bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of thoracic paraspinal block-propofol intravenous general anesthesia on VEGF and TGF-β in patients receiving radical resection of lung cancer
Authors: Sen Yang , Xiyang Hu , Yu Han
Published: November 2019

The objective of this study is to compare the effects of paravertebral nerve block-propofol intravenous general anesthesia (PPA) and sevoflurane inhalation general anesthesia (SGA) on the expression of serum vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β) in patients undergoing radical resection of lung cancer.

Patients undergoing radical resection of lung cancer were divided into PPA group and SGA group. In PPA group, thoracic paraspinal nerve block was performed with 0.5% ropivacaine (2 mg/kg) before general anesthesia. Anesthesia was maintained with 2.5–3.5 μg/mL TCI of propofol. In SGA group, anesthesia was maintained with 1.0–1.5 MAC sevoflurane. The dosage of opioids during and 24 h after operation, the pain score at 2, 8, 24, 48, and 72 h after operation, and the concentrations of serum VEGF and TGF-β before and 24 h after operation were observed in the two groups.

The intraoperative dosage of remifentanil in PPA group was significantly less than that in SGA group (P < 0.05). The dosage of sufentanil in SGA group was significantly less than that in SGA group at 24 h after operation (P < 0.05). The VAS score at 2, 8, and 24 h after operation was significantly lower than that in SGA group (P < 0.05). The serum VEGF and TGF-β concentration in PPA group was significantly lower than that in SGA group (P < 0.05).

Thoracic paravertebral nerve block-propofol intravenous general anesthesia can reduce the dosage of opioids, improve the effect of postoperative analgesia, and reduce the serum concentration of tumor angiogenesis-related factors in patients undergoing radical resection of lung cancer.
Guillain-Barré syndrome associated with myasthenia gravis
Authors: Cao Yayun , Gui Mengcui , Ji Suqiong , Bu Bitao
Published: November 2019

Rationale:

Myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) are 2 common neurologic autoimmune diseases. Although both the diseases can present with acute or subacute onset of muscular weakness involving the limbs and bulb, the coexistence in the same patient is unusual and rarely described in the literature.

Patient concerns:

Three cases of combined MG and GBS at the department of Neurology were described. All the 3 patients developed GBS, who had had MG for 30 years, 6 years, and 6 months, respectively.

Diagnoses:

The newly developed GBS was clinically confirmed by the clinical features, electromyographic (EMG) studies, typical albumino-cytologic dissociation in cerebrospinal fluid (CSF), and positive anti-ganglioside antibodies in serum.

Interventions:

The 3 patients had been treated with intravenous immunoglobulin (IVIG), or plasma-exchange (PE), or IVIG combined with PE in the acute stage of severe muscle weakness. In light of the MG symptoms, they have received glucocorticoids, oral pyridostigmine, and immunosuppressive agents.

Outcomes:

The patient 1 was able to walk longer than 5 m with assistance (Hughes 3). The patient 2 had significantly improved, and completely recovered at the 1-year follow-up (Hughes 0). But unfortunately, the patient 3 was severely disabled and chair-bound at the last interview (Hughes 4).

Lessons:

The combination of MG and GBS is quite rare. Limbs and oculo-bulbar weakness are the cardinal manifestations of both the diseases. Although their characteristics are quite different, there are still some difficulties in diagnosing them when they occur in the same patient. Early diagnosis and proper treatment will yield satisfactory prognosis. Further researches are needed to elucidate the pathogenesis of the coexistence.
Bilateral orbital involvement of IgG4-related disease detected on 18F-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography
Authors: Dong Ping , Wang Li , Li Lin
Published: November 2019

Rationale:

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibro-inflammatory condition, which could involve multiple structures, including the pancreas, salivary glands, and lymph nodes. However, cases of IgG4-RD involving the bilateral orbits, salivary glands, submandibular glands, lymph nodes, and prostate are rare.

Patient concerns:

A 51-year-old man complaining of bilateral exophthalmos, reduced vision, and weight loss of 15 kg over 2 years presented to our department for evaluation.

Diagnoses:

Based on the elevated serum IgG4 level, postoperative pathology, and the features of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), which revealed diffuse increased FDG uptake in many structures, he was diagnosed with IgG4-related disease involving the bilateral orbits, salivary glands, submandibular glands, lymph nodes, and prostate.

Interventions:

Because of the significant bilateral proptosis and exposure keratoconjunctivitis in the right eye, bilateral soft-tissue masses located in the orbits were resected, and the patient was started on oral methylprednisolone with gradual tapering.

Outcomes:

The patient's symptoms gradually relieved after the operation and glucocorticoid therapy. Four months later, cranial axial CT revealed remarkable narrowing of soft-tissue masses in the bilateral orbits, and his serum IgG4 level reduced sharply.

Lessons:

IgG4-RD should be considered in cases of diffuse FDG uptake in the bilateral orbits, salivary glands, submandibular glands, lymph nodes, and prostate on PET/CT.
Thromboelastography versus standard coagulation testing in the assessment and reversal of coagulopathy among cirrhotics: a systematic review and meta-analysis
Authors: Kovalic Alexander J. , Khan Muhammad Ali , Malaver Diego , Whitson Matthew J. , Teperman Lewis W. , Bernstein David E. , Singal Ashwani , Satapathy Sanjaya K.
Published: November 2019

The utility of thromboelastography/thromboelastometry currently has unvalidated clinical benefit in the assessment and reversal of coagulopathy among cirrhotic patients as compared to standard coagulation testing. A novel systematic review and meta-analysis was conducted in order to assess pooled outcome data among patients receiving thromboelastography/thromboelastometry as compared to standard coagulation testing. As compared to standard coagulation testing, there was a significant reduction in the number of patients requiring pRBC, platelet, and fresh frozen plasma transfusions among thromboelastography/thromboelastometry group with pooled OR 0.53 (95% CI 0.32–0.85; P = 0.009), 0.29 (95% CI 0.12–0.74; P = 0.009), and 0.19 (95% CI 0.12–0.31; P < 0.00001), respectively. Similarly, there was a significant reduction in number of pRBC, platelet, and fresh frozen plasma units transfused in the thromboelastography/thromboelastometry group with pooled MD −1.53 (95% CI −2.86 to −0.21; P = 0.02), −0.57 (95% CI −1.06 to −0.09; P = 0.02), and −2.71 (95% CI −4.34 to −1.07; P = 0.001), respectively. There were significantly decreased total bleeding events with pooled OR 0.54 (95% CI 0.31–0.94; P = 0.03) and amount of intraoperative bleeding during liver transplantation with pooled MD −1.46 (95% CI −2.49 to −0.44; P = 0.005) in the thromboelastography/thromboelastometry group. Overall, there was no significant difference in mortality between groups with pooled OR 0.91 (95% CI 0.63–1.30; P = 0.60). As compared to standard coagulation testing, a thromboelastography/thromboelastometry-guided approach to the assessment and reversal of cirrhotic coagulopathy improves overall number of patients exposed to blood product transfusions, quantity of transfusions, and bleeding events.
Clinical implication of 18F-NaF PET/computed tomography indexes of aortic calcification in coronary artery disease patients: correlations with cardiovascular risk factors
Authors: Ryoo Hyun Gee , Paeng Jin Chul , Koo Bon-Kwon , Cheon Gi Jeong , Lee Dong Soo , Kang Keon Wook
Published: November 2019

Objective

Vascular calcification is known to be associated with cardiovascular risk factors. Recently, 18F-NaF PET has been reported to be effective for detecting early and active vascular calcification. In this study, correlations between 18F-NaF PET/computed tomography (CT) findings and cardiovascular risk factors were investigated in patients with suspected coronary artery disease.

Patients and methods

Forty patients with suspected coronary artery disease underwent 18F-NaF PET/CT. The maximum and overall burden of calcifying activity, and the overall burden of calcium deposition in the descending thoracic aorta (DTA) were measured on 18F-NaF PET/CT and they were compared with cardiovascular risk factors, particularly, with those related to metabolic syndrome.

Results

The maximum and overall burden of calcifying activity in DTA measured on 18F-NaF PET were significantly correlated with diabetes mellitus (P = 0.030 and 0.049, respectively) and serum HbA1c level (ρ = 0.433 and 0.344, respectively). In contrast, the overall burden of calcium deposition measured on CT was significantly correlated with hypertension (P < 0.001). The overall burden of calcium deposition was also significantly correlated with metabolic syndrome (P = 0.002) and 10-year cardiovascular disease risk score (P = 0.004)

Conclusion

18F-NaF uptake is closely related to diabetes mellitus, whereas aortic calcification on CT is closely related to hypertension. Although 18F-NaF uptake in DTA can be a potential prognostic factor, aortic calcification on CT is a more significant prognostic factor for overall cardiovascular risk than 18F-NaF uptake.
Chordoma of the Clivus and Acute Myeloid Leukemia: Is There a Connection?
Authors: Larkin Trisha , Macak Rachel , Lagmay Joanne , Horn Biljana
Published: November 2019

Chordoma is a rare cancer in children and understanding the genesis of this tumor may contribute to treatment approaches. Evidence has proposed VDC/IE (vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide) as a treatment option for young patients with chordoma to avoid the long-term effects of radiation therapy. We present a case of acute myeloid leukemia developing during treatment of localized chordoma of the clivus in a 20-month-old male. We propose a genomic relationship that may have contributed to the development of clival chordoma and acute myeloid leukemia without a latency period and advocate for genomic sequencing in children with chordoma before the initiation of systemic therapies.
A Case of Langerhans Cell Histiocytosis With Multifocal, Single-System GI Tract Involvement and Literature Review
Authors: Gotesman Moran , Getachew Ruth , Morales Sonia , Zangwill Kenneth M. , Gershman George , Lee Steven , Lasky Joseph L. , Panosyan Eduard H.
Published: November 2019

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder, characterized by the pathologic clonal proliferation and accumulation of immature Langerhans cells within organs. Multiple organ systems can be affected, resulting in a spectrum of clinical manifestations. Isolated gastrointestinal involvement in LCH is rare and usually presents in childhood as a multisystem disease and usually has poor outcomes. We describe a 20-year-old Hispanic female with multifocal, single-system gastrointestinal LCH. Initially diagnosed from a CD1a, S100, and CD207 (Langerin) positive appendix tissue after an appendectomy and confirmed multifocal with an endoscopy. She had a full clinical and endoscopic resolution of disease with cytarabine therapy.
Swallowing Outcomes and Discharge Destinations in Acute Stroke Tube-Feeding Dependent Dysphagia Patients Treated With Neuromuscular Electrical Stimulation During Inpatient Rehabilitation
Authors: Kushner David S. , Johnson-Greene Doug , Cordero Maite K. , Thomashaw Stacy A. , Rodriguez Jennifer
Published: November 2019

Objective

Inpatient rehabilitation study comparing swallowing outcomes and discharge destinations in acute stroke tube-feeding dependent dysphagia patients treated with neuromuscular electrical stimulation and traditional dysphagia therapy versus those treated with only traditional dysphagia therapy.

Design

Retrospective case-control study including 359 patients with acute stroke having initial Functional Oral Intake Scale scores of 3 or lower (profound to severe tube-feeding dependent dysphagia). One hundred ninety participants received neuromuscular electrical stimulation with traditional dysphagia therapy, and 169 controls received only traditional dysphagia therapy. Treatment occurred in hourly sessions 5 d/wk. Main outcome measures were comparison of Functional Oral Intake Scale scores after treatment (N = 359) and comparison of discharge destinations (n = 267).

Results

The neuromuscular electrical stimulation posttreatment mean ± SD Functional Oral Intake Scale score was 4.21 ± 2.1 versus 2.94 ± 1.96 for controls (t = 5.85, P < 0.001). The neuromuscular electrical stimulation group posttreatment mean ± SD Functional Oral Intake Scale gain was 3.24 ± 2.26 points versus 1.87 ± 2.01 for controls (t = 6.05, P < 0.001). After treatment, 51.6% (98/190) neuromuscular electrical stimulation patients had minimal or no swallowing restrictions (Functional Oral Intake Scale scores = 5–7), whereas only 26.6% (45/169) controls improved with Functional Oral Intake Scale scores of 5–7 (χ2 = 23.3, P < 0.0001). Groups differed by discharge destinations: neuromuscular electrical stimulation having more discharges to community than controls, 60% versus 44% (χ2 = 9.16, P = 0.003), and neuromuscular electrical stimulation having fewer acute care transfers compared with controls, 8% versus 25% (χ2 = 32.7, P < 0.0001).

Conclusions

Neuromuscular electrical stimulation with traditional dysphagia therapy was associated with better discharge swallowing outcomes and Functional Oral Intake Scale scores than traditional dysphagia therapy alone during inpatient rehabilitation in treating acute stroke feeding tube–dependent dysphagia and was associated with more discharges to community and less transfers back to acute care.
Targeted Therapies in Chronic Lymphocytic Leukemia
Authors: Ujjani Chaitra , Cheson Bruce D.
Published: November 2019

Small molecule inhibitors, including B-cell receptor antagonists and B-cell lymphoma - 2 inhibitors, have revolutionized the treatment of chronic lymphocytic leukemia (CLL). These agents have improved outcomes for patients of all prognostic backgrounds, thus securing their role in the frontline setting. Impressive activity has been demonstrated both with monotherapy and in combination with other targeted therapeutics. The most important remaining question is whether to administer small molecule inhibitors in a sequential fashion or in combination with each other and/or anti-CD20–directed therapy. Together, a number of retrospective and prospective clinical trials have provided insight into patient outcomes with different sequencing and combination strategies. While rituximab does not appear to provide significant additional benefit to ibrutinib, the incorporation of venetoclax appears to enable a deeper response and allow for a shorter duration of therapy. How durable of a response this produces and whether patients can be effectively retreated with venetoclax remain unclear. As various targeted therapy doublets and triplets are explored, it is important to investigate whether they produce significant long-term benefits over monotherapy and whether these approaches are appropriate for all patients.
Bruton Tyrosine Kinase Inhibitors
Authors: Burger Jan A.
Published: November 2019

Bruton tyrosine kinase (BTK) is a nonreceptor tyrosine kinase that plays a central role in the signal transduction of the B-cell antigen receptor and other cell surface receptors, both in normal and malignant B lymphocytes. B-cell antigen receptor signaling is activated in secondary lymphatic organs and drives the proliferation of malignant B cells, including chronic lymphocytic leukemia (CLL) cells. During the last 10 years, BTK inhibitors (BTKis) are increasingly replacing chemotherapy-based regimen, especially in patients with CLL and mantle cell lymphoma (MCL). Bruton tyrosine kinase inhibitors are particularly active in patients with CLL and MCL, but also received approval for Waldenström macroglobulinemia, small lymphocytic lymphoma, marginal zone lymphoma, and chronic graft-versus-host disease. Current clinical practice is continuous long-term administration of BTKi, which can be complicated by adverse effects or the development of drug resistance. Alternatives to long-term use of BTKi are being developed, such as combination therapies, permitting for limited duration therapy. Second-generation BTKis are under development, which differ from ibrutinib, the first-in-class BTKi, in their specificity for BTK, and therefore may differentiate themselves from ibrutinib in terms of adverse effects or efficacy.
Relevance of Minimal Residual Disease in the Era of Targeted Agents
Authors: Heltai Silvia , Ghia Paolo , Scarfò Lydia
Published: November 2019

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

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

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

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

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

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

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.
Impaired B-Cell Maturation Contributes to Reduced B Cell Numbers and Poor Prognosis in Sepsis
Authors: Duan Shaoxia , Jiao Yingfu , Wang Jiemin , Tang Dan , Xu Saihong , Wang Ruoxi , Jiang Tao , Shao Jianlin , He Zhenzhou , Yu Weifeng
Published: November 2019

Background:

Reduced B cell numbers play a critical role in sepsis immunosuppression. The role of B-cell maturation regulated by T follicular helper (Tfh) cells in reduced B cell numbers during sepsis remains unclear. We tested the hypothesis that impaired B-cell maturation contributes to reduced B cell numbers.

Design:

Retrospective study and observational prospective cohort study.

Settings:

Critical care units.

Methods:

To identify the exact lymphocyte counts that affect the prognosis of sepsis, we first conducted a retrospective study. Then in the prospective cohort study, differences in B-cell maturation, B cell death, and numbers of circulating Tfh (cTfh) cell were compared between 28-day survivors and 28-day non-survivors, mainly by flow cytometry and enzyme-linked immunosorbent assay.

Main Results:

In retrospective study (n = 123), we found patients with lymphocyte counts less than 0.4 × 109 cells/L had higher mortality than patients with lymphocyte counts above 0.4 × 109 cells/L. In observational prospective cohort study (n = 40), compared with survivors, non-survivors had fewer numbers of mature B cell and circulating Tfh (cTfh) cell (sepsis onset: memory B cells: 3.44% vs. 4.48%, antibody-secreting cells: 4.53% vs. 6.30%, cTfh cells: 3.57% vs. 4.49%; 24 h after sepsis onset: memory B cells: 4.05% vs. 7.20%, antibody-secreting cells: 5.25% vs. 8.78%, cTfh cells: 3.98% vs. 6.15%), while there were no differences in cell death of mature B cells between them. We further noticed the numbers of cTfh cell positively correlated with the numbers of mature B cell and immunoglobulin concentrations.

Conclusions:

Impaired B-cell maturation contributes to reduced B cell numbers, while the numbers of cTfh cell, acting as a warning indicator for sepsis prognosis, may be a new therapeutic target for treating sepsis.
Neutrophil Elastase Inhibition Ameliorates Endotoxin-induced Myocardial Injury Accompanying Degradation of Cardiac Capillary Glycocalyx
Authors: Fukuta Tetsuya , Okada Hideshi , Takemura Genzou , Suzuki Kodai , Takada Chihiro , Tomita Hiroyuki , Suzuki Akio , Oda Kazumasa , Uchida Akihiro , Matsuo Saori , Fukuda Hirotsugu , Yano Hirohisa , Muraki Isamu , Zaikokuji Ryogen , Kuroda Ayumi , Nishio Ayane , Sampei So , Miyazaki Nagisa , Hotta Yasuaki , Yamada Noriaki , Watanabe Takatomo , Morishita Kentaro , Doi Tomoaki , Yoshida Takahiro , Ushikoshi Hiroaki , Yoshida Shozo , Maekawa Yoichi , Ogura Shinji
Published: November 2019

Myocardial injury in sepsis may be caused by a burst of several inflammatory mediators, leading to vascular endothelial injuries. However, the contribution of neutrophil elastase (NE) to myocardial injury in sepsis is still unknown. We aimed to evaluate whether endotoxemia-induced myocardial injury is associated with NE. Lipopolysaccharide (LPS) was injected intraperitoneally at a dose of 20 mg/kg into granulocyte-colony-stimulating-factor knockout mice (G-CSF-KO), which have few neutrophils, and littermate control mice. The survival rate of G-CSF-KO mice 48 hours after LPS injection was significantly greater than that of control mice. The serum level of troponin I in G-CSF-KO mice was significantly lower than that in control mice. In addition, the concentration of inflammatory cytokine interleukin-6 (IL-6) was significantly decreased 6 and 12 hours after LPS administration compared with that in control mice. Ultrastructural analysis revealed that vascular endothelial structures and the endothelial glycocalyx in G-CSF-KO mice were clearly preserved. Next, mice were injected with 0.2 mg/kg sivelestat (an NE inhibitor) after LPS administration. The survival rate was significantly higher and the serum level of troponin I was lower in sivelestat-injected mice than in control mice, respectively. Furthermore, IL-6 levels were significantly decreased 6 and 12 hours after LPS administration compared with those in control mice. Vascular endothelial structures and the endothelial glycocalyx in sivelestat-treated mice were clearly preserved at the ultrastructural level. In conclusion, NE is significantly associated with myocardial injury in endotoxemia. Inhibition of NE may be a useful tool for the management of endotoxemia.
Mitochondrial Dysfunction is Associated With an Immune Paralysis Phenotype in Pediatric Sepsis
Authors: Weiss Scott L. , Zhang Donglan , Bush Jenny , Graham Kathryn , Starr Jonathan , Murray Jennifer , Tuluc Florin , Henrickson Sarah , Deutschman Clifford S. , Becker Lance , McGowan Francis X. , Wallace Douglas C.
Published: November 2019

Objective:

Immune dysregulation is a defining feature of sepsis, but the role for mitochondria in the development of immunoparalysis in pediatric sepsis is not known. We sought to determine if mitochondrial dysfunction measured in peripheral blood mononuclear cells (PBMCs) is associated with immunoparalysis and systemic inflammation in children with sepsis.

Design:

Prospective observational study.

Setting:

Single-academic pediatric intensive care unit (PICU).

Patients:

One hundred sixty-one children with sepsis/septic shock and 18 noninfected PICU controls.

Measurements and Main Results:

Mitochondrial respiration in PBMCs, markers of immune function, and plasma cytokines were measured on days 1 to 2 (T1), 3 to 5 (T2), and 8 to 14 (T3) after sepsis recognition, and once for controls. Immunoparalysis was defined as whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) ≤200 pg/mL or monocyte human leukocyte antigen-DR ≤30%. Mitochondrial respiration was lower in children with versus without immunoparalysis measured at the same timepoint. Mitochondrial respiration measured early (at T1 and T2) was also lower in those with immunoparalysis at T2 and T3, respectively. Although most patients with immunoparalysis exhibited low mitochondrial respiration, this metabolic finding was not specific to the immunoparalysis phenotype. Plasma cytokines, including IL-8, IL-10, TNF-α, and MCP-1, were highest in the subset of sepsis patients with immune paralysis or low mitochondrial respiration at T1.

Conclusions:

Children with sepsis had lower PBMC mitochondrial respiration when immunoparalysis was present compared with those without immunoparalysis. The subsets with immune paralysis and low mitochondrial respiration exhibited the highest levels of systemic inflammation.
Proficiency Level of Novice Technically Qualified Surgeons in Laparoscopic Rectal Resection
Authors: Ichikawa Nobuki , Homma Shigenori , Yoshida Tadashi , Iijima Hiroaki , Kawamata Futoshi , Sibasaki Susumu , Kawamura Hideki , Minagawa Nozomi , Kamiizumi You , Fukasaku Yasutomo , Taketomi Akinobu
Published: November 2019

The actual proficiency levels of surgeons after their qualification by the Endoscopic Surgical Skill Qualification System have not been established. This study aimed to investigate whether technically qualified surgeons could safely perform laparoscopic low anterior resection and to evaluate the proficiency level at the time of certification acquisition. A total of 46 patients (mean age, 63.3 y; male to female ratio, 29:17) who underwent low anterior resection were included. Outcomes of 46 low anterior resections for rectal cancer performed by 3 novice surgeons certified by the Endoscopic Surgical Skill Qualification System from 2013 to 2018 at 2 hospitals were retrospectively assessed. The mean operative time and blood loss were 201 minutes and 12.9 mL, respectively. One patient (2.2%) required conversion to open surgery, and major postoperative complications occurred in 4 patients (8.6%), including anastomotic leakage in 2 patients (4.3%). Histologic R0 resection was achieved in all cases. The operative time moving average for the 3 surgeons gradually decreased from 233 to 158 minutes. In cumulative sum charts, the operative time values continuously decreased after the 12th case compared with the target operative time (180 min). In conclusion, surgeons can safely perform laparoscopic low anterior resection just after their qualification but have the potential to further attain proficiency.