bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets in China
Authors: Zhang Lingxia , Li Zhenfei , Ma Gaiying , Han Xu , Li Cancan , Shan Mingyue , Chen Liping
Published: December 2018

Objective:

In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT).

Method:

A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were “Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets,” and “poisoning,” or “toxicity,” in Chinese and in English.

Result:

Ten articles including 104 patients with CPEHTT intoxication were identified. The ages of the patients ranged from 52 to 82 years. Sixty-seven patients were male and thirty-seven patients were female (the male/female ratio, approximately 2:1). The most common clinical manifestations were dizziness (85%) and ataxia (85%), followed by limb weakness (65%), diplopia (25%), binocular horizontal nystagmus (24%), limb numbness (13%), nausea and vomiting (12%), somnolence (10%), tremor and high muscle tension (7%), lag in response (5%), dysarthria (6%), choking cough (2%), auditory hallucination and visual fantasy (1%), and involuntary movement (1%). All patients had chronic lung disease, and the most common disease was chronic bronchitis. The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients.

Conclusion:

The CPEHTT intoxication caused by phenytoin toxicity represents a drug safety problem in China. The common clinical manifestations, serum phenytoin concentrations, and associated factors of CPEHTT intoxication are important for diagnosis and prevention. These findings may help guide clinicians to correctly attend to the use of CPEHTT and avoid its toxicity.
Fuling Sini decoction for patients with chronic heart failure
Authors: Huang Lijie , Cai Hairong , Zhuang Jieqin , Chen Yanhong , Jin Zilin , Zhang Haobo , Gao Huanjia
Published: December 2018

Background:

Chronic heart failure (CHF) is one of the most important cardiovascular diseases worldly, with high morbidity and mortality. Fuling Sini decoction (FSD) has been used in the management of CHF widely in China, while its effective evidence is not clear. A systematic review and meta-analysis to evaluate FSD for CHF is lacking. Hence, we propose a protocol for systematic evaluation of its efficacy and safety for CHF.

Methods:

We will search the following electronic databases from inception to October 2018, including EMBASE, Cochrane Center Registration Controlled trials (Cochrane Library), PubMed, Medline, WHO International Clinical Trials Registry Platform, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wan-fang database. Only randomized controlled trials (RCTs) of FSD alone or combined with other management for CHF will be included. Two independent reviewers will screen the literature and extract data according to the Cochrane Handbook method. The assessment of bias risk, data synthesis, subgroup analysis, and meta-analyses and finally meta-analysis will be performed by using RevMan V.5.3.5 software.

Results:

This systematic review will provide high-quality evidence and may be the first to evaluate efficacy and safety of FSD in the treatment of CHF.

Conclusion:

This systematic review will provide evidence for judging whether FSD is an effective management for CHF or not.

PROSPERO registration number:

CRD 42018110210.
FIB-4 index serves as a noninvasive prognostic biomarker in patients with hepatocellular carcinoma
Authors: Zhang Yi , Wang Rong , Yang Xianjin
Published: December 2018

Background:

Liver fibrosis index FIB-4 has been reported to be linked with hepatocellular carcinoma (HCC) prognosis, but the results were not consistent. This study aimed to synthetically explore the relationship between FIB-4 and clinical outcomes of HCC.

Methods:

A number of online databases were searched for relevant articles published before March 1, 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated to assess the prognostic value of the FIB-4 index in patients with HCC using Stata SE 12.0.

Results:

Eight articles (including 10 cohort studies) with 3485 HCC patients were finally included for analysis. The pooled results showed that FIB-4 index was significantly associated with overall survival (OS) for patients with HCC (HR = 1.74, 95% CI: 1.41–2.07, P <.001). And HCC patients with higher FIB-4 score were at significantly greater risk of recurrence 1.53 (95% CI: 1.29–1.78, P <.001). Subgroup analysis based on the treatment, stage and analysis type also confirmed the prognostic values of the FIB-4 score for OS and recurrence-free survival (RFS) in HCC.

Conclusions:

FIB-4 index might be a useful predictive marker in patients with HCC.
PRISMA—efficacy and safety of lixisenatide for type 2 diabetes mellitus
Authors: Wei Zhen-gang , Wang Man-cai , Zhang Hui-han , Wang Zhe-yuan , Wang Gen-nian , Wei Feng-xian , Zhang Ya-wu , Xu Xiao-dong , Zhang You-cheng
Published: December 2018

Objective:

We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus.

Methods:

PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety.

Results:

Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75–2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54–3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia.

Conclusions:

Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.
Investigation of the clinical significance and prognostic value of microRNA-145 in human hepatocellular carcinoma
Authors: Li Ping , Fan Hua , He Qiang
Published: December 2018

We aimed to investigate the clinical significance and prognostic value of miR-145 in hepatocellular carcinoma (HCC).

HCC tissue samples and adjacent normal liver tissues were obtained from 139 patients diagnosed with HCC. The relationships between the expression level of miR-145 and clinicopathologic factors were evaluated by Chi square test. Kaplan–Meier survival analysis with the log-rank test was used to evaluate the association between miR-145 expression and HCC prognosis.

miR-145 was significantly down-regulated in HCC tissues compared with the adjacent noncancerous tissues (P < .001). Its expression level was significantly correlated with tumor size (P = .010), tumor number (P = .033), lymph node metastasis (P < .000), TNM stage (P < .001) and tumor differentiation (P < .001). Kaplan–Meier curves with log rank test showed that the overall survival of the patients with low miR-145 expression was significantly shorter in comparison with the high miR-145 expression patients (P = .043). Furthermore, multivariate analysis using the Cox proportional hazards model for all variables showed that miR-145 expression was an independent prognostic factor for overall survival (P = .033).

Our results indicate that low expression of miR-145 is an independent poor prognostic factor for patients with HCC. Further investigations are needed to confirm our findings.
Increased serum levels of MIC1/GDF15 correlated with bone erosion in spondyloarthritis
Authors: Song Yingyu , Cui Yang , Zhang Xiao , Lin Haobo , Zhang Guangfeng , Zeng Hui , Zeng Yonghan
Published: December 2018

Introduction:

To assess the association between growth differentiation factor-15 (GDF15) and radiographic features including bone marrow edema and bone erosion in Spondyloarthritis (SpA).

Methods:

Patients with SpA (n = 120) receiving treatment in the Guangdong General Hospital, China, between August 2012 and December 2016 were retrospectively included. Serum of patients and healthy controls (n = 30) were collected and GDF15 levels were measured using ELISA. Inflammation was assessed by C-reactive protein (CRP), and magnetic resonance imaging (MRI) of the sacroiliac joint using Spondyloarthritis Research Consortium of Canada score and a method of dichotomy to assess fat metaplasia, bone erosion, and ankylosis. Radiographs of the pelvis were scored using the modified New York (mNY) score.

Results:

Serum GDF15 levels were higher in SpA patients compared to controls (503.52 ± 222.92 vs. 190.86 ± 104.18 pg/mL, P < .0001). Patients who suffered from bone erosion on MRI had higher levels of GDF15 (525.72 [186.33, 801.62]vs. 428.06 [255.15, 670.98] pg/mL, P = .0375). There was a positive correlation between serum GDF15 and CRP (r = 0.5442, P < .0001). Moreover, GDF15 levels were related to CRP levels (r = 0.5658, P < .0001) in those X-ray scores were III, according to 1984mNY criteria. Receiver operating characteristic (ROC) analysis showed that GDF15 levels above 501.98pg/mL could predict presence of bone erosion on MRI.

Conclusion:

The present study suggested that serum GDF15 levels are higher in SpA patients than in healthy controls. The GDF15 level was correlated with CRP and may be a surrogate biomarker in bone erosion.
A comparative study of ultrasonic scalpel (US) versus conventional metal clips for closure of the cystic duct in laparoscopic cholecystectomy (LC)
Authors: Ai Xiao-Ming , Ho Li-Chen , Yang Nian-Yin , Han Lu-Lu , Lu Jin-Jing , Yue Xiong
Published: December 2018

Background:

laparoscopic cholecystectomy (LC) has become the gold standard surgery for benign gallbladder diseases. Metal clips are conventionally used to secure the cystic duct and artery, while monopolar electrocautery (ME) predominates during laparoscopic dissection. ultrasonic scalpel (US) has already been explored for sealing the cystic duct and artery as a sole instrument, which has been regarded as a reasonable alternative to clips. The aim of this study was to investigate the safety and effectiveness of US versus clips for securing the cystic duct during LC.

Methods:

We identified eligible studies in PubMed, Medline, Cochrane Library, Embase, and SpringerLink up to 1st May 2018, together with the reference lists of original studies. Meta-analysis was conducted using STATA 14.0. Q-based chi-square test and the I
2 statistics were utilized to assess heterogeneity among the included studies. A P-value below .05 was set for statistical significance. Forest plots of combined Hazard ratios (HRs) with 95% confidence intervals (CIs) were also generated.

Results:

Eight studies met eligibility criteria in this meta-analysis eventually. A total of 1131 patients were included, of whom 529 were contained in the US group, compared to 602 in the clips group, which showed a significant difference (P = .025) without substantial statistical heterogeneity (I
2 = 0.0%). No statistical significance was revealed regarding age (I
2 = 0.0%, P = .957), and sex (I
2 = 0.0%, P = .578) between both groups. The operative time and hospital stay in the US group were significantly shorter than that in the clips group, with I
2 = 95.0%, P = .000 and I
2 = 72.8%, P = .005, respectively. Concerning conversion (I
2 = 48.6%, P = .084), perforation (I
2 = 12.0%, P = .338), along with bile leakage (I
2 = 0.0% P = .594), and overall morbidity (I
2 = 19.1%, P = .289), comparison between both groups exhibited no statistical significance.

Conclusions:

US enabled shorter operative time and hospital stay during LC, compared with clips. Additionally, US was comparable to clips regarding conversion, perforation, along with bile leakage and overall morbidity. Therefore, our meta-analysis concluded that US is clinically superior to the conventional clips in some aspects, or is at least as safe and effective as them, concerning closure of the cystic duct and artery.
Successful treatment of colorectal liver metastasis harboring intrahepatic cholangiocarcinoma
Authors: Cheng Xiaofei , Zhao Feng , Chen Dong , Yang Piao , Zhong Weixiang , Xu Xiangming , Wang Weilin
Published: December 2018

Rationale:

Colorectal liver metastasis develops in 50% of patients diagnosed with colorectal cancer, whereas concurrent intrahepatic cholangiocarcinoma (ICC) and colorectal liver metastases is extremely rare.

Patient concerns:

A 72-year-old man was referred to our hospital complaining of abdominal discomfort, diarrhea, and weakness over the last month.

Diagnoses:

Colorectal liver metastases concurrent intrahepatic cholangiocarcinoma (ICC).

Interventions:

The patient was treated with mFOLFOX6 (5-fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, and oxaliplatin 85 mg/m2) plus bevacizumab 5 mg/kg every 2 weeks for 2 months. However, chemotherapy was not effective for the liver S3 lesion in our case. The possibility of ICC was considered based on the multidisciplinary team (MDT) mode, together with an anomalous increase in cancer antigen 19-9 and a history of hepatolithiasis.

Outcomes:

Simultaneous resection of the colon cancer and liver tumors was performed at 6 weeks after discontinuing bevacizumab. Colorectal liver metastases concurrent ICC was confirmed by postoperative pathology. The patient's disease-free survival time is currently >14 months.

Lessons:

This is the first case report of the diagnosis and timely treatment of colorectal liver metastases harboring ICC. These results suggest that multiple primary tumors should be considered as a differential diagnosis when imaging or laboratory test results are abnormal.
Prostate cancer laparoscopic port site metastasis
Authors: Jundt Michael C. , Broski Stephen M.
Published: December 2018

Introduction:

Laparoscopic port site metastases are a rare but clinically important cause of biochemically recurrent prostate adenocarcinoma. C-11 choline, among other prostate-specific positron emission tomography (PET) radiotracers, has improved radiologist confidence in these otherwise difficult-to-detect sites of recurrence.

Patient Concerns:

A 62-year-old male presented with biochemically recurrent prostate adenocarcinoma after undergoing robotic-assisted radical prostatectomy 5 years earlier.

Diagnosis:

C-11 choline positron emission tomography/computed tomography (PET/CT) demonstrated a choline-avid soft tissue nodule associated with a laparoscopic port site in the right rectus abdominis muscle, with correlative findings on prior magnetic resonance imaging, and biopsy confirming a prostate adenocarcinoma metastasis.

Interventions:

The patient was initiated on chemohormonal therapy.

Outcomes:

His prostate-specific antigen (PSA) became undetectable following chemohormonal therapy. A follow-up C-11 choline PET/CT demonstrated complete resolution of prior abnormal radiotracer activity in the right rectus abdominis muscle.

Lessons:

Port site metastases in prostate adenocarcinoma are rare; however, those who treat prostate cancer patients should be aware of this phenomenon as the number of minimally invasive oncologic procedures increase. C-11 choline PET, among other prostate-specific PET probes, has become an important tool in evaluating patients with biochemically recurrent prostate adenocarcinoma, identifying site-specific metastases in a majority of patients.
Oncological markers CA-125, CA 19-9 and endometriosis
Authors: Fiala Ludek , Bob Petr , Raboch Jiri
Published: December 2018

The endometrium tissue is functionally androgen related which plays an important role in women's fertility regulation. In addition recent findings show that endometrium related pathology is closely linked to disrupted androgen biosynthesis and associated regulatory functions. These findings also suggest that androgens might play an important role in endometrium related cancer pathology with significant implications for treatment.

Based on these findings, we have assessed 50 female outpatients with endometriosis and the clinical investigations were focused on biochemical serum analysis of DHEAS, oncological markers CA-125 and CA 19-9, estradiol, thyreothropic hormone, and prolactin.

The results show significant Spearman correlations of CA-125 and CA 19-9 with dehydroepiandrosterone- DHEA-S (R = 0.52 resp. R = 0.49).

This result represents 1st reported finding documenting androgen related increase of CA-125 and CA 19-9 levels as significant markers of endometrium pathology and it is possible to assume that these potential biomarkers could have clinical importance with respect to timely diagnosis.
Efficacy and safety of Tianmabianchunzhigan in mild to moderate vascular dementia
Authors: Tian Jinzhou , Shi Jing , Wei Mingqing , Li Ting , Ni Jingnian , Zhang Xuekai , Zhang Meng , Li Yang , Wang Yongyan
Published: December 2018

Background:

Vascular dementia (VaD) is the 2nd most common subtype of dementia after Alzheimer disease. Currently, there are no medications approved for treating patients with VaD. Tianmabianchunzhigan (TMBCZG) tablet is an active ingredient extracted from Gastrodia that has been reported to improve memory and other cognition. And the TBMCZG has been approved clinical trial with patients with VaD by center for drug evaluation of China (CFDA). To evaluate the efficacy, safety, and tolerability of TMBCZG tablets in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week, randomized, double-blind, parallel, placebo-controlled, multicenter trial.

Methods:

A total of 160 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either TMBCZG high-dose group (TBMCZG 3 tablets, twice per day); TMBCZG middle-dose group (TMBCZG 2 tablets and placebo 1 tablet twice per day); TMBCZG low-dose group (TMBCZG 1 tablet and placebo 2 tablets, twice per day); placebo group (placebo 3 tablets, twice per day) for 24 weeks, with a follow-up 12 weeks after withdrawn drug treatment. The primary efficacy measurement will be the vascular dementia assessment scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes scale. The secondary efficacy measurements will include the mini mental state examination and activities of daily living. Adverse events will also be reported.

Discussion:

This randomized trial will be the 1st rigorous study on the efficacy and safety of TMBCZG tablets for treating cognitive symptoms in patients with VaD using a rational design.

Trial registration:

ClinicalTrials.gov NCT03230071. Registered on July 26, 2017.
Convergent strabismus fixus after bilateral abducens nerve palsies due to aneurysms
Authors: Oku Hidehiro , Nishikawa Yuko , Kida Teruyo , Tonari Masahiro , Sugasawa Jun , Ikeda Tsunehiko
Published: December 2018

Rationale:

Convergent strabismus fixus is an ocular motor abnormality in which the eye is fixed in adduction. This condition is mostly associated with high myopia and is caused by a displacement of the extraocular muscles. We report a nonmyopic woman with convergent strabismus fixus due to aneurysms.

Patient concerns:

A 79-year-old woman complained of progressive worsening of esotropia about 50 years prior to her visit. Neuroimaging showed that the eye was not dislocated, and the extraocular muscles were not displaced. However, aneurysms were found bilaterally from the intracavernous carotid arteries and the location was on both abducens nerves.

Diagnoses:

Chronic bilateral abducens nerve palsies due to aneurysms.

Interventions:

Endovascular treatment was successfully performed for the aneurysms.

Outcomes:

Convergent strabismus fixus still remained.

Lessons:

Chronic abducens nerve palsies may develop to nonmyopic convergent strabismus fixus without displacement of extraocular muscles, and mass lesions in the brain including aneurysms should be ruled out when orbital MRI cannot explain the condition.
The efficacy of thoracic paravertebral block for thoracoscopic surgery
Authors: Hu Zhi , Liu Dan , Wang Zhi-Zhen , Wang Biao , Dai Tianyang
Published: December 2018

Background:

The efficacy of thoracic paravertebral block for thoracoscopic surgery remains controversial. We conduct a systematic review and meta-analysis to explore the impact of thoracic paravertebral block on thoracoscopic surgery.

Methods:

We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2018 for randomized controlled trials (RCTs) assessing the effect of thoracic paravertebral block on thoracoscopic surgery. This meta-analysis is performed using the random-effect model.

Results:

Six RCTs involving 300 patients are included in the meta-analysis. Overall, compared with control group for thoracoscopic surgery, thoracic paravertebral block results in significantly reduced pain scores within 6 hours (Std. MD = −2.15; 95% CI = −3.67 to −0.62; P = .006), postoperative anesthesia consumption during 48 hours (Std. MD = −1.81; 95% CI = −3.05 to −0.58; P = .004), and hospital stay (Std. MD = −1.19; 95% CI = −2.13 to −0.26; P = .01), but has no important impact on pain scores at 24 hours (Std. MD = −1.10; 95% CI = −2.77–0.57; P = .20), and 48 hours (Std. MD = −1.25; 95% CI = −2.86–0.36; P = .13).

Conclusions:

Thoracic paravertebral block can substantially enhance pain management for thoracoscopic surgery.
Association of allergic rhinitis with obstructive sleep apnea
Authors: Cao Yuan , Wu Shuang , Zhang Liyu , Yang Ying , Cao Sancheng , Li Qiao
Published: December 2018

Background:

The co-existence of allergic rhinitis (AR) and obstructive sleep apnea (OSA) is a common phenomenon in clinical practice. AR has long been considered a risk factor for OSA. However, the relationship is not completely clear. Therefore, we conducted a meta-analysis to evaluate the prevalence of AR in sleep-disordered breathing (SDB) /OSA and their relationship.

Methods:

A comprehensive literature search was performed in PubMed/Medline, Google Scholar, Wiley Online Library, EMBASE, and Web of Science. Data were analyzed and pooled to estimate effect size (ES) /odds ratio (OR) with 95% confidence intervals (95%CI). Heterogeneity was quantified and evaluated by chi-squared-based Q-test and I2 test, withP < .05 andI2 > 50% indicating evidence of heterogeneity.

Results:

44 studies contained 6086 participants were included in this meta-analysis. For adults, the prevalence of AR was 22.8 (95% CI, 15.0–30.6) % in SDB and 35.2 (95% CI, 25.6–44.7) % in OSA. In children with SDB and OSA, the prevalence of AR was 40.8 (95% CI, 24.3–57.2) %, and 45.2 (95% CI, 25.4–65.0) % respectively. The odds ratios of prevalence of the SDB pediatric patients with AR was 2.12 (95%CI, 1.75, 2.57;P < .0001) times higher than that of non-SDB pediatric patients. There were no significant differences between OSA adults with or without AR in BMI (Body Mass Index), neck circumference, apnea hypopnea index (AHI) and epworth sleep scale score (ESS).

Conclusion:

The prevalence of AR in OSA/SDB is considerably high and children with SDB suffering from a higher incidence of AR than non-SDB. OSA adults accompanied with AR do not have any influences on sleep parameters.
Intracranial hemorrhage after carotid artery stenting in both anterior and posterior circulation
Authors: Wang Pian , Wang Yan , Zhang Qingbin
Published: December 2018

Rational:

Intracranial hemorrhage (ICH) after carotid artery stenting (CAS) is a rare but fatal complication, and it primarily occurs in the corresponding vascular distribution area. Herein, a case of ICH after CAS in both anterior and posterior circulation has been described.

Patient concerns:

A 62-year-old female was referred to the hospital for left-side limb weakness and right nasal hemianopia for 1 month.

Diagnosis:

Cerebral MRI following hospitalization revealed cerebral infarction in the right posterior cortical watershed area. Computed tomography angiography (CTA) showed severe stenosis in the right internal carotid artery.

Interventions:

We performed CAS to treat the right internal carotid artery stenosis without any complications.

Outcomes:

After CAS, cerebral hemorrhage occurred under strict control of blood pressure in both anterior and posterior circulation. After 69 days of treatment, the patient was discharged from the hospital.

Lessons:

Hypertension is still one of the causes of ICH after CAS. The control of perioperative BP in patients with severe carotid stenosis is yet a major concern.
Nonsmall cell lung cancer with rare exon 7 p.A289V mutation in the EGFR gene responds to Icotinib treatment
Authors: Dai Limeng , Su Xuejiao , Lu Lin , Lv Donglai
Published: December 2018

Rationale:

Mutation p.A289V involving extracellular region of epidermal growth factor receptor (EGFR) exon 7 has not yet been reported in nonsmall cell lung cancer (NSCLC). Studies have shown p.A289V mutation responding to tyrosine kinase inhibitors (TKIs) in glioblastoma cell lines suggesting the point mutation as a potential therapeutic target. However, sufficient evidence of the effect of TKI treatment on the p.A289V mutation involved in NSCLC is not available.

Patient concerns:

An 80-year-old nonsmoker male with lung mass was suffering from severe bone pain.

Diagnosis:

Needle biopsy and positron emitted tomography/computed tomography were performed. The patient was diagnosed with advanced NSCLC adenocarcinoma with bone and lymphatic metastasis. Next-generation sequencing of circulating tumor DNA was performed, which identified a p.A289V mutation in the EGFR gene of the patient.

Interventions:

Our patient refused to receive chemotherapy and tried Icotinib treatment.

Outcomes:

Our patient had a partial response to Icotinib after treatment for 5 months during the therapeutic trial by TKIs. The patient showed adverse symptoms of mild diarrhea and rash (Common Terminology Criteria for Adverse Events grade 1) during the treatment.

Lessons:

In this case, Icotinib prevented completion of the signal transduction cascade of p.A289V mutant in NSCLC. Our finding may expand the EGFR mutation spectrum for TKI treatment in NSCLC. However, the finding needs to be confirmed at a larger scale with NSCLC in Chinese and other populations.
Posterolateral decompression, bone graft fusion, posterior instrumentation, and local continuous chemotherapy in the surgical treatment of thoracic spinal tuberculosis
Authors: Yin Xin Hua , Yan Liang , Yang Ming , Zhang Ke , He Bao Rong , Liu Zhong Kai , Hao Ding Jun
Published: December 2018

To investigate the clinical efficacy of surgical treatment for thoracic spinal tuberculosis with kyphosis deformity via posterolateral debridement, fusion, posterior instrumentation and local continuous chemotherapy. A total of 25 patients with thoracic tuberculosis received surgery by posterolateral decompression, fusion, posterior instrumentation, and postural drainage with local continuous chemotherapy between June 2009 and October 2011. The clinical outcomes was evaluated using statistical analysis about deformity correction, bone fusion, neurologic status, and the visual analog score (VAS) and erythrocyte sedimentation rate (ESR). All of 25 patients were followed up for 39.0 ± 10.7 months (range, 24–60 months) postoperatively. There was no recurrence of tuberculosis, breakage and looseness of internal fixation. Bony fusion was achieved in all cases with 6.7 ± 1.9 months. The values of ESR recovered to normal within 6 months postoperatively. All patients with neurological deficit had significant improvement at the final follow-up. The average preoperative Cobb angles were significantly decreased to 12.2 ± 2.9° (range, 8–17°) postoperatively, and at final follow-up were 12.9 ± 2.7°. Our results showed that single-stage posterolateral debridement fusion, posterior instrumentation and local continuous chemotherapy can be expected to yield satisfactory clinical and radiographic outcomes in patients with thoracic spinal tuberculosis.
The association between IGF1 Gene 3’-UTR polymorphisms and cancer risk
Authors: Xu Gui-Ping , Chen Wei-Xian , Xie Wen-Yue , Wu Li-Fang
Published: December 2018

Background and Objective:

Insulin-like growth factor 1 (IGF1) gene three prime untranslated region (3’-UTR) polymorphisms have been reported to be associated with cancer risk. However, the conclusions of the relevant studies are not consistent. The present meta-analysis evaluates the relationship between IGF1 gene 3’-UTR polymorphisms (rs5742714, rs6214, and rs6220) and cancer risk.

Methods:

Articles regarding the relationship between IGF1 rs5742714, rs6214, and rs6220 polymorphisms and cancer risk were selected by searching the PubMed, Embase, and Web of Science databases before April 30, 2018. Altogether, we obtained 34 case-controlled studies from 20 articles, including 21,568 cases and 31,199 controls. The strength of associations was quantified using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs).

Results:

In the present meta-analysis, no significant associations were detected between rs5742714, rs6214, and rs6220 and overall cancer risk. Thus, in stratified analyses, we found that rs6214 was associated with a significantly reduced risk of breast cancer under the allele, heterozygote, and dominant models (A vs G: OR, 0.94, 95% CI,0.88–1.00, P = .044; GA vs GG: OR, 0.88, 95% CI, 0.80–0.97, P = .012; AA + GA vs GG: OR, 0.89, 95% CI, 0.81–0.97, P = .011), as well as pancreatic cancer under the recessive model (AA vs GA + GG: OR, 0.68, 95% CI,0.53–0.87, P = .003). Also, rs6220 was associated with a significantly increased risk of breast cancer under the homozygote model (GG vs AA: OR, 1.23, 95% CI, 1.02–1.48, P = .031). In addition, rs6220 was found to increase overall cancer risk among Caucasians under the allele model (G vs A: OR, 1.06, 95% CI, 1.00–1.13, P = .043).

Conclusions:

In this meta-analysis, we investigated and reviewed the relationship between IGF1 gene 3’-UTR polymorphisms (rs5742714, rs6214, and rs6220) and cancer risk based on present epidemiological studies. Further studies are needed to draw more precise conclusions in the future.
Therapeutic efficacy of latanoprost on primary open angle glaucoma
Authors: Dai Hai-yan , Wang Jia-ying , Li Yan-qing , Diao Hui-jie , Zhang Li
Published: December 2018

Background:

Latanoprost is quiet new formulation that is approved for the treatment of primary open angle glaucoma (POAG). However, no updated systematic review has addressed its efficacy for POAG. This systematic review of randomized controlled trials (RCTs) aims to assess its efficacy and safety for the treatment of patients with POAG.

Methods:

This study will search the databases of CENTRAL, EMBASE, MEDILINE, CINAHL, AMED and Chinese databases without language restrictions from their inception to the present. It will only include RCTs of latanoprost for POAG. The quality of the included RCTs will be evaluated by the tool of Cochrane risk of bias. The primary outcomes will be measured by the mean IOP reduction from baseline to the endpoint. The secondary outcomes will be assessed by the mean IOP, adjusted mean IOP reduction at each time point, quality of life, and adverse events. The RevMan V.5.3 software will be used to compute the data synthesis carefully if the meta-analysis is allowed. The summary results of the included RCTs will be conducted by using the models of random-effects or fixed-effects based.

Results:

The results of this study will be published at the peer-reviewed journals. It will provide evidence to determine the efficacy and safety of latanoprost for POAG.

Conclusion:

The results of this study will provide helpful evidence for both clinicians and patients, and for the health policy makers to refer for the policy or guideline making.

Systematic review registration:

PROSPERO CRD42018115416.
Endoscopic submucosal dissection of early gastric cancer with mixed-type histology
Authors: Bang Chang Seok , Choi Jae Ho , Yang Young Joo , Lee Jae Jun , Baik Gwang Ho
Published: December 2018

Background:

Endoscopic submucosal dissection (ESD) is a primary treatment for the early gastric cancer (EGC) who have a negligible risk of lymph node metastasis satisfying specific criteria. These criteria are histologically categorized by EGC with differentiated-type histology (EGC-DH) and undifferentiated-type histology (EGC-UH). However, gastric cancer is histologically heterogenous and there has been no specific criteria for EGC with mixed-type histology (EGC-MH). Moreover, therapeutic outcomes of ESD for EGC-MH have not been clearly described.

Methods:

We will search the core databases (MEDLINE (through PubMed), the Cochrane Library, and Embase) from their inception to November 2018 using pre-established searching strategy by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have EGC-MH, Intervention: ESD, Comparison: none, Outcome: at least one among the rate of complete resection, curative resection, en bloc resection, recurrence or procedure-related adverse event that enabled an evaluation of feasibility of ESD. All types of study design will be sought and publications in English with full-text will be included. The risk of bias will be assessed using the ROBINS-I tool. Descriptive data synthesis is planned and quantitative synthesis will be used if the included studies are sufficiently homogenous (pooled therapeutic outcomes data with 95% confidence intervals). Publication bias will be assessed with quantitative analyses if more than 10 articles are enrolled.

Results:

The results will provide evidence for validity of current ESD criteria in addition to the technical feasibility of ESD for EGC-MH.

Conclusion:

This study will provide evidence of ESD for EGC-MH.
Transthoracic radiofrequency ablation for hepatic tumor located beneath the diaphragm under one-lung ventilation
Authors: Park Sung Wook , Kim Youngsoon , Kang Hee Yong , You Ann Hee , Jeon Jong Mi , Woo Hyunho , Choi Jeong-Hyun
Published: December 2018

Rationale:

Radiofrequency ablation (RFA) has become the reliable, effective, and less invasive treatment for small primary or metastatic hepatic tumors. Hepatic tumors that located immediately beneath the diaphragm are difficult to treat with percutaneous RFA due to poor visualization by percutaneous ultrasonography and the close location of the heart or lung. A transthoracic approach has been proposed to be an alternative for hepatic tumors located beneath the diaphragm that are difficult to access by conventional percutaneous or laparoscopic approaches. There has been no report regarding the anesthetic management of the transthoracic RFA for hepatic tumor.

Patient concerns:

A 69-year-old female had undergone segmentectomy due to hepatocellular carcinoma 4 years ago.

Diagnoses:

Newly developed hepatic tumor located in the liver dome and beneath the diaphragm was diagnosed by follow-up imaging study.

Interventions:

Because the tumor could not be identified by transabdominal ultrasonography (US), transthoracic approach for RFA under one-lung ventilation was planned. General anesthesia was induced with propofol and remifentanil via target-controlled infusion system and rocuronium was administered. Orotracheal intubation with double-lumen endotracheal tube was performed and position of the tube in the trachea was confirmed by bronchoscope. The RFA electrode was introduced percutaneously into the right pleural cavity, guided by visualization through the thoracoscope and inserted into the tumor after visualizing the tumor by US. Radiofrequency waves can be successfully administered through the needle.

Outcomes:

We performed successfully RFA of the hepatic tumor through one-lung ventilation and transthoracic approach. At 5 days postoperatively, she was discharged in a stable condition without any complication.

Lessons:

Transthoracic RFA can be successfully performed under one-lung ventilation, optimal analgesia, and vigilant monitoring.
Relationships Matter: Progress and Challenges in Research on the Health Effects of Intimate Relationships
Authors: Smith Timothy W.
Published: December 2018

Social connections play an important role in health and disease and provide opportunities for clinical and public health interventions. Marriage and similar intimate relationships play a central role in the potential health benefits of positive social connections. This editorial provides an integrative perspective on three papers in this issue of Psychosomatic Medicine that examine intimate relationships and health and illustrates the application of current areas in relationship science. The importance of integrated conceptual models and statistical techniques to disentangle common third factors and overlapping constructs are highlighted, as well as the need for a multi-method approach that goes beyond self-report questionnaires. This editorial concludes with a summary of biobehavioral and psychological mechanisms and directions for future research.
Correlation Between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases After Neoadjuvant Systemic Therapy
Authors: Samiei Sanaz , van Nijnatten Thiemo J. A. , de Munck Linda , Keymeulen Kristien B. M. I. , Simons Janine M. , Kooreman Loes F. S. , Siesling Sabine , Lobbes Marc B. I. , Smidt Marjolein L.
Published: December 2018

Objective:

The aim was to investigate whether pathologic complete response (pCR) in the breast is correlated with absence of axillary lymph node metastases at final pathology (ypN0) in patients treated with neoadjuvant systemic therapy (NST) for different breast cancer subtypes.

Background:

Pathologic complete response rates have improved on account of more effective systemic treatment regimens. Promising results in feasibility trials with percutaneous image-guided tissue sampling for the identification of breast pCR after NST raise the question whether breast surgery is a redundant procedure. Thereby, the need for axillary surgery should be reconsidered as well.

Methods:

Patients diagnosed with cT1-3N0-1 breast cancer and treated with NST, followed by surgery between 2010 and 2016, were selected from the Netherlands Cancer Registry. Patients were compared according to the pathologic response of the primary tumor with associated pathologic axillary outcome. Multivariable analysis was performed to determine clinicopathological variables correlated with ypN0.

Results:

A total of 4084 patients were included for analyses, of whom 986 (24.1%) achieved breast pCR. In clinically node negative patients (cN0), 97.7% (432/442) with breast pCR had ypN0 compared with 71.6% (882/1232) without breast pCR (P < 0.001). In clinically node positive patients (cN1), 45.0% (245/544) with breast pCR had ypN0 compared with 9.4% (176/1866) without breast pCR (P < 0.001). The odds of ypN0 was decreased in case of clinical T3 stage (OR 0.59, 95% CI 0.40–0.87), cN1 (OR 0.03, 95% CI 0.02–0.04) and ER+HER2- subtype (OR 0.30, 95% CI 0.20–0.44), and increased in case of breast pCR (OR 4.53, 95% CI 3.27–6.28).

Conclusions:

Breast pCR achieved after NST is strongly correlated with ypN0 in cN0 patients, especially in ER+HER2+, ER-HER2+, and triple negative subtypes. These results provide data to proceed with future clinical trials to investigate if axillary surgery can be safely omitted in these selected patients when image-guided tissue sampling identifies a breast pCR.
On-site ribosome remodeling by locally synthesized ribosomal proteins in axons
Authors: Shigeoka Toshiaki , Koppers Max , Wong Hovy Ho-Wai , Lin Julie Qiaojin , Dwivedy Asha , de Freitas Nascimento Janaina , Cagnetta Roberta , van Tartwijk Francesca , Ströhl Florian , Cioni Jean-Michel , Carrington Mark , Kaminski Clemens F. , Harris William A. , Jung Hosung , Holt Christine E.
Published: December 2018

Ribosomes are known to be assembled in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding ribosomal proteins (RPs) in axons, far away from neuronal cell bodies. Using subcellular proteomics and live-imaging, we show that locally synthesized RPs incorporate into axonal ribosomes in a nucleolus-independent fashion. We revealed that axonal RP translation is regulated through a novel sequence motif, CUIC, that forms a RNA-loop structure in the region immediately upstream of the initiation codon. Inhibition of axonal CUIC-regulated RP translation leads to defects in local translation activity and axon branching, demonstrating the physiological relevance of the axonal ribosome remodeling. These results indicate that axonal translation supplies cytoplasmic RPs to maintain/modify local ribosomal function far from the nucleolus.
Genotyping-by-sequencing reveals the effects of riverscape, climate and interspecific introgression on the genetic diversity and local adaptation of the endangered Mexican golden trout (Oncorhynchus chrysogaster)
Authors: Escalante Marco A. , Perrier Charles , García-De León Francisco J. , Ruiz-Luna Arturo , Ortega-Abboud Enrique , Manel Stéphanie
Published: December 2018

How environmental and anthropogenic factors influence genetic variation and local adaptation is a central issue in evolutionary biology. The Mexican golden trout (Oncorhynchus chrysogaster), one of the southernmost native salmonid species in the world, is susceptible to climate change, habitat perturbations and the competition and hybridization with exotic rainbow trout (O. mykiss). The present study aimed for the first time to use genotyping-by-sequencing to explore the effect of genetic hybridization withO. mykissand of riverscape and climatic variables on the genetic variation amongO. chrysogasterpopulations. Genotyping-by-sequencing (GBS) was applied to generate 9767 single nucleotide polymorphisms (SNPs), genotyping 272O. chrysogasterandO. mykiss. Population genomics analyses were combined with landscape ecology approaches into a riverine context (riverscape genetics). The clustering analyses detected seven different genetic groups (six forO. chrysogaterand one for aquacultureO. mykiss) and a small amount of admixture between aquaculture and native trout with only two native genetic clusters showing exotic introgression. Latitude and precipitation of the driest month had a significant negative effect on genetic diversity and evidence of isolation by river resistance was detected, suggesting that the landscape heterogeneity was preventing trout dispersal, both for native and exotic individuals. Moreover, several outlier SNPs were identified as potentially implicated in local adaptation to local hydroclimatic variables. Overall, this study suggests thatO. chrysogatermay require conservation planning given i) exotic introgression fromO. mykisslocally threateningO. chrysogatergenetic integrity, and ii) putative local adaptation but low genetic diversity and hence probably reduced evolutionary potential especially in a climate change context.
Comparative RNAi Screens in Isogenic Human Stem Cells RevealSMARCA4as a Differential Regulator
Authors: Güneş Ceren , Paszkowski-Rogacz Maciej , Rahmig Susann , Khattak Shahryar , Wermke Martin , Dahl Andreas , Bornhäuser Martin , Waskow Claudia , Buchholz Frank
Published: December 2018

Large-scale RNAi screens are a powerful approach to identify functions of genes in a cell-type specific manner. For model organisms, genetically identical (isogenic) cells from different cell-types are readily available, making comparative studies meaningful. For humans, however, screening isogenic cells is not straightforward. Here, we show that RNAi screens are possible in genetically identical human stem cells, employing induced pluripotent stem cell as intermediates. The screens revealedSMARCA4(SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4) as a stemness regulator, while balancing differentiation distinctively for each cell type.SMARCA4knockdown in hematopoietic stem progenitor cells (HSPC) caused impaired self-renewalin-vitroandin-vivowith skewed myeloid differentiation; whereas in neural stem cells (NSC), it impaired selfrenewal while biasing differentiation towards neural lineage, through combinatorial SWI/SNF subunit assembly. Our findings pose a powerful approach for deciphering human stem cell biology and attribute distinct roles toSMARCA4in stem cell maintenance.
Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism
Authors: Kapoor Manav , Wang Jen-Chyong , Farris Sean P. , Liu Yunlong , McClintick Jeanette , Gupta Ishaan , Meyers Jacquelyn L. , Bertelsen Sarah , Chao Michael , Nurnberger John , Tischfield Jay , Harari Oscar , Zeran Li , Hesselbrock Victor , Bauer Lance , Raj Towfique , Porjesz Bernice , Agrawal Arpana , Foroud Tatiana , Edenberg Howard J. , Mayfield R. Dayne , Goate Alison
Published: December 2018

Alcohol exposure triggers changes in gene expression and biological pathways in human brain. We explored alterations in gene expression in the Pre-Frontal Cortex (PFC) of 65 alcoholics and 73 controls of European descent, and identified 129 genes that showed altered expression (FDR < 0.05) in subjects with alcohol dependence. Differentially expressed genes were enriched for pathways related to interferon signaling and Growth Arrest and DNA Damage-inducible 45 (GADD45) signaling. A coexpression module (thistle2) identified by weighted gene co-expression network analysis (WGCNA) was significantly correlated with alcohol dependence, alcohol consumption, and AUDIT scores. Genes in the thistle2 module were enriched with genes related to calcium signaling pathways and showed significant downregulation of these pathways, as well as enrichment for biological processes related to nicotine response and opioid signaling. A second module (brown4) showed significant upregulation of pathways related to immune signaling. Expression quantitative trait loci (eQTLs) for genes in the brown4 module were also enriched for genetic associations with alcohol dependence and alcohol consumption in large genome-wide studies included in the Psychiatric Genetic Consortium and the UK Biobank’s alcohol consumption dataset. By leveraging multi-omics data, this transcriptome analysis has identified genes and biological pathways that could provide insight for identifying therapeutic targets for alcohol dependence.