bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conservative recovery and replacement of a ruptured percutaneous endoscopic gastrostomy tube; a case report
Authors: Al Halabi Maan , Wakim Wakim , Moukaddam Hicham , Husari Ahmad 
Published: March 2020

Abstract
Background
Percutaneous Endoscopic Gastrostomy (PEG) feeding tubes are frequently placed in patients to provide enteral nutrition. We report a case of a complete rupture of a PEG tube intra-abdominally with associated peritonitis after more than a month of PEG placement and utilization. To our knowledge, this is a very rare case of a complete PEG rupture with the succeeding replacement and recovery of the fractured segments conservatively.

Case presentation
A 69-year-old female with a PEG in position and in use for more than a month started complaining of severe abdominal pain. Digital subtraction angiography (DSA) tubogram revealed rupture and separation of the PEG tube into two fragments.
Interventional radiology (IR) team was successful with their conservative approach. Both fragments were removed conservatively without the need for laparotomy. The distal fragment was utilized to place a guide wire, and a new PEG was placed in position with no intraabdominal leak.

Conclusion
Ruptured PEG tube should be considered in the differential of patients complaining of sudden abdominal pain, especially after chronic PEG utilization. Conservative approach by IR is a viable option in correcting this mishap.
The independent indicators for differentiating renal cell carcinoma from renal angiomyolipoma by contrast-enhanced ultrasound
Authors: Cao Hongli , Fang Liang , Chen Lin , Zhan Jia , Diao Xuehong , Liu Yingchun , Lu Chen , Zhang Zhengwang , Chen Yue 
Published: March 2020

Abstract
Background
The value of contrast-enhanced ultrasound (CEUS) in differentiating between renal cell carcinoma (RCC) and angiomyolipoma (AML) was analyzed. The purpose of this study was to identify the independent indicators of CEUS for predicting RCC.

Methods
A total of 172 renal tumors (150 RCCs, 22 AMLs) in 165 patients underwent conventional ultrasound (CUS) and CEUS examinations before radical or partial nephrectomy, and the features on CUS and CEUS were analyzed.

Results
There were significant differences in echogenicity, blood flow signals in color Doppler flow imaging (CDFI), peak intensity, homogeneity of enhancement, wash in, wash out, and perilesional rim-like enhancement between RCC and AML (P < 0.05 for all). Multivariate analysis indicated that perilesional rim-like enhancement (P = 0.035, odds ratio [OR] = 9.907, 95% confidence interval [CI]: 1.169–83.971) and fast wash out (P = 0.001, OR = 9.755, 95%[CI]: 2.497–38.115) were independent indicators for predicting RCC. The area under the receiver operating characteristic (ROC) curve (AUC) for perilesional rim-like enhancement was 0.838 (95% CI: 0.774–0.890) with 76.7% sensitivity and 90.9% specificity, while the AUC of fast wash out was 0.833 (95% CI:0.768–0.885) with 74.7% sensitivity and 81.8% specificity.

Conclusions
This study indicated that CEUS has value in differentiating RCC and AML. Present perilesional rim-like enhancement and fast wash out may be important indicators for predicting RCC.
Identification of a novel DDB2 mutation in a Chinese Han family with Xeroderma pigmentosum group E:a case report and literature review
Authors: Yang Rui , Kong Qingtao , Duan Yuanyuan , Li Weiwei , Sang Hong 
Published: March 2020

Abstract
Background
Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis. There are eight complementation groups of XP (XP-A to G and a variant form). XP-E is one of the least common forms, and XP-E patients are generally not diagnosed until they are adults due to a later onset of skin alterations.

Case presentation
We report a case of a 28-year-old Chinese woman with freckle-like hyperpigmented macules in a sun-exposed area who is prone to develop basal cell carcinomas. A genetic study revealed a novel homozygous c.111_112del deletion in exon 1 of the DDB2 gene. Western blotting analysis revealed that the patient lacked the expression of the wild-type mature DDB2 protein. The proband was first diagnosed with XPE on the basis of clinical findings and genetic testing. Sun protection was recommended, and the patient did not develop any skin cancers during the one-year follow-up.

Conclusions
We identified a novel homozygous deletion in DDB2 gene in Chinese XP-E patients having unique clinical features.
Idiopathic brain calcification in a patient with hereditary hemochromatosis
Authors: Scarlini Stefania , Cavallieri Francesco , Fiorini Massimo , Menozzi Elisa , Ferrara Francesca , Cavalleri Francesca , Reale Chiara , Garavaglia Barbara , Pietrangelo Antonello , Valzania Franco , Corradini Elena 
Published: March 2020

Abstract
Background
Detection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported.

Case presentation
A 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D–PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative.

Conclusions
This report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.
Phase II, multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Mycophenolate Mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): rationale and design of the ESMMO trial
Authors: Koonrungsesomboon Nut , Ngamphaiboon Nuttapong , Townamchai Natavudh , Teeyakasem Pimpisa , Charoentum Chaiyut , Charoenkwan Pimlak , Natesirinilkul Rungrote , Sathitsamitphong Lalita , Ativitavas Touch , Chaiyawat Parunya , Klangjorhor Jeerawan , Hongeng Suradej , Pruksakorn Dumnoensun 
Published: March 2020

AbstractBackgroundClinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a substantial need for further research and development to identify and develop more efficacious agents/regimens in order to improve clinical outcomes of patients for whom the prognosis is unfavorable. Recently, mycophenolate mofetil, a prodrug of mycophenolic acid, has been found to have anticancer activity against osteosarcoma in both in vitro and animal experiments, so that further investigation in humans is warranted.MethodsA total of 27 patients with high-grade locally advanced or metastatic osteosarcoma will be enrolled into this phase II, multi-center, open-label, single-arm, two-stage clinical trial. The main objectives of this study are to determine the efficacy and safety of mycophenolate mofetil in the patients. The primary endpoint is progression-free survival at 16 weeks; the secondary endpoints include progression-free survival, overall survival, overall response rate, safety parameters, pharmacokinetic parameters, biomarkers, pain score, and quality of life. Mycophenolate mofetil at the initial dose of 5 g/day or lower will be administered for 4 cycles (28 days/cycle) or until disease progression or unacceptable toxicity. The dose of mycophenolate mofetil may be reduced by 1–2 g/day or withheld for some Grade 3 or Grade 4 toxicities whenever clinically needed. The duration of study participation is approximately 4–5 months, with a minimum of 12 study visits. If mycophenolate mofetil proves beneficial to some patients, as evidenced by stable disease or partial response at 16 weeks, administration of mycophenolate mofetil will continue in the extension period.DiscussionThis trial is the first step in the translation of therapeutic potential of mycophenolate mofetil emerging from in vitro and animal studies into the clinical domain. It is designed to assess the efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma. The results will provide important information about whether or not mycophenolate mofetil is worth further development.Trial registrationThis trial was prospectively registered on Thai Clinical Trials Registry (registration number:TCTR20190701001). The posted information will be updated as needed to reflect protocol amendments and study progress.
CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Authors: Xu Nuo , Liu Fanglei , Wu Shengdi , Ye Maosong , Ge Haiyan , Zhang Meiling , Song Yuanlin , Tong Lin , Zhou Jian , Bai Chunxue 
Published: March 2020

Abstract
Background
Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action.

Methods
By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis.

Results
Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway.

Conclusions
CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.
Outcomes in patients with chronic uveitis: which factors matter to patients? A qualitative study
Authors: Stolk-Vos Aline C. , Kasigar Hamasa , Nijmeijer Karlijn J. , Missotten Tom O. , Busschbach Jan J. , van de Klundert Joris J. , Kranenburg Leonieke W. 
Published: March 2020

Abstract
Purpose
Outcome measurements currently used in chronic uveitis care fail to cover the full patient perspective. The aim of this study is to develop a conceptual model of the factors that adult patients with chronic uveitis consider to be important when evaluating the impact of their disease and treatment.

Methods
A qualitative study design was used. Twenty chronic uveitis patients were recruited to participate in two focus groups. Data were transcribed verbatim and analysed using thematic analysis in ATLAS.ti.

Results
Coding of the transcripts resulted in a total of 19 codes divided over five themes: 1) disease symptoms and treatment; 2) diagnosis and treatment process; 3) impact on daily functioning; 4) emotional impact; and 5) treatment success factors.

Conclusion
The conceptual model resulting from this study can contribute to the development of future uveitis specific measures in adults.
Individualized treat-and-extend regime for optimization of real-world vision outcome and improved patients’ persistence
Authors: Volkmann Ingo , Knoll Katharina , Wiezorrek Mareile , Greb Oliver , Framme Carsten 
Published: March 2020

Abstract
Background
Intravitreal injections are a mandatory treatment for macular edema due to nAMD, DME and RVO. These chronic diseases usually need chronic treatment using intravitreal injections with anti-VEGF agents. Thus, many trials were performed to define the best treatment interval using pro re nata regimes (PRN), fixed regimes or treat-and-extend regimes (TE). However, real-world studies reveal a high rate of losing patients within a 2-year interval of treatment observation causing worse results. In this study we analyzed retrospectively 2 years of real-world experience with an individualized treat-and-extend injection scheme.

Methods
Since 2015 our treatment scheme for intravitreal injections has been switched from PRN to TE. Out of 102 patients 59 completed a follow up time of 2 years. Every patient received visual acuity testing, SD-OCT and slit lamp examination prior to every injection. At each visit an injection was performed and the treatment interval was adjusted mainly on SD-OCT based morphologic changes by increasing or reducing in 2-week steps. Individual changes of the treatment protocol by face-to-face communication between physician and patient were possible.

Results
After 1 year of treatment visual acuity gain in nAMD was 7.4 ± 2.2 ETDRS letters (n = 34; injection frequency: 7.4 ± 0.4) respectively 6.1 ± 4.7 in DME (n = 9; injection frequency: 8.4 ± 1.1) and 9.7 ± 4.5 in RVO (n = 16; injection frequency: 7.6 ± 0.5). After 2 years of treatment results were as following: nAMD: visual acuity gain 6.9 ± 2.1 (injection frequency: 12.6 ± 0.7); DME: 11.1 ± 5.1 (injection frequency: 14.0 ± 1.0); RVO: 7.5 ± 5.0 (injection frequency: 11.2 ± 0.9). Planned treatment exit after 2 year was achieved in 29.4% of patients in nAMD (0% after 1 year); 0% in DME (0% after 1 year); and 31.3% in RVO (0% after 1 year). Patients’ persistence was 94.1% during the follow-up.

Conclusion
Using a consequent and individualized TE regime in daily practice may lead to a high patients’ persistence and visual acuity gains nearly comparable to those of large prospective clinical trials. Crucial factors are face-to-face communication with the patient as well as a stringent management regime. At this time TE may be the only instrument for proactive therapy which should therefore be regarded as a first-line tool in daily practice.
Enhancing communication, informed consent and recruitment in a paediatric urgent care surgical trial: a qualitative study
Authors: Sherratt Frances C. , Beasant Lucy , Crawley Esther M. , Hall Nigel J. , Young Bridget 
Published: March 2020

Abstract
Background
Recruiting patients to paediatric trials can be challenging, especially in trials that compare markedly different management pathways and are conducted in acute settings. We aimed to enhance informed consent and recruitment in the CONTRACT trial (CONservative TReatment of Appendicitis in Children a randomised controlled Trial; ISRCTN15830435) – a feasibility trial that compared non-operative treatment (antibiotics) versus appendicectomy for uncomplicated acute appendicitis.

Methods
Qualitative study embedded within CONTRACT and conducted across three UK children’s hospitals. Data were transcribed audio-recordings of 85 CONTRACT recruitment consultations with 58 families; and semi-structured interviews with 35 health professionals and 28 families (34 parents, 14 children) invited to participate in CONTRACT. Data analysis drew on thematic approaches. Throughout CONTRACT, we used findings from the ongoing qualitative analysis to inform bespoke communication training for health professionals recruiting to CONTRACT. Before and after training we also examined qualitative changes in communication during consultations and quantitative changes in recruitment rates.

Results
Bespoke communication training focussed on presenting the trial arms in a balanced way, emphasising clinical equipoise, exploring family treatment preferences and managing families’ expectations about the trial’s treatment pathways. Analysis of recruitment consultations indicated that health professionals’ presentation of treatment arms became increasingly balanced following training, (e.g. avoiding imbalanced terminology) and recruitment rose from 38 to 62%. However, they remained reluctant to explore families’ treatment preferences and respond with further information to balance these preferences. Analyses of interviews identified the time constraints of the urgent care setting, concerns about coercion, and reservations about exposing children to conversations about treatment risks as reasons for this reluctance. Interviews with families indicated the importance of clear explanations of trial treatment timings and sensitive communication of treatment allocation for both recruitment and retention.

Conclusions
Following bespoke training based on the qualitative analyses, health professionals presented CONTRACT to families in clearer and more balanced ways and this was associated with an increase in the recruitment rate. Despite training, health professionals remained reluctant to explore families’ treatment preferences. We provide several recommendations to enhance communication, informed consent, recruitment and retention in future trials in urgent care settings.
PEBRA trial – effect of a peer-educator coordinated preference-based ART service delivery model on viral suppression among adolescents and young adults living with HIV: protocol of a cluster-randomized clinical trial in rural Lesotho
Authors: Lejone Thabo Ishmael , Kopo Mathebe , Bachmann Nadine , Brown Jennifer Anne , Glass Tracy Renée , Muhairwe Josephine , Matsela Tebatso , Scherrer Ramona , Chere Lebohang , Namane Tilo , Labhardt Niklaus Daniel , Amstutz Alain 
Published: March 2020

Abstract
Background
Despite tremendous progress in controlling the HIV epidemic in sub-Saharan Africa, HIV-related mortality continues to increase among adolescents and young people living with HIV (AYPLHIV). Globally, sub-Saharan Africa accounts for 85% of the AYPLHIV. Overall outcomes along the HIV care cascade are worse among AYPLHIV as compared to all other age groups due to various challenges in accessing and adhering to antiretroviral therapy (ART). New, innovative multicomponent packages of differentiated service delivery (DSD) models, are required to address the specific needs of AYPLHIV. This study aims to evaluate the feasibility and effectiveness of a multicomponent DSD model (PEBRA model) designed for AYPLHIV and coordinated by a peer-educator.

Methods
PEBRA (Peer-Educator Based Refill of ART) is a cluster randomized, open-label, superiority trial conducted at 20 health facilities in three districts of Lesotho, Southern Africa. The clusters (health facilities) are randomly assigned to either the PEBRA model or standard of care in a 1:1 ratio, stratified by district. AYPLHIV aged 15–24 years old in care and on ART at one of the clusters are eligible. In the PEBRA model, a peer-educator coordinates the antiretroviral therapy (ART) services - such as medication pick-up, SMS notifications and support options - according to the preferences of the AYPLHIV. The peer-educator delivers this personalized model using a tablet-based application called PEBRApp. The control clusters continue to offer standard of care: ART services coordinated by the nurse. The primary endpoint is viral suppression at 12 months. Secondary endpoints include self-reported adherence to ART, quality of life, satisfaction with care and engagement in care. The target sample size is 300 AYPLHIV. Statistical analyses are conducted and reported in line with CONSORT guidelines for cluster randomized trials.

Discussion
The PEBRA trial will provide evidence on the feasibility and effectiveness of an inclusive, holistic and preference-based DSD model for AYPLHIV that is coordinated by a peer-educator. Many countries in SSA have an existing peer-educator program. If proven effective, the PEBRA model and PEBRApp have the potential to be scaled up to similar settings.

Trial registration
Clinicaltrials.gov, NCT03969030. Registered on 31 May 2019. More information: www.pebra.info
Comparing hemoglobin distributions between population-based surveys matched by country and time
Authors: Hruschka Daniel J. , Williams Anne M. , Mei Zuguo , Leidman Eva , Suchdev Parminder S. , Young Melissa F. , Namaste Sorrel 
Published: March 2020

AbstractBackgroundValid measurement of hemoglobin is important for tracking and targeting interventions. This study compares hemoglobin distributions between surveys matched by country and time from The Demographic and Health Survey (DHS) Program and the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.MethodsFour pairs of nationally representative surveys measuring hemoglobin using HemoCue® with capillary (DHS) or venous (BRINDA) blood were matched by country and time. Data included 17,719 children (6–59 months) and 21,594 non-pregnant women (15–49 y). Across paired surveys, we compared distributional statistics and anemia prevalence.ResultsSurveys from three of the four countries showed substantial differences in anemia estimates (9 to 31 percentage point differences) which were consistently lower in BRINDA compared to DHS (2 to 31 points for children, 1 to 16 points for women).ConclusionWe identify substantial differences in anemia estimates from surveys of similar populations. Further work is needed to identify the cause of these differences to improve the robustness of anemia estimates for comparing populations and tracking improvements over time.