bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study
Authors: Zhang Xiaobin , Eyck Ben M. , Yang Yang , Liu Jun , Chao Yin-Kai , Hou Ming-Mo , Hung Tsung-Min , Pang Qingsong , Yu Zhen-Tao , Jiang Hongjing , Law Simon , Wong Ian , Lam Ka-On , van der Wilk Berend J. , van der Gaast Ate , Spaander Manon C. W. , Valkema Roelf , Lagarde Sjoerd M. , Wijnhoven Bas P. L. , van Lanschot J. Jan B. , Li Zhigang
Published: March 2020

Background

After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC.

Methods

Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10–12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value.

Discussion

If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial).

Trial registration

The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).
BMI modified the association of current smoking with the incidence of hypertension in Chinese population: a 22-year cohort study
Authors: Yao Feifei , Liu Wenfeng , Zhao Rencheng , Li Guangxiao , Huang Xiaojuan , Chen Yongjie
Published: March 2020

Background

There was little known on how the interaction effect between obesity and current smoking affected the incidence of hypertension. The aim of this study was to investigate how body mass index (BMI) modified the effect of current smoking on the incidence of hypertension.

Methods

Data were obtained from the China Health and Nutrition Survey (CHNS). According to the WHO recommendations for Chinese people, the normal weight, overweight, and obesity were defined using the BMI cutoff values 18.5 kg/m2, 23.0 kg/m2, and 27.5 kg/m, respectively. Current smokers were defined as having smoked at least 100 cigarettes or electronic cigarettes, 20 cigars, or 20 tobacco pipes and other type of tobacco in the last 30 days preceding the survey. Hypertension was defined as systolic blood pressure (SBP)/ diastolic blood pressure (DBP) ≥ 140/90 mmHg, use of anti-hypertensive medications, or a self-reported diagnosis.

Results

This study included 12,900 subjects. There were interaction effects between obesity and current smoking in females (P = 0.030) and the 50–59 years group (P = 0.049). Current smoking was a significant predictor of incident hypertension only in the total and female populations with normal weight (HR: 1.119 and 1.274;HR95%CI: 1.013–1.236 and 1.143–1.415; andP = 0.027 and 0.040, respectively). Stratified by age, current smoking affected the development of hypertension only in the 50–59 years subjects with the normal weight (HR: 1.356;HR95%CI: 1.084–1.697; andP = 0.008).

Conclusions

Current smoking was a significant predictor of incident hypertension only in the female and middle-age populations with normal weight but not in the overweight and obesity as well as the younger and elder populations.
The assessment of spiritual well-being in cancer patients with advanced disease: which are its meaningful dimensions?
Authors: Rabitti Elisa , Cavuto Silvio , Iani Luca , Ottonelli Simona , De Vincenzo Francesco , Costantini Massimo
Published: March 2020

Background

Spirituality is particularly important for patients suffering from life-threatening illness. Despite research showing the benefits of spiritual assessment and care for terminally ill patients, their spiritual needs are rarely addressed in clinical practice. This study examined the factor structure and reliability of the Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp) in patients with advanced cancer. It also examined the clinical meaning and reference intervals of FACIT-Sp scores in cancer patients subgroups through a literature review.

Methods

A forward-backward translation procedure was adopted to develop the Italian version of the FACIT-Sp, which was administered to 150 terminally ill cancer patients. Exploratory factor analysis was used for construct validity, while Cronbach’s α was used to assess the reliability of the scale.

Results

This study replicates previous findings indicating that the FACIT-Sp distinguish well between features of meaning, peace, and faith. In addition, the internal consistency of the FACIT-Sp was acceptable. The literature review also showed that terminal cancer patients have the lowest scores on the Faith and Meaning subscales, whereas cancer survivors have the highest scores on Faith.

Conclusions

The Italian version of the FACIT-Sp has good construct validity and acceptable reliability. Therefore, it can be used as a tool to assess spiritual well-being in Italian terminally ill cancer patients. This study provides reference intervals of FACIT-Sp scores in newly diagnosed cancer patients, cancer survivors, and terminally ill cancer patients and further highlights the clinical meaning of such detailed assessment.
Underlying goals of advance care planning (ACP): a qualitative analysis of the literature
Authors: Fleuren Nienke , Depla Marja F. I. A. , Janssen Daisy J. A. , Huisman Martijn , Hertogh Cees M. P. M.
Published: March 2020

Background

Since the introduction of the concept of advance care planning (ACP), many studies have been conducted exploring beneficial effects. These studies show a heterogeneity in clinical endpoints, which reflects diversity of goals connected to ACP. This study aims to get insight in the range of underlying goals that comprise the legitimacy of ACP.

Methods

Systematic literature search in PubMed, EMBASE, PsychInfo, CINAHL and Cochrane Library. Articles on normative aspects of ACP were included, based on title and abstract. Due to the quantity of inclusions, of which many had similar content, purposive sampling was used to select articles for full text document analysis. Analysis stopped once saturation was reached.

Results

In total, 6497 unique articles were found of which 183 were included. Saturation was reached after document analysis of 55 articles (30%); this yielded 141 codes concerning goals of ACP and also 70 codes about objections against ACP, which shed light on the underlying goals of ACP as well. We identified five underlying goals: respecting individual patient autonomy, improving quality of care, strengthening relationships, preparing for end-of-life, reducing overtreatment.

Conclusions

Five distinctive underlying goals of ACP were identified, each with corresponding objections that need to be considered. Specifying underlying goals of ACP may direct the debate on definitions, methods and preferred outcomes of ACP.

This study was funded by the Netherlands Organisation for Health Research and Development, grant 839120002.
Hepatoprotective effects of gamma-aminobutyric acid-enriched fermented Hovenia dulcis extract on ethanol-induced liver injury in mice
Authors: Park Na-Hye , Lee Seung-Jin , Mechesso Abraham Fikru , Boby Naila , Yixian Quah , Yoon Woong-Kyu , Lee Sam-Pin , Lee Jong-Suk , Park Seung-Chun
Published: March 2020

Background

Various extracts of Hovenia dulcis have been commonly used in Asia for cases of alcohol-related disorders. Fermentation is reported to enhance the level and biological activities of various bio-constituents of plant extracts. Therefore, this study was undertaken to evaluate the effects of fermented H. dulcis extract (FHDE) on ethanol-induced liver injury in mice.

Methods

FHDE was prepared using Bacillus subtilis and Lactobacillus plantarum. The effects of FHDE on ethanol-induced liver injury were evaluated in C57BL/6 N CrSlc mice. A mixed feed preparation containing the fermented extract with and without ethanol was given to mice for 29 days, according to its group. At the end of the experiment, blood and liver samples were collected from all mice in the group. Plasma biochemical analysis and histopathological investigation were performed to evaluate the impacts of treatment on the biomarkers of hepatic damage and inflammatory changes. Besides, the expression of genes that regulate the activities of enzymes associated with alcohol metabolism, antioxidant activity, and fatty acid oxidation was assessed using a quantitative real-time polymerase chain reaction. Moreover, the amino acid contents and the active ingredients of the extract were evaluated before and after fermentation.

Results

Fermentation resulted in a marked increase and decrease in the amount of Gamma-Amino-n-butyric acid (GABA) and glutamic acid, respectively. FHDE enhanced the body weight gain of mice compared to ethanol. Besides, plasma levels of triglyceride, low-density lipoprotein, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly (P < 0.05) reduced in the FHDE-treated groups relative to the ethanol-treated control. FHDE upregulated the expression of genes associated with enzymes involved in alcohol dehydrogenation (Adh1 and Aldh2), antioxidant activity (SOD and CAT), and fatty acid oxidation (PPAR-α and PGC-1α). However, the expressions of Cytochrome peroxidase Cyp2E1 and genes related to lipogenesis (SREBP-1c, FAS, SCD-1, and ACC) were significantly (P < 0.05) downregulated following treatment with the FHDE. Histopathological investigation demonstrated a slight degree of inflammatory cell infiltration and occasional fatty changes in the FHDE-treated groups.

Conclusion

The GABA-enriched fermented H. dulcis extract prevented ethanol-induced hepatic damage by enhancing the antioxidant defense system, fatty acid oxidation, and reducing lipogenesis.
Protection from hydrogen peroxide stress relies mainly on AhpCF and KatA2 in Stenotrophomonas maltophilia
Authors: Li Li-Hua , Shih Yung-Luen , Huang Jing-Yun , Wu Chao-Jung , Huang Yi-Wei , Huang Hsin-Hui , Tsai Yu-Chieh , Yang Tsuey-Ching
Published: March 2020

Background

Aerobically-grown bacteria can be challenged by hydrogen peroxide stress from endogenous aerobic metabolism and exogenously generated reactive oxygen species. Catalase (Kat), alkyl hydroperoxidase (Ahp), and glutathione peroxidase (Gpx) systems are major adaptive responses to H2O2 stress in bacteria. Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacterium equipped with four Kats (KatA1, KatA2, KatMn, and KatE), one Ahp (AhpCF), and three Gpxs (Gpx1, Gpx2, and Gpx3). Here, we systematically investigated how the eight H2O2 scavenging genes differentially contribute to the low-micromolar levels of H2O2 generated from aerobic metabolism and high-millimolar levels of H2O2 from exogenous sources.

Methods

Gene expression was assessed and quantified by reverse transcription-PCR (RT-PCR) and real time quantitative PCR (qRT-PCR), respectively. The contribution of these enzymes to H2O2 stress was assessed using mutant construction and functional investigation.

Results

Of the eight genes, katA2, ahpCF, and gpx3 were intrinsically expressed in response to low-micromolar levels of H2O2 from aerobic metabolism, and the expression of katA2 and ahpCF was regulated by OxyR. AhpCF and KatA2 were responsible for alleviating aerobic growth-mediated low concentration H2O2 stress and AhpCF played a critical role for stationary-phase cells. KatA2 was upregulated to compensate for AhpCF in the case of ahpCF inactivation. After exposure to millimolar levels of H2O2, katA2 and ahpCF were upregulated in an OxyR-dependent manner. KatA2 was the critical enzyme for dealing with high concentration H2O2. Loss-of-function of KatA2 increased bacterial susceptibility to high concentration H2O2.

Conclusions

AhpCF and KatA2 are key enzymes protecting S. maltophilia from hydrogen peroxide stress.
Expression regulation of multiple key genes to improve l-threonine in Escherichia coli
Authors: Zhao Lei , Lu Ying , Yang Jun , Fang Yu , Zhu Lifei , Ding Zhixiang , Wang Chenhui , Ma Wenjian , Hu Xiaoqing , Wang Xiaoyuan
Published: March 2020

Background

Escherichia coliis an important strain forl-threonine production. Genetic switch is a ubiquitous regulatory tool for gene expression in prokaryotic cells. To sense and regulate intracellular or extracellular chemicals, bacteria evolve a variety of transcription factors. The key enzymes required forl-threonine biosynthesis inE. coliare encoded by thethroperon. Thethroperon could coordinate expression of these genes whenl-threonine is in short supply in the cell.

Results

ThethrLleader regulatory elements were applied to regulate the expression of genesiclR,arcA,cpxR,gadE,fadRandpykF, while the threonine-activating promotersPcysH,PcysJandPcysDwere applied to regulate the expression of geneaspC, resulting in the increase ofl-threonine production in anl-threonine producingE. colistrain TWF001. Firstly, different parts of the regulatorthrLwere inserted in theiclRregulator region in TWF001, and the best resulting strain TWF063 produced 16.34 gl-threonine from 40 g glucose after 30 h cultivation. Secondly, the geneaspCfollowing different threonine-activating promoters was inserted into the chromosome of TWF063, and the best resulting strain TWF066 produced 17.56 gl-threonine from 40 g glucose after 30 h cultivation. Thirdly, the effect of expression regulation ofarcA,cpxR,gadE,pykFandfadRwas individually investigated onl-threonine production in TWF001. Finally, using TWF066 as the starting strain, the expression of genesarcA,cpxR,gadE,pykFandfadRwas regulated individually or in combination to obtain the best strain forl-threonine production. The resulting strain TWF083, in which the expression of seven genes (iclR,aspC,arcA,cpxR,gadE,pykF,fadRandaspC) was regulated, produced 18.76 gl-threonine from 30 g glucose, 26.50 gl-threonine from 40 g glucose, or 26.93 gl-threonine from 50 g glucose after 30 h cultivation. In 48 h fed-batch fermentation, TWF083 could produce 116.62 g/Ll‐threonine with a yield of 0.486 g/g glucose and productivity of 2.43 g/L/h.

Conclusion

The genetic engineering through the expression regulation of key genes is a better strategy than simple deletion of these genes to improvel-threonine production inE. coli. This strategy has little effect on the intracellular metabolism in the early stage of the growth but could increasel-threonine biosynthesis in the late stage.
Correction to: Households forgoing healthcare as a measure of financial risk protection: an application to Liberia
Authors: Gabani Jacopo , Guinness Lorna
Published: March 2020

Following publication of the original article [1], we have been notified that part of the Results part of the Abstract text is mentioned with the mistake.
Comprehensive analysis of the cardiac proteome in a rat model of myocardial ischemia-reperfusion using a TMT-based quantitative proteomic strategy
Authors: Lim Sun Ha , Lee Jongwon , Han Mee-Jung
Published: March 2020

Background

Traditional studies of the cardiac proteome have mainly investigated in an animal model by two-dimensional gel electrophoresis (2-DE). However, the results have not been of satisfactory quality for an understanding of the underlying mechanism. Recent quantitative proteomic methods have been improved to overcome these limitations. To comprehensively study the cardiac proteome in a rat model of ischemia-reperfusion (IR), we developed a tandem mass tag (TMT)-based quantitative proteomic strategy. Furthermore, using this strategy, we examined the molecular mechanisms underlying the prevention of myocardial infarction by the intake of Triticum aestivum L. extract (TALE), a representative dietary fiber grain.

Methods

Cardiac proteomes were analyzed by 2-DE as a gel-based approach, and TMT labeling coupled with two-dimensional liquid chromatography (2D-LC) and tandem mass spectrometry (MS/MS) as a non-gel-based quantitative approach. Additionally, gene ontology annotation was conducted by PANTHER database. Several proteins of interest were verified by a Western blot analysis.

Results

Total 641 proteins were identified commonly from two independent MS datasets using 2D-LC MS/MS. Among these, we identified 151 IR-related proteins that were differentially expressed between the sham-operation group and IR group, comprising 62 up-regulated proteins and 89 down-regulated proteins. Most of the reduced proteins were involved in metabolic processes. In addition, 57 of the IR-related proteins were affected by TALE intake, representing 25 up-regulated proteins and 32 down-regulated proteins. In particular, TALE intake leads to a switch in metabolism to reduce the loss of high-energy phosphates and the accumulation of harmful catabolites (especially reactive oxygen species (ROS)) and to maintain cytoskeleton balance, leading to a reduction in cardiac IR injury.

Conclusions

Our study provides a comprehensive proteome map of IR-related proteins and potential target proteins and identifies mechanisms implicated in the prevention of myocardial infarction by TALE intake in a rat IR model.
The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers
Authors: Wang Juan , Nishiyama Akira , Matsuyama Makoto , Wang Zhiyu , Yuan Ying
Published: March 2020

Background

The (pro) renin receptor ((P)RR) plays important roles in various pathways, such as the Wnt/β-catenin, renin-angiotensin system (RAS), MAPK/ERK and PI3K/AKT/mTOR pathways, that are involved in a wide range of physiological and pathological processes incorporating the tumorigenesis. However, our knowledge about (P) RR was mostly limited to its roles in cardiovascular and renal physiological functions and diseases. In the past 5 years, however, compelling evidence has revealed that (P) RR is aberrantly expressed in and contributes to the development of various cancers by different means. For instance, (P) RR was recently demonstrated to induce the oncogenesis of pancreatic, colorectal and brain cancers via the Wnt signaling, while promote the endometrial cancer and glioblastoma through the RAS.

Methods

Combining with the deep analysis of big data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, this review updates and summarizes the recent studies about the newly recognized roles of (P) RR in the pathophysiological processes of cancer development and its detailed functions through related pathways, as well as the novel research progress of (P) RR in related fields including the development and application of soluble (P) RR detection kit and monoclonal (P) RR antibody.

Results

This review provides an overview of the essential roles of (P) RR in the tumorigenesis and progression of various cancers and offers a translational outlook for the future research and clinical practices.

Conclusion

(P) RR in the tumor tissues and/or body fluids of patients may be a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in various cancers.

Graphical abstract
Towards single-cell ionomics: a novel micro-scaled method for multi-element analysis of nanogram-sized biological samples
Authors: Chen Anle , Hansen Thomas H. , Olsen Lene I. , Palmgren Michael , Husted Søren , Schjoerring Jan K. , Persson Daniel Pergament
Published: March 2020

Background

To understand processes regulating nutrient homeostasis at the single-cell level there is a need for new methods that allow multi-element profiling of biological samples ultimately only available as isolated tissues or cells, typically in nanogram-sized samples. Apart from tissue isolation, the main challenges for such analyses are to obtain a complete and homogeneous digestion of each sample, to keep sample dilution at a minimum and to produce accurate and reproducible results. In particular, determining the weight of small samples becomes increasingly challenging when the sample amount decreases.

Results

We developed a novel method for sampling, digestion and multi-element analysis of nanogram-sized plant tissue, along with strategies to quantify element concentrations in samples too small to be weighed. The method is based on tissue isolation by laser capture microdissection (LCM), followed by pressurized micro-digestion and ICP-MS analysis, the latter utilizing a stable µL min−1 sample aspiration system. The method allowed for isolation, digestion and analysis of micro-dissected tissues from barley roots with an estimated sample weight of only ~ 400 ng. In the collection and analysis steps, a number of contamination sources were identified. Following elimination of these sources, several elements, including magnesium (Mg), phosphorus (P), potassium (K) and manganese (Mn), could be quantified. By measuring the exact area and thickness of each of the micro-dissected tissues, their volume was calculated. Combined with an estimated sample density, the sample weights could subsequently be calculated and the fact that these samples were too small to be weighed could thereby be circumvented. The method was further documented by analysis of Arabidopsis seeds (~ 20 µg) as well as tissue fractions of such seeds (~ 10 µg).

Conclusions

The presented method enables collection and multi-element analysis of small-sized biological samples, ranging down to the nanogram level. As such, the method paves the road for single cell and tissue-specific quantitative ionomics, which allow for future transcriptional, proteomic and metabolomic data to be correlated with ionomic profiles. Such analyses will deepen our understanding of how the elemental composition of plants is regulated, e.g. by transporter proteins and physical barriers (i.e. the Casparian strip and suberin lamellae in the root endodermis).
Comparison of different bridging anticoagulation therapies used after mechanical heart valve replacement in Chinese patients - a prospective cohort study
Authors: Li Bo-Xia , Liu Shi-Dong , Qi Liang , Sun Shusen , Sun Wei , Li Yuan-Min , Song Bing , Wu Xin-An
Published: March 2020

Objective

To assess different bridging anticoagulation therapies early after mechanical heart valve replacement (MHVR) in Chinese patients.

Methods

We performed a prospective, single-center, observational cohort study of 305 patients who underwent elective MHVR with different bridging anticoagulation regimens. Patients enrolled in the study were divided into three bridging therapy groups: the unfractionated heparin (UFH) group (n = 109), the low-molecular-weight heparin (LMWH) group (n = 97), and the UFH with sequential LMWH (UFH-LMWH) group (n = 99). All patients were followed for 4 weeks.

Results

Two patients experienced thromboembolic stroke events in the UFH group. The LMWH group was associated with an increase in the incidence of bleeding events compared with the UFH group (10.3% VS 2.8%; P = 0.03). With a comparison of LMWH and UFH group in secondary endpoints, the statistical test for significance indicated a trend of reduced ICU length of stay (P = 0.08), postoperative length of stay (P = 0.08) and time of achieving target INR (P = 0.06). The creatinine level (odds ratio = 1.03; 95% confidence interval = 1.01 to 1.05; P = 0.02) and hypertension (odds ratio = 3.72; 95% confidence interval = 1.35 to 10.28; P = 0.01) were risk factors for bleeding events.

Conclusion

For Chinese patients, the LMWH bridging anticoagulation presents the increased the incidence of bleeding events, but enables patients to benefit from achieving an early anticoagulation effect. Close follow-up and personalized management are required in patients with thromboembolic and bleeding risk factors.

Trial registration

Chinese Clinical Trial Registry ChiCTR1800019841. Registered 2 December 2018 retrospectively.
The volume-outcome relationship among severely injured patients admitted to English major trauma centres: a registry study
Authors: Sewalt Charlie A. , Wiegers Eveline J. A. , Lecky Fiona E. , den Hartog Dennis , Schuit Stephanie C. E. , Venema Esmee , Lingsma Hester F.
Published: March 2020

Background

Many countries have centralized and dedicated trauma centres with high volumes of trauma patients. However, the volume-outcome relationship in severely injured patients (Injury Severity Score (ISS) > 15) remains unclear. The aim of this study was to determine the association between hospital volume and outcomes in Major Trauma Centres (MTCs).

Methods

A retrospective observational cohort study was conducted using the Trauma Audit and Research Network (TARN) consisting of all English Major Trauma Centres (MTCs). Severely injured patients (ISS > 15) admitted to a MTC between 2013 and 2016 were included. The effect of hospital volume on outcome was analysed with random effects logistic regression models with a random intercept for centre and was tested for nonlinearity. Primary outcome was in-hospital mortality.

Results

A total of 47,157 severely injured patients from 28 MTCs were included in this study. Hospital volume varied from 69 to 781 severely injured patients per year. There were small between-centre differences in mortality after adjusting for important demographic and injury severity characteristics (adjusted 95% odds ratio range: 0.99–1.01). Hospital volume was found to be linear and not associated with in-hospital mortality (adjusted odds ratio (aOR) 1.02 per 10 patients, 95% confidence interval (CI) 0.68–1.54, p = 0.92).

Conclusions

Despite the large variation in volume of the included MTCs, no relationship between hospital volume and outcome of severely injured patients was found. These results suggest that centres with similar structure and processes of care can achieve comparable outcomes in severely injured patients despite the number of severely injured patients they treat.
Influence of physical strain at high altitude on the quality of cardiopulmonary resuscitation
Authors: Egger Alexander , Niederer Maximilian , Tscherny Katharina , Burger Josef , Fuhrmann Verena , Kienbacher Calvin , Roth Dominik , Schreiber Wolfgang , Herkner Harald
Published: March 2020

Background

High quality cardiopulmonary resuscitation is a key factor in survival with good overall quality of life after out-of-hospital cardiac arrest. Current evidence is predominantly based on studies conducted at low altitude, and do not take into account the special circumstances of alpine rescue missions. We therefore aimed to investigate the influence of physical strain at high altitude on the quality of cardiopulmonary resuscitation.

Methods

Alpine field study. Twenty experienced mountaineers of the Austrian Mountain Rescue Service trained in Basic Life Support (BLS) performed BLS on a manikin in groups of two for 16 min. The scenario was executed at baseline altitude and immediately after a quick ascent over an altitude difference of 1200 m at 3454 m above sea level. The sequence of scenarios was randomised for a cross over analysis.

Quality of CPR and exhaustion of participants (vital signs, Borg-Scale, Nine hole peg test) were measured and compared between high altitude and baseline using random-effects linear regression models.

Results

The primary outcome of chest compression depth significantly decreased at high altitude compared to baseline by 1 cm (95% CI 0.5 to 1.3 cm, p < 0.01). There was a significant reduction in the proportion of chest compressions in the target depth (at least 5 cm pressure depth) by 55% (95% CI 29 to 82%, p < 0.01) and in the duration of the release phase by 75 ms (95% CI 48 to 101 ms, p < 0.01). No significant difference was found regarding hands-off times, compression frequency or exhaustion.

Conclusion

Physical strain during a realistic alpine rescue mission scenario at high altitude led to a significant reduction in quality of resuscitation. Resuscitation guidelines developed at sea level are not directly applicable in the mountain terrain.
The protocol for a multisite, double blind, randomized, placebo-controlled trial of axillary nerve stimulation for chronic shoulder pain
Authors: Cleland Travis , Jain Nitin B. , Chae John , Hansen Kristine M. , Hisel Terri Z. , Gunzler Douglas D. , Whitehair Victoria C. , Kim Chong H. , Wilson Richard D.
Published: March 2020

Background

Shoulder impingement syndrome is one of the most common causes of shoulder pain, accounting for approximately 30% of all shoulder pain. Approximately 35% of patients with shoulder impingement syndrome are refractory to conservative treatment. For patients who fail conservative treatment, there is no established treatment to successfully treat their chronic pain. Prior randomized control trials have demonstrated efficacy for the use of a single lead intramuscular peripheral nerve stimulation of the axillary nerve at the motor points of the deltoid muscle for treatment of hemiplegic shoulder pain. This is the first controlled trial to utilize the same novel technology to treat shoulder impingement syndrome outside of the stroke population.

Methods

This is a dual-site, placebo-controlled, double-blinded, randomized control trial. Participants will be randomized to two treatment groups. The intervention group will be treated with active peripheral nerve stimulation of the axillary nerve of the affected shoulder and the control group will be treated with sham peripheral nerve stimulation of the axillary nerve of the affected shoulder. Both groups will receive a standardized exercise therapy program directed by a licensed therapist.

Discussion

This study protocol will allow the investigators to determine if this novel, non-pharmacologic treatment of shoulder pain can demonstrate the same benefit in musculoskeletal patients which has been previously demonstrated in the stroke population.

Trial registration

Clinicaltrials.gov,NCT03752619. Registered on 26 November 2018.
Molecular typing of Cyclospora cayetanensis in produce and clinical samples using targeted enrichment of complete mitochondrial genomes and next-generation sequencing
Authors: Cinar Hediye Nese , Gopinath Gopal , Murphy Helen R. , Almeria Sonia , Durigan Mauricio , Choi Dajung , Jang AhYoung , Kim Eunje , Kim RaeYoung , Choi Seonju , Lee Jeongu , Shin Yurim , Lee Jieon , Qvarnstrom Yvonne , Benedict Theresa K. , Bishop Henry S. , da Silva Alexandre
Published: March 2020

Background

Outbreaks of cyclosporiasis, a diarrheal illness caused by Cyclospora cayetanensis, have been a public health issue in the USA since the mid 1990’s. In 2018, 2299 domestically acquired cases of cyclosporiasis were reported in the USA as a result of multiple large outbreaks linked to different fresh produce commodities. Outbreak investigations are hindered by the absence of standardized molecular epidemiological tools for C. cayetanensis. For other apicomplexan coccidian parasites, multicopy organellar DNA such as mitochondrial genomes have been used for detection and molecular typing.

Methods

We developed a workflow to obtain complete mitochondrial genome sequences from cilantro samples and clinical samples for typing of C. cayetanensis isolates. The 6.3 kb long C. cayetanensis mitochondrial genome was amplified by PCR in four overlapping amplicons from genomic DNA extracted from cilantro, seeded with oocysts, and from stool samples positive for C. cayetanensis by diagnostic methods. DNA sequence libraries of pooled amplicons were prepared and sequenced via next-generation sequencing (NGS). Sequence reads were assembled using a custom bioinformatics pipeline.

Results

This approach allowed us to sequence complete mitochondrial genomes from the samples studied. Sequence alterations, such as single nucleotide polymorphism (SNP) profiles and insertion and deletions (InDels), in mitochondrial genomes of 24 stool samples from patients with cyclosporiasis diagnosed in 2014, exhibited discriminatory power. The cluster dendrogram that was created based on distance matrices of the complete mitochondrial genome sequences, indicated distinct strain-level diversity among the 2014 C. cayetanensis outbreak isolates analyzed in this study.

Conclusions

Our results suggest that genomic analyses of mitochondrial genome sequences may help to link outbreak cases to the source.
TGFβ-mediated expression of TGFβ-activating integrins in SSc monocytes: disturbed activation of latent TGFβ?
Authors: van Caam A. , Aarts J. , van Ee T. , Vitters E. , Koenders M. , van de Loo F. , van Lent P. , van den Hoogen F. , Thurlings R. , Vonk M. C. , van der Kraan P. M.
Published: March 2020

Introduction

The pathophysiology of systemic sclerosis (SSc) is closely linked to overactive TGFβ signaling. TGFβ is produced and circulates in latent form, making its activation crucial for signaling. This activation can be mediated via integrins. We investigated the balance between active and latent TGFβ in serum of SSc patients and investigated if this correlates with integrin expression on monocytes.

Methods

A TGFβ/SMAD3- or BMP/SMAD1/5-luciferase reporter construct was expressed in primary human skin fibroblasts. Both acidified and non-acidified sera of ten SSc patients and ten healthy controls were tested on these cells to determine total and active TGFβ and BMP levels respectively. A pan-specific TGFβ1/2/3 neutralizing antibody was used to confirm TGFβ signaling. Monocytes of 20 SSc patients were isolated using CD14+ positive selection, and integrin gene expression was measured using qPCR. Integrin expression was modulated using rhTGFβ1 or a small molecule inhibitor of TGFBR1: SB-505124.

Results

SSc sera induced 50% less SMAD3-reporter activity than control sera. Serum acidification increased reporter activity, but a difference between healthy control and SSc serum was no longer observed, indicating that total TGFβ levels were not different. Addition of a pan-specific TGFβ1/2/3 neutralizing antibody fully inhibited SMAD3-reporter activity of both acidified and not-acidified control and SSc sera. Both HC and SSc sera induced similar SMAD1/5-reporter activity, and acidification increased this, but not differently between groups. Interestingly, expression of two integrin alpha subunits ITGA5 and ITGAV was significantly reduced in monocytes obtained from SSc patients. Furthermore, ITGB3, ITGB5, and ITGB8 expression was also reduced in SSc monocytes. Stimulation of monocytes with TGFβ1 induced ITGA5 and ITGAV but lowered ITGB8 expression, whereas the use of the TGFβ receptor inhibitor SB-505124 had the opposite effect.

Conclusion

Total TGFβ serum levels are not different between SSc patients and controls, but TGFβ activity is. This coincides with a reduced expression of TGFβ-activating integrins in monocytes of SSc patients. Because TGFβ regulates expression of these integrins in monocytes, a negative feedback mechanism possibly underlies these observations.
68Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with 177Lu-PSMA-617
Authors: de Vries Lisa H. , Lodewijk Lutske , Braat Arthur J. A. T. , Krijger Gerard C. , Valk Gerlof D. , Lam Marnix G. E. H. , Borel Rinkes Inne H. M. , Vriens Menno R. , de Keizer Bart
Published: March 2020

Background

Differentiated thyroid carcinoma (DTC) is the most common type of thyroid cancer. Treatment with surgery, radioactive iodine (RAI), and TSH suppression is effective in most patients. Five to 15% of patients become RAI refractory and need alternative therapy; however, treatment options are limited. 68Ga-PSMA PET/CT, originally developed for prostate cancer, is also applicable to other malignancies, including thyroid carcinoma. The uptake of PSMA in thyroid carcinoma gives opportunities for imaging and therapy of RAI-refractory DTC. The aim of this study was to analyze imaging on 68Ga-PSMA PET/CT and evaluate the response to 177Lu-PSMA-617 therapy in patients with RAI-refractory DTC.

Materials and methods

Five patients with RAI-refractory DTC underwent 68Ga-PSMA PET/CT to determine their eligibility for 177Lu-PSMA-617 therapy. 68Ga-PSMA PET/CTs were analyzed visually and quantitatively. Response to 177Lu-PSMA-617 therapy was evaluated using imaging and thyroglobulin (Tg) values.

Results

Tracer uptake suspicious for distant metastases was depicted in all 68Ga-PSMA PET/CTs. Based on tracer uptake, three patients were eligible for 177Lu-PSMA-617 therapy, of whom two were treated. One patient showed disease progression on imaging 1 month later, while her Tg values gradually increased from 18 to 63 μg/L in the months after treatment. Another patient showed partial, temporary response of lung and liver metastases. Her Tg levels initially decreased from 17 to 9 μg/L. However, 7 months after treatment, there was disease progression on imaging and Tg levels had increased to 14 μg/L.

Imaging with 68Ga-PSMA PET/CT could be compared to 18FDG PET/CT in three patients. Two patients showed additional lesions on 68Ga-PSMA PET/CT, and one patient showed concordant imaging.

Conclusion

68Ga-PSMA PET/CT appears to have added value in patients with RAI-refractory DTC, as it is able to detect various types of lesions, some of which were not picked up by 18FDG PET/CT. Furthermore, 68Ga-PSMA PET/CT might be used to identify patients eligible for treatment with 177Lu-PSMA-617. One of the two patients who underwent 177Lu-PSMA-617 therapy showed a modest, temporary response. To draw conclusions about the effectiveness of this therapy, more research is needed.
Profile of regional fat and fat-free soft tissue accumulation in male athletes
Authors: Takai Yohei , Nakatani Miyuki , Aoki Toru , Komori Daisuke , Oyamada Kazuyuki , Murata Kensuke , Fujita Eiji , Akamine Takuya , Urita Yoshihisa , Yamamoto Masayoshi , Kanehisa Hiroaki
Published: March 2020

Background

It is unclear whether or not the breakpoint (BP), at which the proportion of each of fat mass (FM) and fat-free soft tissue mass (FFSTM) to body mass (BM) alter, exists in male athletes. We examined the hypothesis that in male athletes, the regional FM and FFSTM-BM relationships have a BP, but the body mass at BP (BMBP) differs among the arms, trunk, and legs.

Methods

By using a dual X-ray absorptiometry, whole-body and regional FMs and FFSTMs in the arms, trunk, and legs were estimated in 198 male athletes (20.8 ± 2.1 years; 1.73 ± 0.07 m; 72.7 ± 14.8 kg). To detect the BP in the relationship between each of FM and FFSTM and BM, a piecewise linear regression analysis was used. If a BP was detected in the corresponding relationship, the significant difference between the regression slopes above and below the BP was examined.

Results

The regression analysis indicated that the BMBP existed in the FM- and FFSTM-BM relationships regardless of region and whole body. For the whole body, BMBP was 81.8 kg for FM and 82.2 kg for FFSTM. In regional FM-BM relationships, BMBP was 80.5 kg for arms, 82.6 kg for trunk, and 63.3 kg for legs, and the regression slopes above the BMBP became higher than those below the BP, and vice versa in regional FFSTM-BM relationships (BMBP 104.6 kg for arms, 80.9 kg for trunk, and 79.0 kg for legs). The relative differences in the slopes between below and above BMBP in the regional FM-BM relationships were higher in the arms and trunk than in the legs, and those in the regional FFSTM-BM relationships in the legs than in the trunk.

Conclusion

Whole-body and regional FM- and FFSTM-BM relationships for male athletes have breakpoints at which the proportion of the tissue masses to BM alters. The BMBP and differences in the distribution of regional FM and FFSTM around the breakpoint are region specific.
Endoscopic cartilage myringoplasty with the removal of a small rim of the external auditory canal to repair marginal perforations
Authors: Lou Zheng-cai
Published: March 2020

Objective

To evaluate the graft success rate and postoperative hearing gain for marginal perforations using endoscopic cartilage myringoplasty with the removal of a small rim of the external auditory canal (EAC).

Study design

Prospective case series.

Materials and methods

We performed a prospective study in 41 patients with marginal perforations who underwent endoscopic cartilage myringoplasty with the removal of a small rim of EAC. Patients were followed up for 6 months.

Results

Of the 41 patients with unilateral marginal perforation included in this study, the graft success rate was 100% (41/41). The mean ABG improved from 11.31 ± 9.71 dB preoperatively to 7.31 ± 2.32 dB postoperatively for small-and medium-sized perforations ( P = 0.13); the mean ABG improved from 21.46 ± 8.39 dB preoperatively to 9.84 ± 2.41 dB postoperatively for large perforations ( P < 0.05); the mean ABG improved from 28.79 ± 6.74 dB preoperatively to 10.13 ± 3.56 dB postoperatively for subtotal and total perforations ( P < 0.05). There were no cases of graft lateralization or significant blunting or atelectasis or graft adhesions. Three patients developed postoperative otorrhoea and five patients had mild myringitis.

Conclusions

Endoscopic cartilage myringoplasty with the removal of a small rim of the EAC is simple and feasible, showing a high graft success rate and minimal complications for repairing marginal perforations.
Essential in-vitro laboratory diagnostic services provision in accordance with the WHO standards in Guragae zone primary health care unit level, South Ethiopia
Authors: Shumbej Teha , Menu Sofia , Gebru Teklemichael , Girum Tadele , Bekele Fitsum , Solomon Absra , Mesfin Dereje , Jemal Abdulewhab
Published: March 2020

Introduction

Laboratory services are crucial parts of the health system having a great contribution to disease prevention and management. The importance of accurate and reliable laboratory test results is less recognized in developing countries like Ethiopia where most medical decisions are based on clinical judgment. It is time for countries like Ethiopia to not only increase health care coverage but also improve access to essential diagnostic tests. Hence, this proposed study aims to assess essential in-vitro laboratory service provision in accordance with the WHO standards in Guragae Zone primary health care unit level, South Ethiopia.

Methods

Health institution-based cross-sectional study was carried out. 30% randomly selected primary health care units were recruited. Each facility was visited with a WHO checklist by a trained data collector to assess the availability of essential diagnostics service provision. The proportion of available in-vitro diagnostics services was calculated. Results were presented as percentages in tables and figures.

Result

Twenty-one primary health care facilities located in Guragae Zone were assessed between May and July 2019. All surveyed facilities had major gaps in essential test availability. Among essential diagnostic tests listed with WHO like C-reactive protein, lipid profile, Amylase and Lipase, TroponinT/I, hepatitis B e-antigen, IgM-specific antibodies to hepatitis B core antigen, Glucose-6-phosphate dehydrogenase activity, and anti-HIV/p24 rapid test were not provided in any facilities. However, essential diagnostic services like urine dipstick testing, random blood sugar, smear microscopy, and few serological tests were provided at all primary health care units. All surveyed facilities had limited major laboratory equipment and consumables.

Conclusion and recommendation

The present study shows limited access to essential laboratory tests at the primary health care level. Hence, the responsible body should invest to make essential tests accessible at the primary care unit level within the framework of universal health coverage in the study area. The fact that access to essential diagnostic tests is the first key step in improving quality of care; such study has its own efforts to enable the implementation of essential diagnostic lists, and improve access to diagnostics in the country.
Associations between low muscle mass, blood-borne nutritional status and mental health in older patients
Authors: Gariballa Salah , Alessa Awad
Published: March 2020

Background

Although low muscle mass is an important predictor of increased physical morbidity in older patients, information on its impact on mental health and well-being is lacking. The first aim of this report is to look for associations if any between low muscle mass and mental health of older people in clinical practice. The second aim is to study underlying mechanisms including nutritional status.

Methods

In this prospective longitudinal study we randomly selected and studied 432 hospitalized older patients’ baseline demographic data, clinical characteristics and nutritional status on admission, at 6 weeks and at 6 months. Low muscle mass was diagnosed using anthropometric measures based on the European Working Group criteria. Mental health outcome measures including cognitive state, depression symptoms and quality of life were also measured.

Results

Out of 432 patients assessed 44 (10%) were diagnosed with low muscle mass. Patients diagnosed with low muscle mass at admission and over a 6-month follow up period had significantly poor cognitive function, quality of life and increased depression symptoms compared with those with normal muscle mass. After adjustment for poor prognostic indicators, age, disability, severity of acute illness and low muscle mass were associated with poor cognitive function and quality of life and higher depression symptoms in older patients over a 6 months period (p < 0.05). Although patients with low muscle mass had lower micronutrient concentrations compared to those patients with normal muscle mass, only serum albumin showed significant correlations with quality of life at admission and depression symptoms at 6 weeks.

Conclusion

Low muscle mass is associated with poor blood-borne poor nutritional status and mental health in hospitalized older patients, however, this is partly explained by underlying co morbidity.