bluuebunny/crossref_metadata_2025 huggingface dataset:
Rotavirus Infection in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients
Authors: Flerlage Tim , Hayden Randall , Cross Shane J. , Dallas Ronald , Srinivasan Ashok , Tang Li , Sun Yilun , Maron Gabriela
Published: August 2017

Background:

Rotaviruses may produce prolonged and severe disease in allogeneic hematopoietic cell transplant (HCT) recipients. Nitazoxanide and enterally administered human immunoglobulins are potential therapeutic options. This retrospective study describes the clinical course of rotavirus infection in pediatric allogeneic HCT recipients and a single-center experience with nitazoxanide and oral immunoglobulins as potential treatment options.

Methods:

We identified 36 patients who had positive stool rotavirus antigen assays after allogeneic HCT from May 30, 2012, to July 31, 2015. Clinical, microbiologic and treatment data were collected and analyzed using descriptive statistics.

Results:

Forty-nine discrete episodes of rotavirus infection were identified among these 36 patients for a cumulative incidence of 19.7%. For these 49 episodes, the median day to infection after HCT was day 82, and the median duration of diarrhea was 17.5 days (range 4–122). Nitazoxanide and enteral immunoglobulins were prescribed for 41 episodes. The median duration of clinical symptoms after initiation of nitazoxanide was 11 days (range 2–85), 23 days (range 10–107) after enteral immunoglobulins and 26 days (range 6–90) after a combination of nitazoxanide and enteral immunoglobulins (P = 0.1). No adverse effects of either treatment were documented, but efficacy could not be assessed in this patient population.

Conclusions:

In pediatric HCT recipients, the clinical illness produced by rotaviruses is prolonged compared with otherwise healthy children. Nitazoxanide appears safe, but its efficacy for this indication requires further study.
Determinants of Pharmacological Treatment Initiation and Persistence in Publicly Insured Adults With Attention-Deficit/Hyperactivity Disorder
Authors: Li Yan , Liu Wei , Zhu Yanmin , Liu Xinyue , Winterstein Almut Gertrud
Published: August 2017

Objectives

The objectives of this study were to describe the longitudinal trends of pharmacological treatment initiation and persistence in adult patients with attention-deficit/hyperactivity disorder (ADHD) and to explore how patients' sociodemographic and clinical characteristics affect these patterns.

Methods

A retrospective cohort of 23,747 adult patients with new ADHD episodes was assembled using Medicaid extract files of 29 US states from 1999 and 2010. Sociodemographic and clinical characteristics of treatment initiators and noninitiators, and treatment persistent and nonpersistent patients were compared using multivariable logistic regression.

Results

The overall treatment initiation and 1-year persistence rate was 22.5% and 34.2%, respectively. After adjustment, the propensity of initiating pharmacotherapy and being persistent tripled (2010 vs 2000; odds ratio, 3.25; 95% confidence interval, 2.61–4.04) and almost doubled (2009 vs 2000; odds ratio, 1.86; 95% confidence interval, 1.20–2.90) over the study period. Male, racial and ethnic minorities, and younger age groups had a decreased propensity for treatment initiation and persistence. The likelihood of initiating treatment was similar for rural and urban residents but varied among different US states. Severe mental comorbidities and, concordantly, use of antipsychotics or mood stabilizers reduced the propensity of treatment initiation but had little effect on persistence. Patients filling sustained release stimulants were most likely to be persistent. Finally, preexisting cardiovascular conditions reduced the likelihood of receiving treatment but were not associated with persistence.

Conclusions

The propensity to initiate and persist on pharmacological treatment in adults with ADHD has increased in the last decade but remains low. Treatment patterns were closely related to several sociodemographic and clinical determinants. Our findings provide valuable information to ensure appropriate treatment choices for these patients.
Albumin Use in Patients With Cirrhosis in France: Results of the “ALBU-LIVE” Survey
Authors: Garioud Armand , Cadranel Jean-François , Pauwels Arnaud , Nousbaum Jean-Baptiste , Thévenot Thierry , Dao Thong , Louvet Alexandre , Sogni Philippe , Talbodec Nathalie , Antonini Teresa M. , Bureau Christophe , Thabut Dominique , Elkrief Laure , Jouannaud Vincent , Macaigne Gilles , Bernard-Chabert Brigitte , Lison Hortensia , Alric Laurent , Carbonell Nicolas , Labadie Héléne , Amiot Xavier , Abergel Armand , Hanslik Bertrand , Leroy Vincent , De Lédinghen Victor , Denis Jacques
Published: August 2017

Introduction:

The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists.

Methods:

All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations.

Results:

Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax.

Conclusions:

In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.
Changes in Adenoma Detection Rate With Implementation of Full-spectrum Endoscopy
Authors: Nulsen Benjamin , Ungaro Ryan C. , Davis Natalie , Turvall Elliot , Deutsch Lisa , Lewis Blair
Published: August 2017

Goals:

To investigate the effect of implementing full-spectrum endoscopy (Fuse) on adenoma detection rate (ADR) at an ambulatory surgical center (ASC).

Background:

Traditional forward viewing (TFV) endoscopes have 1 camera and provide an angle of view of 140 to 170 degrees, whereas Fuse provides a 330 degrees view through the addition of 2 side cameras. Although randomized studies have shown that Fuse decreases adenoma miss rates, its impact on ADR in a screening population is currently unknown.

Study:

We conducted a retrospective analysis of data from average risk screening colonoscopies at a 5-room ASC. This ASC transitioned from TFV to Fuse in April 2014. The primary outcome was ADR defined as the percentage of patients who underwent screening colonoscopy and were found to have at least 1 adenomatous polyp.

Results:

A total of 1696 screening colonoscopies were performed with TFV and 2302 with Fuse. Overall ADR was 23.7% with TFV and 29.0% with Fuse (P<0.01), an absolute increase of 5.3%. ADR for the proximal colon increased from 13.0% with TFV to 16.7% with Fuse (3.8% increase, P<0.01). ADR for advanced adenomas improved from 3.8% with TFV to 6.0% with Fuse (2.2% increase; P<0.01). The mean number of adenomas detected per colonoscopy increased from 0.32 to 0.41 (P<0.01). In multivariate analysis, the adjusted odds ratio for detecting an adenoma with Fuse versus TFV was 1.30 (P<0.01; 95% confidence interval, 1.11-1.51).

Conclusions:

ADR significantly increased after adopting Fuse endoscopes at an ASC. Further studies are warranted to further understand the effects of Fuse on ADR in real-world settings.
An Adjusted Level of Adenoma Detection Rate is Necessary for Adults Below 50 Years Old
Authors: Yoon Jin Young , Cha Jae Myung , Shin Jeong Eun , Kim Kyeong Ok , Yang Hyo-Joon , Kim Hyun Gun , Cho Young-Seok , Boo Sun-Jin , Lee Jun , Jung Yunho , Lee Hyun Jung , Koo Hoon Sup , Joo Young-Eun
Published: August 2017

Background:

Although adenoma prevalence is lower in younger people compared with screening-aged adults 50 years old and above, there is no adjustment recommendation for the target adenoma detection rate (ADR) in young people. Herein, we estimated a different target ADR for adults below 50 years old based on screening colonoscopy findings.

Materials and Methods:

Asymptomatic, average-risk adults below 50 years old who underwent screening colonoscopy were enrolled at 12 endoscopy centers in Korea between February 2006 and March 2012. Screening colonoscopies were stratified into low or high ADR groups with ADR levels of 20% and 25%, respectively.

Results:

The ADRs from 12 endoscopy centers ranged from 12.1% to 43.8% (median ADR, 24.1%) based on 5272 young adults receiving screening colonoscopies. Using 20% as an ADR level, the risks for metachronous adenoma and advanced adenoma were significantly higher in the low ADR group than the high ADR group (35.4% vs. 25.7%, P<0.001; 8.3% vs. 3.7%, P=0.001, respectively). However, using ADR level of 25%, the risk for metachronous neoplasia was similar in the high and low ADR groups in young adults according to screening colonoscopy. In subgroup analysis, similar findings were found in males, but not in females.

Conclusions:

Optimal target ADR may be different between younger and older populations, and the adoption of a 20% target ADR could be used as a performance indicator for young populations.
Role of Esophageal Motility, Acid Reflux, and of Acid Suppression in Nonobstructive Dysphagia
Authors: Ribolsi Mentore , Biasutto Dario , Giordano Antonio , Balestrieri Paola , Cicala Michele
Published: August 2017

Goals:

The present study was aimed at evaluating, in dysphagic patients, the role of high-resolution manometry (HRM) findings, presence of gastroesophageal reflux disease (GERD), and proton-pump inhibitor (PPI) therapy on dysphagia perception.

Background:

A relevant proportion of patients with nonobstructive dysphagia present normal esophageal HRM findings. Patients with GERD often complain of dysphagia and factors, such as hypersensitivity, might be involved in its occurrence.

Study:

In total, 37 nonerosive reflux disease (NERD) patients with only dysphagia (group 1) and 52 patients with both dysphagia and typical GERD symptoms (group 2) were evaluated with symptom scores, HRM combined with impedance and 24 hours impedance-pH monitoring. In total, 44 NERD patients, not presenting dysphagia, underwent the same protocol. A total of 22/37 group 1 patients [11 with pathologic acid exposure time (AET)] were treated with esomeprazole 40 mg oid for 4 weeks and were reassessed during the last week of therapy.

Results:

A total of 15/37 group 1 patients (40%), 27/52 group 2 patients (52%), and 19/44 (43%) NERD patients presented pathologic AET [P=not significant (NS)]. Group 1 patients with a pathologic AET showed a significantly lower mean distal contractile integral (DCI) and a significant correlation (ρ=−0.71) between individual DCI and total bolus transit time values. During PPI therapy, in group 1 patients with pathologic AET, the mean dysphagia score value decreased significantly [7.5 (range, 3 to 9) before, 4 (range, 2 to 6) during PPI; P<0.01)] and mean DCI value increased significantly.

Conclusions:

In total, 40% of dysphagic patients show a pathologic AET and reduced peristaltic vigor. In these patients, an adequate PPI therapy significantly decreases dysphagia frequency and severity and improves the esophageal peristaltic force.
Time Trends and Predictors of Acute Gastroenteritis in the United States
Authors: Kim Hyun S. , Rotundo Laura , Nasereddin Thayer , Ike Adaugo , Song David , Babar Arooj , Feurdean Mirela , Demyen Michael F. , Ahlawat Sushil K.
Published: August 2017

Goals:

To investigate the time trends of the prevalence and predictors of acute gastroenteritis (AGE) in the United States from 2005 to 2014 using nationally representative data.

Background:

AGE results in numerous visits to emergency departments and outpatient clinics annually in the United States with the estimated attributable cost to the US economy up to $145 billion dollars. However, time trends and predictors of AGE are not fully understood.

Methods:

Data were obtained from the National Health and Nutrition Survey (NHANES) 2005 to 2014, a nationally representative health survey. AGE was defined by a medical question (Do you have a stomach or intestinal illness with vomiting or diarrhea that started during last 30 d?). Prevalence of AGE was estimated in the total population as well as by selected demographic variables. Predictors of AGE and time trends of prevalence over survey periods were also investigated.

Results:

Overall monthly prevalence of AGE was 8.31% (95% confidence interval, 7.81-8.81), corresponding to 22.8 million people. AGE was associated with a younger age group, the highest in ages 0 to 9 years old, females, winter to early spring season, US born, divorced/separated/widowed individuals, current smokers, heavy alcohol users, and low household income. In the trends analyses, the prevalence of AGE significantly decreased over the study periods: 10.23% in 2005 to 2006, 9.89% in 2007 to 2008, 7.58% in 2009 to 2010, 6.44% in 2011 to 2012, and 7.47% in 2013 to 2014 (trend P<0.001).

Conclusion:

In the United States from 2005 to 2014, the monthly prevalence of AGE was 8.31% and has been significantly decreasing over time.
Validation of Lymphocyte-to-Monocyte Ratio as a Prognostic Factor in Advanced Pancreatic Cancer
Authors: Xue Peng , Hang Junjie , Huang Weiyi , Li Shaobo , Li Ning , Kodama Yuzo , Matsumoto Shigemi , Takaori Kyoichi , Zhu Lifei , Kanai Masashi
Published: August 2017

Objectives

Although the prognostic value of lymphocyte-to-monocyte ratio (LMR) has been recently demonstrated in solid tumors, little is known of its impact on advanced pancreatic cancer (APC). This study evaluates and validates the cutoff value of LMR for predicting palliative chemotherapy outcome using a transnational cohort of APC patients.

Methods

A total of 405 APC patients receiving first-line palliative chemotherapy were retrospectively reviewed. Of these, 153 patients were from Shanghai General Hospital (training set) and 252 patients were from Kyoto University Hospital (validation set). The optimal cutoff value of LMR was determined by a generating receiver operating characteristic curve for the training set. The association between LMR and survival was evaluated using log-rank tests, and a Cox regression model was used to validate the independent prognostic significance of LMR in APC patients.

Results

The optimal cutoff value of LMR was 2.8. Overall survival was significantly longer in patients with LMR of 2.8 or greater than those with LMR of less than 2.8 (P < 0.001). Cox regression analysis showed that LMR was an independent prognostic factor. The impact of LMR was widely observed in all subgroups except the performance status 2 subgroup.

Conclusions

Lymphocyte-to-monocyte ratio may be considered as a promising prognostic marker for APC patients receiving palliative chemotherapy.
Increased Circulating CD4+CD25+CD127low/neg Regulatory T-cells as a Prognostic Biomarker in Acute Pancreatitis
Authors: Minkov Georgi A. , Yovtchev Yovcho P. , Halacheva Krasimira S.
Published: August 2017

Objective

Early detection of severe forms with unfavorable outcome is the cornerstone that could provide reduction of morbidity and mortality in acute pancreatitis (AP).

Methods

The percentage of circulating CD4+CD25+CD127low/neg regulatory T-cells (Tregs) was determined at admission, on the 48th hour, and on the fifth day in 72 patients with AP. We divided patients in 2 groups—Sev1, which includes 19 patients (26.4%) with moderate AP and 39 patients (54.2%) with mild disease, and Sev2, which includes 14 patients (19.4%) with severe AP. Seven patients (9.7%) developed septic complications. The mortality in our group was 9.7%.

Results

The patients in Sev2 had higher percentage of Tregs at admission and on the fifth day compared with patients in Sev1 (P = 0.007 and P = 0.033, respectively). There was no significant difference in percentage of Tregs at admission, on the 48th hour, and on the fifth day in patients who developed and did not develop infected necrosis (P = 0.50, P = 0.72, and P = 0.92, respectively). Patients with poor outcome had elevated percentage of Tregs on the fifth day (P = 0.045).

Conclusions

The percentage of circulating Tregs may be implicated in the development of early immune suppression in AP. Elevated percentage of circulating Tregs at admission in AP is an independent prognostic biomarker for severe disease.
Anticancer Effects of Baicalein in Pancreatic Neuroendocrine Tumors In Vitro and In Vivo
Authors: Tian Ye , Zhen Liang , Bai Jian’an , Mei Yumei , Li Zheng , Lin Aihua , Li Xueliang
Published: August 2017

Objectives

Baicalein is a Chinese traditional medicine that inhibits tumor migration and growth. Pancreatic neuroendocrine tumors (pNETs) have a high incidence in China, but there are still no effective treatments. The aim of our study was to investigate whether baicalein could inhibit pNETs.

Methods

In vitro, we used BON1—a cell line of pNETs—to analyze the apoptosis and migration and invasion after baicalein treatment via flow cytometry and Western blot. In vivo, we used a xenograft tumors model to evaluate the size of tumors after baicalein treatment. Western blot was used to analyze the expression of apoptosis and migration-related protein.

Results

In vitro, the Cell Counting Kit 8 assay showed that baicalein decreased BON1 viability, and flow cytometry demonstrated that baicalein induced BON1 apoptosis and protein changes. In addition, baicalein inhibited BON1 migration and invasion as shown via a Transwell assay. In vivo, baicalein inhibited tumor growth and migration and also increased apoptosis-related protein expression.

Conclusions

Baicalein could increase caspase-3 and Bax expression and decrease survivin and Bcl-2 to induce apoptosis. It inhibits migration and invasion by decreasing expression of vascular endothelial growth factor and matrix metalloproteinases 2 and 9.
Transcranial Doppler Screening in 50 Patients With Sickle Cell Hemoglobinopathies in Iran
Authors: Zamani Susan , Borhan Haghighi Afshin , Haghpanah Sezaneh , Karimi Mehran , Bordbar Mohammad R.
Published: August 2017

Background:

As previous studies had discordant results with regard to the correlation of transcranial Doppler (TCD) screening and brain MRI, the aim of this study was to find the correlation between TCD values and silent ischemia in sickle cell disease (SCD) patients.

Method and Materials:

In this cross-sectional study, 50 patients with proven diagnosis of sickle cell hemoglobinopathies based on their hemoglobin electrophoresis were included. Demographic data, their physical exam, information with regard to crises history, and their laboratory data were recorded. Brain MRI and TCD were requested for all patients.

Results:

The mean age of the patients was 10.2±5.8 years. Only 3 patients (6%) showed evidence of ischemia on brain MRI. Normal and ischemic patients were not significantly different with respect to TCD values, sex, splenomegaly, aplastic crisis, and laboratory test results (P-value >0.05). Only platelet count was significantly higher in the ischemic group compared with that in the normal group (P=0.002). The pain crisis was significantly associated with the mean velocity values of RMCA, LMCA, RV, and LV arteries (P-value <0.05).

Conclusion:

On the basis of our results, there was no significant difference in the mean velocity TCD values between patients with and without evidence of ischemic brain damage in brain MRI. The frequency of silent ischemia was much lower than expected. Further studies with larger sample sizes are needed to elucidate the positive predictive value of abnormal TCD in the prediction of silent ischemia in patients with sickle hemoglobinopathy in certain ethnic groups.
Lupus Anticoagulant-hypoprothrombinemia Syndrome (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases
Authors: Komvilaisak Patcharee , Wisanuyotin Suwannee , Jettrisuparb Arunee , Wiangnon Surapon
Published: August 2017

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.
Silencing Intersectin 1 Slows Orthotopic Neuroblastoma Growth in Mice
Authors: Harris Jamie , Herrero-Garcia Erika , Russo Angela , Kajdacsy-Balla Andre , O’Bryan John P. , Chiu Bill
Published: August 2017

Neuroblastoma accounts for 15% of all pediatric cancer deaths. Intersectin 1 (ITSN1), a scaffold protein involved in phosphoinositide 3-kinase (PI3K) signaling, regulates neuroblastoma cells independent of MYCN status. We hypothesize that by silencing ITSN1 in neuroblastoma cells, tumor growth will be decreased in an orthotopic mouse tumor model. SK-N-AS neuroblastoma cells transfected with empty vector (pSR), vectors expressing scrambled shRNA (pSCR), or shRNAs targeting ITSN1 (sh#1 and sh#2) were used to create orthotopic neuroblastoma tumors in mice. Volume was monitored weekly with ultrasound. End-point was tumor volume >1000 mm3. Tumor cell lysates were analyzed with anti-ITSN1 antibody by Western blot. Orthotopic tumors were created in all cell lines. Twenty-five days post injection, pSR tumor size was 917.6±247.7 mm3, pSCR was 1180±159.9 mm3, sh#1 was 526.3±212.8 mm3, and sh#2 was 589.2±74.91 mm3. sh#1-tumors and sh#2-tumors were smaller than pSCR (P=0.02), no difference between sh#1 and sh#2. Survival was superior in sh#2-tumors (P=0.02), trended towards improved survival in sh#1-tumors (P=0.09), compared with pSCR-tumors, no difference in pSR tumors. Western blot showed decreased ITSN1 expression in sh#1 and sh#2 compared with pSR and pSCR. Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis.
The Maternal Gut Microbiome During Pregnancy
Authors: Edwards Sara M. , Cunningham Solveig A. , Dunlop Anne L. , Corwin Elizabeth J.
Published: August 2017

The gut microbiome is a critical component of an individual's metabolism and overall health. The prenatal period is marked by unique inflammatory and immune changes that alter maternal gut function and bacterial composition as the pregnancy advances. The composition of the maternal gut microbiome contributes to obstetric outcomes with long-term health sequelae for mother and child. Estrogen and progesterone also have an impact on gut function, especially during the prenatal period. These physiologic changes in pregnancy allow for adjustments in maternal metabolism and weight necessary to support the pregnancy. Normal hormonal, metabolic, and immunologic changes to the maternal gut microbiome throughout the prenatal period are reviewed, including relevant implications for nurses providing care for pregnant women.
Invasive Micropapillary Carcinoma of the Uterine Cervix: Case Report of a Rare Entity
Authors: Munakata Satoru , Hosoi Ayako , Yamamoto Toshiya
Published: August 2017

Invasive micropapillary carcinoma (IMPC) is a rare subtype of adenocarcinoma found in many organs. Only 1 case of IMPC of the uterine cervix has been reported. We report a rare case of IMPC in the uterine cervix. A 61-yr-old woman presented to our hospital for vaginal bleeding and abdominal pain. A papillary tumor was found in the uterine cervix. Cervical cytology revealed abnormal cells suggesting carcinoma in situ and adenocarcinoma. A follow up biopsy revealed adenocarcinoma. She underwent radical hysterectomy and bilateral adnexectomy. Histologically, carcinoma in situ and IMPC were found in the uterine cervix. Lymphatic infiltration was present in the cerix and in the right cardinal ligament. A pelvic lymph node metastasis was also identified. Clinical FIGO stage was IIb and pathologic stage was pT2bN1M0. Postoperative positron emission tomography-computed tomography revealed paraaortic lymph node metastasis. She is alive with disease 2 yr 9 mo after surgery. Positive p16 immunostaining and high-risk human papilloma virus in situ hybridization revealed human papilloma virus infection. Interleukin-17 was expressed in the tumor cells which might be related to the extensive neutrophilic infiltration and tumor progression. This is the first case report in which interleukin-17 expression is observed in the tumor cells of IMPC.
Perivascular Epithelioid Cell Tumor (PEComa) of the Uterine Cervix: A Case Report of a 43-Yr-Old Woman With Abnormal Uterine Bleeding Treated With Hysterectomy
Authors: Kovac Ondrej , Babal Pavel , Kajo Karol , Kobzova Daniela , Copakova Lucia , Cermak Martin
Published: August 2017

Perivascular epithelioid cell tumor (PEComas) are a group of ubiquitous neoplasms described in different organs that share distinctive morphologic, immunohistochemical, ultrastructural, and genetic features. They have been reported in several organs such as the uterus, lung, kidney, liver, small and large bowel, and prostate. To the best of our knowledge, only 8 cervical PEComa cases have been described. We report the case of a 43-yr-old woman who presented with abnormal uterine bleeding. Clinical diagnosis of a malignant cervical lesion followed an excision, histopathologically evaluated as PEComa. The hysterectomy specimen confirmed the diagnosis by strong HMB-45 positivity, weak S100 positivity, and focal, moderate cytoplasmic TTF-1 positivity, and negative melan A, SMA, desmin, vimentin, cytokeratins, CD1a and other markers. The patient was negative for tuberous sclerosis complex, did not receive additional therapy, and 3 yr later is disease free. Cervical PEComas are very rare tumors but have to be considered in the differential diagnosis of cervical lesions exhibiting unusual cytologic and immunohistochemical characteristics.
An Evaluation of Perceived Health Risk and Depressive Symptoms Before a Disaster in Predicting Postdisaster Inflammation
Authors: Murdock Kyle W. , Stowe Raymond P. , Peek M. Kristen , Lawrence Savannah L. , Fagundes Christopher P.
Published: August 2017

Objective

Exposure to major life stressors is associated with subsequent enhanced inflammation-related disease processes. Depressive symptoms exacerbate stress-induced inflammatory responses. Moreover, those who report a high degree of perceived health risk before being exposed to a major life stressor such as a disaster are at risk for poor health outcomes. The present study examined whether perceived health risk and depressive symptoms before a disaster were associated with postdisaster inflammation markers.

Methods

The sample included 124 participants (mean [standard deviation] age = 55 [16] years; 69% women). At a baseline visit, participants completed self-report measures of perceived health risk and depressive symptoms (Center for Epidemiologic Studies Depression Scale) in addition to a blood draw for the assessment of inflammation markers (C-reactive protein, tumor necrosis factor receptor 1, and interleukin 6). All participants lived near a large petrochemical complex where an unexpected explosion occurred. A second blood sample was obtained 2 to 6 months after the explosion.

Results

No significant differences in inflammation markers were found between predisaster and postdisaster assessment (p > .21). An interaction between predisaster perceived health risk and depressive symptoms in predicting postdisaster circulating inflammation markers was identified (Cohen f
2 = 0.051). Specifically, predisaster perceived health risk was associated with postdisaster circulating inflammation markers if predisaster depressive symptoms were greater than 8.10 on the Center for Epidemiologic Studies Depression Scale.

Conclusions

These findings add to our understanding of the complex interactions between stress, depression, and immune responses. Indeed, findings provide a potential mechanism (i.e., inflammation) explaining the association between exposure to major life stressors and negative mental and physical health outcomes.
Integrating Household Water Treatment, Hand Washing, and Insecticide-Treated Bed Nets Into Pediatric HIV Care in Mombasa, Kenya: Impact on Diarrhea and Malaria Risk
Authors: Sugar Naomi R. , Schilling Katharine A. , Kim Sunkyung , Ahmed Aabid , Ngui Muyanga Dennis , Sivapalasingam Sumathi , Quick Robert
Published: August 2017

Introduction:

In developing countries, HIV-infected children are at higher risk of morbidity and mortality from opportunistic infections than HIV-uninfected children. To address this problem, the Healthy Living Initiative (HLI) in Mombasa, Kenya distributed basic care packages (BCPs) containing improved water storage vessels, water treatment solution, soap, and insecticide-treated bed nets to prevent diarrhea and malaria in children, and had community health workers (CHWs) make bimonthly home visits to encourage adherence to HLI interventions and antiretroviral (ARV) medicine use.

Methods:

To evaluate HLI, we enrolled 500 HIV-infected children from Bomu Hospital. In the implementation phase, from February to August 2011, we conducted surveys of caregivers, then provided free BCPs. In the evaluation phase, from September 2011 to August 2012, CHWs recorded observations of BCP use during home visits. We abstracted hospital data to compare diarrhea and malaria episodes, and pharmacy data on ARVs dispensed, between the 12-month preimplementation baseline phase (February 2010–January 2011) and the evaluation phase.

Results:

The retention rate of children in HLI was 78.4%. In a multivariable logistic regression model adjusting for demographic characteristics, number of CHW home visits, distance to clinic, orphan status, and number of ARVs dispensed, children in HLI had 71% lower risk of diarrhea (relative risk 0.29, P < 0.001) and 87% lower risk of malaria (relative risk 0.13, P = 0.001) during the evaluation phase than the baseline phase; there was no independent association between ARV use and illness.

Conclusions:

HIV-infected children in HLI were less likely to experience diarrhea and malaria during the evaluation phase than the baseline phase.
Repeatability of Non–Contrast-Enhanced Lower-Extremity Angiography Using the Flow-Spoiled Fresh Blood Imaging
Authors: Zhang Yuyang , Xing Zhen , She Dejun , Huang Nan , Cao Dairong
Published: August 2017

Purpose

The aim of this study was to prospectively evaluate the repeatability of non–contrast-enhanced lower-extremity magnetic resonance angiography using the flow-spoiled fresh blood imaging (FS-FBI).

Methods

Forty-three healthy volunteers and 15 patients with lower-extremity arterial stenosis were recruited in this study and were examined by FS-FBI. Digital subtraction angiography was performed within a week after the FS-FBI in the patient group. Repeatability was assessed by the following parameters: grading of image quality, diameter and area of major arteries, and grading of stenosis of lower-extremity arteries. Two experienced radiologists blinded for patient data independently evaluated the FS-FBI and digital subtraction angiography images. Intraclass correlation coefficients (ICCs), sensitivity, and specificity were used for statistical analysis.

Results

The grading of image quality of most data was satisfactory. The ICCs for the first and second measures were 0.792 and 0.884 in the femoral segment and 0.803 and 0.796 in the tibiofibular segment for healthy volunteer group, 0.873 and 1.000 in the femoral segment, and 0.737 and 0.737 in the tibiofibular segment for the patient group. Intraobserver and interobserver agreements on diameter and area of arteries were excellent, with ICCs mostly greater than 0.75 in the volunteer group. For stenosis grading analysis, intraobserver ICCs range from 0.784 to 0.862 and from 0.778 to 0.854, respectively. Flow-spoiled fresh blood imaging yielded a mean sensitivity and specificity to detect arterial stenosis or occlusion of 90% and 80% for femoral segment and 86.7% and 93.3% for tibiofibular segment at least.

Conclusions

Lower-extremity angiography with FS-FBI is a reliable and reproducible screening tool for lower-extremity atherosclerotic disease, especially for patients with impaired renal function.
Multidetector Computed Tomography Versus Staging Laparoscopy for the Detection of Peritoneal Metastases in Esophagogastric Junctional and Gastric Cancer
Authors: Leeman Matthew F. , Patel Dilip , Anderson Judith , O'Neill J. Robert , Paterson-Brown Simon
Published: August 2017

Objective:

Staging laparoscopy (SL) is the gold standard investigation for detecting peritoneal metastases (PM) in patients with esophagogastric cancer but computed tomography (CT) has undergone significant improvements in recent years. The aim of this study was to investigate whether CT can replace SL in the detection of PM.

Materials and Methods:

Patients undergoing SL between January 2008 and December 2009 were identified from a prospectively collected database, operation notes were reviewed for the detection of PM. Corresponding CTs were reassessed by 2 experienced gastrointestinal radiologists, blinded to the SL results.

Results:

In total, 74 patients undergoing SL were included. Sensitivity and specificity of SL for PM were 94.1% (95% confidence interval, 69.2-99.7) and 100% (90.7-100). Sensitivity and specificity of CT were 58.8% (33.5-80.6) and 89.6% (76.6-96.1), respectively. Area under the curve of receiver operating characteristic curves for SL and CT were 0.971 (SE, 0.033) and 0.742 (SE, 0.78), respectively.

Conclusions:

CT cannot replace SL for the detection of PM in lower esophageal and gastric cancer.
Imputation strategies in the trauma registration
Authors: de Munter Leonie , ter Bogt Nancy C.W. , Hesselink Danique D. , de Jongh Mariska A.C.
Published: August 2017

BACKGROUND

Trauma databases often contain relatively high proportions of missing physiologic values. Multiple imputation (MI) could be a possible adequate solution for the missing values. This study aimed to demonstrate the influence of more simplified imputation models on standardized W statistic (Ws) (number of excess survivors per hundred patients that would be achieved if the study center treated identically the same case mix as the reference population).

METHODS

Data from three trauma care networks in the Netherlands were used to investigate local differences in missing data. Five different imputation models (MI 1 to 5) were created based on literature and expert opinion. A sixth database was created using maximal single imputation and a seventh database with only complete case analysis (CCA). The Ws values were calculated for the three regions separately.

RESULTS

A total of 8,853, 24,487, and 8,599 observations were examined in region 1, region 2, and region 3, respectively. The Ws in region 1 ranged from −0.48 (95% confidence interval [CI], −1.71 to 0.80) for CCA to 0.53 (95% CI, −0.19 to 1.26) for MI 4 and a range of 0.40 (95% CI, −0.91 to 0.10) for CCA to −0.32 (−0.69, 0.04) for MI 1 and MI 4 was found in region 2. The Ws for region 3 ranged from −0.19 (−0.83 to 0.45) in all MI data sets to −0.12 (−0.76 to 0.52) in the CCA data set. Although there were no significant differences between the Ws of the imputation data sets and the CCA analysis, large differences were found in the region with the most missing values.

CONCLUSION

Different imputation strategies did influence Ws values. Supplementary variables showed no additional value for the imputation process and a more simplified imputation model could be used to adequately impute missing data.

LEVEL OF EVIDENCE

Prognostic, level II.
How does marijuana affect outcomes after trauma in ICU patients? A propensity-matched analysis
Authors: Singer Matt , Azim Asad , O’Keeffe Terence , Khan Muhammad , Jain Arpana , Kulvatunyou Narong , Gries Lynn , Jehan Faisal , Tang Andrew , Joseph Bellal
Published: August 2017

INTRODUCTION

In the United States, marijuana abuse and dependence are becoming more prevalent among adult and adolescent trauma patients. Unlike several studies that focus on the effects of marijuana on the outcomes of diseases, our aim was to assess the relationship between a positive toxicology screen for marijuana and mortality in such patients.

METHODS

A 5-year (2008–2012) analysis of adult trauma patients (older than 18 years old) in Arizona State Trauma Registry. We included patients admitted to the intensive care unit (ICU) with a positive toxicology screen for marijuana. We excluded patients with positive alcohol or other substance screening. Outcome measures were mortality, ventilator days, ICU, and hospital length of stay. We matched patients who tested positive for marijuana (marijuana positive) to those who tested negative (marijuana negative) using propensity score matching in a 1:1 ratio controlling for age, injury severity score, and Glasgow Coma Scale.

RESULTS

We included a total of 28,813 patients, of which 2,678 were matched (1,339, marijuana positive; 1,339, marijuana negative). The rate of positive screening for marijuana was 7.4% (2,127/28,813). Mean age was 31 ± 9 years, and injury severity score was 13 (8–20). There was no difference between the two groups in hospital (6.4 days vs. 5.4 days, p = 0.08) or ICU (3 days vs. 4 days, p = 0.43) length of stay. Of the marijuana-positive patients, 55.3% received mechanical ventilation, while 32% of marijuana-negative patients received mechanical ventilation (p < 0.001). On subanalysis of patients who received mechanical ventilation, the marijuana-positive patients had a higher number of ventilator days (2 days vs. 1 day, p = 0.02) and a lower mortality rate (7.3% vs. 16.1%, p < 0.001) than those who were marijuana negative.

CONCLUSION

A positive marijuana screen is associated with decreased mortality in adult trauma patients admitted to the ICU. This association warrants further investigation of the possible physiologic effects of marijuana in trauma patients.

LEVEL OF EVIDENCE

Prognostic studies, level III.
Treatment Response in Pediatric Patients With Pseudotumor Cerebri Syndrome
Authors: Tovia Eliel , Reif Shimon , Oren Asaf , Mitelpunkt Alexis , Fattal-Valevski Aviva
Published: August 2017

Background:

Pseudotumor cerebri syndrome (PTCS) is a disorder defined by increased intracranial pressure in the absence of an intracranial space-occupying lesion. This retrospective study aimed to examine the outcomes in children with PTCS.

Methods:

Data was collected retrospectively from the charts of consecutive pediatric patients treated for PTCS at our hospital between 2000 and 2007 (60 patients; 36 females, 24 males).

Results:

Forty-six patients (76.6%) responded well to acetazolamide therapy, with full resolution of symptoms, including papilledema (average treatment duration 1 year; range: 1 month–5 years). Of the 14 patients with no response to treatment, 9 (23.4%) required surgical intervention. Nonresponders tended to be younger at presentation (8.7 vs 11.5 years, P = 0.04). Twelve patients (26%) experienced relapse after acetazolamide was discontinued. The group that experienced relapse was significantly younger than the nonrelapsers (8.9 vs 12.1 years, P < 0.05).

Conclusions:

Younger age at presentation with PTCS was found to be a risk factor for treatment failure or relapse.
SEA: The small RNA Expression Atlas
Authors: Rahman Raza-Ur , Bansal Vikas , Fiosins Maksims , Liebhoff Anna-Maria , Rajput Ashish , Sattar Abdul , Magruder Daniel Sumner , Madan Sumit , Sun Ting , Gautam Abhivyakti , Heins Sven , Liwinski Timur , Bethune Jörn , Trenkwalder Claudia , Fluck Juliane , Mollenhauer Brit , Bonn Stefan
Published: August 2017

We present the Small RNA Expression Atlas (SEA), a web application that allows for the interactive querying, visualization, and analysis of known and novel small RNAs across ten organisms. It contains sRNA and pathogen expression information for over 4,200 published samples with standardized search terms and ontologies. In addition, SEA allows for the interactive visualization and re-analysis of 879 differential expression and 514 classification comparisons. SEA’s user model enables sRNA researchers to compare and re-analyze user-specific and published datasets, highlighting common and distinct sRNA expression patterns.

We provide evidence for SEA’s fidelity by (i) generating a set of 591 tissue specific miRNAs across 30 tissues, (ii) finding known and novel bacterial and viral infections across diseases, and (iii) determining a Parkinson’s disease-specific blood biomarker signature using novel data.

We believe that SEA’s simple semantic search interface, the flexible interactive reports, and the user model with rich analysis capabilities will enable researchers to better understand the potential function and diagnostic value of sRNAs or pathogens across tissues, diseases, and organisms.

Availability and Implementation

SEA is implemented in Java, J2EE, spring, Django, html5, css3, JavaScript, Bootstrap, Vue.js, D3, mongodb and neo4j. It is freely available athttp://sea.ims.bio/.
Substrate binding and specificity appear as major forces in the functional diversification of eqolisins
Authors: Revuelta María Victoria , Stocchi Nicolas , Castronuovo Priscila Ailín Lanza , Vera Mariano , Have Arjen ten
Published: August 2017

Background

Eqolisins are rare acid proteases found in archaea, bacteria and fungi. Certain fungi secrete acids as part of their lifestyle and interestingly these also have many eqolisin paralogs, up to nine paralogs have been recorded. This suggests functional redundancy and diversification, which was the subject of the research we performed and describe here.

Results

We identified eqolisin homologs by means of iterative HMMER analysis of the NR database. The identified sequences were scrutinized for which we defined novel hallmarks, identified by molecular dynamics simulations of mutants of highly conserved positions, using the structure of an eqolisin that was crystallized in the presence of a transition state inhibitor. Four conserved glycines were shown to be required for functionality. A substitution of W67F is shown to be accompanied by the L105W substitution. Molecular dynamics shows that the W67 binds to the substrate via a π-π stacking and a salt bridge, the latter being stronger in a virtual W67F/L105W double mutant of the resolved structure of Scytalido-carboxyl peptidase-B (PDB ID: 2IFW)). Additional likely fatal mutants are discussed.

Upon sequence scrutiny we obtained a set of 233 sequences that in all likelihood lack false positives. This was used to reconstruct a Bayesian phylogenetic tree. We identified 14 putative specificity determining positions (SDPs) of which four are explained by mere structural explanations and nine seem to correspond to functional diversification related wit substrate binding ans specificity. A first sub-network of SDPs is related to substrate specificity whereas the second sub-network seems to affect the dynamics of three loops that are involved in substrate binding.

Highlights

Eqolisins are acid proteases found in prokaryotes and fungi only.

The recently co-evolved W67F-L105W substitutions promote substrate binding

Two Specificity Determining Networks, SDN1 and 2, were identified

SDN1 has four Specificity Determining Positions involved in substrate specificity

SDN2 has five Specificity Determining Positions involved in loop-substrate dynamics
Piper longum: A review of its phytochemicals and their network pharmacological evaluation
Authors: Choudhary Neha , Singh Vikram
Published: August 2017

Piper longumL. (P. longum, also called as long pepper) is one of the common culinary herb and has been extensively used as an important constituent of various indigenous medicines, specifically in traditional Indian medicinal system known as Ayurveda. Towards obtaining a global regulatory framework ofP. longum’s constituents, in this work we first reviewed phytochemicals present in this herb and then studied their pharmacological and medicinal features using network pharmacology approach. We developed high-confidence level tripartite networks consisting of phytochemicals – protein targets – disease association and explain the role of its phytochemicals to various chronic diseases. 7 drug-like phytochemicals in this herb were found as the potential regulators of 5 FDA approved drug targets; and 28 novel drug targets were also reported. 105 phytochemicals were linked with immunomodulatory potency by pathway level mapping in human metabolic network. A sub-network of human PPI regulated by its phytochemicals was derived and various modules in this sub-network were successfully associated with specific diseases.

Graphical abstract

Abbreviations

P. longum

Piper longumL.

PC

Phytochemical

PT

Protein target

BP

Biological pathways

DA

Disease asscociation

PCt

Number of protein targets corresponding to a particular phytochemical

Tt

Total number of protein targets ofP. longum

ADMET

Absorption, Distribution, Metabolism, Excretion and Toxicity.
Protection of the human gut microbiome from antibiotics
Authors: Gunzburg Jean de , Ghozlane Amine , Ducher Annie , Le Chatelier Emmanuelle , Duval Xavier , Ruppé Etienne , Armand-Lefevre Laurence , Sablier-Gallis Frédérique , Burdet Charles , Alavoine Loubna , Chachaty Elisabeth , Augustin Violaine , Varastet Marina , Levenez Florence , Kennedy Sean , Pons Nicolas , Mentré France , Andremont Antoine
Published: August 2017

Background

Antibiotics are life-saving drugs but severely affect the gut microbiome with short term consequences including diarrhoea,Clostridium difficileinfections and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.

Methods

We performed a randomized controlled trial (ClinicalTrials.govNCT02176005) in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in two parallel groups, with or without DAV132 co-administration. Two control goups of 8 volunteers each receiving DAV132 alone, or a non-active substitute, were added.

Results

The co-administration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibioticsex-vivo.

Conclusions

DAV132 was highly effective to protect the gut microbiome of moxifloxacin - treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.