bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury
Authors: Shi Zhipeng , Wu Jing , Yang Qiang , Xia Hong , Deng Min , Yang Yuxia
Published: December 2020

Background:

Tuberculosis is an infectious disease caused by mycobacterium tuberculosis. It may occur in multiple parts and organs of the patients body, and the lung is the most common. It is a major health threat worldwide. Hepatotoxicity is a common adverse reaction of commonly used clinical anti-tuberculosis drugs, as well as one of the important factors leading to poor prognosis of tuberculosis. Milk thistle is a traditional Chinese medicine extract derived from the mature fruit of Silybum marianum. Clinical practice shows that milk thistle has a good anti-liver injury effect and can be used to prevent anti-tuberculosis drug-induced liver injury. However, there is a lack of evidence-based medicine. The research carried out in this protocol is to systematically evaluate the efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury, and to improve the evidence-based basis for clinical application of milk thistle in the preventive treatment of anti-tuberculosis drug-induced liver injury.

Method:

Computer search of English databases (PubMed, the Cochrane Library, Embase, Web of Science) and Chinese databases (CNKI, VIP, Wanfang, China Biology Medicine disc (CBMdisc)) was performed. From the establishment of database to October 2020, 2 researchers independently extracted and evaluated the data included in the randomized controlled clinical research of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury, and used RevMan5.3 software to conduct a meta-analysis of the included literature.

Result:

In this research, the efficacy and safety of milk thistle preventive treatment of anti-tuberculosis drug-induced liver injury were evaluated by indicators such as the incidence of liver injury, bilirubin levels, and liver enzyme levels.

Conclusion:

In this research, reliable evidence-based evidence for the clinical application of milk thistle in the preventive treatment of anti-tuberculosis drug-induced liver injury was provided.

OSF Registration number:

DOI: 10.17605/OSF.IO/VC3RM.
Peripheral follicular cytotoxic T -like cells in Kawasaki disease with coronary artery aneurysms
Authors: Xu Meng , Liu Jinxiang , Pan Lu , Yang Sirui
Published: December 2020

Introduction:

Kawasaki disease (KD) is the leading cause of acquired heart abnormalities during childhood. The infiltration of CD8+ T cells plays an essential role in the formation of coronary aneurysms. Follicular cytotoxic T (Tfc) cells are a newly defined subset of CD8+ T cells that express CXC-chemokine receptor 5. The role of Tfc cells in KD is unclear. However, in this report, we present 2 KD children with sustained coronary artery aneurysms (CAA), and we found that their peripheral C-X-C Chemokine Receptor 5+ T cells contained quite amounts of CD4 negative cells. Importantly, these cells have never been reported in KD.

Patients concerns:

Case 1 was a 3-year-old boy with a complaint of continuous fever for 6 days and conjunctival injection for 3 days. Case 2 was a 6-month-old boy who was hospitalized because of persistent fever for 5 days, rashes and conjunctival injection for 1 day.

Diagnosis:

Case 1 was diagnosed with KD according to typical symptoms and signs including fever over 5 days, conjunctival injection, rashes, swelling cervical lymph nodes and a strawberry tongue. Case 2 had atypical symptoms including persistent fever for 5 days, rashes and conjunctival injection, and he was diagnosed with KD based on the echocardiographic findings.

Intervention:

Both the 2 patients received intravenous immunoglobulin and oral aspirin. Besides, case 1 was given the second infusion of intravenous immunoglobulin, intravenous prednisolone and low-molecular-weight heparin.

Outcomes:

The CAA of case 1 did not regress until the 12th month after disease onset. The CAA of patient 2 began to regress at the third month after disease onset. During the months from disease onset to the recent follow-up, no cardiovascular events had occurred.

Conclusions:

We speculate that Tfc cells may be associated with the formation of CAA. Further studies with larger sample size and functional analysis of these cells are needed.
The role of bone grafts in displaced intra-articular calcaneal fractures
Authors: He Zhi-xiang , Lu Zheng-hao , Ou Jun , Wu Zhi-liang
Published: December 2020

Background:

Whether the bone graft is needed in treating the displaced intra-articular calcaneal fractures (DIACFs) is still controversial. Therefore, in our study, we will explore the results of 2 approaches for the DIACFs surgical treatment.

Methods:

The present report follows the Consolidated Standards of Reporting Trials (CONSORT) guidelines. All patients will be assigned randomly into 2 different groups through tossing the coins. Three experienced surgeons are assigned randomly to each group to implement the surgeries utilizing any of the surgical approach. Assignments are concealed in a sealed opaque envelope. Patients who meet the following conditions will be included in this experiment:

Patients are asked to finish 2 questionnaires, namely, American Orthopaedic Foot and Ankle Society score and short form 36. The ranges of motion of the ankle and the subtalar joint will be also measured. Postoperative complications such as deep infection, wound infection, and wound edge necrosis, the injury of sural nerve, and hematoma are recorded.

Results:

Our study can provide significant information on the necessity of bone graft in DIACFs internal fixation treatment.

Trial registration:

This study protocol was registered in Research Registry (researchregistry6246).
Evaluation of perfusion MRI value for tumor progression assessment after glioma radiotherapy
Authors: Wang Longlong , Wei Lizhou , Wang Jingjian , Li Na , Gao Yanzhong , Ma Hongge , Qu Xinran , Zhang Ming
Published: December 2020

Objectives:

This study aimed to evaluate the diagnostic performance of magnetic resonance perfusion-weighted imaging (PWI) as a noninvasive method to assess post-treatment radiation effect and tumor progression in patients with glioma.

Methods:

A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases up to March 2020. The quality of the included studies was assessed by the quality assessment of diagnostic accuracy studies 2. Data were extracted to calculate sensitivity, specificity, and diagnostic odds ratio (DOR), 95% Confidence interval (CI) and analyze the heterogeneity of the studies (Spearman correlation coefficient, I
2 test). We performed meta-regression and subgroup analyses to identify the impact of study heterogeneity.

Results:

Twenty studies were included, with available data for analysis on 939 patients and 968 lesions. All included studies used dynamic susceptibility contrast (DSC) PWI, four also used dynamic contrast-enhanced PWI, and three also used arterial spin marker imaging PWI. When DSC was considered, the pooled sensitivity and specificity were 0.83 (95% CI, 0.79 to 0.86) and 0.83 (95% CI, 0.78 to 0.87), respectively; pooled DOR, 21.31 (95% CI, 13.07 to 34.73); area under the curve (AUC), 0.887; Q∗, 0.8176. In studies using dynamic contrast-enhanced, the pooled sensitivity and specificity were 0.73 (95% CI, 0.66 to 0.80) and 0.80 (95% CI, 0.69 to 0.88), respectively; pooled DOR, 10.83 (95% CI, 2.01 to 58.43); AUC, 0.9416; Q∗, 0.8795. In studies using arterial spin labeling, the pooled sensitivity and specificity were 0.79 (95% CI, 0.69 to 0.87) and 0.78 (95% CI, 0.67 to 0.87), respectively; pooled DOR, 15.63 (95% CI, 4.61 to 53.02); AUC, 0.8786; Q∗, 0.809.

Conclusions:

Perfusion magnetic resonance imaging displays moderate overall accuracy in identifying post-treatment radiation effect and tumor progression in patients with glioma. Based on the current evidence, DSC-PWI is a relatively reliable option for assessing tumor progression after glioma radiotherapy.
Cardiovascular outcomes associated with Ultrathin bioresorbable polymer sirolimus eluting stents versus thin, durable polymer everolimus eluting stents following percutaneous coronary intervention in patients with type 2 diabetes mellitus
Authors: Deng Shibing , Yi Xuying , Tian Zhiming
Published: December 2020

Background:

Percutaneous coronary intervention with the new generation drug eluting stents (DES) is 1 among the revascularization procedures required to treat patients with coronary artery disease (CAD). Since late stent thrombosis and silent myocardial infarction are highly associated with type 2 diabetes mellitus (T2DM), an analysis comparing the newer generation DES in this specific subgroup of patients would be scientifically relevant.

In this analysis, we aimed to systematically compare the cardiovascular outcomes observed with the ultrathin bioresorbable polymer sirolimus eluting stents (SES) versus thin, durable polymer everolimus eluting stents (EES) following percutaneous coronary intervention in patients with T2DM.

Methods:

Through online databases, relevant studies comparing ultrathin bioresorbable polymer SES versus the durable polymer EES were carefully searched. The cardiovascular outcomes were assessed during a follow-up time period of 1 year and more than 1 year (1–5 years) respectively. This meta-analysis was carried out by the latest version of the RevMan software. Following analysis, the results were represented by odds ratios (OR) with 95% confidence intervals (CI).

Results:

A total number of 1967 patients with T2DM were included in this analysis. During a 1 year follow-up time period, target lesion failure (TLF) (OR: 0.59, 95% CI: 0.34–1.02; P = .06, target vessel revascularization (TVR) (OR: 0.97, 95% CI: 0.55–1.70; P = .91) and target lesion revascularization (TLR) (OR: 0.91, 95% CI: 0.44–1.87; P = .79) were similarly observed with ultrathin bioresorbable polymer SES versus the thin, durable polymer EES in these patients with T2DM. Other cardiovascular outcomes including myocardial infarction (MI), major adverse cardiac events, all-cause mortality (OR: 0.72, 95% CI: 0.37–1.40; P = .34), cardiac death and stent thrombosis (OR: 0.85, 95% CI: 0.45–1.62; P = .63) were also similarly observed with these 2 types of new stents. During a follow-up time period above 1 year (1–5 years), still no significant difference was observed in TLF, TVR, TLR, major adverse cardiac events, MI, all-cause mortality, cardiac death and stent thrombosis (OR: 0.62, 95% CI: 0.33–1.16; P = .14).

Conclusions:

The ultrathin bioresorbable polymer SES were similar to the durable polymer EES in these patients with T2DM. These 2 types of new generation stents were comparable in terms of cardiovascular outcomes. Hence, they might be recommended in patients with T2DM. Upcoming trials should be able to confirm this hypothesis.
Nursing case management for people with hypertension
Authors: Song Chunjing , Li Xianhong , Ning Xueling , Song Shiqiang
Published: December 2020

Objective:

To explore the effect of management of nursing case on blood pressure control in hypertension patients.

Method:

This is a randomized controlled study which will be carried out from May 2021 to May 2022. The experiment was granted through the Research Ethics Committee of the People's Hospital of Chengyang District (03982808). Our research includes 200 patients. Patients who meet the following conditions will be included in this experiment: the patients aged 18 to 60 years; the patients had the diagnosis of hypertension; and the urban residents. While patients with the following conditions will be excluded: having renal failure, liver failure, heart and respiratory failure; and known pregnancy. Primary result is blood pressure, while secondary results are treatment compliance, waist circumference, body mass index (BMI), type and number of antihypertensive agents used, and the existence of metabolic and cardiovascular comorbidities.

Results:

Table 1 shows the clinical outcomes between the two groups.

Conclusion:

Nursing case management is effective to improve the prognosis of hypertension patients.
Burkitt lymphoma associated with human immunodeficiency virus infection and pulmonary tuberculosis
Authors: Birlutiu Victoria , Birlutiu Rares-Mircea , Zaharie Ioan Sorin , Sandu Mariana
Published: December 2020

Introduction:

The association of human immunodeficiency virus (HIV) infection with Burkitt lymphoma is related to the presence of Epstein Barr virus infection and the impact of the HIV antigen on the expansion of B-polyclonal cells. In Southeast Europe, the association is rare, and recognizing this is important in the therapeutic decision to increase patient survival rate. The association of HIV with Burkitt lymphoma and tuberculosis is even more rarely described in the literature.

Patient concerns:

We present the case of a 40-year-old patient who presented with a 3-week history of fever (max. 38.7 °C), painful axillary swelling on the right side, lumbar pain, gait disorders, headache, and night sweats. Clinical manifestations included marked weight loss (about 30 kg in the last 2 months before his admission).

Diagnosis:

A LyCD4 count of 38/μL and a HIV1 viral load of 384,000/mm3, classified the patient into a C3 stage. A biopsy of the right axillary lymph node was performed for suspected ganglionic tuberculosis due to immunodeficiency. Histopathological examination confirmed the diagnosis of Burkitt lymphoma. Cultures on Löwenstein-Jensen medium from sputum harvested at first admission were positive for Mycobacterium tuberculosis.

Interventions:

Highly active antiretroviral therapy, chemotherapeutic agents for Burkitt lymphoma, anti-tuberculous drug therapy, neurosurgical intervention of spinal cord decompression, and antibiotic therapy of the associated bacterial infection.

Outcome:

Burkitt lymphoma disseminated rapidly, with central nervous system, spinal cord, osteomuscular, adrenal, and spleen involvement. The evolution under treatment was unfavorable, with patient death occurring 6 months after diagnosis.

Conclusions:

The association of HIV infection with Burkitt lymphoma and tuberculosis is rare in the highly active antiretroviral therapy (HAART) era, posing prompt and multidisciplinary therapeutic management issues. Similar cases of HIV-TB and Burkitt lymphoma association have been described, but none of the other cases showed the involvement of the central nervous system or of the bilateral adrenal glands.
Psychometric properties of quality of life questionnaires for patients with breast cancer-related lymphedema
Authors: Meilani Estu , Zanudin Asfarina , Nordin Nor Azlin Mohd
Published: December 2020

Background:

Breast-cancer related lymphedema (BCRL) is a common condition among breast cancer survivors that could impact the quality of life (QoL) of patients. Exploring the QoL of the patients with BCRL using valid and reliable QoL is crucial to capture the status of this important aspect hence appropriate intervention could be implement to patient. However, so far no scientific review is available, which reports the psychometric properties of the QoL questionnaires used in BCRL. The purpose of this systematic review is to comprehensively assess the psychometric properties of QoL questionnaires in patients with BCRL.

Methods:

We will perform comprehensive searches of published studies in electronic databases such as Medline (via Ovid), EBSCOhost, PubMed, Scopus, and Web of Science by using the following search terms: “quality of life”; “breast cancer”; “upper limb”; “lymphedema”; “questionnaire”; and “measurement properties.” Only full-text articles in English language are included. Two reviewers will independently conduct the article selection, data extraction, and quality assessment. Any possible conflict between the 2 reviewers is going to be solved with the help of a third reviewer. The Consensus-based Standards for the Selection of Health Measurement Instrument (COSMIN) checklist and manual will be used to assess the selected study quality.

Results:

This review will provide an updated overview of available lymphedema-specific questionnaires used in BCRL population and then recommend the most valid and reliable QoL questionnaire for clinical and research use in patients with BCRL.

Conclusion:

This review may help the clinician and researcher to find an updated overview of various questionnaires used to assess BCRL patients’ QoL.

Ethics and dissemination:

This review will use data from published studies. Therefore, ethical approval is not required prior to this review. The results of this review will be published in a peer-reviewed journal or presented at conferences.

Study Registration:

OSF osf.io/8xwym.
Analysis of risk factors for perioperative death in patients undergoing aortic valve replacement using biological valves
Authors: Li Qi , Gao Hongbo , Ji Qiuxia , Song Jianshu , Li Longfei , Liu Xu
Published: December 2020

Background:

Aortic valve disease has become one of the important factors affecting human health. Aortic valve disease is a progressive disease, if not actively treated, the prognosis is poor. Aortic valve replacement (AVR) surgery is an important treatment for aortic valve disease. At present, the AVR surgery using biological valve accounts for about 40% of the total number of AVR surgery. There are still more perioperative deaths in China due to the large number of AVR patients using biological valves. The objective of this study is to explore measures to reduce perioperative mortality of patients after AVR surgery with biological valves.

Methods:

The clinical data of patients undergoing AVR surgery with biological valves in Affiliated Hospital of Qingdao University from November 15, 2020 to December 31, 2022 were reviewed and analyzed. Patients were divided into death group and survival group according to their perioperative survival. Risk factors that may influence perioperative mortality were analyzed and compared between the 2 groups.

Discussion:

This study was a retrospective analysis of risk factors that may influence perioperative mortality in patients undergoing AVR surgery using biological valves. The conclusions of this study can be used to guide clinical decisions-making and relevant guidelines-developing for perioperative treatment of patients undergoing AVR surgery using biological valves.
Warming yang method in traditional Chinese medicine for depression
Authors: Deng Jiashuai , Wang Changhong , Jiang Yong
Published: December 2020

Background:

Depression is a chronic psychological disease with low emotion, interest, cognition, thinking and disorder of physiological function, even numbness, or hallucination, delusion and other psychotic symptoms. Traditonal Chinese medicine plays an important role in the treatment of mental diseases in China and East Asia. The aim of this study is to assess the efficacy and safety of warming yang method in traditional Chinese medicine for depression.

Methods:

We search the following databases: PubMed, the Cochrane Library, Chinese Science and Technique Journals Database, Chinese Biomedical Literature Database, Excerpt Medica Database, MEDLINE, Chinese National Knowledge Infrastructure Database, and the Wanfang Database. Other sources will also be searched like Google Scholar and gray literatures. All databases mentioned above are searched from the start date to November 2020. Randomised controlled trials will be included which recruiting depression participants to assess the efficacy and safety of warming yang method in traditional Chinese medicines against controls (placebo or other therapeutic agents). Primary outcomes will include the reduction ratio of Hamilton Depression Rating Scale and security index. Secondary outcomes include the Yang deficiency improves. Two authors will independently scan the searched articles, extract the data from attached articles and import them into Endnote X8 and use Microsoft Excel 2013 to manage data and information. We will assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the participation of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. The meta-analysis in this review will use RevMan 5.3 software.

Results:

The study is aim to evaluate the efficacy and safety of warming yang method in traditional Chinese medicine for depression.

Conclusion:

This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice.

INPLASY registration number:

INPLASY2020110129
Effect of Changes in Body Mass Index on the Risk of Cardiovascular Disease and Diabetes Mellitus in HIV-Positive Individuals: Results From the D:A:D Study
Authors: Petoumenos Kathy , Kuwanda Locadiah , Ryom Lene , Mocroft Amanda , Reiss Peter , De Wit Stephane , Pradier Christian , Bonnet Fabrice , Phillips Andrew , Hatleberg Camilla I. , d'Arminio Monforte Antonella , Weber Rainer , Sabin Caroline A. , Lundgren Jens , Law Matthew G. ,   for the D:A:D Study Group
Published: December 2020

Background:

Weight gain is common among people with HIV once antiretroviral treatment is commenced. We assess the effect of changes in body mass index (BMI), from different baseline BMI levels, on the risk of cardiovascular disease (CVD) and diabetes mellitus (DM).

Methods:

D:A:D participants receiving antiretroviral treatment were followed from their first BMI measurement to the first of either CVD or DM event, or earliest of January 2, 2016 or 6 months after last follow-up. Participants were stratified according to their baseline BMI, and changes from baseline BMI were calculated for each participant. Poisson regression models were used to assess the effects of changes on BMI on CVD or DM events.

Results:

There were 2104 CVD and 1583 DM events over 365,287 and 354,898 person-years [rate: CVD 5.8/1000 (95% confidence interval: 5.5 to 6.0); DM 4.5/1000 (95% confidence interval: 4.2 to 4.7)]. Participants were largely men (74%), baseline mean age of 40 years, and median BMI of 23.0 (IQR: 21.0–25.3). A risk of CVD by change in BMI from baseline, stratified by baseline BMI strata showed little evidence of an increased risk of CVD with an increased BMI in any baseline BMI strata. An increase in BMI was associated with an increased risk of DM across all baseline BMI strata.

Conclusions:

Although increases in BMI across all levels of baseline BMI were not associated with an increased risk of CVD, such changes were consistently associated with an increased risk of DM. There was also some evidence of an increased risk of CVD with a decrease in BMI.
Adult Saethre-Chotzen Syndrome: A Unique Abnormal Breathing Pattern
Authors: den Ottelander Bianca , Gaillard Linda , Yang Sumin , de Goederen Robbin , Bredero-Boelhouwer Hansje , van Veelen Marie-Lise , Tasker Robert , Joosten Koen , Mathijssen Irene
Published: December 2020

A 35-year-old male with Saethre-Chotzen syndrome presented with severe complaints. Neuroimaging showed a Chiari-I malformation, mild ventriculomegaly, a syrinx of the wide central canal, and various cerebral vascular anomalies including a large occipital emissary vein on the right. Ultrasound of this vein confirmed blocking of the outflow-track when turning his head to the right, which also provoked the headaches and bruit. Polysomnography revealed severe positional sleep apnea with a mixed breathing pattern, the central components consisted of periodic breathing with, at times, crescendo-decrescendo reminiscent of a Cheyne-Stokes versus Biot breathing pattern, pointing to possible brain stem/pontine problems. Continuous positive airway pressure was initiated, and the patient was instructed to avoid sleeping in the right lateral position. One year later, nearly all his complaints have resolved. A questionnaire was sent to all adult Saethre-Chotzen patients in our craniofacial unit, none reported any of the severe symptoms as described by our index case.
Enhancing the Biopsychosocial Approach to Perioperative Care
Authors: Hadlandsmyth Katherine , Conrad Mandy , Steffensmeier Kenda Stewart , Van Tiem Jennifer , Obrecht Ashlie , Cullen Joseph J. , Vander Weg Mark W.
Published: December 2020

Objective:

The current study aimed to pilot the PePS intervention, based on principles of cognitive behavioral therapy (CBT), to determine feasibility and preliminary efficacy for preventing chronic pain and long-term opioid use.

Summary Background Data:

Surgery can precipitate the development of both chronic pain and long-term opioid use. CBT can reduce distress and improve functioning among patients with chronic pain. Adapting CBT to target acute pain management in the postoperative period may impact longer-term postoperative outcomes.

Methods:

This was a mixed-methods randomized controlled trial in a mixed surgical sample with assignment to standard care or PePS, with primary outcomes at 3-months postsurgery. The sample consisted of rural-dwelling United States Military Veterans.

Results:

Logistic regression analyses found a significant effect of PePS on odds of moderate-severe pain (on average over the last week) at 3-months postsurgery, controlling for preoperative moderate-severe pain: Adjusted odds ratio = 0.25 (95% CI: 0.07–0.95, P < 0.05). At 3-months postsurgery, 15% (6/39) of standard care participants and 2% (1/45) of PePS participants used opioids in the prior seven days: Adjusted Odds ratio = 0.10 (95% CI: 0.01–1.29, P = .08). Changes in depression, anxiety, and pain catastrophizing were not significantly different between arms.

Conclusions:

The findings from this study support the feasibility and preliminary efficacy of the PePS intervention.
Improved Preoperative Risk Assessment Tools Are Needed to Guide Informed Decision Making before Esophagectomy
Authors: Gray Katherine D. , Nobel Tamar B. , Hsu Meier , Tan Kay See , Chudgar Neel , Yan Shi , Rusch Valerie W. , Jones David R. , Rocco Gaetano , Molena Daniela , Isbell James M.
Published: December 2020

Objective:

We sought to evaluate the performance of 2 commonly used prediction models for postoperative morbidity in patients undergoing open and minimally invasive esophagectomy.

Summary Background Data:

Patients undergoing esophagectomy have a high risk of postoperative complications. Accurate risk assessment in this cohort is important for informed decision-making.

Methods:

We identified patients who underwent esophagectomy between January 2016 and June 2018 from our prospectively maintained database. Predicted morbidity was calculated using the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (SRC) and a 5-factor National Surgical Quality Improvement Programderived frailty index. Performance was evaluated using concordance index (C-index) and calibration curves.

Results:

In total, 240 consecutive patients were included for analysis. Most patients (85%) underwent Ivor Lewis esophagectomy. The observed overall complication rate was 39%; the observed serious complication rate was 33%.

The SRC did not identify risk of complications in the entire cohort (C-index, 0.553), patients undergoing open esophagectomy (C-index, 0.569), or patients undergoing minimally invasive esophagectomy (C-index, 0.542); calibration curves showed general underestimation. Discrimination of the SRC was lowest for reoperation (C-index, 0.533) and highest for discharge to a facility other than home (C-index, 0.728). Similarly, the frailty index had C-index of 0.513 for discriminating any complication, 0.523 for serious complication, and 0.559 for readmission.

Conclusions:

SRC and frailty index did not adequately predict complications after esophagectomy. Procedure-specific risk-assessment tools are needed to guide shared patient-physician decision-making in this high-risk population.
Consensus Guidelines for the Use of Fluorescence Imaging in Hepatobiliary Surgery
Authors: Wang Xiaoying , Teh Catherine S. C. , Ishizawa Takeaki , Aoki Takeshi , Cavallucci David , Lee Ser-Yee , Panganiban Katherine M. , Perini Marcos V. , Shah Sudeep R. , Wang Hongguang , Xu Yinzhe , Suh Kyung-Suk , Kokudo Norihiro
Published: December 2020

Objective:

To establish consensus recommendations for the use of fluorescence imaging with indocyanine green (ICG) in hepatobiliary surgery.

Background:

ICG fluorescence imaging has gained popularity in hepatobiliary surgery in recent years. However, there is varied evidence on the use, dosage, and timing of administration of ICG in clinical practice. To standardize the use of this imaging modality in hepatobiliary surgery, a panel of pioneering experts from the Asia-Pacific region sought to establish a set of consensus recommendations by consolidating the available evidence and clinical experiences.

Methods:

A total of 13 surgeons experienced in hepatobiliary surgery and/or minimally invasive surgery formed an expert consensus panel in Shanghai, China in October 2018. By the modified Delphi method, they presented the relevant evidence, discussed clinical experiences, and derived consensus statements on the use of ICG in hepatobiliary surgery. Each statement was discussed and modified until a unanimous consensus was achieved.

Results:

A total of 7 recommendations for the clinical applications of ICG in hepatobiliary surgery were formulated.

Conclusions:

The Shanghai consensus recommendations offer practical tips and techniques to augment the safety and technical feasibility of ICG fluorescence-guided hepatobiliary surgery, including laparoscopic cholecystectomy, liver segmentectomy, and liver transplantation.
Preoperative Single-dose Methylprednisolone Prevents Surgical Site Infections After Major Liver Resection
Authors: Bressan Alexsander K. , Isherwood Susan , Bathe Oliver F. , Dixon Elijah , Sutherland Francis R. , Ball Chad G.
Published: December 2020

Objective:

The primary aim of this study was to evaluate the efficacy of a single preoperative dose of methylprednisolone for preventing postoperative complications after major liver resections.

Summary Background Data:

Hepatic resections are associated with a significant acute systemic inflammatory response. This effect subsequently correlates with postoperative morbidity, mortality, and length of recovery. Multiple small trials have proposed that the administration of glucocorticoids may modulate this effect.

Methods:

This study was a parallel, dual-arm, double-blind randomized controlled trial. Adult patients undergoing elective major hepatic resection (≥3 segments) at a quaternary care institution were included (2013–2019). Patients were randomly assigned to receive a single preoperative 500 mg dose of methylprednisolone versus placebo. The main outcome measure was postoperative complications after liver resection, within 90 days of the index operation. Standard statistical methodology was employed (P < 0.05 = significant).

Results:

A total of 151 patients who underwent a major hepatic resection were randomized (mean age = 62.8 years; 57% male; body-mass-index = 27.9). No significant differences were identified between the intervention and control groups (age, sex, body-mass-index, preoperative comorbidities, hepatic function, ASA class, portal vein embolization rate) (P > 0.05). Underlying hepatic diagnoses included colorectal liver metastases (69%), hepatocellular carcinoma (18%), noncolorectal liver metastases (7%), and intrahepatic cholangiocarcinoma (6%). There was a significant reduction in the overall incidence of postoperative complications in the methylprednisolone group (31.2% vs 47.3%; P = 0.042). Patients in the glucocorticoid group also displayed less frequent organ space surgical site infections (6.5% vs 17.6%; P = 0.036), as well as a shorter length of hospital stay (8.9 vs 12.5 days; P = 0.015). Postoperative serum bilirubin and prothrombin timeinternational normalized ratio (PT-INR) levels were also lower in the steroid group (P = 0.03 and 0.04, respectively). Multivariate analysis did not identify any additional significant modifying factor relationships (estimated blood loss, duration of surgery, hepatic vascular occlusion (rate or duration), portal vein embolization, drain use, etc) (P > 0.05).

Conclusions:

A single preoperative dose of methylprednisolone significantly reduces the length of hospital stay, postoperative serum bilirubin, and PT-INR, as well as infectious and overall complications following major hepatectomy.
cAMP prevents antibody-mediated thrombus formation in COVID-19
Authors: Zlamal Jan , Althaus Karina , Jaffal Hisham , Pelzl Lisann , Singh Anurag , Witzemann Andreas , Häberle Helene , Mirakaj Valbona , Rosenberger Peter , Bakchoul Tamam
Published: December 2020

Thromboembolic events are frequently reported in patients infected with the SARS-CoV-2 virus. However, the exact mechanisms of thromboembolic events remain elusive. In this work, we show that immunoglobulin G (IgG) subclass in patients with COVID-19 trigger the formation of procoagulant PLTs in a Fc-gamma-RIIA (FcγRIIA) dependent pathway leading to increased thrombus formation in vitro. Most importantly, these events were significantly inhibited via FcγRIIA blockade as well as by the elevation of PLTs’ intracellular cyclic-adenosine-monophosphate (cAMP) levels by the clinical used agent Iloprost. The novel findings of FcγRIIA mediated prothrombotic conditions in terms of procoagulant PLTs leading to higher thrombus formation as well as the successful inhibition of these events via Iloprost could be promising for the future treatment of the complex coagulopathy observed in COVID-19 disease.

Key points

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Fc-gamma-receptor IIA mediated PS externalization on the PLT surface triggers increased thrombus formation

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Inductors of cAMP inhibit antibody-mediated thrombus formation and may have potential therapeutic advantage in COVID-19
Functional multispectral optoacoustic tomography imaging of hepatic steatosis development in mice
Authors: Huang Shan , Blutke Andreas , Feuchtinger Annette , Klemm Uwe , Tom Robby Zachariah , Hofmann Susanna , Stiel Andre C. , Ntziachristos Vasilis
Published: December 2020

The increasing worldwide prevalence of obesity, fatty liver diseases, as well as the emerging understanding of the importance of lipids in multi-faceted aspects of various other diseases is generating significant interest in lipid research. Lipid visualization in particular can play a critical role in understanding functional relations in lipid metabolism. In this study, we investigate the potential of multispectral optoacoustic tomography (MSOT) as a novel modality to non-invasively visualize lipids in laboratory mice. Using an obesity-induced non-alcoholic fatty liver disease (NAFLD) mouse model, we examined whether MSOT could detect and differentiate different grades of hepatic steatosis and monitor the accumulation of lipids in the liver quantitatively over time, without the use of contrast agents,i.e.in label free mode. Moreover, we demonstrate the efficacy of using the real-time clearance kinetics of indocyanine green (ICG) in the liver as a biomarker to evaluate the organs’ function and assess the severity of NAFLD. This study demonstrates MSOT as an efficient imaging tool for lipid visualization in preclinical studies, particularly for the assessment of NAFLD.
Deep Learning Identification of Stiffness Markers in Breast Cancer
Authors: Sneider Alexandra , Kim Joo Ho , Kiemen Ashley , Wu Pei-Hsun , Habibi Mehran , White Marissa , Phillip Jude M. , Gu Luo , Wirtz Denis
Published: December 2020

While essential to our understanding of solid tumor progression, the study of cell and tissue mechanics has yet to find traction in the clinic. Determining tissue stiffness, a mechanical property known to promote a malignant phenotypein vitroandin vivo, is not part of the standard algorithm for the diagnosis and treatment of breast cancer. Instead, clinicians routinely use mammograms to identify malignant lesions and radiographically dense breast tissue is associated with an increased risk of developing cancer. Whether breast density is related to tumor tissue stiffness, and what cellular and non-cellular components of the tumor contribute the most to its stiffness are not well understood. Through training of a deep learning network and mechanical measurements of fresh patient tissue, we create a bridge in understanding between clinical and mechanical markers. The automatic identification of cellular and extracellular features from hematoxylin and eosin (H&E)-stained slides reveals that global and local breast tissue stiffness best correlate with the percentage of straight collagen. Global breast tissue mechanics correlate weakly with the percentage of blood vessels and fibrotic tissue, and non-significantly with the percentage of fat, ducts, tumor cells, and wavy collagen in tissue. Importantly, the percentage of dense breast tissue does not directly correlate with tissue stiffness or straight collagen content.
Role of FBXW2 in explant culture of bovine periosteum-derived cells
Authors: Akiyma Mari
Published: December 2020

Osteoporosis and bone fracture decrease quality of life. Bone regeneration is a notable technique for osteoporosis treatment. A previous study reported that F-box and WD-40 domain-containing protein 2 (FBXW2) and osteocalcin have the same shape in the periosteum after 5 weeks. However, the osteoblastic functions of FBXW2 are not clear. In this study, double fluorescent immunostaining revealed a small amount of osteocalcin in the area of FBXW2 aggregation at 1 week, periosteal cells, and osteocalcin pushed toward the edge of periosteum, and, apart from FBXW2 tubes at 2 weeks, multilayered periosteum-derived cells at 3 weeks and sticking of osteocalcin in the periosteum with cells at 4 weeks. At 5 weeks, FBXW2 disappeared at the root of periosteum-derived cells, while osteocalcin and cells remained. Based on these results, it is hypothesized that FBXW2 maintains tissue shapes and prevents escape of inner periosteal cells, and the disappearance of FBXW2 causes migration of periosteum-derived cells out of the periosteum along with osteocalcin. Furthermore, FBXW2 may play a role in dynamic tissue remodeling and bone formation.
NirA is an alternative nitrite reductase fromPseudomonas aeruginosawith potential as an anti-virulence target
Authors: Fenn Samuel , Dubern Jean-Frédéric , Cigana Cristina , De Simone Maura , Lazenby James , Juhas Mario , Schwager Stephan , Bianconi Irene , Döring Gerd , Elmsley Jonas , Eberl Leo , Williams Paul , Bragonzi Alessandra , Cámara Miguel
Published: December 2020

The opportunistic pathogenPseudomonas aeruginosaproduces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipeline drying up, anti-virulence therapy has become an attractive alternative strategy to the traditional use of antibiotics to treatP. aeruginosainfections. To identifyP. aeruginosagenes required for virulence in multiple hosts, a random library of Tn5 mutants in PAO1-L was previously screenedin vitrofor those showing pleiotropic effects in the production of virulence phenotypes. Using this strategy, we have identified a Tn5 mutant with an insertion in PA4130 showing reduced levels in a number of virulence traitsin vitro. Construction of an isogenic mutant in this gene presented similar results as those from the Tn5 mutant. Furthermore, the PA4130 isogenic mutant showed substantial attenuation in disease models ofDrosophila melanogaster,Caenorhabditis elegansas well as decreased toxicity in human cell lines. This mutant also presented an 80% increased survival in murine acute and agar-bead lung infection models. PA4130 codes for a protein with homology to nitrite and sulphite reductases. Overexpression of PA4130 in the presence of the siroheme synthase CysG enabled its purification as a soluble protein. Methyl viologen oxidation assays with purified PA4130 showed that this protein is a nitrite reductase operating in a siroheme and 4Fe-4S dependant manner. The preference for nitrite and the production of ammonium revealed that PA4130 is an ammonia:ferredoxin nitrite reductase and hence was named as NirA.
Mechanical Unloading is Associated with Decreased DNA Content in Cardiomyocytes Independent of Nucleation State
Authors: Luo Jun , Farris Stephen D. , Helterline Deri , Stempien-Otero April
Published: December 2020

Background

Cardiomyocytes increase DNA content in response to stress in humans. Proliferation has been reported in cardiomyocytes in failing hearts and following LVAD unloading which may represent a resolution of this process through cell division. However, cardiac recovery from LVAD is rare.

Methods

We quantified cardiomyocyte nuclear number, cell size, DNA content and the frequency of cell cycling markers by imaging flow cytometry from human subjects undergoing LVAD implantation or primary transplantation.

Results

Cardiomyocyte size was 15 percent smaller in unloaded versus loaded samples without differences in the percentage of mono-, bi, or multi-nuclear cells. DNA content per nucleus was significantly decreased in unloaded hearts versus loaded controls. Cell cycle markers, Ki67 and phosphohistone H3 (H3P) were not increased in unloaded versus failing samples.

Conclusions

Unloading of failing hearts is associated with decreased DNA content of nuclei independent of nucleation state within the cell. As these changes were associated with a trend to decreased cell size but not increased cell cycle markers, they may represent a regression of hypertrophic nuclear remodeling and not proliferation.
SARS-CoV-2 infections among personnel providing home care services for the elderly in Stockholm, Sweden
Authors: Hassan Sadaf Sakina , Seigerud Åsa , Mühr Laila Sara Arroyo , Kleppe Sara Nordqvist , Pin Elisa , Månberg Anna , Hober Sophia , Nilsson Peter , Engstrand Lars , Elfström K. Miriam , Blomqvist Jonas , Lundgren Kalle Conneryd , Dillner Joakim
Published: December 2020

Background

In March 2020, Stockholm, Sweden was hit by a severe outbreak of SARS-CoV-2. Four weeks later, a systematic study of testing for past or present infections among healthcare workers in the region was launched. Only a minority of COVID-19 related deaths occurred at hospitals and the study was therefore extended to employees in companies providing home care services for the elderly.

Methods

Five companies offered participation to 438 employees at work and 405 employees (92.5%) were enrolled. Serum samples were analyzed for IgG to SARS-CoV-2 and throat swabs were tested by for the SARS-CoV-2 virus by PCR.

Results

Among home care employees, 20.1% (81/403) were seropositive, about twice as many as in a simultaneously enrolled reference population (healthcare workers entirely without patient contact, n=3,671; 9.7% seropositivity). Only 13/379 employees (3.4%) had evidence of a current infection (PCR positivity). Among these, 5 were also seropositive (a sign of past infection or lingering infection after symptoms have resolved) and 3 were positive with only low amounts of virus. The combination of high amounts of virus and no antibodies, a characteristic for pre-symptomatic COVID-19, was thus present only in 5 employees (1.3%).

Conclusions

Personnel providing home service for the elderly appear to be a risk group for SARS-CoV-2 infection. Employees likely to be pre-symptomatic for COVID-19 can be readily identified by screening. Increased attention for protection of employees as well as of the elderly they serve is warranted.
Vimentin provides target search efficiency and mechanical resilience for dendritic cell migration
Authors: Da Cunha Stankevicins Luiza , Shaebani M. Reza , Vesperini Doriane , Urbanska Marta , Flormann Daniel A. D. , Terriac Emmanuel , Gad Annica K. B. , Cheng Fang , Eriksson John E. , Lautenschläger Franziska
Published: December 2020

Dendritic cells use amoeboid migration to pass through confined tissues to reach the lymph nodes, and this homing function is crucial for immune responses. The underlying mechanisms for this type of migration remain unknown. As vimentin intermediate filaments regulate adhesion-dependent migration, we analyzed whether they have a similar effect on amoeboid migration. We show that lack of vimentin impairs amoeboid migrationin vitroin confined environments, and blocks lymph-node homing in micein vivo. Importantly, we show that vimentin-deficient dendritic cells have a lower coupling factor between cell speed and persistence and reduced target search efficiency (e.g., finding a pathogen, or another cell). These data show that the characteristics of vimentin in its dynamic regulation of cell stiffness and load-bearing, and also elastic capacity, appear to explain the coupling between their migratory ability and search efficiency. Taken together, these data show that vimentin provides the specific mechano-dynamics required for dendritic cell migration and for efficient target searching.

Summary statement

Vimentin contributes to the mechanical stiffness of cells required for amoeboid cell migration through confined spaces, and improves cell-search efficiency. Vimentin-deficient cells migrate more slowly and their migration speed is less coupled to persistence compared to control cells.
Machine Learning-based Biomarkers Identification and Validation from Toxicogenomics - Bridging to Regulatory Relevant Phenotypic Endpoints
Authors: Rahman Sheikh Mokhlesur , Lan Jiaqi , Kaeli David , Dy Jennifer , Alshawabkeh Akram , Gu April Z.
Published: December 2020

High-throughput in vitro assays and AOP-based approach is promising for the assessment of health and ecotoxicological risks from exposure to pollutants and their mixtures. However, one of the major challenges in realization and implementations of the Tox21 vision is the urgent need to establish quantitative link betweenin-vitroassay molecular endpoint andin-vivophenotypic toxicity endpoint. Here, we demonstrated that, using time series toxicomicsin-vitroassay along with machine learning-based feature selection (MRMR) and classification method (SVM), an “optimal” number of biomarkers with minimum redundancy can be identified for prediction of phenotypic endpoints with good accuracy. We included two case studies forin-vivocarcinogenicity and Ames genotoxicity prediction with 20 selected chemicals including model genotoxic chemicals and negative controls, respectively, using anin-vitrotoxicogenomic assay that captures real-time proteomic response data of 38 GFP-fused proteins ofS. cerevisiaestrains covering biomarkers indicative of all known DNA damage and repair pathways in yeast. The results suggested that, employing the adverse outcome pathway (AOP) concept, molecular endpoints based on a relatively small number of properly selected biomarker-ensemble involved in the conserved DNA-damage and repair pathways among eukaryotes, were able to predict bothin-vivocarcinogenicity in rats and Ames genotoxicity endpoints. The specific biomarkers identified are different for the two different phenotypic genotoxicity assays. The top-ranked five biomarkers for thein-vivocarcinogenicity prediction mainly focused on double strand break repair and DNA recombination, whereas the selected top-ranked biomarkers for Ames genotoxicity prediction are associated with base- and nucleotide-excision repair. Current toxicomics approach still mostly rely on large number of redundant markers without pre-selection or ranking, therefore, selection of relevant biomarkers with minimal redundancy would reduce the number of markers to be monitored and reduce the cost, time, and complexity of the toxicity screening and risk monitoring. The method developed in this study will help to fill in the knowledge gap in phenotypic anchoring and predictive toxicology, and contribute to the progress in the implementation of tox 21 vision for environmental and health applications.

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