bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of renal replacement therapy strategies for septic-acute kidney injury
Authors: Zha Junjing , Li Chuan , Cheng Gaoxiang , Huang Lijuan , Bai Zhaoqing , Fang Changtai
Published: April 2019

Background:

Renal replacement therapy (RRT) is the main treatment for patients with sepsis-induced acute kidney injury (SAKI). However, the choice of RRT strategy remains controversial.

Objective:

This study assessed the effectiveness of RRT variants in SAKI patients by a network meta-analysis.

Methods:

This study searched the literature in the PubMed, EmBase, and Cochrane Library databases up to August 18, 2018. The outcomes of the analysis were the survival rate, renal recovery rate, intensive care unit (ICU) duration, and hospital duration.

Results:

Twenty-two articles were included in the analysis. The results showed that only the negative control was inferior to the regimens of RRT with polymyxin B-immobilized fiber (PMXF), PMXF alone, continuous venovenous hemofiltration (CVVH), CVVH plus alkaline phosphatase (AP), continuous venovenous hemodialysis (CVVHD), high-volume CVVH, and extra high-volume CVVH in terms of the survival rate. According to the surface under the cumulative ranking , RRT with PMXF (84.4%) and PMXF (84.3%) were the treatments most likely to improve the survival rate among SAKI patients, followed by CVVH plus AP (69%). Continuous venovenous hemodiafiltration (CVVHDF), extra high-volume CVVHDF, intermittent venovenous hemodiafiltration (IVVHDF), and low-volume CVVHDF resulted in very similar survival rates. CVVH plus AP conferred relative advantages in the renal recovery rate and ICU duration.

Conclusion:

CVVH, CVVHD, and their derived RRT strategies can improve survival rates in SAKI patients, but there is no significant difference among the RRT strategies. There was also no significant difference in the survival rate among CVVHDF, IVVHDF, and their derived strategies. More high-quality randomized controlled trials with large sample sizes are needed for further research.
Spontaneous rotational dislocation of the lumbar spine in type 1 neurofibromatosis
Authors: Jia Fei , Cui Xingang , Wang Guodong , Liu Xiaoyang , Sun Jianmin
Published: April 2019

Rationale:

Scoliosis is the most common form of dystrophic spinal deformities in type 1 neurofibromatosis, whereas a spontaneous rotational dislocation of the lumbar spine is a rare entity. Former researchers had advocated the use of circumferential fusion performed through combined anterior-posterior approaches as the mode of treatment of this situation, but we managed to achieve a solid circumferential fusion equally using posterior approach alone.

Patient concerns:

A 51-year-old lady presented with severe back pain and no history of trauma, fever, or loss of weight. On examination, she showed several café-au-lait spots on her body and no neurologic deficit.

Diagnoses:

The imageology revealed a rotational dislocation of the L2 to L3. The diagnosis of neurofibroma was confirmed by biopsy.

Interventions:

The patient underwent posterior reduction, combined intervertebral-posterolateral fusion, and internal fixation with screws and rods.

Outcomes:

The patient was satisfied with the back pain relief after surgery and able to live a normal life at follow-up. The imageology showed a good correction of the deformity with a solid bony fusion.

Lessons:

Special attention must be paid to patients who have neurofibromatosis and unexplained back pain for early diagnosis. Early circumferential fusion to reconstruct a stable spine is the key to treatment. Given the result of this case, the prognosis is promising following posterior surgery alone.
Diagnostic challenges of spinal gout
Authors: Ma Shaolong , Zhao Jianhui , Jiang Rui , An Quanming , Gu Rui
Published: April 2019

Introduction:

Spinal gout is rarely encountered in clinical practice, is easily misdiagnosed, and often remains undiagnosed. This paper aims to provide some clues that are the salient diagnostic features of spinal gout, particularly axial pain, radiculopathy, and myelopathy, as determined on the basis of our experience with a few cases as well as a literature review.

Methods:

We retrospectively reviewed the clinical data of 5 patients that were treated for axial pain and neurological symptoms associated with spinal gout between 2014 and 2017 in our hospital. Herein, we systematically describe the clinical characteristics of 5 patients with spinal gout. The 5 patients included 4 men and 1 woman, aged between 24 and 75 years. The most common clinical presentation included spinal pain, radiculopathy, and myelopathy. Four of the 5 patients had a history of gout and elevated serum uric acid levels.

Results:

Four patients underwent surgery, while the remaining patient underwent conservative treatment and biopsy due to poor general condition. Pathological examination of the surgical samples in the 4 surgical cases and the biopsy sample in the remaining case confirmed the presence of spinal gout tophi. The neurological symptoms of all 5 patients were relieved after treatment.

Conclusion:

Due to its rarity and lack of typical defining criteria, the diagnosis of spinal gout is quite difficult. We recommend that patients presenting with axial pain; radicular pain or myelopathy; and especially high uric acid levels, with or without a history of gout, should be evaluated for spinal gout. Timely pathological examination of surgical or biopsy samples would help confirm the diagnosis and enable practitioners to provide the appropriate treatment to prevent disease progression.
Cluster analysis to define distinct clinical phenotypes among septic patients with bloodstream infections
Authors: Guilamet Maria Cristina Vazquez , Bernauer Michael , Micek Scott T. , Kollef Marin H.
Published: April 2019

Prior attempts at identifying outcome determinants associated with bloodstream infection have employed a priori determined classification schemes based on readily identifiable microbiology, infection site, and patient characteristics. We hypothesized that even amongst this heterogeneous population, clinically relevant groupings can be described that transcend old a priori classifications.

We applied cluster analysis to variables from three domains: patient characteristics, acuity of illness/clinical presentation and infection characteristics. We validated our clusters based on both content validity and predictive validity.

Among 3715 patients with bloodstream infections from Barnes-Jewish Hospital (2008–2015), the most stable cluster arrangement occurred with the formation of 4 clusters. This clustering arrangement resulted in an approximately uniform distribution of the population: Cluster One “Surgical Outside Hospital Transfers” (21.5%), Cluster Two “Functional Immunocompromised Patients” (27.9%), Cluster Three “Women with Skin and Urinary Tract Infection” (28.7%) and Cluster Four “Acutely Sick Pneumonia” (21.8%). Staphylococcus aureus distributed primarily to Clusters Three (40%) and Four (25%), while nonfermenting Gram-negative bacteria grouped mainly in Clusters Two and Four (31% and 30%). More than half of the pneumonia cases occurred in Cluster Four. Clusters One and Two contained 33% and 31% respectively of the individuals receiving inappropriate antibiotic administration. Mortality was greatest for Cluster Four (33.8%, 27.4%, 19.2%, 44.6%; P < .001), while Cluster One patients were most likely to be discharged to a nursing home.

Our results support the potential for machine learning methods to identify homogenous groupings in infectious diseases that transcend old a priori classifications. These methods may allow new clinical phenotypes to be identified potentially improving the severity staging and development of new treatments for complex infectious diseases.
Liuwei Dihuang Decoction for primary osteoporosis
Authors: Liu Yu , Wang Ping , Shi Xiuqun , Li Huijin , Zhang Xionghui , Zeng Shenghu , Xu Zhoufa , Lai Dongqing , Zhang Minling
Published: April 2019

Background:

Primary osteoporosis (POP) is one kind of global disease, as a serious threat to human health. Liuwei Dihuang Decoction (LWDHD) has been recommended to treat osteoporosis alone or combined with medicine in China; however, its efficacy is unclear. The object of this systematic review and meta-analysis is to evaluate the efficacy and safety of LWDHD in the management of POP.

Methods:

We will search The Cochrane Library, Medline, PubMed, Elsevier, Springer, Web of Science, Ovid, WHO ICTRP, CNKI, CBM, VIP, and WanFang Database from their inception to February 2019. All randomized controlled trials (RCTs) of LWDHD for the treatment of POP will be included. The language is limited to Chinese and English. The fracture incidence will be accepted as the primary outcomes. Data synthesis, subgroup analysis, sensitivity analysis will be performed by using RevMan V.5.3.5 software.

Results:

A high-quality synthesis of current evidence for the treatment of POP with LWDHD will be provided from efficacy and safety.

Conclusion:

This systematic review will generate evidence for judging whether LWDHD is an effective and safe intervention for POP or not.

PROSPERO registration number:

PROSPERO CRD 4201926066.
Case report of long-term survival with metastatic triple-negative breast carcinoma
Authors: Chue Ben Man-Fai , La Course Bryce Douglas
Published: April 2019

Rationale:

Breast cancer is the most common as well as one of the most devastating cancers among women in the United States. Prognosis is poor for patients with metastatic breast cancer, especially for patients with so-called “triple-negative” disease. The lack of effective therapies for metastatic triple-negative breast cancer outlines the need for novel and innovative treatment strategies.

Patient concerns:

A 58-year-old underwent a mastectomy which revealed a recurrent triple-negative breast carcinoma. Afterward, she presented with a growing mass in her left axilla and chest wall. A computed tomography scan showed axillary and supraclavicular adenopathy, nodules in the left upper and lower lobe of the lungs, and 2 areas of disease in the liver. A bone scan showed lesions in the ribs.

Diagnosis:

The patient was diagnosed with a recurrent metastatic triple-negative breast carcinoma that spread to the lung, liver, and bones.

Interventions:

The patient was treated with metronomic chemotherapy, sequential chemotherapy regimens, and immunotherapy.

Outcomes:

The patient is now over 15 years out from her diagnosis of metastatic disease without any evidence of recurrent disease, likely due to the patient's treatment strategy which included sequential metronomic chemotherapy regimens and immunotherapy.

Lessons:

Sequential metronomic chemotherapy regimens in combination with immunotherapy might be an effective treatment option for patients with metastatic triple-negative breast cancer. We hope that this case can provide some guidance for the treatment of metastatic triple-negative breast cancer and motivate research that can potentially lead to more cases of long-term survival for patients who develop this dismal disease.
A very rare presentation of reoperation combined both old Monteggia fracture and secondary distal radioulnar joint dislocation in adult
Authors: Zhang Yanchao , Xiao Wan’an , Li Jianjun
Published: April 2019

Rationale:

The old Monteggia fracture is an uncommon lesion pattern in adult, which may lead to the potential complications such as recurrent dislocation of the radial head, heterotopic ossification of the elbow, nerve palsy, malunion of the ulna, and residual forearm deformity. However, the secondary distal radioulnar joint (DRUJ) dislocation is rarely reported in the similar lesion. Here we present a unique reoperation of old Monteggia fracture combined with secondary DRUJ disruption after the initial operation failure.

Patient concerns:

A 38-year-old male presented to our hospital outpatient office complaining of left elbow stiffness and ongoing wrist dysfunction with a history of injury to the left forearm caused by a forklift accident that occurred 5 months previously.

Diagnosis and interventions:

At the local hospital, the patient underwent successively fasciotomy and decompression, ulnar open reduction, and internal fixation due to osteofascial compartment syndrome and a misdiagnosed ulnar fracture. Upon examination, the secondary dorsal dislocation of the DRUJ was obvious both clinically and radiographically. We performed a revision surgery called ulnar osteotomy, radioulnar ligament repair, and temporary fixation of the DRUJ with a Kirschner wire.

Outcomes:

The patient received a satisfactory result without observed redislocation and relapse according to the 1-year follow-up.

Lessons:

Considering the notoriously poor outcomes, the importance of early recognition and accurate treatment should be emphasized repeatedly in similar lesions. Paying close and continuous attention to the clinical and radiographic examinations of the elbow and wrist joint is necessary to avoid misdiagnosis and missed diagnosis.
Progressive sacroiliitis due to accessory sacroiliac joint mimicking ankylosing spondylitis
Authors: Song Ran , Lee Soyun , Lee Sang-hoon
Published: April 2019

Rationale:

An accessory sacroiliac (SI) joint usually has little clinical significance. However, severe arthritic changes can cause chronic buttock or low back pain and can be misdiagnosed as another disease presenting with sacroiliitis such as ankylosing spondylitis (AS).

Patient concerns:

A 33-year-old woman was diagnosed with AS due to chronic buttock pain and progressive sacroiliitis on plain X-ray and magnetic resonance imaging (MRI). Her buttock and low back pain gradually worsened despite proper treatment for AS.

Diagnosis:

Computed tomography revealed an accessory SI joint with arthritic changes.

Interventions:

Nonsteroidal anti-inflammatory drugs (NSAIDs) and restricted movement were prescribed.

Outcomes:

The symptoms were controlled with NSAIDs, rest, and restriction of excessive movement. The medication could be stopped after the pain subsided.

Lessons:

An accessory SI joint can be a cause of chronic back pain and can be misdiagnosed as AS with sacroiliitis when progressive arthritic changes are observed. Therefore, additional imaging studies other than conventional X-ray or MRI may be required for accurate diagnosis.
Clinical features, surgical management, and long-term prognosis of intraventricular meningiomas
Authors: Chen Cheng , Lv Liang , Hu Yu , Yin Senlin , Zhou Peizhi , Jiang Shu
Published: April 2019

Intraventricular meningiomas are rather rare and only represent a small proportion of all intracranial meningiomas. Data are still limited toward this peculiar entity and surgical resection remains challenging for neurosurgeons. The purpose of present study is to demonstrate clinical features, surgical treatment, and potential risk factors determined long-term prognosis of intraventricular meningiomas.

A total of 89 surgically treated and histopathologically confirmed intraventricular meningiomas were identified in our institution from 2008 to 2018. Clinical features, neuroimaging findings, surgical records, and prognosis data were extracted and reviewed retrospectively. Group comparison and recurrence-free survival analysis were performed.

Female predominance was well established with a sex radio of 2.1:1. Raised intracranial pressure and decline of visual acuity were 2 chief symptoms that patients generally complained of. Preoperative magnetic resonance imaging (MRI) scans were performed in all patients and there was a trend toward lateral ventricular meningiomas were larger in size than others (P = .07). Superior parietal lobule and temporal approach were widely adopted and lateral/4th ventricular meningiomas were more easily to acquire total tumor resection as compared with 3rd ventricular meningiomas (P = .03). After an average follow-up of 57.3 months, 6 patients experienced recurrence of disease in our series. Individuals with subtotal resection (P < .001) and higher World Health Organization classification (P = .001) were more prone to relapse.

Intraventricular meningiomas presented with a wide variety of symptoms. Surgery remained 1st treatment of choice and optimal surgical approach should be planned individually based on preoperative MRI evaluation. Patients underwent subtotal tumor resection and with malignant tumor nature should be carefully monitored during follow-up.
A meta-analysis on the prognosis of exosomal miRNAs in all solid tumor patients
Authors: Zhou Jiupeng , Guo Hui , Yang Yuanli , Zhang Yongfeng , Liu Heng
Published: April 2019

Background:

It has been reported that the encapsulated miRNAs from exosomes are potential biomarkers of tumors prognosis. Yet, the results are controversial, so it is obliged to do a meta-analysis to reach a definite conclusion.

Materials and methods:

Studies were searched for published in PubMed, Embase, and Web of Science databases until April 20, 2018. A meta-analysis was conducted to appraise the role of exosomal miRNAs in prognosis of cancer patients.

Results:

The different exosomal miRNAs expression was remarkably related to overall survival (OS) (hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.84–2.21) and disease-free survival (DFS) (HR = 2.43, 95% CI: 1.86–3.17) of cancer patients. High exosomal miR-21 expression was associated with poor OS (HR = 2.59; 95% CI: 1.71–3.90) and DFS (HR = 1.84; 95% CI: 1.37–2.47). High exosomal miR-451a expression was associated with poor OS (HR = 4.81; 95% CI: 2.33–9.93) and DFS (HR = 2.64; 95% CI: 1.62–4.31). High exosomal miR-1290 expression was associated with poor OS (HR = 1.73; 95% CI: 1.29–2.33). Low exosomal miR-638 expression was associated with poor OS (HR = 2.25; 95% CI: 1.46–3.46).

Conclusion:

The expression levels of exosomal miRNAs, particularly miR-21, miR-451a, miR-1290, and miR-638 could strongly predict prognosis of solid tumor patients and might be a potential target for tumor treatment.
Hepatocellular carcinoma in the noncirrhotic liver: a literature review
Authors: Zhang Yanan , Wang Chunguang , Xu Hongqin , Xiao Peng , Gao Yanhang
Published: April 2019

Development of hepatocellular carcinoma (HCC) is usually preceded by chronic liver injury and ongoing liver diseases. Liver cirrhosis reflects the outcome of long-term liver injury and is associated with an increased risk of developing HCC. However, HCC also arises in individuals without cirrhosis and bears several characteristics distinct from HCC in the cirrhotic liver. The molecular characteristics, prognosis, and surveillance of noncirrhotic HCC have not been adequately studied. In this review, we update readers and researchers in the field with the latest understanding of the epidemiology, etiology, clinical features, diagnosis, treatment strategies, prognosis, and surveillance of noncirrhotic HCC.
Comparison of risk scores and shock index in hemodynamically stable patients presenting to the emergency department with nonvariceal upper gastrointestinal bleeding
Authors: Jung Dae Ho , Ko Byuk Sung , Kim Youn-Jung , Kim Won Young
Published: April 2019

Objective

Risk assessment in nonvariceal upper gastrointestinal bleeding (UGIB) is not well validated and remains unclear in hemodynamically stable patients at emergency department admission. We compared the prognostic value of risk-scoring systems for predicting adverse outcomes in patients with nonvariceal UGIB and normotension.

Participants and methods

A single-center prospective observational study was carried out. Patients with consecutive nonvariceal UGIB, presenting with normotension (systolic blood pressure ≥90 mmHg) to the emergency department, were included. We compared the areas under the curves (AUC) of Glasgow Blatchford score (GBS), the pre-endoscopy Rockall score, AIMS65, the shock index, and the modified shock index with respect to adverse outcomes defined as embolization, surgery, ICU admission, rebleeding, and in-hospital mortality.

Results

In total, 1233 patients were included. Adverse outcomes occurred in 165 (13.4%) patients; in-hospital mortality was 1.2%. AUC of the GBS for adverse outcome was higher than that of the shock index, but not significantly different (0.647 vs. 0.569, P=0.23). AUC values of the modified shock index, AIMS65, and the pre-endoscopy Rockall score were 0.565, 0.593, and 0.533, respectively. The cut-off value of the GBS (≥8) was associated with 85% sensitivity and 35% specificity for predicting adverse outcome.

Conclusion

Pre-existing risk scores have shown suboptimal predictive ability for adverse events in normotensive patients with nonvariceal UGIB. The GBS (≥8) might help to identify patients prone to adverse events; however, further studies with risk scores or new scores are needed because of the low accuracy of these scores.
Costs and Trends of Emergency Department Utilization Pre-ACA and Post-ACA
Authors: Vernon Marlo , Goggans Steven , De Leo Gianluca , Heboyan Vahé
Published: April 2019

Background:

A high volume of emergency department (ED) visits in the rural United States may be the result of barriers to accessing primary care. The Affordable Care Act (ACA) increased the number of insured, which may improve patient access to primary care and therefore reduce ED utilization. The objective of this study is to estimate the trends and cost of ED utilization pre-ACA and post-ACA implementation in a rural United States.

Data and Methods:

We use 2009–2013 ED utilization data from a rural Georgia hospital to estimate trends and costs by demographic characteristics, referring source, and payor information. T tests and log-linear regression models are used to assess the sociodemographic factors impacting ED inflation-adjusted costs before (2009–2010) and after ACA (2011–2013) implementation.

Results:

During 2009–2013, 39,970 ED encounters were recorded with an average cost (AC) of $2002 per visit. Results indicate that during pre-ACA, on average, 8702 encounters were recorded per year with an AC of $1759. During post-ACA, there were 7521 annual visits, with an annual AC of $2241. Regression model results indicate that AC were significantly higher for men, older adults, nonblack patients, those with private insurance, and during the post-ACA period.

Conclusions:

Results suggest that post-ACA, declining ED visits may be due to more patients with insurance accessing primary care instead of ED. We further hypothesize that increased AC during this period may be due to ED visits being of an emergent nature, which require more resources to treat. Further comprehensive investigation is warranted to study the impact of ACA on ED utilization for nonemergency purposes among rural and nonrural hospitals.
Maryland’s Global Hospital Budgets
Authors: Beil Heather , Haber Susan G. , Giuriceo Katherine , Amico Peter , Morrison Marisa , Beadles Christopher , Berzin Olivia , Cole-Beebe Maggie , Greenwald Leslie , Jiang Linda , Perry Rebecca , Wright Alton
Published: April 2019

Background:

Global budgets have been proposed as a way to control health care expenditures, but experience with them in the United States is limited. Global budgets for Maryland hospitals, the All-Payer Model, began in January 2014.

Objectives:

To evaluate the effect of hospital global budgets on health care utilization and expenditures.

Research Design:

Quantitative analyses used a difference-in-differences design modified for nonparallel baseline trends, comparing trend changes from a 3-year baseline period to the first 3 years after All-Payer Model implementation for Maryland and a matched comparison group.

Subjects:

Hospitals in Maryland and matched out-of-state comparison hospitals. Fee-for-service Medicare beneficiaries residing in Maryland and comparison hospital market areas.

Measures:

Medicare claims were used to measure total Medicare expenditures; utilization and expenditures for hospital and nonhospital services; admissions for avoidable conditions; hospital readmissions; and emergency department visits. Qualitative data on implementation were collected through interviews with senior hospital staff, state officials, provider organization representatives, and payers, as well as focus groups of physicians and nurses.

Results:

Total Medicare and hospital service expenditures declined during the first 3 years, primarily because of reduced expenditures for outpatient hospital services. Nonhospital expenditures, including professional expenditures and postacute care expenditures, also declined. Inpatient admissions, including admissions for avoidable conditions, declined, but, there was no difference in the change in 30-day readmissions. Moreover, emergency department visits increased for Maryland relative to the comparison group.

Conclusions:

This study provides evidence that hospital global budgets as implemented in Maryland can reduce expenditures and unnecessary utilization without shifting costs to other parts of the health care system.
Medicare Beneficiaries With a Specialist as Their Personal Doctor Report Better Experiences With Care
Authors: Collins Rebecca L. , Elliott Marc N. , Burkhart Q , Haviland Amelia , Gaillot Sarah , Orr Nate , Friedberg Mark W.
Published: April 2019

Background:

Health plans often require that patients have a personal doctor. Older adults rely on specialists for much of their care and may use a specialist in this role, but little is known about how many or which Medicare beneficiaries use specialists as their personal doctor and how their care experiences differ from others’.

Objective:

To examine the prevalence and characteristics of Medicare beneficiaries with a specialist as a personal doctor and compare their patient experiences and immunization to other beneficiaries’.

Research Design:

Logistic regression predicted having a specialist as a personal doctor from beneficiary characteristics. Doubly-robust models compared 7 patient experience and 2 immunization measures for beneficiaries with and without a specialist as their personal doctor. Interactions of a specialist indicator and beneficiary characteristics tested for moderators.

Study Population:

A total of 227,642 Medicare beneficiaries aged 65+ who reported having a personal doctor on the 2014 Medicare CAHPS survey.

Results:

In total, 20% of beneficiaries reported that their personal doctor was a specialist, fewer than previously reported for the most frequently visited physician (43%); beneficiaries who were older, less healthy, less educated, racial/ethnic minorities, had fee-for-service coverage, or had lower income were more likely to do so. They also reported better patient experiences than those with nonspecialist personal physicians on 6 of 7 measures and more immunizations; the largest difference was for care coordination. Having a specialist personal doctor was associated with particularly positive patient experience for low income, Black, Hispanic, and less healthy beneficiaries.

Conclusion:

Future research should investigate whether specialists as personal doctors may reduce patient-experience disparities for vulnerable patients.
Influence of Peer Physicians on Intensity of End-of-Life Care for Cancer Decedents
Authors: Keating Nancy L. , O’Malley Alistair James , Onnela Jukka-Pekka , Gray Stacy W. , Landon Bruce E.
Published: April 2019

Background:

The intensity of end-of-life care varies substantially both within and between areas. Differing practice patterns of individual physicians are likely influenced by their peers.

Objective:

To assess whether intensity of end-of-life care previously provided by a physician’s peers influences patterns of care at the end-of-life for that physician’s patients.

Research Design:

Observational study.

Subjects:

A total of 185,947 fee-for-service Medicare enrollees with cancer who died during 2006–2010 who were treated by 26,383 physicians.

Measures:

Spending in the last month of life, >1 emergency room visit, >1 hospitalization, intensive care unit admission in the last month of life, chemotherapy within 2 weeks of death, no/late hospice, terminal hospitalization.

Results:

Mean (SD) spending in the last month of life was $16,237 ($17,124). For each additional $1000 of spending for a peer physician’s patients in the prior year, spending for the ego physician’s patients was $83 higher (P<0.001). Among physicians with peers both in and out of their practice, more of the peer effect was explained by physicians outside of the practice ($72 increase for each $1000 increase by peer physicians’ patients, P<0.001) than peer physicians in the practice ($27 for each $1000 increase by within-practice peer physicians’ patients, P=0.01). Results were similar across the other measures of end-of-life care intensity.

Conclusions:

Physician’s peers exert influence on the intensity of care delivered to that physician’s patients at the end-of-life. Physician education efforts led by influential providers and provider organizations may have potential to improve the delivery of high-value end-of-life care.
An update in the management of pediatric sarcoma
Authors: Sandler Gideon , Yokoi Akiko , Hayes-Jordan Andrea
Published: April 2019

Purpose of review

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) is a rare subgroup of malignancy in childhood that is composed of a variety of soft tissue and bony tumors. Prognosis for resectable localized disease is usually good and improved with systemic treatment. However, survival from locally advanced and metastatic disease remains poor. There have been numerous preclinical and clinical studies to define histopathology, biology, and genetic alteration of sarcomas. The purpose of this review is to clarify the progress in the management of NRSTS.

Recent findings

Genomic analysis, including the use of next-generation sequencing, has revealed fusion transcripts or specific genetic alterations which provide diagnostic biomarkers and potential targets for novel therapies.

Most cases are sporadic, but some are associated with genetic predispositions. Most present as a painless mass and diagnosis is frequently delayed because of a low index of suspicion. There is a wide array of histopathological subtypes. Investigations usually involve core, incisional or excisional biopsy for tissue diagnosis, and cross-sectional and nuclear imaging for staging. Management of pediatric sarcoma is largely dependent on the patient's histopathological diagnosis, age, disease stage, and co-morbidities but usually involves a combination of systemic and local therapies. Preclinical studies and phase I/II trials of newer targeted therapies are ongoing.
The meaning of donor-specific antibodies after heart transplant
Authors: Barten Markus J. , Zuckermann Andreas
Published: April 2019

Purpose of review

Antibody-mediated rejection (AMR) is a major contributor of impaired long-term survival after heart transplantation (HTx). The presence of circulating donor-specific antihuman leukocyte antigen (HLA) antibodies (DSAs) is considered as a mandatory criterion for AMR after HTx. DSA are known prognostic biomarkers of outcome, for example, recipients with de-novo DSA have a three-fold increased risk of mortality.

Recent findings

Although the awareness of the impact and prognosis of DSA on the survival has been increased in the HTx community over the last decade, the management of DSA pre and posttransplant varies among centers and is mainly based on the experience of transplant physicians. Thus, firm consensus strategies for each HTx recipient should be established by a center advisory board of experts in the field of HLA genetics, transplantation immunology, and HTx to evaluate the immunological risk preoperatively and also continuously during the posttransplant course. Consequently, the recent advances of invasive and noninvasive diagnostic tools should be applied, according to the risk, laboratory findings, and clinical events of the recipient. Such individual strategy will result in tailored therapeutic options.

Novel standards for the management of DSA in HTx recipients on the basis of an interdisciplinary approach of experts will improve diagnostics for personalized medicine.
Fostering Academic-Clinical Research Partnerships
Authors: Albert Nancy M. , Chipps Esther , Falkenberg Olson Ann C. , Hand Linda Liu , Harmon Michelle , Heitschmidt Mary G. , Klein Colleen J. , Lefaiver Cheryl , Wood Teresa
Published: April 2019

Academic-clinical research partnerships can benefit academic and clinical partners when goals are clearly articulated and mutually determined and include increased research dissemination and lower research costs. This article explores the history of academic-clinical research partnerships and discusses the drivers of collaborative academic-clinical research relationships, resources from academia and clinical sites, and sustainability of collaborative partnerships. Through collaboration, academic-clinical partners can improve clinical outcomes and reduce healthcare costs.
Men Who Have Sex With Men With Mycoplasma genitalium–Positive Nongonococcal Urethritis Are More Likely to Have Macrolide-Resistant Strains Than Men With Only Female Partners: A Prospective Study
Authors: McIver Ruthy , Jalocon Dean , McNulty Anna , Jeoffreys Neisha J. , Chen Sharon Chih-Ann , Power Melissa , Couldwell Deborah Leone
Published: April 2019

Background

Mycoplasma genitalium was previously less common among men who have sex with men (MSM) compared with men with only female partners (MSW) in men with nongonococcal urethritis (NGU) in Sydney, Australia. We aimed to determine the prevalence of M. genitalium and of macrolide-resistant M. genitalium in men with NGU and to compare differences between prevalence and resistance rates between MSM and MSW.

Methods

We enrolled 588 men with NGU in a prospective study at two urban sexual health services. The ResistancePlus MG assay (SpeeDx, Australia) was used to detect both M. genitalium, and macrolide resistance-associated mutations in first-void urine samples. Demographic, behavioral and clinical data were analyzed to investigate associations with M. genitalium infection or the presence of macrolide resistance.

Results

Mycoplasma genitalium prevalence was 12.8% (75 of 588) overall and among MSM (12.8% [39 of 306]) and MSW (12.8% [36 of 282]; risk ratio [RR], 1.00; 95% confidence interval [CI], 0.65–1.52). Overall, 70.7% (53 of 75) of M. genitalium strains were macrolide-resistant, with significantly more resistance among MSM (89.7%, 35 of 39) than MSW (50%, 18 of 36) (RR, 1.80; 95% CI, 1.27–2.54; P = 0.001). On multivariate analysis, the presence of M. genitalium macrolide resistance mutations was independently associated with having male sexual partners compared with having only female partners (RR, 1.55; 95% CI, 1.02–2.38; P = 0.042).

Conclusions

Prevalence of M. genitalium among men with NGU is now similar for MSW and MSM and has increased locally from 5.2% to 12.8% within the last 10 years. Men who have sex with men are significantly more likely than MSW to harbor macrolide-resistant M. genitalium infections. This has treatment implications.
Local and Visiting Physician Perspectives on Short Term Surgical Missions in Guatemala
Authors: Coughran Alanna J. , Merrell Sylvia Bereknyei , Pineda Carlos , Sceats Lindsay A. , Yang George P. , Morris Arden M.
Published: April 2019

Objective:

To explore the impact of short-term surgical missions (STMs) on medical practice in Guatemala as perceived by Guatemalan and foreign physicians.

Summary Background Data:

STMs send physicians from high-income countries to low and middle-income countries to address unmet surgical needs. Although participation among foreign surgeons has grown, little is known of the impact on the practice of foreign or local physicians.

Methods:

Using snowball sampling, we interviewed 22 local Guatemalan and 13 visiting foreign physicians regarding their perceptions of the impact of Guatemalan STMs. Interviews were transcribed verbatim, iteratively coded, and analyzed to identify emergent themes. Findings were validated through triangulation and searching for disconfirming evidence.

Results:

We identified 2 overarching domains. First, the delivery of surgical care by both Guatemalan and foreign physicians was affected by practice in the STM setting. Differences from usual practice manifested as occasionally inappropriate utilization of skills, management of postoperative complications, the practice of perioperative care versus “pure surgery,” and the effect on patient–physician communication and trust. Second, both groups noted professional and financial implications of participation in the STM.

Conclusions:

While Guatemalan physicians reported a net benefit of STMs on their careers, they perceived STMs as an imperfect solution to unmet surgical needs. They described missed opportunities for developing local capacity, for example through education and optimal resource planning. Foreign physicians described costs that were manageable and high personal satisfaction with STM work. STMs could enhance their impact by strengthening working relationships with local physicians and prioritizing sustainable educational efforts.
Decision Aid Video for Treatment Selection in Latinas With Symptomatic Pelvic Organ Prolapse: A Randomized Pilot Study
Authors: Montoya T. Ignacio , Rondeau Nancy U. , Maldonado P. Antonio , Mallett Veronica T.
Published: April 2019

Objectives

To assess impact of a decision aid video in Latina patients with symptomatic pelvic organ prolapse (POP) on knowledge, satisfaction and decisional conflict related to initial treatment selection.

Methods

Pilot study with randomized prospective design. Thirty Latina women with symptomatic POP were randomized to a decision aid intervention plus standard care (N = 15) or standard care alone (N = 15) group. Decision aid intervention consisted of a 10-minute video presented at time of initial evaluation for POP. Outcome measures included the Prolapse and Incontinence Knowledge Quiz (“Knowledge”), the Satisfaction with Decision (“Satisfaction”) and Decisional Conflict (DCS) scales, and were assessed at 4 different timepoints: after initial visit, and at 1, 3 and 6 months after. Data was analyzed using repeated-measures ANOVA and pairwise between-group comparisons.

Results

Demographic and baseline data were similar between groups. There was a significant interaction between groups and time on the Knowledge scores (P = 0.03). Knowledge scores were higher at the initial visit in the intervention group (10.6 ± 0.8 vs 9.53 ± 1.4, P = 0.014). Satisfaction scores were lower in the intervention group on longitudinal analysis, indicating higher satisfaction (P = 0.02). There was no difference on overall Decisional Conflict scores between groups. The intervention group had lower scores on the “effective decision” DCS subscale at 3 and 6 months and “informed” DCS subscale at 3 months.

Conclusions

A decision aid video intervention in Latina women with POP used at the time of initial evaluation may help the patient make a more informed treatment decision by increasing condition-related knowledge and lead to greater long-term satisfaction.
Altered monocyte and NK cell phenotypes correlate with posttrauma infection
Authors: Seshadri Anupamaa , Brat Gabriel A. , Yorkgitis Brian K. , Giangola Matt , Keegan Joshua , Nguyen Jennifer P. , Li Wei , Nakahori Yasutaka , Wada Takeshi , Hauser Carl , Salim Ali , Askari Reza , Lederer James A.
Published: April 2019

BACKGROUND

Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection.

METHODS

Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons.

RESULTS

The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection.

CONCLUSION

This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients.

LEVEL OF EVIDENCE

Prognostic study, level II.
Congenital Cranial Dysinnervation Disorder: An Unusual Phenotype With Multiple Cranial Neuropathies and Novel Neuroimaging Findings
Authors: Salman Michael S. , Mulholland Conor , Wrogemann Jens , Marin Samantha E.
Published: April 2019

Congenital cranial dysinnervation disorders result from a maldevelopment of brainstem nuclei and/or cranial nerves. In some cases, specific genetic abnormalities have been identified. We expand the clinical phenotype of these disorders with the report of a 28-month-old girl who was initially evaluated for seizures and was found to have right sixth nerve palsy, small optic discs with reduced vision in her right eye. Her development was delayed. Brain MRI showed multiple abnormalities involving other cranial nerves, the optic chiasm and brainstem. Her developmental delay and seizure disorder suggest additional cortical involvement.
Functional Genomic Complexity Defines Intratumor Heterogeneity and Tumor Aggressiveness in Liver Cancer
Authors: Kwon So Mee , Budhu Anuradha , Woo Hyun Goo , Chaisaingmongkol Jittiporn , Dang Hien , Forgues Marshonna , Harris Curtis C. , Zhang Gao , Auslander Noam , Ruppin Eytan , Mahidol Chulabhorn , Ruchirawat Mathuros , Wang Xin Wei
Published: April 2019

Background

Chronic inflammation and chromosome aneuploidy are major traits of primary liver cancer (PLC), which represent the second most common cause of cancer related death worldwide. Increased cancer fitness and aggressiveness of PLC may be achieved by enhancing tumoral genomic complexity that alters tumor biology.

Method

Here, we developed a scoring method, namely functional genomic complexity (FGC), to determine the degree of molecular heterogeneity among 580 liver tumors with diverse ethnicities and etiologies by assessing integrated genomic and transcriptomic data.

Results

We found that tumors with higher FGC scores are associated with chromosome instability and TP53 mutations, and a worse prognosis, while tumors with lower FGC scores have elevated infiltrating lymphocytes and a better prognosis. These results indicate that FGC scores may serve as a surrogate to define genomic heterogeneity of PLC linked to chromosomal instability and evasion of immune surveillance.

Conclusion

Our findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy.

STATEMENT OF SIGNIFICANCE

Genomic heterogeneity contributes to therapeutic failure and poor outcome in patients with liver cancer and poses a challenge in defining targeted therapy. Our findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy. \body
Single cell RNA sequencing reveals cellular diversity of trisomy 21 retina
Authors: Wu Jihong , Ding Xiangning , Hu Fangyuan , Xu Zaoxu , Zhang Shenghai , Liang Langchao , Chai Chaochao , Zhong Jixing , Wang Shiyou , Lin Xiumei , Chen Yin , Feng Qikai , Zhu Jiacheng , Jiang Sanjie , Xia Jun , Li Wei , Gao Ya , Li Jiankang , Zhang Jingxuan , He Zhikai , Xue Shen , Guo Guanglin , Xu Ping , Gao Fengjuan , Wang Dandan , Zhang Daowei , Chen Dongsheng , Sun Xinghuai , Chen Fang
Published: April 2019

Retina is a crucial tissue for the capturing and processing of light stimulus. Characterization of the retina at single cell level is essential for the understanding of its biological functions. A variety of abnormalities in terms of morphology and function were reported in T21 retina. To evaluate the effects of chromosome aneuploidy on retina development, we characterized single cell transcriptional profiles of a T21 fetus and performed comprehensive bioinformatic analyses. Our data revealed the diversity and heterogeneity of cellular compositions in T21 retina. In total, we identified seven major cell types, and detected several subtypes within each cell type, followed by the detection of corresponding molecular markers including previously reported ones and a series of novel markers. Our analyses identified extensive communication networks between distinct cellular types, among which a few ligand-receptor interactions were associated with the development of retina and immunoregulatory interactions. Taken together, our data provided the first single cell transcriptome profile for human T21 retina which facilitates our understanding on the dosage effects of chromosome 21 on the development of retina.
Slow andad hoc: Unravelling the two features characterizing the development of bacterial resistance to membrane active peptides
Authors: Majumder Ayan , Prakash Meher K.
Published: April 2019

Membrane disrupting drugs such as antimicrobial peptides are being considered as a solution to counter the problem of antibiotic resistance. Although it can be intuitively imagined that bacteria will eventually develop resistance to this class of drugs as well, the concern has largely been ignored. Drawing upon the experimental data from the resistance ofStaphylococcus aureusto antimicrobial peptides, we theoretically model the membrane adaptation under drug pressure. Using our model, we simulate the serial passage experiments with and without the drug pressure, and use the comparisons with experiments to estimate the unknown kinetic parameters. While the development of resistance to enzyme or membrane targeting drugs are both driven by spontaneous mutations, an additional lysylation step required in the latter slows the development of resistance. By quantifying the tradeoff between the gain in fitness under drug pressure and a loss in growth due to membrane modification, our model shows a fast reversal of membrane composition in drug free conditions, re-sensitizing the bacterium to the drugs.