bluuebunny/crossref_metadata_2025 huggingface dataset:
Breastfeeding with and without the WHO/UNICEF baby-friendly hospital initiative
Authors: Marinelli Alessandra , Del Prete Viola , Finale Enrico , Guala Andrea , Pelullo Concetta Paola , Attena Francesco
Published: November 2019

The World Health Organization and United Nations Children's Fund's Baby-Friendly Hospital Initiative is aimed at the global promotion, protection and support of breastfeeding. In this study, we compared breastfeeding-related information received, knowledge and behaviours among postpartum women in Baby-Friendly Hospital Initiative accredited and non-accredited hospitals. We selected 10 hospitals: 9 non-accredited hospitals in the Campania region in southern Italy and one accredited hospital in the Piedmont region in northern Italy. In total, 786 women (580 (73.8%) in Campania and 206 (26.2%) in Piedmont) in the hospitals’ maternity wards completed a questionnaire comprising 5 sections within 24 to 72hours after giving birth. The questionnaire investigated breastfeeding activities in the days immediately following childbirth, as well as the information provided by health personnel, knowledge about breastfeeding before and during hospitalisation, and participation in antenatal classes. To evaluate the comparison between the 2 regions, we performed at first a bivariate analysis and then a multinomial and a multivariate logistic regression. Compared with Piedmont, in Campania hospitals there was a rate of breastfeeding of 44.3% vs 89.3%, a skin-to-skin contact between mother and child of 74.5% vs 90.7% and first milk feed within 2hours of 15.0% vs 87.2%. The Campania group had fewer problems with child latching. The Campania group reported receiving less information about breastfeeding in general compared with the Piedmont group. In general, both groups showed good basic knowledge about different aspects of breastfeeding. In both regions, about 90% reported that the information received during the antenatal classes simplified the breastfeeding experience. Our study confirms the importance of systematic promotion of breastfeeding and subsequent delivery of adequate support to maternity departments, in accordance with international guidelines.
Differences between congenital-syphilis presenting as sepsis and neonatal sepsis
Authors: Liu Yang , Zhu Yu , Wang Yibin , Wan Chaomin
Published: November 2019

Congenital syphilis (CS) can cause serious impact on the fetus. However, congenital syphilis presenting as sepsis is a critical condition but hardly identified by the clinic for the first time. In this study, we aimed to identify the benefit of earlier and accurate diagnosis for the infants who suffer congenital syphilis presenting as sepsis.

A retrospective study was performed with patients diagnosed of congenital syphilis presenting as sepsis who were the inpatients in the West China Second Hospital between 2011 and 2018. The control group was collected in the neonatal sepsis patients whose blood culture are positive.

Fifty-eight patients were included in the study. In the congenital syphilis group, one patient died and 12 (41.3%) patients get worse to MODS (multiple organ dysfunction syndrome). Symptoms, signs, and lab examinations are found to be significantly different (P < .05) between two groups as below, including rash, palmoplantar desquamation, abdominal distension, splenomegaly, hepatomegaly, etc. And, at the aspect of Hb, PLT, WBC, CRP, ALT, AST, these differences occurred in the different groups. It is obvious that the prognosis of children with syphilis is worse. According to a comparison between the different outcomes in the CS, the worse outcome subgroup of patients is significantly younger and have more severely impaired liver function.

Because of the high mortality of these infants, pediatricians should improve awareness of CS. Syphilis screening is recommended for pregnant women.
Adverse reactions after the use of SonoVue contrast agent
Authors: Hu Chenlu , Feng Yinger , Huang Pintong , Jin Jingfen
Published: November 2019

The aim of this study was to analyze the clinical manifestations of adverse reactions after the use of SonoVue contrast agent from a large retrospective database, and to evaluate the nursing care strategies and the efficacy of standardized procedure for adverse reactions of SonoVue (SPARS).

From January 1, 2012 to December 30, 2018, 34,478 cases of contrast-enhanced ultrasonography were performed in our center. The clinical manifestations of adverse reactions after the use of SonoVue contrast agent were identified and analyzed. The nursing care strategies were evaluated and the outcomes of patients with moderate and severe adverse reactions before and after the application of SPARS were compared.

Of the 34,478 cases, 40 cases (0.12%) of adverse reactions after the use of SonoVue were identified. Adverse reactions included anaphylatic shock, skin allergies, nausea or vomiting, dizziness or headache, numbness, chest distress, back pain, and local reactions of the injection site. Most of the adverse reactions were mild and self-limited. Only 3 cases of anaphylatic shock and 2 cases of severe rash underwent further treatments. The 3 patients who were managed by SPARS recovered quicker and spent less comparing with the other 2 patients who were not.

SonoVue was a safe contrast agent, with few and mostly mild adverse reactions. SPARS may be an efficient way in tackling moderate to severe adverse reactions, although of which the incidence was rare.
Early diagnosis improving the outcome of an infant with epileptic encephalopathy with cytoplasmic FMRP interacting protein 2 mutation
Authors: Zhong Min , Liao Shuang , Li Tingsong , Wu Peng , Wang Yanqin , Wu Fangrui , Li Xiujuan , Hong Siqi , Yan Lisi , Jiang Li
Published: November 2019

Rationale:

Early infantile epileptic encephalopathy (EIEE) 65 was recently shown to be caused by the cytoplasmic FMRP interacting protein 2 (CYFIP2) mutation. To date, only 5 cases have been reported in two articles, and all the outcomes in all cases were poor.

Patient concerns:

In this study, we reported an 8-month-old girl with a 1 month-long history of seizures and developmental delay. Over 1 month later, she developed epileptic spasms in clusters with hypsarrhythmia on electroencephalography.

Diagnosis:

The patient was diagnosed with EIEE 65 and trio-based whole-exome sequencing revealed a causative de novo CYFIP2 mutation c.260G >T (p.Arg87Leu).

Interventions:

The proband was successively treated with multiple antiepileptic drugs, including levetiracetam, phenobarbital, VitB6, topiramate, methylprednisolone, prednisone, valproic acid and vigabatrin.

Outcomes:

After resistance to multiple anti-epileptic drugs over 2 months of treatment, she finally achieved seizure-free several days after vigabatrin administration and her developmental delay steadily improved.

Lessons: Our

case confirmed that CYFIP2 was the pathogenic gene of EIEE 65. We also first demonstrated vigabatrin might be effective for control of seizures and helpful for the improved outcomes of these patients.
A rare case of pituicytoma presenting with severe Cushing disease
Authors: Li Xiaoman , Liu Yang , Miao Yuan , Wang Jinping , Wang Liang , Wang En-Hua
Published: November 2019

Rationale:

Pituicytomas are exceptional rare tumors in the sellar and suprasellar regions with clinical manifestations, such as headache, visual disturbance, hypopituitarism, and decreased libido. Unlike that of common pituitary adenoma, the association between pituicytoma and Cushing disease (CD) is extremely rare. There were only 6 reported cases till now. In the current study, we describe an unusual case of pituicytoma associated with severe CD with a recurrence-free follow-up period of 49 months.

Patient concerns:

A 32-year-old woman was referred to our hospital with moon face, central obesity, and purple stripes on the lower limbs.

Diagnoses:

The plasma cortisol level was 1122 nmol/L. The low-dose dexamethasone suppression test failed to suppress plasma cortisol. This test provided evidence of nonpituitary-dependent CD. However, magnetic resonance imaging demonstrated a sellar mass measuring approximately 7.6 × 5.7 mm. The patient was diagnosed with pituitary microadenoma. Histopathological analysis of the tissue sections based on the findings from the immunohistochemical staining diagnosed it as pituicytoma.

Interventions:

Transsphenoidal surgery was performed to remove the pituitary mass.

Outcomes:

Within 2 months postoperatively, the patient's blood pressure and cortisol level decreased gradually and normalized on the 6th month when other symptoms of CD also disappeared. The patient is presently free from recurrence 49 months after the initial diagnosis.

Lessons:

Based on the postoperative remission, CD was caused by pituitary disorders. A reasonable assumption is that an extremely small coexisting adenoma was not detected by the surgeon and washed out during the dissection. Another possible explanation might be the mass effect caused by this intrasellar lesion.
An unruptured posterior communicating artery aneurysm ruptured during angiography
Authors: Guo Songtao , Wu Xi
Published: November 2019

Introduction

Cerebrovascular imaging is the gold standard for diagnosis of intracranial aneurysms. Rupture of intracranial aneurysm is rare in cerebrovascular angiography, especially in unruptured intracranial aneurysm.

Patient concerns

A 74-year-old woman was admitted to the hospital for sudden onset of left eyelid ptosis for 1 day with no obvious inducement. The patient had a history of hypertension. Physical examination revealed that she had clear consciousness and normal speech, but the left eyelid drooped. The left pupil diameter was 5 mm and light reflex was absent. The left eyeball could not move, and the right eye examinations were normal. The limb muscle strength and muscle tension were normal.

Diagnosis

Bilateral internal carotid artery posterior communicating aneurysm, severe stenosis of the origin of left carotid artery, and right oculomotor nerve palsy.

Interventions

After the hospital, the aneurysm ruptured and hemorrhaged during radiography, and the patient improved after immediate rescue and treatment. On the third day after angiography, the patient's the condition gradually stabilized. Under the general anesthesia, left carotid artery stenosis stent implantation and left posterior communicating artery aneurysm stent assisted coil embolization were performed successfully. On the second day after embolization, the patient's head computed tomography (CT) showed subarachnoid hemorrhage with hydrocephalus. The patient underwent external ventricular drainage. A month later, the patient underwent ventriculoperitoneal shunt.

Outcomes

Six months later, the patient visited our hospital for a follow-up, and she was clear-headed, aphasia, right limb hemiplegia with muscle strength grade II, left side autonomous activities, and the GOS score was 2 points. Head CT showed the ventricles were normal.

Conclusions

Acute oculomotor palsy may be a risk factor for rupture of ipsilateral unruptured aneurysms, but more basic research and clinical trial evidence of intracranial aneurysms are needed to confirm this.
Identification of modules and hub genes associated with platinum-based chemotherapy resistance and treatment response in ovarian cancer by weighted gene co-expression network analysis
Authors: Zhang Luoyan , Zhang Xuejie , Fan Shoujin , Zhang Zhen
Published: November 2019

High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and malignant ovarian tumor.

To identify co-expression modules and hub genes correlated with platinum-based chemotherapy resistant and sensitive HGSOC, we performed weighted gene co-expression network analysis (WGCNA) on microarray data of HGSOC with 12 resistant samples and 16 sensitive samples of GSE51373 dataset.

A total of 5122 genes were included in WGCNA, and 16 modules were identified. Module-trait analysis identified that the module salmon (cor = 0.50), magenta (cor = 0.49), and black (cor = 0.45) were discovered associated with chemotherapy resistant, and the significance for these platinum-resistant modules were validated in the GSE63885 dataset. Given that the black module was validated to be the most related one, hub genes of this module, alcohol dehydrogenase 1B, cadherin 11, and vestigial like family member 3were revealed to be expressional related with platinum resistance, and could serve as prognostic markers for ovarian cancer.

Our analysis might provide insight for molecular mechanisms of platinum-based chemotherapy resistance and treatment response in ovarian cancer.
Comparison of admission serum albumin and hemoglobin as predictors of outcome in children with moderate to severe traumatic brain injury
Authors: Luo Hong-chun , Fu Yue-qiang , You Cheng-yan , Liu Cheng-jun , Xu Feng
Published: November 2019

Hypoalbuminemia and anemia are frequent among in patients with traumatic brain injury (TBI). We assess whether serum albumin and hemoglobin at admission can predict outcome in children with moderate to severe TBI.

This retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale of ≤13.

A total of 213 patients were included of whom 45 died in hospital. Multivariate logistic regression showed that hypoalbuminemia (serum albumin <30 g/L) was independently associated with mortality (adjusted odds ratio [OR] = 3.059; 95% confidence interval [CI]: 1.118–8.371;P = .030) in children with moderate to severe TBI, while anemia (hemoglobin <90 g/L) was not independently associated with mortality (adjusted OR = 1.742; 95% CI: 0.617–4.916;P = .295). Serum albumin was significantly superior to hemoglobin (area under the curve [AUC] 0.738 vs AUC 0.689,P < .05) under receiver operating characteristic curve analysis. Hypoalbuminemia was also associated with reduced 14-day ventilation-free days, 14-day intensive care unit (ICU)-free days, and 28-day hospital-free days.

Serum albumin at admission was superior to hemoglobin in predicting the mortality in children with moderate to severe TBI and also associated with reduced ventilator-free, ICU-free, and hospital-free days.
The genetic variants in calcium signaling related genes influence anti-tuberculosis drug induced liver injury
Authors: Lyu Mengyuan , Zhou Jian , Chen Hao , Bai Hao , Song Jiajia , Liu Tangyuheng , Cheng Yuhui , Ying Binwu
Published: November 2019

Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.

The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.

Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (P
Bonferroni
correction = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686–6.139, P
Bonferroni correction = .003) or dominant model (P
Bonferroni correction = .003), as well as rs117806152 (Additive model: P
Bonferroni correction = .05; dominant model: P
Bonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (P
Bonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (P
Bonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487–6.896, P
Bonferroni correction = .02) and dominant model (P
Bonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.

Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.
Lymph node identification in skin malignancy using indocyanine green transcutaneously study
Authors: Lese Ioana , Leckenby Jonathan Ian , Taddeo Adriano , Constantinescu Mihai , Olariu Radu
Published: November 2019

Introduction:

The incidence of malignant melanoma has been rising steadily over the past decades and Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor with a high mortality rate. Sentinel lymph node (SLN) biopsy is a recommended prognostic tool in primary cutaneous malignant melanomas of intermediate thickness and in all clinically node-negative Merkel cell carcinomas. The gold standard method for identification of SLNs is lymphoscintigraphy, which involves radioactive tracers. Indocyanine green-based near-infrared fluorescence imaging (NIRFI) has been also used for intraoperative SLN identification. We aim to evaluate the diagnostic sensitivity of the VisionSense VS3 NIRFI device for SNL identification. This device uses stereoscopic 3D high definition for both fluorescence and visible light imaging. Our hypothesis is that SLNs may be identified transcutaneously using fluorescent dye injections and NIRFI; therefore, obviating the need for lymphoscintigraphy in the future.

Methods and analysis:

lymph node identification in skin malignancy using indocyanine green transcutaneously is a prospective diagnostic sensitivity study conducted at the Department of Plastic and Hand Surgery at the University Hospital Berne, Inselspital, Switzerland. The study aims at recruiting 93 patients (start date September 2017) to compare the accuracy of VisionSense VS3 camera at identifying SLNs transcutaneously with the current gold standard, lymphoscintigraphy. Moreover, a secondary objective is to determine if anatomical location of the SLN and patient factors (eg, body mass index, age) have an impact on the ability of VisionSense to detect SLNs when compared with the same gold standard.

Trial registration number:

ClinicalTrials.gov NCT 03545334.
Impact of WNT1-inducible signaling pathway protein-1 (WISP-1) genetic polymorphisms and clinical aspects of breast cancer
Authors: Wang Yan , Yang Shi-Hui , Hsu Ping-Wen , Chien Szu-Yu , Wang Chao-Qun , Su Chen-Ming , Dong Xiao-Fang , Zhao Yong-Ming , Tang Chih-Hsin
Published: November 2019

Breast cancer is the most common diagnosed malignancy in women. This study genotyped blood samples from 236 Han Chinese women with breast cancer and 128 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, and rs62514004, to determine whether these WNT1-inducible signaling pathway protein 1 (WISP-1) genetic polymorphisms increase the risk of developing breast cancer. Compared with wild-type (AA) carriers, those carrying the WISP1 rs62514004 AG or AG + GG genetic variants had a greater risk of developing breast cancer. In an evaluation of the association between clinicopathological aspects and the WISP1 SNP rs62514004 in the breast cancer cohort, patients with the GG genotype were less likely than those with the AA genotype to develop stage III/IV disease. Patients carrying the WISP1 rs2929973 GG + TT variant were almost twice as likely as those carrying the GT genotype to have estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors, while those with the WISP1 rs62514004 AG + GG genetic variants were around twice as likely as those with the AA genotype to have HER2-positive tumors. This study details risk associations between WISP1 SNPs and breast cancer susceptibility in women of Han Chinese ethnicity.
The role of IL22 polymorphisms on liver cirrhosis in patients with hepatitis B virus
Authors: Gao Yan-Hang , Li Qing-Quan , Wang Chun-Guang , Sun Jing , Wang Xiao-Mei , Li Ya-Jun , He Xiu-Ting , Xu Hong-Qin , Niu Jun-Qi
Published: November 2019

Glycogen storage disease (GSD) type IX, characterized by liver enlargement and elevated aminotransferase levels, is the most frequent type of GSD. The global incidence of GSD type IXa is only about 1/100,000 individuals. Case reports of GSD type IX are rare in China. We present the first case report of GSD type IXa in Northeast China caused by mutation of PHKA2.

An 11-year-old boy was referred to our hospital because of liver enlargement with consistently elevated transaminase levels over 6 months.

Histopathological results following an ultrasound-guided liver biopsy confirmed a diagnosis of GSD. Further genetic testing showed that the patient had GSD type IXa caused by the c.133C>T mutation in PHAK2.

We placed the patient on a high-protein and high-starch diet and provided hepatoprotective and supportive therapy.

The patient's transaminase levels decreased significantly and were nearly normal at 10-month follow-up.

This is the first reported case of GSD type IXa in Northeast China. We hope that the detailed and complete report of this case will provide a reference for the diagnosis of liver enlargement of unknown etiology in future clinical practice.
Low dose of propranolol treatment is associated with better survival in cirrhotic patients with hepatic encephalopathy
Authors: Lee Pei-Chang , Chen Yu-Ju , Chou Yueh-Ching , Lee Kuei-Chuan , Chen Ping-Hsien , Kao Wei-Yu , Huang Yi-Hsiang , Huo Teh-Ia , Lin Han-Chieh , Hou Ming-Chih , Lee Fa-Yauh , Wu Jaw-Ching , Su Chien-Wei
Published: November 2019

Objective

The use of nonselective beta blockers in cirrhotic patients experiencing complications is controversial. We aimed to investigate the association between propranolol treatment and outcomes for cirrhotic patients with hepatic encephalopathy.

Methods

Using data from the Taiwan National Health Insurance Research Database, we identified 4754 cirrhotic patients newly diagnosed with hepatic encephalopathy between 2001 and 2010. Among them, 519 patients received propranolol treatment and the other 519 patients without exposure to propranolol were enrolled into our study, both of which were matched by sex, age, and propensity score. The Kaplan–Meier method and time-dependent–modified Cox proportional hazards models were employed for survival and multivariate-stratified analyses.

Results

The median overall survival (OS) was significantly longer in the propranolol-treated cohort than in the untreated cohort (3.46 versus 1.88 years, P < 0.001). A dose-dependent increase in survival was observed (median OS: 4.49, 3.29, and 2.46 years in patients treated with propranolol more than 30 , 20–30 , and less than 20 mg/day, respectively [P < 0.001, P = 0.001, and P = 0.079 versus the untreated group]). In addition to reduce the risk of mortality (adjusted hazard ratio, 0.58; P < 0.001), propranolol also diminished the risk of sepsis-related death (adjusted hazard ratio, 0.31; P = 0.006) according to the multivariate analysis. However, the risk of circulatory or hepatic failure was nonsignificantly altered by propranolol treatment.

Conclusion

Low dose of propranolol treatment was associated with a better OS in cirrhotic patients with hepatic encephalopathy and its effects were dose dependent.
Diagnostic performance of real-time tissue elastography in chronic hepatitis C patients with sustained virological response
Authors: Tachi Yoshihiko , Hirai Takanori , Kojima Yuko , Tachino Haruhiko , Hosokawa Chikao , Ohya Takahiro , Yasue Yuji , Kurokawa Yuta , Torii Yoshinori , Yamamoto Satoshi , Matsuura Hironao , Kobayashi Takashi , Miyoshi Hironao , Inui Kazuo , Katano Yoshiaki
Published: November 2019

Background and aims:

Real-time tissue elastography is a non-invasive method for measuring liver elasticity. However, there are no reports evaluating the value of real-time tissue elastography for liver fibrosis in hepatitis C virus-infected patients with sustained virological response. The aim of this study is to clarify the diagnostic performance of real-time tissue elastography in patients with sustained virological response.

Methods:

In this prospective study, we enrolled 425 chronic hepatitis C patients who underwent liver biopsy: 118 patients with sustained virological response (45.8% women) and 307 patients with hepatitis C virus (51.1% women). The post-sustained virological response biopsy was performed 5.9 ± 1.8 years after the therapy. Liver fibrosis index measurements as assessed using real-time tissue elastography were performed on the same day of biopsy.

Results:

The respective mean liver fibrosis index values for fibrosis stages F0, F1, F2, F3, and F4 were 2.82 ± 0.33, 2.90 ± 0.51, 3.06 ± 0.58, 3.65 ± 0.24, and 3.83 ± 0.65, respectively, in patients with sustained virological response. The diagnostic accuracies expressed as areas under the receiver operating characteristic curves in patients with sustained virological response were 0.776 for the diagnosis of significant fibrosis (≥F2), 0.885 for severe fibrosis (≥F3), and 0.860 for cirrhosis (F4), respectively. The optimum cut-off values liver fibrosis index were 3.14 for ≥F2, 3.24 for ≥F3, and 3.30 for F4 in patients with sustained virological response.

Conclusion:

Real-time tissue elastography is an acceptable method for predicting the severity of fibrosis in hepatitis C virus patients with sustained virological response.
Correlation of serum zinc levels with pathological and laboratory findings in patients with nonalcoholic fatty liver disease
Authors: Ito Takanori , Ishigami Masatoshi , Ishizu Yoji , Kuzuya Teiji , Honda Takashi , Ishikawa Tetsuya , Toyoda Hidenori , Kumada Takashi , Fujishiro Mitsuhiro
Published: November 2019

Objective

Chronic liver diseases are associated with zinc (Zn) deficiency. However, no previous studies have examined the relationship between serum Zn levels and hepatic pathological findings in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the serum Zn levels in NAFLD patients based on pathological/laboratory findings.

Methods

We evaluated a total of 191 NAFLD patients who underwent liver biopsy with the goal of identifying laboratory markers and pathological findings associated with serum Zn levels.

Results

Zn levels significantly decreased along with progression of hepatic fibrosis (P = 0.039), but there were no significant differences among inflammatory grades. Zn levels were most strongly correlated with albumin levels (r = 0.410, P < 0.001). In addition, Zn levels were significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) (r = −0.284, P < 0.001), hyaluronic acid (r = −0.230, P < 0.001), branched chain amino acid/tyrosine molar ratio (BTR) (r = 0.278, P < 0.001), FIB-4 index (r = −0.238, P < 0.001), and NAFLD fibrosis score (NFS) (r = −0.261, P < 0.001). In multivariate analysis, albumin [odds ratio (OR), 9.244 (per 1 g/dL decrease) [95% confidence interval (CI), 2.261–32.744]; P < 0.001], BTR [OR, 1.545 (per 1 decrease) (95% CI, 1.115–2.140); P = 0.009], and HOMA-IR [OR, 1.048 (per 1 increase) (95% CI, 1.019–1.167); P = 0.028] were significantly associated with Zn deficiency.

Conclusion

The progression of liver fibrosis, but not inflammation, is associated with lower serum Zn levels in biopsy-proven NAFLD patients. Serum Zn levels were correlated with nutrition markers and insulin resistance.
Validating the New Primary Care Measure in the Medical Expenditure Panel Survey
Authors: Olaisen R. Henry , Flocke Susan A. , Smyth Kathleen A. , Schluchter Mark D. , Koroukian Siran M. , Stange Kurt C.
Published: November 2019

Background:

The advancement of primary care research requires reliable and validated measures that capture primary care processes embedded within nationally representative datasets.

Objective:

The objective of this study was to assess the validity of a newly developed measure of primary care processes [Medical Expenditure Panel Survey (MEPS)-PC] with preliminary evidence of moderate to excellent reliability.

Study Design:

A retrospective cohort study of community-dwelling adults with history of office-based provider visit/s using the MEPS (2013–2014).

Methods:

The 3 MEPS-PC subscales (Relationship, Comprehensiveness, and Health Promotion) were tested for construct validity against known measures of primary care: Usual Source of Care, Known Provider, and Family-Usual Source of Care. Concurrent and predictive logistic regression analyses were calculated and compared with a priori hypotheses for direction and strength of association.

Results:

For concurrent validity, all odds ratio estimates conformed with hypotheses, with 91% displaying statistical significance. For predictive validity, all estimates were in the direction of hypotheses, with 92% displaying statistically significant results. Although Relationship and Health Promotion subscales conformed uniformly with hypotheses, the Comprehensiveness subscale yielded significant results in 60% of bivariate odds ratio estimates (P<0.05).

Conclusion:

The MEPS-PC composite measures display modest to strong preliminary evidence of concurrent and predictive validity relative to known indicators of primary care.

Implications for Policy and Practice:

The MEPS-PC composite measures display preliminary evidence of concurrent and predictive construct validity, and it may be useful to researchers investigating primary care processes and complexities in the health care environment.
Evaluating the Role of Past Clinical Information on Risk Adjustment
Authors: Lin John K. , Hong Juliette , Phibbs Ciaran , Almenoff Peter , Wagner Todd
Published: November 2019

Objective:

The objective of this study was to evaluate whether incorporating historical clinical information beyond 1 year improves risk adjustment.

Data Sources:

Administrative data from the Department of Veterans Affairs and Medicare (for veterans concurrently enrolled in Medicare) for fiscal years (FYs) 2011–2015.

Study Design:

We regressed total annual costs on Medicare hierarchical condition category indicators and risk scores for FY 2015 in both a concurrent and a prospective model using 5-fold cross-validation. Regressions were repeated incorporating clinical information from FY 2011 to 2015. Model fit was appraised using R
2 and mean squared predictive error (MSPE).

Data Collection:

All veterans affairs users (n=3,254,783) with diagnostic information FY 2011–2015.

Principal Findings:

In a concurrent model, adding additional years of historical clinical information (FY 2011–2014) did not result in substantive gains in fit (R
2 from 0.671 to 0.673) or predictive capability (MSPE from 1956 to 1950). In a prospective model, adding additional years of historical clinical information also did not result in substantive gains in fit (R
2 from 0.334 to 0.344) or predictive capability (MSPE from 3988 to 3940).

Conclusion:

Incorporating historical clinical information yielded no material gain in risk adjustment fit.
Changes in Medicaid Acceptance by Substance Abuse Treatment Facilities After Implementation of Federal Parity
Authors: Geissler Kimberley H. , Evans Elizabeth A.
Published: November 2019

Background:

Adequate access for mental illness and substance use disorder (SUD) treatment, particularly for Medicaid enrollees, is challenging. Policy efforts, including the Mental Health Parity and Addiction Equity Act (MHPAEA), have targeted expanded access to care. With MHPAEA, more Medicaid plans were required to increase their coverage of SUD treatment, which may impact provider acceptance of Medicaid.

Objectives:

To identify changes in Medicaid acceptance by SUD treatment facilities after the implementation of MHPAEA (parity).

Research Design:

Observational study using an interrupted time series design.

Subjects:

2002–2013 data from the National Survey of Substance Abuse Treatment Services (N-SSATS) for all SUD treatment facilities was combined with state-level characteristics.

Measures:

Primary outcome is whether a SUD treatment facility reported accepting Medicaid insurance.

Results:

Implementation of MHPAEA was associated with a 4.6 percentage point increase in the probability of an SUD treatment facility accepting Medicaid (P<0.001), independent of facility and state characteristics, time trends, and key characteristics of state Medicaid programs.

Conclusions:

After parity, more SUD treatment facilities accepted Medicaid payments, which may ultimately increase access to care for individuals with SUD. The findings underscore how parity laws are critical policy tools for creating contexts that enable historically vulnerable and underserved populations with SUD to access needed health care.
Precision Medicine in Pancreatic Disease—Knowledge Gaps and Research Opportunities
Authors: Lowe Mark E. , Andersen Dana K. , Caprioli Richard M. , Choudhary Jyoti , Cruz-Monserrate Zobeida , Dasyam Anil K. , Forsmark Christopher E. , Gorelick Fred S. , Gray Joe W. , Haupt Mark , Kelly Kimberly A. , Olive Kenneth P. , Plevritis Sylvia K. , Rappaport Noa , Roth Holger R. , Steen Hanno , Swamidass S. Joshua , Tirkes Temel , Uc Aliye , Veselkov Kirill , Whitcomb David C. , Habtezion Aida
Published: November 2019

A workshop on research gaps and opportunities for Precision Medicine in Pancreatic Disease was sponsored by the National Institute of Diabetes and Digestive Kidney Diseases on July 24, 2019, in Pittsburgh. The workshop included an overview lecture on precision medicine in cancer and 4 sessions: (1) general considerations for the application of bioinformatics and artificial intelligence; (2) omics, the combination of risk factors and biomarkers; (3) precision imaging; and (4) gaps, barriers, and needs to move from precision to personalized medicine for pancreatic disease. Current precision medicine approaches and tools were reviewed, and participants identified knowledge gaps and research needs that hinder bringing precision medicine to pancreatic diseases. Most critical were (a) multicenter efforts to collect large-scale patient data sets from multiple data streams in the context of environmental and social factors; (b) new information systems that can collect, annotate, and quantify data to inform disease mechanisms; (c) novel prospective clinical trial designs to test and improve therapies; and (d) a framework for measuring and assessing the value of proposed approaches to the health care system. With these advances, precision medicine can identify patients early in the course of their pancreatic disease and prevent progression to chronic or fatal illness.
FGD4 (Frabin) Overexpression in Pancreatic Neuroendocrine Neoplasms
Authors: Shahid Mohammad , George Tarra B. , Saller James , Haija Mohammad , Sayegh Zena , Boulware David , Strosberg Jonathan , Chakrabarti Ratna , Coppola Domenico
Published: November 2019

Objective

The pathogenesis of pancreatic neuroendocrine tumors (PNETs) is still unclear. We propose Frabin as a new molecular alteration in PNETs. Frabin is a guanine nucleotide exchange factor playing a role in mediating actin cytoskeleton changes during cell migration, morphogenesis, polarization, and division.

Methods

Patients with PNETs of different grades were assessed for Frabin expression using immunohistochemistry and tissue microarray. The tissue microarray included 12 grade 1 and 3 grade 2 PNETs and 14 grade 3 pancreatic neuroendocrine carcinomas (PECAs). Frabin immunostain was scored with Allred system. Statistical analysis used SAS and R software. Immunohistochemistry scores were correlated with tumor grade and stage. The Spearman correlation coefficient was calculated with P values.

Results

Pancreatic neuroendocrine tumors were graded according to the World Health Organization 2017 guidelines. Frabin was expressed by 24 (82.7%) of the PNET/PECA studied. Only 5 (17.2%) of the 29 PNETs/PECA evaluated were Frabin negative. Frabin expression was cytoplasmic in all cases. We found a significant positive correlation (ρ = 0.47) between Frabin immunohistochemistry score and tumor grade (P = 0.01). No correlation was found between Frabin expression and tumor stage (P = 0.91).

Conclusions

We report Frabin overexpression as a novel molecular alteration occurring in PNETs/PECAs.
Severe Acute Pancreatitis in Autopsies Associated With Surgeries and Severe Inflammatory Diseases
Authors: Matsuda Yoko , Masuda Yoshishige , Shimoji Keigo , Matsukawa Miho , Kinowaki Yuko , Fukumura Yuki , Kikuyama Masataka , Arai Tomio
Published: November 2019

Objective

We clarified clinicopathological characteristics of acute pancreatitis in terminal patients.

Methods

Pathological changes in the entire pancreas from serial autopsies (N = 183) classified lesions into the following 3 categories: focal neutrophil infiltration, focal necrotizing pancreatitis, and diffuse necrotizing pancreatitis. The former two are possible precursors of diffuse necrotizing pancreatitis. Immunohistochemical staining was performed to analyze pancreatic stellate cells and inflammatory cells.

Results

There were pathologically acute pancreatitis in 45 patients (24.6%), and no patients were diagnosed with it before autopsy. Focal neutrophil infiltration was present in 22 cases, focal necrotizing pancreatitis in 18 cases, and diffuse necrotizing pancreatitis in 5 cases. Severe inflammatory disease and surgery were associated with acute pancreatitis. Sepsis due to viral or bacterial infection was the most common cause of acute pancreatitis. Patients with diffuse necrotizing pancreatitis showed low white blood cell counts, while amylase levels were not increased. Increase in α-smooth muscle actin and nestin-positive stellate cell numbers in acute pancreatitis was correlated to increase in numbers of CD34-positive vascular endothelium, CD68- or CD163-positive macrophages, CD138-positive plasmacytes, CD3-positive T lymphocytes, and myeloperoxidase-positive leucocytes.

Conclusions

Necrotizing pancreatitis without typical clinical signs was frequently detected in autopsy samples. Clinicians must be mindful of necrotizing pancreatitis in terminal patients.
Drug-Induced Acute Pancreatitis in Adults
Authors: Simons-Linares C. Roberto , Elkhouly Mohamed A. , Salazar Miguel J.
Published: November 2019

Drug-induced acute pancreatitis (DIAP) is a rare entity that is often challenging for clinicians. The aim of our study was to provide updated DIAP classes considering the updated definition of acute pancreatitis (AP) and in light of new medications and new case reports. A MEDLINE search (1950–2018) of the English language literature was performed looking for all adult (≥17 years old) human case reports with medication/drug induced as the cause of AP. The included case reports were required to provide the name of the drug, and diagnosis of AP must have been strictly established based on the revised Atlanta Classification criteria. A total of 183 medications were found to be implicated in 577 DIAP cases. A total of 78 cases were excluded because of minimal details or lack of definite diagnosis of AP. Drug-induced AP is rare, and most drugs cause mild DIAP. Only 2 drugs are well described in the literature to explain causation rather than association (azathioprine and didanosine). Larger case-control studies and a formal standardized DIAP reporting system are essential to study the true potential of the DIAP-implicated drugs described in this review.
Performance Characteristics of Magnetic Resonance Imaging in Patients With Pancreas Divisum
Authors: Shah Rushikesh , Mekaroonkamol Parit , Patel Vaishali A. , Raphael Kara , Dacha Sunil , Keilin Steven A. , Cai Qiang , Mittal Pardeep , Willingham Field F.
Published: November 2019

Objective

This study was designed to assess the diagnostic accuracy of standard nonsecretin-enhanced preprocedural magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) in patients with and without pancreas divisum.

Methods

Patients undergoing MRI/MRCP followed by endoscopic retrograde cholangiopancreatography with between 2009 and 2016 were reviewed. The diagnostic accuracy of the MRI/MRCP was evaluated against the pancreatography. A subsequent independent blinded re-review performed by an expert abdominal radiologist was also evaluated. Multivariate binary logistic regression was performed to assess the impact of clinicopathologic factors on the diagnostic accuracy.

Results

A total of 189 patients were included in analysis. The sensitivity, specificity, positive predictive value, and negative predictive value of MRI/MRCP for pancreas divisum were 63%, 97%, 94%, and 82% initially and 81%, 91%, 91%, and 82% on the expert review. Motion artifact, the presence of pancreatic tumor, and pancreatic necrosis were not found to significantly impact the accuracy. A normal diameter pancreatic duct (P = 0.04) and complete divisum anatomy were correlated with improved accuracy (P = 0.001).

Conclusions

Although expert review, normal duct diameter, and complete divisum are associated with increased sensitivity, pancreas divisum may be uncharacterized by preprocedural MRI in 19% to 37% of patients before the index endoscopic retrograde cholangiopancreatography.
Xenografts Derived From Patients' Ascites Recapitulate the Gemcitabine Resistance Observed in Pancreatic Cancer Patients
Authors: Machinaga Akihito , Hori Yuichi , Shimizu Kazuya , Okahara Kyohei , Yanagita Emmy , Miyoshi Makoto , Itoh Tomoo , Sasai Ken
Published: November 2019

Objectives

Most patient-derived pancreatic ductal adenocarcinoma (PDAC) xenografts have been established from surgical specimens of patients who have not received chemotherapy. However, xenografts have rarely been established from chemotherapy-resistant, advanced PDACs, because such cases are usually inoperable. The purpose of this study is to establish patient-derived xenografts using PDAC cells refractory to chemotherapy.

Methods

Clinical PDAC cells obtained from ascites of patients who had received continuous chemotherapy were implanted into the flanks of immunocompromised mice. Growth and histological features of the xenografts with and without gemcitabine treatment were then analyzed.

Results

Ascites-derived PDAC cells were successfully expanded through serial xenograft passage without changes in histological appearance. While treatment with gemcitabine substantially inhibited the growth of all PDAC xenografts tested, the tumor volume gradually increased, and the tumors showed marked regrowth even under continued gemcitabine treatment. These findings are consistent with the actual clinical course of the corresponding patients for each xenograft.

Conclusions

Ascites-derived xenograft models represent a valuable experimental system for testing the efficacy of currently available therapeutic compounds on chemotherapy-resistant PDAC cells and for elucidation of the mechanisms underlying chemotherapy resistance.
The Adolescent and Caregiver Sickle Cell Disease Self-management Skills Checklist: Preliminary Reliability and Validity
Authors: Loew Megan , Williams Justin L. , Russell Kathryn , Rupff Rebecca , Hankins Jane S. , Porter Jerlym
Published: November 2019

Adolescents with sickle cell disease (SCD) need assistance in developing the knowledge and skills that contribute to increased disease self-management and successful transition to adult-based health care. This study evaluated the preliminary psychometric properties of the Self-Management Skills Checklist (SMSC and SMSC-C; Adolescent and Caregiver versions), a measure of perceived SCD-specific knowledge and skills. A retrospective cohort study included 114 adolescents (mean=15.6 y) and their caregivers. We examined internal structure and reliability, score changes over time, and group differences. Cronbach coefficient alphas were 0.79 and 0.74 for caregiver-reported Skills and caregiver-reported knowledge, respectively, and 0.77 and 0.44 for adolescent-reported skills and adolescent-reported knowledge, respectively, indicating good internal consistency for 3 of the subscales. Poor reliability in the adolescent-reported knowledge summary score and factor analysis suggest an interpretation item-by-item, independent of one another. Participant group differences in age and chronic transfusion treatment existed in both summary and subscale scores of the SMSC and SMSC-C. Follow-up administrations of the scales indicated an increase in caregiver-reported skills for their adolescents from time 1 scores (M=3.72±0.83) to time 2 scores (M=3.99±0.63) (t16=2.178,P=0.045). Findings provide preliminary support for the usage of the SMSC and continued development to improve its psychometrics.
Dasatinib-induced Chylothorax in Chronic Myelogenous Leukemia in Pediatric Patient: Report of a Case and Review of Literature
Authors: Hickman Kyle , Diaz Elizabeth , Graham Robert , Adams Roberta , Ngwube Alex
Published: November 2019

Dasatinib is a second-generation potent and efficacious oral tyrosine kinase inhibitor frequently used for imatinib-resistant or intolerant BCR-ABL–positive chronic myeloid leukemia and for Philadelphia chromosome–positive acute lymphocytic leukemia. Dasatinib is known to cause adverse pulmonary events such as chylothorax and has been described in the adult literature but not pediatric literature. The authors present a pediatric case of dasatinib-related chylothorax, subsequent management, and a review of the literature of adult cases with dasatinib-related chylothorax.
Pediatric Extraskeletal Ewing Sarcoma Originating in the Heart: A Case Report and Review of the Literature
Authors: Buffoni Isabella , Nuri Halkawt , Pome’ Giuseppe , Sementa Angela R. , Stagnaro Nicola , Barra Salvina , Manzitti Carla , Garaventa Alberto
Published: November 2019

Extraosseous Ewing sarcoma of primary cardiac origin is an extremely rare variety among pediatric cardiac neoplasms. We report a case of extraosseous Ewing sarcoma of primary cardiac origin in a 9-year-old girl, treated with debulking surgery, adjuvant chemotherapy, and radiotherapy.
Primary Pancreatic Neuroblastoma in an Infant
Authors: Morrison Zachary D. , Sun Yeping , Manalang Michelle , Dominguez Kathleen
Published: November 2019

A 2-month-old girl with conjugated hyperbilirubinemia was found at the surgery and by computed tomography to have a large mass originating in the pancreas. Histopathology, molecular testing, and staging evaluations showed this to be a stage 3, MYCN unamplified, intermediate-risk neuroblastoma. The patient had a partial response to risk-stratified chemotherapy. The mass remained unresectable, but the response was sustained after 18 months. Although fewer than a dozen cases of primary pancreatic neuroblastoma have been reported, our experience and a literature review suggest that these tumors can be managed in the same way as similar-risk neuroblastoma of other sites.