bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definitive Repair of Injuries to the Liver During Initial Trauma Laparotomy
Authors: Hashavia Eyal , Goldstein Adam Lee , Nachmany Ido , Shimonov Abigail , Klausner Joseph M. , Soffer Dror 
Published: December 2020

Introduction Numerous surgical approaches and hemostatic techniques are used and have been described when operating on the traumatized liver. Despite a substantial decline in operative liver trauma, there still remains a debate on the optimal surgical approach, and goals, during the initial trauma laparotomy. Hepatic resection during the first operation, including the damage control settings, is advocated and practiced in only a select few institutions and remains highly controversial. Here, we describe our success with hepatic resection, repair, and/or hepatic vascular repair, during the trauma laparotomy with our emphasis on the collaboration between the trauma and hepatobiliary surgical teams. Case Series From 207 patients with liver injuries during the study period, 7 patients had definitive liver resection or repair during the initial trauma laparotomy. One had hepatic tissue repair, 1 had hepatic vein repair, and 5 had liver resections. All the operations involved a hepatobiliary surgeon together with the trauma team. There were no fatalities in the liver operation group, no sepsis, or need for emergent angiography because of hemorrhage. Four patients needed endoscopic retrograde cholangiopancreatography (ERCP) and stenting because of biliary leak. Three patients were discharged home and 4 to rehabilitation. Discussion Hepatic resection, and/or definitive hepatic repair, may be safe and beneficial to the patients during the initial operation even in a damage control setting when the patients’ overall condition allows. We emphasize the benefit of collaboration with experienced and trained liver surgery, especially in lower volume trauma centers. ERCP is commonly needed for postoperative biliary leak and should be readily utilized.
Layla’s Got You: Developing a tailored contraception chatbot for Black and Hispanic young women
Authors: Bonnevie Erika , Lloyd Tiffany D , Rosenberg Sarah D , Williams Kara , Goldbarg Jaclyn , Smyser Joe 
Published: December 2020

Introduction: In Onondaga County, New York, around half of all births to Black and Hispanic teenage girls are unintended. The Layla’s Got You campaign consists of a chatbot and social media campaign designed to increase contraception knowledge among 16- to 25-year-old Black and Hispanic women in Onondaga County. Methods: The campaign was co-created with local women in the target audience and employed digital and grassroots community building strategies. Focus groups were conducted among 31 women, during which participants selected the campaign’s logo and chatbot name and created the tagline. Participants reviewed chatbot responses and designed Layla’s appearance and features, and Black/Hispanic women are featured in website and promotional photos. A community campaign manager pairs digital strategies with grassroots partnerships among a diverse group of stakeholders, including social media influencers, hair salons and health clinics. Results: Since implementation, the chatbot has received 4,390 messages related to contraception or sexual health. Across social media accounts, the campaign has showed 2,483,683 impressions, average daily reach of 1,710 for Facebook and 943 for Instagram, and 32,816 total engagements across all platforms. Conclusion: Layla’s Got You provides young women with a confidential place in which to find locally tailored and trustworthy information about contraception. By merging innovative technology-driven strategies, participatory creation techniques and grassroots community building, the initiative delivers impactful, easily updated health information on a large scale. This strategy has promising implications for increasing knowledge and positive attitudes towards contraception among specific at-risk audiences.
Methodology for Development of a Community Level Intervention Module for Physical Illness in Persons with Mental Illness (CLIPMI)
Authors: Govindan Ramanujam , Rangaswamy Thara , John Sujit , Kandasamy Sunitha 
Published: December 2020

Background and Objectives: Medical illnesses seen in persons with psychiatric disorders are important but often ignored causes of increased morbidity and mortality. Hence, a community level intervention program addressing the issue is proposed. Materials and Methods: Patients with severe mental illnesses will be identified by a door-to-door survey and assessed for comorbid physical illnesses like anemia, hypertension, diabetes, and so on. They will then be randomized into two groups. The treatment as usual (TAU) group will not receive intervention from the trained community level workers, while the Intervention group will receive it. Results: The two groups will be compared for the prevalence and severity of comorbid physical illnesses. The expected outcome is compared to the TAU group, the intervention group will have a greater reduction in the morbidity due to physical illnesses and improved mental health. Conclusion: If successful, the module can be incorporated into the community level mental health delivery system of the District Mental Health Program (DMHP).
A meta-ethnographic study of fathers’ experiences of caring for a child with a life-limiting illness
Authors: Postavaru Gianina-Ioana , Swaby Helen , Swaby Rabbi 
Published: December 2020

Background: There is a growing body of qualitative studies examining parents’ experiences of caring for a child with a life-limiting condition, coinciding with recent evidence that indicates an increasing incidence of paediatric life-limiting conditions. However, research focusing on fathers’ needs remains sparse and is often diluted among a predominant ‘mother’s voice’, raising questions about whether practices in clinical settings meet fathers’ needs. Aim: To provide an in-depth assembly of the current state of knowledge around fathers’ experiences of caring for their children diagnosed with life-limiting conditions and understand the implications for healthcare services and policies. Design: A meta-ethnography was conducted to synthesise findings from existing qualitative studies exploring fathers’ experiences of caring. Data sources: Four electronic databases (PubMed, PsycINFO, CINAHL and Science Direct) were searched up until April 2020. Qualitative studies exploring fathers’ care experience and published in English language were included. The Critical Appraisal Skills Programme (CASP) checklist was employed for study quality appraisal. No temporal limits were used. Results: Sixty-three studies met the inclusion criteria. Thirty life-limiting conditions were included. Based on responses from 496 fathers, a conceptual model was developed which translates key experiences within the fathers’ caregiving journeys. The overarching concepts identified were: the paradox of support, challenges in the caring process, ‘nobody thinks of men’, impact on family life and the fall of the curtain: an irrevocably altered world. These and associated sub-concepts are discussed, with recommendations for future research and practice provided. Conclusion: The findings indicate the value of a family-oriented approach to develop psychosocial interventions and support channels for fathers, thus empowering them whilst reducing the care-giving burden on the family unit.
Preplanned participation of paramedics in end-of-life care at home: A retrospective cohort study
Authors: Surakka Leena K , Peake Minna M , Kiljunen Minna M , Mäntyselkä Pekka , Lehto Juho T 
Published: December 2020

Background: Paramedics commonly face acute crises of patients in palliative care, but their involvement in end-of-life care is not planned systematically. Aim: To evaluate a protocol for end-of-life care at home including pre-planned integration of paramedics and end-of-life care wards. Design: Paramedic visits to patients in end-of-life care protocol were retrospectively studied. Setting/Participants: All of the patients who had registered for the protocol between 1 March 2015 and 28 February 2017 in North Karelia, Finland, were included in this study. Results: A total of 256 patients were registered for the protocol and 306 visits by paramedic were needed. A need for symptom control (38%) and transportation (29%) were the most common reasons for a visit. Paramedics visited 43% and 70% of the patients in areas with and without 24/7 palliative home care services, respectively ( p < 0.001); while 58% of all the visits were done outside of office hours. Problems were resolved at home in 31% of the visits. The patient was transferred to a pre-planned end-of-life care ward and to an emergency department in 48% and 16% of the cases, respectively. More patients died in end-of-life care wards in areas without (54%) than with (33%) 24/7 home care services ( p = 0.001). Conclusions: Integration of paramedics into end-of-life care at home is reasonable especially in rural areas without 24/7 palliative care services and outside of office hours. The majority of patients can be managed at home or with the help of an end-of-life care ward without an emergency visit.
Postcardiotomy mechanical support in patients with mitral valve prostheses is associated with poor survival
Authors: Pingpoh Clarence , Salama Alaa , Diab Nawras , Kreibich Maximillian , Puiu Paul , Czerny Martin , Benk Christoph , Beyersdorf Friedhelm , Siepe Matthias 
Published: December 2020

Aims: To elaborate on early survival in patients with mitral valve replacement requiring temporary extracorporeal life support system (ECLS). Methods: We analyzed survival, significant bleeding, wound infection, and ECLS duration in 421 from 14,400 patients with postoperative need for ECLS from January 2008 to December 2017 at our institution. Finally, patients were stratified according to the type of surgery performed: the mitral group (mitral valve replacement) n = 63 and the control group (any cardiac surgery excluding the mitral valve) n = 358. In order to adjust for preoperative patient characteristics, a propensity matching analysis was performed. Differences in in-hospital mortality were analyzed accordingly. Results: In-hospital mortality was significantly higher in the mitral group as compared to the control group before and after adjustment ( p < 0.001). Median duration of ECLS was 4 days in both groups. Perioperative bleeding ( p < 0.001) and wound infection ( p < 0.001) also showed significant worse outcome parameters in the mitral group. The main causes of death in the mitral group were multiorgan failure, n = 48 (76%), stroke, n = 7 (12%), and intracardiac thrombus formation, n = 5 (10%). Conclusions: ECLS is associated with a high in-hospital mortality rate in patients after mitral valve replacement.
Low intratumor heterogeneity correlates with increased response to PD-1 blockade in renal cell carcinoma
Authors: Ran Xia , Xiao Jinyuan , Zhang Yi , Teng Huajing , Cheng Fang , Chen Huiqian , Zhang Kaifan , Sun Zhongsheng 
Published: December 2020

Background: Intratumor heterogeneity (ITH) has been shown to be inversely associated with immune infiltration in several cancers including clear cell renal cell carcinoma (ccRCC), but it remains unclear whether ITH is associated with response to immunotherapy (e.g. PD-1 blockade) in ccRCC. Methods: We quantified ITH using mutant-allele tumor heterogeneity, investigated the association of ITH with immune parameters in patients with ccRCC ( n = 336) as well as those with papillary RCC (pRCC, n = 280) from The Cancer Genome Atlas, and validations were conducted in patients with ccRCC from an independent cohort ( n = 152). The relationship between ITH and response to anti-PD-1 immunotherapy was explored in patients with metastatic ccRCC from a clinical trial of anti-PD-1 therapy ( n = 35), and validated in three equal-size simulated data sets ( n = 60) generated by random sampling with replacement based on this clinical trial cohort. Results: In ccRCC, low ITH was associated with better survival, more reductions in tumor burden, and clinical benefit of anti-PD-1 immunotherapy through modulating immune activity involving more neoantigens, elevated expression of HLA class I genes, and higher abundance of dendritic cells. Furthermore, we found that the association between the level of ITH and response to PD-1 blockade was independent of the mutation status of PBRM1 and that integrating both factors performed better than the individual predictors in predicting the benefit of anti-PD-1 immunotherapy in ccRCC patients. In pRCC, increased immune activity was also observed in low- versus high-ITH tumors, including higher neoantigen counts, increased abundance of monocytes, and decreased expression of PD-L1 and PD-L2. Conclusions: ITH may be helpful in the identification of patients who could benefit from PD-1 blockade in ccRCC, and even in pRCC where no genomic metrics has been found to correlate with response to immune checkpoint inhibitors.
Causes of delayed exploration of the acute scrotum in a regional tertiary centre
Authors: Storey Benjamin , Shugg Nathan , Blatt Alison 
Published: December 2020

Background: Testicular torsion is an organ-threatening surgical emergency with a limited timeframe for intervention. Objective: To identify the delays to surgical exploration of patients with an acute scrotum in a tertiary hospital to prevent adverse outcomes associated with this time critical emergency. Methods: A retrospective review of medical records for all patients who underwent scrotal exploration for acute scrotal pain in a tertiary hospital in regional New South Wales between January 2008 to December 2018 was performed. Results: Retrospective review identified 242 patients, of whom 161 had testicular torsion and 56 resultant orchidectomies. No statistically significant difference in pre-hospital delays between paediatric or adult populations was found. The average time from presentation to theatre was 4 h 36 min. Patients who were delayed > 6 h from presentation to surgical exploration had significantly increased rates of orchidectomy. Delays that significantly affected rates of orchidectomy were transfer from peripheral sites, late presentation, misdiagnosis and representation after discharge. Conclusion: The most common reason for delay was diagnostic error with the patient later re-presenting to hospital. Patient transfer from the primary hospital to a tertiary institution and subsequent delayed surgical exploration also contributed to significantly higher rates of orchidectomy. Level of Evidence: 3
Long-term follow-up of Holmium-YAG laser vaporisation of bladder urothelial carcinoma
Authors: Bazo Alvaro , Gowda Arjun , Yao Henry Han-I , Radcliffe Robert , Goodall Phillip , Green William , Sherwood Benedict 
Published: December 2020

Introduction: Many patients with non-muscle invasive bladder cancer (NMIBC) will develop recurrences of their tumour after their first resection. Flexible cystoscopy under local anaesthesia with Holmium-YAG laser ablation of tumour (FHoLAT) is safe, well tolerated procedure with significant cost savings when compared to cystoscopy under general or regional anaesthesia. We retrospectively analysed the outcomes of a large series of patients undergoing FHoLAT at our institution between April 2006 and September 2013. Patients and methods: Patients were offered FHoLAT if the tumour recurrence was small and/or they were deemed unfit for regional or general anaesthesia. Patient data was extracted from medical records. The primary outcomes were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS) and recurrence-free survival (RFS). Results: 232 patients with a total 522 FHoLAT procedures were included. The median follow-up was 74.8 (43.5–101) months; 18% were discharged after a recurrence free follow-up duration; 52.2% had one FHoLAT, 19.8% had two FHoLATs, 11.2% had three FHoLATs and 16.8% had four or more FHoLAT. At initial diagnosis 24.1% of patients had G1pTa, 47% G2pTa, 9.9% G3pTa and T1 in 18.9%. 4.3% had concurrent carcinoma in situ. At 10 years, OS was 47.4%, CSS was 94.1%, PFS was 82.1%, RFS was 15.8%. Conclusions: FHoLAT for bladder tumour recurrences has an acceptable CSS and PFS for patients with small low-grade tumours or patients with high-grade or T1 tumours who are unfit for regional or general anaesthesia. The role of FHoLAT in unfit patients seems clear, but further prospective trials are needed to define its role in other patient groups, particularly high-grade NMIBC. Level of evidence: 3b-4
Notch signaling promotes disease initiation and progression in murine chronic lymphocytic leukemia
Authors: Tardivon Delphine , Antoszewski Mateusz , Zangger Nadine , Nkosi Marianne , Sordet-Dessimoz Jessica , Hendriks Rudi , Koch Ute , Radtke Freddy 
Published: December 2020

AbstractNOTCH1 gain-of-function mutations are recurrent in B-cell chronic lymphocytic leukemia (B-CLL), where they are associated with accelerated disease progression and refractoriness to chemotherapy. The specific role of NOTCH1 in the development and progression of this malignancy is unclear. Here, we assess the impact of loss of Notch signaling and pathway hyperactivation in an in vivo mouse model of CLL (IgH.TEμ) that faithfully replicates many features of the human pathology. Ablation of canonical Notch signaling using conditional gene inactivation of RBP-J in immature hematopoietic or B-cell progenitors delayed CLL induction and reduced incidence of mice developing disease. In contrast, forced expression of a dominant active form of Notch resulted in more animals developing CLL with early disease onset. Comparative analysis of gene expression and epigenetic features of Notch gain-of-function and control CLL cells revealed direct and indirect regulation of cell cycle–associated genes, which led to increased proliferation of Notch gain-of-function CLL cells in vivo. These results demonstrate that Notch signaling facilitates disease initiation and promotes CLL cell proliferation and disease progression.
Subsequent malignant neoplasms among children with Hodgkin lymphoma: a report from the Children’s Oncology Group
Authors: Giulino-Roth Lisa , Pei Qinglin , Buxton Allen , Bush Rizvan , Wu Yue , Wolden Suzanne L. , Constine Louis S. , Kelly Kara M. , Schwartz Cindy L. , Friedman Debra L. 
Published: December 2020

Abstract
Survivors of Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMNs). Response-adapted treatment may decrease this risk by reducing exposure to therapy associated with SMN risk. The Children’s Oncology Group study AHOD0031 evaluated response-adapted therapy for children and adolescents with intermediate-risk HL. We report the SMNs among 1711 patients enrolled in AHOD0031. Patients were treated with 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without involved-field radiation therapy (RT). Patients with a slow early response to initial chemotherapy were randomized to 2 additional cycles of dexamethasone, etoposide, cisplatin and cytarabine or no additional chemotherapy, and all received RT. At a median follow-up of 7.3 years, an analysis of SMNs was performed. The 10-year cumulative incidence of SMN was 1.3% (95% confidence interval [CI], 0.6-2.0). SMNs included 3 patients with acute myeloid leukemia (AML), 11 with solid tumors, and 3 with non-Hodgkin lymphoma. Sixteen of 17 patients with an SMN had received combined modality therapy. The standardized incidence ratio for SMN was 9.5 (95% CI, 4.5-15.2) with an excess absolute risk of 1.2 per 1000 person-years. The cumulative incidence of SMNs was higher among patients who received RT (P = .037). In multivariate analysis, RT, B symptoms, and race were associated with SMN risk. Given the latency from exposure, we have likely captured all cases of secondary leukemia and myelodysplastic syndrome (MDS). Longer follow-up is needed to determine the risk of solid tumors. Avoidance of RT without sacrificing disease control should remain a goal for future therapeutic approaches. This trial was registered at www.clinicaltrials.gov as #NCT00025259.
To portray clonal evolution in blood cancer, count your stem cells
Authors: Lyne Anne-Marie , Laplane Lucie , Perié Leïla 
Published: December 2020

Abstract
Clonal evolution, the process of expansion and diversification of mutated cells, plays an important role in cancer development, resistance, and relapse. Although clonal evolution is most often conceived of as driven by natural selection, recent studies uncovered that neutral evolution shapes clonal evolution in a significant proportion of solid cancers. In hematological malignancies, the interplay between neutral evolution and natural selection is also disputed. Because natural selection selects cells with a greater fitness, providing a growth advantage to some cells relative to others, the architecture of clonal evolution serves as indirect evidence to distinguish natural selection from neutral evolution and has been associated with different prognoses for the patient. Linear architecture, when the new mutant clone grows within the previous one, is characteristic of hematological malignancies and is typically interpreted as being driven by natural selection. Here, we discuss the role of natural selection and neutral evolution in the production of linear clonal architectures in hematological malignancies. Although it is tempting to attribute linear evolution to natural selection, we argue that a lower number of contributing stem cells accompanied by genetic drift can also result in a linear pattern of evolution, as illustrated by simulations of clonal evolution in hematopoietic stem cells. The number of stem cells contributing to long-term clonal evolution is not known in the pathological context, and we advocate that estimating these numbers in the context of cancer and aging is crucial to parsing out neutral evolution from natural selection, 2 processes that require different therapeutic strategies.
Therapeutic inhibition of HIF-2α reverses polycythemia and pulmonary hypertension in murine models of human diseases
Authors: Ghosh Manik C. , Zhang De-Liang , Ollivierre Wade H. , Noguchi Audrey , Springer Danielle A. , Linehan W. Marston , Rouault Tracey A. 
Published: December 2020

AbstractPolycythemia and pulmonary hypertension are 2 human diseases for which better therapies are needed. Upregulation of hypoxia-inducible factor-2α (HIF-2α) and its target genes, erythropoietin (EPO) and endothelin-1, causes polycythemia and pulmonary hypertension in patients with Chuvash polycythemia who are homozygous for the R200W mutation in the von Hippel Lindau (VHL) gene and in a murine mouse model of Chuvash polycythemia that bears the same homozygous VhlR200W mutation. Moreover, the aged VhlR200W mice developed pulmonary fibrosis, most likely due to the increased expression of Cxcl-12, another Hif-2α target. Patients with mutations in iron regulatory protein 1 (IRP1) also develop polycythemia, and Irp1-knockout (Irp1-KO) mice exhibit polycythemia, pulmonary hypertension, and cardiac fibrosis attributable to translational derepression of Hif-2α, and the resultant high expression of the Hif-2α targets EPO, endothelin-1, and Cxcl-12. In this study, we inactivated Hif-2α with the second-generation allosteric HIF-2α inhibitor MK-6482 in VhlR200W, Irp1-KO, and double-mutant VhlR200W;Irp1-KO mice. MK-6482 treatment decreased EPO production and reversed polycythemia in all 3 mouse models. Drug treatment also decreased right ventricular pressure and mitigated pulmonary hypertension in VhlR200W, Irp1-KO, and VhlR200W;Irp1-KO mice to near normal wild-type levels and normalized the movement of the cardiac interventricular septum in VhlR200Wmice. MK-6482 treatment reduced the increased expression of Cxcl-12, which, in association with CXCR4, mediates fibrocyte influx into the lungs, potentially causing pulmonary fibrosis. Our results suggest that oral intake of MK-6482 could represent a new approach to treatment of patients with polycythemia, pulmonary hypertension, pulmonary fibrosis, and complications caused by elevated expression of HIF-2α.