bluuebunny/crossref_metadata_2025 huggingface dataset:
Algorithms to identify COPD in health systems with and without access to ICD coding: a systematic review
Authors: Gothe Holger , Rajsic Sasa , Vukicevic Djurdja , Schoenfelder Tonio , Jahn Beate , Geiger-Gritsch Sabine , Brixner Diana , Popper Niki , Endel Gottfried , Siebert Uwe
Published: October 2019

Background

Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide. Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected. This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute. The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available.

Methods

A systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters. Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables.

Results

In total, the systematic search yielded 151 publications. After title and abstract screening, 38 publications were included into the systematic assessment. In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits. Only four out of 38 studies used methods other than ICD coding. In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided. Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies. Only five studies used spirometry, two used surgery and one used oxygen therapy.

Conclusions

A variety of different criteria is used for the identification of COPD from routine data. The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data. Further health services research should focus on the application of more systematic internal and/or external validation approaches.
The advanced care coordination program: a protocol for improving transitions of care for dual-use veterans from community emergency departments back to the Veterans Health Administration (VA) primary care
Authors: Miller Lindsay B. , Sjoberg Heidi , Mayberry Ashlea , McCreight Marina S. , Ayele Roman A. , Battaglia Catherine
Published: October 2019

Background

Veterans who access both the Veterans Health Administration (VA) and non-VA health care systems require effective care coordination to avoid adverse health care outcomes. These dual-use Veterans have diverse and complex needs. Gaps in transitions of care between VA and non-VA systems are common. The Advanced Care Coordination (ACC) quality improvement program aims to address these gaps by implementing a comprehensive longitudinal care coordination intervention with a focus on Veterans’ social determinants of health (SDOH) to facilitate Veterans’ transitions of care back to the Eastern Colorado Health Care System (ECHCS) for follow-up care.

Methods

The ACC program is an ongoing quality improvement study that will enroll dual-use Veterans after discharge from non-VA emergency department (EDs), and will provide Veterans with social worker-led longitudinal care coordination addressing SDOH and providing linkage to resources. The ACC social worker will complete biopsychosocial assessments to identify Veteran needs, conduct regular in-person and phone visits, and connect Veterans back to their VA care teams.

We will identify non-VA EDs in the Denver, Colorado metro area that will provide the most effective partnership based on location and Veteran need. Veterans will be enrolled into the ACC program when they visit one of our selected non-VA EDs without being hospitalized. We will develop a program database to allow for continuous evaluation. Continuing education and outreach including the development of a resource guide, Veteran Care Cards, and program newsletters will generate program buy-in and bridge communication. We will evaluate our program using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, supported by the Practical, Robust Implementation and Sustainability Model, Theoretical Domains Framework, and process mapping.

Discussion

The ACC program will improve care coordination for dual-use Veterans by implementing social-work led longitudinal care coordination addressing Veterans’ SDOH. This intervention will provide an essential service for effective care coordination.
Implementation of a national policy for improving health and social care: a comparative case study using the Consolidated Framework for Implementation Research
Authors: Strehlenert Helena , Hansson Johan , Nyström Monica Elisabeth , Hasson Henna
Published: October 2019

Background

Comprehensive policies are becoming common for addressing wicked problems in health and social care. Success of these policies often varies between target organizations. This variation can often be attributed to contextual factors. However, there is a lack of knowledge about the conditions for successful policy implementation and how context influences this process. The aim of this study was to investigate county-level actors’ perspectives on the implementation of a comprehensive national policy in three Swedish counties. The policy focused on developing quality of care for elderly based on the use of national quality registries (NQRs) and to improve coordination of care.

Methods

A comparative case study approach was used. Data was collected longitudinally through documents and interviews. The Consolidated Framework for Implementation Research (CFIR) guided the analysis.

Results

All three counties shared the view that the policy addressed important issues. Still, there was variation regarding how it was perceived and managed. Adaptable features—i.e., NQRs and improvement coaches—were perceived as relevant and useful. However, the counties differed in their perceptions of another policy component—i.e., senior management program—as an opportunity or a disturbance. This program, while tackling complex issues of collaboration, fell short in recognizing the counties’ pre-existing conditions and needs and also offered few opportunities for adaptations. Performance bonuses and peer pressure were strong incentives for all counties to implement the policy, despite the poor fit of policy content and local context.

Conclusions

Comprehensive health policies aiming to address wicked problems have better chances of succeeding if the implementation includes assessments of the target organizations’ implementation capacity as well as the implicit quid pro quos involved in policy development. Special attention is warranted regarding the use of financial incentives when dealing with wicked problems since the complexity makes it difficult to align incentives with the goals and to assess potential consequences. Other important aspects in the implementation of such policies are the use of collaborative approaches to engage stakeholders with differing perspectives, and the tailoring of policy communication to facilitate shared understanding and commitment.
MAP4K3/GLK in autoimmune disease, cancer and aging
Authors: Chuang Huai-Chia , Tan Tse-Hua
Published: October 2019

MAP4K3 (also named GLK) is a serine/threonine kinase, which belongs to the mammalian Ste20-like kinase family. At 22 years of age, GLK was initially cloned and identified as an upstream activator of the MAPK JNK under an environmental stress and proinflammatory cytokines. The data derived from GLK-overexpressing or shRNA-knockdown cell lines suggest that GLK may be involved in cell proliferation through mTOR signaling. GLK phosphorylates the transcription factor TFEB and retains TFEB in the cytoplasm, leading to inhibition of cell autophagy. After generating and characterizing GLK-deficient mice, the important in vivo roles of GLK in T-cell activation were revealed. In T cells, GLK directly interacts with and activates PKCθ through phosphorylating PKCθ at Ser-538 residue, leading to activation of IKK/NF-κB. Thus, GLK-deficient mice display impaired T-cell-mediated immune responses and decreased inflammatory phenotypes in autoimmune disease models. Consistently, the percentage of GLK-overexpressing T cells is increased in the peripheral blood from autoimmune disease patients; the GLK-overexpressing T cell population is correlated with disease severity of patients. The pathogenic mechanism of autoimmune disease by GLK overexpression was unraveled by characterizing T-cell-specific GLK transgenic mice and using biochemical analyses. GLK overexpression selectively promotes IL-17A transcription by inducing the AhR-RORγt complex in T cells. In addition, GLK overexpression in cancer tissues is correlated with cancer recurrence of human lung cancer and liver cancer; the predictive power of GLK overexpression for cancer recurrence is higher than that of pathologic stage. GLK directly phosphorylates and activates IQGAP1, resulting in induction of Cdc42-mediated cell migration and cancer metastasis. Furthermore, treatment of GLK inhibitor reduces disease severity of mouse autoimmune disease models and decreases IL-17A production of human autoimmune T cells. Due to the inhibitory function of HPK1/MAP4K1 in T-cell activation and the promoting effects of GLK on tumorigenesis, HPK1 and GLK dual inhibitors could be useful therapeutic drugs for cancer immunotherapy. In addition, GLK deficiency results in extension of lifespan in Caenorhabditis elegans and mice. Taken together, targeting MAP4K3 (GLK) may be useful for treating/preventing autoimmune disease, cancer metastasis/recurrence, and aging.
DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study
Authors: JIMÉNEZ-SOUSA María Ángeles , JIMÉNEZ José Luis , FERNÁNDEZ-RODRÍGUEZ Amanda , BELLÓN José María , RODRÍGUEZ Carmen , RIERA Melchor , PORTILLA Joaquín , CASTRO Ángeles , MUÑOZ-FERNÁNDEZ María Ángeles , RESINO Salvador
Published: October 2019

Background

Most of the circulating Vitamin D (VitD) is transported bound to vitamin D-binding protein (DBP), and several DBP single nucleotide polymorphisms (SNPs) have been related to circulating VitD concentration and disease. In this study, we evaluated the association among DBP SNPs and AIDS progression in antiretroviral treatment (ART)-naïve-HIV-infected patients.

Methods

We performed a retrospective study in 667 patients who were classified according to their pattern of AIDS progression (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)) and 113 healthy blood donors (HIV, HCV, and HBV negative subjects). We genotyped seven DBP SNPs (rs16846876, rs12512631, rs2070741, rs2282679, rs7041, rs1155563, rs2298849) using Agena Bioscience’s MassARRAY platform. The genetic association was evaluated by Generalized Linear Models adjusted by age at the moment of HIV diagnosis, gender, risk group, and VDR rs2228570 SNP. Multiple testing correction was performed by the false discovery rate (Benjamini and Hochberg procedure; q-value).

Results

All SNPs were in HWE (p > 0.05) and had similar genotypic frequencies for DBP SNPs in healthy-controls and HIV-infected patients. In unadjusted GLMs, we only found significant association with AIDS progression in rs16846876 and rs12512631 SNPs. In adjusted GLMs, DBP rs16846876 SNP showed significant association under the recessive inheritance model [LTNPs vs. RPs (adjusted odds ratio (aOR) = 3.53; q-value = 0.044) and LTNPs vs. MPs (aOR = 3.28; q-value = 0.030)] and codominant [LTNPs vs. RPs (aOR = 4.92; q-value = 0.030) and LTNPs vs. MPs (aOR = 3.15; q-value = 0.030)]. Also, we found DBP rs12512631 SNP showed significant association in the inheritance model dominant [LTNPs vs. RPs (aOR = 0.49; q-value = 0.031) and LTNPs vs. MPs (aOR = 0.6; q-value = 0.047)], additive [LTNPs vs. RPs (aOR = 0.61; q-value = 0.031)], overdominant [LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)], and codominant [LTNPs vs. RPs (aOR = 0.52; q-value = 0.036) and LTNPs vs. MPs (aOR = 0.55; q-value = 0.032)]. Additionally, we found a significant association between DBP haplotypes (composed by rs16846876 and rs12512631) and AIDS progression (LTNPs vs RPs): DBP haplotype AC (aOR = 0.63; q-value = 0.028) and the DBP haplotype TT (aOR = 1.64; q-value = 0.028).

Conclusions

DBP rs16846876 and rs12512631 SNPs are related to the patterns of clinical AIDS progression (LTNP, MP, and RP) in ART-naïve HIV-infected patients. Our findings provide new knowledge about AIDS progression that may be relevant to understanding the pathogenesis of HIV infection.
Host immune response to anti-cancer camptothecin conjugated cyclodextrin-based polymers
Authors: Chen Yi-Fan , Wang Yen-Hsin , Lei Cing-Syuan , Changou Chun A. , Davis Mark E. , Yen Yun
Published: October 2019

Introduction

Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics.

Methods

In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems.

Results

In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only.

Conclusions

Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment.
Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo
Authors: Danov Olga , Lasswitz Lisa , Obernolte Helena , Hesse Christina , Braun Armin , Wronski Sabine , Sewald Katherina
Published: October 2019

Background

Antiviral drugs such as rupintrivir may have an immune-modulatory effect in experimentally induced allergic asthma with subsequent RV infection. We infected lung slices of house-dust mite (HDM)-sensitized asthmatic mice ex vivo with human rhinovirus (RV) and investigated the effect of the antiviral drug rupintrivir on RV-induced cytokine response in lung tissue of HDM-sensitized mice ex vivo.

Methods

Mice were sensitized with HDM. Precision-cut lung slices (PCLS) were prepared from HDM-sensitized or non-sensitized mice. Lung slices were infected ex vivo with RV or RV together with rupintrivir. Modulation of immune responses was evaluated by cytokine secretion 48 h post infection.

Results

In vivo HDM sensitization resulted in a TH-2/TH-17-dominated cytokine response that persisted in PCLS ex vivo. RV infection of PCLS from non-sensitized mice resulted in the induction of an antiviral and pro-inflammatory immune response, as indicated by the secretion of IFN-α, IFN-β, IFN-γ, TNF-α, MCP-1, IP-10, IL-10, and IL-17A. In contrast, PCLS from HDM-sensitized mice showed an attenuated antiviral response, but exaggerated IL-4, IL-6, and IL-10 secretion upon infection. Rupintrivir inhibited exaggerated pro-inflammatory cytokine IL-6 and TH-2 cytokine IL-4 in HDM-sensitized mice.

Conclusions

In summary, this study demonstrates that treatment with rupintrivir influences virus-induced IL-4 and IL-6 cytokine release under experimental conditions ex vivo.
Global prevalence of asthma-COPD overlap (ACO) in the general population: a systematic review and meta-analysis
Authors: Hosseini Mostafa , Almasi-Hashiani Amir , Sepidarkish Mahdi , Maroufizadeh Saman
Published: October 2019

Background

Asthma-COPD overlap (ACO) is a term that encompasses patients with features of both asthma and COPD. To date, the global prevalence of ACO in the general population remains unknown. The objective of this study was to estimate the prevalence of ACO in the general population using a systematic review and meta-analysis.

Methods

A systematic search of ISI Web of Knowledge, MEDLINE/PubMed, and Scopus was performed up to May 2019 to identify studies reporting the prevalence of ACO. Reference lists from identified studies and relevant review articles were also searched. Eligibility criteria were studies reporting the prevalence of ACO, performed in general population, and published in English language. Pooled prevalence of ACO with 95% confidence interval (CI) was calculated using random effects Meta-analysis.

Results

A total of 27 studies were included in this meta-analysis. The Cochran Q test and I2 statistics revealed substantial heterogeneity among studies. Based on the random-effects model, the pooled prevalence of ACO was 2.0% (95% CI: 1.4–2.6%) in the general population, 26.5% (95% CI: 19.5–33.6%) among patients with asthma, and 29.6% (95% CI: 19.3–39.9%) among patients with COPD. In addition, for included studies, the global prevalence of asthma-only was 6.2% (95% CI: 5.0–7.4%) and COPD-only was 4.9% (95% CI: 4.3–5.5%).

Conclusion

We estimated the global prevalence of ACO based on population-based studies and found that 2.0% of the general population is affected. However, the prevalence of ACO depends on its diagnostic criteria. Therefore, there is a vital need to better define the ACO diagnostic criteria, management and treatment. It is worth noting that the limitations of the present study include lack of studies in some region of the world and small number of studies included in the subgroup analyses.
Efficacy of visceral fat estimation by dual bioelectrical impedance analysis in detecting cardiovascular risk factors in patients with type 2 diabetes
Authors: Omura-Ohata Yoko , Son Cheol , Makino Hisashi , Koezuka Ryo , Tochiya Mayu , Tamanaha Tamiko , Kishimoto Ichiro , Hosoda Kiminori
Published: October 2019

Background

Visceral fat area (VFA) is a good surrogate marker of obesity-related disorders, such as hypertension, dyslipidemia and glucose intolerance. Although estimating the VFA by X-ray computed tomography (CT) is the primary index for visceral obesity, it is expensive and requires invasive radiation exposure. Dual bioelectrical impedance analysis (BIA) is a simple and reliable method to estimate VFA; however, the clinical usefulness of dual BIA remains unclear in patients with type 2 diabetes (T2D).

Methods

We estimated the VFAs by dual BIA and CT in 98 patients with T2D and assessed anthropometric parameters, blood test results, and the presence of comorbid hypertension and dyslipidemia. We compared the correlation between the VFAs examined by dual BIA and CT. Furthermore, we performed the receiver operating characteristic (ROC) analyses for the VFAs to detect the presence of comorbid hypertension and/or dyslipidemia with T2D, which are major comorbidities of visceral obesity, and estimated the area under the curve (AUC).

Results

The measurement error between the VFAs by dual BIA and CT was significantly higher among patients with brain natriuretic peptide (BNP) ≥ 100 pg/mL than those with BNP < 100 pg/mL (39.2% ± 31.1% vs. 24.1% ± 18.6%, P < 0.05). After excluding patients with BNP ≥ 100 pg/mL, the VFA by dual BIA significantly correlated with the VFA by CT (r = 0.917; P < 0.0001). The AUC in the ROC analysis for the VFA by dual BIA to detect the presence of comorbid hypertension and/or dyslipidemia with T2D was almost equivalent to that for the VFA by CT.

Conclusions

In patients with T2D without elevated BNP > 100 pg/mL as indicator for fluid accumulation interfering with BIA, estimation of the VFA by dual BIA significantly correlated with that by CT and also detected comorbid hypertension and/or dyslipidemia with T2D equivalent to those detected by CT. Hence, dual BIA could be an alternative to CT as a standard method for estimating the VFA in patients with diabetes.
The predictive value of dynamic monitoring of peripheral blood lymphocyte to monocyte ratio in patients with extranodal NK/T cell lymphoma
Authors: Zhang Shengnan , Li Mengjuan , Yuan Fangfang , Chen Lin , Mi Ruihua , Wei Xudong , Song Yongping , Yin Qingsong
Published: October 2019

Background

To investigate the value of dynamic monitoring peripheral blood lymphocyte-to-monocyte (LMR) ratio in evaluating the treatment response and prognosis of patients with extranodal NK/T cell lymphoma (ENKTL).

Methods

A total of 148 patients with ENKTL were retrospectively analyzed in the Affiliated Tumor Hospital of Zhengzhou University between March 2012 and March 2018. The optimal cut-off value of LMR was determined using the receiver operating characteristic curve (ROC) method, then patients were divided into low LMR group and high LMR group. The LMR level was dynamically measured at various time points, and the relationships between LMR and therapeutic response, and survival were analyzed.

Results

The complete remission rate (CR) was 85.7% in patients with high LMR at diagnosis, which was remarkably higher than that of patients with low LMR at diagnosis (64.9%) (P = 0.009). The 5-year overall survival (OS) and progression-free survival (PFS) were 49.28% and 44.89% in the low LMR group, respectively; 5-year OS and PFS in the high LMR group were 84.50% and 67.12%, respectively, significantly longer (P values were < 0.001 and 0.034, respectively). The OS and PFS of patients with elevated LMR after treatment were longer than those with decreased LMR after treatment (all P values < 0.05). The LMRs at relapse were significantly lower in both high and low LMR groups than those of the last follow-up (P values were 0.001 and 0.016, respectively). Univariate and multivariate analysis demonstrated that low LMR was an independent risk factor for poor prognosis in ENKTL patients (P values were < 0.001 and 0.009, respectively).

Conclusions

Lymphocyte to monocyte ratio can be used as an indicator of treatment response, prognosis and recurrence in patients with ENKTL. Low LMR before and after treatment is a poor prognostic factor.
3D kernel-density stochastic model for more personalized glycaemic control: development and in-silico validation
Authors: Uyttendaele Vincent , Knopp Jennifer L. , Davidson Shaun , Desaive Thomas , Benyo Balazs , Shaw Geoffrey M. , Chase J. Geoffrey
Published: October 2019

Background

The challenges of glycaemic control in critically ill patients have been debated for 20 years. While glycaemic control shows benefits inter- and intra-patient metabolic variability results in increased hypoglycaemia and glycaemic variability, both increasing morbidity and mortality. Hence, current recommendations for glycaemic control target higher glycaemic ranges, guided by the fear of harm. Lately, studies have proven the ability to provide safe, effective control for lower, normoglycaemic, ranges, using model-based computerised methods. Such methods usually identify patient-specific physiological parameters to personalize titration of insulin and/or nutrition. The Stochastic-Targeted (STAR) glycaemic control framework uses patient-specific insulin sensitivity and a stochastic model of its future variability to directly account for both inter- and intra-patient variability in a risk-based insulin-dosing approach.

Results

In this study, a more personalized and specific 3D version of the stochastic model used in STAR is compared to the current 2D stochastic model, both built using kernel-density estimation methods. Fivefold cross validation on 681 retrospective patient glycaemic control episodes, totalling over 65,000 h of control, is used to determine whether the 3D model better captures metabolic variability, and the potential gain in glycaemic outcome is assessed using validated virtual trials. Results show that the 3D stochastic model has similar forward predictive power, but provides significantly tighter, more patient-specific, prediction ranges, showing the 2D model over-conservative > 70% of the time. Virtual trial results show that overall glycaemic safety and performance are similar, but the 3D stochastic model reduced median blood glucose levels (6.3 [5.7, 7.0] vs. 6.2 [5.6, 6.9]) with a higher 61% vs. 56% of blood glucose within the 4.4–6.5 mmol/L range.

Conclusions

This improved performance is achieved with higher insulin rates and higher carbohydrate intake, but no loss in safety from hypoglycaemia. Thus, the 3D stochastic model developed better characterises patient-specific future insulin sensitivity dynamics, resulting in improved simulated glycaemic outcomes and a greater level of personalization in control. The results justify inclusion into ongoing clinical use of STAR.
The relationship between serum triglyceride levels and acute pancreatitis in an animal model and a 14-year retrospective clinical study
Authors: Zhang Qiyue , Qin Mengbin , Liang Zhihai , Huang Huali , Tang Yongfeng , Qin Lingyan , Wei Zhenping , Xu Mengtao , Tang Guodu
Published: October 2019

Objectives

The aim of the current study was to evaluate influence of serum triglyceride levels on the course of acute pancreatitis (AP).

Methods

Rats models of hypertriglyceridemic were used in animal experiments. Following induction of acute pancreatitis, amylase, and pancreas histological scores were all compared. In addition, in a clinical study, clinical data were collected from 1681 AP patients admitted from 2003 to 2016 who were divided into 4 groups based on their serum triglyceride (TG) levels. The clinical features among these 4 groups were compared, and a receiver operating characteristic (ROC) curve analysis was also performed on TG values to estimate their relationship with severity.

Results

In animal experiments, the hypertriglyceridemic pancreatitis (HTGP) group had markedly higher serum amylase, and histological scores relative to the other animal groups. In the clinical study, we identified significant differences in gender, age, body mass index (BMI), cost, and incidence of partial complications among the 4 TG-based groups. Importantly, the TG levels on day 3–4 after admission could be used to accurately predict disease severity.

Conclusions

Hypertriglyceridemia (HTG) can aggravate pancreatic injury, and hypertriglyceridemia patients are more likely to suffer from severe pancreatic injury with a higher possibility of complications. In addition, triglyceride levels are correlated with the severity of AP positively.
Isolation of the Arawete and Asurini Indians keeps the tribes free from HTLV infection during 36 years of follow-up
Authors: Vallinoto Antonio C. R. , Otake Mateus I. , Sousa Paulo V. N. R. , Lopes Felipe T. , Sacuena Eliene R. P. , Queiroz Maria A. F. , Costa Greice L. C. , Ishak Marluísa O. G. , Cayres-Vallinoto Izaura M. V. , Guerreiro João F. , Ishak Ricardo
Published: October 2019

Arawete and Asurini Indian tribes were revisited after a 36-year follow-up in search of HTLV infections. 46 persons (23 from each tribe) were tested for HTLV-1/2 antibodies and viral DNA. None were positive; this was probably because of their social/cultural isolation from neighboring tribes where HTLV-2c is hyperendemic.
Ventilation feedback device for manual ventilation in simulated respiratory arrest: a crossover manikin study
Authors: Khoury Abdo , De Luca Alban , Sall Fatimata S. , Pazart Lionel , Capellier Gilles
Published: October 2019

Background

Studies have shown that providing adequate ventilation during CPR is essential. While hypoventilation is often feared by most caregivers on the scene, the most critical problem remains hyperventilation. We developed a Ventilation Feedback Device (VFD) for manual ventilation which monitors ventilatory parameters and provides direct feedback about ventilation quality to the rescuer. This study aims to compare the quality of conventional manual ventilation to ventilation with VFD on a simulated respiratory arrest patient.

Methods

Forty healthcare providers were enrolled and instructed to ventilate a manikin simulating respiratory arrest. Participants were instructed to ventilate the manikin for 5 min with and without the VFD in random order. They were divided in two groups of 20 people, one group ventilating through a mask and the other through an endotracheal tube.

Results

Ventilation with the VFD improved from 15 to 90% (p < 0.001) with the mask and from 15 to 85% (p < 0.001) with the endotracheal tube (ETT) by significantly reducing the proportion of hyperventilation. The mean ventilation rates and tidal volumes were in the recommended ranges in respectively 100% with the mask and 97.5% of participants with the ETT when using the VFD.

Conclusion

VFD improves the performance of manual ventilation by over 70% in different simulated scenarios. By providing the rescuer direct feedback and analysis of ventilatory parameters, this device can significantly improve ventilation while performing CPR and thus save lives.
Targeting of prostate-specific membrane antigen for radio-ligand therapy of triple-negative breast cancer
Authors: Morgenroth Agnieszka , Tinkir Ebru , Vogg Andreas T. J. , Sankaranarayanan Ramya Ambur , Baazaoui Fatima , Mottaghy Felix M.
Published: October 2019

Background

Triple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT).

Methods

Tube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy. A binding study with 68Ga-labeled PSMA-addressing ligand was used to indicate targeting potential of PSMA on tumor-conditioned HUVEC cells. For mimicking of the therapeutic application, tube formation potential and vitality of tumor-conditioned HUVEC cells were assessed following an incubation with radiolabeled PSMA-addressing ligand [177Lu]-PSMA-617. For in vivo experiments, NUDE mice were xenografted with triple-negative breast cancer cells MDA-MB231 or estrogen receptor expressing breast cancer cells MCF-7. Biodistribution and binding behavior of [68Ga]-PSMA-11 was investigated in both tumor models at 30 min post injection using μPET. PSMA- and CD31-specific staining was conducted to visualize PSMA expression and neovascularization in tumor tissue ex vivo.

Results

The triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of PSMA was efficiently addressed by radiolabeled PSMA-specific ligands. 177Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. In vivo, as visualized by μPET, radiolabeled PSMA-ligand accumulated specifically in the triple-negative breast cancer xenograft MDA-MB231 (T/B ratio of 43.3 ± 0.9), while no [68Ga]-PSMA-11 was detected in the estrogen-sensitive MCF-7 xenograft (T/B ratio of 1.1 ± 0.1). An ex vivo immunofluorescence analysis confirmed the localization of PSMA on MDA-MB231 xenograft-associated endothelial cells and also on TNBC cells.

Conclusions

Here we demonstrate PSMA as promising target for two-compartment endogenous radio-ligand therapy of triple-negative breast cancer.
NARD: whole-genome reference panel of 1779 Northeast Asians improves imputation accuracy of rare and low-frequency variants
Authors: Yoo Seong-Keun , Kim Chang-Uk , Kim Hie Lim , Kim Sungjae , Shin Jong-Yeon , Kim Namcheol , Yang Joshua Sung Woo , Lo Kwok-Wai , Cho Belong , Matsuda Fumihiko , Schuster Stephan C. , Kim Changhoon , Kim Jong-Il , Seo Jeong-Sun
Published: October 2019

Here, we present the Northeast Asian Reference Database (NARD), including whole-genome sequencing data of 1779 individuals from Korea, Mongolia, Japan, China, and Hong Kong. NARD provides the genetic diversity of Korean (n = 850) and Mongolian (n = 384) ancestries that were not present in the 1000 Genomes Project Phase 3 (1KGP3). We combined and re-phased the genotypes from NARD and 1KGP3 to construct a union set of haplotypes. This approach established a robust imputation reference panel for Northeast Asians, which yields the greatest imputation accuracy of rare and low-frequency variants compared with the existing panels. NARD imputation panel is available at https://nard.macrogen.com/.
Diagnostic value of transcranial ultrasonography for selecting subjects with large vessel occlusion: a systematic review
Authors: Antipova Daria , Eadie Leila , Macaden Ashish Stephen , Wilson Philip
Published: October 2019

Introduction

A number of pre-hospital clinical assessment tools have been developed to triage subjects with acute stroke due to large vessel occlusion (LVO) to a specialised endovascular centre, but their false negative rates remain high leading to inappropriate and costly emergency transfers. Transcranial ultrasonography may represent a valuable pre-hospital tool for selecting patients with LVO who could benefit from rapid transfer to a dedicated centre.

Methods

Diagnostic accuracy of transcranial ultrasonography in acute stroke was subjected to systematic review. Medline, Embase, PubMed, Scopus, and The Cochrane Library were searched. Published articles reporting diagnostic accuracy of transcranial ultrasonography in comparison to a reference imaging method were selected. Studies reporting estimates of diagnostic accuracy were included in the meta-analysis.

Results

Twenty-seven published articles were selected for the systematic review. Transcranial Doppler findings, such as absent or diminished blood flow signal in a major cerebral artery and asymmetry index ≥ 21% were shown to be suggestive of LVO. It demonstrated sensitivity ranging from 68 to 100% and specificity of 78–99% for detecting acute steno-occlusive lesions. Area under the receiver operating characteristics curve was 0.91. Transcranial ultrasonography can also detect haemorrhagic foci, however, its application is largely restricted by lesion location.

Conclusions

Transcranial ultrasonography might potentially be used for the selection of subjects with acute LVO, to help streamline patient care and allow direct transfer to specialised endovascular centres. It can also assist in detecting haemorrhagic lesions in some cases, however, its applicability here is largely restricted. Additional research should optimize the scanning technique. Further work is required to demonstrate whether this diagnostic approach, possibly combined with clinical assessment, could be used at the pre-hospital stage to justify direct transfer to a regional thrombectomy centre in suitable cases.
The impact of yoga on teachers’ self-rated emotions
Authors: Telles Shirley , Sharma Sachin Kumar , Gupta Ram Kumar , Pal Deepak Kumar , Gandharva Kumar , Balkrishna Acharya
Published: October 2019

Objectives

To assess (i) if teachers’ age or gender could predict their baseline levels of mental well-being and anxiety and any change after yoga. (ii) Whether mental well-being or anxiety changed following 15 days of yoga in primary school teachers. Primary school teachers took part in this single group longitudinal trial (n = 302, group mean age ± SD; 41.8 ± 5.90 years). They received 240 min of yoga practice and 120 min of yoga theory each day. At baseline and after 15 days of yoga the assessments were (i) mental well-being (Warwick-Edinburgh scale) and (ii) state anxiety (Spielberger’s State Trait Anxiety Inventory).

Results

Gender acted as a significant predictor for mental well-being scores (P = 0.001) and state anxiety (P = 0.005) in the group at baseline. Females showed higher anxiety scores and lower mental well-being scores. Following yoga the teachers showed a significant increase in mental well-being by 5.84% and a decrease in state anxiety by 4.48%.

Trial registration The trial was registered retrospectively (August 15, 2019; Trial Registration Number: ISRCTN90253431).
Nurse roles in antimicrobial stewardship: lessons from public sectors models of acute care service delivery in the United Kingdom
Authors: Castro-Sánchez Enrique , Gilchrist Mark , Ahmad Raheelah , Courtenay Molly , Bosanquet Jo , Holmes Alison H.
Published: October 2019

Background

Health care services must engage all relevant healthcare workers, including nurses, in optimal antimicrobial use to address the global threat of drug-resistant infections. Reflecting upon the variety of antimicrobial stewardship (AMS) nursing models already implemented in the UK could facilitate policymaking and decisions in other settings about context-sensitive, pragmatic nurse roles.

Methods

We describe purposefully selected cases drawn from the UK network of public sector nurses in AMS exploring their characteristics, influence, relations with clinical and financial structures, and role content.

Results

AMS nursing has been deployed in the UK within ‘vertical’, ‘horizontal’ or ‘hybrid’ models. The ‘vertical’ model refers to a novel, often unique consultant-type role ideally suited to transform organisational practice by legitimising nurse participation in antimicrobial decisions. Such organisational improvements may not be straightforward, though, due to scalability issues. The ‘horizontal’ model can foster coordinated efforts to increase optimal AMS behaviours in all nurses around a narrative of patient safety and quality. Such model may be unable to address tensions between the required institutional response to sepsis and the inappropriate use of antibiotics. Finally, the ‘hybrid’ model would increase AMS responsibilities for all nurses whilst allocating some expanded AMS skills to existing teams of specialists such as sepsis or vascular access nurses. This model can generate economies of scale, yet it may be threatened by a lack of clarity about a nurse-relevant vision.

Conclusions

A variety of models articulating the participation of nurses in antimicrobial stewardship efforts have already been implemented in public sector organisations in the UK. The strengths and weaknesses of each model need considering before implementation in other settings and healthcare systems, including precise metrics of success and careful consideration of context-sensitive, resource dependent and pragmatic solutions.
Revisiting the musculocutaneous external oblique flap as a versatile alternative in large thoracic wall defects
Authors: Matera David , Huynh Richard , Hanley Terrance , Behnam Amir B.
Published: October 2019

Background

The external oblique myocutaneous flap has been previously described for reconstruction of chest-thoracic wall defects smaller than 400–500 cm2. However, it is utilized less often than workhorse flaps such as the omental, pectoralis, rectus abdominis, and latissimus dorsi myocutaneous flaps as many plastic surgeons are not aware that the flap can cover larger areas than previously documented.

Case presentation

We report a 57-year-old female tobacco user who underwent a resection of a grade 3 breast angiosarcoma resulting in a high left chest wall soft tissue defect approximating 900 cm2. The patient underwent an external oblique myocutaneous pedicle flap reconstruction of the defect, most notably in anticipation of postoperative adjuvant radiation therapy. No gross flap complications and or patient impairment were noted. Thirteen months status post flap reconstruction, the patient underwent an aortic valve replacement requiring re-elevation of the same flap for exposure. The flap demonstrated excellent viability during the procedure and postoperatively.

Conclusion

The pedicled external oblique myocutaneous flap should be considered when reconstructing larger high chest wall defects when other more common flaps used in chest reconstruction may not be indicated. The external oblique myocutaneous flap is an excellent tool in the armamentarium of any reconstructive surgeon; it is a straightforward and versatile flap that can be safely and reliably used in durable reconstruction of defects of the chest wall and covers defects larger than previously described in the literature.
Gastric calcifying fibrous tumor suspected to be complicated with immunoglobulin G4-related disease treated by laparoscopy and endoscopy cooperative surgery: a case report
Authors: Hamura Ryoga , Koyama Tomoki , Kawamura Masahiko , Kawamura Takeshi , Nakamura Mayo , Yanaga Katsuhiko
Published: October 2019

Background

Calcifying fibrous tumor (CFT) is a rare benign soft tissue lesion.

Case presentation

A 30-year-old woman was admitted to our hospital with complaints of epigastralgia. A 15-mm submucosal tumor was identified in the greater curvature of the superior body of the stomach by upper gastrointestinal endoscopy. Endoscopic ultrasonography revealed a hypoechoic lesion with an acoustic shadow consistent with calcification. Computed tomography showed a gastric tumor with calcification. A gastrointestinal stromal tumor was diagnosed, and gastric wedge resection was performed by laparoscopy and endoscopy cooperative surgery. On pathological examination, the tumor was identified to be a CFT. Postoperative serum IgG4 levels were 26.0 mg/dl, which supported the diagnosis of probable immunoglobulin G (IgG) 4-related disease, according to the comprehensive diagnostic criteria of IgG4-related disease. The patient was discharged on postoperative day 7 and remains well with no evidence of tumor recurrence for 2 years after resection.

Conclusion

We herein reported a patient with a gastric CFT suspected to be complicated with immunoglobulin G4-related disease that was successfully treated by laparoscopy and endoscopy cooperative surgery.
Protocol for a two-arm feasibility RCT to support postnatal maternal weight management and positive lifestyle behaviour in women from an ethnically diverse inner city population: the SWAN feasibility trial
Authors: Bick Debra , Taylor Cath , Avery Amanda , Bhavnani Vanita , Craig Victoria , Healey Andy , Khazaezadeh Nina , McMullen Sarah , Oki Bimpe , Oteng-Ntim Eugene , O’Connor Sheila , Poston Lucilla , Seed Paul , Roberts Sarah , Ussher Michael
Published: October 2019

Introduction

A high BMI during and after pregnancy is linked to poor pregnancy outcomes and contributes to long-term maternal obesity, hypertension, and diabetes. Evidence of feasible, effective postnatal interventions is lacking. This randomised controlled trial will assess the feasibility of conducting a future definitive trial to determine effectiveness and cost-effectiveness of lifestyle information and access to Slimming World® (Alfreton, UK) groups for 12 weeks commencing from 8 to 16 weeks postnatally, in relation to supporting longer-term postnatal weight management in women in an ethnically diverse inner city population.

Methods/analysis

Women will be recruited from one maternity unit in London. To be eligible, women will be overweight (BMI 25–29.9 kg/m2) or obese (BMI ≥ 30 kg/m2) as identified at their first antenatal contact, or have a normal BMI (18.5–24.9 kg/m2) at booking but gain excessive gestational weight as assessed at 36 weeks gestation. Women will be aged 18 and over, can speak and read English, expecting a single baby, and will not have accessed weight management groups in this pregnancy. Women will be randomly allocated to standard care plus lifestyle information and access to Slimming World® (Alfreton, UK) groups or standard care only. A sample of 130 women is required.

Feasibility trial objectives reflect those considered most important inform a decision about undertaking a definitive future trial. These include estimation of impact of lifestyle information and postnatal access to Slimming World® (Alfreton, UK) on maternal weight change between antenatal booking weight and weight at 12 months postbirth, recruitment rate and time to recruitment, retention rate, influence of lifestyle information and Slimming World® (Alfreton, UK) groups on weight management, diet, physical activity, breastfeeding, smoking cessation, alcohol intake, physical and mental health, infant health, and health-related quality of life 6 and 12 months postnatally. An embedded process evaluation will assess acceptability of study processes and procedures to women.

Ethics/dissemination

London–Camberwell St Giles Research Ethics Committee, reference: 16/LO/1422. Outcomes will be disseminated in peer-reviewed journals and presentations at national and international conferences.

Trial registration

Trial registration number:ISRCTN 39186148. Protocol version number: v7, 13 August 17. Trial sponsor: King’s College London.
Acute compartment syndrome of the lower leg causing cardiac arrest after resection of the right external iliac vein for autologous graft: a case report
Authors: Hoshino Koji , Nakamura Toru , Hayakawa Mineji , Itosu Yusuke , Saito Hitoshi , Hirano Satoshi , Morimoto Yuji
Published: October 2019

Background

The right external iliac vein (REIV) is often used for portal vein reconstruction in patients undergoing pancreatoduodenectomy with portal-superior mesenteric vein resection. We report a case of cardiac arrest caused by acute lower leg compartment syndrome as a result of REIV resection.

Case presentation

A 53-year-old man underwent pancreatoduodenectomy with portal vein resection. Hyperkalemia progressed during surgery due to intestinal reperfusion injury, which caused recurrent ventricular arrhythmia required for cardio-pulmonary resuscitation. The surgery was discontinued after resuscitation, and portal vein reconstruction using the REIV was performed 2 days post-operatively. Acute compartment syndrome was diagnosed immediately following the surgery. Hyperkalemia progressed, causing pulseless ventricular tachycardia. Emergent fasciotomy was performed, but right leg dysfunction persisted after discharge.

Conclusion

REIV resection can cause lower-extremity acute compartment syndrome. The status, including intracompartmental pressure, of the lower extremity should be carefully observed after REIV resection during and after surgery.