bluuebunny/crossref_metadata_2025 huggingface dataset:
Urodynamic assessment of bladder storage function after radical hysterectomy for cervical cancer
Authors: Cao Ting-Ting , Wen Hong-Wu , Gao Yu-Nong , Lyu Qiu-Bo , Liu Hui-Xin , Wang Sha , Wang Shi-Yan , Sun Hua-Xin , Yu Na , Wang Hai-Bo , Li Yi , Wang Zhi-Qi , Chang Olivia H. , Sun Xiu-Li , Wang Jian-Liu
Published: September 2020

Background

After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.

Methods

A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.

Results

Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.

Conclusion

A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.
Impacts of smoking status on the clinical outcomes of coronary non-target lesions in patients with coronary heart disease: a single-center angiographic study
Authors: Xu Hao-Bo , Wang Juan , Chen Ji-Lin , Guo Chao , Yuan Jian-Song , Duan Xin , Hu Feng-Huan , Yang Wei-Xian , Luo Xiao-Liang , Liu Rong , Cui Jin-Gang , Liu Sheng-Wen , Gao Xiao-Jin , Chun Yu-Shi , Qiao Shu-Bin
Published: September 2020

Background

Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions.

Methods

Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes.

Results

A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04–8.62, P = 0.042).

Conclusion

Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.
Impact of metabolic syndrome on short-term outcome of carotid revascularization: a large sample size study in Chinese population
Authors: Bai Xue-Song , Feng Yao , Wang Tao , Zhang Xiao , Yang Chang-Lin , Wang Ya-Bing , Hua Yang , Lu Jie , Zhu Feng-Shui , Chen Yan-Fei , Gao Peng , Yang Ren-Jie , Ma Yan , Jiao Li-Qun
Published: September 2020

Background

Metabolic syndrome (MetS) is relatively common worldwide and an important risk factor for cardiovascular diseases. It is closely linked to arterial stiffness of the carotid artery. However, the association of MetS with the safety of carotid revascularization has been rarely studied. The aim of this study was to observe the current status of MetS and its components in Chinese carotid revascularized patients, and investigate the impact on major adverse clinical events (MACEs) after carotid endarterectomy (CEA) or carotid artery stenting (CAS).

Methods

From January 2013 to December 2017, patients undergoing CEA or CAS in the Neurosurgery Department of Xuanwu Hospital were retrospectively recruited. The changes in prevalence of MetS and each component with time were investigated. The primary outcome was 30-day post-operative MACEs. Univariable and multivariable analyses were performed to identify the impact of MetS on CEA or CAS.

Results

A total of 2068 patients who underwent CEA (766 cases) or CAS (1302 cases) were included. The rate of MetS was 17.9%; the prevalence rate of MetS increased with time. The occurrence rate of MACEs in CEA was 3.4% (26 cases) and in CAS, 3.1% (40 cases). There was no statistical difference between the two groups (3.4%vs. 3.1%,P = 0.600). For CEA patients, univariate analysis showed that the MACE (+) group had increased diabetes history (53.8%vs. 30.9%,P = 0.014) and MetS (34.6%vs. 15.8%,P = 0.023). For CAS patients, univariate analysis showed that the MACE (+) group had increased coronary artery disease history (40.0%vs. 21.6%,P = 0.006) and internal carotid artery tortuosity (67.5%%vs. 37.6%,P < 0.001). Furthermore, the MACE (+) group had higher systolic blood pressure (143.38 ± 22.74vs. 135.42 ± 17.17 mmHg,P = 0.004). Multivariable analysis showed that the influencing factors for MACEs in CEA included history of diabetes (odds ratio [OR] = 2.345; 95% confidence interval [CI] = 1.057–5.205;P = 0.036) and MetS (OR = 2.476; 95% CI = 1.065–5.757;P = 0.035). The influencing factors for MACEs in CAS included systolic blood pressure (OR = 1.023; 95% CI = 1.005–1.040;P = 0.010), coronary artery disease (OR = 2.382; 95% CI = 1.237–4.587;P = 0.009) and internal carotid artery tortuosity (OR = 3.221; 95% CI = 1.637–6.337;P = 0.001).

Conclusions

The prevalence rate of MetS increased with time in carotid revascularized patients. MetS is a risk for short-term MACEs after CEA, but not CAS.
DnaJA4 is involved in responses to hyperthermia by regulating the expression of F-actin in HaCaT cells
Authors: Liu Rui-Jiao , Niu Xue-Li , Yuan Jin-Ping , Chen Hong-Duo , Gao Xing-Hua , Qi Rui-Qun
Published: September 2020

Background

Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia.

Methods

Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein.

Results

DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P < 0.05). In response to hyperthermia, F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia (WT cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.34 ± 0.02 vs. 0.24 ± 0.01, 0.31 ± 0.01, P < 0.001, P < 0.05; DnaJA4-KO cells: unheated vs. 6 h after hyperthermia or 24 h after hyperthermia: 0.44 ± 0.01 vs. 0.30 ± 0.01, 0.51 ± 0.02, P < 0.001, P < 0.01). WT cells restored to baseline levels observed in the unheated condition, while DnaJA4-KO cells exceeded baseline levels in the recovery. As the upstream factors of F-actin, a similar profile in rho-associated serine/threonine kinase 1 (ROCK 1) and RhoA expressions was observed after hyperthermia. While E-cadherin expression was decreased in response to hyperthermia, it was increased in DnaJA4-KO cells compared with WT cells.

Conclusions

Hyperthermia affects the expression levels of F-actin in HaCaT cells. DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia. DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.
Association between blood cadmium and vitamin D levels in the Yangtze Plain of China in the context of rapid urbanization
Authors: Chen Chi , Zhang Hao-Jie , Zhai Hua-Ling , Chen Yi , Han Bing , Li Qin , Xia Fang-Zhen , Wang Ning-Jian , Lu Ying-Li
Published: September 2020

Background

China has experienced rapid urbanization in the past 30 years. We aimed to report blood cadmium level (BCL) in the rapidly urbanized Yangtze Plain of China, and explore the association between BCL and 25-hydroxyvitamin D (25(OH)D).

Methods

Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cross-sectional study (ChiCTR-ECS-14005052, www.chictr.org). We enrolled 3234 subjects from 12 villages in the Yangtze Plain. BCLs were measured by atomic absorption spectrometry. 25(OH)D was measured with a chemiluminescence assay.

Results

A total of 2560 (79.2%) subjects were diagnosed with vitamin D deficiency. The median (interquartile range) BCL was 1.80 μg/L (0.60–3.42) for men and 1.40 μg/L (0.52–3.10) for women. In women, mean 25(OH)D concentrations were inversely associated with BCL (0.401, 95% confidence interval: –0.697 to –0.105 nmol/L lower with each doubling of the BCL) after adjustment for age, educational status, current smoking, body mass index, diabetes, and season. However, there was no significant difference in 25(OH)D across the BCL tertiles for men.

Conclusions

BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries. An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment. Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships, and to elucidate the exact mechanisms involved.
Astrocyte elevated gene-1 serves as a target of miR542 to promote glioblastoma proliferation and invasion
Authors: Li Chong , Liu Hai-Long , Zhou Yu-Mei , Shi Yan-Chun , Zhang Zhi-Bin , Chen Ling , Feng Shi-Yu
Published: September 2020

Background:

Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle.

Methods:

The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored.

Results:

MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT.

Conclusion:

The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.
Topoisomerase II alpha promotes gallbladder cancer proliferation and metastasis through activating phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway
Authors: Lyu Wen-Jie , Shu Yi-Jun , Liu Ying-Bin , Dong Ping
Published: September 2020

Background

: Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC.

Methods

: Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.

Results

: TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR.

Conclusion

: Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.
Secukinumab provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis: results from the 52-week, Phase III China-centric study, MEASURE 5
Authors: Huang Feng , Sun Fei , Wan Wei-Guo , Wu Li-Jun , Dong Ling-Li , Zhang Xiao , Kim Tae-Hwan , Sengupta Raj , Šenolt Ladislav , Wang Yi , Qiu Hao-Min , Porter Brian , Haemmerle Sibylle
Published: September 2020

Background

Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study.

Methods

MEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China vs. non-China).

Results

Of 458 patients (secukinumab 150 mg, N = 305; placebo, N = 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16 vs. placebo (58.4% vs. 36.6%; P < 0.0001); corresponding rate in the Chinese population was 56.0% vs. 38.5% (P < 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52.

Conclusions

Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations.

Trial registration

ClinicalTrials.gov, NCT02896127; https://clinicaltrials.gov/ct2/show/NCT02896127?term=NCT02896127&draw=2&rank=1.
Multi-center investigation of the clinical and pathological characteristics of inflammatory breast cancer based on Chinese Society of Breast Surgery (CSBrs-007)
Authors: Zhou Qi , Zhang Hai-Ping , Zhao Ya-Ting , Wang Xiao-Hong , Xiong Wei , Liu Yun-Jiang , Zhang Jing-Hua
Published: September 2020

Background

Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC.

Methods

We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed bypost hocanalyses.

Results

Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) (41.5%) and HR−/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR−/HER2− (19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2− and HR−/HER2− tumors (adjustedP = 0.008), and Ki-67 expression significantly differed in HR−/HER2+ and HR+/HER2+ molecular subtypes (adjustedP = 0.008).

Conclusion

Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies.

Trial registration

chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx?proj=45030
Incidental Coronary Artery Calcium on Breast Radiation Therapy Planning Scans Identifies Patients for Cardiac Preventive Therapy
Authors: Amin Neha P. , Kim Samuel M. , Lasio Giovanni , Zhou Jinghao , Romar Linda , Shipman Kalin , Dukes Kelly , Amin Nivee P.
Published: September 2020

Purpose/Objective(s):

The presence of coronary artery calcium (CAC>0) is associated with increased cardiac-related mortality and is a common indication to initiate statin therapy to prevent future long-term cardiac-related adverse events. CAC is also well visualized on noncontrast chest computed tomography simulation (CT sim) scans used for breast radiation planning. We hypothesize that by screening for incidental CAC on CT sims, radiation oncologists could help identify patients who may benefit from additional preventive medical interventions with their primary care physician or cardiologist.

Methods:

A retrospective analysis of 126 consecutive patients with breast cancer treated with external beam radiation therapy at a single institution was performed. Noncontrast CT sim scans were reviewed for the presence of CAC and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated to identify patients who may benefit from initiating statin therapy. Patients with CAC>0 and/or ASCVD risk >20% were identified as those who may benefit from statin therapy.

Results:

Out of 72 patients with CAC>0, only 12(16%) had reported pre-existing coronary artery disease and 32(44%) were not already on recommended statin therapy. CAC>0 visualized on CT sim was able to identify 29 additional patients who would benefit from statin beyond what the ASCVD risk calculator could identify.

Conclusion:

Observation of incidental CAC on breast radiation-planning CT scans identified patients who could benefit from cardiac-related preventive strategies. By increasing attention, awareness, and reporting of incidental CAC visible on CT sims, radiation oncologists may fulfill a unique role to bridge a potential gap in cardiovascular preventive medicine.
Optimizing Outcomes With Physical Therapy Treatment for IndividuALs Surviving an Intensive Care Units Admission for COVID-19 (OPTImAL)—A Protocol for a Single Center Prospective Study
Authors: Mayer Kirby P. , Steele Angela K. , Joshi Rajan R. , Soper Melissa K. , Dupont-Versteegden Esther E. , Morris Peter E. , Montgomery Ashley A. , Parry Selina M.
Published: September 2020

Purpose:

Survivors of acute respiratory failure develop persistent muscle weakness and deficits in cardiopulmonary endurance leading to limited physical function. Early data from the COVID-19 pandemic suggest a high incidence of critically ill patients admitted to intensive care units (ICU) will require mechanical ventilation for acute respiratory failure. Patients with COVID-19 that survive an admission to the ICU are expected to suffer from physical and cognitive impairments that will limit quality of life and return to prehospital level of function. The primary aim of this study is to evaluate the safety and feasibility of providing combined ICU aftercare (ICU Recovery Clinic) and 8 weeks of physical therapy treatment for patients surviving an admission to ICU for COVID-19. The secondary aims will be to explore trends of effect on physical, mental, and cognitive recovery as well as the impact on return to work, readmission rates, and mortality.

Methods:

This is a protocol to describe a single-center, prospective phase I feasibility study in patients surviving ICU admission for COVID-19. We hypothesize that this novel combination is (1) feasible to provide for patients surviving COVID-19, will (2) improve physical function and exercise capacity measured by performance on 6-minute walk test and Short Performance Physical Battery, and (3) reduce incidence of anxiety, depression, and post-traumatic stress assessed with Hospital Anxiety and Depression Scale and the Impact of Events Scale-Revised. Safety will be assessed based on occurrence of adverse events and feasibility will be measured by adherence and attrition. Repeated measures analysis of variance will be used to assess change in outcomes from baseline to 3- and 6-months after institutional discharge.

Results:

We present the protocol of this study that has already received ethics approval at the University of Kentucky with enrollment commenced on May 1, 2020. Conclusions: The results of this study will support the feasibility of providing ICU follow-up treatment and physical therapy treatment for patients surviving critical illness for COVID-19 and will assess the effectiveness. We plan to disseminate study results in peer-reviewed journals as well as presentation at physical therapy and critical care national and international conferences.
Ultrasound-guided supraclavicular vs. retroclavicular block of the brachial plexus: comparison of ipsilateral diaphragmatic function
Authors: Georgiadis Paige L. , Vlassakov Kamen V. , Patton Megan E. , Lirk Philipp B. , Janfaza David R. , Zeballos Jose L. , Quaye Aurora N. , Patel Vijay , Schreiber Kristin L.
Published: September 2020

BACKGROUND

The ultrasound-guided retroclavicular block (RCB) is a recently described alternative approach to brachial plexus blockade at the level of the cords. Although more distal blockade of the brachial plexus is thought to be associated with a lower incidence of phrenic nerve block, the impact of RCB on ipsilateral diaphragmatic function has not been formally investigated.

OBJECTIVE

To compare the effects of supraclavicular and retroclavicular brachial plexus block on diaphragmatic function.

SETTING

A single tertiary hospital, study period from December 2017 to May 2019.

DESIGN

Double-blinded, randomised study.

PATIENTS

A total of 40 patients undergoing upper extremity surgery below the axilla. Exclusion criteria included significant pulmonary disease, BMI more than 40 and contra-indication to peripheral nerve block.

INTERVENTIONS

Patients were randomised to supraclavicular or retroclavicular brachial plexus block with ropivacaine 0.5%.

OUTCOME MEASURES

Phrenic block was assessed by measuring changes in diaphragmatic excursion using M-mode ultrasound, and maximum inspiratory volume on incentive spirometry from baseline, at 15 and 30 min postblock, and postoperatively. Comparative assessment of block characteristics included timing and distribution of sensory and motor block onset in the upper extremity, and scanning and block performance times.

RESULTS

The incidence of phrenic block in the supraclavicular group was higher by ultrasound imaging (70 vs. 15%) and also by pulmonary function testing (55 vs. 5%), with both diaphragmatic excursion and maximum inspiratory volume decreasing to a greater extent after supraclavicular block (SCB) compared with RCB at 15, 30 min and postoperative time points (repeated measures analysis of variance, P < 0.001). There was no difference in timing and extent of distal arm block, but suprascapular and axillary nerves were more consistently blocked after SCB than after RCB.

CONCLUSION

The current study confirms the hypothesis that a RCB is significantly less likely to affect ipsilateral diaphragmatic function than a SCB.

TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT02631122.
Pain impairs consolidation, but not acquisition or retrieval of a declarative memory
Authors: Lazzarim Mayla K. , Targa Adriano , Sardi Natalia F. , Hack Gabriela R. , Tobaldini Glaucia , Martynhak Bruno J. , Fischer Luana
Published: September 2020

Among the physical conditions that impair memory performance, pain is one of the most prevalent. However, the mechanisms by which pain impairs memory are largely unknown. In this study, we asked whether pain affects memory acquisition, consolidation and retrieval as well as whether memory impairment depends on pain intensity. Wistar rats received a hind paw injection of formalin (1%) at different phases of object recognition test. The injection of formalin after training but not before training or testing impaired object recognition memory. We concluded that pain impairs the consolidation but not acquisition or retrieval of object recognition memory, which is a subtype of declarative memory. Morphine, at a dose that did not affect object recognition memory in control rats, drastically reduced formalin-induced nociceptive behavior without reversing memory impairment. A lower dose of formalin (0.25%) induced less nociceptive behavior, but similar memory impairment. There is no statistical correlation between the intensity of nociceptive response and the performance in object recognition test. However, when formalin-induced nociceptive response was blocked by a local anesthetic, memory impairment was prevented. These findings suggest that pain-induced impairment in the consolidation of object recognition memory does not directly depend on the intensity of nociceptive activity.
Anti-inflammatory and anti-hypersensitive effects of the chalcone isocordoin and its semisynthetic derivatives in mice
Authors: Da Silva Gislaine Francieli , De Campos Buzzi Fátima , Santin José Roberto , Yam-Puc Alejandro , Escalante-Erosa Fabiola , Sosa Karlina-García , Klein Luiz Carlos , Peña Rodriguez Luis Manuel , Cechinel Filho Valdir , Quintão Nara Lins Meira
Published: September 2020

Isocordoin (1), a chalcone isolated from different plants, has been found to present a range of interesting biological properties. This study aimed to evaluate the anti-hypersensitive and anti-inflammatory effects of isocordoin (1) and several natural and semisynthetic derivatives (2–10). Initial evaluation of (1), dihydroisocordoin (2) and six semisynthetic derivatives (3–8) in the inhibition of abdominal writhes induced by acetic acid model showed that only isocordoin dimethylether (5) caused more than 70% of inhibition. Further evaluation of 5 for its anti-oedematogenic activity and anti-hypersensitivity effect induced by carrageenan, lipopolysaccharide (LPS), bradykinin (BK), prostaglandin E2 (PGE2), and epinephrine showed that isocordoin dimethylether (5) presented a discrete inhibition of carrageenan- and LPS-induced hypersensitivity, and of carrageenan-induced paw oedema, and that it was able to significantly reduce both the oedema and hypersensitivity induced by BK. Furthermore, when tested in the PGE2 model, 5 interfered only with the paw-oedema, without showing any effect against the paw-hypersensitivity. Evaluation of the natural isocordoin (1), together with the semisynthetic derivatives isocordoin dimethylether (5), isocordoin methylether (9), and dihydroisocordoin methylether (10) in the BK-induced oedema and hypersensitivity showed that the monoalkylated derivatives 10 and 9 had the strongest antinociceptive activity. The results of this investigation indicate that both monoalkylation of the C-4′ phenolic hydroxyl group and reduction of the double bond in the α,β-unsaturated system of the chalcone skeleton favor activity.
The antinociceptive mechanisms of melatonin: role of l-arginine/nitric oxide/cyclic GMP/KATP channel signaling pathway
Authors: Fakhri Sajad , Ahmadpour Yasaman , Rezaei Hoda , Kooshki Leila , Moradi Seyed Zachariah , Iranpanah Amin , Gravandi Mohammad Mehdi , Abbaszadeh Fatemeh , Ghanbarveisi Farnia
Published: September 2020

Pain is one of the most common medical challenges, reducing life quality. Despite the progression in pain management, it has remained a clinical challenge, which raises the need for investigating novel antinociceptive drugs with correspondence signaling pathways. Besides, the precise antinociceptive mechanisms of melatonin are not revealed. Accordingly, owing to the critical role of l-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/KATP in the antinociceptive responses of various analgesics, the role of this signaling pathway is evaluated in the antinociceptive effects of melatonin. Male NMRI mice were intraperitoneally pretreated with the injection of l-arginine (NO precursor, 100 mg/kg), N(gamma)-nitro-l-arginine methyl ester [l-NAME, NO synthase (NOS) inhibitor, 30 mg/kg], S-nitroso-N-acetylpenicillamine (SNAP, NO donor, 1 mg/kg), sildenafil (phosphodiesterase inhibitor, 0.5 mg/kg), and glibenclamide (KATP channel blocker, 10 mg/kg) alone and before the administration of the most effective dose of melatonin amongst the intraperitoneal doses of 50, 100, and 150 mg/kg. The formalin test (2%, 25 µL, intra-plantarly) was done following the melatonin administration, then the nociceptive responses of mice were evaluated during the early phase for 5 min and the late phase for 15 min. The results showed that 100 mg/kg dose of melatonin carried out the most antinociceptive effects. While the antinociceptive effect of melatonin was increased by l-arginine, SNAP, and sildenafil, it was significantly reduced by l-NAME and glibenclamide in both phases of the formalin test, with no relation to the sedative effects of melatonin evaluated by the inclined plane test. In conclusion, the antinociceptive effect of melatonin is mediated through the l-arginine/NO/cGMP/KATP pathway.
Neuroimaging reveals functionally distinct neuronal networks associated with high-level alcohol consumption in two genetic rat models
Authors: Pallarés Vicente , Dudek Mateusz , Moreno Andrea , Pérez-Ramírez Úrsula , Moratal David , Haaranen Mia , Ciccocioppo Roberto , Sommer Wolfgang H. , Canals Santiago , Hyytiä Petri
Published: September 2020

Human imaging data suggest that the motivational processes associated with alcohol reward are reflected in the patterns of neural activation after alcohol or alcohol-related cues. In animal models of alcohol drinking, however, the changes in brain activation during voluntary alcohol ingestion are poorly known. In order to improve the translational utility of animal models, we examined alcohol-induced functional brain activation in Alko Alcohol (AA) and Marchigian-Sardinian alcohol-preferring (msP) rats that drink voluntarily high levels of alcohol, but exhibit widely different neurochemical and behavioral traits cosegregated with alcohol preference. Brain imaging was performed using manganese-enhanced MRI (MEMRI), which is based on accumulation of Mn2+ ions in activated neurons, allowing the identification of functional neuronal networks recruited during specific behaviors in awake animals during a subsequent imaging session under anesthesia. MEMRI was performed following 4 weeks of voluntary alcohol drinking, using water drinking as the control. Despite similar levels of alcohol drinking, strikingly different alcohol-induced neuronal activity patterns were observed in AA and msP rats. Overall, functional activation in the AA rats was more widespread, involving large cortical areas and subcortical structures, such as the bed nucleus of the stria terminalis, preoptic area, hypothalamus, periaqueductal grey, and substantia nigra. In the msP rats, however, alcohol-related activation was largely confined to prefrontal cortical regions and insular cortex, and olfactory areas. Overlapping areas of activation found in both rat lines included the nucleus accumbens, prelimbic, orbital, and insular cortex. In conclusion, our data reveal strikingly different brain circuits associated with alcohol drinking in two genetically different rat lines and suggest innately different motivational and behavioral processes driving alcohol drinking. These findings have important implications for the use of these lines in translational alcohol research.
Effects of the GluN2B antagonist, Ro 25-6981, on extinction consolidation following adolescent- or adult-onset methamphetamine self-administration in male and female rats
Authors: Westbrook Sara R. , Gulley Joshua M.
Published: September 2020

Previous work suggests adolescent rats have deficient extinction consolidation relative to adults. Although the mechanisms underlying this age difference are currently unknown, studies in adult rats have implicated GluN2B-containing N-methyl-d-aspartate (NMDA) receptor function in extinction consolidation of drug-associated memory. Importantly, GluN2B neurotransmission emerges during adolescent development, and drugs of abuse during adolescence may delay the development of extinction consolidation by disrupting the ontogeny of GluN2B function. Here, we trained Sprague–Dawley rats of both sexes to self-administer methamphetamine [METH, 0.1 mg/kg/infusion intravenous (i.v.)] beginning during adolescence [postnatal (P) day 41] or adulthood (P91). Rats were given short access (2 h) to self-administer METH in seven daily sessions followed by 14 sessions with long access (6 h). Subsequently, rats underwent four daily 30-minute extinction sessions with immediate postsession injections of either a GluN2B antagonist [Ro25–6981; 6 mg/kg, intraperitoneal (i.p.)] or a vehicle solution. After four daily 2-h extinction sessions, a priming injection (1 mg/kg METH, i.p.) was given prior to a final 2-h reinstatement session. During LgA, adolescent-onset rats earn more METH than adult-onset rats and display greater drug-loading behavior. Rats reduced their drug-seeking behavior across the extinction sessions, with no significant group differences. Rats reinstated drug-seeking following the METH-priming injection, with females displaying greater reinstatement than males. These results do not support our a priori hypothesis that adolescent-onset METH use disrupts the ontogeny of GluN2B transmission and contributes to age-of-onset differences in extinction of METH-seeking. However, our findings suggest that age-of-onset contributes to excessive METH-taking, while sex confers vulnerability to relapse to METH-seeking.
The orexin receptors in the ventral tegmental area are involved in the development of sensitization to expression of morphine-induced preference in rats
Authors: Mahmoudi Dorna , Assar Nasim , Mousavi Zahra , Katebi Seyedeh-Najmeh , Azizi Pegah , Haghparast Abbas
Published: September 2020

Recent studies have shown that orexin neurons in the lateral hypothalamus send a compelling project to the ventral tegmental area (VTA). Besides, orexin-1 (OX1) and orexin-2 (OX2) in the VTA are necessary for the development of morphine-induced place preference. Also, sensitivity to morphine can reinforce the rewarding effects of morphine. The current study aims to determine the role of VTAs orexin receptors in morphine sensitization in rats. In 84 adult male albino Wistar rats, two separate cannulae bilaterally implanted into the VTA. They received intra-VTA infusions of SB334867 (0.1, 1 and 10 nM) and TCS OX2 29 (1, 7 and 20 nM) as OX1 and OX2 receptor antagonists, respectively, 10 min before subcutaneous administration of morphine (5 mg/kg) during 3-day sensitization period. After a 5-day drug-free period, the conditioned place preference (CPP) paradigm induced by subthreshold doses of morphine (0.5 mg/kg), and CPP scores were measured by EthoVision software. The results revealed that the blockade of both OX1 and OX2 receptors within the VTA reduced the expression of morphine-induced CPP in the sensitized rats. It is plausible that VTAs orexin receptors are involved in the development/acquisition of sensitization to morphine-induced CPP in the rats.
Appropriateness of the Direct Oral Anticoagulants Dosing in the Middle East Gulf Region
Authors: Anouassi Zohour , Atallah Bassam , Alsoud Leen Oyoun , El Nekidy Wasim , Al Mahmeed Wael , AlJaabari Mohamed , Almuti Khalid
Published: September 2020

Direct oral anticoagulants (DOACs) have proven efficacy to prevent cardioembolic strokes. Data are scarce about the appropriateness of DOAC dosing in the Middle East. We investigated the prevalence of inappropriate DOAC dosing in the region. A cross-sectional study was conducted at our hospital between April 2015 and February 2019 of patients receiving 1 of the 3 available DOACs. Patients with incomplete data sets, those prescribed DOACs for indications other than atrial fibrillation, on DOACs for <30 days, and dialysis patients were excluded. A total of 608 met the inclusion criteria. The mean age was 65.2 ± 13.9 years, and most were men (58.6%). The mean CHA2DS2-VASc score was 3.8 ± 2.0. There were 346 (56.9%) on apixaban, 123 (20.2%) on dabigatran, and 139 (22.9%) on rivaroxaban. The logistic regression model showed that for the 3 agents together, age, eGFR, major bleeding history, and history of prior stroke were significantly associated with the decision to inappropriately underdose (P < 0.05). Fifteen patients had an ischemic stroke after apixaban initiation (5 underdosed and 3 overdosed). Among patients with at least one follow-up encounter, major bleeding occurred in 13 patients (11.7%) with inappropriate dosing compared with 29 patients (6.0%) with appropriate dosing (P = 0.04). Ischemic stroke occurred in 11 patients (9.9%) with inappropriate dosing compared with 15 patients (3.1%) with appropriate dosing (P < 0.01). We concluded that inappropriate DOAC underdosing is common in our region, particularly with apixaban and rivaroxaban. It is associated with increased risk of stroke and bleeding. More education targeting prescribers is needed to encourage adherence to standard dosing criteria.
Body Surface Area Dosing of High-Dose Methotrexate Should Be Reconsidered, Particularly in Overweight, Adult Patients
Authors: Gallais Fanny , Oberic Lucie , Faguer Stanislas , Tavitian Suzanne , Lafont Thierry , Marsili Sabrina , Brice Aurélie , Chatelut Etienne , Puisset Florent
Published: September 2020

Background:

High-dose methotrexate is used for treating several types of cancer. However, it is associated with a high risk of acute kidney injury (AKI), especially in patients with high MTX concentrations. Although therapeutic drug monitoring is performed to monitor MTX concentrations, it is unclear what concentration should be considered critical, thus requiring rescue protocols to prevent nephrotoxicity.

Methods:

Patients treated with high-dose methotrexate for lymphoma or acute lymphoblastic leukemia and those benefited from therapeutic drug monitoring were included. The relationship between MTX concentrations and the presence or absence of AKI was assessed. MTX concentrations were analyzed using a population pharmacokinetic approach. Specific attention was given to morphological covariates because MTX doses are individualized according to body surface area (BSA).

Results:

In total, 328 patients and 657 cycles of treatment were analyzed. Higher MTX concentrations were observed in the AKI+ group. For cycle 1, all patients showing an MTX concentration >6 µM at 36 hours or >2 µM at 48 hours after infusion developed nephrotoxicity. The final pharmacokinetic model had 2 compartments and included the effect of age on clearance (CL) and of body weight on peripheral distribution volume. None of the morphological covariates tested on CL led to significant improvement in the model. Higher MTX concentrations were observed in patients with extreme BSA values (≥2 m2) or body mass index (≥25 kg/m2). Patients with AKI who received at least 1 cycle had higher BSA and BMI.

Conclusions:

The results from this study provide additional information on the relationship between MTX concentration and nephrotoxicity. Patients with a plasma MTX concentration >6 µM at 36 hours were more likely to manifest AKI. In addition, the results suggest that overweight patients have a high AKI risk and that BSA-based adjustment of MTX dose is not appropriate.
Updates in treating fecal incontinence in women
Authors: Kim Youngwu , Ortega Marcus , Von Bargen Emily
Published: September 2020

Purpose of review

Fecal incontinence is a chronic condition that can significantly affect a woman's quality of life. The pathogenesis of fecal incontinence is multifaceted and management ranges from supportive care, medical therapy to more invasive surgical procedures. This review will discuss the recent advancements in treating fecal incontinence.

Recent findings

The pelvic floor disorder consortium has created a consensus document with recommendations on pelvic floor symptom measurement tools, patient-reported instruments, and questionnaires that should be used when evaluating fecal incontinence. There is new robust data reinforcing the importance of conservative management prior to proceeding with more invasive treatment. Lastly, several novel therapies that were developed in the past decade now have longer term data on safety and efficacy.

Management of fecal incontinence is challenging, as no one therapy has been proven to be predominately effective. We should continue to first optimize patients with conservative therapy followed by induction of more advanced therapies. There needs to be continued efforts to develop and evaluate effective treatment guidelines and therapies for fecal incontinence.
Penetrating atherosclerotic ulcer
Authors: Evangelista Arturo , Moral Sergio
Published: September 2020

Purpose of review

Penetrating aortic ulcer (PAU) is defined as ulceration of an aortic atherosclerotic plaque penetrating through the internal elastic lamina into the media. With the advances in imaging techniques, the differential diagnosis between PAU and other aortic ulcers remains a challenge. This review aims to summarize the latest insight into PAU, based on clinical context and the newest imaging characteristics, to aid treatment decision-making.

Recent findings

Most PAUs are asymptomatic and do not require urgent invasive treatment. Nevertheless, when PAU leads to an acute aortic syndrome, emergency invasive therapy is recommended. A differential diagnosis with other lesions, such as ulcerated plaques or intimal disruptions within the context of an aortic intramural hematoma, is required as the risk of complications and management differ. Imaging technique plays a pivotal role in the correct diagnosis of aortic ulcers.

The differential diagnosis of PAU with other aortic ulcers based on clinical and imaging technique information is mandatory as it may imply different prognosis and management. This diagnosis is particularly important when PAU is the cause of acute aortic syndromes as urgent invasive treatment should be recommended.
Generalizability of Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial in patients with a history of coronary artery bypass graft surgery
Authors: Kosmopoulos Andrew , Verma Subodh , Meglis Gus , Bhatt Deepak L. , Verma Raj , Mazer C. David , Voisine Pierre
Published: September 2020

Purpose of review

Following coronary artery bypass grafting (CABG), there remains persistent risk of ischemic events despite secondary prevention strategies, including low-density lipoprotein cholesterol lowering. Although REDUCE-IT recently demonstrated the benefits of icosapent ethyl (IPE) on reducing ischemic events in a broad population of primary and secondary prevention patients, its generalizability to a contemporary CABG population is not known. This article aims to ascertain the proportion of patients with a history of CABG that would be eligible for IPE treatment.

Recent findings

A review of recent literature highlights the presence of residual ischemic following CABG. Using the Québec Heart Database, a repository of contemporary Canadian cardiac patient information, was searched between 1 January 2006 and 31 December 2016, to ascertain generalizability of IPE.

In a large (N = 12 641), contemporary, Canadian cohort of patients with a history of CABG and currently on statin therapy, 21.9, 33.6 and 26.4% would be eligible for IPE, according to REDUCE-IT, Health Canada, and Food and Drug Administration criteria, respectively. These analyses would support IPE as an adjunct to secondary prevention therapies post-CABG.