bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of secondary hip arthritis from shell fragment and gunshot injury in the Syrian civil war
Authors: Özden Raif , Davut Serkan , Doğramacı Yunus , Kalacı Aydıner , Duman İbrahim Gökhan , Uruç Vedat 
Published: October 2020

Abstract
Background
In gunshot and shell fragment injuries to the hip joint, orthopedic intervention includes wound assessment and care, osteosynthesis of fractures, and avoiding of infection and osteoarthritis. Individuals injured in the Syrian civil war were frequently transferred to the authors’ institution in neighboring city. Orthopedic trauma exposures were determined in approximately 30% of these patients. The aim of this study was to evaluate the outcomes of the patients with secondary hip arthritis due to prior gunshot and shell fragment (shrapnel) injuries who underwent primary total hip arthroplasty.

Methods
This retrospective study reviewed 26 patients (24 males, 2 females) who underwent hip arthroplasty due to prior gunshot and shell fragment injuries from November 2013 to January 2019. For all patients, the Harris Hip Score (HHS) was evaluated preoperatively and after surgery.

Results
Mean age was 31.5 (range, 19–48) years. The mean preoperative HHS was 52.95 points, and the mean postoperative HHS was 79.92 points at the final follow-up after surgery. Patients with shell fragment injuries to the hip joint had higher infection rates, but it is not statistically significant.

Conclusions
An anatomic reduction of the fracture may not be possible in these cases as a result of significant bone and/or cartilage loss. Total hip arthroplasty can be done after gunshot- and shell fragment-related posttraumatic arthritis. It is an effective treatment choice to reduce pain and improve function, but the surgeon must be very careful because of high rate of infection.
Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspected transthyretin amyloidosis
Authors: Paulsson Rokke Hedvig , Sadat Gousheh Nima , Westermark Per , Suhr Ole B. , Anan Intissar , Ihse Elisabet , Pilebro Björn , Wixner Jonas 
Published: October 2020

Abstract
Background
The diagnostic accuracy of histopathological detection of transthyretin amyloid (ATTR) by Congo red staining of abdominal fat samples has been questioned since low sensitivity has been reported, especially for patients with ATTR cardiomyopathy. However, the outcome of surgically obtained fat pad biopsies has not yet been evaluated. The aim was to evaluate the diagnostic accuracy of skin punch biopsies from abdominal fat in patients with suspected ATTR amyloidosis.

Material and methods
Data were evaluated from patients who had undergone abdominal fat pad biopsies using a skin punch due to suspected amyloidosis from 2006 to 2015. The biopsies had been analysed using Congo red staining to determine the presence of amyloid, and immunohistochemistry or Western blot to determine the type of amyloidosis. The final diagnosis was based on the clinical picture, biopsy results and DNA sequencing. Minimum follow-up after the initial biopsy was 3 years.

Results
Two hundred seventy-four patients (61% males) were identified, and in 132 (48%), a final diagnosis of amyloidosis had been settled. The majority (93%) had been diagnosed with hereditary transthyretin (ATTRv) amyloidosis, and therefore subsequent analyses were focused on these patients. Overall, our data showed a test specificity of 99% and a sensitivity of 91%. Ninety-eight (94%) of the patients had neuropathic symptoms at diagnosis, whereas 57 (55%) had signs of amyloid cardiomyopathy. Subgroup analyses showed that patients with merely neuropathic symptoms displayed the highest test sensitivity of 91%, whereas patients with pure cardiomyopathy displayed the lowest sensitivity of 83%. However, no significant differences in sensitivity were found between patients with or without cardiomyopathy or between the sexes.

Conclusions
Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspect ATTRv amyloidosis, including patients presenting with cardiomyopathy. In addition, the method enables typing not only of the precursor protein but also of the amyloid fibril type, which is related to the phenotype and to the outcome of the disease.
Endosomal dysfunction in iPSC-derived neural cells from Parkinson’s disease patients with VPS35 D620N
Authors: Bono Keiko , Hara-Miyauchi Chikako , Sumi Shunsuke , Oka Hisayoshi , Iguchi Yasuyuki , Okano Hirotaka James 
Published: October 2020

AbstractMutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons from PD patients with the VPS35 D620N mutation and addressed relevant disease mechanisms. In the disease group, dopaminergic (DA) neurons underwent extensive apoptotic cell death. The movement of Rab5a- or Rab7a-positive endosomes was slower, and the endosome fission and fusion frequencies were lower in the PD group than in the healthy control group. Interestingly, vesicles positive for cation-independent mannose 6-phosphate receptor transported by retromers were abnormally localized in glial cells derived from patient iPSCs. Furthermore, we found α-synuclein accumulation in TH positive DA neurons. Our results demonstrate the induction of cell death, endosomal dysfunction and α -synuclein accumulation in neural cells of the PD group. PARK17 patient-derived iPSCs provide an excellent experimental tool for understanding the pathophysiology underlying PD.
Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML
Authors: Yilmaz Musa , Alfayez Mansour , DiNardo Courtney D. , Borthakur Gautam , Kadia Tapan M. , Konopleva Marina Y. , Loghavi Sanam , Kanagal-Shamanna Rashmi , Patel Keyur P. , Jabbour Elias J. , Garcia-Manero Guillermo , Pemmaraju Naveen , Pierce Sherry A. , Ghayas Issa , Short Nicholas J. , Montalban-Bravo Guillermo , Takahashi Koichi , Assi Rita , Alotaibi Ahmad S. , Ohanian Maro , Andreeff Michael , Cortes Jorge E. , Kantarjian Hagop M. , Ravandi Farhad , Daver Naval G. 
Published: October 2020

Abstract
Background
Second-generation FLT3-inhibitors (FLT3i) demonstrated single-agent composite CR rates (CRc) of 45–55% in patients with relapsed/refractory (R/R) FLT3-mutated AML in phase II/III trials. However, > 85% of patients treated were prior FLT3i naïve. The response rates to sequential FLT3i exposure remain poorly defined.

Methods
We retrospectively reviewed patients with FLT3-mutated AML between November 2006 and December 2019.

Results
In frontline patients treated with a FLT3i (cohort 1), the CRc rates and median overall survival (OS) with the first (n = 56), second (n = 32), and third FLT3i-based (n = 8) therapy were 77%, 31%, and 25%, and 16.7 months, 6.0 months, and 1.4 months, respectively. In patients receiving a FLT3i-based therapy for the first time in a R/R AML setting (cohort 2), the CRc rates and median OS were 45%, 21%, and 10%, and 7.9 months, 4.0 months, and 4.1 months with the first (n = 183), second (n = 89), and third/fourth (n = 29) FLT3i-based therapy, respectively.
In cohort 1, CRc rates with single-agent FLT3i (n = 21) versus FLT3i-based combinations (n = 19) in second/third sequential FLT3i exposures were 19% versus 42%, respectively. In cohort 2, the CRc rates with single-agent FLT3i (n = 82) versus FLT3i-based combinations (n = 101) in first FLT3i exposure were 34% versus 53%, respectively, and those with single-agent FLT3i (n = 63) versus FLT3i-based combinations (n = 55) in second/third/fourth sequential FLT3i exposures were 13% versus 25%, respectively.

Conclusion
CRc rates drop progressively with sequential exposure to FLT3i’s in FLT3-mutated AML. In all settings, CRc rates were higher with FLT3i-based combinations compared with single-agent FLT3i therapy in similar FLT3i exposure settings.
Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition
Authors: Iannelli Federica , Roca Maria Serena , Lombardi Rita , Ciardiello Chiara , Grumetti Laura , De Rienzo Simona , Moccia Tania , Vitagliano Carlo , Sorice Angela , Costantini Susan , Milone Maria Rita , Pucci Biagio , Leone Alessandra , Di Gennaro Elena , Mancini Rita , Ciliberto Gennaro , Bruzzese Francesca , Budillon Alfredo 
Published: October 2020

Abstract
Background
Despite the introduction of several novel therapeutic approaches that improved survival, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease. Herein we report the synergistic antitumor interaction between two well-known drugs used for years in clinical practice, the antiepileptic agent with histone deacetylase inhibitory activity valproic acid and the cholesterol lowering agent simvastatin, in mCRPC models.

Methods
Synergistic anti-tumor effect was assessed on PC3, 22Rv1, DU145, DU145R80, LNCaP prostate cancer cell lines and EPN normal prostate epithelial cells, by calculating combination index (CI), caspase 3/7 activation and colony formation assays as well as on tumor spheroids and microtissues scored with luminescence 3D-cell viability assay. Cancer stem cells (CSC) compartment was studied evaluating specific markers by RT-PCR, western blotting and flow cytometry as well as by limiting dilution assay. Cholesterol content was evaluated by 1H-NMR. Overexpression of wild-type YAP and constitutively active YAP5SA were obtained by lipofectamine-based transfection and evaluated by immunofluorescence, western blotting and RT-PCR. 22Rv1 R_39 docetaxel resistant cells were selected by stepwise exposure to increasing drug concentrations. In vivo experiments were performed on xenograft models of DU145R80, 22Rv1 parental and docetaxel resistant cells, in athymic mice.

Results
We demonstrated the capacity of the combined approach to target CSC compartment by a novel molecular mechanism based on the inhibition of YAP oncogene via concurrent modulation of mevalonate pathway and AMPK. Because both CSCs and YAP activation have been associated with chemo-resistance, we tested if the combined approach can potentiate docetaxel, a standard of care in mCRCP treatment. Indeed, we demonstrated, both in vitro and in vivo models, the ability of valproic acid/simvastatin combination to sensitize mCRPC cells to docetaxel and to revert docetaxel-resistance, by mevalonate pathway/YAP axis modulation.

Conclusion
Overall, mCRPC progression and therapeutic resistance driven by CSCs via YAP, can be tackled by the combined repurposing of two generic and safe drugs, an approach that warrants further clinical development in this disease.
Recommendations from the Italian Society of Pediatric Orthopaedics and Traumatology for the management of pediatric orthopaedic patients during the COVID19 pandemic and post-pandemic period in Italy
Authors: Trisolino Giovanni , Origo Carlo Enrico , De Sanctis Nando , Dibello Daniela , Farsetti Pasquale , Gigante Cosimo , Guida Pasquale , Marengo Lorenza , Panuccio Elena , Toniolo Renato Maria , Verdoni Fabio , Memeo Antonio 
Published: October 2020

AbstractThe rapid spread of the COVID-19 outbreak in Italy has dramatically impacted the National Healthcare System, causing the sudden congestion of hospitals, especially in Northern Italy, thus imposing drastic restriction of almost all routine medical care. This exceptional adaptation of the Italian National Healthcare System has also been felt by non-frontline settings such as Pediatric Orthopaedic Units, where the limitation or temporary suspension of most routine care activities met with a need to maintain continuity of care and avoid secondary issues due to the delay or suspension of the routine clinical practice. The Italian Society of Pediatric Orthopaedics and Traumatology formulated general and specific recommendations to face the COVID-19 outbreak, aiming to provide essential care for children needing orthopaedic treatments during the pandemic and early post-peak period, ensure safety of children, caregivers and healthcare providers and limit the spread of contagion.
Effects of visualization of successful revascularization on chest pain and quality of life in chronic coronary syndrome: study protocol for the multi-center, randomized, controlled PLA-pCi-EBO-pilot-trial
Authors: Wester Michael , Koll Franziska , Zeman Florian , Dempfle Astrid , Koller Michael , Frey Norbert , Maier Lars S. , Sossalla Samuel 
Published: October 2020

Abstract
Background
Stable coronary artery disease (CAD), recently termed chronic coronary syndrome (CCS), is a highly prevalent disease. Current treatment strategies often include a relevant placebo effect. The hypothesis is that visual angiographic demonstration of the coronary arteries before and after successful percutaneous coronary intervention (PCI) by itself reduces the symptom burden of stable CAD/CCS.

Design and methods
The PLA-pCi-EBO-pilot-trial is a prospective, multi-center, randomized, controlled investigator-initiated pilot trial to study the effect of visual demonstration of successful PCI on quality of life (QoL) and angina pectoris (AP) in patients with symptomatic stable CAD/CCS. All patients with stable CAD/CCS and successful PCI will be screened. One hundred forty four patients with a frequency of AP ≥ 2/week will be randomized 1:1 stratified for AP frequency > 1/day. The control group will receive the common written procedural report on the procedure. Patients in the intervention group will additionally be given a printout picture of their coronary angiogram both before and after PCI. Primary endpoints are change in the Seattle Angina Questionnaire (SAQ)-derived QoL score 1 and 6 months after PCI. Secondary endpoints are changes in other SAQ-derived scores and dyspnea (NYHA score) 1 and 6 months after PCI.

Discussion
The PLA-pCi-EBO-pilot-trial evaluates the effect of visual angiographic result demonstration on disease symptoms and QoL in patients with stable CAD/CCS on top of PCI. A positive outcome of our study would encourage the routine use of angiographic picture demonstration and has thus the potential to change daily routine in the catheterization laboratory.

Trial registration
German Clinical Trials Register DRKS00017524. Registered on 5 July 2019
The TOPSY pessary self-management intervention for pelvic organ prolapse: a study protocol for the process evaluation
Authors: Bugge Carol , Kearney Rohna , Dembinsky Melanie , Khunda Aethele , Graham Margaret , Agur Wael , Breeman Suzanne , Dwyer Lucy , Elders Andrew , Forrest Mark , Goodman Kirsteen , Guerrero Karen , Hemming Christine , Mason Helen , McClurg Doreen , Melone Lynn , Norrie John , Thakar Ranee , Hagen Suzanne 
Published: October 2020

Abstract
Background
Process evaluations have become a valued component, alongside clinical trials, of the wider evaluation of complex health interventions. They support understanding of implementation, and fidelity, related to the intervention and provide valuable insights into what is effective in a practical setting by examining the context in which interventions are implemented. The TOPSY study consists of a large multi-centre randomised controlled trial comparing the effectiveness of pessary self-management with clinic-based care in improving women’s condition-specific quality of life, and a nested process evaluation. The process evaluation aims to examine and maximise recruitment to the trial, describe intervention fidelity and explore participants’ and healthcare professionals’ experiences.

Methods
The trial will recruit 330 women from approximately 17 UK centres. The process evaluation uses a mixed-methods approach. Semi-structured interviews will be conducted with randomised women (18 per randomised group/n = 36), women who declined trial participation but agreed to interview (non-randomised women) (n = 20) and healthcare professionals recruiting to the trial (n ~ 17) and delivering self-management and clinic-based care (n ~ 17). The six internal pilot centres will be asked to record two to three recruitment discussions each (total n = 12–18). All participating centres will be asked to record one or two self-management teaching appointments (n = 30) and self-management 2-week follow-up telephone calls (n = 30). Process data (quantitative and qualitative) will be gathered in participant completed trial questionnaires. Interviews will be analysed thematically and recordings using an analytic grid to identify fidelity to the intervention. Quantitative analysis will be predefined within the process evaluation analysis plan.

Discussion
The wide variety of pessary care delivered across the UK for women with pelvic organ prolapse presents specific localised contexts in which the TOPSY interventions will be implemented. Understanding this contextual variance is central to understanding how and in what circumstances pessary self-management can be implemented (should it be effective). The inclusion of non-randomised women provides an innovative way of collecting indispensable information about eligible women who decline trial participation, allowing broader contextualisation and considerations of generalisability of trial findings. Methodological insights from examination of recruitment processes and mechanisms have the potential to inform recruitment mechanisms and future recruitment strategies and study designs.

Trial registration
ISRCTN62510577. Registered on 6 October 2017.
Clinical and cost-effectiveness of vaginal pessary self-management compared to clinic-based care for pelvic organ prolapse: protocol for the TOPSY randomised controlled trial
Authors: Hagen Suzanne , Kearney Rohna , Goodman Kirsteen , Melone Lynn , Elders Andrew , Manoukian Sarkis , Agur Wael , Best Catherine , Breeman Suzanne , Dembinsky Melanie , Dwyer Lucy , Forrest Mark , Graham Margaret , Guerrero Karen , Hemming Christine , Khunda Aethele , Mason Helen , McClurg Doreen , Norrie John , Karachalia-Sandri Anastasia , Thakar Ranee , Bugge Carol 
Published: October 2020

Abstract
Background
Pelvic organ prolapse (or prolapse) is a common condition in women where the pelvic organs (bladder, bowel or womb) descend into the vagina and cause distressing symptoms that adversely affect quality of life. Many women will use a vaginal pessary to treat their prolapse symptoms. Clinic-based care usually consists of having a pessary fitted in a primary or secondary care setting, and returning approximately every 6 months for healthcare professional review and pessary change. However, it is possible that women could remove, clean and re-insert their pessary themselves; this is called self-management. This trial aims to assess if self-management of a vaginal pessary is associated with better quality of life for women with prolapse when compared to clinic-based care.

Methods
This is a multicentre randomised controlled trial in at least 17 UK centres. The intervention group will receive pessary self-management teaching, a self-management information leaflet, a follow-up phone call and access to a local telephone number for clinical support. The control group will receive the clinic-based pessary care which is standard at their centre. Demographic and medical history data will be collected from both groups at baseline. The primary outcome is condition-specific quality of life at 18 months’ post-randomisation. Several secondary outcomes will also be assessed using participant-completed questionnaires. Questionnaires will be administered at baseline, 6, 12 and 18 months’ post-randomisation. An economic evaluation will be carried out alongside the trial to evaluate cost-effectiveness. A process evaluation will run parallel to the trial, the protocol for which is reported in a companion paper.

Discussion
The results of the trial will provide robust evidence of the effectiveness of pessary self-management compared to clinic-based care in terms of improving women’s quality of life, and of its cost-effectiveness.

Trial registration
ISRCTN Registry ISRCTN62510577. Registered on June 10, 2017.
Associations between pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in women with polycystic ovary syndrome
Authors: Zhang Lirui , Zheng Wei , Liu Cheng , Liang Xin , Zhang Li , Tian Zhihong , Li Guanghui 
Published: October 2020

Abstract
Background
The influence of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on perinatal outcomes of women with polycystic ovary syndrome (PCOS) remains unclear. Therefore, we explored how the above indicators influence pregnancy outcomes in women with PCOS.

Methods
A retrospective study was conducted involving the baseline characteristics, laboratory data, and pregnancy outcomes of 722 pregnant women with PCOS. Subjects were grouped in a way to find out risks in their pregnancy outcomes. Multivariable logistic regression analysis was performed to investigate how BMI and GWG were associated with perinatal outcomes.

Results
Among women with PCOS, underweight increased the risk of small for gestational age (SGA) (OR 12.35, 95% CI 3.56–42.82), but reduced the risk of large for gestational age (LGA). Overweight but not obese women were more susceptible to developing preeclampsia (PE) than women with normal weight. In PCOS women with BMI < 25 kg/m2 before pregnancy, inadequate GWG was a protective factor for gestational hypertension (GH) and postpartum hemorrhage (PPH), excessive GWG exhibited a positive correlation with LGA. But in PCOS women with BMI ≥ 25 kg/m2, excessive GWG increased the probability of undergoing a cesarean section. Inadequate GWG did not reduce the likelihood of LGA in women with BMI ≥ 25 kg/m2, and excessive GWG did not reduce the probability of SGA in women with BMI < 25 kg/m2.

Conclusion
The impacts of pre-pregnancy BMI, GWG on maternal and infant outcomes among PCOS women are similar to reported results in general pregnant women. However, some unique trends were also observed in PCOS women. While the underweight factor significantly increased the risk of SGA birth, overweight but not obesity was correlated with the risk of PE. Inadequate GWG was a protective factor for GH and PPH only in women with pregestational BMI < 25 kg/m2. Inadequate GWG did not reduce the probability of LGA in women with BMI ≥ 25 kg/m2, and similarly, excessive GWG did not reduce the probability of SGA in women with BMI < 25 kg/m2. Overall, these findings indicate that women with PCOS should begin weight management before pregnancy.