bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevance of Minimal Residual Disease in the Era of Targeted Agents
Authors: Heltai Silvia , Ghia Paolo , Scarfò Lydia 
Published: November 2019

Abstract
The evaluation of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) has evolved in parallel with the enormous progresses in the therapeutic armamentarium and the application of cutting-edge diagnostic techniques the CLL community witnessed in the past few years. Minimal residual disease is considered an objective measure of disease status defined by the number of residual leukemic cells detected in a sample of peripheral blood and/or bone marrow as proportion of the total white blood cells and defined undetectable if fewer than 1 CLL cell among 10,000 white blood cells (10−4 or 0.01%) is detected. In this review, we aim at shedding light on how to evaluate MRD, what we already know about MRD from the experience with chemoimmunotherapy, and why MRD evaluation remains still relevant in the era of targeted agents.
Targeted Therapy in Chronic Lymphocytic Leukemia
Authors: Kipps Thomas J. , Choi Michael Y. 
Published: November 2019

Abstract
Despite a prevailing view that advances in cancer therapy will come through selective targeting of enzymes encoded by mutated oncogenes responsible for the neoplastic phenotype, recent advances in the treatment of patients with chronic lymphocytic leukemia (CLL) have instead exploited knowledge of its biology. Indeed, CLL cells depend on interactions with cells and soluble factors present in the tumor microenvironment for proliferation and survival. B-cell receptor signaling and chemokine-receptor signaling play prominent roles. Elucidation of these signaling pathways has defined physiologic targets for drugs, such as ibrutinib, which inhibit Bruton tyrosine kinase and are therapeutically effective. The characteristic high-level expression of BCL2 in CLL that can enhance leukemia-cell survival has now become an Achilles heel targeted by clinically effective drugs such as venetoclax. Here we discuss advances in such targeted therapy and highlight other disease attributes, such as the distinctive expression of ROR1, which may be targeted for clinical benefit, alone or in combination with other targeted therapies.
The Impact of Microsurgery on the Treatment of Ring Avulsion Injuries
Authors: Chiu David T. W. , Matthew Michael K. , Patel Anup 
Published: November 2019

Background:
Treating ring avulsion injuries continues to challenge the reconstructive hand surgeon. The complex operation draws from plastic surgery and orthopedic surgery principles to provide soft-tissue coverage, skeletal fixation, tendon repair, and neurovascular reconstruction. Furthermore, the application of microsurgical techniques has enabled the revascularization and replantation of completely avulsed fingers.

Methods:
A retrospective review of 22 consecutive ring avulsion injuries (seven amputations, five replantations, and 10 revascularizations) from 1987 to 2015 performed by a single senior surgeon (D.T.W.C.) was conducted.

Results:
Of these 22 ring avulsions, 10 revascularizations, five replantations, and seven amputations (five because of clinical factors, and two because of patient request) were performed. None of the 15 replantations and revascularizations resulted in loss of the ring finger or necrosis of the revascularized tip.

Conclusions:
With proper patient selection, appropriate level of injury identification, and meticulous surgical execution, the restoration of form and function to the hand is feasible in ring avulsion injuries.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Fat Grafting for the Treatment of Scleroderma
Authors: Strong Amy L. , Rubin J. Peter , Kozlow Jeffrey H. , Cederna Paul S. 
Published: November 2019

Background:
Scleroderma is a chronic connective tissue disease that results in fibrosis of the skin and internal organs. Although internal organ involvement corresponds with poor prognosis, systemic agents are effective at improving the effects of scleroderma on internal organs. In contrast, skin manifestations are universally present in all patients diagnosed with scleroderma, yet no systemic agents have been shown to be successful. Fat grafting has been shown to improve skin quality and improve contour irregularities and may be helpful in the treatment of patients with scleroderma.

Methods:
The authors performed a thorough review of the pathophysiology of scleroderma and the current treatment options for scleroderma. The efficacy of fat grafting for the treatment of scleroderma and the mechanism by which fat grafting improves outcomes was also discussed.

Results:
Scleroderma is characterized by chronic inflammation and vascular compromise that leads to fibrosis of the skin and internal organs. Fat grafting has recently been the focus of significant basic science research. It has been shown to reduce inflammation, reduce fibrosis by limiting extracellular matrix proteins and increasing collagenase activity, and provide structural support through stem cell proliferation and differentiation. The adipocytes, adipose stem cells, endothelial cells, and vascular smooth muscle cells in the processed fat likely contribute to the effectiveness of this treatment.

Conclusions:
Fat grafting in scleroderma patients likely improves skin manifestations by recreating fullness, correcting contour deformities, and improving skin quality. The injected fat provides a mixture of cells that influences the recipient site, resulting in improved outcomes.
Crowdsourcing Methods to Enhance HIV and Sexual Health Services: A Scoping Review and Qualitative Synthesis
Authors: Wu Dan , Ong Jason J. , Tang Weiming , Ritchwood Tiarney D. , Walker Jennifer S. , Iwelunmor Juliet , Tucker Joseph D. 
Published: November 2019

Background:
Crowdsourcing is increasingly used to improve community engagement in HIV and sexual health research. In this scoping review, we reviewed studies using crowdsourcing approaches in HIV and sexual health research to identify strengths, opportunities for expansion, and limitations of such approaches.

Methods:
We searched CINAHL, Web of Science, Embase, and PubMed. Studies were included if they involved crowdsourcing activities, were in the field of HIV or sexual health, and described the methodology in sufficient detail. We conducted a qualitative synthesis of eligible articles.

Results:
Our search strategy yielded 431 nonduplicate articles. After screening, 16 articles met the inclusion criteria, including 4 publications that described research from high-income countries, 7 from middle-income countries, 1 from a low-income country, and 4 that had a global focus. There were 4 categories of crowdsourcing: open contests, hackathons, open forums, and incident reporting systems. We identified common phases for data acquisition and dissemination: (1) preparation; (2) problem framing and crowd solicitation; (3) judging submissions; and (4) sharing selected submissions. Strengths of using crowdsourcing approaches include greater innovation due to crowd heterogeneity, encouragement of multisectoral collaboration, empowerment of vulnerable populations, cost-effectiveness, and relevance to local cultures and styles. Weaknesses among some methods include reliance on the internet, temporal transience, and difficulty in sustaining long-term community engagement.

Conclusions:
Crowdsourcing may be useful for HIV implementation research. Further research on crowdsourcing related to HIV and sexual health is needed.
Implementation Science Using Proctor's Framework and an Adaptation of the Multiphase Optimization Strategy: Optimizing a Financial Incentive Intervention for HIV Treatment Adherence in Tanzania
Authors: Packel Laura , Fahey Carolyn , Njau Prosper , McCoy Sandra I. 
Published: November 2019

Background:
Ambitious targets have been set to end the HIV epidemic by 2030. Such targets assume that tools to end HIV exist and are successfully being deployed across populations, albeit unequally. Implementation science approaches are needed to understand the drivers of disparities and how to bring effective interventions to those most in need. We describe a hybrid implementation science approach, adapting a strategy to facilitate retention and viral suppression (VS) among people living with HIV/AIDS in Tanzania.

Methods/Design:
We used Proctor framework and the multiphase optimization strategy to optimize a cash transfer to improve antiretroviral therapy adherence and VS among people living with HIV/AIDS in Tanzania. This involved 3 trials. The first trial tested the efficacy of cash and food assistance compared with the standard of care in improving antiretroviral therapy adherence among treatment initiators. Cash transfers were superior to the standard of care and noninferior, less expensive, and logistically simpler to implement compared with food. The second trial is dose-finding: identifying the optimal amount of cash for a 20% improvement in VS at 6 months. Before this, components were simplified to maximize reach, align with local policies, and reduce staff time. We assessed implementation science constructs to understand barriers to uptake and sustainability. Trial 3 is a cluster randomized controlled trial, testing the effectiveness of the optimized intervention in multiple settings.

Discussion/Implications:
Our process illustrates the utility of applying multiple implementation science frameworks to arrive at an optimal implementation strategy to bridge the know-do gap with data to show efficacy and maximum potential for scalability and sustainability.
Qualitative Contributions to Implementation Research on HIV Prevention and Treatment
Authors: Ware Norma C. 
Published: November 2019

Background:
The advantages of conducting implementation research as part of the development, as well as delivery and use of HIV prevention and treatment interventions, are increasingly being recognized. Qualitative methods are gaining recognition in implementation-oriented research on HIV as vehicles for examining particular implementation outcomes and for identifying barriers and facilitators to intervention uptake. However, they have more to offer. This article presents 3 case examples illustrating the use of qualitative research to explain intervention processes and outcomes, with the goal of clarifying “how and why” they work.

Methods/Case Examples:
The first example identifies active ingredients in an intervention aimed at improving antiretroviral therapy (ART) adherence. The second proposes an explanation of the processes through which community-based HIV testing with follow-up support may bring about linkage to care and prevention services. The third unpacks the dynamics of a novel strategy of delivering oral pre-exposure prophylaxis and ART to HIV serodiscordant couples, showing how the organization of services positively impacted participating couples, enabling them to use oral pre-exposure prophylaxis and ART effectively to prevent HIV transmission.

Results/Discussion:
Qualitative methods contribute to implementation research for HIV intervention development by (1) offering an alternative to framework-driven investigation, (2) providing tools for understanding user experience of interventions, and (3) developing local explanations of intervention processes and outcomes.

Conclusion:
In various ways, qualitative methods contribute to implementation research by deepening and “thickening” conceptualization of implementation problems. Stronger conceptualizations lead to stronger implementation strategies and, thus, to increased use of evidence-based interventions for HIV prevention and treatment as they are made available to the public worldwide.
Employing the Payback Framework to Assess Implementation Science Research Utilization: Lessons From the USAID's PEPFAR HIV/AIDS Implementation Science Awards
Authors: Castor Delivette , Kimmel Allison L. , McFall Allison , Padian Nancy , Yansaneh Aisha , Wiant Sarah , Sandison Sarah , Holmes Charles , Lucas Rachel , Stanton David , Goosby Eric , Kottiri Benny 
Published: November 2019

Background:
Stakeholders question whether implementation science (IS) is successful in conducting rigorous science that expedites the inclusion of health innovations into policies and accelerates the pace and scale of health service delivery into clinical and public health practice. Using the Payback Framework (PF) for research utilization (RU), we assessed the impact of USAID's IS investment on a subset of studies examining HIV prevention, care, and treatment.

Setting:
Selected USAID-funded IS awards implemented between 2012 and 2017 in 9 sub-Saharan African countries.

Methods:
A modified version of a RU framework, the PF, was applied to 10 USAID-funded IS awards. A semistructured, self-administered/interviewer-administered questionnaire representing operational items for the 5 categories of the modified PF was used to describe the type and to quantify the level of payback achieved. The raw score was tallied within and across the 5 PF categories, and the percentage of “payback” achieved by category was tabulated. Distribution of payback scores was summarized by tertiles.

Results:
Knowledge production had the highest level of payback (75%), followed by benefits to future research (70%), benefits to policy (45%), benefits to health and the health system (18%), and broader economic benefits (5%).

Conclusions:
All awards achieved some level of knowledge production and benefits to future research, but translation to policy and programs was low and variable. We propose the use of policy, health system, and economic monitoring indicators of RU throughout the research process to increase IS studies' impact on health practice, programs, and policy.
Latissimus Dorsi-Myocutaneous Flap in the Repair of Titanium Mesh Exposure and Scalp Defect After Cranioplasty
Authors: Dong Liwei , Dong Yulin , Liu Chaohua , Geng Jian , Liu Hengxin , Pei Jiaomiao , Hao Dongyue , Ma Xianjie , Xia Wensen 
Published: November 2019

Abstract
Titanium mesh was widely used for cranium defect repair but associated with high complication rates. In this study, the authors describe a method using latissimus dorsi-myocutaneous flap in the repair of titanium mesh exposure and scalp defect after cranioplasty, and the plate retaining is also achieved. Fifteen patients from April 2012 to May 2016 underwent this procedure, the age ranged from 32 to 62 years and 47 years old on average, and all the patient had plate exposure combined with surgical site infection and variation of scalp defect. All the patients had fully flap survive, and follow up ranged from 6 months to 24 months, 1 patient had titanium mesh re-expose and received additional operation to remove the plate. The free latissimus dorsi musculocutaneous flap could supply large size of bulky tissue coverage with good blood supply and strong anti-infection ability. This method was an option for retaining the titanium mesh and repairing the exposure for the mild infection with small size scalp defect patient.
Modeling and Clinical Application of Incision Space in Facial Contour Surgery
Authors: Lin Li , Sun Mengzhe , Gao Yuan , Chai Gang , Xu Haisong , Yang Xianxian , Xie Le 
Published: November 2019

Abstract
Virtual simulation surgical system is a good way to develop surgical instruments, make surgical plan, and train surgeons. At present, due to the deformation of intraoperative soft tissue after retraction and the lack of effective data collection, the surgical simulation of facial contour surgery can only be conducted according to the preoperative computed tomography data. Due to the difficulty of obtaining real operative spatial data, it is difficult for the virtual surgery trajectory planning process to yield a good effect on surgeon training. In this study, an optical tracking device was used to record the actual posture of surgical instruments, patient position, and incision space in the surgical environment, so as to construct a more accurate actual surgical space. The clinical data obtained in this study can be used for virtual simulation of surgical instrument movement and osteotomy, as well as selection, planning, and teaching purposes of surgical programs.
Parents’ Experiences of Their Child's Craniosynostosis and the Initial Care Process
Authors: Zerpe Anna Stenson , Nowinski Daniel , Ramklint Mia , Öster Caisa 
Published: November 2019

Abstract
Craniosynostosis is usually diagnosed in early infancy. Treatment almost always involves surgery and care is optimally organized around an interdisciplinary team of specialists at a craniofacial center. This study aimed to investigate Swedish parents’ experiences of having a child with craniosynostosis and their perceptions of the initial care process. Semistructured telephone interviews were conducted with 20 parents (10 fathers and 10 mothers) of children with nonsyndromic craniosynostosis who were undergoing surgery at the Uppsala Craniofacial Center. A thematic data analysis revealed 6 themes presented in a timeline following the parents’ journey from detection of their child's abnormal skull shape to waiting for surgery: Detection of the abnormal skull shape, thoughts, and feelings before the appointment with the craniofacial team, an appointment with the craniofacial team, searching the Internet and social media, waiting for surgery, and suggestions for improvement. Although meeting with the craniofacial team was considered informative, parents expressed concerns about surgery and their infant's long-term prognosis were evident. Most parents had no previous knowledge about craniosynostosis and craniofacial syndromes and wished for more information already at the time of its detection. The Internet was used both at the time of suspicion that something was wrong with the child and later to learn about risks and consequences, alternative treatments and prognosis.
A Modified Method Using Double Computed Tomography Scan Procedure to Maintain Mandibular Width in Mandibular Reconstruction
Authors: Shen Shunyao , Yang Chengshuai , Wu Jinyang , Zhang Lei , Wang Xudong , Shi Jun , Zhang Shilei 
Published: November 2019

Objective:
The purpose of this study was to evaluate the use of a modified template system and double computed tomography scan procedure to maintain mandibular width in cases of mandibular reconstruction.

Study Design:
Ten patients who underwent mandibular reconstruction with a fibular flap were enrolled. The surgeries were planned with a computer-aided surgical simulation (CASS) planning method. Following double computed tomography scan procedure, the template system was designed in a computer and was fabricated using a three-dimensional printing technique. The cutting guides were designed with the holes of the conventional reconstruction plate on the remnant mandibular segments. After surgery, the outcome evaluation was compared by first superimposing the post-operative computed tomography model onto the planned model and then measuring the differences between the planned and actual outcomes.

Results:
All surgeries were completed successfully using the template system. With the use of the templates, the largest linear root-mean-square deviation (RMSD) between the planned and post-operative remnant segments was 1.01 mm, and the largest angular RMSD was 4.05°.

Conclusions:
The authors conclude that this template system and double computed tomography scan procedure provides a reliable method to maintain mandibular width in mandibular reconstruction using a fibular flap.
Hidden Preauricular Sinus as a Cause of Persistent Infection After Facelift
Authors: Lee Da Woon , Choi Hwan Jun , Kim Jun Hyuk , Oh Mee-Hye 
Published: November 2019

Abstract
The facelift is one of the most popular cosmetic surgery methods of antiaging. There are many complications in facelift, but infections rarely occur relatively. The authors would like to introduce a patient who developed infection after a facelift procedure. The cause of the infection was preauricular sinus, one of the congenital anomalies. The patient was treated with complete excision of sinus tract and the patient was treated without any further complications. Based on this clinical report, surgeons performing cosmetic surgery need to be interested in rare congenital lesions such as preauricular sinus.
Therapeutic and Adverse Effects of Thrombomodulin Alfa to Treat Sepsis-Induced Disseminated Intravascular Coagulation
Authors: Imaura Masaharu , Tsumori Miki , Nagase Satoshi , Omura Kazuya , Takahashi Hiroyuki , Hatoyama-Tanaka Saori , Katagiri Fumihiko , Takayanagi Risa , Kanno Hiroshi , Yamada Yasuhiko 
Published: November 2019

ABSTRACT
In the treatment of disseminated intravascular coagulation (DIC), which is a complication of underlying diseases such as infections and malignant tumors, effective plasma concentrations of thrombomodulin (TM) alfa range from 300 to 900 ng/mL; however, appropriate concentrations when treating sepsis-induced DIC are unknown. Thus, our aim was to determine the relationship between plasma concentrations of TM alfa and its therapeutic effects, and hemorrhagic adverse events. First, we calculated the plasma trough concentrations of TM alfa in septic DIC patients. Next, we divided patients into two groups according to their plasma concentrations into a low- and high-concentration group based on a cut-off value of 600 ng/mL. Fourteen and 35 patients were included in the low- and high-concentration groups, respectively. The Japanese Association for Acute Medicine DIC diagnostic criteria score 4 days after TM alfa administration decreased significantly by 2.06 points from baseline in the high-concentration group compared with 0.71 points in the low-concentration group. The 90-day survival rate was significantly higher in the high-concentration group (85.4%) than in the low-concentration group (49.0%) (hazard ratio, 0.27; 95% confidence interval: 0.09–0.86). In contrast, the incidence of serious hemorrhage was not significantly different between the groups. The recommended plasma concentration of TM alfa in the treatment of septic DIC was determined to be higher than 600 ng/mL, and a dose of 380 U/kg (0.06 mg/kg) was necessary to achieve this concentration.