bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of low central venous pressure on hepatic surgical field bleeding and serum lactate in patients undergoing partial hepatectomy: a prospective randomized controlled trial
Authors: Yu Ling , Sun Hongwei , Jin Huangmo , Tan Hongyu
Published: February 2020

Background

This prospective randomized controlled study was designed to evaluate the effect of fluid restriction alone versus fluid restriction + low central venous pressure (CVP) on hepatic surgical field bleeding, intraoperative blood loss, and the serum lactate concentration in patients undergoing partial hepatectomy.

Methods

One hundred forty patients undergoing partial hepatectomy with intraoperative portal triad clamping were randomized into a fluid restriction group (Group F) or fluid restriction + low CVP group (Group L). Both groups received limited fluid infusion before the liver lesions were removed. Ephedrine was administered if the systolic blood pressure (SBP) decreased to <90 mmHg for 1 min. When the urine output was <20 ml/h or the SBP was <90 mmHg for 1 min more than three times, an additional 200 ml of crystalline solution was quickly infused within 10 min. In addition to fluid restriction, patients in Group L received continuous nitroglycerin and esmolol infusion to maintain a low CVP. The duration of portal triad clamping, frequency of additional fluid infusion, frequency of ephedrine administration, intraoperative blood loss, extent of liver resection, and bleeding score of the hepatic surgical field were recorded. Arterial blood gas analysis was performed before anesthesia (T1), after liver dissection and immediately before liver resection (T2), 10 min after removal of the liver lesion (T3), and before the patient was discharged from the postanesthesia care unit (T4).

Results

Being in the fluid restriction Group (Group F) (odds ratio = 5.04) and cirrhosis (odds ratio = 3.28) were risk factors for hepatic surgical field bleeding. Factors contributing to intraoperative blood loss were the operation time, duration of portal triad clamping, and extent of resection. No significant between-group difference was observed for blood loss or blood transfusion. The serum lactate concentration peaked at T3 in both groups.

Conclusions

Maintaining a lower CVP during hepatectomy provides an optimal surgical field but has no significant effect on intraoperative blood loss. Moreover, lower CVP does not increase the serum lactate concentration.

Trial registration

“A comparative study of the effect fluid restriction and low CVP pressure on the oozing of blood in liver wounds and blood lactate in patients undergoing partial hepatectomy” was prospectively registered as a trial (registration number:ChiCTR-INR-17014172, date of registration: 27 December 2017).
Limited utility of qPCR-based detection of tumor-specific circulating mRNAs in whole blood from clear cell renal cell carcinoma patients
Authors: Simonovic Sinisa , Hinze Christian , Schmidt-Ott Kai M. , Busch Jonas , Jung Monika , Jung Klaus , Rabien Anja
Published: February 2020

Background

RNA sequencing data is providing abundant information about the levels of dysregulation of genes in various tumors. These data, as well as data based on older microarray technologies have enabled the identification of many genes which are upregulated in clear cell renal cell carcinoma (ccRCC) compared to matched normal tissue. Here we use RNA sequencing data in order to construct a panel of highly overexpressed genes in ccRCC so as to evaluate their RNA levels in whole blood and determine any diagnostic potential of these levels for renal cell carcinoma patients.

Methods

A bioinformatics analysis with Python was performed using TCGA, GEO and other databases to identify genes which are upregulated in ccRCC while being absent in the blood of healthy individuals. Quantitative Real Time PCR (RT-qPCR) was subsequently used to measure the levels of candidate genes in whole blood (PAX gene) of 16 ccRCC patients versus 11 healthy individuals. PCR results were processed in qBase and GraphPadPrism and statistics was done with Mann-Whitney U test.

Results

While most analyzed genes were either undetectable or did not show any dysregulated expression, two genes, CDK18 and CCND1, were paradoxically downregulated in the blood of ccRCC patients compared to healthy controls. Furthermore, LOX showed a tendency towards upregulation in metastatic ccRCC samples compared to non-metastatic.

Conclusions

This analysis illustrates the difficulty of detecting tumor regulated genes in blood and the possible influence of interference from expression in blood cells even for genes conditionally absent in normal blood. Testing in plasma samples indicated that tumor specific mRNAs were not detectable. While CDK18, CCND1 and LOX mRNAs might carry biomarker potential, this would require validation in an independent, larger patient cohort.
Shared decision making with oncologists and palliative care specialists effectively increases the documentation of the preferences for do not resuscitate and artificial nutrition and hydration in patients with advanced cancer: a model testing study
Authors: Huang Hsien-Liang , Tsai Jaw-Shiun , Yao Chien-An , Cheng Shao-Yi , Hu Wen-Yu , Chiu Tai-Yuan
Published: February 2020

Background

Communication in do not resuscitate (DNR) and artificial nutrition and hydration (ANH) at the end of life is a key component of advance care planning (ACP) which is essential for patients with advanced cancer to have cares concordant with their wishes. The SOP model (Shared decision making with Oncologists and Palliative care specialists) aimed to increase the rate of documentation on the preferences for DNR and ANH in patients with advanced cancer.

Methods

The SOP model was implemented in a national cancer treatment center in Taiwan from September 2016 to August 2018 for patients with advanced cancer visiting the oncology outpatient clinic. The framework was based on the model of shared decision making as “choice talk” initiated by oncologists with “option talk” and “decision talk” conducted by palliative care specialists.

Results

Among 375 eligible patients, 255 patients (68%) participated in the model testing with the mean age of 68.5 ± 14.7 years (mean ± SD). Comparing to 52.3% of DNR documentation among patients with advanced cancer who died in our hospital, the rate increased to 80.9% (206/255) after the decision talk in our model. Only 6.67% (n = 17) of the participants documented their preferences on ANH after the model. A worse Eastern Cooperative Oncology Group Performance Status was the only statistically significant associating factor with a higher rate of DNR documentation in the multiple logistic regression model.

Conclusions

The SOP model significantly increased the rate of DNR documentation in patients with advanced cancer in this pilot study. Dissemination of the model could help the patients to receive care that is concordant with their wishes and be useful for the countries having laws on ACP.
Prompt Mental Health Care (PMHC): work participation and functional status at 12 months post-treatment
Authors: Knapstad Marit , Sæther Solbjørg Makalani Myrtveit , Hensing Gunnel , Smith Otto Robert Frans
Published: February 2020

Background

Anxiety and depression are associated with substantial functional impairment. Prompt Mental Health Care (PMHC), the Norwegian adaptation of IAPT is currently piloted across Norway, as a means to improve access to evidence-based care for adults with anxiety disorders (including subthreshold cases) and minor to moderate depression. The aims of the current paper were to examine the change in work status and functional status from pre- to post-treatment and 12 months post-treatment among clients at the first 12 PMHC pilot sites, and whether degree of change differed across sociodemographic characteristics.

Methods

A prospective cohort design was used, including working age clients receiving treatment between October 2014 and December 2016 (n = 1446, participation rate = 61%). Work status and functional status were self-reported, the latter by the Work and Social Adjustment Scale (WSAS). Changes in work status and WSAS score were examined through multilevel models based on maximum likelihood estimation. Likelihood ratio tests were performed to determine whether the interaction between time and the respective background variables were statistically significant.

Results

A substantial increase in regular work participation was observed from pre- to post-treatment, which further had increased at 12 months post-treatment. The increase was driven by a corresponding reduction in proportion of clients working and receiving benefits (OR 0.38 [0.29–0.50] baseline to final treatment, OR = 0.19 [0.12–0.32] final treatment to 12-months post-treatment), while no statistically significant change was observed in proportion out of work. Large improvement (ES = − 0.89) in WSAS score was observed from pre- to post treatment. WSAS score at 12 months post-treatment remained at the post-treatment level.

Conclusions

Previous research has shown substantial symptom improvement among clients receiving treatment in PMHC. The current findings indicate that PMHC might also be able to aid adults struggling with mild to moderate anxiety and depression in returning to usual level of functioning. The degree to which the observed improvements are attributable to the treatment need nonetheless to be confirmed in a trial including a control group and with more complete follow-up data from registries.
A landscape of genomic alterations at the root of a near-untreatable tuberculosis epidemic
Authors: Klopper Marisa , Heupink Tim Hermanus , Hill-Cawthorne Grant , Streicher Elizabeth Maria , Dippenaar Anzaan , de Vos Margaretha , Abdallah Abdallah Musa , Limberis Jason , Merker Matthias , Burns Scott , Niemann Stefan , Dheda Keertan , Posey James , Pain Arnab , Warren Robin Mark
Published: February 2020

Background

Atypical Beijing genotype Mycobacterium tuberculosis strains are widespread in South Africa and have acquired resistance to up to 13 drugs on multiple occasions. It is puzzling that these strains have retained fitness and transmissibility despite the potential fitness cost associated with drug resistance mutations.

Methods

We conducted Illumina sequencing of 211 Beijing genotype M. tuberculosis isolates to facilitate the detection of genomic features that may promote acquisition of drug resistance and restore fitness in highly resistant atypical Beijing forms. Phylogenetic and comparative genomic analysis was done to determine changes that are unique to the resistant strains that also transmit well. Minimum inhibitory concentration (MIC) determination for streptomycin and bedaquiline was done for a limited number of isolates to demonstrate a difference in MIC between isolates with and without certain variants.

Results

Phylogenetic analysis confirmed that two clades of atypical Beijing strains have independently developed resistance to virtually all the potent drugs included in standard (pre-bedaquiline) drug-resistant TB treatment regimens. We show that undetected drug resistance in a progenitor strain was likely instrumental in this resistance acquisition. In this cohort, ethionamide (ethA A381P) resistance would be missed in first-line drug-susceptible isolates, and streptomycin (gidB L79S) resistance may be missed due to an MIC close to the critical concentration. Subsequent inadequate treatment historically led to amplification of resistance and facilitated spread of the strains. Bedaquiline resistance was found in a small number of isolates, despite lack of exposure to the drug. The highly resistant clades also carry inhA promoter mutations, which arose after ethA and katG mutations. In these isolates, inhA promoter mutations do not alter drug resistance, suggesting a possible alternative role.

Conclusion

The presence of the ethA mutation in otherwise susceptible isolates from ethionamide-naïve patients demonstrates that known exposure is not an adequate indicator of drug susceptibility. Similarly, it is demonstrated that bedaquiline resistance can occur without exposure to the drug. Inappropriate treatment regimens, due to missed resistance, leads to amplification of resistance, and transmission. We put these results into the context of current WHO treatment regimens, underscoring the risks of treatment without knowledge of the full drug resistance profile.
Physical integrity and survivorship of long-lasting insecticidal nets distributed to households of the same socio-cultural community in Benin, West Africa
Authors: Ahogni Idelphonse B. , Salako Albert S. , Akinro Bruno , Sovi Arthur , Gnanguenon Virgile , Azondekon Roseric , Dagnon Jean F. , Akogbeto Pamela , Tokponon Filémon , Akogbeto Martin C.
Published: February 2020

Background

Long-lasting insecticidal nets (LLINs) are designed to survive and sustain their physical barrier for 3 years in household conditions. However, studies have shown that most of these nets are usually torn or no longer present in the households in less than 3 years. This study was initiated in Benin to compare the survivorship and physical integrity of seven types of LLINs in a same socio-geographic area.

Methods

In August 2017, 1890 households were selected in 9 villages in the municipality of Zagnanado in central Benin. Each one of the selected households received one of the seven LLIN products: Aspirational®, DawaPlus® 2.0, OlysetNet®, PermaNet® 2.0, PermaNet® 3.0, Royal Sentry® and Yorkool®. Overall, 270 LLINs of each type were freely distributed in Zagnanado, at a rate of 30 LLINs per type per village. These bed nets have been monitored and evaluated every 6 months to identify the most resilient and preferred LLINs in the community. Net survivorship was assessed using the rate of net loss and physical condition.

Results

The survivorship of all types of LLIN was estimated at 92% (95% CI 90.33–92.96) after 6 months and 70% (95% CI 67.25–71.81) after a year of use. At 12 months, all bed nets monitored were below the NetCalc model threshold of 92.8% for an LLIN with a lifespan of 3 years. Only 1.73% of all types of LLIN had a visible loss of integrity after 6 months with a median proportionate hole index (PHI) estimated at zero. The percentage significantly increased after 12 months with 10.41% of damaged nets (all types of LLINs). The median PHI for each brand of net was 23, 196, 141, 23, 23, 121 and 72, respectively for Aspirational®, DawaPlus® 2.0, OlysetNet®, PermaNet® 2.0, PermaNet® 3.0, Royal Sentry® and Yorkool®. A significant difference was noted between the PHI at 6 and 12 months (p < 0.0001). After 12 months, the DawaPlus®2.0, OlysetNet® and Royal Sentry® suffered significantly more damage compared to the others (p < 0.001).

Conclusion

The results of this study showed that after a year of use, the survivorship of the 7 LLIN products in households was lower than expected. However, all the LLIN products successfully met WHO standards for physical integrity after 12 months of use. The monitoring continues. The next steps will help to identify the most sustainable LLINs.
Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization
Authors: Liu Wei , Rong Yuluo , Wang Jiaxing , Zhou Zheng , Ge Xuhui , Ji Chengyue , Jiang Dongdong , Gong Fangyi , Li Linwei , Chen Jian , Zhao Shujie , Kong Fanqi , Gu Changjiang , Fan Jin , Cai Weihua
Published: February 2020

Background

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction with high disability and mortality. In recent years, mesenchymal stem cell (MSC)-secreted nano-sized exosomes have shown great potential for promoting functional behavioral recovery following SCI. However, MSCs are usually exposed to normoxia in vitro, which differs greatly from the hypoxic micro-environment in vivo. Thus, the main purpose of this study was to determine whether exosomes derived from MSCs under hypoxia (HExos) exhibit greater effects on functional behavioral recovery than those under normoxia (Exos) following SCI in mice and to seek the underlying mechanism.

Methods

Electron microscope, nanoparticle tracking analysis (NTA), and western blot were applied to characterize differences between Exos and HExos group. A SCI model in vivo and a series of in vitro experiments were performed to compare the therapeutic effects between the two groups. Next, a miRNA microarray analysis was performed and a series of rescue experiments were conducted to verify the role of hypoxic exosomal miRNA in SCI. Western blot, luciferase activity, and RNA-ChIP were used to investigate the underlying mechanisms.

Results

Our results indicate that HExos promote functional behavioral recovery by shifting microglial polarization from M1 to M2 phenotype in vivo and in vitro. A miRNA array showed miR-216a-5p to be the most enriched in HExos and potentially involved in HExos-mediated microglial polarization. TLR4 was identified as the target downstream gene of miR-216a-5p and the miR-216a-5p/TLR4 axis was confirmed by a series of gain- and loss-of-function experiments. Finally, we found that TLR4/NF-κB/PI3K/AKT signaling cascades may be involved in the modulation of microglial polarization by hypoxic exosomal miR-216a-5p.

Conclusion

Hypoxia preconditioning represents a promising and effective approach to optimize the therapeutic actions of MSC-derived exosomes and a combination of MSC-derived exosomes and miRNAs may present a minimally invasive method for treating SCI.
HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options
Authors: Jespersen S. , Månsson F. , Lindman J. , Wejse C. , Medina C. , da Silva Z. J. , Te DdS , Medstrand P. , Esbjörnsson J. , Hønge B. L.
Published: February 2020

Despite advances in the treatment quality of HIV throughout the world, several countries are still facing numerous obstacles in delivering HIV treatment at a sufficiently high quality, putting patients’ lives in jeopardy. The aim of this status article is to give an overview of HIV treatment outcomes in the West African country, Guinea-Bissau, and to assess how newer treatment strategies such as long-acting injectable drugs or an HIV cure may limit or stop the HIV epidemic in this politically unstable and low-resource setting. Several HIV cohorts in Guinea-Bissau have been established and are used as platforms for epidemiological, virological, immunological and clinical studies often with a special focus on HIV-2, which is prevalent in the country. The Bandim Health Project, a demographic surveillance site, has performed epidemiological HIV surveys since 1987 among an urban population in the capital Bissau. The Police cohort, an occupational cohort of police officers, has enabled analyses of persons seroconverting with estimated times of seroconversion among HIV-1 and HIV-2-infected individuals, allowing incidence measurements while the Bissau HIV Cohort and a newer Nationwide HIV Cohort have provided clinical data on large numbers of HIV-infected patients. The HIV cohorts in Guinea-Bissau are unique platforms for research and represent real life in many African countries. Poor adherence, lack of HIV viral load measurements, inadequate laboratory facilities, high rates of loss to follow-up, mortality, treatment failure and resistance development, are just some of the challenges faced putting the goal of “90–90–90″ for Guinea-Bissau well out of reach by 2020. Maintaining undetectable viral loads on treatment as a prerequisite of a cure strategy seems not possible at the moment. Thinking beyond one-pill-once-a-day, long-acting antiretroviral treatment options such as injectable drugs or implants may be a better treatment option in settings like Guinea-Bissau and may even pave the way for an HIV cure. If the delivery of antiretroviral treatment in sub-Saharan Africa in a sustainable way for the future should be improved by focusing on existing treatment options or through focusing on new treatment options remains to be determined.
LncRNA Gm12664–001 ameliorates nonalcoholic fatty liver through modulating miR-295-5p and CAV1 expression
Authors: Zhang Qiao , Wang Jiemei , Li Hongyin , Zhang Yuan , Chu Xia , Yang Jianjun , Li Ying
Published: February 2020

Background

Our study aims to investigate the mechanisms of lncRNA Gm12664–001 improved hepatic lipid accumulation-initiated NAFLD via regulating miR-295-5p and CAV1 in AML12 cells.

Methods

The animals were divided into normal control (NC) group and high fat diet (HFD) group (20 mice per group) for 8w. The steatotic liver was measured by hematoxylin eosin (HE) staining and kits. We performed systematical analyses on hepatic expression profiles of long noncoding RNAs (lncRNAs) and microRNAs in a high-fat diet (HFD)-induced steatotic animal model. The expression profile of targets was confirmed by bioinformatics analysis, luciferase assay, RT-PCR and western blot in AML12 cells.

Results

HFD treatment markedly observed hepatic fatty degeneration with primarily fat vacuoles, and increased TG level compared with control. According to microarray data, we found that transfection of Gm12664–001 siRNA (siRNA-118,306) obviously enhanced TG accumulation and repressed CAV1 in AML12 cells. Furthermore, the TG accumulation markedly increased by siRNA-mediated knockdown of CAV1 in AML12 cells. By bioinformatics prediction, AML12 cells were transfected of siRNA-118,306 obviously upregulated miR-295-5p. Transfection of miR-295-5p mimics significantly increased TG accumulation and obviously suppressed the target CAV1.

Conclusions

The results revealed that lncRNA Gm12664–001 attenuated hepatic lipid accumulation through negatively regulating miR-295-5p and enhancing CAV1 expression in AML12 cells.
A case-series of patients with musculoskeletal conditions in an underserved community in Moca, Dominican Republic
Authors: da Silva-Oolup Sophia , Nordin Margareta , Stern Paula , Outerbridge Geoff , Côté Pierre
Published: February 2020

Purpose

To describe characteristics and activity limitations of new patients with musculoskeletal conditions presenting to the World Spine Care (WSC) clinic located in the underserved community of Moca, Dominican Republic.

Methods

We conducted a prospective case series of consecutive adults between October 12 and December 5, 2015. A survey of valid and reliable measures including: Body pain diagram, Wong-Baker FACES® pain rating scale, Spine Functional Index (SFI), Lower Limb Functional Index (LLFI), Upper Limb Functional Index (ULFI) and the 12-item Short Form Health Survey (SF-12v2) was administered to collect socio-demographics, expectation of recovery, comorbidities, and self-reported health status data.

Results

Forty-two patients (23 females and 19 males) were included. The most common primary complaint was lower back pain (40.5%; 17/42) and 57% (24/42) of individuals reported pain that interfered with their ability to function and engage in daily activities. Half of the patients presented with two complaints. Complaints were similar between genders. Most patients (64%; 27/42) reported chronic pain (> 6 months) and 97% (41/42) reported believing that they would recover. Twenty-one percent (9/42) self-reported being diagnosed with depression and/or anxiety at some point in their life. In addition, most (57%; 24/42) individuals reported below average physical and mental health related quality of life.

Conclusions

This study is the first to describe characteristics of patients seeking care at the WSC clinic in Moca, Dominican Republic. Most patients attending the clinic suffer from persistent spine complaints that interfere with their ability to function and engage in daily activities. Nevertheless, the patients have positive expectations of recovery.
The role of CD68+ macrophage in classical Hodgkin lymphoma patients from Egypt
Authors: Mohamed Osama , El Bastawisy Ahmed , Allahlobi Nasr , Abdellateif Mona S. , Zekri Abdel Rahman N. , Shaarawy Sabry , Korany Zeinab , Mohanad Marwa , Bahnassy Abeer A.
Published: February 2020

Background

CD68+ tumor-associated macrophages (TAM) play an important role in the progression of classical Hodgkin lymphoma (cHL). We assessed the role of CD20 and CD68 + TAM in a cohort of cHL patients from Egypt and correlated the number of CD68 + cells with patients’ characteristics, response to treatment, overall and progression free survival rates (OS & PFS).

Methods

CD20 expression and CD68 + TAM numbers were assessed in representative tumor tissues obtained from 81 cHL patients using flowcytometry (FCM), immunohistochemistry (IHC), and Rt-PCR techniques.

Results

The expression levels of CD68 protein by IHC was high in 27 (33.3%), moderate in 15 (18.5%), low in 15 (18.5%), and negative in 24 (29.6%) patients (p = 0.13). CD68-mRNA expression was high in 43/81(53.1%), and low in 38(46.9%) patients (p = 0.6). The number of CD68 + TAM (by FCM) was low (< 20 cells) in 42/81 (51.9%), and high (≥20 cells) in 39/81 (48.1%) patients (p = 0.74). CD68 expression (by FCM, IHC& Rt-PCR) associated significantly with poor response to treatment, decreased CD20 expression, reduced OS and PFS rates (p < 0.001 for all). CD68 expression (by Rt-PCR only) associated significantly with advanced disease stage (p = 0.04). The age of the patients, high CD20 expression & high CD68+ macrophage number were independent prognostic factors for OS (p= 0.02, p = 0.008 & p = 0.009; respectively). However, the age of the patient, high CD20, and high CD68+ macrophage expression (by FCM&IHC) were independent prognostic factors for DFS (p. = 0.004, p. = 0.01, p. = 0.007 and p. = 0.01; respectively).

Conclusion

CD68 + TAM expression (by Rt-PCR, FCM and/or IHC) can identify patients with poor response to treatment and reduced survival rates (OS& PFS). Assessment of CD68 + positive macrophages by FCM is superior to other methods (Rt-PCR and IHC) as a prognostic factor for DFS and OS rates.
Exclusive breastfeeding cessation and associated factors among employed mothers in Dukem town, Central Ethiopia
Authors: Kebede Tolossa , Woldemichael Kifle , Jarso Habtemu , Bekele Bayu Begashaw
Published: February 2020

Background

Employed women tend to exclusively breastfeed less than non-employed women. Early returning to work has been major reason why employed women stop exclusive breastfeeding. The aim of this study was to investigate exclusive breastfeeding (EBF) cessation and associated factors among employed mothers in Dukem town, Central Ethiopia.

Methods

A cross-sectional study was conducted from February to March 2015 using total sample of 313 randomly selected permanently employed women. Information regarding participants’ work-related factors, health service and sociodemographic factors were collected by face to face interview using structured questionnaire. Data were checked for completeness, entered and analyzed by SPSS version 20. Binary logistic regression was done to identify factors associated with exclusive breastfeeding cessation. The strength of association was measured using odds ratio with 95% confidence intervals.

Results

Prevalence of exclusive breastfeeding cessation was 75.7% (95% CI 71.0, 80.5%). Having a short duration of maternity leave (AOR 9.3; 95% CI 3.8, 23), being a full time employee (AOR 3.5; 95% CI 1.7, 11), being private organization employee (AOR=2.1, 95% CI(1, 4.3)), lack of flexible work time (AOR 3.0; 95% CI 1.2, 7.5), not pumping breast milk (AOR 4.3; 95% CI 1.7, 11), lack of a lactation break (AOR 6.7; 95% CI 3,14.5) and work place far away from her child (AOR 3.1; 95% CI 3.1, 6.3), were significantly associated with cessation of EBF among employed mothers.

Conclusion

Prevalence of exclusive breastfeeding cessation was much higher than the international and national expectation. The concerned governmental bodies should consider improving the legislation of the 3 months postpartum maternity leave to reduce employed mother’s exclusive breastfeeding cessation.
Addressing low-value pharmacological prescribing in primary prevention of CVD through a structured evidence-based and theory-informed process for the design and testing of de-implementation strategies: the DE-imFAR study
Authors: Sanchez Alvaro , Pijoan Jose Ignacio , Pablo Susana , Mediavilla Marta , de Rozas Rita Sainz , Lekue Itxasne , Gonzalez-Larragan Susana , Lantaron Gaspar , Argote Jon , García-Álvarez Arturo , Latorre Pedro Maria , Helfrich Christian D. , Grandes Gonzalo
Published: February 2020

Background

De-implementation or abandonment of ineffective or low-value healthcare is becoming a priority research field globally due to the growing empirical evidence of the high prevalence of such care and its impact in terms of patient safety and social inefficiency. Little is known, however, about the factors, barriers, and facilitators involved or about interventions that are effective in promoting and accelerating the de-implementation of low-value healthcare. The De-imFAR study seeks to carry out a structured, evidence-based, and theory-informed process involving the main stakeholders (clinicians, managers, patients, and researchers) for the design, deployment, and assessment of de-implementation strategies for reducing low-value pharmacological prescribing.

Methods

A phase I formative study using a systematic and comprehensive framework based on theory and evidence for the design of implementation strategies—specifically, the Behavior Change Wheel (BCW)—will be conducted to design and model de-implementation strategies to favor reductions in low-value pharmacological prescribing of statins in primary prevention of cardiovascular disease (CVD) by main stakeholders (clinicians, managers, patients, and researchers) in a collegiate way. Subsequently, a phase II comparative hybrid trial will be conducted to assess the feasibility and potential effectiveness of at least one active de-implementation strategy to reduce low-value pharmacological prescribing of statins in primary prevention of CVD compared to the usual procedures for dissemination of clinical practice guidelines (“what-not-to-do” recommendations). A mixed-methods evaluation will be used: quantitative for the results of the implementation at the professional level (e.g., adoption, reach and implementation or execution of the recommended clinical practice); and qualitative to determine the feasibility and perceived impact of the de-implementation strategies from the clinicians’ perspective, and patients’ experiences related to the clinical care received.

Discussion

The DE-imFAR study aims to generate valid scientific knowledge about the design and development of de-implementation strategies using theory- and evidence-based methodologies suggested by implementation science. It will explore the effectiveness of these strategies and their acceptability among clinicians, policymakers, and patients. Its ultimate goal is to maximize the quality and efficiency of our health system by abandoning low-value pharmacological prescribing.

Trial registration

Clinicaltrials.gov identifier: NCT04022850. Registered 17 July 2019
Stereotactic body radiotherapy (SBRT) for adrenal metastases of oligometastatic or oligoprogressive tumor patients
Authors: König Laila , Häfner Matthias F. , Katayama Sonja , Koerber Stefan A. , Tonndorf-Martini Eric , Bernhardt Denise , von Nettelbladt Bastian , Weykamp Fabian , Hoegen Philipp , Klüter Sebastian , Susko Matthew S. , Debus Jürgen , Hörner-Rieber Juliane
Published: February 2020

Introduction

Local ablative treatment strategies are frequently offered to patients diagnosed with oligometastatic disease. Stereotactic body radiotherapy (SBRT), as ablative treatment option, is well established for lung and liver metastases, whereas for isolated adrenal gland metastases the level of evidence is scarce.

Material and methods

This single-institution analysis of oligometastatic or oligoprogressive disease was limited to patients who received SBRT to adrenal metastasis between 2012 and 2019. Patient, tumor, treatment characteristics, and dosimetric parameters were analyzed for evaluation of their effect on survival outcomes.

Results

During the period of review 28 patients received ablative SBRT to their adrenal gland metastases. Most common primary tumors were non-small cell lung cancers (46%) with most patients diagnosed with a single adrenal gland metastasis (61%), which occurred after a median time of 14 months. SBRT was delivered to a median biological effective dose at α/β of 10 (BED10) of 75 Gy (range: 58–151 Gy). Median gross tumor volume (GTV) and median planning target volume (PTV) were 42 and 111 mL, respectively. The homogeneity and conformity indices were 1.17 (range: 1.04–1.64) and 0.5 (range: 0.4.0.99), respectively, with the conformity index being affected by dose restrictions to organs at risk (OARs) in 50% of the patients. Overall response rate based on RECIST criteria was 86% (CR = 29%, PR = 57%) with 2-year local control (LC) of 84.8%, 2-year progression-free survival (PFS) of 26.3%, and 1-and 2-year overall survival (OS) of 46.6 and 32.0%, respectively. During follow up, only two local recurrences occurred. A trend for superior LC was seen if BED10 was ≥75Gy (p = 0.101) or if the PTV was < 100 ml (p = 0.072). SBRT was tolerated well with only mild toxicity.

Conclusion

SBRT for adrenal metastases resulted in promising LC with low toxicity. Treatment response appeared to be superior, if SBRT was applied with higher BED. As the close proximity of OARs often limits the application of sufficiently high doses, further dose escalations strategies and techniques should be investigated in future.
Radiotherapy for geriatric head-and-neck cancer patients: what is the value of standard treatment in the elderly?
Authors: Haehl Erik , Rühle Alexander , David Hélène , Kalckreuth Tobias , Sprave Tanja , Stoian Raluca , Becker Christoph , Knopf Andreas , Grosu Anca-Ligia , Nicolay Nils H.
Published: February 2020

Background

Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, and the number of elderly patients diagnosed with HNSCC is increasing. However, as elderly HNSCC patients are underrepresented in clinical trials, current clinical decision making for this cohort largely lacks clinical evidence.

Methods

Elderly patients (≥65 years) with HNSCC undergoing (chemo)radiotherapy from 2010 to 2018 at Freiburg University Medical Center were assessed for patterns of care, locoregional control (LRC), progression-free (PFS) and overall survival (OS) regarding definitive and adjuvant treatments. Acute and late therapy-associated toxicities were quantified according to CTCAE v5.0.

Results

Two hundred forty-six patients were included in this analysis, of whom 166 received definitive and 80 adjuvant treatment. Two-year rates for OS, PFS and LRC were 56.9, 44.9 and 75.5%, respectively. Survival differed significantly between age groups with an OS of 40 and 22 months and a PFS of 23 and 12 months for patients aged 65–74 or ≥ 75 years, respectively (p < 0.05). Concomitant chemotherapy resulted in improved OS in patients aged 65–74 years compared to radiotherapy alone (p < 0.05) for definitive treatments, while patients ≥75 years did not benefit (p = 0.904). For adjuvant chemoradiotherapy, a trend towards superior OS rates was observed for patients aged 65–74 years (p = 0.151). Low performance status (HR = 2.584, 95% CI 1.561–4.274;p < 0.001) and smoking (HR = 1.960, 95% CI 1.109–3.464,p < 0.05) were the strongest independent prognostic factor in the multivariate analysis for decreased OS. One hundred thirty-eight patients (56.1%) experienced acute grade 3/4 and 45 patients (19.9%) chronic grade 3 toxicities.

Conclusion

Radiotherapy is a feasible treatment modality for elderly HNSCC patients. The relatively low OS compared to high LRC may reflect age and comorbidities. Concomitant chemotherapy should be critically discussed in elderly HNSCC patients.
Effects of inhaled nitric oxide for postoperative hypoxemia in acute type A aortic dissection: a retrospective observational study
Authors: Zhang Hang , Liu Yaoyang , Meng Xiangdong , Yang Dicheng , Shi Sheng , Liu Jian , Yuan Zhongxiang , Gu Tongtong , Han Lin , Lu Fanglin , Xu Zhiyun , Liu Yang , Yu Min
Published: February 2020

Background

Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes. This study aimed to analyze the efficacy of low-dose (5–10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery.

Methods

In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected. Patients with postoperative hypoxemia were classified as iNO and control groups. Clinical characteristics and outcomes were compared using a propensity score-matched (PSM) analysis.

Results

Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO. After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio. iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3–47.8) vs. 69.0 h (47.8–110.3), p < 0.001) and ICU stay (122.0 h (80.8–155.0) vs 179.5 h (114.0–258.0), p < 0.001). There were no significant between-group differences in mortality, complications, or length of hospital stay.

Conclusions

In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay. No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment. These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA.
Efficacy and safety of endoscopic submucosal tunnel dissection for superficial esophageal neoplastic lesions: a systematic review and meta-analysis
Authors: Peng Wei , Tan Shali , Ren Yutang , Li Huan , Peng Yan , Fu Xiangsheng , Tang Xiaowei
Published: February 2020

Background

Presently, endoscopic submucosal tunnel dissection (ESTD) has been a novel therapy for superficial esophageal neoplastic lesions (SENL), especially for circumferential neoplastic lesions. A number of studies have reported the clinical application of ESTD with promising outcomes. Therefore, we conducted a systematic review and meta-analysis to evaluated the efficacy and safety of ESTD for SENL .

Methods

From 2013 to November 2018, Pubmed, Embase and Cochrane databases were searched to determine studies reporting ESTD treatment of SENL. Weighted pooled rates (WPR) were calculated for en bloc resection, R0 resection and complication of ESTD. Risk ratios (RR) were calculated and pooled to compare the clinical outcomes of ESTD with ESD for SENL.

Results

A total of 9 studies involving 494 patients with 518 esophageal neoplastic lesions were included in our study. WPR for en bloc resection and R0 resection of ESTD was 97.0% (95% CI: 94.7–98.3%) and 84.1% (95% CI: 80.5–87.1%), respectively. WPR for complication was 40.0% (95% CI: 25.8–56.1%). Two studies with 265 patients compared the performance of ESTD with ESD. Pooled RR for en bloc resection and R0 resection was 1.04 (95% CI: 0.95–1.14, P = 0.42) and 1.01 (95% CI: 0.93–1.10, P = 0.73), respectively. Pooled RR for complication was 0.68 (95% CI: 0.46–1.01, P = 0.05).

Conclusion

Our study showed that ESTD is effective for treating SENL with high en bloc resection rate and R0 resection rate, but accompanying by a relatively high complications.
13-Methylberberine improves endothelial dysfunction by inhibiting NLRP3 inflammasome activation via autophagy induction in human umbilical vein endothelial cells
Authors: Peng Zhihua , Zhan Hong , Shao Yijia , Xiong Yan , Zeng Lijin , Zhang Cong , Liu Zhihao , Huang Zhenhua , Su Huanxing , Yang Zhen
Published: February 2020

Background

Atherosclerosis, the underlying cause of the majority of cardiovascular diseases, is a lipid-driven, inflammatory disease of the large arteries. Atherosclerotic cardiovascular disease (ASCVD) threatens human lives due to high morbidity and mortality. Many studies have demonstrated that atherosclerosis is accelerated via activation of the NLRP3 inflammasome. The NLRP3 inflammasome plays a critical role in the development of vascular inflammation and atherosclerosis. In atherosclerotic plaques, excessive generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome. 13-Methylberberine (13-MB) is a newly synthesized compound used in traditional Chinese medicine that has outstanding antibacterial, antitumor, and antiobesity activities, especially anti-inflammatory activity. However, the role of 13-MB in atherosclerosis needs to be explored.

Methods

CCK-8 assays and flow cytometry were conducted to determine the cell viability and apoptotic profiles of human umbilical vein endothelial cells (HUVECs) treated with 13-MB. Carboxy-DCFH-DA and JC-10 assays were used to measure ROS and determine mitochondrial membrane potential. Western blot analysis was performed to investigate proteins that are associated with the NLRP3 inflammasome and autophagy. ELISA was used to detect and quantify inflammatory cytokines related to the NLRP3 inflammasome. Transfection and confocal microscopy were conducted to observe autophagy.

Results

Pretreatment with 13-MB markedly reduced cytotoxicity and apoptosis, as well as intracellular ROS production, in H2O2-induced HUVECs. Moreover, 13-MB showed a protective effect in maintaining mitochondrial membrane potential. 13-MB also suppressed NLRP3 inflammasome activation and promoted autophagy induction in HUVECs.

Conclusion

13-MB exerts cytoprotective effects in an H2O2-induced cell injury model by inhibiting NLRP3 inflammasome activation via autophagy induction in HUVECs. These anti-inflammatory and autophagy induction activities may provide valuable evidence for further investigating the potential role of 13-MB in atherosclerosis.
Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes
Authors: Carmody Leigh C. , Blau Hannah , Danis Daniel , Zhang Xingman A. , Gourdine Jean-Philippe , Vasilevsky Nicole , Krawitz Peter , Thompson Miles D. , Robinson Peter N.
Published: February 2020

Background

Defects in the glycosylphosphatidylinositol (GPI) biosynthesis pathway can result in a group of congenital disorders of glycosylation known as the inherited GPI deficiencies (IGDs). To date, defects in 22 of the 29 genes in the GPI biosynthesis pathway have been identified in IGDs. The early phase of the biosynthetic pathway assembles the GPI anchor (Synthesis stage) and the late phase transfers the GPI anchor to a nascent peptide in the endoplasmic reticulum (ER) (Transamidase stage), stabilizes the anchor in the ER membrane using fatty acid remodeling and then traffics the GPI-anchored protein to the cell surface (Remodeling stage).

Results

We addressed the hypothesis that disease-associated variants in either the Synthesis stage or Transamidase+Remodeling-stage GPI pathway genes have distinct phenotypic spectra. We reviewed clinical data from 58 publications describing 152 individual patients and encoded the phenotypic information using the Human Phenotype Ontology (HPO). We showed statistically significant differences between the Synthesis and Transamidase+Remodeling Groups in the frequencies of phenotypes in the musculoskeletal system, cleft palate, nose phenotypes, and cognitive disability. Finally, we hypothesized that phenotypic defects in the IGDs are likely to be at least partially related to defective GPI anchoring of their target proteins. Twenty-two of one hundred forty-two proteins that receive a GPI anchor are associated with one or more Mendelian diseases and 12 show some phenotypic overlap with the IGDs, represented by 34 HPO terms. Interestingly, GPC3 and GPC6, members of the glypican family of heparan sulfate proteoglycans bound to the plasma membrane through a covalent GPI linkage, are associated with 25 of these phenotypic abnormalities.

Conclusions

IGDs associated with Synthesis and Transamidase+Remodeling stages of the GPI biosynthesis pathway have significantly different phenotypic spectra. GPC2 and GPC6 genes may represent a GPI target of general disruption to the GPI biosynthesis pathway that contributes to the phenotypes of some IGDs.
Epidemiological and advanced therapeutic approaches to treatment of uveitis in pediatric rheumatic diseases: a systematic review and meta-analysis
Authors: Jari Mohsen , Shiari Reza , Salehpour Omid , Rahmani Khosro
Published: February 2020

Background

Despite the low prevalence of uveitis in pediatric rheumatic diseases, potential problems as well as high disease burden can complicate its management. In this review, we systematically assessed the epidemiological, etiological, and managerial aspects of uveitis in pediatric rheumatic diseases.

Methods

This current study was conducted in accordance with the established methods and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). We searched the manuscript databases, including Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane for all eligible studies in line with the considered keywords. We also conducted the statistical analysis using the Stata software.

Results

Considering studies focusing on uveitis in Juvenile Idiopathic Arthritis (JIA) yielded a pooled prevalence of 11.8% (95%CI: 11.2 to 12.4%) for uveitis following JIA. In this regard, the prevalence rate of uveitis related to Behçet,s disease and Systemic Lupus Erythematosus (SLE( was estimated to be 15.0 and 0.8%, respectively. The pooled response rate to Adalimumab and Infliximab was estimated to be 68.0% (95%CI: 65.4 to 70.6%), 64.7% (95%CI: 59.8 to 69.3%), respectively. The documents for the systematical assessment of other biological medications (e.g. Tocilizumab, Daclizumab and Rituximab) were inadequate; however, the mean response rate for these drugs was 59, 75 and 80%, respectively. Our meta-analysis showed a pooled response rate of 40.0% (95%CI, 36.0% to 44.2) to Methotrexate. Significant heterogeneity and significant diffusion bias were demonstrated by reviewing studies.

Conclusions

The pooled prevalence of uveitis in pediatric rheumatic diseases widely varied based on the underlying disease requiring more investigations in different subtypes of rheumatic diseases. The biologic medications, especially Adalimumab are the most effective treatments for uveitis in pediatric rheumatic diseases; however, a combination of the safe, available alternatives is preferred to achieve the most desirable treatment response.