bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Feasibility and Acceptability of a Community-Based Parenting Support Intervention for Refugee Parents From Burma
Authors: Hoffman Sarah J. , Walstad Alexis , Law Law Loo Julyna , Moe Moses , Thao Josalyza , Albert Arian , Mathiason Michelle A. , Porta Carolyn M.
Published: November 2019

Refugee families negotiate stressors as they adjust to communities of resettlement, which can result in shifting family dynamics. The purpose of this community-engaged, explanatory, mixed-methods pilot study was to evaluate the feasibility and acceptability of a culturally oriented, community-based parenting curriculum. Through a partnership with a prominent refugee-serving organization, the curriculum was delivered to 50 Karen refugee mothers and fathers of adolescent youth resettled in the United States. Results demonstrated the potential for impact on key constructs of family adaptability and cohesion, as well as parent self-efficacy. Participants were highly engaged with the program and attrition was low.
No difference in medication regimes and dosing in study participants with and without blood pressure control: longitudinal data of the population-based Heinz Nixdorf Recall Study
Authors: Brandt Isabelle , Puth Marie-Therese , Kersting Christine , Moebus Susanne , Erbel Raimund , Jöckel Karl-Heinz , Weltermann Birgitta
Published: November 2019

Background:

To achieve blood pressure (BP) control adequate dosing of first-line antihypertensive medications is recommended in addition to life-style changes. Given observations that dosing of antihypertensive agents is frequently insufficient, we compared the changes of BP control rates and antihypertensive drug regimens in a prospective German population using a new strategy to analyze medication dosing.

Methods:

This analysis is based on data of the baseline (2000–2003) and the first follow-up examination (2005–2008) of the population-based Heinz Nixdorf Recall study. Participants with hypertension at baseline (BP ≥140/90 mmHg or at least one antihypertensive agent) who participated in both examinations were included.

Results:

Of the 4157 participants, 2289 (55.1%) had hypertension at baseline. The prevalence of participants on antihypertensive agents was 60.3% at baseline and increased to 75.1% at follow-up. The mean number of antihypertensive agents was 2 [±1 SD (standard deviation)] initially and at follow-up. The prevalence of medication-controlled BP did not improve over time (baseline: 54.5%, follow-up: 56.5%). When stratifying by medication-controlled BP, the medication dosing rate slightly increased over time without differences between groups [controlled versus uncontrolled BP: 40.9 versus 46.2% (baseline); 50.1 versus 51.9% (follow-up)].

Conclusion:

Although the prevalence of antihypertensive medication use increased in the study period, the BP control rate did not. In contrast to clinical reasoning, participants with uncontrolled BP did neither receive more agents nor higher dosing despite outcome-relevant hypertension. Our approach to analyze medication dosing suggests a potential to improve cardiovascular outcomes by increasing dosages of antihypertensive agents.
Pancreatic plasticity: epigenetic mechanisms and connections to neoplasia
Authors: David Charles J.
Published: November 2019

To counterbalance cellular losses due to age or injury, adult tissues must produce replacement cells appropriate in type and number. In different tissues, evolution has arrived at distinct solutions to this problem, depending on the nature of the tissue. Tissues with a large amount of cell turnover, such as the intestine, harbor a dedicated pool of stem cells dedicated to the constant replenishment of lost cells. In contrast, the pancreas is a relatively quiescent organ that lacks a clear population of resident stem cells. Instead, occasional self-duplication appears to be the major form of cellular replacement in the normal pancreas. Upon injury, however, the epigenetic barriers between cell types begin to fall, resulting in cell identity interconversion between multiple cell types in the pancreas. The epigenetic basis for these transdifferentiation events, involves the down-regulation of lineage-determining transcription factors specifying 1 cell fate and their replacement with factors specifying the alternate cell fate. The signals that underpin the switching of transcriptional programs are beginning to be unraveled. One important form of pancreatic plasticity, acinar-to-ductal metaplasia, occurs in response to injury-induced inflammatory stimuli. This form of metaplasia is associated with pancreatitis, a known risk factor for pancreatic cancer. The resulting ductal structures reactivate signaling pathways associated with embryonic pancreatic progenitors, and have been proposed to contribute to pancreatic regeneration. Consistent with a progenitor-like phenotype, in the presence of oncogenic stimuli, these metaplastic ducts are highly sensitive to neoplastic transformation, for reasons that are beginning to come to light.
Providing effective asthma care at a pediatric patient-centered medical home
Authors: Kennedy Christopher M. , Jolles Diana R.
Published: November 2019

Background:

A recent assessment of the national annual burden of the cost of asthma among school-aged children was nearly $6 million. In a Midwestern county, the incidence of childhood asthma was 15.8%, which was above both state and national levels.

Local problem:

Effective asthma care was not being provided at a rural, pediatric patient-centered medical home due to a lack of standardization. This quality improvement (QI) initiative aimed to increase the mean effective asthma care score to 78% for patients with asthma over the course of 90 days.

Methods:

This right care initiative was implemented using a rapid-cycle Plan-Do-Study-Act methodology. Tests of change in the areas of team engagement, patient engagement, and two process measures were analyzed through chart audits and run charts over four cycles. Likert scale surveys were used to analyze qualitative data.

Interventions:

Interventions included developing the Asthma Patient Identification Tool, implementing an asthma education protocol with teach-back, creating standardized smart phrases for effective documentation, and initiating asthma care huddles.

Results:

The delivery of effective asthma care increased to 84%. The number of patients receiving the asthma education protocol increased to 65%, with 80% of the patients participating in effective teach-back sessions. The mean effective documentation score increased to 92%.

Conclusions:

A standardized approach to asthma care grounded in evidence-based guidelines positively affected the delivery of care. Nurse practitioners are effective team leaders for clinical QI initiatives.
Preoperative platelet morphology parameters as prognostic predictors for endometrial malignant carcinoma stage and progesterone receptor
Authors: Song Jianrong , Lai Xiaohong , Zhang Yulong , Zheng Xiangqin , Su Jiangcheng
Published: November 2019

To investigate preoperative platelet morphology parameters and other whole blood cells in patients of malignant endometrial carcinoma compared with benign disease.

Retrospective analysis was performed through collecting patients’ hematological parameters before performing total abdominal/vaginal hysterectomy and standard radical surgery due to benign and malignant endometrial disease between 2006 and 2017. Parameters required included white blood cell (WBC), hemoglobin, platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet thrombocytocrit (PCT). And neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. For malignant carcinoma, Ki-67 percentage and progesterone receptor (PR) status were further collected.

A total of 288 patients were included with 145 benign cases and 143 malignant cases. Patients of confirmed endometrial carcinoma showed a significant lower value of PDW (55.21 ± 4.72 vs 49.54 ± 5.89, P < .001), meanwhile significant higher values of MPV (7.12 ± 1.56 vs 8.89 ± 1.67, P < .001) and PCT (24.18 ± 6.89 vs 27.93 ± 8.93, P = .003). Further analysis of endometrial carcinoma patients showed that no significant difference in platelet parameters was found between patients with stage I to II and stage III to IV (P > .05), while increased value in PDW and reduced value in MPV was found in PR negative compared with positive patients.

Preoperative platelet morphology parameters seemed to be used as one kind of predictive factors to discriminate malignant and benign endometrial disease. Limited by present study design, further prospective studies are required to support this finding.
Contrast enhancement on 100- and 120 kVp hepatic CT scans at thin adults in a retrospective cohort study
Authors: Masuda Takanori , Nakaura Takeshi , Funama Yoshinori , Sato Tomoyasu , Higaki Toru , Matsumoto Yoriaki , Yamashita Yukari , Imada Naoyuki , Kiguchi Masao , Baba Yasutaka , Yamashita Yasuyuki , Awai Kazuo
Published: November 2019

Purpose:

To assess the probability of achieving optimal contrast enhancement in 100 kVp and 120 kVp-protocol on hepatic computed tomography (CT) scans.

Materials and methods:

We enrolled 200 patients in a retrospective cohort study. Hundred patients were scanned with 120 kVp setting, and other 100 patients were scanned with 100 kVp setting. We measured the CT number in the abdominal aorta and hepatic parenchyma on unenhanced scans and hepatic arterial phase (HAP)-, and portal venous phase (PVP). The aortic enhancement at HAP and the hepatic parenchymal enhancement at PVP were compared between the two scanning protocols. Bayesian inference was used to assess the probability of achieving optimal contrast enhancement in each protocol.

Results:

The Bayesian analysis indicated that when 100 kVp-rotocol was used, the probability of achieving optimal aortic enhancement (>280 HU) was 98.8% ± 0.6%, whereas it was 88.7% ± 2.5% when 120 kVp-protocol was used. Also, the probability of achieving optimal hepatic parenchymal enhancement (>50 HU) was 95.3% ± 1.5%, whereas it was 64.7% ± 3.8% when 120 kVp-protocol was used.

Conclusion:

Bayesian inference suggested that the post-test probability of optimal contrast enhancement at hepatic dynamic CT was lower under the 120 kVp than the 100 kVp-protocol
Oral steroid decreases the progression of joint destruction of large joints in the lower extremities in rheumatoid arthritis
Authors: Doi K. , Ito H. , Tomizawa T. , Murata K. , Hashimoto M. , Tanaka M. , Murakami K. , Nishitani K. , Azukizawa M. , Okahata A. , Saito M. , Mimori T. , Matsuda S.
Published: November 2019

To identify the risk factors for destruction of large joints in the lower extremities in patients with rheumatoid arthritis (RA) during a 4-year follow-up period in a prospective study.

We enrolled consecutive patients who participated in both 2012 and 2016. Clinical data, disease activity, and types of medication were collected in 2012. Standard anteroposterior radiographs of weight-bearing joints (hips, knees, and ankles) were taken in 2012 and 2016. Radiographic progression was defined as progression in the Larsen grade or the need for joint arthroplasty or arthrodesis. The association between baseline characteristics and the incidence of radiographic progression was statistically assessed.

A total of 213 patient were enrolled, and, after exclusion, 186 patients were analyzed. Sixty 9 patients (37.1%) showed radiographic progression in 1 of the large joints in the lower extremities. Multivariate regression analysis showed that radiographic progression was associated with older age, higher disease activity, and the presence of radiographic destruction at the baseline. The lower dosage of oral prednisolone was a significant risk factor compared with higher dosage when used.

Patients with the risk factors should be followed closely to limit the progression of large joint destruction in the lower extremities.
A comparison of sotagliflozin therapy for diabetes mellitus between week 24 with week 52
Authors: Zhang Nie , Gu Zhi-Qun , Ding Yun-Long , Yang Liu , Chen Mao-Bing , Zheng Qi-Han
Published: November 2019

Background:

According to the centers for disease control and prevention, 14% of American adults have diabetes – 10% know it, and more than 4% go undiagnosed. Sotagliflozin is a new type of diabetes drug This study is to compare the efficacy of Sotagliflozin therapy for Diabetes Mellitus (DM) between week 24 with week 52.

Methods and analysis:

Through to October 2019, Web of Science, PubMed Database, Cochrane Library, EMBASE, Clinical Trials and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA therapy for DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software. We will provide practical and targeted results assessing the lost efficacy of SOTA therapy for DM from week 24 to week 52, to provide reference for clinicians.

Ethics and dissemination:

The stronger evidence about the lost efficacy of SOTA for DM from week 24 to week 52 will be provided for clinicians.

Trial registration number:

PROSPERO CRD42019133027.

Strengths and limitations of this study:

Whether the efficacy of SOTA could last for a long time is still inconclusive, high quality research is still lacking, and this study attempts to explore this issue; The efficacy of SOTA at different times will be compared by direct comparisons and indirect comparisons, this can lead to more accurate and reliable results; The quality of the included literatures are uneven, and some data might be estimated by calculation, which may affect the quality of this study.
One-stage posterior debridement with transverse process strut as bone graft in the surgical treatment of single-segment thoracic tuberculosis
Authors: Liang Xin-Jie , Zhong Weiyang , Tang Ke , Quan Zhengxue , Luo Xiao-Ji , Jiang Dian-Ming
Published: November 2019

This retrospective study investigated the effect of the novel bone graft transverse process strut (TPS) in single segmental thoracic spinal tuberculosis (TB) with the one-stage posterior approach of debridement, fusion, and internal instrumentation. Thirty patients treated in our department from March 2014 to October 2016 were retrospectively analyzed. Surgical time, blood loss, hospitalization time, drainage volume, and follow-up (FU) duration were recorded. The visual analog scale (VAS), Oswestry Disability Index (ODI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), American Spinal Injury Association (ASIA) grade, segmental angle, and bone fusion were compared between preoperative and final FU. All the patients were followed for a mean 50.10 ± 25.10 months; the mean age, surgical time in minutes, blood loss, hospitalization time, and drainage volume were 46.23 ± 17.20 years, 195.08 ± 24.0 minutes, 280.77 ± 189.90 mL, 17.31 ± 4.23 days, 436.92 ± 193.81 mL, respectively. VAS and ODI scores were significantly improved at the final FU. The ESR and CRP returned to normal. All patients achieved bony fusion with a mean time of 5.85 ± 1.82 months and a mean segmental angle of 18.77 ± 2.49° preoperatively, which significantly decreased to 9.31 ± 1.54° at the final FU (P < .05). No complications, such as bone graft failure, pleural effusion, fistula, or wound infection were recorded except for cerebrospinal fluid leakage (one case), water electrolyte imbalance (5 cases), superficial infection (1 case), and mild intestinal obstruction (1 case). TPS as a bone graft is reliable, safe, and effective for segmental stability reconstruction for surgical management of single-segment thoracic spinal TB.
Cardiac sarcoidosis: worse pulmonary function due to left ventricular ejection fraction?
Authors: Martusewicz-Boros Magdalena M. , Boros Piotr W. , Wiatr Elżbieta , Zych Jacek , Kempisty Anna , Kram Marek , Piotrowska-Kownacka Dorota , Wesołowski Stefan , Baughman Robert P. , Roszkowski-Sliż Kazimierz
Published: November 2019

Dyspnea and exercise intolerance are usually attributed to pulmonary disease in sarcoidosis patients. However, cardiac involvement may also be responsible for these symptoms. Data regarding the impact of heart involvement on lung function in cardiac sarcoidosis (CS) is limited.

The aim of study was to compare the results of pulmonary function tests (PFTs) in patients with and without heart involvement. We performed a retrospective analysis of PFTs in a group of sarcoidosis patients both with and without heart involvement evaluated by cardiovascular magnetic resonance (CMR) study. The study was performed in the period between May 2008 and April 2016.

We included data of sarcoidosis patients who underwent testing for possible CS (including CMR study) at a national tertiary referral center for patients with interstitial lung diseases. All patients had histopathologicaly confirmed sarcoidosis and underwent standard evaluation with PFTs measurements including spirometry, plethysmography, lung transfer factor (T
L,CO), and 6-minute walking test (6MWT) assessed using the most recent predicted values.

We identified 255 sarcoidosis patients (93 women, age 42 ± 10.7 y): 103 with CS and 152 without CS (controls). CS patients had significantly lower left ventricular ejection fraction (LVEF; 56.9 ± 7.0 vs 60.4 ± 5.4, P < .001). Any type of lung dysfunction was seen in 63% of CS patients compared with 31% in the controls (P = .005). Ventilatory disturbances (obstructive or restrictive pattern) and low T
L,CO were more frequent in CS group (52% vs 23%, P < .001 and 38% vs 18% P < .01 respectively). CS (OR = 2.13, 95% CI: 1.11–4.07, P = .02), stage of the disease (OR = 3.13, 95% CI: 1.4–7.0, P = .006) and LVEF (coefficient = –0.068 ± 0.027, P = .011) were independent factors associated with low FEV1 but not low T
L,CO. There was a significant correlation between LVEF and FEV1 in CS group (r = 0.31, n = 89, P = .003). No significant difference in 6MWD between CS patients and controls was observed.

Lung function impairment was more frequent in CS. Lower LVEF was associated with decreased values of FEV1. Relatively poor lung function may be an indication of cardiac sarcoidosis.
Conservative interventions for the treatment of pelvic organ prolapse
Authors: Sun Yuanjie , Chen Huan , Liu Yan , Jiao Ruimin , Yuan Jingxue , Zhang Xuecheng , Liu Zhishun
Published: November 2019

Background:

Pelvic organ prolapse (POP) is the downward descent of vaginal walls, affecting the health of 32% to 76% female patients. Conservative interventions are considered as priority before seeking help from surgery. We plan to make the systematic review to assess the effectiveness of conservative intervention for adult women with POP.

Methods:

Studies will be searched in PubMed, EMBASE, and the Cochrane Library from inception to July 2017. Primary outcomes are specific POP-related symptom, severity of prolapse, Prolapse-related, and general health-related quality of life and other non-POP-specific symptoms.

Results:

The data will be synthesized if possible using MD, SMD or RR. A descriptive analysis will be made if the data cannot be synthesized.

Discussion:

The systematic review might provide solid evidence for the treatment of POP by conservative intervention.
Inverted internal limiting membrane flap technique and an autologous platelet concentrate to treat an Nd:YAG laser-induced macular hole
Authors: Yang Young Hoon , Chung Young Taek , Kim Bu Ki , Moon Jun Hyung , Mun Su Joung
Published: November 2019

Rationale:

Nd:YAG laser-induced macular holes (MHs) feature more extensive anatomical defects and worse functional outcomes than idiopathic MHs. Although new treatment options for large refractory MHs have been suggested, the current literature on Nd:YAG laser-induced MHs suggests only conventional pars plana vitrectomy combined with internal limiting membrane (ILM) peeling, which is the same treatment as for idiopathic MHs.

Patient concerns:

A 40-year-old dermatologist was referred to us because of a sudden decrease in visual acuity following exposure to a floor-tile-reflected single-shot Nd:YAG laser beam while not wearing protective goggles.

Diagnoses:

An Nd:YAG laser-induced MH was diagnosed based on fundoscopy and optical coherence tomography (OCT).

Interventions:

Pars plana vitrectomy using an inverted ILM flap technique and autologous platelet concentrate (APC) was performed.

Outcomes:

Postoperative spectral domain OCT and en-face OCT showed “U-shaped” closure of the MH and a decreased ellipsoid zone defect, while the best-corrected visual acuity improved from 20/500 to 20/25.

Lessons:

The inverted ILM flap technique combined with APC is an effective option to achieve successful MH closure and visual improvement in patients with an Nd:YAG laser-induced MH.
Compatibility of [99mTc]Tc-EDDA/HYNIC-TOC and [68Ga] Ga-DOTA-TOC in a syringe for intravenous administration
Authors: Chaib Sarah , Hallouard François , Chennell Philip , Darcissac Caroline , Morelec Isabelle , Rioufol Catherine , Sautou Valérie , Fraysse Marc
Published: November 2019

Objective

Drug quality in medical devices is not evaluated during the marketing authorization of radiopharmaceuticals. Therefore, the extemporaneous change of packaging made for preparation of patient unit doses in a syringe is the responsibility of radiopharmacists. The present study aimed to determine the impact of packaging and storage in a polypropylene syringe on the quality of hydrophilic drugs [99mTc]Tc-EDDA/HYNIC-TOC (Tektrotyd) and [68Ga]Ga-DOTA-TOC (Somakit-TOC).

Methods

Appearance, pH, radiochemical purity, sterility, and endotoxin tests were performed according the current European Pharmacopoeia. Subvisible and visible particles tests of the European Pharmacopoeia were adapted due to limited preparation volume (<25 ml). Sorption tests were performed according to the literature.

Results

After 2 h storage in a syringe, drug sorption of Tektrotyd and Somakit-TOC was of less than 2.5% and similar to other 99mTc-radiopharmaceuticals (range: from 1.1 ± 0.5% to 4.2 ± 0.6%). For Tektrotyd, this sorption phenomenon was positively influenced by the drug concentration and a short contact with the medical device (4.8 ± 0.2% up to 5 s vs. 2.3 ± 0.2%, n = 4; P < 0.001). For Somakit-TOC, the duration of contact with syringe had no impact (1.6 ± 0.2% up to 5 s vs. 1.7 ± 0.6%; P = 1.000). No drug radiolysis or alteration of microbiological aspects were observed. No impurity from a 3-piece-syringe was observed according to drug aspect, pH, and subvisible and visible particles, which remained within specification of the current European Pharmacopoeia.

Conclusion

This study found that drug sorption to packaging was compatible with clinical use and absence of drug alteration of Tektrotyd and Somakit-TOC after repackaging in a syringe in polypropylene and prolonged storage during 2 h.
Sequential PET/diffusion-weighted imaging in the evaluation of myocardial perfusion and viability in coronary artery disease: a preliminary study
Authors: Ling Xueying , Chen Jianxin , Shang Jingjie , Tang Yongjin , Cheng Yong , Xu Hao
Published: November 2019

Objectives

To evaluate the utility of sequential F-18 fluorodeoxyglucose PET/diffusion-weighted imaging in assessing myocardial perfusion and viability in coronary artery disease.

Methods

Fourteen coronary artery disease patients and five non-coronary artery disease subjects underwent sequential cardiac F-18 fluorodeoxyglucose PET/diffusion-weighted imaging using a trimodality PET/computed tomography-MRI system. The perfusion data were acquired by measuring low b-values apparent diffusion coefficient using diffusion-weighted imaging. Regional myocardial viability was determined by perfusion/metabolism patterns. The perfusion/metabolism patterns obtained by low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake were analyzed and compared with the results from the combination of rest 99mmethoxyisobutylisonitrile (99mTc-MIBI) myocardial perfusion single-photon emission computed tomography with F-18 fluorodeoxyglucose PET/computed tomography.

Results

Ten coronary artery disease patients and five non-coronary artery disease subjects were included in the final analysis. Low b-values apparent diffusion coefficient defects involved with 25 myocardial regions were demonstrated in nine coronary artery disease patients, while 99mTc-MIBI defects involved with 21 myocardial regions were shown in the same patients. The agreement between low b-values apparent diffusion coefficient and MIBI uptake was good in coronary artery disease patients (κ = 0.627, P < 0.001) and was better still in the whole subjects (κ = 0.733, P < 0.001). Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake demonstrated mismatch patterns in six coronary artery disease patients and MIBI/fluorodeoxyglucose uptake revealed mismatch patterns in seven coronary artery disease patients. Agreement in the evaluation of regional myocardial viability between low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake and MIBI/fluorodeoxyglucose uptake was high in coronary artery disease patients (κ = 0.627, P < 0.001) and all subjects (κ = 0.728, P < 0.001).

Conclusions

Low b-values apparent diffusion coefficient/fluorodeoxyglucose uptake is comparable to MIBI/fluorodeoxyglucose uptake in assessing perfusion/metabolism patterns, indicating that microperfusion might dominate the diffusion signal at low b-values and sequential PET/diffusion-weighted imaging might be useful to evaluate myocardial viability in coronary artery disease patients.
Prognostic value of dual-point fluorine-18 fluorodeoxyglucose PET imaging, partial volume correction and glucose transporter-1 expression in resected nonsmall cell lung cancer patients.
Authors: Kaida Hayato , Azuma Koichi , Kawahara Akihiko , Takamori Shinzo , Akiba Jun , Fujimoto Kiminori , Ishii Kazunari , Ishibashi Masatoshi
Published: November 2019

Objective

To investigate the relationship between the prognosis and glucose transporter-1 (Glut-1) expression or fluorine-18 fluorodeoxyglucose uptake using partial volume correction and dual-point imaging in surgically resected nonsmall cell lung cancer (NSCLC) patients.

Methods

Our patient population consisted of 108 NSCLC cases. The early maximum standardized uptake value (ESUVmax), delayed SUVmax (DSUVmax), partial volume correction SUVmax (cSUVmax) and retention index of primary lesions were calculated. Cox proportional hazard model was applied to evaluate the effects of PET parameters and Glut-1 expression. Overall survival (OS) and disease-free survival (DFS) were evaluated by Kaplan–Meier methods, and the difference in survival between subgroups was analyzed by log-rank test.

Results

On the Cox regression analysis, ESUVmax, DSUVmax, cSUVmax and Glut-1 were significantly related to DFS [ESUVmax, hazard ratio

 = 2.301, 95% confidential interval (CI) = 1.146–4.618, P = 0.019; DSUVmax, hazard ratio = 2.483, 95% CI = 1.257–4.905, P = 0.009; cSUVmax, hazard ratio = 2.205, 95% CI = 1.038–4.686, P = 0.04; Glut-1, hazard ratio = 2.095, 95% CI = 1.086–4.041, P = 0.001] and OS (ESUVmax, hazard ratio = 3.197, 95% CI = 1.339–7.633, P = 0.009; DSUVmax, hazard ratio = 3.599, 95% CI = 1.521–8.516, P = 0.004; cSUVmax, hazard ratio = 8.655, 95% CI = 2.048–36.658, P = 0.003; Glut-1, hazard ratio = 2.427, 95% CI = 5.140, P = 0.021). Retention index had no significant association with DFS or OS. On the Kaplan–Meier survival curves, the patients with high ESUVmax, DSUVmax, cSUVmax and Glut-1 showed significantly worse prognosis than those with low values (ESUVmax: DFS, P = 0.001, OS, P = 0.003; DSUVmax: DFS, P = 0.002, OS, P = 0.004; cSUVmax: DFS, P < 0.001, OS, P = 0.013; Glut-1: DFS, P = 0.012, OS, P = 0.002).

Conclusions

cSUVmax, ESUVmax, DSUVmax and Glut-1 may be more useful biomarkers than retention index for predicting outcomes in NSCLC patients.
Radiation Exposure in Pediatric Sarcoma Patients Receiving Initial Curative Chemotherapy
Authors: Danley Kelsey , Sane Nitin P. , Kent Paul M.
Published: November 2019

The objective of our study is to estimate the radiation exposure to pediatric patients with sarcoma getting required (or highly recommended) ionizing radiation scans during initial chemotherapy and to determine how often distant progressive disease was discovered. Data from the last 25 years from the Children’s Oncology Group open phase III protocols were reviewed for the most common pediatric sarcomas: osteosarcoma, Ewing’s sarcoma, and rhabdomyosarcoma. The number of required/recommended ionizing radiation scans, including chest radiographs, chest computed tomography, positron emission tomography scans, and bone scans during induction, consolidation, and maintenance chemotherapy, were recorded and the total radiation dose per patient was calculated. In addition, the number of patients who were removed from protocol during chemotherapy because of new or distant progressive disease was documented. In our analysis of 5845 patients, the average pediatric patient with sarcoma on protocol was exposed to an ionizing radiation dose of 37.1 mGy, equivalent to the lifetime dose of nuclear power plant workers, whereas the progression of disease was detected at most in 5.4% of the patients. Our study is meant to inform pediatric oncologists more precisely of the actual risks and benefits of mandated surveillance scans during chemotherapy in patients with sarcoma.
Leveraging Interprofessional Team-Based Care Toward Case Management Excellence
Authors: Fink-Samnick Ellen
Published: November 2019

Health care teams are constructive and efficient ways to approach, assess, coordinate, plan, and facilitate the client-centric and population-based care. Some iteration of team is in place across most practice settings, comprising different professionals and specialists, from multidisciplinary, interdisciplinary, and transdisciplinary to the most recent interprofessional model. This 2-part article series sets the tone for how interprofessional team-based care (IPTBC) empowers the care process. Part 1 focused on the history and fundamental concepts of interprofessional models, with outcomes to promote the value proposition for IPTBC implementation.

This Part 2 article focuses on the identification of seminal group development and team processes. An original model, the Interprofessional Team Activation Cycle (ITAC), is presented, as well as defined tactics for professional case managers to promote successful implementation of IPTBC in their organizations.

Purpose/Objectives:

This article:

Identifies deterrents to implementing IPTBC;

Explores timely and successful IPTBC models across the industry;

Discusses models of group and team development;

Explores the ITAC for professional case management; and

Identifies 10 tactics for case managers to sustain successful IPTBC.

Primary Practice Setting(s):

Applicable to all health and behavioral health settings where case management is practiced.

Findings/Conclusions:

Shifts in reimbursement models, organizational cultures, and client populations have yielded emphasis on the swift IPTBC implementation. In addition, the recognition of team development as a fluid process endemic to achieve client-centric outcomes and organizational return on investment mandates a keen eye to the phases of a team implementation, especially those that are interprofessional in scope.

Implications for Case Management Practice:

With case management so closely linked to the fiscal imperatives of organizations, engagement in IPTBC is a necessity for every practice setting yet not always implemented properly or successfully. Poor team collaboration contributes to unsuccessful outcomes for clients, increased costs, and concerning quality and risk management issues for the organization. Models focused on group development serve to support how health and behavioral health organizations consider and implement interprofessional teams.
BCL-2 Inhibitors, Present and Future
Authors: Ryan Christine E. , Davids Matthew S.
Published: November 2019

The members of the B-cell leukemia/lymphoma-2 (BCL-2) family of proteins are key regulators of the intrinsic apoptotic pathway; dysregulation of this pathway leads to pathologic survival of cancer cells. B-cell leukemia/lymphoma-2 had long been viewed as a promising target for the treatment of several hematologic malignancies, specifically chronic lymphocytic leukemia (CLL), yet for many years the development of a drug to successfully target this protein remained elusive. The approval of the BCL-2 inhibitor venetoclax for relapsed/refractory del(17p) CLL in 2016 represented the culmination of decades of molecular and clinical research and has paved the way for new combination therapy regimens in CLL, including the venetoclax + rituximab regimen approved for relapsed/refractory CLL in 2018 and the venetoclax + obinutuzumab regimen approved for frontline CLL treatment in 2019. Here, we provide an overview of the mechanism of action of BCL-2 inhibition, the role of this approach in the current treatment paradigm of CLL, and an in-depth focus on the clinical trials in CLL involving venetoclax. Additionally, we review key areas of active research including the integration of minimal residual disease as a marker of clinical efficacy in current clinical trials as well as the emergence of venetoclax resistance mechanisms and potential strategies to overcome this resistance. Given the success of venetoclax in the clinical setting thus far, it is likely that BCL-2 inhibition will take on an increasingly important role in the treatment of CLL going forward.
Rasch Analysis of the Patient and Observer Scar Assessment Scale in Linear Scars: Suggestions for a Patient and Observer Scar Assessment Scale v2.1
Authors: Franchignoni Franco , Giordano Andrea , Vercelli Stefano , Bravini Elisabetta , Stissi Valeria , Ferriero Giorgio
Published: November 2019

Background:

The Patient and Observer Scar Assessment Scale (POSAS) v2.0 is a widely used instrument to evaluate postsurgical scars. Its two subscales respectively investigate the patient’s and clinician’s opinion on the scar quality. However, psychometric studies of the POSAS have indicated that its metric performance is suboptimal, and structural adjustments may be appropriate. The authors aimed to verify through Rasch analysis the measurement properties of the POSAS v2.0, and propose eventual structural refinements for an easier and more confident use of the scale in clinical practice and research.

Methods:

Consecutive patients admitted to two rehabilitation centers for postsurgery rehabilitation over a 2-year period underwent scar assessments with the POSAS v2.0. We performed Rasch analysis to examine the scale’s dimensionality, rating categories, item fit, reliability indices, local item independence, and differential item functioning.

Results:

The study population consisted of 115 patients. The 10 response options of the POSAS showed malfunctioning, and thus were collapsed, forming a parsimonious five-level rating scale, which helped to improve the measurement accuracy. After that, unidimensionality of both subscales was confirmed. Then, internal construct validity of the POSAS v2.0 was demonstrated (through item fit to the Rasch model). Reliability indices were high (≥0.80). No significant differential item functioning was detected concerning age or sex.

Conclusion:

This study demonstrates the good psychometric properties of a simplified Rasch-based version of the Patient and Observer Scar Assessment Scale with five response options (POSAS v2.1) in patients with postsurgical linear scars, and provides insights for future refinement of the tool.
Activated PD-1+ CD4+ T cells represent a short-lived part of the viral reservoir and predict poor immunologic recovery upon initiation of ART
Authors: Eller Michael A. , Hong Ting , Creegan Matthew , Nau Martin E. , Sanders-Buell Eric , Slike Bonnie M. , Krebs Shelly J. , Ratto-Kim Silvia , McElrath M. Juliana , Katabira Elly T. , Bolton Diane L. , Michael Nelson L. , Robb Merlin L. , Tovanabutra Sodsai , Baeten Jared M. , Sandberg Johan K.
Published: November 2019

Objective:

Activated (CD38+HLA-DR+) PD-1+ CD4+ T cells are strongly associated with virus replication and disease progression in untreated HIV-1 infection, and viral persistence in individuals on ART. Few studies have examined cell-associated viral load (CAVL) in different activated CD4+ T-cell populations to measure relative contributions to viral reservoirs.

Design:

Longitudinal assessment of HIV-1 chronically infected Ugandans initiating ART, to investigate activated CD4+ T-cell populations and their contribution to viral reservoirs.

Methods:

We followed 32 HIV-1 chronically infected individuals from Kampala, Uganda, and determined their CD4+ T-cell counts and viral load at baseline, 6, and 12 months after the initiation of ART. T-cell populations were sorted based on activation profiles and gag DNA was measured to determine CAVL within these populations. Soluble factors associated with inflammation were measured in plasma using a multiplexed platform.

Results:

Concomitant with viral load decline and CD4+ T-cell count rebound, the activated PD-1+ CD4+ T-cell population contracted upon initiation of ART. Baseline levels of activated PD-1+ CD4+ T cells correlated with plasma levels of IP-10 and TNFRII. Interestingly, a higher baseline level of activated PD-1+ CD4+ T cells was associated with poorer CD4+ T-cell recovery after 12 months of ART. This population contributed significantly to the cell-associated HIV DNA load at baseline, whereas their contribution declined on ART, indicating high turnover.

Conclusion:

Activated PD-1+ CD4+ T cells are predictors of poor immunologic recovery on ART and may represent a short-lived component of HIV-1 reservoirs.
Using Implementation Science to Better Integrate Novel Long-Acting Injectable Therapy Into Routine HIV Care
Authors: Czarnogorski Maggie
Published: November 2019

Background:

The key to maximizing the value of implementation science data is to get the learnings early. A critical contributor to early clinical research data is the biopharmaceutical industry. In partnership with the implementation research community, industry has an opportunity to play a major role to increase the value of implementation research data through earlier integration of implementation questions in the development continuum.

Methods:

This article suggests that by using more hybrid implementation-effectiveness study designs in phase III trials, researchers can accelerate the availability of implementation data closer to the initial introduction of novel treatments into community settings. The biopharmaceutical industry is uniquely poised to lead or collaborate on these trials.

Results:

The first LAI HIV medications are being studied for both HIV prevention and treatment. This paradigm shift in the provision of HIV care is an opportunity to blend implementation research into clinical trials earlier so that the public health community is armed with tested implementation strategies to maximize access and impact when these new medications become available. CUSTOMIZE, a novel phase IIIB—hybrid III implementation-effectiveness trial—is the first-of-its-kind study to examine different implementation strategies to overcome challenges of delivering a LAI antiretroviral medication in various types of HIV clinical settings the US health care system.

Conclusions:

Industry can play a complimentary and additive role by partnering with implementation science researchers to understand the implementation strategies sooner in the development pipeline. These collaborations may allow for earlier, more informed, and strategic HIV public health programs in the future.
Surgical Management of Complex Syndromic Craniosynostosis: Experience With a Rare Genetic Variant
Authors: Celie Karel-Bart , Yuan Melissa , Hoffman Caitlin , O’Connor Ashley , Bogue Jarrod , Imahiyerobo Thomas
Published: November 2019

Patients with syndromic craniosynostosis (CS) can present with both intracranial and extracranial manifestations. Extracranial features include proptosis, exorbitism, and midface hypoplasia. Intracranial manifestations can include elevated intracranial pressure (ICP), brainstem compression, foramen magnum stenosis or jugular foramen hypoplasia with resultant venous hypertension and anomalous drainage. While fronto-orbital advancement, cranial vault remodeling, and posterior fossa decompression are standard surgical approaches to normalizing orbito-cranial volume and morphology, associated hydrocephalus, anomalous venous drainage, and tonsillar herniation often affect the timing, safety, and selection of corrective interventions. The surgical decision-making to circumvent venous emissaries, effectively time treatment of hydrocephalus, and address posterior versus anterior pathology primarily has not been widely described in the literature, and is important in the development of guidelines in these complex cases. In this report, we describe the surgical management of a patient with Jackson-Weiss syndrome presenting with delayed, but rapidly progressive bilateral lambdoid CS, severe proptosis, midface hypoplasia, elevated ICP, hydrocephalus, tonsillar ectopia, and severe venous hypertension with anomalous drainage. We review the literature related to management of complex synostosis and present our surgical decision-making in the setting of complex syndromic synostosis to aid in the formation of guidelines toward approaching these cases.
A screening platform based on epitope editing for drug discovery
Authors: Zhu Biyue , Yang Jing , Van Richard , Ran Kathleen , Yin Keyi , Liang Yingxia , Shen Xunuo , Yin Wei , Choi Se Hoon , Lu Ying , Wang Changning , Shao Yihan , Tanzi Rudolph E. , Zhang Can , Cheng Yan , Zhang Zhirong , Ran Chongzhao
Published: November 2019

The interaction between an antibody and its epitope has been daily utilized in various biological studies; however it has been rarely explored whether small molecules can alter the interaction. We discovered that small molecules could alter/edit surface properties of amyloid beta (Aβ) epitopes, and consequently inhibit or enhance corresponding antibody recognition. Remarkably, this editing effect could generate functional changes including protein aggregation behaviors, cell cytokine secreting and in vivo microglia activation. According to this discovery, we proposed ascreenplatform based onepitopeediting fordrug discovery (SPEED). With a small library of compounds, we validated that SPEED could be used to seek new leads for Aβ species. We also demonstrated that this platform could potentially be extended to other targets including tau protein and PD-L1 protein. The SPEED is a simple, fast and label-free screening method. We believe that the SPEED strategy could be universally applicable for seeking and validating drug candidates and imaging ligands.
Drivers of phyllosphere microbial functional diversity in a neotropical forest
Authors: Lajoie Geneviève , Maglione Rémi , Kembel Steven W.
Published: November 2019

Background

The phyllosphere is an important microbial habitat but our understanding of how plant hosts drive the composition of their associated leaf microbial communities and whether taxonomic associations between plants and phyllosphere microbes represent adaptive matching remains limited. In this study we quantify bacterial functional diversity in the phyllosphere of 17 tree species in a diverse neotropical forest using metagenomic shotgun sequencing. We ask how hosts drive the functional composition of phyllosphere communities and their turnover across tree species, using host functional traits and phylogeny. We compare functional predictions inferred from 16S gene sequencing with functions estimated from metagenomic shotgun sequencing.

Results

Neotropical tree phyllosphere communities are dominated by functions related to the metabolism of carbohydrates, amino acids and energy acquisition, along with environmental signalling pathways involved in membrane transport. While most functional variation was observed within communities, there is non-random assembly of microbial functions across host species possessing different leaf traits. Metabolic functions related to biosynthesis and degradation of secondary compounds, along with signal transduction and cell-cell adhesion were particularly important in driving the match between microbial functions and host traits. These microbial functions were also evolutionarily conserved across the host phylogeny. Functional predictions inferred from 16S gene sequences were weakly correlated with functional annotations from the same samples through metagenomic shotgun sequencing, especially for finer-scale functional annotations.

Conclusions

Functional profiling based on metagenomic shotgun sequencing offers evidence for the presence of a core functional microbiome across phyllosphere communities of neotropical trees. While functional turnover across phyllosphere communities is relatively small, the association between microbial functions and leaf trait gradients among host species supports a significant role for plant hosts as selective filters on phyllosphere community assembly. This interpretation is supported by the presence of phylogenetic signal for the microbial traits driving inter-community variation across the host phylogeny. Our comparison of functional annotations derived from 16S genes versus metagenomic shotgun sequencing suggests caution in using functions inferred from 16S genes for studying ecological dynamics in phyllosphere communities. Taken together, our results suggest that there is adaptive matching between phyllosphere microbes and their plant hosts.
A classification of functional pitcher types in Nepenthes (Nepenthaceae)
Authors: Cheek Martin , Jebb Matthew , Murphy Bruce
Published: November 2019

We classify Nepenthes species into 12 functional pitcher types, based on combinations of traits that appear to comprise different syndromes for capturing nutrients, usually from animals. For nine of these types the trapping syndromes are already documented, six targeting live animals (hence carnivorous), and three targeting other nutrient sources (non-carnivorous). Yet, for three pitcher types here is no previous documentation of the syndrome and we do not yet know what sources of nutrients are being targeted. Mapping all these pitcher types on the latest, near comprehensive species-level phylogenomic tree of Nepenthes (Murphy et al. 2019) shows that apart from the ancestral pitcher type 1, most of the remaining pitcher types have evolved independently, in different parts of the phylogenetic tree, usually in several different places. Each of the 12 pitcher types is characterised morphologically and illustrated, its trapping syndrome discussed, and example species are given. An identification key to the 12 pitcher types is presented. The possibility of additional pitcher types being present is discussed.
The host antiviral ribonuclease L protein supports Zika virus replication factory formation to enhance infectious virus production
Authors: Whelan Jillian N , Hatterschide Joshua , Renner David M. , Dong Beihua , Silverman Robert H , Weiss Susan R
Published: November 2019

The flavivirus Zika virus (ZIKV) activates ribonuclease L (RNase L) catalytic antiviral function during infection, yet deletion of RNase L decreases ZIKV production, suggesting a proviral role of RNase L. In this study, we reveal that latent RNase L supports ZIKV replication factory (RF) assembly. Deletion of RNase L induced broader cellular distribution of ZIKV dsRNA and NS3 compared with densely concentrated RFs detected in WT cells. An inactive form of RNase L was sufficient to contain ZIKV genome and dsRNA within a smaller area, which increased levels of viral RNA within RFs as well as infectious ZIKV released from the cell. We used a microtubule stabilization drug to demonstrate that RNase L deletion impaired the cytoskeleton rearrangements that are required for proper generation of RFs. During infection with dengue or West Nile Kunjin viruses, RNase L decreased virus production, suggesting that RNase L proviral function is specific to ZIKV.