bluuebunny/crossref_metadata_2025 huggingface dataset:
Staphylococcus aureus Bacteremia in Children: Antibiotic Resistance and Mortality
Authors: Gordon Oren , Cohen Matan J. , Gross Itai , Amit Sharon , Averbuch Dina , Engelhard Dan , Milstone Aaron M. , Moses Allon E.
Published: September 2018

Background:

Staphylococcus aureus (SA) is a major cause of bacteremia in children. Methicillin-resistant SA (MRSA) is considered a public health threat; however, the differences in the prognosis of children with methicillin-susceptible SA (MSSA) versus MRSA bacteremia are not well defined.

Methods:

Data from all SA bacteremia events in children (0–16 years) from 2002 to 2016 in a single Israeli tertiary center were collected. Positive cultures within 48 hours of hospitalization were considered community associated (CA). Those obtained afterward or from children hospitalized within the previous year were considered health-care associated (HA).

Results:

We recorded 427 events, 284 (66%) were HA, 64 (15%) were MRSA and 9 (2%) were CA-MRSA. There was no increase in MRSA during the study period. In-hospital, 30-day and 1-year mortality were 3% (12 cases), 3.5% (16 cases), and 12% (50 cases), respectively. A multivariable analysis controlling for demographics, admitting department and prior morbidity showed an increased 1-year mortality in children with HA bacteremia (hazard ratio [HR] 4.1; 95% confidence interval [CI]: 1.3–12) and prior chronic disease (HR 3.4; 95% CI 1.2 to 9.0). MRSA was not independently associated with increased one-year mortality compared with MSSA: HR (95% CI: 1.4 [0.6–3.1]).

Conclusions:

Short-term pediatric mortality after SA bacteremia is low. HA-SA bacteremia has an increased long-term risk for mortality, particularly in children with chronic diseases. Our data suggest mortality was not increased for MRSA compared with MSSA bacteremia. The very low rate of CA-MRSA bacteremia justifies the current practice not to include glycopeptides in the empiric treatment of CA bacteremia in Israel.
Concussion Epidemiology in Athletes Who Are Deaf or Hard-of-Hearing Compared With Athletes Who Are Hearing
Authors: Brancaleone Matthew P. , Clifton Daniel R. , Onate James A. , Boucher Laura C.
Published: September 2018

Objective:

To compare the epidemiology of concussion between athletes who are deaf or hard-of-hearing (D/HoH) and athletes who are hearing.

Design:

Descriptive epidemiology study.

Setting:

Data were collected from 2 Division III athletic programs. One institution is the world's only university designed to be barrier-free for students who are D/HoH.

Participants:

Six hundred ninety-three athletes who are D/HoH and 1284 athletes who are hearing were included in this study. Athletes participated in collegiate athletics during the 2012 to 2013 through the 2016 to 2017 academic years.

Interventions:

Concussion data were provided by the athletic training staff at each institution.

Main Outcome Measures:

Concussion counts, concussion rate, and injury rate ratios (IRRs) with 95% confidence intervals (95% CIs).

Results:

Thirty athletes who are D/HoH and 104 athletes who are hearing suffered concussions. Athletes who are hearing had an increased injury rate compared with athletes who are D/HoH for all sports combined (IRR = 1.87, 95% CI, 1.26-2.78). Football athletes who are hearing also had an increased injury rate compared with football athletes who are D/HoH (IRR = 3.30, 95% CI, 1.71-6.37). Concussion rate was higher for male athletes who are hearing than male athletes who are D/HoH (IRR = 2.84, 95% CI, 1.62-4.97). No other significant differences regarding concussion risk were identified.

Conclusions:

Athletes who are D/HoH in sex-comparable sports may not have a higher rate of concussion than athletes who are hearing. Rate of concussion in football may be greater among athletes who are hearing compared with athletes who are D/HoH.
Comparison of Electrosurgical Devices for Cervical Conization: Novel Monopolar Scalpel (VIO) Versus Ultrasonic Scalpel
Authors: Akazawa Munetoshi , Saito Toshiaki , Okadome Masao , Ariyoshi Kazuya
Published: September 2018

Objective

The aim of this study was to compare the outcomes associated with the use of a novel monopolar scalpel with those associated with the use of an ultrasonic scalpel for cervical conization of cervical intraepithelial neoplasia.

Materials and Methods

We conducted a retrospective cross-sectional study in patients treated in our institute between April 2010 and March 2017. We used either the VIO monopolar scalpel (VIO) or Harmonic ultrasonic scalpel (HS) for cervical conization. We analyzed operative outcomes, postoperative complications, and pathological findings associated with the use of the 2 devices.

Results

In 500 patients treated with cervical conization, VIO and HS were used in 249 and 251 patients, respectively. No significant difference in patient background was found between the groups. The mean operative time was shorter with VIO than with HS (18.2 min vs. 27.4 min). The mean estimated blood loss was greater with VIO (7.2 g vs. 3.1 g), but the postoperative bleeding rate was higher with HS (5% vs. 20%). Regarding other complications, cervical stenosis was only noted with VIO (4 cases, 1.6%). The positive margin (11% vs. 16%) and positive endocervical curettage rates (7% vs 10%) were not significantly different between the groups. No significant differences were also found in the pathological results and need for additional treatment (the rate of the additional treatment: 20% vs. 23%).

Conclusions

Considering short operating time and less postoperative bleeding, VIO was preferred to HS. However, the excessive coagulation in VIO is considered to lead to cervical stenosis.
Fact or Fiction? Adipose-Derived Stem Cells and Platelet-Rich Plasma for the Treatment of Vulvar Lichen Sclerosus
Authors: Eshtiaghi Panteha , Sadownik Leslie Ann
Published: September 2018

Objective

The aim of the study was to summarize and review the evidence for the efficacy and safety of adipose-derived stem cells (ADSCs) and platelet-rich plasma (PRP) for the treatment of vulvar lichen sclerosus (LS).

Materials and Methods

PubMed/MEDLINE, Ovid, Web of Science, and clinicaltrials.gov were searched from inception up to May 7, 2018.

Results

Seven observational studies were identified, with a total of 98 patients. Both ADSCs and PRP were reported to improve symptoms, quality of life measures, as well as clinical and histological signs of vulvar LS. There is a strong risk of biased estimates of treatment effect.

Conclusions

Current evidence is weak for ADSCs and/or PRP as treatment for vulvar LS. Further research is needed before recommending this therapy.
Has Rotavirus Vaccination Decreased the Prevalence of Biliary Atresia?
Authors: Danial Elizabeth , Fleck-Derderian Shannon , Rosenthal Philip
Published: September 2018

Objectives:

Biliary atresia (BA) is a rare neonatal liver disease that causes cholestasis and is the leading indication for pediatric liver transplantation. Although the exact etiology of BA remains unknown, evidence from murine models supports the role of rotavirus infection in the development of BA. In 2006, universal rotavirus vaccination was implemented in the United States. The goal of this study was to determine if the prevalence of BA correlated with the number of annual rotavirus infections.

Methods:

We utilized data from the 1997 to 2012 Kids’ Inpatient Database and the 1988 to 2015 Organ Procurement and Transplantation Network to determine the annual number of infant discharges with a primary diagnosis of BA and the number of infants with BA who received a liver transplant, respectively. We obtained the number of annual rotavirus infections from the National Respiratory and Enteric Virus Surveillance System and examined whether trends existed between the data from these 3 sources over time.

Results:

From 1997 to 2006, the number of positive rotavirus antigen tests remained steady, however a rapid decrease was observed from 2006 to 2012 (8774 to 1277), coinciding with the uptake of rotavirus immunizations nationwide. The number of BA discharges doubled from 1997 to 2003 and again increased from 2006 to 2012 (67 to 137 and 117 to 156), while the number of liver transplants for BA changed very little from 1997 to 2012.

Conclusions:

The recent implementation of rotavirus vaccination has not had any substantial influence on the prevalence of BA in the United States.
Insurance Coverage and Utilization Improve for Latino Youth but Disparities by Heritage Group Persist Following the ACA
Authors: Kemmick Pintor Jessie , Chen Jie , Alcalá Héctor E. , Langellier Brent A. , McKenna Ryan M. , Roby Dylan H. , Ortega Alexander N.
Published: September 2018

Objective:

Latino youth experience worse access to and utilization of health care compared with non-Latino “white” youth, with inequities persisting following the implementation of the Affordable Care Act (ACA). To better understand these disparities, we examine changes in youth’s access and utilization associated with the ACA for different Latino heritage groups relative to whites.

Study Design:

We use 6 years (2011–2016) of National Health Interview Survey data to examine Latino youth’s insurance coverage and health care utilization by heritage group, nativity, and parental language. The dependent measures of utilization included well-child, emergency department, and physician visits. We used multivariable logistic regression models to estimate the odds of each dependent measure and interacted heritage group and time period [2011–2013 (pre-ACA) versus 2014–2016 (post-ACA)] to examine how changes associated with the ACA varied by group.

Results:

Insurance coverage and well-child visits improved among youth overall following implementation of the ACA. Although Mexican and Central or South American youth experienced the largest absolute increase in coverage, they still had high levels of uninsurance post-ACA (9.9% and 9.1%, respectively). Disparities in coverage between Puerto Rican and white youth improved, while disparities in well-child visits between Mexican and white youth worsened. Little to no movement was observed in disparities by nativity and parental language.

Conclusions:

Most disparities in insurance and utilization across Latino heritage groups and white youth persisted post-ACA despite significant gains within groups. Although disparities for Puerto Rican youth have improved, Mexican and Central or South American youth continue to experience disparities.
The Prevalence of Culture Change Practice in US Nursing Homes
Authors: Miller Susan C. , Schwartz Margot L. , Lima Julie C. , Shield Renée R. , Tyler Denise A. , Berridge Clara W. , Gozalo Pedro L. , Lepore Michael J. , Clark Melissa A.
Published: September 2018

Background and Objectives:

Given the dynamic nursing home (NH) industry and evolving regulatory environment, depiction of contemporary NH culture-change (person/resident-centered) care practice is of interest. Thus, we aimed to portray the 2016/2017 prevalence of NH culture change-related processes and structures and to identify factors associated with greater practice prevalence.

Research Design and Methods:

We administered a nationwide survey to 2142 NH Administrators at NHs previously responding to a 2009/2010 survey. Seventy-four percent of administrators (1583) responded (with no detectable nonresponse bias) enabling us to generalize (weighted) findings to US NHs. From responses, we created index scores for practice domains of resident-centered care, staff empowerment, physical environment, leadership, and family and community engagement. Facility-level covariate data came from the survey and the Certification and Survey Provider Enhanced Reporting system. Ordered logistic regression identified the factors associated with higher index scores.

Results:

Eighty-eight percent of administrators reported some facility-level involvement in NH culture change, with higher reported involvement consistently associated with higher domain index scores. NHs performed the best (82.6/100 weighted points) on the standardized resident-centered care practices index, and had the lowest scores (54.8) on the family and community engagement index. Multivariable results indicate higher index scores in NHs with higher leadership scores and in states having Medicaid pay-for-performance with culture change-related quality measures.

Conclusions:

The relatively higher resident-centered care scores (compared with other domain scores) suggest an emphasis on person-centered care in many US NHs. Findings also support pay-for-performance as a potential mechanism to incentivize preferred NH practice.
Retinitis pigmentosa: recent advances and future directions in diagnosis and management
Authors: Fahim Abigail
Published: September 2018

Purpose of review

Retinitis pigmentosa is a group of genetically diverse inherited blinding disorders for which there are no treatments. Owing to recent advances in imaging technology, DNA sequencing, gene therapy, and stem cell biology, clinical trials have multiplied and the landscape is rapidly changing. This review provides a relevant and timely update of current trends and future directions for the diagnosis and management of this disease.

Recent findings

This review will highlight the use of retinal imaging to measure progression of disease, next-generation sequencing for genetic diagnosis, the use of electronic retinal implants as well as noninvasive digital low-vision aids, and the current state of preclinical and clinical research with gene therapy and cell-based therapies.

Retinitis pigmentosa has historically been an untreatable condition. Recent advances have allowed for limited improvement in visual outcomes for select patients. Retinal degenerative disease is on the cutting edge of regenerative medicine. Gene therapy and stem cell therapeutic strategies are currently under investigation and are expected to radically impact management of inherited retinal disease in the coming years.

Video abstract

http://links.lww.com/MOP/A33.
The overlap between allergy and immunodeficiency
Authors: Sokol Kristin , Milner Joshua D.
Published: September 2018

Purpose of review

The mechanisms underlying the overlap of, and relationship between, atopy and immunodeficiency are just beginning to be recognized, through the identification of novel genetic conditions and the reexamination of well known primary immunodeficiencies. The present review seeks both to frame the topic and to highlight the most recent literature combining allergy in the context of immunodeficiency.

Recent findings

The true prevalence of atopic disorders in the setting of primary immunodeficiency as a whole is difficult to pinpoint, however there have been recent attempts to measure prevalence. Individual immunodeficiency disorders have been more carefully dissected for atopic disease and the mechanisms underlying the atopic phenotypic, whereas several newly described immune deficiencies because of single gene mutations are highly associated with atopic phenotypes. Finally, a number of novel genetic conditions with atopy being the primary feature, even in the absence of overt immune deficiency, have been described, providing instrumental clues into the diagnostic dilemmas these syndromes create.

Defining and examining diseases with primary features of atopy and infection allow for a better understanding of the interplay between the two in rare disease, and hopefully sheds light on fundamental pathways involved in atopy and host defense in the general population.
Interleukin 9 Alters Epithelial Barrier and E‐cadherin in Eosinophilic Esophagitis
Authors: Doshi Ashmi , Khamishon Rebecca , Rawson Renee , Duong Loan , Dohil Lucas , Myers Stephen J. , Bell Braxton , Dohil Ranjan , Newbury Robert O. , Barrett Kim E. , Kurten Richard C. , Aceves Seema S.
Published: September 2018

Background:

Eosinophilic esophagitis (EoE) is a chronic TH2‐assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of interleukin 9 (IL‐9) expressing inflammatory cells. While IL‐9 is known to affect barrier function in the intestine, the functional effects of IL‐9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL‐9 receptor and effects of IL‐9 on the epithelium in EoE.

Methods:

We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL‐9 receptor, the adherens junction protein E‐cadherin and the tight junction protein claudin‐1. We treated primary human esophageal epithelial cells with IL‐9 to understand its effects on E‐cadherin expression and function.

Results:

Active EoE subjects had increased epithelial expression of IL‐9 receptor mRNA and protein (P < 0.05) and decreased membrane bound E‐cadherin (P < 0.01) and claudin‐1 (P < 0.05) expression. IL‐9 receptor expression and mislocalized claudin‐1 positively correlated and while membrane bound E‐cadherin expression negatively correlated with the degree of histologic epithelial remodeling (P < 0.05). IL‐9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (P < 0.01) and membrane bound E‐cadherin in epithelial cell monolayers (P < 0.01).

Conclusions:

These data suggest that IL‐9, its receptor, and its effects on E‐cadherin may be important mechanisms for epithelial barrier disruption in EoE.
Lower 6‐MMP/6‐TG Ratio May Be a Therapeutic Target in Pediatric Autoimmune Hepatitis
Authors: Bolia Rishi , Rajanayagam Jeremy , Hardikar Winita
Published: September 2018

Background:

Azathioprine (AZA) is the mainstay of maintenance therapy in pediatric autoimmune hepatitis (AIH). The use of thiopurines metabolites to individualize therapy and avoid toxicity has not, however, been clearly defined.

Methods:

Retrospective analysis of children ⩽18 years diagnosed with AIH between January 2001 and 2016. Standard definitions were used for treatment response and disease flare. Thiopurine metabolite levels were correlated with the corresponding liver function test.

Results:

A total of 56 children (32 girls) were diagnosed with AIH at a median age of 11 years (interquartile range [IQR] 9). No difference in 6‐thioguanine‐nucleotide (6‐TG) levels (271[IQR 251] pmol/8 × 108 red blood cell vs 224 [IQR 147] pmol/8 × 108 red blood cell, P = 0.06) was observed in children in remission when compared with those who were not in remission. No correlation was observed between the 6‐TG and alanine aminotransferase levels (r = −0.179, P = 0.109) or between 6‐methyl‐mercaptopurine (6‐MMP) and alanine aminotransferase levels (r = 0.139, P = 0.213). The 6‐MMP/6‐TG ratio was significantly lower in patients who were in remission (2[7] vs 5 (10), P = 0.04). Using a quartile analysis, we found that having a ratio of <4 was significantly associated with being in remission with OR 2.50 (95% confidence interval 1.02–6.10), P = 0.047. Use of allopurinol with low‐dose AZA in 6 children with preferential 6‐MMP production brought about remission in 5/6 (83.3%).

Conclusions:

Thiopurine metabolite levels should be measured in patients with AIH who have experienced a loss of remission. A 6‐MMP/6‐TG ratio of <4 with the addition of allopurinol could be considered in these patients.
Chronic Acalculous Cholecystitis in Children With Biliary Symptoms
Authors: Kwatra Neha S. , Nurko Samuel , Stamoulis Catherine , Falone Anthony E. , Grant Frederick D. , Treves S. Ted
Published: September 2018

Objectives:

Chronic acalculous cholecystitis (CAC) increasingly is being diagnosed as a cause of recurring biliary symptoms in children, but its clinical diagnosis remains challenging. The primary objective was to evaluate the utility of hepatocholescintigraphy in pediatric patients with suspected CAC. A secondary objective was to describe their clinical follow‐up after diagnosis.

Methods:

Medical records of patients (aged 9–20 years) who underwent hepatocholescintigraphy from February 2008 to January 2012 were reviewed. Patients with gallstones, and with ⩽1 year of clinical follow‐up, and studies without gallbladder (GB) stimulation were excluded. GB ejection fraction (GBEF) of <35% after sincalide or fatty meal (Lipomul) stimulation were considered abnormal. Diagnosis of CAC was based on histopathology after cholecystectomy. Patients with negative GB pathology, or complete resolution of symptoms without surgery, or alternative diagnoses for persistent symptoms were considered to not have CAC.

Results:

Eighty‐three patients formed the study group (median age 14.9 years), of which 81.9% were girls. Median duration of symptoms and clinical follow‐up were 6 months and 2.9 years, respectively. Fifty‐two patients had at least 1 study with sincalide and 36 patients had at least 1 study with Lipomul. Initial cholescintigraphy was 95.0% sensitive and 73.0% specific in diagnosing CAC, with a negative predictive value of 97.9%. Of the 31 patients with abnormal GBEF, 22 underwent cholecystectomy with improvement in pain in 72.7%, whereas all of the 9 without surgery improved.

Conclusions:

Hepatocholescintigraphy is useful for excluding CAC, although the clinical implications of an abnormal GBEF need to be further defined.
Hepatic Steatosis Is Prevalent Following Orthotopic Liver Transplantation in Children With Cystic Fibrosis
Authors: Cortes‐Santiago Nahir , Leung Daniel H. , Castro Eumenia , Finegold Milton , Wu Hao , Patel Kalyani R.
Published: September 2018

Objectives:

Systematic study of allograft liver histology in children undergoing orthotopic liver transplantation (LT) for cystic fibrosis‐related liver disease (CFLD).

Methods:

Retrospective clinicopathologic review of explants and allograft liver biopsies from 13 children and adolescents with CFLD.

Results:

In this study, the median age at LT for CFLD was 15.7 years. Notably, 10 of 13 (77%) CF explants had >5% steatosis and 8 of 13 (61.5%) demonstrated variable fibrosis. The median age, sex, type of transplant (liver vs liver‐lung), pancreatic insufficiency status, body mass index (BMI) percentile, genotype, and prevalence of diabetes were comparable in those with and without explant steatosis. More than half of allograft biopsies showed significant steatosis (17/31, 54.8%) and lobular inflammation (16/31, 51.6%). Hepatocyte ballooning was less frequent (5/31, 16.1%). Overall, 6 patients (46.2%) had allograft steatosis that worsened over time in 2 patients (33%). None had advanced fibrosis (≥stage 3). Patients with allograft steatosis had significantly more biopsies, were more likely to be “liver only” recipients, had a shorter interval since transplant and higher body mass index percentile (although <85). Patients without explant steatosis never demonstrated allograft steatosis, whereas 60% of patients with explant steatosis (n = 6) developed varying degrees of allograft steatosis. The degree of explant steatosis did not predict its severity in allografts (P = 0.3).

Conclusion:

This is the first study highlighting the development of allograft steatosis in CF patients. Our findings suggest that allograft steatosis in patients with CF may be related to pre‐existing steatosis in native livers, regardless of other risk factors and may have implications on patient management and long‐term graft/patient survival.
The Relationship Between Sleep Disturbance and Disease Activity in Pediatric Patients With Inflammatory Bowel Disease
Authors: Jarasvaraparn Chaowapong , Zlomke Kimberly , Vann Noelle C. , Wang Bin , Crissinger Karen D. , Gremse David A.
Published: September 2018

Objective:

The aim of this prospective cross sectional study was to assess the prevalence of sleep disturbance in children with inflammatory bowel disease (IBD), including the relationships between sleep, inflammatory markers, and disease activity of pediatric patients with IBD.

Methods:

Pediatric patients with IBD and parents were enrolled in the study. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Pediatric Daytime Sleepiness Scale, and the Adolescent Sleep Wake Scale (ASWS) surveys. Parents completed the Child Sleep Habits Questionnaire (CSHQ). Disease activity for Crohn disease (CD) was determined by the Pediatric Crohn Disease Activity Index and the Pediatric Ulcerative Colitis Activity Index was used to define disease activity in ulcerative colitis (UC)/indeterminate colitis patients.

Results:

Fifty‐three pediatric patients with IBD (38 CD, 12 UC, and 3 indeterminate colitis) participated in the study. The significant correlations between the CSHQ and Pediatric Crohn Disease Activity Index (P = 0.002) and the PSQI and Pediatric Ulcerative Colitis Activity Index (P = 0.04) were found. Youth with UC and indeterminate colitis significantly reported more sleep disturbance than patients with CD, (P = 0.03, 0.05, and 0.04; PSQI, Pediatric Daytime Sleepiness Scale, ASWS, respectively). Patients self‐reported significantly more sleep disturbance than was observed by parents (P < 0.0001). This study showed the significant correlations between CSHQ score compared to erythrocyte sedimentation rate and albumin (P = 0.001 and 0.03, respectively).

Conclusions:

Results suggest that increased disease activity is associated with adverse effects on sleep quality. Based on the results of this study, pediatric patients with IBD should be screened for sleep disturbance.
Drug resistance of clinical and environmental isolates of Brucella species in Iran: a meta-analysis
Authors: Khademi Farzad , Yousefi-Avarvand Arshid , Sahebkar Amirhossein , Mohammadi-Ghalehbin Behnam , Arzanlou Mohsen , Peeridogaheh Hadi
Published: September 2018

Background:

Brucellosis is a contagious and febrile disease endemic to Iran. Increased antibiotic resistance in endemic areas may lead to increased risk of treatment failure and the risk of disease relapse. This systematic review and meta-analysis was performed to determine the antibiotic susceptibility profiles of Brucella species isolated from clinical and environmental samples in Iran.

Methods:

Using national and international databases and extracted keywords from the MeSH database, a fully computerized search was done until 11 June 2018. Of 385 collected studies on the prevalence of drug resistance of Brucella species isolated in Iran, six articles were included in the meta-analysis using predefined eligibility criteria.

Results:

Overall resistance rates of Brucella species to different antibiotics in Iran were as follows: doxycycline: 0%, tigecycline: 5.1%, trimethoprim/sulfamethoxazole: 5.7%, ciprofloxacin: 2.7%, streptomycin: 5%, rifampin: 9.5%, tetracycline: 4.6%, gentamicin: 3.9%, moxifloxacin: 0%, erythromycin: 33.3%, azithromycin: 5.8% and ceftriaxone: 6.3%.

Conclusion:

Our study revealed that the prevalence of drug resistance of Brucella species isolated from clinical and environmental samples in Iran was acceptable and low. However, care should be exercised in the use of common antibiotics for the treatment of brucellosis to prevent the spread of drug resistance.
What Has Happened to Hysteria?
Authors: Cramer Phebe
Published: September 2018

This article traces the history of the diagnosis of hysteria from the earliest medical formulations in the 17th century to the present, including the presence of this diagnosis in the five iterations of the Diagnostic Statistical Manual (DSM) of the American Psychiatric Association. Several different types of hysteria are discussed, with alternative causal explanations. Research focusing on this disorder is summarized.
Updating Apathy: Using Research Domain Criteria to Inform Clinical Assessment and Diagnosis of Disorders of Motivation
Authors: Thant Thida , Yager Joel
Published: September 2018

Clinical observations regarding apathy and motivation derived from many psychiatric and neurological conditions have generated divergent descriptions of apathy-related syndromes. Stimulated by complex cases presenting with prominent apathy, uses of the term “apathy” and “related phenomena” in the Diagnostic and Statistical Manual of Mental Disorders, diagnostic proposals for apathy as a syndrome and disorder of motivation, Research Domain Criteria (RDoC) systems governing motivational processes, and their clinical intersections are reviewed. Clinical apathy and associated dysfunctions can be addressed using constructs suggested by the RDoC domain of Positive Valence Systems, including approach motivation and component processes of reward valuation, effort valuation/willingness to work, expectancy/reward prediction error, and responses to reward and reward learning. Although apathy syndromes have been validated, defining potentially distinct disorders of motivation (not simply subordinated to mood, psychotic, cognitive, or substance use disorders) will require additional research to better delineate etiology and pathogenesis, predictive validators, reliable diagnostic methods, treatments, and demonstrations of use for these diagnostic proposals.
Acute Polymorphic Psychotic Disorder
Authors: Castagnini Augusto , Foldager Leslie , Berrios German E.
Published: September 2018

The ICD-11 International Classification of Diseases and Related Health Problems will move toward a narrower concept of “acute and transient psychotic disorders” (ATPD) characterized by the remnant “polymorphic psychotic disorder” (APPD) of the current ICD-10 category, also including schizophrenic and predominantly delusional subtypes. To assess the validity of APPD, relevant articles published between January 1993 and September 2017 were found through searches in PubMed and Web of Science. APPD is a rare mental disorder and affects significantly more women than men in early-middle adulthood. Its diagnostic reliability is relatively low, and its consistency reaches just 53.8% on average over 8.8 years, but is significantly greater than either of ATPD subtypes, which are more likely to progress to schizophrenia and related disorders. Although APPD has distinctive features and higher predictive power, its rarity and the fleeting and polymorphic nature of its symptoms could reduce its usefulness in clinical practice and discourage research.
Association of CTRP13 With Liver Enzymes and Cognitive Symptoms in Nonalcoholic Fatty Liver Disease
Authors: An Kyungeh , Starkweather Angela , Sturgill Jamie , Salyer Jeanne , Sterling Richard K.
Published: September 2018

Background

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease in which patients present with metabolic dysregulation and obesity as well as fat accumulation in the liver. Those with NAFLD frequently have symptoms of fatigue, sleep disturbance, depression, and cognitive dysfunction. C1q/TNF-related protein 13 (CTRP13) regulates glucose metabolism and obesity in mice, yet the role of CTRP13 in human NAFLD has not been elucidated.

Aims

Our aims were to examine whether the plasma levels of CTRP13 are (a) increased in patients with NAFLD; (b) associated with metabolic dysregulation, obesity, liver enzymes, and dyslipidemia; and (c) associated with putative symptoms of NAFLD.

Methods

An observational study was conducted with 23 adults with confirmed NAFLD. Plasma levels of CTRP13, insulin resistance, insulin sensitivity, HbA1C, lipid profile, and liver enzymes were collected. Anthropometric analysis (body mass index, waist–hip circumference ratio) and bioelectrical impedance analysis of body composition were used to assess obesity. Symptom questionnaires were used to assess putative symptoms of NAFLD. Plasma levels of CTRP13 were measured in 21 age- and sex-matched control samples from a biobank. Paired t test was used for comparison of the CTRP13 between NAFLD and controls. Pearson’s correlation coefficients were used to examine associations among variables.

Results

Plasma levels of CTRP13 were significantly higher in patients with NAFLD than in normal controls (p < .001), were associated with higher levels of aspartate aminotransferase, alanine aminotransferase (both p < .05), triglycerides (p < .001), and poorer cognitive function, particularly visuospatial memory (p < .001).

Conclusions

CTRP13 may be a surrogate biomarker of NAFLD symptoms and associated with hepatocellular damage, dyslipidemia, and cognitive dysfunction.
Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates in Yaoundé, Cameroon From 2009 to 2014
Authors: Tayimetha Carolle Y. , Unemo Magnus
Published: September 2018

We investigated the antimicrobial resistance in gonococci 2009 to 2014 in Yaoundé, Cameroon, and recommend revisions of the Cameroonian treatment guideline. We observed a high resistance to ciprofloxacin (17.6%) but no ceftriaxone resistance. Ceftriaxone should replace ciprofloxacin as the recommended first-line treatment for urethral/vaginal discharge. Enhanced resistance surveillance in Africa is essential.
Gastric-type Adenocarcinoma of the Cervix: Tumor With Wide Range of Histologic Appearances
Authors: Pirog Edyta C. , Park Kay J. , Kiyokawa Takako , Zhang Xun , Chen Wen , Jenkins David , Quint Wim
Published: September 2018

Gastric-type endocervical adenocarcinoma (GAS) is a recently described diagnostic entity originally characterized as a tumor with (1) voluminous cytoplasm that is (2) clear or pale eosinophilic, and (3) cells showing distinct cell borders. Since the initial tumor description there has been accumulating experience that the neoplasm, in addition to classic features, may show a wide spectrum of morphologic appearances. This paper describes and illustrates cases of GAS with focal or diffuse findings that include: densely eosinophilic cytoplasm, foamy cytoplasm, goblet cells, glands with elongated, stratified nuclei, glands with small cuboidal cells, glands with flattened cells, papillary growth, single cell infiltration and infiltration with microcystic elongated and fragmented pattern. All these patterns may bring up a differential diagnosis with other cervical malignancies such as usual, intestinal, endometrioid, clear cell, serous, and mesonephric adenocarcinoma. The paper describes the patterns of immunostaining of respective lesions that may aid in the diagnostic process and summarizes the main points of the differential diagnosis. GAS is associated with somatic and germline STK11 mutations and TP53 mutations but is invariably negative for human papilloma virus when tumor only is tested. It shows variation in incidence between countries. Awareness of the spectrum of morphologic appearances in GAS is important for accurate and confident diagnosis. Correct identification of GAS is important due to its propensity for ovarian and other distant metastases, markedly worse prognosis as compared with usual endocervical adenocarcinoma, and its relative resistance to chemotherapy.
Expanding the Spectrum of Genetic Alterations in Pseudomyogenic Hemangioendothelioma With Recurrent Novel ACTB-FOSB Gene Fusions
Authors: Agaram Narasimhan P. , Zhang Lei , Cotzia Paolo , Antonescu Cristina R.
Published: September 2018

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon, rarely metastasizing vascular neoplasm with predilection to affect young adults. The tumors often present as multiple nodules involving various tissue planes, including superficial and deep soft tissues as well as bone. Recurrent SERPINE1-FOSB gene fusions have been reported as the hallmark genetic abnormality in PHE, however, in our experience, a number of cases with typical histology lack this genetic abnormality. In this study, we identify a novel ACTB-FOSB gene fusion, which is as prevalent as the initial translocation reported. We selected 15 consecutive cases of PHE with typical morphologic features which had material for molecular testing. The cohort included 10 males and 5 females, ranging in age from 17 to 58 years (median age: 33 y; mean age: 35.3 y). Eight (53%) cases were located in the lower extremities (foot, calf, tibia, thigh), 5 (33%) were located in the trunk, abdomen or pelvis (abdominal wall—2, shoulder, back, ischium) and 2 (13%) were located in the upper extremity (humerus and hand). Ten (67%) cases had multifocal presentation and 5 (33%) presented as solitary lesions. Three (20%) cases were located only in the superficial dermis and subcutaneous tissues, 4 (27%) involved the superficial and deep soft tissue and 8 (53%) cases involved only the deep soft tissue and bone. Using fluorescence in situ hybridization and ARCHER fusionplex analysis we identified a novel ACTB-FOSB gene fusion in 7 cases, while the remaining 8 had the previously described SERPINE1-FOSB fusion. The clinicopathologic features and behavior of PHE associated with the ACTB-FOSB gene fusion were similar to those harboring the SERPINE1-FOSB; except that tumors with the ACTB variant were more often associated with solitary presentation. In conclusion, our results expand the spectrum of genetic alterations in PHE with a novel gene fusion identified in half of the cases. We speculate that some of the novel targeted therapies that have shown promise in SERPINE1-FOSB-positive PHE might also be beneficial in this molecular subset.
Cancerization of the Pancreatic Ducts
Authors: Hutchings Danielle , Waters Kevin M. , Weiss Matthew J. , Wolfgang Christopher L. , Makary Martin A. , He Jin , Cameron John L. , Wood Laura D. , Hruban Ralph H.
Published: September 2018

Invasive pancreatic ductal adenocarcinoma (PDAC) can infiltrate back into and spread along preexisting pancreatic ducts and ductules in a process known as cancerization of ducts (COD). Histologically COD can mimic high-grade pancreatic intraepithelial neoplasia (HG-PanIN). We reviewed pancreatic resections from 100 patients with PDAC for the presence or absence of ducts with histologic features of COD. Features supporting COD included adjacent histologically similar invasive PDAC and an abrupt transition between markedly atypical intraductal epithelium and normal duct epithelium or circumferential involvement of a duct. As the TP53 and SMAD4 genes are frequently targeted in invasive PDAC but not HG-PanIN, paired PDAC and histologically suspected COD lesions were immunolabeled with antibodies to the p53 and Smad4 proteins. Suspected COD was identified on hematoxylin and eosin sections in 89 (89%) of the cases. Immunolabeling for p53 and Smad4 was performed in 68 (76%) of 89 cases. p53 was interpretable in 55 cases and all 55 (100%) cases showed concordant labeling between COD and invasive PDAC. There was matched aberrant p53 immunolabeling in 37 (67%) cases including overexpression in 30 (55%) cases and lack of expression in 7 (13%) cases. Smad4 immunolabeling was interpretable in 61 cases and 59 (97%) cases showed concordant labeling between COD and invasive PDAC. Matched loss of Smad4 was seen in 28 (46%) cases. The immunolabeling of invasive PDAC and COD for p53 and Smad4 supports the high prevalence of COD observed on hematoxylin and eosin and highlights the utility of p53 and Smad4 immunolabeling in differentiating COD and HG-PanIN.
FIGO Versus Silverberg Grading Systems in Ovarian Endometrioid Carcinoma
Authors: Parra-Herran Carlos , Bassiouny Dina , Vicus Danielle , Olkhov-Mitsel Ekaterina , Cesari Matthew , Ismiil Nadia , Nofech-Mozes Sharon
Published: September 2018

The International Federation of Obstetrics and Gynecology (FIGO) grading system for endometrial carcinoma is currently applied to ovarian endometrioid carcinoma (OEC) in many practices. However, previous reports claim superior prognostication by using the Silverberg grading system for ovarian carcinoma. Thus, a thorough comparison between FIGO and Silverberg in OEC is still warranted. A total of 72 OECs diagnosed at our institution were independently graded using both systems. Grade (G) following Silverberg was based on combined scores for architecture, nuclear atypia, and mitotic activity. FIGO grading was based on the % of nonsquamous solid component; severe atypia warranted upgrade to the architectural FIGO grade (G1 to G2 or G2 to G3). Case grouping by grade was correlated with disease-free (DFS), disease-specific (DSS), and overall (OS) survival. Eleven (15.3%) OECs were bilateral, 26 (36.1%) had ovarian surface involvement, and 12 (16.7%) had lymphovascular space invasion. Forty-seven OECs were stage I (65%), 16 (22%) stage II, and 9 (13%) stage III. Median follow-up period was 62 months (range: 1 to 179 mo). Median DFS was 60.5 months (1 to 179 mo); median OS was 61 months (1 to 179 mo). Sixteen (22%) OECs recurred and 9 (13%) patiets died of disease. In univariate analysis, both FIGO and Silverberg correlated significantly with DFS, DSS, and OS (all with P<0.05). However, when compared in multivariate analysis, only Silverberg retained statistical correlation with survival (P<0.05). G1+G2 OEC by Silverberg had significantly better DFS, DSS, and OS compared with G3; such separation was not seen with FIGO. Survival was similar in Silverberg G1 and G2 tumors even 5 years after diagnosis, whereas FIGO G2 tumors had survival approaching G1 in the first 5 years, but declined after the 5-year mark approaching G3 tumors. Tumor laterality, lymphovascular space invasion, and stage also correlated with outcome. Stage showed prognostication superior to all other variables in multivariate analysis. As currently defined, the Silverberg grading system is a better predictor of survival than FIGO. Such differences may be explained by the G2 OEC groups, with G2 Silverberg clustering with G1 tumors, and having a more favorable behavior compared with G2 FIGO. Thus, Silverberg may be preferable in order to stratify patients in low and high-risk categories for prognosis and disease management.
A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors Suggesting Different Modes of Teratoma Development
Authors: Kao Chia-Sui , Bangs Charles D. , Aldrete Galina , Cherry Athena M. , Ulbright Thomas M.
Published: September 2018

Mediastinal teratomas are enigmatic; those in children and women are almost invariably benign but in men they may be benign or malignant. There are few data on the chromosome 12p status of mediastinal germ cell tumors (GCT), whereas increased 12p copy number is virtually uniform in malignant testicular GCTs. We therefore studied chromosome 12p copy number in 34 diverse mediastinal GCTs and correlated the results with morphology and follow-up to gain insight into possible pathogenesis. Four prepubertal (below 12 y) children (3 females and 1 male), 7 postpubertal females (14 to 52 y) and 6 postpubertal males (12 to 40 y old) had pure, previously untreated teratomas; 15 were mature and 2 had low-grade immaturity. All lacked 12p copy number increase and cytologic atypia, and most (14/17) showed organoid morphology. On follow-up of 16, 1 died of postoperative complications and the remaining 15 were disease free (1 to 119 mo, mean: 39 mo). Eight postpubertal males (19 to 44 y old) had pure teratomas in postchemotherapy resections; 5/8 showed 12p copy number increase. All 8 had distinct cytologic atypia, with organoid morphology in 3. On follow-up, 6 were disease free after surgical resection (1.5 to 94 mo, mean 38 mo); 1 died of disease at 14.5 months, and 1 was alive with metastases at 176 months. Two postpubertal patients, 1 male (29 y) and 1 female (31 y), had teratoma with secondary somatic-type malignancies, with positive 12p copy number increase in the former but not the latter. The man’s tumor occurred after chemotherapy and was a nonorganoid teratoma with primitive neuroectodermal tumor and malignant glioma; the woman’s was a previously untreated organoid teratoma with an undifferentiated carcinoma component. The man died of disease (16 mo) and the woman was alive with metastases (27 mo). Seven patients had resections for mixed GCTs (4) or pure nonteratomatous tumors, all after chemotherapy; 5/7 had positive 12p copy number increase. The teratoma component of the 2 cases having one showed distinct cytologic atypia and lacked organoid morphology. On follow-up, 1 died of disease (5 mo), 2 were alive with disease (1, 1.5 mo), 3 were disease free (1 to 43 mo; mean: 18 mo), and 1 was alive with unknown status (31 mo). Our results support that mediastinal teratomas likely develop from 2 separate pathways. Those in children, women and some men arise as pure neoplasms from a nontransformed precursor cell and, therefore, lack 12p copy number increase, show no cytologic atypia, often have organoid morphology and are benign. Common 12p copy number increase, uniform atypia, infrequent organoid structures and malignant behavior support that pure teratomas after chemotherapy in postpubertal males derive from a malignantly transformed precursor cell. Interestingly, we identified organoid pancreatic differentiation only in the benign group and neuroglia more commonly in the malignant teratomas.
Pediatric Ventilator-Associated Events: Analysis of the Pediatric Ventilator-Associated Infection Data
Authors: Willson Douglas F. , Hall Mark , Beardsley Andrew , Hoot Michelle , Kirby Aileen , Hays Spencer , Erickson Simon , Truemper Edward , Khemani Robinder
Published: September 2018

Objectives:

To compare the prevalence of infection applying the proposed pediatric ventilator-associated events criteria versus clinician-diagnosed ventilator-associated infection to subjects in the pediatric ventilator-associated infection study.

Design:

Analysis of prospectively collected data from the pediatric ventilator-associated infection study.

Setting:

PICUs of 47 hospitals in the United States, Canada, and Australia.

Patients:

Two-hundred twenty-nine children ventilated for greater than 48 hours who had respiratory secretion cultures performed to evaluate for suspected ventilator-associated infection.

Interventions:

None.

Measurements and Main Results:

Applying the proposed pediatric ventilator-associated event criteria, 15 of 229 subjects in the ventilator-associated infection study qualified as “ventilator-associated condition” and five of 229 (2%) met criteria for “infection-related ventilator-associated complication.” This was compared with 89 of 229 (39%) diagnosed as clinical ventilator-associated infection (Kappa = 0.068). Ten of 15 subjects identified as ventilator-associated condition did not meet criteria for infection-related ventilator-associated complication primarily because they did not receive 4 days of antibiotics. Ventilator-associated condition subjects were similar demographically to nonventilator-associated condition subjects and had similar mortality (13% vs 10%), PICU-free days (6.9 ± 7.7; interquartile range, 0–14 vs 9.8 ± 9.6; interquartile range, 0–19; p = 0.25), but fewer ventilator-free days (6.6 ± 9.3; interquartile range, 1–15 vs 12.4 ± 10.7; interquartile range, 0–22; p = 0.04). The clinical ventilator-associated infection diagnosis in the ventilator-associated infection study was associated with fewer PICU-free days but no difference in mortality or ventilator-free days.

Conclusions:

The ventilator-associated event criteria appear to be insensitive to the clinical diagnosis of ventilator-associated infection. Differentiation between ventilator-associated condition and infection-related ventilator-associated complication was primarily determined by the clinician decision to treat with antibiotics rather than clinical signs and symptoms. The utility of the proposed pediatric ventilator-associated event criteria as a surrogate for ventilator-associated infection criteria is unclear.