinase, cause an infantile hepatocerebral type of mitochondrial depletion syndrome (MDS). We report 6 MDS patients harboring bi‐allelic DGUOK mutations, of which 3 are novel, including a large intragenic Austrian founder deletion. One patient was diagnosed with hepatocellular carcinoma aged 6 months, supporting a link between mitochondrial DNA depletion and tumorigenesis; liver transplantation proved beneficial with regard to both tumor treatment and psychomotor development.
Diet and Exercise in Pediatric Liver Transplant Recipients
Authors: Chambers Julia H. , Zerofsky Melissa , Lustig Robert H. , Rosenthal Philip , Perito Emily R.
Published: September 2018

Objective:

The aim of the study is to analyze the impact of physical activity and eating behaviors on precursors of cardiovascular disease—including overweight/obesity, hypertension, low high‐density lipoprotein, and impaired glucose tolerance—in pediatric liver transplant (LT) recipients and matched controls.

Method:

Cross‐sectional study of pediatric LT recipients 8 to 30 years, matched to controls from the National Health and Nutrition Examination Survey. Dietary intake assessed with 24‐hour recall. Physical activity assessed by standardized questionnaires. LT recipients ≥12 years completed a confidential survey on alcohol consumption.

Results:

LT recipients (n = 90) were 0.9 to 24.7 years post‐transplant. LT recipients and controls were equally likely to consume excess carbohydrates (32% vs 34%) and sugar, per age‐ and gender‐specific recommended dietary intake guidelines. LT recipients spent more hours sedentary or on the computer daily and fewer days each week physically active for >60 minutes than controls. More overweight/obese LT recipients spent 3+ hours at the computer than non‐overweight LT recipients (49% vs 27%; P = 0.02). Normal weight LT recipients spent more days doing vigorous activity each week (median 5 days, interquartile range 2–6) than did the overweight/obese LT recipients (median 3 days, interquartile range 2–4; P = 0.01). Among LT recipients, neither dietary intake nor physical activity were consistently associated with measures of hypertension, glucose intolerance, or dyslipidemia. Among LT adolescents and young adults (n = 38), 36% reported ever consuming alcohol; 38% of these reported significant alcohol consumption by frequency or quantity.

Conclusions:

Additional counseling during routine post‐LT care on the importance of physical activity and healthy diet may be useful. However, it is unlikely that these factors alone explain the increased prevalence of metabolic syndrome components in pediatric LT recipients.
Recurrent Abdominal Pain in Children
Authors: Singh Harveen K. , Ee Looi C.
Published: September 2018

Recurrent abdominal pain (RAP) in children is common, with most functional in origin. Colonoscopy has sometimes been performed to exclude pathology but its role is unclear. Our aim therefore was to assess the diagnostic yield and role of colonoscopy in these children. Retrospective review of consecutive colonoscopies in a tertiary pediatric hospital between November 2011 and October 2015 was undertaken. Only those with RAP as an indication for procedure were included. Chart review of patients with pain was undertaken to ensure they fulfilled Rome IV criteria. Patient demographics, indication for procedure, and adjunct preprocedure tests were noted. Statistical analyses were performed with SPSS software. A total of 652 colonoscopies were performed, of which 68 (10%) had abdominal pain as one of the indications, and was the sole indication in 15 (2%) patients. All 68 patients had preprocedure serum inflammatory markers measured and 53% (36/68) had stool calprotectin. Positive histology was found in 10% (7/68) including Crohn disease (n = 3), polyps (n = 2), and microscopic colitis (n = 2). The remaining 61 patients had normal colonoscopy and ileocolonic biopsies. Of the 36 patients 5 had raised fecal calprotectin, and all had abnormal histology. Serum inflammatory markers were raised in 4 patients and all also had abnormal calprotectin. No patient with isolated abdominal pain had positive histology. Rectal bleeding was the only associated indication to predict abnormal histology (P = 0.019). Colonoscopy is likely not warranted in children with RAP without bleeding, weight loss, or altered bowel habit. Fecal calprotectin is useful in helping predict positive findings.
Red Spot Lesions in the Duodenal Bulb Are a Highly Specific Endoscopic Sign of Celiac Disease
Authors: Silvester Jocelyn A. , Faucher Elizabeth A. , McCarty Caitlin E. , Kalansky Adie , Hintze Zackary J. , Mitchell Paul D. , Goldsmith Jeffrey D. , Weir Dascha C. , Leichtner Alan M.
Published: September 2018

We have recognized red spot lesions (RSLs) in the duodenal bulb in children with celiac disease (CD) and believe they may represent an underappreciated and distinct endoscopic sign of CD. A total of 171 pediatric patients undergoing esophagogastroduodenoscopy with duodenal biopsy for symptoms consistent with CD were prospectively recruited. There were 75 patients who met criteria for CD and the remaining 96 patients served as symptomatic controls. As compared to endoscopic markers frequently mentioned in literature, RSLs had comparable sensitivity, specificity, positive predictive value, and negative predictive value of 31%, 94%, 80%, and 64%, respectively. If RSLs are noted during endoscopy in a patient with gastrointestinal symptoms that might be the result of CD, then sufficient duodenal biopsies to make the diagnosis of CD should be obtained.
The Effect of Biologics on Postoperative Complications in Children With Inflammatory Bowel Disease and Bowel Resection
Authors: Mitsuya Jennifer B. , Gonzalez Raquel , Thomas Ron , El‐Baba Mohammad
Published: September 2018

Objectives:

There has been limited investigation of pediatric patients with inflammatory bowel disease (IBD) who have been treated with biologic agents and undergo operative management. Postoperative complications in the adult setting have been mixed and in the pediatric population the data have been limited. This study compares children with IBD treated with biologic agents to patients treated with nonbiologic therapy before bowel resection.

Methods:

This is a single‐center, retrospective chart review study of 62 children with IBD who underwent bowel resection between 2001 and 2017. Analysis included patient demographics, medications used before surgery, incidence of postoperative complications, indication for surgery, type of operation, and additional surgeries required. Postoperative complications were defined as superficial skin infection, leak at anastomotic site, intra‐abdominal abscess, wound dehiscence, and so on. Complications were compared based on medical therapy.

Results:

Of the 62 children reviewed, 21 carried the diagnosis of ulcerative colitis, 40 had Crohn disease, and 1 had IBD‐unspecified. Thirty‐seven of the patients were treated with infliximab, adalimumab, or vedolizumab before their bowel resection. There were 4 complications documented within 30 days of the operation, with an overall complication rate of 6.45%. There were 2 complications in each of the cohorts, including intra‐abdominal abscess (2), abdominal wall abscess (1), and pouchitis (1).

Conclusion:

The number of complications was the same between those who did and did not receive a preoperative biologic agent. This study suggests that biologics may be safe to use in patients undergoing bowel resection.
Proliferative Cells From Kaposiform Lymphangiomatosis Lesions Resemble Mesenchyme Stem Cell–like Pericytes Defective in Vessel Formation
Authors: Glaser Kathryn , Dickie Peter , Dickie Belinda Hsi
Published: September 2018

Kaposiform lymphangiomatosis (KLA) is a vascular anomaly featuring lymphatic expansion. It has no known cause, no effective treatment, and is associated with high morbidity. Proliferative cells from 3 KLA patient lesions were characterized relative to adiopose-derived mesenchyme stem cells (ADSCs) and cells derived from a patient with the related disease kaposiform hemangioendothelioma (KHE). KLA cells variably expressed markers of mesenchyme stem cells (CD73, CD90, CD105, CD146) and lacked endothelial cell markers (CD31, CD34) as determined by flow cytometry. They expressed markers of vascular pericytes (neural/glial antigen 2, alpha-smooth muscle actin, platelet-derived growth factor-beta receptor, and CXCL12) as determined by quantitative reverse transcription polymerase chain reaction. Lesion cells transcribed vascular markers VEGFC and VEGFD, as well as VCAM-1, the latter of which was confirmed by flow cytometry, consistent with angiogenic MSC-like pericytes. Furthermore, conditioned medium from each was shown to promote the proliferation of growth factor–starved lymphatic endothelial cells. Unlike kaposiform hemangioendothelioma-derived MSC-like pericytes and ADSCs, KLA isolates were defective in support of vascular network formation in co-cultures with either vascular or lymphatic endothelial cells. Genetic analysis by whole exome sequencing revealed novel variant alleles in 2 populations of KLA cells (BAD, TSC1) that may bear on aberrant pericyte growth and function.
Maternal Prenatal Thyroid Function and Offspring ADHD: Findings From the ALSPAC Cohort
Authors: Fetene Dagnachew Muluye , Betts Kim S. , Alati Rosa
Published: September 2018

Thyroid hormone plays a pivotal role in the developing brain and may affect the development of attention deficit hyperactivity disorder (ADHD). This study aimed to examine the role of maternal thyroid function during pregnancy on offspring ADHD. A total of 2912 mother-child pairs were included from the Avon Longitudinal Study of Parents and Children. Thyroid parameters were assessed during the first trimester of pregnancy. Offspring ADHD was assessed using the Development and Well-Being Assessment at the ages of 7.5 and 15 years. The odds of presenting with ADHD were estimated using generalized estimating equations. Levels of thyroid-stimulating hormone (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.48–1.75), free thyroxine (OR, 1.07; 95% CI, 0.87–1.32), and thyroid peroxidase antibodies (OR, 1.00; 95% CI, 0.80–1.25) were not associated with ADHD in children aged 7.5 and 15 years. This study showed no association between maternal thyroid function and offspring ADHD.
Exploring NCLEX Failures and Standardized Assessments
Authors: Emory Jan
Published: September 2018

Background

Nurse educators seek valid and reliable tools to assist in early identification and intervention for students at-risk of NCLEX-RN failure.

Purpose

The purpose of this cross-sectional study was to use principal component analysis to explore relationships within standardized assessment (SA) scores from a sample of students who failed the NCLEX-RN on the first attempt.

Methods

Standardized assessment scores were collected from prelicensure programs between 2009 and 2016 (n = 296). Mixed modeling sought to reveal SA scores that represented redundancy or duplication.

Results

The principal component analysis found 2 distinct components emerging from the 8 SAs included in the study, signifying duplication in the content assessed. Within these 2 components, maternal newborn and pharmacology had the strongest correlations among the SA scores.

Conclusions

Discovering those SAs that assess similar content and have the strongest correlations can provide additional information for decision making when implementing these tests throughout the nursing curriculum.
Risk Factor Reversal in Studies of Infectious Disease: Making Counterintuitive Results Intuitive Again
Authors: Kaufman Jay S. , Banack Hailey R. , Adams Joëlla W. , Marshall Brandon D. L. , Stovitz Steven D.
Published: September 2018

A previously published study reported the seemingly paradoxical finding that men who have sex with men status was strongly protective and recent sexual abstinence strongly deleterious in relation to mortality prognosis. We explain why these results are entirely logical and that the counterintuitive direction of the effects derives from the comparison group implied by the study design.
High and Stable Human Immunodeficiency Virus Prevalence Among Transwomen With Low Income Recruited With Respondent-driven Sampling, San Francisco, 2010–2016
Authors: Raymond Henry F. , Wilson Erin C. , Packer Tracey , Ick Theresa , Lin Jess , McFarland Willi
Published: September 2018

Background

Studies have documented high human immunodeficiency virus (HIV) prevalence among transwomen in the United States; however, to our knowledge, no studies have documented trends in HIV prevalence in this population.

Methods

We used respondent-driven sampling to sample transwomen in San Francisco for 3 HIV prevalence and behavioral surveys in 2010, 2013, and 2016. Our analysis of point estimates and trends were weighted for the sampling method.

Results

Human immunodeficiency virus prevalence by serological testing in the survey was 38.8% (95% confidence interval [CI], 32.4–45.2), 33.7% (95% CI, 25.9–41.5), and 31.6% (95% CI, 12.2–38.1) in 2010, 2013, and 2016, respectively. Disparities in higher HIV prevalence by black, Latino, and Asian race/ethnicity and lower education level persisted through 2016.

Conclusions

Based on a statistical test for trend, HIV prevalence among transwomen has remained high and stable from 2010 to 2016. Human immunodeficiency virus infection is still highest at 31.6% compared to any other group in San Francisco. We also observed that older transwomen had significantly higher odds of living with HIV than younger women over the last 2 waves of data collection. Taken together, these trends suggest that there is declining incidence of new HIV infections among low-income transwomen in San Francisco. Moreover, among transwomen, HIV disproportionately affects transwomen of color.
Anaplastic Kaposi’s Sarcoma of the Adrenal in an HIV-negative Patient With Literature Review
Authors: Bisceglia Michele , Minenna Elena , Altobella Andrea , Sanguedolce Francesca , Panniello Gaetano , Bisceglia Stefano , Ben-Dor David J.
Published: September 2018

Kaposi’s sarcoma (KS) is a peculiar tumor of viral etiology, with the HHV8 rhadinovirus playing a fundamental role in its development. Several epidemiological categories of KS have been identified, of which the sporadic, endemic, iatrogenic, and the epidemic are the main ones. Several histologic disease morphologies have been described, such as inflammatory, angiomatous, spindle cell, mixed, and the anaplastic (sarcomatous) subtypes. The skin of the limbs is most commonly affected, but any other organ or site may be involved. Microscopically KS may enter the differential diagnosis with several different entities, and for this purpose the immunohistochemical detection of the viral latent nuclear antigen-1 (LNA-1) may be crucial. Sporadic KS is usually benign, but rarely it may be aggressive. Anaplastic histology heralds an ominous course in any clinical context. We report a case of anaplastic retroperitoneal KS, occurring in an HIV-negative adult man. This patient presented with a huge left suprarenal mass, which was totally resected, and initially diagnosed as inflammatory leiomyosarcoma, because of the monomorphic spindle cell tumor morphology. After 12 years the tumor recurred locally as an unresectable mass, which was biopsied and examined. At the time of recurrence, the histologic slides of the primary tumor were reviewed, and the previous diagnosis was changed to that of atypical KS. Histologically the recurrent tumor showed both spindle cell and epithelioid appearances. Strongly diffuse HHV8/LAN-1 immunopositivity was documented in both tumors. The final diagnosis for the entire case was anaplastic KS. Then, the patient died in a few months.
A “Clearer” View of Pancreatic Pathology: A Review of Tissue Clearing and Advanced Microscopy Techniques
Authors: Hong Seung-Mo , Noë Michaël , Hruban Carolyn A. , Thompson Elizabeth D. , Wood Laura D. , Hruban Ralph H.
Published: September 2018

Although pathologic lesions in the pancreas are 3-dimensional (3D) complex structures, we currently use thin 2D hematoxylin and eosin stained slides to study and diagnose pancreatic pathology. Two technologies, tissue clearing and advanced microscopy, have recently converged, and when used together they open the remarkable world of 3D anatomy and pathology to pathologists. Advances in tissue clearing and antibody penetration now make even dense fibrotic tissues amenable to clearing, and light sheet and confocal microscopies allow labeled cells deep within these cleared tissues to be visualized. Clearing techniques can be categorized as solvent-based or aqueous-based techniques, but both clearing methods consist of 4 fundamental steps, including pretreatment of specimens, permeabilization and/or removal of lipid, immunolabeling with antibody penetration, and clearing by refractive index matching. Specialized microscopes, including the light sheet microscope, the 2-photon microscope, and the confocal microscope, can then be used to visualize and evaluate the 3D histology. Both endocrine and exocrine pancreas pathology can then be visualized. The application of labeling and clearing to surgically resected human pancreatic parenchyma can provide detailed visualization of the complexities of normal pancreatic anatomy. It also can be used to characterize the 3D architecture of disease processes ranging from precursor lesions, such as pancreatic intraepithelial neoplasia lesions and intraductal papillary mucinous neoplasms, to infiltrating pancreatic ductal adenocarcinomas. The evaluation of 3D histopathology, including pathology of the pancreatic lesions, will provide new insights into lesions that previously were seen, and thought of, only in 2 dimensions.
Inflammation, Active Fibroplasia, and End-stage Fibrosis in 172 Biliary Atresia Remnants Correlate Poorly With Age at Kasai Portoenterostomy, Visceral Heterotaxy, and Outcome
Authors: Bove Kevin E. , Thrasher Andrew D. , Anders Robert , Chung Catherine T. , Cummings Oscar W. , Finegold Milton J. , Finn Laura , Ranganathan Sarangarajan , Kim Grace E. , Lovell Mark , Magid Margret S. , Melin-Aldana Hector , Russo Pierre , Shehata Bahig , Wang Larry , White Francis , Chen Zhen , Spino Catherine , Magee John C.
Published: September 2018

Published histologic studies of the hilar plate or entire biliary remnant at the time of Kasai portoenterostomy (KHPE) have not provided deep insight into the pathogenesis of biliary atresia, relation to age at surgery, prognosis or the basis for successful drainage. We report detailed histologic findings in 172 centrally reviewed biliary remnants with an average of 6 sections per subject. Active lesions were classified as either necroinflammatory (rare/clustered in a few subjects) or active concentric fibroplasia with or without inflammation (common). Inactive lesions showed bland replacement by collagen and fibrous cords with little or no inflammation. Heterogeneity was common within a given remnant; however, relatively homogenous histologic patterns, defined as 3 or more inactive or active levels in the hepatic ducts levels, characterized most remnants. Homogeneity did not correlate with age at KHPE, presence/absence of congenital anomalies at laparotomy indicative of heterotaxy and outcome. Remnants from youngest subjects were more likely than older subjects to be homogenously inactive suggesting significantly earlier onset in the youngest subset. Conversely remnants from the oldest subjects were often homogenously active suggesting later onset or slower progression. More data are needed in remnants from subjects <30 days old at KHPE and in those with visceral anomalies. Prevalence of partially preserved epithelium in active fibroplastic biliary atresia lesions at all ages suggests that epithelial regression or injury may not be a primary event or that reepithelialization is already underway at the time of KHPE. We hypothesize that outcome after KHPE results from competition between active fibroplasia and reepithelialization of retained, collapsed but not obliterated lumens. The driver of active fibroplasia is unknown.