bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Rotavirus Vaccine Introduction in Children Less Than 2 Years of Age Presenting for Medical Care With Diarrhea in Rural Matlab, Bangladesh
Authors: Schwartz Lauren M , Zaman K , Yunus Md , Basunia Ahasan-ul H , Faruque Abu Syed Golam , Ahmed Tahmeed , Rahman Mustafizur , Sugimoto Jonathan D , Halloran M Elizabeth , Rowhani-Rahbar Ali , Neuzil Kathleen M , Victor John C
Published: February 2019

Background

Following the conclusion of a human rotavirus vaccine (HRV) cluster-randomized, controlled trial (CRT) in Matlab, Bangladesh, HRV was included in Matlab’s routine immunization program. We describe the population-level impact of programmatic rotavirus vaccination in Bangladesh in children <2 years of age.

Methods

Interrupted time series were used to estimate the impact of HRV introduction. We used diarrheal surveillance collected between 2000 and 2014 within the 2 service delivery areas (International Centre for Diarrhoeal Disease Research, Bangladesh [icddr,b] service area [ISA] and government service area [GSA]) of the Matlab Health and Demographic Surveillance System, administered by icddr,b. Age group–specific incidence rates were calculated for both rotavirus-positive (RV+) and rotavirus-negative (RV–) diarrhea diagnoses of any severity presenting to the hospital. We used 2 models to assess the impact within each service area: Model 1 used the pre-vaccine time period in all villages (HRV– and control-only) and Model 2 combined the pre-vaccine time period and the CRT time period, using outcomes from control-only villages.

Results

Both models demonstrated a downward trend in RV+ diarrheal incidences in the ISA villages during 3.5 years of routine HRV use, though only Model 2 was statistically significant. Significant impacts of HRV on RV+ diarrhea incidences in GSA villages were not observed in either model. Differences in population-level impacts between the 2 delivery areas may be due to the varied rotavirus vaccine coverage and presentation rates to the hospital.

Conclusions

This study provides initial evidence of the population-level impact of rotavirus vaccines in children <2 years of age in Matlab, Bangladesh. Further studies are needed of the rotavirus vaccine impact after the nationwide introduction in Bangladesh.
Transmission-blocking Effects of Primaquine and Methylene Blue Suggest Plasmodium falciparum Gametocyte Sterilization Rather Than Effects on Sex Ratio
Authors: Bradley John , Soumaré Harouna M , Mahamar Almahamoudou , Diawara Halimatou , Roh Michelle , Delves Michael , Drakeley Chris , Churcher Thomas S , Dicko Alassane , Gosling Roly , Bousema Teun
Published: February 2019

Gametocyte density and sex ratio can predict the proportion of mosquitoes that will become infected after feeding on blood of patients receiving nongametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.
Trade and nationalism: market integration in interwar Yugoslavia*
Authors: Miladinović Luka
Published: February 2019

This article empirically analyses the relationship between nationalism and regional economic integration in the Kingdom of Yugoslavia between the First and the Second World War. It argues that prevailing nationalism had a negative impact on the economic integration of the regions within the Kingdom and further contributed to the political disintegration of the Kingdom. The analysis implies that the ideology of nationalism increased trade costs and thus retarded economic interconnectivity in the Kingdom of Yugoslavia, notwithstanding the favorable trade environment and the desire of the central elites to discourage ethnocentric sentiment.
Ochratoxin A suppresses proliferation of Sertoli and Leydig cells in mice
Authors: Park Hahyun , Park Hee Seo , Lim Whasun , Song Gwonhwa
Published: February 2019

Ochratoxin A (OTA) is a mycotoxin originating from Penicillium and Aspergillus. In addition to toxic effects in various tissues and cells, including neurons, immune cells, hepatocytes, and nephrons, it also causes carcinogenesis and teratogenesis. Although the negative effects of OTA with respect to the pathogenesis of diseases and the malfunction of various organs have been studied widely, the biological signaling mechanisms in testicular cells are less well known. Therefore, we determined the hazardous effect of OTA in two types of testicular cells: TM3 (mouse Leydig cells) and TM4 (mouse Sertoli cells). Treatment with OTA led to a significant decrease in the proliferation of both cell lines, as revealed by an increased proportion of cells in the sub-G1 phase. In addition, the phosphorylation of signaling molecules belonging to the PI3K (Akt, P70S6K, and S6) and MAPK (ERK1/2 and JNK) pathways was regulated by OTA in a dose-dependent manner in TM3 and TM4 cells. Furthermore, the combination treatment of OTA and signaling inhibitors (LY294002, U0126, or SP600125) exerted synergistic antiproliferative effects in TM3 and TM4 cells. OTA also reduced the concentration of calcium ions in the cytosol and mitochondria, which disrupted the calcium homeostasis necessary for maintaining the normal physiological functions of testicular cells. In conclusion, the results of the present study demonstrate the mechanism underlying the antiproliferative effects of OTA in mouse testicular cells. Exposure to OTA may result in abnormal sperm maturation and the failure of spermatogenesis, which leads to male infertility.
The Price of Natural American Spirit Relative to Other Cigarette Brands
Authors: Epperson Anna E , Johnson Trent O , Schleicher Nina C , Henriksen Lisa
Published: February 2019

Introduction

American Spirit cigarettes feature American Indian/Alaska Native (AI/AN) imagery in the branding and are marketed as environmentally friendly, without additives, and four varieties contain organic tobacco. This study is the first to examine retail price of American Spirit relative to other cigarette brands and to assess how its price varies by neighborhood demography.

Methods

In a random sample of licensed tobacco retailers (n = 1277), trained data collectors recorded availability and price of American Spirit, Pall Mall, Newport, Marlboro, and the cheapest cigarettes regardless of brand. Data were collected in January–March 2017 in California, the state with the largest AI/AN population. Paired t tests assessed prices (before sales tax) of American Spirit relative to others. Ordinary least squares regressions modeled prices as a function of neighborhood demography, adjusting for store type.

Results

American Spirit was sold in 77% of stores at an average price of $7.03 (SD = 0.66), which was $0.75–$1.78 (12.0%–34.4%) higher than Pall Mall, Newport, and Marlboro in the same stores. American Spirit costs significantly less in neighborhoods with a higher proportion of school-age residents; however, this pattern was not unique to that brand. Contrary to expectation, American Spirit did not cost less in neighborhoods with a higher proportion of AI/ANs.

Conclusion

This study is the first to document lower prices for American Spirit in neighborhoods with a higher proportion of school-age youth. Future research should consider whether the ultra-premium price of American Spirit contributes to misperceptions that the brand is organic and less harmful than other cigarettes.

Implications

In a large random sample of licensed tobacco retailers in California, American Spirit costs significantly more than other brands, 12.0%–34.4% more than Pall Mall, Newport, and Marlboro in the same stores. After controlling for store type, American Spirit price was significantly lower in neighborhoods with a higher proportion of school-age residents. Research about how an ultra-premium price contributes to misperceptions that all American Spirit varieties are organic and the brand is less harmful and less addictive than other cigarette brands would be informative for ongoing litigation and product regulation.
Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease
Authors: Nakatsuka Yoshinari , Handa Tomohiro , Nakashima Ran , Tanizawa Kiminobu , Kubo Takeshi , Murase Yuko , Sokai Akihiko , Ikezoe Kohei , Hosono Yuji , Watanabe Kizuku , Tokuda Shinsaku , Uno Kazuko , Yoshizawa Akihiko , Tsuruyama Tatsuaki , Uozumi Ryuji , Nagai Sonoko , Hatta Kazuhiro , Taguchi Yoshio , Mishima Michiaki , Chin Kazuo , Mimori Tsuneyo , Hirai Toyohiro
Published: February 2019

Objective

We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD).

Methods

We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed.

Results

Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions.

Conclusion

Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.
Wheat Virus Identification Within Infected Tissue Using Nanopore Sequencing Technology
Authors: Fellers John P. , Webb Christian , Fellers Madison C. , Shoup Rupp Jessica , De Wolf Erick
Published: February 2019

Viral diseases are a limiting factor to wheat production. Viruses are difficult to diagnose in the early stages of disease development and are often confused with nutrient deficiencies or other abiotic problems. Immunological methods are useful to identify viruses, but specific antibodies may not be available or require high virus titer for detection. In 2015 and 2017, wheat plants containing Wheat streak mosaic virus (WSMV) resistance gene, Wsm2, were found to have symptoms characteristic of WSMV. Serologically, WSMV was detected in all four samples. Additionally, High Plains wheat mosaic virus (HPWMoV) was also detected in one of the samples. Barley yellow dwarf virus (BYDV) was not detected, and a detection kit was not readily available for Triticum mosaic virus (TriMV). Initially, cDNA cloning and Sanger sequencing were used to determine the presence of WSMV; however, the process was time-consuming and expensive. Subsequently, cDNA from infected wheat tissue was sequenced with single-strand, Oxford Nanopore sequencing technology (ONT). ONT was able to confirm the presence of WSMV. Additionally, TriMV was found in all of the samples and BYDV in three of the samples. Deep coverage sequencing of full-length, single-strand WSMV revealed variation compared with the WSMV Sidney-81 reference strain and may represent new variants which overcome Wsm2. These results demonstrate that ONT can more accurately identify causal virus agents and has sufficient resolution to provide evidence of causal variants.
Hypoalbuminemia Is an Independent Risk Factor for 30-Day Mortality, Postoperative Complications, Readmission, and Reoperation in the Operative Lower Extremity Orthopaedic Trauma Patient
Authors: Wilson Jacob M. , Lunati Matthew P. , Grabel Zachary J. , Staley Christopher A. , Schwartz Andrew M. , Schenker Mara L.
Published: February 2019

Introduction:

Malnutrition, as indicated by hypoalbuminemia, is known to have detrimental effects on outcomes after arthroplasty, geriatric hip fractures, and multiple general surgeries. Hypoalbuminemia has been examined in the critically ill but has largely been ignored in the orthopaedic trauma literature. We hypothesized that admission albumin levels would correlate with postoperative course in the nongeriatric lower extremity trauma patient.

Methods:

Patients with lower extremity (including pelvis and acetabulum) fracture who underwent operative intervention were collected from the ACS-NSQIP database. Patients younger than 65 years were included. Patient demographic data, complications, length of stay, reoperation rate, and readmission rate were collected, and patient modified frailty index scores were calculated. Poisson regression with robust error variance was then conducted, controlling for potential confounders.

Results:

Five thousand six hundred seventy-three patients with albumin available were identified, and 29.6% had hypoalbuminemia. Hypoalbuminemic patients had higher rates of postoperative complications [9.3% vs. 2.6%; relative risk (RR) 1.63] including increased rates of: mortality (3.2% vs. 0.4%; RR 4.86, 95% confidence interval 2.66–8.87), sepsis (1.5% vs. 0.5%, RR 2.35), and reintubation (2.3% vs. 0.4%; RR 3.84). Reoperation (5.5% vs. 2.6%, RR 1.74) and readmission (11.4% vs. 4.1%; RR 2.53) rates were also higher in patients with low albumin.

Conclusion:

Hypoalbuminemia is a powerful predictor of acute postoperative course and mortality after surgical fixation in nongeriatric, lower extremity orthopaedic trauma patients. Admission albumin should be a routine part of the orthopaedic trauma workup. Further study into the utility of supplementation is warranted, as this may represent a modifiable risk factor.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Minimally Invasive Surgery for the Treatment of Traumatic Monosegmental Thoracolumbar Burst Fractures
Authors: Trungu Sokol , Forcato Stefano , Bruzzaniti Placido , Fraschetti Flavia , Miscusi Massimo , Cimatti Marco , Raco Antonino
Published: February 2019

Study Design:

This was a retrospective study of the clinical and radiologic outcomes of traumatic thoracolumbar (TL) burst fractures.

Objectives:

We aimed to evaluate the clinical and radiologic outcomes after 6 years of follow-up of 144 patients with monosegmental TL burst fractures treated with percutaneous short-segment pedicle screw fixation, comparing two groups with versus without placement of an intermediate screw at the fractured vertebra.

Summary of Background Data:

Traumatic TL fractures are the most common vertebral fractures, especially at the TL junction (T10–L2). Minimally invasive surgery (MIS) is a valuable treatment option for traumatic TL burst fractures.

Materials and Methods:

The clinical outcomes and radiologic parameters (Cobb angle, midsagittal index, and sagittal index) of 144 patients with traumatic monosegmental TL fractures treated with MIS were evaluated preoperatively, postoperatively, and after 3 and 6 years of follow-up. Patients were categorized into a nonintermediate screw group (nISG) and an intermediate screw group (ISG), and the groups were compared.

Results:

There were 71 patients (49.3%) in the nISG and 73 patients (50.7%) in the ISG. The radiologic parameters improved significantly more from the preoperative evaluation to the 6-year follow-up in the ISG than in the nISG (P<0.025). There were no significant differences in the mean Oswestry Disability Index (ODI) and Visual Analog Scale scores at the 6-year follow-up between the ISG and the nISG: 15.6% (ISG) versus 16.8% (nISG) for ODI (P<0.1) and 2.2 (ISG) versus 2.4 (nISG) for Visual Analog Scale score (P<0.85) (P<0.73).

Conclusions:

MIS showed good clinical outcomes 6 years after surgery in both the ISG and the nISG. The additional intermediate screw significantly improved radiologic parameters but not clinical outcomes.
α5GABAA receptors play a pronociceptive role and avoid the rate-dependent depression of the Hoffmann reflex in diabetic neuropathic pain and reduce primary afferent excitability
Authors: Hernández-Reyes José E. , Salinas-Abarca Ana B. , Vidal-Cantú Guadalupe C. , Raya-Tafolla Guadalupe , Elias-Viñas David , Granados-Soto Vinicio , Delgado-Lezama Rodolfo
Published: February 2019

Diabetic neuropathy is an incapacitating complication in diabetic patients. The cellular and molecular mechanisms involved in this pathology are poorly understood. Previous studies have suggested that the loss of spinal GABAergic inhibition participate in painful diabetic neuropathy. However, the role of extrasynaptic α5 subunit-containing GABAA (α5GABAA) receptors in this process is not known. The purpose of this study was to investigate the role of α5GABAA receptors in diabetes-induced tactile allodynia, loss of rate-dependent depression (RDD) of the Hoffmann reflex (HR), and modulation of primary afferent excitability. Intraperitoneal administration of streptozotocin induced tactile allodynia. Intrathecal injection of α5GABAA receptor inverse agonist, L-655,708, produced tactile allodynia in naive rats, whereas it reduced allodynia in diabetic rats. In healthy rats, electrical stimulation of the tibial nerve at 5 Hz induced RDD of the HR, although intrathecal treatment with L-655,708 (15 nmol) abolished RDD of the HR. Streptozotocin induced the loss of RDD of the HR, while intrathecal L-655,708 (15 nmol) restored RDD of the HR. L-655,708 (15 nmol) increased tonic excitability of the primary afferents without affecting the phasic excitability produced by the primary afferent depolarization. α5GABAA receptors were immunolocalized in superficial laminae of the dorsal horn and L4 to L6 dorsal root ganglion. Streptozotocin increased mean fluorescence intensity and percentage of neurons expressing α5GABAA receptors in dorsal horn and L4 to L6 dorsal root ganglia in 10-week diabetic rats. Our results suggest that spinal α5GABAA receptors modulate the HR, play an antinociceptive and pronociceptive role in healthy and diabetic rats, respectively, and are tonically active in primary afferents.
Nonadherence in Hemodialysis Patients and Related Factors: A Multicenter Study
Authors: Ozen Nurten , Cinar Fatma Ilknur , Askin Dilek , Mut Dilek , Turker Turker
Published: February 2019

Background

Nonadherence to dietary and fluid restrictions, hemodialysis (HD), and medication treatment has been shown to increase the risks of hospitalization and mortality significantly. Sociodemographic and biochemical parameters as well as psychosocial conditions such as depression and anxiety are known to affect nonadherence in HD patients. However, evidence related to the relative importance and actual impact of these factors varies among studies.

Purpose

The aim of this study was to identify the factors that affect nonadherence to dietary and fluid restrictions, HD, and medication treatment.

Methods

This descriptive study was conducted on 274 patients who were being treated at four HD centers in Turkey. The parameters used to determine nonadherence to dialysis treatment were as follows: skipping multiple dialysis sessions during the most recent 1-month period, shortening a dialysis session by more than 10 minutes during the most recent 1-month period, and Kt/V < 1.4. The parameters used to determine nonadherence to dietary and fluid restriction were as follows: serum phosphorus level > 7.5 mg/dl, predialysis serum potassium level > 6.0 mEq/L, and interdialytic weight gain > 5.7% of body weight. The Morisky Green Levine Medication Adherence Scale was performed to determine nonadherence to medication treatment. A patient was classified as nonadherent if he or she did not adhere to one or more of these indices. The Hospital Anxiety and Depression Scale was used to identify patient risk in terms of anxiety and depression. Logistic regression was used to determine the predictors of nonadherence.

Results

The nonadherence rate was 39.1% for dietary and fluid restrictions, 33.6% for HD, and 20.1% for medication. The risk of nonadherence to dietary and fluid restriction was found to be 4.337 times higher in high school graduates (95% CI [1.502, 12.754], p = .007). The risk of nonadherence to HD treatment was 2.074 times higher in men (95% CI [1.213, 3.546], p = .008) and 2.591 times higher in patients with a central venous catheter (95% CI [1.171, 5.733], p = .019). Longer duration in HD resulted in 0.992 times decrease in risk of nonadherence to treatment (95% CI [0.986, 0.998], p = .005).

Conclusions/Implications for Practice

Educational status, being male, having a central venous catheter, and having a short HD duration were found to be risk factors for nonadherence. Nurses must consider the patient's adherence to the dietary and fluid restrictions, HD, and medication treatment at each visit.
Efficacy and toxicity of apatinib combined with or without chemotherapy for patients with advanced or metastatic chemotherapy-refractory gastric adenocarcinoma
Authors: Guo Yesong , Tang Jinhai , Huang Xin-En , Cao Jie
Published: February 2019

Apatinib (Jiangsu HengRui Medicine Co. Ltd), a vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, has been proven to be safe and to significantly prolong survival in advanced chemotherapy-refractory gastric cancer. This study aimed to assess and compare the efficacy and safety of apatinib combined with chemotherapy with that of chemotherapy alone as second- or higher-line treatment in patients with advanced and metastatic gastric or those with metastatic gastroesophageal junction adenocarcinoma (mGC).

Patients with chemotherapy-refractory mGC at Jiangsu Cancer Hospital & Research Institute were prospectively enrolled and assigned into 2 groups at a 2:1 ratio. The first group (combination group) comprised patients with combination treatment (apatinib + chemotherapy), while the second group comprised patients treated with chemotherapy alone (chemotherapy group). The dose of apatinib was 500 mg/d, and the chemotherapy regimens were based on fluoropyrimidine, platinum, and paclitaxel or irinotecan. The primary end points were progression-free survival (PFS).

Between November 2014 and December 2016, 175 patients were enrolled. PFS was significantly improved in the combination group compared with that in the chemotherapy group (8.5 months [95% confidence interval [CI], 6.45–10.54] vs 7.0 months [95% CI, 5.12–8.88] P = .021; hazard ratio (HR): 0.645 [95% CI: 0.429–0.969] P = .035). The disease control rate (DCR) was also higher in the combination group than that in the chemotherapy group (58.4% vs 41.9%, P = .041). Moreover, the incidence of Grade 3 to 4 hand-foot syndrome, proteinuria, and hypertension was significantly different between the 2 groups. Combined therapy (P = .040) and metastatic sites <2 (P = .008) were the independent prognostic factors for disease progression.

Compared with chemotherapy alone, the addition of apatinib to chemotherapy could better improve PFS and DCR with an acceptable safety profile for mGC refractory to 1 or more line of prior chemotherapy.
Clinical significance of tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma
Authors: Han Lu , Li Yun-Jie , Zhang Wei-Di , Song Ping-Ping , Li Hao , Li Sheng
Published: February 2019

Circulating tumor cells (CTCs) are suspected of predicting the prognosis of malignant tumor, but there are few relevant reports specific to esophageal squamous cell carcinoma (ESCC). This study investigated the clinical significance of CTCs in patients with ESCC.

Sixty patients with ESCC were enrolled, from whom CTCs had been tested by our team previously. Peripheral blood samples were obtained from these patients before treatment; and CTCs were assayed by isolation by size of epithelial tumor cells (ISET). Associations between the presence of CTCs and patients’ clinicopathological parameters and clinical outcomes were analyzed.

CTCs were detected in 20 patients (33.3%), who experienced significantly shorter progression-free survival (PFS) than did the CTC-negative patients. Overall, PFS was negatively associated with the number of CTCs. Multivariate analyses showed that a CTC count >2 was a strong independent prognostic indicator of tumor recurrence (hazard ratio [HR] 5.63; 95% confidence interval [CI] 1.77–17.89; P = .003). In the subgroup of 50 patients who underwent R0 resection and postoperative adjuvant radiotherapy or chemotherapy, CTC was a strong, independent, and prognostic indicator of tumor recurrence (HR 10.70; 95% CI, 1.40–81.91; P = .022). The number of CTCs correlated with the T stage (r = 0.26, P = .043) but not with the N or M stage. For subgroups in stages II or I-IIIB or T3 or T3 + T4, the PFS of patients with CTCs > 1 or > 2 was significantly shorter than that of the patients with CTCs ≤ 1 or CTCs ≤ 2. In the stage III or T3 + T4 groups, the PFS of patients with CTCs > 0 was significantly shorter than that of patients with CTC = 0.

This is the first study to report that the CTC detected by ISET is an independent and prognostic indicator of patients’ outcome in ESCC. Consideration of CTCs may improve the accuracy of preoperative staging in ESCC.
Neuromyelitis optica spectrum disorder coincident with renal clear cell carcinoma
Authors: Jin Haiqiang , Hao Hongjun , Nan Ding , Luo Jingjing , Wang Lei , Gao Feng , Huang Yining
Published: February 2019

Rationale:

Detection of aquaporin-4 (AQP4) antibody in cerebrospinal fluid (CSF) was not suggested for the diagnosis of neuromyelitis opica spectrum disorders (NMOSD). However, some patients with NMOSD have only AQP4 antibody positive in CSF but not in serum with unknown cause. Besides, it is rarely reported that NMOSD complicated with renal clear cell carcinoma. So, the relationship between AQP4-Ab, NMOSD and malignant tumors warrants an investigation.

Patients concerns:

A 31-year-old female presented in our hospital with chief complaints of urinary retention and weakness in bilateral lower extremities for more than 10 days.

Diagnoses:

The patient was diagnosed as NMOSD by neuroimaging and laboratory examination, with AQP4 antibody positive only in CSF. Besides, asymptomatic clear cell carcinoma was also found in left kidney.

Interventions:

The patient underwent 2-month immunosuppressive therapy for NMOSD at first, including intravenous administration of immunoglobulin (IVIG) and methylprednisone, with oral drugs of predisone and tacrolimus. After that, Partial nephrectomy of left kidney was performed.

Outcomes:

The patient demonstrated almost complete remission for NMOSD after immunosuppressive therapy, and the renal tumor was cured by partial nephrectomy.

Lesson:

This case indicates that neuromyelitis optica (NMO)-IgG positive only in CSF could have potential association with the etiology of NMOSD, and renal clear cell carcinoma could be found complicated with NMOSD coincidently. Besides, it is necessary to examine NMO-IgG in CSF for patients suspicious with NMOSD, even when the serum test is negative, especially for those with complicated malignant tumors.
Meta-analysis of efficacy and safety of custirsen in patients with metastatic castration-resistant prostate cancer
Authors: Zhang Xuebao , Liu Chu , Li Kui , Wang Ke , Zhang Qiqiang , Cui Yuanshan
Published: February 2019

Custirsen is the second-generation antisense oligonucleotide (ASO), which can reduce cellular levels of clusterin to increase the cytotoxic effect of chemotherapeutic drugs. Our study assessed the efficacy and safety of custirsen in patients with metastatic castration-resistant prostate cancer (mCRPC).

We conducted a comprehensive search to identify all the randomized controlled trials (RCTs) of custirsen for the treatment of mCRPC. The reference lists of the retrieved studies were investigated.

Three publications involving a total of 1709 patients were used in the analysis. We found that overall survival (OS) (P = .25) was not statistically significant in the comparison. Safety assessments indicated custirsen were often associated with complications resulting from neutropenia (P < .001), anaemia (P < .001), thrombocytopenia (P < .001), and diarrhea (P = .002).

Our meta-analysis shows that custirsen has no obvious effect on improving the OS of patients with mCRPC. Adverse reactions were more common among those patients treated with custirsen as compared to those treated with placebo.
Helicobacter pylori infection and risk of salmonella infection
Authors: Salama Rasha I. , Emara Mohamed H. , Mostafa Hanan M. , Abd-Elsalam Sherief , Alnabawy Sherein Mohamed , Elshweikh Samah A. , Zaghloul Mariam Salah
Published: February 2019

Helicobacter pylori (H pylori) infection is the most frequent infection worldwide and it has been postulated that it predisposes to multiple enteric pathogens and diarrheal diseases. Salmonella infection is common in tropical and under developed communities and is associated with wide range of diseases from gastroenteritis to typhoid fever. This study aimed at detecting the impact of H pylori infection on the incidence of salmonella infections.

The study participants were sampled from cohorts of patients in four university hospitals in different Egyptian Governorates. Their age ranged from 20 to 59 years and followed up for a rising Widal test. Case patients (n = 109) were subjects who visited the outpatient clinic because of diarrhea and typhoid like illness. They were either positive for H pylori stool antigen (n = 53) or negative to it (n = 56). All patients were subjected to thorough history taking, clinical examination, routine laboratory investigations, abdominal ultrasonography, H pylori stool antigen detection, and serial Widal test assay.

The proportion of salmonella-infected subjects was lower among case patients with H pylori infection (22.6%) than among those negative for H pylori (33.9%) albeit not statistically significant (adjusted odds ratio [OR], 0.57; 95% confidence interval [CI], 0.24–1.33; P = .21). The association persisted nonsignificant after adjusting for sociodemographic variables (adjusted OR, 0.5; 95% CI, 0.18–1.39; P = .18). In a multivariate analysis that adjusted for sex, dietary habits, socioeconomic status, and educational level subjects who eat outdoors were associated with a significantly greater risk of salmonella typhi infection.

Our findings suggest that there is no association between H pylori infection and salmonella infection in patients presented with typhoid fever or typhoid like illness.
Weighted gene co-expression network analysis reveals modules and hub genes associated with the development of breast cancer
Authors: Qiu Juanjuan , Du Zhenggui , Wang Yao , Zhou Yuting , Zhang Yuanxin , Xie Yanyan , Lv Qing
Published: February 2019

This study aimed to identify modules associated with breast cancer (BC) development by constructing a gene co-expression network, and mining hub genes that may serve as markers of invasive breast cancer (IBC).

We downloaded 2 gene expression datasets from the Gene Expression Omnibus (GEO) database, and used weighted gene co-expression network analysis (WGCNA) to dynamically study the changes of co-expression genes in normal breast tissues, ductal carcinoma in situ (DCIS) tissues, and IBC tissues. Modules that highly correlated with BC development were carried out functional enrichment analysis for annotation, visualization, and integration discovery. The hub genes detected by WGCNA were also confirmed using the Oncomine dataset.

We detected 17 transcriptional modules in total and 4 — namely tan, greenyellow, turquoise, and brown — were highly correlated with BC development. The functions of these 4 modules mainly concerned cell migration (tan module, P = 3.03 × 10−4), the cell cycle (greenyellow module, P = 3.08 × 10−13), cell–cell adhesion (turquoise module, P = .002), and the extracellular exosome (brown module, P = 1.38 × 10−22). WGCNA also mined the hub genes, which were highly correlated with the genes in the same module and with BC development. The Oncomine database confirmed that the expressions levels of 6 hub genes were significantly higher in BC tissues than in normal tissues, with fold changes larger than 2 (all P < .05). Apart from the 2 well-known genes EPCAM and MELK, during the development of BC, KRT8, KRT19, KPNA2, and ECT2 also play key roles, and may be used as new targets for the detection or treatment of BC.

In summary, our study demonstrated that hub genes such as EPCAM and MELK are highly correlated with breast cancer development. However, KRT8, KRT19, KPNA2, and ECT2 may also have potential as diagnostic and prognostic biomarkers of IBC.
Association of serum adiponectin with breast cancer
Authors: Yu Zeping , Tang Shenli , Ma Hongbing , Duan Hong , Zeng Yong
Published: February 2019

Background:

Emerging published studies have indicated that adiponectin is involved in tumorigenesis of breast cancer. However, the results of available studies were inconsistent. The aim of this updated meta-analysis was to assess the association of adiponectin with breast cancer.

Materials and methods:

PubMed, EMBASE, Wanfang databases, and the China National Knowledge Infrastructure (CNKI) were systematically searched from inception to June 2018. The mean difference (MD) with 95% confidence interval (CI) were estimated and pooled to investigate the effect sizes.

Results:

Twenty-seven eligible articles that met the study criteria were included in the current meta-analysis. Overall, there was an evident inverse association between serum adiponectin levels and breast cancer (MD = −0.29, 95%CI = (−0.38, −0.21), P < .001). Asian subgroup showed a significant negative association between serum adiponectin concentrations and breast cancer in subgroup analysis by ethnicity (MD = −2.19, 95%CI = (−3.45, −0.94), P < .001). However, no statistical significance was found in Caucasian subgroup (MD = −0.65, 95%CI = (−1.47, 0.17), P = 0.12). Additionally, a further subgroup analysis of Asian stratified by menopausal status showed higher concentrations of adiponectin in healthy control group, whether they were premenopausal (MD = −0.85, 95%CI = (−1.50, −0.19), P = .01) or postmenopausal (MD = −2.17, 95%CI = (−4.17, −0.18), P = .03). No significant difference was observed concerning the association between serum adiponectin and breast cancer metastasis (MD = −1.56, 95%CI = (−4.90, 1.78), P = .36).

Conclusion:

The current meta-analysis suggests that the serum adiponectin may be inversely associated with breast cancer. Decreased serum adiponectin levels in premenopausal women may also be inversely associated with breast cancer risk other than postmenopausal status. In addition, low serum adiponectin levels in Asian women were more likely to be associated with breast cancer risk than Caucasian women.
Assessment of nutritional status by dual X-Ray absorptiometry in women with rheumatoid arthritis
Authors: Reina Delia , Gómez-Vaquero Carmen , Díaz-Torné Cesar , Solé Joan Miquel Nolla
Published: February 2019

Rheumatoid arthritis (RA) has been related to an impairment of the nutritional status. Body mass index (BMI) has been used but questions arise about how to properly evaluate nutritional status in RA patients. Few studies have evaluated it by dual-energy X-ray absorptiometry.

In women with RA, to analyze:

Case–control study including 89 women with RA. The control group was composed by 100 patients affected by non-inflammatory rheumatic disorders. Study variables included age, RA duration, history, activity and disability, and in relation to nutritional status: BMI, serum albumin (ALB), whole body DXA assessment, and skeletal muscle index (SMI).

Mean age of patients was 62 ± 8 years, mean duration of RA was 14 ± 9 years, mean disease activity score (DAS28) was 3.7 ± 1.4 and mean Health Assessment Questionnaire was 0.88 ± 0.77. BMI was 27.43 ± 5.16 Kg/m2 in patients and 27.78 ± 3.98 Kg/m2 in controls (P: ns). ALB was within normal range in all patients.

By whole body DXA, RA patients presented a statistically significant lower lean mass in all locations and lower fat mass in limbs than controls. Patients had a redistribution of fat mass to trunk. Lean mass directly correlated with fat mass.

Neither BMI nor ALB correlated with DXA parameters.

BMI, appendicular lean mass and SMI correlated inversely with disease duration. Trunk lean mass correlated inversely, and fat mass directly, with RA disability parameters.

RA patients fulfilled criteria of sarcopenia in 44% of cases versus 19% of controls (P <.001). In RA patients, regarding SMI, BMI showed a high specificity to detect sarcopenia (94% of the patients with low BMI had sarcopenia) but low sensitivity (47% of the patients with normal BMI or overweight had sarcopenia).

RA patients have an impairment of nutritional status associated to disease duration that looks like sarcopenia and that is not predicted by BMI.
Clinical characteristics and surgical outcome of prolactinoma in patients under 14 years old
Authors: Zhao Yi , Jin Di , Lian Wei , Xing Bing , Feng Ming , Liu Xiaohai , Wang Renzhi
Published: February 2019

Prolactinoma is one of the most common pituitary tumors, but relatively uncommon in patients under 14 years old. Surgery is the second-line treatment for prolactinoma when patients show resistance or intolerance to medical therapy. There are only a few published series of children who underwent surgery treatment. This study is performed to investigate the clinical manifestation and surgical outcome of pituitary prolactinoma in patients under 14 years old who are resistant or intolerant to medical therapy of dopamine agonist.

Thirty-six cases were included in a retrospective review of patients under 14 years old operated for prolactinoma between December 1987 and December 2015. Preoperative radiological and endocrinal evaluation was performed on every patient. All patients received operation with trans-sphenoidal approach.

Based on enhanced pituitary magnetic resonance imaging (MRI) taken 2 months after the surgery, total resection was achieved in 16 patients (44.4%) and subtotal resection in 20 (55.6%). Thirty-four cases (94.4%) showed remarkable decrease of prolactin (PRL) level 7 days after surgery, and 16 (44.4%) returned to normal. All patients were followed up for 2 years. Tumor regrowth or recurrence occurred in 5 patients and secondary treatment was applied, including drug treatment in 2 patients, second surgery in 2, and radiotherapy in 1.

Trans-sphenoidal pituitary surgery is an effective treatment for prolactinoma in patient under 14 years old. There is no significant difference between the patients under 14 years old and adults for prolactinoma in characteristics and treatment.
Photobiomodulation with simultaneous use of red and infrared light emitting diodes in the treatment of temporomandibular disorder: study protocol for a randomized, controlled and double-blind clinical trial
Authors: Sousa Dowglas Fernando Magalhães de , Gonçalves Marcela Letícia Leal , Politti Fabiano , Lovisetto Renan Didier de Paula , Fernandes Kristianne Porta Santos , Bussadori Sandra Kalil , Mesquita-Ferrari Raquel Agnelli
Published: February 2019

Introduction:

Temporomandibular disorder (TMD) is considered the main cause of orofacial pain of non-dental origin, and a public health problem. The symptomatology is muscular and/or articular pain, restriction of the mandibular range of motion, and changes in the mandibular movement pattern. Due to its complexity there are already treatments using various forms of therapy. Photobiomodulation using light sources, such as low-level laser or light emitting diodes (LED), with different wavelengths, in a single or combined form, allows one more therapeutic resource to be explored. The objective of this study is to evaluate the effects of photobiomodulation with the simultaneous use of red and infrared LEDs, on pain, range of mandibular movements, and on the electrical activity of masticatory muscles in individuals with TMD.

Methods:

A randomized, controlled, double-blind clinical trial is proposed, which will involve 33 individuals (n = 11 per group) of both sexes, ages 18 to 45 years in 3 groups: LED group; placebo group; and control group, submitted to 6 non-consecutive sessions of photobiomodulation totaling 2 weeks of treatment. The Research Diagnostic Criteria for Temporomandibular Disorders—RDC/TMD will be used to assess and determine the participants’ TMD. The pain will be assessed using the Visual Analog Scale – VAS, the mandibular range of motion will be determined with the aid of a digital caliper, and the electrical activity of the masticatory muscles will be verified by electromyography. A mixed plate of 18 red LEDs—660 nm and 18 infrared LEDs—850 nm with power of 3.5 mW per LED, 4.45 mW/cm2, radiant exposure of 5.35 J/cm2, will be used for photobiomodulation. The irradiated area will be 14.13 cm2, and energy of 75.6 J, in the TMJ region and in the bilateral masseter and temporal muscles. Participants from all groups will be reassessed after the first therapeutic intervention, and at the end of treatment.

Discussion:

We expect the use of photobiomodulation with LEDs, infra and red, to reduce pain, improve temporomandibular joint function in patients with TMD, and thus improve the general conditions of the patient.
Association between perioperative hypothermia and surgical site infection
Authors: Bu Ning , Zhao Enfa , Gao Yuan , Zhao Sha , Bo Wang , Kong Zhidong , Wang Qiang , Gao Wei
Published: February 2019

Background:

A majority of reports in the past decade have demonstrated that perioperative hypothermia increases susceptibility to surgical site infection (SSI). However, in recent years, an increasing number of studies did not find an association between hypothermia and the risk of SSI. These contradictory results have given rise to a conflicting issue on whether perioperative hypothermia is associated with SSI risk in surgical patients.

Methods:

We examined the association between perioperative hypothermia and SSI incidence and then integrated available evidence by searching the databases, such as PubMed, Web of Science, Embase, and Cochrane library for potential papers from inception to April 2018. We included studies that reported original data or odds ratio (OR) with 95% confidence intervals (CIs) of the associations. Using fixed-effects models combined the OR with 95% CIs, randomized controlled trials and observational studies were analyzed, respectively, and cohort studies were further analyzed. Sensitivity analyses were performed by omitting each study iteratively, and publication bias was detected using Begg's tests.

Results:

We screened 384 studies, and identified 8 eligible studies, including 2 randomized controlled trials and 6 observational studies (1 case–control study and 5 cohort studies). The pooled OR results in the randomized controlled studies showed that perioperative hypothermia could increase the risk of SSI without heterogeneity (OR, 1.60; 95% CI, 1.14–2.23; I
2 = 0.0%, P = .845). The fixed-effect meta-analysis indicated no association between perioperative hypothermia and SSI risk in observational studies (OR, 0.98; 95% CI, 0.96–1.01; I
2 = 53.2%, P = .058). Furthermore, cohort studies were performed to pool OR by using the fixed-effect model, and the incorporated results also suggested a similar relationship (OR, 1.13; 95% CI, 0.97–1.33; I
2 = 46.4%, P = .113).

Conclusion:

The meta-analysis suggests that perioperative hypothermia is not associated with SSI in surgical patients. However, the 8 eligible studies were mostly cohort studies. Thus, further randomized controlled trials are required to confirm this finding.
Global diabetic kidney disease research from 2000 to 2017
Authors: Zou Lu-Xi , Sun Ling
Published: February 2019

Background:

This study aimed to analyze the scientific outputs of diabetic kidney disease (DKD) research and explore its hotspots and frontiers from 2000 to 2017, using bibliometric methods.

Methods:

Articles in DKD research between 2000 and 2017 were retrieved from the Web of Science Core Collection (WoSCC). We used the VOSviewer 1.6.8 and CiteSpace 5.2 to analyze publication years, journals, countries, institutions, authors, references, and keywords. Keywords with citation bursts were used to analyze the research hotspots and emerging trends.

Results:

We identified 27,577 publications in DKD research from 2000 to 2017. The annual publication number increased with time. Nephrology Dialysis Transplantation published the highest number of articles. The United States was the most influential country with most publications and collaborations with other countries. Harvard University was the leading institute. Parving had the most cited publications. Keywords analysis indicated that the renin–angiotensin system inhibition used to be the most prevalent research topic, while recent research hotspots were podocyte, inflammation, and biomarker. The biomarkers for DKD screening, diagnosis, and prognosis could be a research frontier.

Conclusions:

The number of DKD related publications rapidly increased over the past 2 decades. Our study revealed the structure, hotspots, and evolution trends of DKD research. Further studies and more collaborations are needed.
Severe acute interstitial nephritis induced by valsartan
Authors: Chen Tong , Xu Peng-cheng , Hu Shui-yi , Yan Tie-kun , Jiang Jian-Qing , Jia Jun-ya , Wei Li , Shang Wen-ya
Published: February 2019

Rationale:

Angiotensin receptor blocker (ARB) can increase serum creatinine or potassium levels in patients with renal insufficiency, renal artery stenosis, heart failure or hypovolemia, but hardly cause severe kidney injury in patients without any risk factors. A case of severe acute interstitial nephritis (AIN) induced by valsartan was reported here.

Patient concerns:

A 62-year-old female with nausea for 1 month and acute deterioration of kidney function for 2 weeks was admitted. She had a history of hypertension for 5 months and had taken valsartan 40 mg daily for 4 months. Although the valsartan had been stopped for 2 weeks, the serum creatinine continuously increased after admission. Kidney biopsy demonstrated the eosinophils infiltration in interstitium.

Diagnoses:

AIN induced by valsartan.

Interventions:

The patient was treated with glucocorticoid.

Outcomes:

The serum creatinine decreased gradually and got back to normal level 5 months later. Then therapy of glucocorticoid was stopped. Renal artery stenosis was excluded by computed tomography angiography (CTA).

Lessons:

Although valsartan-induced allergy has been reported previously, AIN was firstly recognized as a severe complication of this drug. We suggest when there is a ARB-associated continuous deterioration of kidney function for patients without renal insufficiency, renal artery stenosis, heart failure or hypovolemia, AIN should be thought of and therapy with glucocorticoid should be considered if necessary.