bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of core genes and clinical outcomes in tumors originated from endoderm (gastric cancer and lung carcinoma) via bioinformatics analysis
Authors: Shi Yewen , Chang Dongmin , Li Wenhan , Zhao FengYu , Ren Xiaoyong , Hou Bin
Published: March 2021

During last decade, bioinformatics analysis has provided an effective way to study the relationship between various genes and biological processes. In this study, we aimed to identify potential core candidate genes and underlying mechanisms of progression of lung and gastric carcinomas which both originated from endoderm. The expression profiles, GSE54129 (gastric carcinoma) and GSE27262 (lung carcinoma), were collected from GEO database. One hundred eleven patients with gastric carcinoma and 21 health people were included in this research. Meanwhile, there were 25 lung carcinoma patients. Then, 75 differentially expressed genes were selected via GEO2R online tool and Venn software, including 31 up-regulated genes and 44 down-regulated genes. Next, we used Database for Annotation, Visualization, and Integrated Discovery and Metascpe software to analyze Kyoto Encyclopedia of Gene and Genome pathway and gene ontology. Furthermore, Cytoscape software and MCODE App were performed to construct complex of these differentially expressed genes . Twenty core genes were identified, which mainly enriched in extracellular matrix-receptor interaction, focal adhesion, and PI3K-Akt pathway (P < .01). Finally, the significant difference of gene expression between cancer tissues and normal tissues in both lung and gastric carcinomas was examined by Gene Expression Profiling Interactive Analysis database. Twelve candidate genes with positive statistical significance (P < .01), COMP CTHRC1 COL1A1 SPP1 COL11A1 COL10A1 CXCL13 CLDN3 CLDN1 matrix metalloproteinases 7 ADAM12 PLAU, were picked out to further analysis. The Kaplan–Meier plotter website was applied to examine relationship among these genes and clinical outcomes. We found 4 genes (ADAM12, SPP1, COL1A1, COL11A1) were significantly associated with poor prognosis in both lung and gastric carcinoma patients (P 
< .05). In conclusion, these candidate genes may be potential therapeutic targets for cancer treatment.
Increased bleeding events with the addition of apixaban to the dual anti-platelet regimen for the treatment of patients with acute coronary syndrome
Authors: Jin Jing , Zhuo Xiaojun , Xiao Mou , Jiang Zhiming , Chen Linlin , Devi Shamloll Yashvina
Published: March 2021

Background:

Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel has been the mainstay of treatment for patients with acute coronary syndrome (ACS). However, the recurrence of thrombotic events, potential aspirin and clopidogrel hypo-responsiveness, and other limitations of DAPT have led to the development of newer oral anti-thrombotic drugs. Apixaban, a new non-vitamin K antagonist, has been approved for use. In this meta-analysis, we aimed to compare the bleeding outcomes observed with the addition of apixaban to DAPT for the treatment of patients with ACS.

Methods:

Online databases including EMBASE, Cochrane Central, http://www.ClinicalTrials.gov, MEDLINE and Web of Science were searched for English based publications comparing the use of apixaban added to DAPT for the treatment of patients with ACS. Different categories of bleeding events and cardiovascular outcomes were assessed. The analysis was carried out by the RevMan software version 5.4. Odds ratios (OR) with 95% confidence intervals (CI) were used to represent the data following analysis.

Results:

This research analysis consisted of 4 trials with a total number of 9010 participants. Thrombolysis in myocardial infarction (TIMI) defined major bleeding (OR: 2.45, 95% CI: 1.45–4.12; P = .0008), TIMI defined minor bleeding (OR: 3.12, 95% CI: 1.71–5.70; P = .0002), International society of thrombosis and hemostasis (ISTH) major bleeding (OR: 2.49, 95% CI: 1.80–3.45; P = .00001) and Global Use of Strategies to Open Occluded Arteries (GUSTO) defined severe bleeding (OR: 3.00, 95% CI: 1.56–5.78; P = .01) were significantly increased with the addition of apixaban to DAPT versus DAPT alone in these patients with ACS. However fatal bleeding (OR: 10.96, 95% CI: 0.61–198.3; P = .11) was not significantly different.

Conclusions:

Addition of the novel oral anticoagulant apixaban to the DAPT regimen significantly increased bleeding and therefore did not show any beneficial effect in these patients with ACS. However, due to the extremely limited data, we apparently have to rely on future larger studies to confirm this hypothesis.
Relationship between SCN5A gene H558R polymorphism and atrial fibrillation in Tibetan and Han nationalities at high altitude
Authors: Liu Jiang , Yao Fengcai , Han Kaiyue , Chai Jinping , Tian Dekuan , Zhang Jinwei , Wang Rong , Li Wei , Shen Yanmei , Ma Yuanfeng , Geng Sang , Su Xiaoling
Published: March 2021

This study aimed to explore the relationship between H558R polymorphism of the SCN5A gene and atrial fibrillation (AF) in Tibetan and Han nationalities at high altitude.

A total of 50 Tibetan and 50 Han patients with AF at the same altitude (2260 m) were included. Meanwhile, the general clinical data of patients without AF (50 Tibetan and 50 Han) matched with the data of patients with AF were included during the same period. The blood samples of patients were collected to extract DNA. The DNA sequencing was performed by Xi’an Zhenpin Biotechnology Co., Ltd. The mutation loci of the sequence were located and identified by DNA sequencing. The general information, laboratory examination, color Doppler echocardiography, and genotypes and alleles of each group were analyzed. The multivariate logistic regression analysis was used to determine the independent risk factors for AF.

The genotype and allele frequencies of the H558R locus of the SCN5A gene in the AF groups of Tibetan and Han nationalities were significantly different from those in the non-AF groups (P < .05). The genotype and allele frequency of the H558R locus of the SCN5A gene in the AF group of Tibetan nationalities were not significantly different from those in the AF group of Han nationalities (P > .05). The logistic regression analysis of the total population revealed that coronary heart disease, age, total cholesterol (TC), left atrial diameter, and G allele were independent risk factors for AF occurrence.

The occurrence of AF in Tibetan and Han nationalities at high altitude is associated with the polymorphism of H558R locus of the SCN5A gene. The G allele is an independent risk factor for the occurrence of AF in Tibetan and Han nationalities.
Little needle-scalpel for piriformis syndrome
Authors: Zhu Qingyuan , Zhu Siyuan , Xiong Jun , Lu Lunbin , Chen Jun , Zhong Zhiying , Tang Genhua
Published: March 2021

Background:

Piriformis syndrome (PS) is a condition in which the sciatic nerve is compressed when passing through the inferior mouth of the piriformis muscle, mainly caused by pain in one hip and leg. In severe cases, patients may experience severe buttock and lower limb pain, discomfort, difficulty walking, and claudication. It is estimated that the annual incidence of low back pain and sciatica is about 40 million cases, and the annual incidence of piriformis syndrome is about 2.4 million cases. The aim of this systematic review is to assess the effectiveness and safety of Little needle-scalpel therapy for Piriformis syndrome.

Methods:

Two reviewers will electronically search the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; China National Knowledge Infrastructure (CNKI); Chinese Biomedical Literature Database (CBM); Chinese Scientific Journal Database (VIP database); and Wan-Fang Database from the inception, without restriction of publication status and languages. Additional searching including researches in progress, the reference lists, and the citation lists of identified publications. Study selection, data extraction, and assessment of study quality will be performed independently by 2 reviewers. If it is appropriate for a meta-analysis, RevMan 5.4 statistical software will be used; otherwise, a descriptive analysis will be conducted. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The results will be presented as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and weight mean difference (WMD) or standard mean difference (SMD) 95% CIs for continuous data.

Results:

This study will provide a comprehensive review of the available evidence for the treatment of Little needle-scalpel with piriformis syndrome.

Conclusions:

The conclusions of our study will provide an evidence to judge whether Little needle-scalpel is an effective and safe intervention for patients with piriformis syndrome.

Ethics and dissemination:

This systematic review will be disseminated in a peer-reviewed journal or presented at relevant conferences. It is not necessary for a formal ethical approval because the data are not individualized.

Trial registration number:

INPLASY2020110092.
Psychosis in a primary hyperparathyroidism patient with mild hypercalcemia
Authors: Otsuki Koji , Izuhara Muneto , Miura Shoko , Yamashita Satoko , Nagahama Michiharu , Hayashida Maiko , Hashioka Sadayuki , Miyaoka Tsuyoshi , Hotta Yukie , Shimizu Yasuhiko , Inagaki Masatoshi
Published: March 2021

Introduction:

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and an elevated level of serum parathyroid hormone (PTH). PHPT presents with a complex set of renal, skeletal, and neuropsychological symptoms. Parathyroidectomy (PTX) is a radical treatment that is recommended for all physically symptomatic patients with PHPT. However, psychiatric symptoms are not considered as an indication for surgery. There remains an important issue from the view of perioperative management of whether PTX should be performed with the presence of uncontrolled psychiatric symptoms or deferred until severe psychiatric symptoms have been controlled. We report a case of mild hypercalcemia that caused severe psychosis in PHPT, which improved dramatically following PTX and resulted in successful postoperative management.

Patient concern:

Our patient was a 68-year-old Japanese woman. She was diagnosed with PHPT, which was triggered by mild hypercalcemia. She was due to receive an operation for osteoporosis and kidney stones. She had severe psychosis, despite medication. Blood examinations revealed mild hypercalcemia (10.4 mg/dL, 8.8–10.1 mg/dL) and elevated serum levels of intact PTH (184.0 pg/mL, 10–65 pg/mL).

Diagnosis:

She was diagnosed with severe psychosis caused by mild hypercalcemia in PHPT.

Interventions:

Although she was treated with 37.5 mg quetiapine and 2 mg risperidone daily, she was excessively sedated and rejected oral treatment. Therefore, we decided to perform the operation.

Outcomes:

Immediately following surgery, serum levels of calcium, and intact PTH were normalized. Her psychotic symptoms ceased completely 5 days after surgery.

Conclusion:

We emphasize that PHPT presents with various severe psychiatric symptoms, even in mild hypercalcemia. Psychiatric symptoms may be the only salient symptoms in PHPT, and thus clinicians should suspect PHPT in patients with psychiatric symptoms and mild hypercalcemia. Furthermore, PTX is recommended for PHPT—even in the presence of severe uncontrolled psychiatric symptoms, which carries risks for postoperative management—because psychiatric symptoms are expected to improve and good postoperative management is possible.
Effectiveness and safety of massage in the treatment of obesity
Authors: Jin Mengke , Jiao Lin , Li Jun , Zhu Daocheng , Xu Wei , Zhong Genping , Cao Zhiwen , Liu Xuefang
Published: March 2021

Background:

Obesity has become one of the largest chronic diseases in the world. It is a chronic metabolic disease caused by various factors. In recent years, massage has been used more and more widely in the treatment of obesity diseases. However, the effectiveness and safety of massage in the treatment of adult obesity are still unclear. The purpose of this study is to evaluate the effectiveness and safety of massage in the treatment of adult obesity.

Methods:

We will conduct a comprehensive review in Medline, PubMed, Cochrane System Evaluation Database, embbase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wang Fang Database, Chinese Science Journal Database. There is no language restriction for the literature search from its establishment to February 2021. In addition, we will manually search for references to unpublished studies and originally included articles. Reviewers will identify the research, extract the data, and independently assess the quality. Results of interest include: total effective rate; total nasal symptom score; rhinitis quality-of-life questionnaire; visual analog scale; laboratory test indicators: IgE, IL6, IL10, or TNF-α levels; recurrence rate; adverse events. Randomized clinical trials will be collected, the Cochrane bias risk assessment tool will be used to assess methodological quality, and recommendations, evaluation, development, and evaluation methods will be used to assess the level of evidence. The meta-analysis will be performed using RevMan 5.4.0 software. A heterogeneity test will be conducted between studies, and P <.1 and I2> 50% are the thresholds for testing. According to the degree of heterogeneity, we will use a fixed effects model or a random effects model.

Results:

The results of this study will provide sufficient evidence to judge whether massage is an effective and safe treatment for adult obesity.

Conclusions:

This study will provide evidence to determine whether massage is an effective intervention for Adult obesity. The research results will also be published in a peer-reviewed journal.

INPLASY registration number:

INPLASY 202120061
Moxibustion therapy for treating psoriasis vulgaris
Authors: Zou Jiahua , Huang Gang , Hu Chuxiang , Yan Juan , Zhang Feiyan , Shi Haiyong , Yuan Xian , Fu Jiajun , Gong Liping
Published: March 2021

Background:

Psoriasis vulgaris (PV) is an immune-mediated skin disease, which has seriously affected the quality of life of patients. At present, moxibustion therapy has been widely used in the treatment of PV. The purpose of this study is to provide high-quality evidence-based medicine to evaluate the effectiveness and safety of moxibustion for PV.

Methods:

We will search the following Electronic databases from their inceptions to February 2021 without any language limitation: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Science Journal Database, Chinese Biomedical Literature Database. What's more, the grey literature and the references of all included literature will also be retrieved manually. Any clinical randomized controlled trials (RCTs) related to moxibustion therapy for PV will be taken into. In order to complete data synthesis and assess the risk of bias, we will use the RevMan V.5.3 software.

Results:

This systematic review will provide an assessment of the current state of moxibustion for PV, aiming to assess the efficacy and safety of moxibustion for patients with PV.

Conclusion:

This systematic review will establish convincing evidence to prove the effectiveness and safety of moxibustion for PV.

INPLASY registration number:

INPLASY202120008.
Remarkable response to anti-PD1 immunotherapy in refractory metastatic high-grade myxofibrosarcoma patient
Authors: Luo Yi , Min Li , Zhou Yong , Tang Fan , Lu Minxun , Xie Hongmei , Wang Yitian , Duan Hong , Zhang Wenli , Tu Chongqi
Published: March 2021

Introduction:

Myxofibrosarcoma (MFS) is a locally aggressive tumor and has the potential to be fatal because of distant metastasis. Immunotherapy targeting either programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) has recently shown a curative effect on multiple cancers including melanoma, non-small cell lung cancer, and renal cell carcinoma. Although the immunotherapy has been applied in sarcoma, there is little information about the efficiency to treat metastatic MFS.

Patient concerns:

A 42-year-old male presented to the clinic with a mass in the left thigh. Mass resection and ligament replacement surgery were performed.

Diagnoses:

The patient was diagnosed as high-grade MFS (federation nationale des centres de lutte contre le cancer, Grade 3) with pulmonary metastasis.

Interventions:

In the past few years, he was treated with surgery, chemoradiotherapy, and Anlotinib (an angiogenesis inhibitor), but the metastatic lesion continued to progress. About 40% to 50% of tumor cells in his pulmonary tissues were showed positive PD-L1 expression and his tumor mutational burden was 215Muts. Thus, he received Camrelizumab (PD-1 inhibitor).

Outcomes:

Six months after the initiating immunotherapy of Camrelizumab, the size of pulmonary lesions showed marked shrinkage, indicating a partial response. After a follow-up of 18 months, the patient remained in good condition without progressive disease.

Conclusion:

This case described here demonstrated that immunotherapy of PD-1 inhibitor is a promising treatment option for refractory MFS with PD-L1 positive or tumor mutational burden -high, which could contribute to effective tumor response.
Xiaochaihu decoction for nonalcoholic fatty liver disease
Authors: Zhu Wenyu , Luo Huan , Xiong Min , Shen Tao
Published: March 2021

Background:

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive deposition of fat in hepatocytes except for alcohol and other specific hepatic factors. Xiaochaihu decoction (XD) has been widely used to treat NAFLD in China. However, there is no systematic review found. In order to evaluate the efficacy and safety of XD in the treatment of NAFLS, we need to conduct a meta-analysis and systematic evaluation.

Methods:

There are enrolled randomized controlled trials (RCTs) evaluating the effectiveness and safety of XD in the treatment of NAFLD. Data come mainly from 4 Chinese databases (CNKI, CBM, Wanfang, and VIP Database) and 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till September 30, 2021. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software.

Results:

This study will provide high-quality evidence for the effectiveness and safety of XD in the treatment of NAFLD.

Conclusion:

The results of the study will help us determine whether XD can effectively treat NAFLD.

Ethics and dissemination:

This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.

OSF registration number:

DOI 10.17605/OSF.IO/A5XEM
Clinical outcomes in 21-hydroxylase deficiency
Authors: Nordenström Anna , Lajic Svetlana , Falhammar Henrik
Published: March 2021

Purpose of review

The introduction of synthetic glucocorticoids 70 years ago made survival possible in classic 21-hydroxylase deficiency (21OHD). The currently used glucocorticoid therapy may lead to unphysiological dosing with negative consequencies on health in addition to the problems that may arise due to androgen over-exposure.

Recent findings

Fertility in females with 21OHD seemed to be impaired, especially in the salt-wasting (SW) phenotype but when pregnancies did occur there was a higher risk for gestational diabetes and cesearean section. Increased fat mass, body mass index, insulin resistance and frequency of autoimmune disorders as well as impaired echocardiographic parameters and lower bone mineral density were found in 21OHD compared to controls. Negative effects on cognitive functions have been identified. Adrenal tumors, especially myelolipomas, were prevalent. Increased knowledge on steroid metabolism in 21OHD and urine steroid profiling may improve assessment of treatment efficacy. Nevanimibe, abiraterone acetate and anastrozole may have a place in the future management of 21OHD. Long-acting glucocorticoids may be a less favorable, especially dexamethasone.

The various clinical outcomes need regular monitoring. Negative consequencies are to large extent the result of the unphysiological glucocorticoid replacement. Modern management with improved follow-up and future addition of new drugs may improve outcomes.
Approach to large adrenal tumors
Authors: Ambroziak Urszula
Published: March 2021

Purpose of review

To summarize the data concerning approach to large adrenal tumors (LAT's), since recent guidelines published in 2016 recommend individual approach rather than clear size cut-off of a tumor that should be removed.

Recent findings

Although the risk of malignancy clearly correlates with the size of a lesion, tumor size of more than 4 cm in diameter represents only 31–61% specificity for the diagnosis of malignant tumor. Therefore, the risk of malignancy and decision about surgery should not be based only on the size of a tumor but assessed in terms of imaging studies, growth pattern during follow-up and new tool that is urine/serum steroid metabolomics.

Approach to patients with LAT's should be individualized. Patients with LAT's should be managed by an expert multidisciplinary team, that includes an endocrinologist, a radiologist, a pathologist, and an adrenal surgeon.
Long-term real-life efficacy and safety of infliximab and adalimumab in the treatment of inflammatory bowel diseases outpatients
Authors: Tursi Antonio , Mocci Giammarco , Lorenzetti Roberto , Allegretta Leonardo , Brandimarte Giovanni , Cassieri Claudio , Colucci Raffaele , De Medici Antonio , Faggiani Roberto , Ferronato Antonio , Fiorella Serafina , Forti Giacomo , Franceschi Marilisa , Gallina Sara , Giorgetti GianMarco , Grasso Giuseppina , Larussa Tiziana , Luzza Francesco , Penna Antonio , Pica Roberta , Piergallini Simona , Porciello Sarah , Pranzo Giuseppe , Rodino’ Stefano , Scorza Stefano , Sebkova Ladislava , Zampaletta Costantino , Elisei Walter , Picchio Marcello
Published: March 2021

Background

Infliximab and adalimumab are widely used for the treatment of Crohn’s disease and ulcerative colitis.

Aim

To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn’s disease and ulcerative colitis patients reflecting real-life clinical practice.

Methods

Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn’s disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36–72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36–84).

Results

In Crohn’s disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P < 0.000); mucosal healing and steroid-free remission were maintained in 80.6% of adalimumab vs. 77.0% of infliximab patients (P = 0.494) and in 90.2% of adalimumab vs. 87.5% of infliximab patients (P = 0.662), respectively. At the multivariate analysis, ileocolonic location and simple endoscopic score for Crohn’s disease >10 were predictors of failure in Crohn’s disease; treatment with adalimumab, BMI ≥30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P < 0.000).

Conclusion

Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.
The prognostic value of P-wave dispersion and left atrial functions assessed with three-dimensional echocardiography in patients with cirrhosis
Authors: Ozersari Sevil , Ünal Bariş , Kemal Çabuk Ali , Eren Hazir Kutluhan , Çağri Şimşek Ersin , Ekmekci Cenk , Küçükukur Murat , Betül Paköz Zehra , Günay Süleyman , Sari Cenk
Published: March 2021

Background

Cirrhotic cardiomyopathy (CCM) is a well-known entity. The aim of this study was to compare left atrial three-dimensional (3D) volume and P-wave dispersion (PWd) in patients with cirrhosis and a healthy population. The secondary purpose was to assess the left phasic volumes and reservoir functions with 3D echocardiography for the prediction of an increased risk of poor outcomes in patients with cirrhosis.

Methods

The study included 50 patients with cirrhosis and 43 healthy control subjects without atrial fibrillation. All patients were assessed with two-dimensional (2D), 3D, and tissue Doppler transthoracic echocardiography. The PWd was calculated using a 12-lead surface electrocardiogram (ECG). Cirrhotic patients were followed up for 2.5 years for the evaluation of poor outcomes and the development of atrial fibrillation.

Results

Patients with cirrhosis were observed to have significantly higher left atrial phasic volumes such as minimal left atrial volume (3D-LAVmin, P = 0.004) and indexed LAVmin (3D-LAVImin, P = 0.0001), and significantly decreased left atrial reservoir functions such as left atrial emptying volume (3D-LAEV, P = 0,001), left atrial ejection fraction (3D-LAEF, P = 0,001) on 3D echocardiography. PWd was determined to be significantly longer in the cirrhotic group compared with the control group (P = 0.003). In the 2.5-year follow-up period, poor outcomes occurred in 34 patients (22 patients died, six patients had liver transplantation, six patients developed atrial fibrillation/AHRE episodes). In Cox regression analysis, the MELD score (HR, 1.16 (1.06–1.26), P = 0.001) and 3D-LAVImin (HR, 0.95 (0.86–1.00), P = 0.040) were significantly associated with all-cause mortality. Cirrhotic patients with LAVImin of >15 ml/m2 were seen to have poor survival (long rank P = 0.033).

Conclusion

The results of this study showed that patients with cirrhosis had higher left atrial volume, longer PWd and worse diastolic functions compared with the control group. Higher disease severity scores were associated with left atrial function and volume. In addition, left atrial volume measured with 3DE was a strong predictor of future adverse events, and minimal left atrial volumes had a higher prognostic value than any other left atrial function indices.
Perioperative therapy in renal cancer in the era of immune checkpoint inhibitor therapy
Authors: Kuusk Teele , Abu-Ghanem Yasmin , Mumtaz Faiz , Powles Thomas , Bex Axel
Published: March 2021

Purpose of review

Immune checkpoint inhibitor (ICI) combination therapy has revolutionized therapy of metastatic renal cancer. The success of immunotherapy has renewed an interest to study these agents in adjuvant and neoadjuvant settings and prior to cytoreductive nephrectomy. This narrative review will give an overview of ongoing trials and early translational research outcomes.

Recent findings

In nonmetastatic renal cell carcinoma (RCC), five phase 3 adjuvant and neoadjuvant trials with ICI monotherapy or combinations are ongoing with atezolizumab (IMmotion 010; NCT03024996), pembrolizumab (KEYNOTE-564; NCT03142334), nivolumab (PROSPER; NCT03055013), nivolumab with or without ipilimumab (CheckMate 914; NCT03138512) and durvalumab with or without tremelimumab (RAMPART; NCT03288532). Phase 1b/2 neoadjuvant trials demonstrate safety, efficacy and dynamic changes of immune infiltrates and provide rationales for neoadjuvant trial concepts as well as prediction of response to therapy. In primary metastatic RCC, two phase 3 trials investigate the role of deferred cytoreductive nephrectomy following pretreatment with ICI combination (NORDICSUN; NCT03977571 and PROBE; NCT04510597).

The outcomes of the major phase 3 trials are awaited as early as 2023. Meanwhile, translational data from phase 1b/2 studies enhance our understanding of the tumour immune microenvironment and its dynamic changes.
Preoperative Delirium Nursing Model Initiatives to Determine the Incidence of Postoperative Delirium Among Elderly Orthopaedic Patients
Authors: Wu Huixin , Kapur Anshika , Gibson Barbara , Bubb Kelsi , Alrawashdeh Mohammad , Cipkala-Gaffin Janet
Published: March 2021

Delirium is a common neurocognitive disorder prevalent in hospitalized older adults. The development of delirium is associated with adverse health outcomes, including functional decline and mortality. This study aimed to investigate the incidence and risk factors of postoperative delirium in older adults (≥60 years) who underwent orthopaedic surgery. Elderly orthopaedic patients were recruited from a large urban hospital over 12 months. Patients were preoperatively screened for delirium and followed up at least once daily postoperatively until discharge. Of the 124 patients in the sample, 21 (16.9%) had postoperative delirium. There were no significant differences in any of the baseline characteristics between the delirious and nondelirious patients. Patients using antidepressants were more likely to develop postoperative delirium compared with those not using antidepressants (odds ratio: 2.72, p = .05). Postoperative delirium was common in this sample of older adults who underwent orthopaedic surgery. Aiming prevention strategies toward patients using antidepressants may help reduce the incidence of delirium in this population.
Safety and Feasibility of Discharge Without an Opioid Prescription for Patients Undergoing Gynecologic Surgery
Authors: Margolis Benjamin , Andriani Leslie , Baumann Katherine , Hirsch Anna M. , Pothuri Bhavana
Published: March 2021

(Abstracted from Obstet Gynecol 2020;136:1126–1134)

Hysterectomy is the second most common surgical procedure among women in the United States, with approximately 600,000 hysterectomies performed annually. Opioids are prescribed to reduce postoperative pain from these and other gynecologic procedures.
Introduction to Artificial Intelligence in Ultrasound Imaging in Obstetrics and Gynecology
Authors: Drukker L. , Noble J. A. , Papageorghiou A. T.
Published: March 2021

(Abstracted from Ultrasound Obstet Gynecol 2020;56:498–505)

Artificial intelligence (AI) uses specific algorithms to come to conclusions and process human intelligence possibly better than humans can. Thus far, AI has had relatively little impact in the field of obstetrics and gynecology, although in the field providers rely on ultrasound images to make diagnoses.
Reduction in Twin Stillbirth Following Implementation of NICE Guidance
Authors: Khalil A. , Giallongo E. , Bhide A. , Papageorghiou A. T. , Thilaganathan B.
Published: March 2021

(Abstracted from Ultrasound Obstet Gynecol 2020;56:566–571)

In the United Kingdom, the rate of stillbirths in twin pregnancies has been on the decline. The rate of stillbirths dropped from 11.1 per 1000 births in 2014 to 6.6 in 2016 (95% confidence interval, 9.8–12.5 and 5.2–7.2, respectively).
Cytokine Release Syndrome Biology and Management
Authors: Cobb Dustin A. , Lee Daniel W.
Published: March 2021

The successful application of chimeric antigen receptor (CAR) T cells for the treatment of relapsed and refractory B-cell malignancies has ushered in a new frontier for the immunotherapy of cancer. Despite its successes, CAR T-cell therapy presents several challenges. Cytokine release syndrome (CRS) triggered by robust and exponential CAR T-cell expansion is the most common adverse effect and may be severe or life-threatening. Although modulation of the interleukin 6 axis was appreciated early on as a means to manage CRS, the exact underlying mechanisms leading to severe CRS remain to be elucidated. What is clear is that severe CRS involves recruitment of the broader immune system into a hyperinflammatory and unregulated state. Myeloid-derived cells appear to play a critical role in this regard and are at the center of active investigation. In this article, we will focus on important elements of CRS, the clinical manifestations, underlying biology, and management strategies including grading, supportive care, and treatment via immunosuppression.
Quantitative Morphometric Analysis of Anatomical Landmarks Involved in Bilateral Sagittal Split Osteotomy in Different Skeletal Malocclusions Using Cone-Beam Computed Tomography
Authors: Khalighi Sigaroudi Ali , Nazarpour Yousefdeh Ali , Dalili Kajan Zahra , Rafiei Elahe
Published: March 2021

Background:

To assess and compare the anatomical landmarks involved in bilateral sagittal split osteotomy (BSSO) in different skeletal malocclusions quantitatively using cone-beam computed tomography (CBCT).

Methods:

This retrospective study evaluated 63 CBCT scans of the three malocclusion classes (n = 21). Twenty-one quantitative variables were measured and compared between different malocclusion classes. One-way ANOVA, Welch test, Kruskal Wallis test and the Mann–Whitney test with Bonferroni adjustment were used for data analysis. The level of significance was set at ≤0.05.

Results:

The patients had a mean age of 26.35 years (range 18–58 years). The width of the lateral cortex in the posterior third (T1-P) of ramus in the left side, and the mean value in the right and left sides were significantly different between different classes of malocclusion (P = 0.049) such that class II patients had significantly thinner lateral cortex. No other significant differences were noted between different malocclusion classes in other variables.

Conclusion:

The quantitative morphological assessment of the mandible in BSSO of different malocclusion classes did not reveal significant differences. There is no superiority in the dimensions of discussed landmarks involved in BSSO among different malocclusion classes. So the risk or the safety of this kind of surgery is similar for these classes. Thus, diagnostic preoperative workup by CBCT is imperative for selection of a surgical approach with minimal postoperative complications.
Sports-Related Cervical Spine Injuries – Background, Triage, and Prevention
Authors: Basil Gregory W. , Burks S. Shelby , Green Barth A.
Published: March 2021

Cervical spinal injuries are a rare, but potentially devastating occurrence in sports. Although many of these injuries occur in unsupervised sports, they are also seen in organized sports – most commonly in football, wrestling, and ice hockey. Additionally, although each sport is associated with its own unique injury patterns, axial loading remains a common theme seen in cervical injuries associated with significant neurologic impairment. Regardless of the mechanism, a cautious and conservative approach should be taken with regards to evaluation, management, and return to play.
Trauma outcome predictor: An artificial intelligence interactive smartphone tool to predict outcomes in trauma patients
Authors: Maurer Lydia R. , Bertsimas Dimitris , Bouardi Hamza Tazi , El Hechi Majed , El Moheb Mohamad , Giannoutsou Katerina , Zhuo Daisy , Dunn Jack , Velmahos George C. , Kaafarani Haytham M.A.
Published: March 2021

BACKGROUND

Classic risk assessment tools often treat patients’ risk factors as linear and additive. Clinical reality suggests that the presence of certain risk factors can alter the impact of other factors; in other words, risk modeling is not linear. We aimed to use artificial intelligence (AI) technology to design and validate a nonlinear risk calculator for trauma patients.

METHODS

A novel, interpretable AI technology called Optimal Classification Trees (OCTs) was used in an 80:20 derivation/validation split of the 2010 to 2016 American College of Surgeons Trauma Quality Improvement Program database. Demographics, emergency department vital signs, comorbidities, and injury characteristics (e.g., severity, mechanism) of all blunt and penetrating trauma patients 18 years or older were used to develop, train then validate OCT algorithms to predict in-hospital mortality and complications (e.g., acute kidney injury, acute respiratory distress syndrome, deep vein thrombosis, pulmonary embolism, sepsis). A smartphone application was created as the algorithm’s interactive and user-friendly interface. Performance was measured using the c-statistic methodology.

RESULTS

A total of 934,053 patients were included (747,249 derivation; 186,804 validation). The median age was 51 years, 37% were women, 90.5% had blunt trauma, and the median Injury Severity Score was 11. Comprehensive OCT algorithms were developed for blunt and penetrating trauma, and the interactive smartphone application, Trauma Outcome Predictor (TOP) was created, where the answer to one question unfolds the subsequent one. Trauma Outcome Predictor accurately predicted mortality in penetrating injury (c-statistics: 0.95 derivation, 0.94 validation) and blunt injury (c-statistics: 0.89 derivation, 0.88 validation). The validation c-statistics for predicting complications ranged between 0.69 and 0.84.

CONCLUSION

We suggest TOP as an AI-based, interpretable, accurate, and nonlinear risk calculator for predicting outcome in trauma patients. Trauma Outcome Predictor can prove useful for bedside counseling of critically injured trauma patients and their families, and for benchmarking the quality of trauma care.
Modelling the population-level protection conferred by COVID-19 vaccination
Authors: Padmanabhan Pranesh , Desikan Rajat , Dixit Narendra M.
Published: March 2021

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines work predominantly by eliciting neutralizing antibodies (NAbs), how the protection they confer depends on the NAb response to vaccination is unclear. Here, we collated and analysed in vitro dose-response curves of >70 NAbs and constructed a landscape defining the spectrum of neutralization efficiencies of NAbs elicited. We mimicked responses of individuals by sampling NAb subsets of known sizes from the landscape and found that they recapitulated responses of convalescent patients. Combining individual responses with a mathematical model of within-host SARS-CoV-2 infection post-vaccination, we predicted how the population-level protection conferred would increase with the NAb response to vaccination. Our predictions captured the outcomes of vaccination trials. Our formalism may help optimize vaccination protocols, given limited vaccine availability.

One sentence summary

Viremic control by the spectrum of neutralizing antibodies elicited by vaccination determines COVID-19 vaccine efficacies.
Improving postpartum hemorrhage risk prediction using longitudinal electronic medical records
Authors: Zheutlin Amanda B , Vieira Luciana , Li Shilong , Wang Zichen , Schadt Emilio , Gross Susan , Stone Joanne , Schadt Eric , Li Li
Published: March 2021

Objective

Postpartum hemorrhage (PPH) remains a leading cause of preventable maternal mortality in the US. Our goal was to develop a novel risk assessment tool and compare its accuracy to those used in current practice.

Materials and Methods

We used a PPH digital phenotype we developed and validated previously to identify 6,639 cases from our delivery cohort (N=70,948). Using a vast array of known and potential risk factors extracted from electronic medical records available prior to delivery, we trained a gradient boosting model in a subset of our cohort. In a held-out test sample, we compared performance of our model to three clinical risk tools and one previously published model.

Results

Our 24-feature model achieved an area under the curve (AUC) of 0.71 (95% confidence interval [CI], 0.69-0.72), higher than all other tools (research-based AUC: 0.67 [95%CI, 0.66-0.69], clinical AUCs: 0.55 [95%CI, 0.54-0.56] to 0.61 [95%CI, 0.59-0.62]). Five features were novel including red blood cell indices and infection markers measured standardly upon admission. Additionally, we identified inflection points for several vital signs and labs where risk rose substantially. Most notably, patients with median intrapartum systolic blood pressure above 132mmHg had an 11% [interquartile range, 4%] median increase in relative risk for PPH.

Conclusions

We developed a novel approach for predicting PPH and identified clinical feature thresholds that can guide intrapartum monitoring for PPH risk. Our results suggest our model is an excellent candidate for prospective evaluation and could ultimately reduce PPH morbidity and mortality through early detection and prevention.
A Longitudinal Study of BNT162b2 Vaccine-Induced Humoral Response and Reactogenicity in Health Care Workers with Prior COVID-19 Disease
Authors: Kelsen Steven G. , Braverman Alan S. , Aksoy Mark O. , Hayman Jacob A. , Patel Puja , Rajput Charu , Zhao Huaqing , Fisher Susan G. , Ruggieri Michael R. , Gentile Nina T.
Published: March 2021

Background

Current recommendations in the United States are that subjects with a previous history of COVID-19 disease receive the full 2 dose mRNA vaccine regimen. We tested the hypothesis that humoral immune responses and reactogenicity to a SARS-CoV-2 mRNA vaccine (BNT-162b2) differ qualitatively and quantitatively in subjects with prior SARS-CoV-2 infection versus infection-naïve subjects.

Methods

Health care workers (n=61) from a single academic institution with and without prior COVID-19 received two 30 µg doses of BNT162b2 vaccine 3 weeks apart. The COVID group (n=30) received vaccine approximately 7 months post infection. IgG antibody against the Spike receptor-binding domain (RBD), serum neutralizing activity and vaccine adverse reactions were assessed every 2 weeks for 56 days after the 1st injection. A longitudinal design and long study duration allowed the onset, maximum response and initial decay rate of Spike IgG antibody to be assessed in each subject. In addition, Spike IgG antibody levels are expressed as µg / mL to provide normal values for clinical decision making.

Findings

Spike IgG responses were highly variable in both groups. However, the COVID group manifested rapid increases in Spike IgG antibody and serum neutralizing activity post 1st vaccine dose but little or no increase in Spike IgG or serum neutralizing activity after the 2nd dose. In fact, Spike IgG was maximum prior to the 2nd dose in 36% of the COVID group and 0% of controls. Peak IgG antibody was lower but appeared to fall more slowly in the COVID than in the control group. Finally, adverse systemic reactions e.g., fever, headache and malaise, after both the 1st and 2nd injection were more frequent and lasted longer in the COVID group than in the control group.

Conclusions

Health care workers with prior COVID-19 demonstrate a robust, accelerated humoral immune response to the 1st dose of the COVID-19 mRNA vaccine but attenuated response to the 2nd dose. They also experience greater reactogenicity than controls. Accordingly, subjects with prior COVID-19 may require only a single dose of vaccine.
A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment
Authors: Roy Maggie , Fortier Mélanie , Rheault François , Edde Manon , Croteau Etienne , Castellano Christian-Alexandre , Langlois Francis , St-Pierre Valérie , Cuenoud Bernard , Bocti Christian , Fulop Tamas , Descoteaux Maxime , Cunnane Stephen C.
Published: March 2021

INTRODUCTION

White matter (WM) energy supply is crucial for axonal function and myelin maintenance. Providing ketones, the brain’s alternative fuel to glucose, is a therapeutic strategy to bypass the brain’s glucose-specific energy deficit in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in specific WM fascicles in MCI has not previously been described.

METHODS

This 6-month interventional study included MCI participants randomized to a placebo (n = 16) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre- and post-intervention. WM fascicle uptake of ketone and glucose and structural properties were assessed using positron emission tomography and diffusion imaging, respectively.

RESULTS

Ketone uptake was increased by 2.5 to 3.2-fold in nine fascicles of interest (P < 0.001) only in the kMCT group, an effect seen both in deep WM and in fascicle cortical endpoints. Improvement in processing speed was associated with WM ketone uptake globally and in individual fascicles, most importantly the fornix (r = +0.61; P = 0.014).

DISCUSSION

A 6-month ketogenic supplementation in MCI improved WM energy supply globally. The significant positive association with processing speed suggests that ketones may have a role in myelin integrity in MCI.
Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality
Authors: Brunet-Ratnasingham Elsa , Anand Sai Priya , Gantner Pierre , Moquin-Beaudry Gaël , Dyachenko Alina , Brassard Nathalie , Beaudoin-Bussières Guillaume , Pagliuzza Amélie , Gasser Romain , Benlarbi Mehdi , Point Floriane , Prévost Jérémie , Laumaea Annemarie , Niessl Julia , Nayrac Manon , Sannier Gérémy , Boutin Marianne , Descôteux-Dinelle Jade , Gendron-Lepage Gabrielle , Goyette Guillaume , Bourassa Catherine , Medjahed Halima , Orban Catherine , Butler-Laporte Guillaume , Morrison David , Zhou Sirui , Nakanishi Tomoko , Laurent Laetitia , Richard Jonathan , Dubé Mathieu , Fromentin Rémi , Rébillard Rose-Marie , Arbour Nathalie , Prat Alexandre , Larochelle Catherine , Durand Madeleine , Brent Richards J , Chassé Michaël , Tétreault Martine , Chomont Nicolas , Finzi Andrés , Kaufmann Daniel E.
Published: March 2021

Despite advances in COVID-19 management, it is unclear how to recognize patients who evolve towards death. This would allow for better risk stratification and targeting for early interventions. However, the explosive increase in correlates of COVID-19 severity complicates biomarker prioritisation. To identify early biological predictors of mortality, we performed an immunovirological assessment (SARS-CoV-2 viral RNA, cytokines and tissue injury markers, antibody responses) on plasma samples collected from 144 hospitalised COVID-19 patients 11 days after symptom onset and used to test models predicting mortality within 60 days of symptom onset. In the discovery cohort (n=61, 13 fatalities), high SARS-CoV-2 vRNA, low RBD-specific IgG levels, low SARS-CoV-2-specific antibody-dependent cellular cytotoxicity, and elevated levels of several cytokines and lung injury markers were strongly associated with increased mortality in the entire cohort and the subgroup on mechanical ventilation. Model selection revealed that a three-variable model of vRNA, age and sex was very robust at identifying patients who will succumb to COVID-19 (AUC=0.86, adjusted HR for log-transformed vRNA=3.5; 95% CI: 2.0-6.0). This model remained robust in an independent validation cohort (n=83, AUC=0.85). Quantification of plasma SARS-CoV-2 RNA can help understand the heterogeneity of disease trajectories and identify patients who may benefit from new therapies.