bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of artificial ascites to assist thermal ablation of liver cancer adjacent to the gastrointestinal tract in patients with previous abdominal surgery
Authors: Huang Qiannan , Li Jianguo , Zeng Qingjing , Tan Lei , Zheng Rongqin , He Xuqi , Li Kai
Published: August 2020

Background

To evaluate the feasibility and effectiveness of artificial ascites to assist thermal ablation of liver cancer adjacent to the gastrointestinal tract in patients with previous abdominal surgery.

Methods

Thirty-nine patients with a total of 40 liver malignant tumors were enrolled between January 2016 and June 2019. All had histories of hepatectomy, splenectomy, cholecystectomy, and intestinal surgery. The distance between the tumor and the gastrointestinal tract was < 5 mm. Normal saline was used as artificial ascites to protect the gastrointestinal tract during thermal ablation. The success rate of the procedure, incidence of major complications, and the technical efficacy of ablation were recorded. Patients were followed for local tumor progression (LTP), and overall survival (OS).

Results

The use of artificial ascites was successful in 38 of the 40 procedures (95%). Major complications occurred in two of the 39 patients (5.1%) following the procedure. One was an intestinal fistula that occurred in a failed case and was associated with an infection. The other was a liver abscess that occurred in a successful case. The technical efficacy of ablation was 100% (40/40 procedures). The median follow-up was 16 months. The 1-, 2-, and 3-year LTP rates were 2.9, 5.7 and 5.7%. The 1-, 2-, and 3-year OS rates were 97.1, 86.8 and 69.5%.

Conclusion

In patients with previous abdominal surgery, artificial ascites is feasible and effective for assisting thermal ablation of liver cancer adjacent to the gastrointestinal tract.
Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome
Authors: Ciappuccini Renaud , Heutte Natacha , Lasne-Cardon Audrey , Saguet-Rysanek Virginie , Leroy Camille , Le Hénaff Véronique , Vaur Dominique , Babin Emmanuel , Bardet Stéphane
Published: August 2020

Background

In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome.

Methods

This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or18FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively.

Results

PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively,p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9–12 months after initial therapy (71, 20 and 7%, respectively;p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively;p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and18FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit.

Conclusions

The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.
Examining the implementation of the Icelandic model for primary prevention of substance use in a rural Canadian community: a study protocol
Authors: Halsall Tanya , Lachance Lisa , Kristjansson Alfgeir L.
Published: August 2020

Background

The Icelandic Prevention Model (IPM) is a collaborative upstream model that was designed to influence risk and protective factors related to substance use within the community, school, peer and family contexts. By engaging whole communities, the IPM has been found to be effective in reducing youth substance use behaviours across Iceland. As an extension to the IPM’s participatory approach, this research will examine how youth involvement can enhance outcomes. In addition, this research will evaluate whether the IPM approach is beneficial for mental health promotion and general youth wellbeing.

Methods

The present research protocol applies the bioecological model within a participatory mixed-method case study design to examine the implementation of the IPM in a rural community in Canada. This study was designed to identify whether the Icelandic substance use prevention model is effective in reducing substance use and promoting mental health and development for Canadian youth. It will also explore how to engage youth within the approach and how this adaptation influences implementation and outcomes.

Discussion

The findings from this study will contribute to our understanding of upstream prevention of youth substance use and will be used to support scaling of the IPM across Canada.
LINC02418 promotes malignant behaviors in lung adenocarcinoma cells by sponging miR-4677-3p to upregulate KNL1 expression
Authors: Wang Tao , Zhai Ruiren , Lv Xiuhua , Wang Ke , Xu Junqing
Published: August 2020

Background

Lung adenocarcinoma (LAD) is a prevalent type of bronchogenic malignant tumor and one of the most critical factors related to human death. Long noncoding RNAs (lncRNAs) are involved in many complex biological processes and have been emerged as extremely important regulators of various cancers. LINC02418, a novel lncRNA, hasn’t been mentioned in previous studies on cancer development. Therefore, it’s important to define the potential function of LINC02418 in LAD.

Methods

Gene expression was examined by RT-qPCR or western blot. CCK-8, colony formation, TUNEL, and transwell assays were utilized to study the role of LINC02418 in LAD. The interaction of miR-4677-3p with LINC02418 (or KNL1) was verified through luciferase reporter, RIP and RNA pull-down assays.

Results

High expression of LINC02418 was observed in LAD specimens and cells. Downregulation of LINC02418 obstructed the proliferation and motility of LAD cells. Moreover, LINC02418 negatively modulated miR-4677-3p expression and miR-4677-3p overexpression could repress cell proliferation and migration. Moreover, kinetochore scaffold 1 (KNL1) expression was negatively modulated by miR-4677-3p but positively regulated by LINC02418. Furthermore, miR-4677-3p could bind with LINC02418 (or KNL1). Finally, KNL1 overexpression reversed the inhibitory function of LINC02418 deficiency in the malignant behaviors of LAD cells.

Conclusions

LINC02418 contributes to the malignancy in LAD via miR-4677-3p/KNL1 signaling, providing a probable therapeutic direction for LAD.
Lung nodules and IgG4 related disease: a single-center based experience
Authors: Xie Yan , Xiong Anji , Marion Tony , Liu Yi
Published: August 2020

Background

This study was undertaken in an attempt to characterize the frequency and clinical features of lung nodules in IgG4 related disease (IgG4-RD) patients as an insight for help with the diagnosis of lung nodules.

Methods

A retrospective study was carried out in West China Hospital, Sichuan University from January 2012 to December 2018, 89 patients with definite IgG4-RD were enrolled.

Results

Fifty of 89 patients with definite IgG4-RD had radiologically confirmed lung nodules, 6 of whom were diagnosed with definite IgG4 related lung disease. Lung nodules detected in more than 40 patients were small and solid, always with regular margins. Multiple (41/50) and bilateral (34/50) distributions was also a major characteristic of these lung nodules. Lobulation and speculation were simultaneously detected in 3 patients, including 2 patients combined with pleural indentation. Calcification of nodules was detected in only one patient. Thirty-seven patients also had additional radiological abnormalities of lungs, including ground-glass opacity (21/50), thickening of pleura (9/50), thickening of interlobular septa (4/50), thickening of bronchial wall (3/50), pleural effusion (4/50), mass (3/50), interstitial changes (5/50), and mediastinal or hilar lymphadenopathy (32/50). Most patients (44/50) were treated with glucocorticoids alone or combined with immunosuppressive agents. Sixteen patients received a re-examination by chest computed tomography (CT) scan after treatment, 10 of whom showed a decrease in the size and/or the number of nodules.

Conclusions

The incidence of lung nodules in IgG4-RD patients can be high. For an IgG4-RD patient with lung nodules, the possibility that the lung nodules related to IgG4-RLD is high. It is hard to differentiate IgG4 related lung nodules from other lung diseases, in particular, lung cancer. Radiological characteristics and positive responses to glucocorticoids and immunosuppressive agents can help with the differential diagnosis. For these patients, regular follow-up is also important.
Knowledge, attitude, practice, and predictors of female genital mutilation in Degadamot district, Amhara regional state, Northwest Ethiopia, 2018
Authors: Melese Gedif , Tesfa Mulugeta , Sharew Yewbmirt , Mehare Tsegaye
Published: August 2020

Background

Female genital mutilation is defined as all procedures that involve partial or total removal of external female genitalia, or other injuries to the female genital organs for cultural and religious purposes. In Ethiopia, the prevalence of female genital mutilation practice was 70.8% according to Ethiopian demographic and health survey 2016. This practice is against females’ reproductive health rights with many serious consequences in physical, mental, social and psychological makeup. Therefore, this study aimed to assess knowledge, attitude, practice, and predictors of female genital mutilation in Degadamot district.

Methods

A community-based cross-sectional study design was conducted. Three hundred twenty-five mothers who had under 5 years old female children were selected using systematic random sampling from seven kebeles of Degadamot district. Data were collected using an adapted semi-structured face to face interview questionnaire. Data were entered into Epi-data version 3.1 and then exported to SPSS version 20 for analysis. Logistic regression analysis with 95% confidence intervals was carried out to determine the associations between predictor variables and outcome variables.

Result

The finding of this study revealed that 56.6% of mothers had good knowledge about female genital mutilation and 54.2% of participants had a favorable attitude about female genital mutilation. 70.8% of under 5 years old female children’s had female genital mutilation. Marital status AOR = 7.19(95%CI3.22–16.03), monthly income AOR = 1.97(95% CI 0.26–3.81), custom AOR = 2.13(95% CI 1.20–3.78), belief AOR =2.47(95% CI 1.39–4.39), value AOR = 0.37(95% CI 0.22–0.63), and attitude AOR = 24.4(95% CI 20.01–34.76) towards female genital mutilation had significant association with female genital mutilation practice.

Conclusion

Prevalence of FGM practices among female children of under 5 years of age was found to be high as compared to the national level (64%). 56.6% of mothers had good knowledge about FGM. The majority of the women had a favorable attitude to keep FGM practice among their under 5 years old daughters. Marital status, monthly income, custom, belief, value, and attitude had a significant association with FGM practice.
Electronic ordering and the management of treatment interdependencies: a qualitative study of paediatric chemotherapy
Authors: Lichtner Valentina , Franklin Bryony Dean , Dalla-Pozza Luciano , Westbrook Johanna I.
Published: August 2020

Background

There are serious safety risks associated with chemotherapy, often associated with interdependencies in regimens administered over months or years. Various strategies are used to manage these risks. Computerized provider order entry (CPOE) systems are also implemented to improve medication safety. Little is known regarding the effect of CPOE on how clinicians manage chemotherapy interdependencies and their associated safety strategies.

Methods

We conducted a multi-method qualitative study in a paediatric hospital. We analysed 827 oncology incidents reported following CPOE implementation and carried out semi-structured interviews with doctors (n = 10), nurses (n = 6), a pharmacist, and oncology CPOE team members (n = 2). Results were interpreted according to safety models (ultra-safe, high-reliability organisations [HROs], or ultra-adaptive).

Results

Incident reports highlighted two interrelated types of interdependencies: those within organisation of clinical activities and those inherent in chemotherapy regimens. Clinicians reported strategies to address chemotherapy risks and interdependencies. These included rigid rules and ‘no go’ contexts for treatment to proceed, typical of the ultra-safe model; use of time (e.g. planning only so far ahead) and sensitivity to operations, typical of HROs. We identified three different time horizons in CPOE use in relation to patients’ treatments: life-long, the whole regimen, and the ‘here and now’. CPOE supported ultra-safe strategies through automation and access to rules/standardisation, but also created difficulties and contributed to incidents. It supported the ‘here and now’ better than a life-long or whole regimen view of a patient treatment. Sensitivity to operations was essential to anticipate and resolve uncertainties, hazards, CPOE limitations, and mismatches between CPOE processes and workflow in practice.

Conclusions

Within oncology, CPOE appears to move the ‘mix’ of risk strategies towards ultra-safe models of safety and protocol-mandated care. However, in order to operate ultra-safe strategies embedded in CPOE and stay on protocol it is essential for clinicians to be thoughtful and show sensitivity to operations in CPOE use. CPOE design can be advanced by better consideration of mechanisms to support interdependencies.
Structure evaluation of the implementation of geriatric models in primary care: a multiple-case study of models involving advanced geriatric nurses in five municipalities in Norway
Authors: Antypas Konstantinos , Kirkevold Marit
Published: August 2020

Background

The Advanced Geriatric Nurse role recently has been introduced into Norway’s primary healthcare system, and our study’s purpose was to examine the implementation of models of care developed for Advanced Geriatric Nurse in primary care. With a structure evaluation, we tried to identify conditions that affect the implementation of different models of care and understand how these conditions affected the realisation of each model’s intentions and goals.

Methods

An embedded multiple-case study was used that included five Norwegian municipalities and seven AGNs. The study included data from August 2014 through September 2018. We used data from 25 semi-structured face-to-face interviews with AGNs and stakeholders, documents and statistical information. We used a cross-case procedure with an emphasis on case findings for the analysis of the multiple case study.

Results

We analysed the structure-related conditions on two levels: the meso-level and the micro-level. On the meso-level, we found that the conditions that affected the implementation of the different models of care were related to each municipality’s structure characteristics, stakeholders’ involvement in the design of the models of care, the clarity of the models and their goals, the evaluation of the models and their adaptation. At the micro-level, we found that the conditions that affected the models’ implementation were related to the collaboration within the implemented models of care, the role clarity of Advanced Geriatric Nurses themselves and adjustments within the models.

Conclusions

The implementation of the AGN role in Norway seems to have been implemented in ways that can impact patients and municipalities positively. Potential improvements include extensive stakeholder involvement, improved roles, goal clarity and better documentation of structures and outcomes. The models’ dynamic nature seemed to be a beneficial characteristic, but adaptation should be systematic and a necessary time should be considered for a new model of care to be integrated and produce results.
Hospital characteristics associated with low-value care in public hospitals in New South Wales, Australia
Authors: Badgery-Parker Tim , Pearson Sallie-Anne , Elshaug Adam G.
Published: August 2020

Background

Rates of low-value care vary between hospitals in New South Wales, Australia. Understanding factors associated with this variation will help in understanding the drivers of low-value care and in planning initiatives to reduce low-value care.

Methods

For eight low-value procedures, we used Poisson regression of the number of low-value episodes at each hospital to assess the association between low-value care and hospital characteristics. We also used hierarchical clustering on the low-value procedures used and their rates at each hospital to try to identify groups of hospitals with higher or lower rates of low-value care across multiple procedures.

Results

Some hospital characteristics, such as hospital peer group and proportion of total episodes that involve the specific procedure, showed associations for some procedures, but none were consistent across all eight procedures. We clustered hospitals into five groups, but low-value care rates did not differ much between these groups.

Conclusion

Available hospital variables show little association with rates of low-value care and no patterns across different low-value procedures. We need to investigate factors within hospitals, such as clinician knowledge and beliefs about low-value care.
Indirect implications of COVID-19 prevention strategies on non-communicable diseases
Authors: Modesti Pietro A. , Wang Jiguang , Damasceno Albertino , Agyemang Charles , Van Bortel Luc , Persu Alexandre , Zhao Dong , Jarraya Faical , Marzotti Ilaria , Bamoshmoosh Mohamed , Parati Gianfranco , Schutte Aletta E.
Published: August 2020

Background

After its outbreak in China, the novel COronaVIrus Disease 19 is spreading across the globe. It is an emergency the world has never seen before.

Main text

The attention of health systems is mainly focused on COronaVIrus Disease 19 patients and on the risk that intensive care units might be overwhelmed by the serious pulmonary complications. Different countries are also attempting to establish infection prevention and control strategies which proved effective in China where the outbreak was initially reported. We reflect on important lessons to be learnt from different countries. The effects that infection prevention and control strategies, such as social distancing or isolation, can have on the care of millions of patients with non-communicable diseases, who may be indirectly affected, have not been taken into consideration so much.

Conclusions

When dealing with COronaVIrus Disease 19, policy makers and healthcare personnel should consider the indirect effects on the treatment of non-communicable diseases.
Effects of canola or olive oil on plasma lipids, lipoprotein-associated phospholipase A2 and inflammatory cytokines in patients referred for coronary angiography
Authors: Khandouzi Nafiseh , Zahedmehr Ali , Nasrollahzadeh Javad
Published: August 2020

Background

The potential cardioprotective benefits of olive oil (OO) and canola oil (CO) consumption have been shown in some studies. The present study compared the effects of CO and OO on plasma lipids, some inflammatory cytokines, and lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity in patients undergoing coronary angiography.

Methods

The current randomized, controlled, parallel-arm, clinical trial involved 48 patients (44 men and 4 women, aged 57.63 ± 6.34 years) with at least one classic cardiovascular risk factor (hypertension, dyslipidemia, or diabetes) who referred for coronary angiography. Patients were randomly divided into two groups and received 25 mL/day refined olive oil (n = 24) or canola oil (n = 24) for 6 weeks. Plasma lipids, some selected inflammatory markers, and Lp-PLA2 levels were measured at baseline and after the intervention.

Results

CO consumption produced a significant reduction in plasma Lp-PLA2 mass (− 0.97 ± 1.84 vs. 0.34 ± 1.57 ng/mL, p = 0.008 for CO and OO, respectively), whereas the mean changes in interleukine-6 concentration were significantly lower after OO consumption compared with CO (− 9.46 ± 9.46 vs. -0.90 ± 6.80 pg/mL, p = 0.008 for OO and CO, respectively). After 6 weeks of intervention, no significant changes were observed in plasma Lp-PLA2 activity, complement C3, C4, or lipid profiles in the two intervention groups.

Conclusions

Comparing the two vegetable oils in subjects with cardiovascular risk factors showed that the consumption of olive oil is more effective in reducing the level of inflammatory cytokine interleukine-6, whereas canola oil was more effective in lowering Lp-PLA2 levels; however, this finding should be interpreted with caution, because Lp-PLA2 activity did not change significantly.

Trial registration

IRCT20160702028742N5 at www.irct.ir (04/19/2019).
Estimating EQ-5D utilities based on the Short-Form Long Term Conditions Questionnaire (LTCQ-8)
Authors: Tsiachristas Apostolos , Potter Caroline M. , Rocks Stephen , Peters Michele , Cundell Maureen , McShane Rupert , Batchelder Laurie , Fox Diane , Forder Julien E. , Jones Karen , Waite Felicity , Freeman Daniel , Fitzpatrick Ray
Published: August 2020

Purpose

The aim of this work was to develop a mapping algorithm for estimating EuroQoL 5 Dimension (EQ-5D) utilities from responses to the Long-Term Conditions Questionnaire (LTCQ), thus increasing LTCQ’s potential as a comprehensive outcome measure for evaluating integrated care initiatives.

Methods

We combined data from three studies to give a total sample of 1334 responses. In each of the three datasets, we randomly selected 75% of the sample and combined the selected random samples to generate the estimation dataset, which consisted of 1001 patients. The unselected 25% observations from each dataset were combined to generate an internal validation dataset of 333 patients. We used direct mapping models by regressing responses to the LTCQ-8 directly onto EQ-5D-5L and EQ-5D-3L utilities as well as response (or indirect) mapping to predict the response level that patients selected for each of the five EQ-5D-5L domains. Several models were proposed and compared on mean squared error and mean absolute error.

Results

A two-part model with OLS was the best performing based on the mean squared error (0.038) and mean absolute error (0.147) when estimating the EQ-5D-5L utilities. A multinomial response mapping model using LTCQ-8 responses was used to predict EQ-5D-5L responses levels.

Conclusions

This study provides a mapping algorithm for estimating EQ-5D utilities from LTCQ responses. The results from this study can help broaden the applicability of the LTCQ by producing utility values for use in economic analyses.
Assessment of the risk of permanent stoma after low anterior resection in rectal cancer patients
Authors: Zeman Marcin , Czarnecki Marek , Chmielarz Andrzej , Idasiak Adam , Grajek Maciej , Czarniecka Agnieszka
Published: August 2020

Background

One of the most severe complications of low anterior rectal resection is anastomotic leakage (AL). The creation of a loop ileostomy (LI) reduces the prevalence of AL requiring surgical intervention. However, up to one-third of temporary stomas may never be closed.

The first aim of the study was to perform a retrospective assessment of the impact of LI on the risk of permanent stoma (PS) and symptomatic AL. The second aim of the study was to assess preoperative PS risk factors in patients with LI.

Methods

A total of 286 consecutive patients who underwent low anterior rectal resection were subjected to retrospective analysis. In 101 (35.3%) patients, diverting LI was performed due to low anastomosis, while in the remaining 185 (64.7%) patients, no ileostomy was performed. LIs were reversed after adjuvant treatment. Analyses of the effect of LI on symptomatic AL and PS were performed. Among the potential risk factors for PS, clinical factors and the values of selected peripheral blood parameters were analysed.

Results

PS occurred in 37.6% and 21.1% of the patients with LI and without LI, respectively (p < 0.01). Symptomatic ALs were significantly more common in patients without LI. In this group, symptomatic ALs occurred in 23.8% of patients, while in the LI group, they occurred in 5% of patients (p < 0.001). In the LI group, the only significant risk factor for PS in the multivariate analysis was preoperative plasma fibrinogen concentration (OR = 1.007, 97.5% CI 1.002–1.013, p = 0.013).

Conclusions

Although protective LI may reduce the incidence of symptomatic AL, it can be related to a higher risk of PS in this group of patients. The preoperative plasma fibrinogen concentration can be a risk factor for PS in LI patients and may be a useful variable in decision-making models.
Correlation of low serum vitamin-D with uterine leiomyoma: a systematic review and meta-analysis
Authors: Mohammadi Ramin , Tabrizi Reza , Hessami Kamran , Ashari Hoda , Nowrouzi-Sohrabi Peyman , Hosseini-Bensenjan Mahnaz , Asadi Nasrin
Published: August 2020

Background

There is a growing body of evidence on low serum vitamin-D levels and the risk of uterine leiomyomas (UL). Therefore, this systematic review and meta-analysis was conducted to investigate the association between serum vitamin D levels and UL occurrence.

Methods

Searches were systematically conducted of the electronic databases PubMed, Scopus, EMBASE, Web of Science (ISI), Cochrane library, Ovid, and Google Scholar to identify relevant studies from inception until February 6, 2020. Heterogeneity across the included studies was examined using Cochran’s Q and I-square (I2). Data was pooled using random effects modeling and expressed as standardized mean differences (SMDs).

Results

Nine eligible studies with a total of 1730 participants (835 patients with UL and 895 controls) were included in the current meta-analysis. Pooled results with random effects modeling indicated that serum vitamin D levels were significantly lower in patients with UL than in the control group (n = 9, SMD = − 0.67; 95% CI, − 0.98, − 0.35, p < 0.001; I2 = 89.3%, p < 0.001). Based on the findings of subgroup analyses, it was found that the SMD values across the included studies from Asia (n = 4, SMD = − 1.20; 95% CI, − 1.45, − 0.96, p < 0.001; I2 = 30.6%, p = 0.229) were lower than those from Europe (n = 3, SMD = − 0.34; 95% CI, − 0.49, − 0.18, p < 0.001; I2 = 0.0%, p = 0.602) and Africa (n = 2, SMD = − 0.13; 95% CI, − 0.29, 0.04, p = 0.128; I2 = 0.0%, p = 0.417), although the difference was not significant in Africa. Publication year was also found to be a potential contributor’s variable in the pooled SMD using the meta-regression method (t = − 3.00, p = 0.02).

Conclusions

To the best of our knowledge, the current meta-analysis showed for the first time that serum vitamin D levels were significantly lower in women with UL in selected populations.
Therapeutic Trem2 activation ameliorates amyloid-beta deposition and improves cognition in the 5XFAD model of amyloid deposition
Authors: Price Brittani R. , Sudduth Tiffany L. , Weekman Erica M. , Johnson Sherika , Hawthorne Danielle , Woolums Abigail , Wilcock Donna M.
Published: August 2020

Background

Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer’s disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action in an aggressive mouse model of amyloid deposition.

Methods

To determine whether agonism of Trem2 results in therapeutic benefits, we designed both intracranial and systemic administration studies. 5XFAD mice in the intracranial administration study were assigned to one of two injection groups: AL002a, a Trem2-agonizing antibody, or MOPC, an isotype-matched control antibody. Mice were then subject to a single bilateral intracranial injection into the frontal cortex and hippocampus and euthanized 72 h later. The tissue from the left hemisphere was histologically examined for amyloid-beta and microglia activation, whereas the tissue from the right hemisphere was used for biochemical analyses. Similarly, mice in the systemic administration study were randomized to one of the aforementioned injection groups and the assigned antibody was administered intraperitoneally once a week for 14 weeks. Mice underwent behavioral assessment between the 12- and 14-week timepoints and were euthanized 24 h after their final injection. The tissue from the left hemisphere was used for histological analyses whereas the tissue from the right hemisphere was used for biochemical analyses.

Results

Here, we show that chronic activation of Trem2, in the 5XFAD mouse model of amyloid deposition, leads to reversal of the amyloid-associated gene expression signature, recruitment of microglia to plaques, decreased amyloid deposition, and improvement in spatial learning and novel object recognition memory.

Conclusions

These findings indicate that Trem2 activators may be effective for the treatment of AD and possibly other neurodegenerative disorders.
Barriers of access and utilization of reproductive health services by adolescents-Khartoum state-Sudan-2020: study protocol
Authors: Elnimeiri Mustafa Khidir Mustafa , Satti Shahenaz Seifaldeen Mustafa , Ibrahim Mohanad Kamaleldin Mahmoud
Published: August 2020

Background

Adolescence is widely defined as the time in life when the developing individual attains the skills and attributes necessary to become a productive and reproductive adult. Most adolescents are healthy, but there is still substantial premature death, illness, and injury among adolescents. Illnesses can hinder their ability to grow and develop to their full potential. Alcohol or tobacco use, lack of physical activity, unprotected sex and/or exposure to violence can jeopardize not only their current health, but also their health as adults or even health of their future children.

Method

Community and institutional-based cross sectional study will be conducted in Khartoum State the seven localities will be included. This state is the national capital of Sudan, which has an area of 22,122 km2. The sample size of participant is estimated using the population formula (n = N/1+ (n*d2)). The sample will be drawn using multistage cluster sampling. Also the concerned bodies involved in the delivery of reproductive health services for adolescents included in this study. Data will be collected using interviews with key informants and administered pre-coded, pretested closed ended questionnaire with community participants. Data will be managed and analyzed using Statistical Package for Social Sciences version 21. Analysis is mostly univariate descriptive and bi-variate with Chi Square & Fischer Exact test analysis to find associations between variables of interest.

Discussion

The census of adolescents mounted to 25% of the population and thus it is important to care for such significant portion of the population to document their reproductive health problems and their access to health care services. The study is expected to generate base-line indicators about barriers of access to reproductive health services by adolescents that can be used for better planning, monitoring and evaluation of the delivered services. The research about barriers of access to reproductive health services by adolescents in Sudan is still limited and the information is scanty and scattered. Thus, it is necessary to conduct such study to enrich the current database.
Validation of family planning tool in the pastoralist community
Authors: Alemayehu Mussie , Medhanyie Araya Abrha , Reed Elizabeth , Bezabih Afework Mulugeta
Published: August 2020

Background

Pastoralist community, Afar, women felt that they are embedded in strong cultural and religious perspectives which promotes a high number of children, and discourages family planning (FP) use. They are multifaced factors which hinder women not to use FP and it is time to develop a context-based tool to understand the situation at the ground. However, we have a dearth of evidence on a reliable and valid tool. Therefore, this study aims in developing a reliable and valid tool that considers the women’s knowledge, male involvement, attitude, and belief about whether most people approve or disapprove of the behavior to use or not use of FP.

Methods

A total of 891 married women participated in the study. Reviewing the literature, piloting, pretesting, and collecting the actual data were the steps we used to develop a reliable and valid tool. We used the integrated behavioral model (IBM) as a conceptual framework for developing the tool. The developing tool consists of 1) knowledge 2) perceived male involvement and 3) constructs of integrated behavioral model (IBM); expressional and instrumental attitude, subjective norm, self-efficacy, perceived control and intention to use of FP. The IBM items composed of direct and indirect measurement. In the analysis of the data, exploratory and confirmatory factor analysis was done. Independent t. test with cohen’s d was used to calculate the effect size. The correlation coefficient was carried between the direct and indirect measurements of the items of the integrated behavioral model (IBM).

Results

A total of 891 pastoralist married women were included in the analysis of the reliability and validity of the tool. The mean age of the participants was 26.74(±6.45). The KMO value for all items was greater than 0.83 with a Bartlett test of sphericity of (p < 0.00). Thirteen items were used to measure the knowledge of the respondent towards FP use. The tool had 64.92 variances explained and Cronbach alpha of 0.85. Acceptable values of the fitness indices were obtained in the confirmatory factor analysis (CFA) The items of knowledge towards FP had normed chi-square of 4.5, RMSEA with 90% CI of 0.064(0.056,.0.071), SRMR of 0.039, CFI of 0.969 and TLI of 0961. All the developed items had a Cohen’sdranges from 0.5 to 2. Moreover, the correlation test of the IBM ranges from 0.6 to 0.7 which shows a higher correlation between the measurement direct and indirect items.

Conclusion

The pastoralist community version of the FP questionnaire is a valid and reliable tool and can be used to measure future family planning use. The indirect measurement of the IBM constructs was a good item to measure FP. However, as a limitation of the study respondents may face difficulty in realizing the difference one item to another especially when items on the scale look so similar to her.
Lumbar degenerative disease after oblique lateral interbody fusion: sagittal spinopelvic alignment and its impact on low back pain
Authors: Li Jia , Zhang Di , Shen Yong , Qi Xiangbei
Published: August 2020

Background

We determined the incidence and risk factors of low back pain (LBP) in patients with lumbar degenerative disease after single-level oblique lateral interbody fusion (OLIF).

Methods

We retrospectively reviewed 120 lumbar degenerative disease patients who underwent single-level OLIF. We compared preoperative and postoperative radiographic parameters, including segmental lordosis (SL), lumbar lordosis (LL), disk height (DH), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), and C7-sagittal vertical axis (SVA). Clinical outcomes were evaluated using the Oswestry Disability Index (ODI) scores and visual analog scale (VAS) scores for back and leg pain. All patients were followed up for at least 2 years.

Results

Thirty-eight patients had postoperative LBP (VAS score for back pain ≥3; LBP group); the remaining 82 patients were in the non-LBP group. Age (P= 0.082), gender (P= 0.425), body mass index (P= 0.138), diagnosis (degenerative spondylolisthesis vs. lumbar spinal stenosis;P= 0.529), surgical level (P= 0.651), blood loss (P= 0.889), and operative time (P= 0.731) did not differ between the groups. In both groups, the ODI and VAS scores for back pain and leg pain significantly improved at the final follow-up compared with the preoperative scores (P= 0.003). Except for the VAS score for back pain (P= 0.000), none of the scores significantly differed between the two groups at the final follow-up (P> 0.05). In the non-LBP group, LL, SL, DH, TK, and SS significantly improved, while PT and C7-SVA significantly decreased at the final follow-up as compared with the preoperative values. In both groups, DH significantly improved postoperatively, with no significant between-group difference (P= 0.325). At the final follow-up, LL, PI-LL mismatch, PT, and C7-SVA showed significantly greater improvement in the non-LBP group than in the LBP group (P< 0.05). Multivariate analysis identified PT, PI-LL mismatch, and C7-SVA as significant risk factors for LBP after OLIF.

Conclusion

OLIF for single-level lumbar degenerative disease had satisfactory clinical outcomes. PT, PI-LL mismatch, and C7-SVA were significant risk factors for postoperative LBP. Patients with appropriately decreased PT, improved C7-SVA, and PI-LL match experienced less LBP.
Intra-aortic balloon pump placement in coronary artery bypass grafting patients by day of admission
Authors: del Carmen Gabriel A. , Axtell Andrea , Chang David , Melnitchouk Serguei , Sundt Thoralf M. , Fiedler Amy G.
Published: August 2020

Introduction

Intra-Aortic Balloon Pumps (IABPs) can be utilized to provide hemodynamic support in high risk patients awaiting coronary artery bypass grafting (CABG). There are many indications for IABP and institutional practice patterns regarding the placement of IABPs is variable. As a result, the preoperative placement of an IABP in a patient awaiting CABG is not standardized and may vary according to non-clinical factors. We hypothesize that the rate of IABP placement varies by day of the week.

Methods

A retrospective cohort analysis of the Office of Statewide Health Planning and Development database from 2006 to 2010 was performed. All patients admitted for CABG were included. Patients who died within 24 h of admission and those who had absolute contraindications to IABP placement were excluded. The primary outcome was preoperative IABP placement versus non-placement. A multivariable logistic regression analysis to identify predictors of IABP placement was performed, adjusting for patient demographics, clinical factors, and system variables.

Results

A total of 46,347 patients underwent CABG, of which 7695 (16.60%) had an IABP placed preoperatively. On unadjusted analysis, IABP rates were significantly higher on weekends versus weekdays (20.83% vs. 15.70%,p < 0.001). On adjusted analysis, patients awaiting CABG were 1.30 times more likely to have an IABP placed on weekends than on weekdays (OR: 1.30, 95% CI 1.20–1.40,p < 0.001).

Conclusion

The odds of preoperative IABP placement prior to CABG is significantly increased on weekends compared to weekdays, even when controlling for clinical factors. Further exploration of this phenomenon and its associations are warranted.
Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial
Authors: Miller Joseph , Bruen Charles , Schnaus Michael , Zhang Jeffrey , Ali Sadia , Lind April , Stoecker Zachary , Stauderman Kenneth , Hebbar Sudarshan
Published: August 2020

Background

Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia.

Methods

A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study.

Results

In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, − 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2 = 101–200.

Conclusions

Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study.

Trial registration

ClinicalTrials.gov, NCT04345614. Submitted on 7 April 2020.

Graphical abstract
Docking-based virtual screening of TβR1 inhibitors: evaluation of pose prediction and scoring functions
Authors: Wang Shuai , Jiang Jun-Hao , Li Ruo-Yu , Deng Ping
Published: August 2020

To improve the reliability of virtual screening for transforming growth factor-beta type 1 receptor (TβR1) inhibitors, 2 docking methods and 11 scoring functions in Discovery Studio software were evaluated and validated in this study. LibDock and CDOCKER protocols were performed on a test set of 24 TβR1 protein–ligand complexes. Based on the root-mean-square deviation (RMSD) values (in Å) between the docking poses and co-crystal conformations, the CDOCKER protocol can be efficiently applied to obtain more accurate dockings in medium-size virtual screening experiments of TβR1, with a successful docking rate of 95%. A dataset including 281 known active and 8677 inactive ligands was used to determine the best scoring function. The receiver operating characteristic (ROC) curves were used to compare the performance of scoring functions in attributing best scores to active than inactive ligands. The results show that Ludi 1, PMF, Ludi 2, Ludi 3, PMF04, PLP1, PLP2, LigScore2, Jain and LigScore1 are better scoring functions than the random distribution model, with AUC of 0.864, 0.856, 0.842, 0.812, 0.776, 0.774, 0.769, 0.762, 0.697 and 0.660, respectively. Based on the pairwise comparison of ROC curves, Ludi 1 and PMF were chosen as the best scoring functions for virtual screening of TβR1 inhibitors. Further enrichment factors (EF) analysis also supports PMF and Ludi 1 as the top two scoring functions.
Bariatric surgery in obese patients with ventricular assist devices
Authors: daSilva-deAbreu Adrian , Alhafez Bader Aldeen , Curbelo-Pena Yuhamy , Lavie Carl J. , Ventura Hector O. , Loro-Ferrer Juan Francisco , Mandras Stacy A.
Published: August 2020

Objectives

Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight, which may prevent them from receiving heart transplantation (HT) if their body mass index (BMI) reaches ≥ 35 kg/m2. The objective was to synthesize all cases available in the literature and describe the most important outcomes of bariatric surgery (BS) in VAD patients, including BMI trends, reaching a BMI < 35 kg/m2, listing for HT, achieving HT, myocardial recovery, and mortality. These data were obtained for an individual participant data (IPD) meta-analysis and include available IPD for every case in the scientific literature describing VAD patients undergoing BS during VAD support with documented postoperative BMI (and time of measurement) during follow-up.

Data description

These data include baseline, periprocedural, and long-term outcomes for the 29 patients meeting selection criteria. The composite outcome includes reaching a BMI < 35 kg/m2, listing for HT, receiving HT, and myocardial recovery, indicating significant BMI loss associated with major ESHF outcomes. As multiple centers are becoming more experienced in this field, the present data can be merged with their databases to form larger samples that will allow to perform further statistical analysis to identify outcome predictors and improve clinical protocols and outcomes.
Potential therapeutic application of mesenchymal stem cell-derived exosomes in SARS-CoV-2 pneumonia
Authors: Akbari Ali , Rezaie Jafar
Published: August 2020

Background

The outbreak of a new virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become the main health concern all over the world. Since effective antiviral treatments have not been developed until now, SARS-CoV-2 is severely affecting countries and territories around the world.

Methods

At the present review, articles in PubMed were searched with the following terms: mesenchymal stem cells, exosomes, coronavirus, and SARS-CoV-2, either alone or in a combination form. The most relevant selected functions were mesenchymal stem cell-derived exosomes and SARS-CoV-2 virus infection.

Results

SARS-CoV-2 could damage pulmonary cells and induce secretion of different types of inflammatory cytokines. In the following, these cytokines trigger inflammation that damages the lungs and results in lethal acute respiratory distress syndrome (ARDS). The main characteristic of ARDS is the onset of inflammation in pulmonary, hyaline formation, pulmonary fibrosis, and edema. Mesenchymal stem cell-derived exosomes (MSC-Exo) are believed to have anti-inflammatory effects and immune-modulating capacity as well as the ability to induce tissue regeneration, suggesting a significant therapeutic opportunity that could be used to SARS-CoV-2 pneumonia treatment. Besides, exosomes may serve as a biomarker, drug delivery system, and vaccine for the management of the patient with SARS-CoV-2.

Conclusion

MSC-Exo may serve as a promising tool in the treatment of SARS-CoV-2 pneumonia. However, further work needs to be carried out to confirm the efficacy of exosomes in the treatment of SARS-CoV-2 pneumonia.