bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the survival prognosis of lung adenocarcinoma based on the cancer genome atlas database using artificial neural network
Authors: Jiang Na , Xu Xianrong
Published: May 2019

The aim of this study was to investigate the clinical factors affecting the survival prognosis of lung adenocarcinoma, and to establish a predictive model of survival prognosis of lung adenocarcinoma by artificial neural network.

Download the cancer genome atlas (TCGA) database for lung adenocarcinoma research data, perform cox regression analysis and descriptive statistics on the obtained clinical data, draw the survival curve by Kaplan–Meier method, select the independent variables that are statistically significant for constructing the artificial neural networks (ANN) model, and establish artificial neural network model.

The number of valid cases included in the study was 524, including 280 men and 244 women, with an age range of 33 to 88 years, mean age 66.87 years, and median progression-free survival (PFS) was 37.7 months. The median overall survival time (OS) was 41.1 months. Cox multivariate analysis showed that smoking history, tumor stage, and surgical margin resection status were independently associated with PFS, and tumor stage and surgical margin resection status were independently associated with OS. The accuracy of the established ANN model itself was predicted to be 65.8%. The accuracy of correctly predicting the prognosis of the predicted samples was 75.0%, and the area under the receiver operating characteristic curve was 0.712.

The clinical prognostic factors of lung adenocarcinoma include: smoking history, tumor stage, and surgical margin resection status. The established ANN model can be used to predict the prognosis of lung adenocarcinoma.
Template matching for benchmarking hospital performance in the veterans affairs healthcare system
Authors: Vincent Brenda M. , Wiitala Wyndy L. , Luginbill Kaitlyn A. , Molling Daniel J. , Hofer Timothy P. , Ryan Andrew M. , Prescott Hallie C.
Published: May 2019

Comparing hospital performance in a health system is traditionally done with multilevel regression models that adjust for differences in hospitals’ patient case-mix. In contrast, “template matching” compares outcomes of similar patients at different hospitals but has been used only in limited patient settings.

Our objective was to test a basic template matching approach in the nationwide Veterans Affairs healthcare system (VA), compared with a more standard regression approach.

We performed various simulations using observational data from VA electronic health records whereby we randomly assigned patients to “pseudo hospitals,” eliminating true hospital level effects. We randomly selected a representative template of 240 patients and matched 240 patients on demographic and physiological factors from each pseudo hospital to the template. We varied hospital performance for different simulations such that some pseudo hospitals negatively impacted patient mortality.

Electronic health record data of 460,213 hospitalizations at 111 VA hospitals across the United States in 2015.

We assessed 30-day mortality at each pseudo hospital and identified lowest quintile hospitals by template matching and regression. The regression model adjusted for predicted 30-day mortality (as a measure of illness severity).

Regression identified the lowest quintile hospitals with 100% accuracy compared with 80.3% to 82.0% for template matching when systematic differences in 30-day mortality existed.

The current standard practice of risk-adjusted regression incorporating patient-level illness severity was better able to identify lower-performing hospitals than the simplistic template matching algorithm.
First successful combination of extracorporeal membrane oxygenation (ECMO) with video-assisted thoracic surgery (VATS) of pulmonary bullae resection in the management of refractory pneumothorax in a critically ill patient with H7N9 pneumonia and acute respiratory distress syndrome
Authors: Huang Jinbao , Li Hongyan , Chen Shuxing , Lan Changqing , Lin Qinghua , Weng Heng
Published: May 2019

Rationale:

At present, data regarding refractory pneumothorax treated with video-assisted thoracic surgery (VATS) in combination with extracorporeal membrane oxygenation (ECMO) in critically ill patients with H7N9 pneumonia have never been reported.

Patient concerns:

A laboratory-confirmed case of human infection with avian influenza A (H7N9) virus was treated in our hospital. Acute respiratory distress syndrome (ARDS) developed and the patient was oxygenated via veno-venous ECMO due to the failure of mechanical ventilation. Unfortunately, a right refractory pneumothorax occurred. Despite treatment with pleural drainage and select bronchial occlusion, the patient still failed to improve.

Diagnosis:

Fatal H7N9 pneumonia complicated with severe ARDS, pulmonary bullae, and refractory pneumothorax.

Interventions:

Successful combination of ECMO with VATS of pulmonary bullae resection was performed and pneumothorax was cured.

Outcomes:

One week after the operation, ECMO was removed. However, the patient finally developed multiorgan failure (MOF) complicated by refractory hypoxemia due to progressive lung fibrosis and died 36 days after admission.

Lessons:

Although the patient died of MOF triggered by severe lung fibrosis at last, the successful treatment of refractory pneumothorax by combination of ECMO with VATS is encouraging. Thus, when refractory pneumothorax in a patient with severe pulmonary dysfunction fails to improve through routine therapy, the treatment of pneumothorax by VATS based on ECMO support can be considered as a feasible selection.
Extensive intravesical benign hyperplasia induced by an extravesical migrated intrauterine device
Authors: Zhang Peng , Wang Ting , Yang Lu
Published: May 2019

Rationale:

Intravesical migrated intrauterine devices (IUDs) have been reported to cause bladder perforation, stone formation, or malignant transition. However, such extensive intravesical benign hyperplasia caused by an extravesical migrated IUD is firstly reported.

Patient concerns:

A 38-year-old woman suffered from recurrent urinary urgency and dysuria and without macroscopic hematuria for about 1 month.

Diagnoses:

Urinary ultrasound and abdominal contrast-enhanced computed tomography (CT) revealed thickening of the bladder walls. Diagnostic transurethral resection and pathology initially misdiagnosed the intravesical lesions as non-invasive urothelial carcinoma. Further diagnostic and therapeutic transurethral resections and pathology confirmed the intravesical lesions to be extensive benign hyperplasia, which was extremely likely caused by the extravesical migrated IUD.

Interventions:

The intravesical lesions received therapeutic transurethral resections. Then the migrated IUD was removed by open surgery.

Outcomes:

After above treatments, the patient's lower urinary tract symptoms gradually disappeared. No recurrent lesion was found in the bladder through CT 3 months later.

Lessons:

Even an extravesical migrated IUD could silently cause extensive intravesical lesions. Whether symptomatic or not, any migrated IUD including extravesical and intravesical ones should be treated seriously, if possible, removed as soon as possible.
Efficacy of Xianling Gubao capsule in treating sarco-osteopenia
Authors: Chen Qunqun , Zeng Junxiang , Chen Yi , Yang Yalan , Zhang Tian , Luo Tao , Huang Hongxing
Published: May 2019

Background:

Sarco-osteopenia (SOP) is a new type of geriatric syndrome, resulting from the combination of sarcopenia (SP) and osteoporosis (OP). Xianling Gubao capsule (XLGBC), made from several traditional Chinese medicine, is reported to have a therapeutic effect on diseases of bones and joints. This protocol will be designed to assess the efficacy of XLGBC in the treatment of SOP.

Methods:

Relevant randomized controlled trial literatures evaluating the effect of XLGBC on patients with SOP will be obtained by searching the following 7 electronic databases: Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Chinese Biomedical and Medical Database (CBM), and Wanfang Database, from inception to March 2019. The primary outcomes will be bone mineral density, skeletal muscle mass index, handgrip strength, and gait speed. Stata V.13.0 software will be used for data synthesis and analysis, sensitivity analysis, subgroup analysis, and risk of bias assessment. Reporting bias will be evaluated utilizing a funnel, with Egger tests assessing funnel plot symmetries. Quality of evidence will be evaluated according to guidance of the Recommendations Assessment, Development, and Evaluation guideline.

Result:

This study will provide a rational synthesis of current evidences for XLGBC on SOP.

Conclusion:

The conclusion of this study will provide evidence to judge the effectiveness and safety of XLGBC on SOP.

Ethics and dissemination:

This systematic review will be contributed to peer-reviewed publications, aiming to provide evidence about efficacy of XLGBC on SOP.

Trial registration number:

CRD42019128223.
A phase II study of biweekly oxaliplatin plus S-1 combination chemotherapy as a first-line treatment for patients with metastatic or advanced gastric cancer in China
Authors: Xiao Cheng , Qian Jiong , Zheng Yulong , Song Fang , Wang Qiangfeng , Jiang Haiping , Mao Chenyu , Xu Nong
Published: May 2019

Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3 weeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.

Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85 mg/m2 on day 1, while S-1 was administered orally in doses of 80, 100, or 120 mg/day depending on different body surface areas of <1.25 m2, 1.25–1.5 m2, or >1.5 m2 respectively; the total dose of S-1 was administered twice daily on days 1–7 followed by a 7-day rest. This schedule was repeated every 2 weeks until disease progressed or intolerable toxicity occurred.

Forty-six patients (M/F = 33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4 months (95% CI, 3.37–5.36 months) and 10.3 months (95% CI, 8.88–11.3 months), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).

The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.
Proposal of a multidimensional strategic-management dashboard for use in a rehabilitation respiratory unit
Authors: Vitacca Michele , Vitacca Mauro
Published: May 2019

Health information systems are the core support to decision-making in health organizations. Economic and clinical managements often function separately, while a governance system for quality and safety functions with quality checks and performance accountability, could improve efficiency. The aims of this study were, within a respiratory rehabilitation unit (RRU), to: develop a management-strategy dashboard based on key performance areas (KPAs), identify key performance indicators (KPIs) for each KPA which allow multidimensional assessment; estimate the expected results from the implementation of this dashboard using the balanced score card (BSC) method.

In December 2017, a working group was set up at the RRU to develop the dashboard by selecting criteria for KPA and determining the KPIs with their rationale, weight, calculation method, measurements, supply system, target values, and working rules.

After 3 meetings, 6 KPAs and 12 KPIs for the financial area, 3 KPAs and 15 KPIs for internal processes, 6 KPAs and 8 KPIs for innovation and growth, and 4 KPAs and 5 KPIs for the Clients’ Perspective were approved. A strategic map showing the cause/effect relations between the different KPAs was drawn.

A BSC-based quality measurement integrating economic and clinical management dimensions is possible also in an RRU. The proposed dashboard can improve communication, strategy, information dissemination, information communication technology management, budget negotiations, organizational quality, and accountability to stakeholders.
Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients
Authors: Yang Wenwei , Li Shuquan , Yang Qingrui
Published: May 2019

Background:

Programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are promising cancer immunotherapy. Their dermatologic safety profiles are still poorly understood. The purpose of this article is to evaluate the incidence of selected dermatologic and mucosal adverse effects (AEs) and determine the risk of developing these adverse events associated with PD-1/PD-L1 inhibitors, compared with chemotherapy or ipilimumab.

Methods:

PubMed was searched for eligible studies (up to February 21, 2019). Only phase II and phase III randomized controlled trials (RCTs) compared with chemotherapy or ipilimumab monotherapy were included in this meta-analysis.

Results:

A total 11,465 patients from 18 clinical trials were included in this meta-analysis. Rash and pruritus were the most frequently reported dermatologic AE, with incidence 11.8% and 12.2% respectively. Compared with patients receiving chemotherapy, PD-1/PD-L1 inhibitor treated patients had higher risk of developing rash (RR = 1.84), pruritus (RR = 3.74) and vitiligo (RR = 9.54), and also lower risk in developing mucosal inflammation (RR = 0.26), stomatitis (RR = 0.26), and alopecia (RR = 0.03). Additionally, anti-PD1/PD-L1 drugs had similar risk of developing rash and lower risk of inducing pruritus compared to ipilimumab. In the subgroup analysis, PD-L1 inhibitor demonstrated better safety than PD-1 inhibitor in developing rash, with RR = 1.38 and RR = 2.11, respectively.

Conclusion:

Our meta-analysis concluded that anti PD-1/PD-L1 drugs have different dermatological and mucosal safety profile compared to conventional therapy, and differences of dermatological toxicity between PD-1 and PD-L1 inhibitor warrant further investigation.
Intravitreal ranibizumab injection at the end of vitrectomy for diabetic vitreous hemorrhage (Observational Study)
Authors: Liang Xu , Zhang Yue , Wang Jia-Xing , Wang Li-Fei , Huang Wan-Rong , Tang Xin
Published: May 2019

To evaluate the outcomes and complications of intravitreal injections of ranibizumab in patients during pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. This retrospective, observational, comparative study included 103 patients (103 eyes) who underwent pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. Sixty-six patients received an intravitreal injection of 0.05 mg (0.05 cc) of ranibizumab at the end of surgery. Main outcome measures were the occurrence of recurrent early vitreous hemorrhage, reoperation, intraocular pressure, best corrected visual acuity. Mean follow-up time was 6 months. The rate of rebleeding in the intravitreal ranibizumab (IVR) group was 6.1% (4 eyes), which is significantly lower than the control group (24.3%, 9 eyes, P < .01). The incidence of postoperative diabetic vitreous hemorrhage (PDVH) was significantly lower in the IVR group than the control group, OR=0.26, 95% CI= (0.06, 0.95). Visual acuity 6 months after operation was better in IVR group (P<.01) There was no difference in mean intraocular pressure between the 2 groups (P=.56). The present clinical study suggests that intravitreal injection of ranibizumab is effective in the prevention of postoperative diabetic vitreous hemorrhage in eyes undergoing pars plana vitrectomy for the treatment of diabetic vitreous hemorrhage.
Synchronous occurrence of benign mesothelioma and adenomatoid tumor of uterus
Authors: Shen Ping-Rong , Cen Jin , Qian Xue-Qian , Shen Yuan-Ming , Cheng Xiao-Dong , Wan Xiao-Yun
Published: May 2019

Introduction:

Synchronous occurrence of benign cystic mesothelioma and adenomatoid tumor of uterus (UAT) are very rare and few cases have been published in the English literature. They are easily misdiagnosed as malignant by clinicians, due to the lack of reports.

Patient concerns:

A case of benign mesothelial combined with uterus adenomatoid tumor (UAT) in a 48-year-old Chinese woman was reported. Our patient presented with abdominal pain and surgery showed a large subserous mass (12.0 × 11.4 × 9.8 cm) combined with a small intramural solid nodule (2.0 × 1.0 × 1.0 cm), and multiple minute neoplastic growth on the ovary.

Diagnosis:

Due to the patient's symptoms, pathological findings, she was diagnosed with synchronous occurrence of benign mesothelioma and UAT.

Interventions:

We treated her with a total hysterectomy and bilateral adnexectomy.

Outcomes:

The patient is now in stable condition, without any signs of recurrence during 1 year of follow-up.

Lessons:

Most mesotheliomas are malignant, synchronous occurrence of benign mesothelioma and UAT are extremely rare. And they are often misdiagnosed as malignancy by clinicians. Our case report can improve the awareness of the disease and avoid excessive treatment.
Feasibility and Outcomes of an Electronic Health Record Intervention to Improve Hypertension Management in Immigrant-serving Primary Care Practices
Authors: Lopez Priscilla M. , Divney Anna , Goldfeld Keith , Zanowiak Jennifer , Gore Radhika , Kumar Rashi , Laughlin Phoebe , Sanchez Ronald , Beane Susan , Trinh-Shevrin Chau , Thorpe Lorna , Islam Nadia
Published: May 2019

Background:

South Asians experience a disproportionate burden of high blood pressure (BP) in the United States, arguably the most preventable risk factor for cardiovascular disease.

Objective:

We report 12-month results of an electronic health record (EHR)-based intervention, as a component of a larger project, “Implementing Million Hearts for Provider and Community Transformation.” The EHR intervention included launching hypertension patient registries and implementing culturally tailored alerts and order sets to improve hypertension control among patients treated in 14 New York City practices located in predominantly South Asian immigrant neighborhoods.

Design:

Using a modified stepped-wedge quasi-experimental study design, practice-level EHR data were extracted, and individual-level data were obtained on a subset of patients insured by a Medicaid insurer via their data warehouse. The primary aggregate outcome was change in proportion of hypertensive patients with controlled BP; individual-level outcomes included average systolic BP (SBP) and diastolic BP (DBP) at last clinic visit. Qualitative interviews were conducted to assess intervention feasibility.

Measures:

Hypertension was defined as having at least 1 hypertension ICD-9/10 code. Well-controlled hypertension was defined as SBP<140 and DBP<90 mm Hg.

Results:

Postintervention, we observed a significant improvement in hypertension control at the practice level, adjusting for age and sex patient composition (adjusted relative risk, 1.09; 95% confidence interval, 1.04–1.14). Among the subset of Medicaid patients, we observed a significant reduction in average SBP and DBP adjusting for time, age, and sex, by 1.71 and 1.13 mm Hg, respectively (P<0.05). Providers reported feeling supported and satisfied with EHR components.

Conclusions:

EHR initiatives in practices serving immigrants and minorities may enhance practice capabilities to improve hypertension control.
Adapting Patient Experience Data Collection Processes for Lower Literacy Patient Populations Using Tablets at the Point of Care
Authors: Tieu Lina , Hobbs Alicia , Sarkar Urmimala , Nacev Erin C. , Lyles Courtney R.
Published: May 2019

Background:

Patient experience surveys are widely used to capture the patient-reported quality of care and are increasingly being used for formal reporting purposes. There is evidence that certain patient subgroups are less likely to respond to traditional CAHPS surveys. As patient-facing technologies become more common, it is important to examine whether tablet-based patient experience surveys have the potential to promote responses from more diverse populations.

Objectives:

To develop, gain perspectives about, and pilot an English and Spanish low-literacy adaptation of the Consumer Assessment of Healthcare Providers & Systems Clinician & Group Survey (CG-CAHPS) administered on a tablet device at the point of care.

Research Design:

Cognitive testing and evaluation of a quality improvement pilot comparing a tablet-based adaptation and traditional paper-based versions of the CG-CAHPS survey.

Subjects:

English-speaking and Spanish-speaking patients receiving primary care in an urban community clinic.

Measures:

To compare the acceptability of low-literacy tablet-based and traditional paper-based patient experience surveys, we examined the concordance of responses between survey modes and preferences for modality, as well as perspectives on usability and reporting care experiences. We examined demographic differences in responses to tablet-based versus mailed surveys from a quality improvement pilot.

Results:

The majority of cognitive interview participants preferred a low-literacy, tablet-based survey over a paper-based survey with traditional wording. In a quality improvement pilot comparing tablet-based administration at the point of care versus mailed surveys, respondents to the tablet-based survey were more likely to be younger and Latino.

Conclusions:

If designed with patient input, tablet-based surveys have the potential to improve the collection of patient experience data among diverse populations.
Clinician Experiences and Attitudes Regarding Screening for Social Determinants of Health in a Large Integrated Health System
Authors: Schickedanz Adam , Hamity Courtnee , Rogers Artair , Sharp Adam L. , Jackson Ana
Published: May 2019

Background:

Clinical screening for basic social needs—such as food and housing insecurity—is becoming more common as health systems develop programs to address social determinants of health. Clinician attitudes toward such programs are largely unexplored.

Objective:

To describe the attitudes and experiences of social needs screening among a variety of clinicians and other health care professionals.

Research Design:

Multicenter electronic and paper-based survey.

Subjects:

Two hundred fifty-eight clinicians including primarily physicians, social workers, nurses, and pharmacists from a large integrated health system in Southern California.

Measures:

Level of agreement with prompts exploring attitudes toward and barriers to screening and addressing social needs in different clinical settings.

Results:

Overall, most health professionals supported social needs screening in clinical settings (84%). Only a minority (41%) of clinicians expressed confidence in their ability to address social needs, and less than a quarter (23%) routinely screen for social needs currently. Clinicians perceived lack of time to ask (60%) and resources (50%) to address social needs as their most significant barriers. We found differences by health profession in attitudes toward and barriers to screening for social needs, with physicians more likely to cite time constraints as a barrier.

Conclusions:

Clinicians largely support social needs programs, but they also recognize key barriers to their implementation. Health systems interested in implementing social needs programs should consider the clinician perspective around the time and resources required for such programs and address these perceived barriers.
Age and Tumor Location Predict Survival in Nonmetastatic Osteosarcoma in Upper Egypt
Authors: Morsy Ahmed M. , Ahmed Badawy M. , Rezk Khalid M. , Ramadan Islam K.-A. , Aboelgheit Amir M. , Eltyb Hanan A. , Abd Elbadee Osama M. , El-Naggar Maha S.
Published: May 2019

Aim:

The aims of this study were to assess survival outcome of pediatric patients with localized osteosarcoma of the extremities in Upper Egypt, identify factors of prognostic significance for survival, and to determine factors predictive of surgical methods used in these patients, as well as developing a clinical model for risk prediction.

Patients and Methods:

A retrospective analysis of data assembled from medical records of 30 pediatric patients with a histologically verified nonmetastatic osteosarcoma of the extremities treated at South Egypt Cancer Institute with a unified chemotherapy protocol between January 2001 and December 2015 was carried out. Prognostic factors were determined using univariable and multivariable methods. A model for surgical outcomes in these patients based on the baseline clinical factors, and the parameters predictive of their tumor response to chemotherapy, was developed.

Results:

With a median follow-up of 63 months for the study population, the estimates for event-free survival and overall survival (OS) at 3 and 5 years were 69.5% and 79% and 65.2% and 65.3%, respectively. Age 16 years or above was independently associated with both worse metastasis-free survival (hazard ratio [HR]=6.05, 95% confidence interval [CI]: 1.43-25.6, P=0.015) and OS (HR=7.9, 95% CI: 1.71-36.2, P=0.008). In the multivariable analysis, a proximal location within the limb gained a statistical significance to be independently associated with worse OS (HR=2.4, 95% CI: 1.13-22.1, P=0.003). Poor response to chemotherapy was marginally associated with worse metastasis-free survival (HR=4.9, 95% CI: 1.02-23.8, P=0.047) only in the univariable analysis. The patients found to be more likely to undergo an amputation surgery (odds ratio=14.1, 95% CI: 1.34-149.4, P=0.028) were those in whom a tumor was poorly responding to chemotherapy.

Conclusion:

In Upper Egypt, despite the reasonable survival outcomes in nonmetastatic osteosarcoma, a relatively high limb amputation rate has been encountered. The development of a clinical prediction model for future planning of possible outcome improvement in these patients, however, is still feasible.
Microsecretory Adenocarcinoma
Authors: Bishop Justin A. , Weinreb Ilan , Swanson David , Westra William H. , Qureshi Hina S. , Sciubba James , MacMillan Christina , Rooper Lisa M. , Dickson Brendan C.
Published: May 2019

Salivary gland adenocarcinoma not otherwise specified (NOS) is a heterogenous group, likely containing distinct tumors not yet characterized. A growing number of low to intermediate-grade salivary carcinomas are now known to harbor tumor-specific gene fusions. On occasion, identifying a novel fusion allows for recognition of a new salivary tumor type, in addition to representing a potential diagnostic tool. We sought to characterize a distinctive salivary gland adenocarcinoma that would previously have been regarded as adenocarcinoma NOS. On the basis of the recognition of 5 morphologically identical, distinct low-grade salivary adenocarcinomas, we used targeted RNA sequencing (RNA-Seq) to determine whether these could be differentiated from other fusion-associated salivary gland tumors. RNA-Seq was performed on all 5 low-intermediate grade adenocarcinomas NOS with near-identical histologic appearances, as well as 23 low-intermediate grade control adenocarcinoma NOS cases that did not resemble the index cases. All 5 index cases harbored a novel MEF2C-SS18 gene fusion, which was independently confirmed by reverse transcriptase-polymerase chain reaction. The MEF2C-SS18-positive cases arose in the oral cavity (4/5) and parotid gland (1/5) of 3 women and 2 men ranging from 21 to 80 years (mean: 46) and shared near-identical histologic features: intercalated duct-like cells with eosinophilic to clear cytoplasm and small, uniform oval nuclei, infiltrative microcysts and cords, abundant intraluminal secretions, and cellular fibromyxoid stroma. Mitotic rates were low; necrosis was absent. All MEF2C-SS18-positive tumors were positive for S100 and p63 and negative for p40, smooth muscle actin, calponin, and mammaglobin. One of the 23 control cases, a parotid tumor, was found to contain a SS18-ZBTB7A gene fusion; it demonstrated similar, but not identical histologic and immunophenotypic features compared with the MEF2C-SS18 cases. The remaining control cases were negative for SS18 and MEF2C rearrangements. A novel MEF2C-SS18 gene fusion and unique histologic and immunophenotypic features characterize a heretofore undefined low-grade salivary adenocarcinoma for which we propose the term “microsecretory adenocarcinoma.” RNA-Seq helped establish this entity as a distinct tumor type, and identified one possibly related case with a different SS18-related fusion. The recognition of microsecretory adenocarcinoma and its separation from other adenocarcinomas NOS will facilitate a more complete understanding of the clinical and pathologic characteristics of this previously unrecognized neoplasm.
Tumor Budding Is an Objective High-risk Factor Associated With Metastasis and Poor Clinical Prognosis in Cutaneous Squamous Cell Carcinoma Sized <4 cm
Authors: Fujimoto Masakazu , Yamamoto Yuki , Takai Toshihiro , Fujimoto Noriki , Ogawa Kohei , Yoshikawa Takanori , Matsuzaki Ibu , Takahashi Yuichi , Iwahashi Yoshifumi , Warigaya Kenji , Kojima Fumiyoshi , Jinnin Masatoshi , Murata Shin-ichi
Published: May 2019

Although most cases of early cutaneous squamous cell carcinoma (CSCC) are indolent, a small subset metastasize and can be fatal. However, high-risk features of CSCC are controversial, and it is difficult to predict the biological behavior. In this study, we have tested the prognostic significance of tumor budding in CSCCs <4 cm in diameter. Hematoxylin and eosin–stained sections of surgically resected CSCCs (24 metastasizing and 24 nonmetastasizing cases) <4 cm in size were reviewed retrospectively. Tumor bud, defined as an isolated cancer cell or a cluster comprising<5 cells, was counted at a hot spot (1.23 mm2), and graded between 1 and 3; grade 1: 0 to 4 buds; grade 2: 5 to 9 buds; and grade 3: ≥10 buds. Cases with grades 2 or 3 were regarded as positive for tumor budding. We found that tumor budding was positive in 83.3% of metastasizing CSCC, and 37.5% of nonmetastasizing CSCC (P<0.01). Moreover, CSCCs with grade 3 tumor budding showed worse disease-specific survival (P<0.01). Regarding interobserver reproducibility, the median κ value for tumor budding was significantly higher than that for histologic differentiation (P<0.01). In conclusion, tumor budding may be a valuable histologic marker for risk stratification of early CSCC in routine practice. Patients with tumor budding positive CSCC may benefit from evaluation and close follow-up for regional node metastasis.
Updates on Current Role and Practice of Lung Ablation
Authors: Abtin Fereidoun , De Baere Thierry , Dupuy Damian E. , Genshaft Scott , Healey Terrance , Khan Sarah , Suh Robert
Published: May 2019

Interventional oncology and management of thoracic malignancies with ablative techniques are becoming ever more recognized therapeutic options. With increased understanding, development, and utility of the ablative techniques, the indications are expanding and efficacy improving. Lung cancer was among the first indications for lung ablation and remains most challenging with multiple therapeutic options. For inoperable patients, the current literature demonstrates equivalent survivals between ablation, sublobar resection, and stereotactic body radiation. Oligometastatic disease remains the most common indication for lung ablation and is gaining acceptance among the oncology community, as lung ablation provides limited patient downtime, repeatability, and minimal to no loss of respiratory function. Other indications for ablation are being explored, including recurrent mesothelioma, drop metastasis from thymoma, and limited pleural metastasis, with excellent local control of tumor and limited complications. Follow-up after ablation is essential to detect early complications, observe the natural evolution of the ablation zone, and detect recurrence. Standardized imaging follow-up allows for these goals to be achieved and provides a framework for oncology practice. In this article, the role of ablation in the management of thoracic neoplasms and postablation imaging features are reviewed. The radiologists, in particular, thoracic radiologists should be able to identify candidates who can benefit from ablation familiarize themselves with postablation imaging features, and recognize the evolution of the postablation zone and hence detect early recurrence.
Quantitative Evaluation of Shear Wave Elastography on Radiation-Induced Neck Fibrosis in Patients With Nasopharyngeal Carcinoma
Authors: Wen Xin , Yu Xiwen , Cheng Wen , Li Yang , Tian Jiawei
Published: May 2019

The value of shear wave elastography (SWE) for quantitatively assessing neck fibrosis induced by radiotherapy (RT) in patients with nasopharyngeal carcinoma was evaluated over time. We prospectively observed 56 patients with nasopharyngeal carcinoma before and after therapeutic neck irradiation. The elasticity parameters including Emax and Emean were used to measure the stiffness of the bilateral sternocleidomastoid muscles. Twenty-seven patients completed a 1.5-year follow-up, with examinations beginning at 3, 6, 12, and 18 months after RT. Forty controls were recruited for reliability tests (along with the patients) and measurement comparisons. The consistency of SWE measurements with the Late Effects Normal Tissue Task Force–Subjective, Objective, Management and Analytic (LENT-SOMA) scale was tested. The intraclass correlation coefficients of elasticity indices for both patients and controls were higher than 0.75. The Emax and Emean of bilateral sternocleidomastoid muscles in the pre-RT patient group were comparable with those of the controls, and increased with increasing postirradiation duration (r = 0.514–0.555; P < 0.01). Significant increases in the Emax and Emean were observed 18 months after RT. The SWE correlated well with the LENT-SOMA score when assessing radiation-induced neck fibrosis 1.5 years after RT (r = 0.557–0.649; P < 0.01). Furthermore, both the Emax and Emean in the LENT-SOMA grade 0 subtype were higher 18 months after RT than before RT (P < 0.01). Because of its high reliability and good consistency with the LENT-SOMA score and better stiffness reflection at grade 0, SWE may be used to objectively and quantitatively evaluate the variation trend of radiation-induced neck fibrosis.
Ultrasound Features of Uterine Sarcomas
Authors: Oh Jiyun , Park Sung Bin , Park Hyun Jeong , Lee Eun Sun
Published: May 2019

Uterine sarcomas include leiomyosarcoma, smooth muscle tumor of uncertain malignant potential, endometrial stromal sarcoma, undifferentiated sarcoma, carcinosarcoma, adenosarcoma, and rhabdomyosarcoma. Leiomyosarcomas are the most common uterine sarcomas and list some potential others. Uterine sarcomas have a wide histopathological spectrum that may display various imaging features, making the preoperative diagnosis challenging. The purpose of this review was to discuss the clinical features of uterine sarcomas, as well as their imaging appearances and characteristics. From this, practitioners can ensure that suspicious sonographic findings of uterine sarcomas, including a large-size, heterogeneous echotexture, central cystic change or necrosis, and hypervascularity, are recognized to facilitate further evaluation. Familiarity with the clinical presentations and imaging features of uterine sarcomas can lead to a more accurate diagnosis and appropriate management.
Top-tier emergency general surgery hospitals: Good at one operation, good at them all
Authors: DeWane Michael P. , Sukumar Nitin , Stolar Marilyn J. , Gill Thomas M. , Maung Adrian A. , Schuster Kevin M. , Davis Kimberly A. , Becher Robert D.
Published: May 2019

BACKGROUND

There is a longstanding interest in the field of management science to study high performance organizations. Applied to medicine, research on hospital performance indicates that some hospitals are high performing, while others are not. The objective of this study was to identify a cluster of high-performing emergency general surgery (EGS) hospitals and assess whether high performance at one EGS operation was associated with high performance on all EGS operations.

METHODS

Adult patients who underwent one of eight EGS operations were identified in the California State Inpatient Database (2010–2011), which we linked to the American Hospital Association database. Beta regression was used to estimate a hospital's risk-adjusted mortality, accounting for patient- and hospital-level factors. Centroid cluster analysis grouped hospitals by patterns of mortality rates across the eight EGS operations using z scores. Multinomial logistic regression compared hospital characteristics by cluster.

RESULTS

A total of 220 acute care hospitals were included. Three distinct clusters of hospitals were defined based on assessment of mortality for each operation type: high-performing hospitals (n = 66), average performing (n = 99), and low performing (n = 55). The mortality by individual operation type at the high-performing cluster was consistently at least 1.5 standard deviations better than the low-performing cluster (p < 0.001). Within-cluster variation was minimal at high-performing hospitals compared with wide variation at low-performing hospitals. A hospital's high performance in one EGS operation type predicted high performance on all EGS operation types.

CONCLUSION

High-performing EGS hospitals attain excellence across all types of EGS operations, with minimal variability in mortality. Poor-performing hospitals are persistently below average, even for low-risk operations. These findings suggest that top-performing EGS hospitals are highly reliable, with systems of care in place to achieve consistently superior results. Further investigation and collaboration are needed to identify the factors associated with high performance.

LEVEL OF EVIDENCE

Prognostic, level III.
A preliminary investigation on the dependence of arthropod diversity on vegetation diversity across four contrasting ecosystems in Hanthana mountain range of Sri Lanka
Authors: Weerathunga W.A.M.T. , Athapaththu A.M.G.K. , Amarasinghe L.D.
Published: May 2019

Arthropods contribute significantly to biodiversity and vegetation provides a habitat and resources for them to survive, exist and propagate. We report a preliminary investigation on the extent to which arthropod diversity is dependent upon vegetation diversity across different ecosystems in a humid tropical climate. We determined the diversity of arthropods in four ecosystems closely-located ecosystems with different vegetation. Vegetation surrounding an aquatic environment (AQ), a broad-leaved wet, evergreen forest ecosystem (BL), aPinus caribaeamonoculture plantation (PN) and aPinusplantation artificially enriched with indigenous broad-leaved tree species (PNEN) located in the Hanthana mountain range in Central Sri Lanka were selected. In each environment, arthropods were sampled in three randomly-selected sites (5 m x 5 m) using four sampling methods. Collected arthropods were identified upto the highest possible taxa using standard identification keys. Simultaneously, vegetation diversity was determined via a plant census. Arthropod and vegetation diversities were computed separately for each site using Shannon-Wiener Index (H).

Within the 300 m2area of observation plots, arthropod individuals belonging to 68 species and 43 families were found. AQ had the greatest arthropod diversity (H=2.642), dominated byOliosspp. followed by BL (H=2.444), dominated by three arthropods, namely, a tettigonid species,Oxytatespp. andPsechrusspp. PN had the next highest arthropod diversity (H=1.411), dominated byDicaldispaspp. The lowest arthropod diversity was found at PNEN (H=1.3500), dominated by an ant species. Contrastingly, PNEN had the highest plant diversity (H=2.614) and PN the lowest (H=0.879). AQ (H=1.810) and BL (H=1.871) had intermediate values.

In a regression involving data from AQ, BL and PN, arthropod diversity was linearly dependent on plant diversity (R2=0.423) whereas it was not so when PNEN was also included (R2=0.008). This finding supports the hypothesis that while higher plant diversity contributes to greater arthropod diversity in ecosystems where human intervention is minimal, artificial enrichment of plant diversity does not necessarily increase arthropod diversity in the short-to medium-term. Further investigations are needed to substantiate these preliminary findings and validate the above hypothesis.
Causal network perturbations for instance-specific analysis of single cell and disease samples
Authors: Buschur Kristina L. , Chikina Maria , Benos Panayiotis V.
Published: May 2019

Complex diseases involve perturbation in multiple pathways and a major challenge in clinical genomics is characterizing pathway perturbations in individual samples. This can lead to patient-specific identification of the underlying mechanism of disease thereby improving diagnosis and personalizing treatment. Existing methods rely on external databases to quantify pathway activity scores. This ignores the data dependencies and that pathways are incomplete or condition-specific.

ssNPA is a new approach for subtyping samples based onderegulationof their gene networks. ssNPA learns a causal graph directly from control data. Sample-specific network neighborhood deregulation is quantified via the error incurred in predicting the expression of each gene from its Markov blanket. We evaluate the performance of ssNPA on liver development single-cell RNAseq data, where the correct cell timing is recovered. In all analyses ssNPA consistently outperforms alternative methods, highlighting the advantage of network-based approaches.
Systemic sclerosis is a disease of a prematurely senescent, inflammatory and activated immunome
Authors: Paleja Bhairav , Low Hsiu Ling Andrea , Kumar Pavanish , Saidin Suzan , Lajam Ahmad , Nur Hazirah Sharifah , Chua Camillus , Li Yun Lai , Albani Salvatore
Published: May 2019

Systemic sclerosis (SSc) is an autoimmune disease characterised by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets have been reported in SSc, however there is lack of systematic studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers targeted intervention. In the current study we sought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients. Mononuclear cells from blood of SSc patients and healthy controls (HC) were analysed by mass cytometry using a 36 marker (cell-surface and intracellular) panel. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and MAIT cells in patients, accompanied with increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. Overall this study provides an in-depth analysis of the systemic immunome in SSc, highlighting the potential pathogenic role of inflammation and chronic stimulation mediated “premature senescence” of immune cells.

ONE SENTENCE SUMMARY

The immune architecture in Systemic sclerosis is altered and reminiscent of chronic stimulatory environment led premature senescence of immune cells.
Gene knock-ins inDrosophilausing homology-independent insertion of universal donor plasmids
Authors: Bosch Justin A. , Colbeth Ryan , Zirin Jonathan , Perrimon Norbert
Published: May 2019

Targeted genomic knock-ins are a valuable tool to probe gene function. However, knock-in methods involving homology-directed repair (HDR) can be laborious. Here, we adapt the mammalian CRISPaint homology-independent knock-in method forDrosophila melanogaster, which uses CRISPR/Cas9 and non-homologous end joining (NHEJ) to insert universal donor plasmids into the genome. This method is a simple and fast alternative to HDR for certain strategies such as C-terminal tagging and gene disruption. Using this method in cultured S2R+ cells, we efficiently tagged four endogenous proteins with the bright fluorescent protein mNeonGreen, thereby demonstrating that an existing collection of CRISPaint universal donor plasmids is compatible with insect cells. In addition, we inserted the transgenesis marker3xP3-RFPinto seven genes in the fly germ line, producing heritable loss of function alleles that were isolated by simple fluorescence screening. Unlike in cultured cells, indels always occurred at the genomic insertion site, which prevents predictably matching the insert coding frame to the target gene. Despite this effect, we were able to isolateT2A-Gal4insertions in four genes that serve as in vivo expression reporters. Finally, we apply this fast knock-in method to uncharacterized small open reading frame (smORF) genes. Therefore, homology-independent insertion is a useful genome editing technique inDrosophilathat will better enable researchers to dissect gene function.

Article summary

We report a fast and simple genomic knock-in method inDrosophilato insert large DNA elements into any target gene. Using CRISPR-Cas9 and non-homologous end joining (NHEJ), an entire donor plasmid is inserted into the genome without the need for homology arms. We demonstrate its usefulness in cultured cells to fluorescently tag endogenous proteins and in the fly germ line to generate heritable insertions that disrupt gene function and can act as expression reporters.