tbuckley/cabot-search huggingface dataset:
RARE-12. PITUITARY ADENOMA SURGERIES IN COVID-19 ERA: EARLY LOCAL EXPERIENCE FROM EGYPT
Authors: Mohamed Arnaout
Journal: Neuro-Oncology (2021)

Abstract Background The pandemic of COVID-19 has a great impact on all health-care services worldwide. Neurosurgical recommendations are to postpone the endoscopic endonasal pituitary surgeries during the pandemic. We would like to express our experience with urgent pituitary adenomas during the current COVID-19 pandemic. Methods In our country, COVID-19 has started to become a paramount problem by March 2020. Nine cases of pituitary adenomas have presented with urgent manifestations. The endoscopic endonasal approach was performed in eight patients, while a craniotomy was selected for a recurrent pituitary adenoma. Pre- and postoperative thorough clinical evaluations with chest CT scans were performed. Other strict infection control measures have been applied. Results In 8 weeks duration starting from the past days of February 2020, we have operated on four females and five males of pituitary adenomas. Visual deterioration was the main presenting symptom. The driving factor for surgery was saving vision in eight patients. Fortunately, the postoperative course was uneventful for all patients. No suspected COVID-19 infection has been reported in any patient or health-care team except one patient. In our city, PCR test was routinely not available. Conclusion In the era of COVID-19, strict infection control precautions should be employed to limit the possibility of transmission of any possible infection to patient or any of the surgical team. We believe that the risk of getting such infection is not increased by the endonasal approach. Long-term follow-up and large numbers of prospective studies are recommended to delineate the impact of COVID-19 infection on pituitary surgeries.
Is first-line immune checkpoint inhibitors (ICI) beneficial to platinum-eligible patients (pts) with advanced urothelial carcinoma (aUC)? a meta-analysis.
Authors: Ce Cheng, Iloabueke Gabriel Chineke, Ali McBride, Juan Chipollini, Edward Paul Gelmann, Alejandro Recio-Boiles
Journal: Journal of Clinical Oncology (2021)

e16506 Background: ICI have proven to benefit patients diagnosed with aUC who are platinum-ineligible. The role of platinum-eligible patients, in the first-line setting is being further elucidated after single positive randomized clinical trial (RCT) with ICI. Hence, we performed a meta-analysis to interpret the association of Overall Survival (OS) and PD-1 or PD-L1 inhibitors as first-line therapies in platinum-eligible patients with aUC. Methods: Randomized controlled trials were retrieved from PubMed, Web of Science, and Cochrane Library according to established inclusion criteria. Each article was assessed by the Newcastle-Ottawa Scale. The Hazard Risk (HR) and 95% confidence intervals (CI) were calculated. Random effect or fixed-effect model was used to calculate the pooled HR, based on heterogeneity significance. Sensitivity analysis and publication bias detection were performed. All statistical analysis were performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0.05. Results: Sixty-seven articles were obtained from the database search, and based on inclusion/exclusion criteria, five RCTs were selected involving 4063 patients. All studies were considered moderate to high quality. A statistically significant association was found between initiation of immunotherapy as first-line treatment to platinum-eligible patients and increased OS (HR 0.87; 95% CI: 0.81,0.94, p = 0.004, I 2 = 38%). The subgroup analysis included positive PD1 (HR 0.81; 95% CI: 0.70,0.94, p = 0.004, I 2 = 34%) vs. negative expression (HR 0.96; 95% CI: 0.83,1.11, p = 0.58, I 2 = 0%); cisplatin (HR 0.81; 95% CI: 0.69,0.96, p = 0.02, I 2 = 47%) vs. carboplatin administration (HR 0.87; 95% CI: 0.76,1.01, p = 0.06, I 2 = 21%); male (HR 0.87; 95% CI: 0.77,0.97, p = 0.01, I 2 = 44%) vs. female (HR 0.85; 95% CI: 0.70,1.04, p = 0.11, I 2 = 0%); ECOG score 0 (HR 0.77; 95% CI: 0.67,0.89, p = 0.0005, I 2 = 0%) vs. ≥ 1 (HR 0.90; 95% CI: 0.78,1.02, p = 0.11, I 2 = 6%); Caucasian (HR 0.81; 95% CI: 0.73, 0.91, p = 0.0003, I 2 = 39%) vs. other race (HR 0.92; 95% CI: 0.75, 1.13, p = 0.44, I 2 = 0%). Similar association regardless of visceral lesion or age. Funnel plot, Egger's test (p = 0.6944), and Begg's test (0.7726) found no publication bias of analysis. Conclusions: This meta-analysis showed improved OS in platinum-eligible patients receiving first-line ICI in aUC. Furthermore, a subgroup analysis yielded an increased OS and cisplatin, positive PD1 status, ECOG 0, male gender, and Caucasian race. In this rapidly evolving clinical practice changes, our meta-analysis provides support to currently recommended avelumab maintenance after platinum induction therapy in the first-line setting and further provide guidance on patient selection for aUC.
Differential expression of long noncoding RNAs in patients with metastatic and nonmetastatic colorectal cancer.
Authors: Denis S. Kutilin, Marina A. Gusareva, Natalia G Kosheleva, Mikhail S. Zinkovich, Astanda K. Gvaramiya, M. A. Gappoeva, Natalya B. Fatkina, Julia N. Krokhmal, Ekaterina O. Vasilieva, Elena A. Karnauhova, Aliya K. Donskaya, Lyudmila Ya. Rozenko, Vladislav M. Legostaev, Olga V. Shlyakhova, Natalia A. Lyman, Gennady V. Balitsky, A. B. Kravchenko, V. A. Nosov, Oleg Y. Babenkov
Journal: Journal of Clinical Oncology (2021)

e15023 Background: Long non-coding RNAs (lncRNA) play an important role in many biological processes, and their dysregulation can lead to various diseases, including colorectal cancer (CRC). In recent years, interactions between lncRNA, miRNA and mRNAs in development of CRC have attracted more and more attention. However, the currently obtained data on the complex regulatory interactions between lncRNA and microRNA during metastasis in patients with CRC are fragmentary, often contradictory and obtained on samples that are not significant in size. Therefore, the aim of the study was to analyze the features of lncRNA expression in CRC patients without metastases, with lymph nodes metastases and with liver metastases. Methods: The study included 200 patients with colon adenocarcinoma. The patients were divided into 3 groups: without metastases (T2N0MO, group 1, n = 100), with lymph node metastases (T2-3N1-2M0, group 2, n = 60) and with liver metastases (T3N2M1-2, group 3, n = 40). RNA isolation was performed by guanidine-thiocyanate-phenol-chloroform extraction. The lncRNA list was generated based on bioinformatic analysis. The relative expression of 20 lncRNAs (NEAT1, HELLPAR, AP000766.1, LINC00265, MIRLET7BHG, OLMALINC, AC245884.8, MEOX2-AS1, MEG3, NORAD, HCG11, WASIR2, AC005332.7, PURLN, OIP5-AS1, SNHG14, TUG1, XIST, MALAT1, FAM66E) was evaluated by RT-qPCR method. Differences were assessed using the Mann-Whitney test, and the Bonferroni correction was used to correct multiple comparisons. Results: Differential expression of 5 lncRNA (MALAT1, TUG1, XIST, LINC00265, HELLPAR) was found between CRC patients without metastases and patients with metastases to lymph nodes and liver. Thus, in group 1, expressions of MALAT1, TUG1 and HELLPAR were lower by 2.5, 4.0 and 5.5 times (p &lt; 0.005) than in combined group of patients with metastases to lymph nodes and liver, and XIST and LINC00265 expressions were higher by 2.2 and 3.4 times (p &lt; 0.05), respectively. Differential expression of 2 lncRNA (NORAD, WASIR2) was also found between group 2 and group 3. The NORAD expression in patients in group 3 was 5.5 times (p &lt; 0.05) lower than in patients in group 2, and WASIR2 expression, on the contrary, was 2.5 times (p &lt; 0.05) higher in patients in group 3. Conclusions: Thus, differential expression of lncRNA (MALAT1, TUG1, XIST, LINC00265, HELLPAR, NORAD and WASIR2), associated with regulation of proliferation and invasive ability of tumor cells, was found in 3 groups of CRC patients.
Resetting the agenda for antibiotic resistance through a health systems perspective
Authors: Otto Cars, Sujith J Chandy, Mirfin Mpundu, Arturo Quizhpe Peralta, Anna Zorzet, Anthony D So
Journal: The Lancet Global Health (2021)

Although the individual and societal consequences of antibiotic resistance spiral upwards, coordinated action has not kept pace on a global scale. The COVID-19 pandemic has highlighted the need for resilient health systems and has resulted in an unprecedented rate of collaboration in scientific, medical, social, and political dimensions. The pandemic has also created a renewed awareness of the importance of infectious diseases and is a substantial entry point for reigniting the momentum towards containing the silent pandemic of antibiotic resistance. In this Viewpoint, we discuss the limitations in the current narrative on antibiotic resistance and how it could be improved, including concerted efforts to close essential data gaps. We discuss the need for capacity building and coordination at the national and global levels to strengthen the understanding of the importance of sustainable access to effective antibiotics for all health systems that could generate tangible links to current processes for global health and development.
Blood-based tumor mutational burden from circulating tumor DNA (ctDNA) across advanced solid malignancies using a commercially available liquid biopsy assay.
Authors: Leylah Drusbosky, Mehmet Asim Bilen, Georges Azzi, Pedro C. Barata, Patrick M Boland, Alan Haruo Bryce, Young Kwang Chae, Jeremy Meyer Force, Martin Gutierrez, Pashtoon Murtaza Kasi, Hiba I. Dada, Caroline Weipert, Chuck Hensel, Lesli A. Kiedrowski, Che-Yu Lee, Martina Lefterova, David R. Gandara
Journal: Journal of Clinical Oncology (2021)

3040 Background: Pembrolizumab was recently FDA approved across solid tumors for TMB scores ≥ 10mut/Mb as assessed by next-generation sequencing (NGS) of tissue (tTMB). A prior study of advanced cancer patients treated with immunotherapy found that higher somatic TMB, as defined by the 80 th percentile in each histology, was associated with better overall survival. Previously, bTMB assessed by ctDNA from patients with newly diagnosed advanced NSCLC at a score of 16 mut/MB correlated with a tTMB score of 10 mut/MB. TMB levels vary by cancer type, line of treatment, and therapy received; the distribution of bTMB scores across solid tumor types has not been well characterized. Here we report the distribution of bTMB scores in patients with advanced malignancies. Methods: We queried 5,610 samples from patients with different cancer types undergoing clinical cell-free DNA testing (Guardant360; Redwood City, CA) and assessed bTMB scores from October 2020 - January 2021. bTMB score was derived via a previously described computational algorithm examining the total number of synonymous and non-synonymous SNVs and indels across a 1.0MB genomic footprint. We assessed the success rate of bTMB evaluation, overlap with microsatellite instability (MSI) status, and defined the distribution of bTMB levels across indications in this dataset. Results: bTMB score was successfully assessed in 4,275/5,610 (76.3%) samples (Table). The majority of samples (58%) were tested at disease progression as compared to initial diagnosis (42%). The median turnaround time from sample receipt to clinical reporting was 11 days and decreased to 9 days over the course of the study. For the majority of cancer types the 80th percentile TMB was ≥ 16 mut/MB tissue equivalency. Conclusions: Our analysis demonstrates the feasibility of measuring bTMB using a commercially available liquid biopsy assay. bTMB scores trended higher than tTMB previously reported in these cancer types, reflecting the ability of ctDNA to better capture tumor heterogeneity. cfDNA may allow for exploration of bTMB evolution throughout treatment. TMB should be interpreted in the context of disease, treatment, and method; these data establish a pan-cancer benchmark for bTMB which will serve as a resource for further studies.[Table: see text]
Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and hemoglobin (Hb) predict immunotherapy outcomes in patients with advanced or metastatic gastric cancer.
Authors: Miaomiao Gou, Yong Zhang, Huan Yan, Haiyan Si, Zhikuan Wang, Guanghai Dai
Journal: Journal of Clinical Oncology (2021)

e16075 Background: This study aimed to confirm the prognostic role of pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), hemoglobin (Hb) levels as effective and convenient biomarkers for patients with advanced or metastatic gastric cancer (AGC or MGC) receiving immunotherapy. Methods: patients with AGC and MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The receiver operating characteristic analyses for predicting 6 months PFS by the NLR, PLR was used to identify an appropriate cut-off value. The study analyzed the association of NLR, PLR, Hb and overall survival (OS) or progression-free survival (PFS) and anti-tumor response rate with immunotherapy respectively. Results: 137 patients were included in the final analysis. 71 patients were administered immunotherapy in the first line and the rest of the patients in the second or further line. 92 patients had received immunotherapy combined with chemotherapy, whereas 45 patients had undertaken immunotherapy monotherapy or with anti-angiogenesis. The best cut-off value for NLR was 3.23 and for PLR was 816.43. NLR &lt;3.23 was associated with longer OS (HR = 0.38, 95% CI, 0.26-0.57, p &lt; 0.001) and PFS (HR = 0.42, 95% CI, 0.29-0.62, p &lt; 0.001) in patients with AGC or MGC. Patients in PLR&lt;816.43 group had prolonged PFS (7.9m vs 4.3m, p&lt;0.001) and OS (11.1m vs9.2m, p&lt;0.001) than in PLR&gt;=816.43 group. The median PFS was 7.8m in the normal Hb level group (Hb&gt;=110g/L) and 4.3m in the decreased Hb group (Hb&lt;110g/L) (HR=0.5, 95% CI 0.31, 0.81, P=0.004). The OS was 14.4m with normal Hb level as compared with 8.2m with decreased Hb level( HR=0.59, 95% CI 0.37, 0.94, P=0.024). No significant difference was observed in objective response rate (ORR) and disease control rate (DCR) in the different NLR, PLR, Hb group, respectively. Univariate and multivariate analysis found that NLR, PLR, Hb were independent prognostic biomarkers for PFS and OS (p&lt;0.05). Conclusions: pre-treatment NLR, PLR, Hb was significantly associated with PFS and OS in patients with AGC and MGC who received immunotherapy. Clinicians need to consider patients with elevated NLR and PLR or decreased Hb level for decisions on immunotherapy strategy.
Abstract 15088: Anti-Thrombin Nanoparticles Minimize Kidney Ischemia-Reperfusion Injury by Reducing Inflammation and Preserving Vascular Integrity
Authors: Ian A Vargas, Daniel Stephenson, Charles Chalfant, Hua Pan, Samuel Wickline
Journal: Circulation (2019)

Introduction: Acute kidney injury (AKI) confers a 25% chance of developing chronic kidney disease and a 50% increase in 10-year mortality risk. Clinical trials completed in 2018 indicated that targ...
Study on the correlation between the expression of basic transcription factor 3 (BTF3) and the efficacy and prognosis of patients with malignant melanoma (MM).
Authors: Ning Ning Niu, Yong Qi Li, Liang Guo, Qiong Yang Liu, Yi Qun Zhang, Zhen Guo, Shi Jie Lan, Di Wu
Journal: Journal of Clinical Oncology (2021)

e21554 Background: BTF3 is an RNA polymerase II transcription factor, studies have confirmed that BTF3 is abnormally expressed in several types of tumors and closely related to the proliferation and prognosis of gastrointestinal tumors. However, the function of BTF3 in MM remains unknown. The present study aim to detect the expression and proliferation of BTF3，to explore the correlation between the BTF3 expression and the efficacy and prognosis of MM patients. Methods: We explored the effect of BTF3 through silencing BTF3 expression by siRNA transfection with lentivirus in human melanoma cell lines. The cell proliferation, cell cycle and apoptosis were determined by methyl-thaizolyl-tetrazolium assay, flow cytometry and western blot, respectively. Then we investigated the effect of BTF3 in nude mice by tumor formation experiment. The expression of BTF3 was determined by immunohistochemistry (IHC) from 32 patients with different subtypes of MM during October 2014 to October 2020. Among them, 28 cases could be resected (stage I-III), 4 cases could not be resected (stage III-IV). Cutaneous MM 7 cases, Acral MM 14 cases, mucosal MM 9 cases, unknown primary MM 2 cases. The correlation of BTF3 expression and RFS (recurrence-free survival) /OS (overall survival) in 28 patients with resected MM was explored by Student’s t test. Results: The increased viability of negative control virus infection group was 4.706 times than that of BTF3-siRNA group. Compared with the former, BTF3-siRNA group had more cells in G1 and S phase (P&lt; 0.05) and more apoptotic cells (P&lt; 0.05). BTF3-siRNA reduced tumor formation in the nude mice (P&lt;0.01). The relative IHC scores of BTF3 was 5.50±3.19 in tumor tissues (the higher the score, the higher the expression of BTF3), 6.52±4.13 in adjacent noncancerous tissues. The expression of BTF3 in different subtypes of MM tissues are shown in the table. In the median follow-up time of 27 months (6-68 months), 13 cases survived without recurrence or metastasis, 10 cases survived with recurrence or metastasis, 8 cases died. In 28 resectable MM patients, the median RFS/OS of high BTF3 expression (IHC score&gt;5) and low expression (IHC score:0-4) were 18.57 / 24.62 months and 20.42 / 22.78 months. The corresponding RFS/OS P values of patients with high and low expression were 0.323 and 0.607. Conclusions: The study suggests that BTF3 play a role in the proliferation, cell cycle regulation, apoptosis and tumorigenicity of MM. Preliminary small-sample retrospective clinical study did not suggest that BTF3 was related to the efficacy and prognosis of patients, which needs to be further verified by large-sample prospective studies.[Table: see text]
A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2/FOXC1 axis
Authors: Tailin He, Jialin Shang, Chenglong Gao, Xin Guan, Yingyi Chen, Liwen Zhu, Luyong Zhang, Cunjin Zhang, Jian Zhang, Tao Pang
Journal: Acta Pharmaceutica Sinica B (2020)

Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (Foxc1) is a key gene evoked by MDL-811 stimulation and is required for the anti-inflammatory effects of MDL-811. We found MDL-811-activated SIRT6 directly interacted with enhancer of zeste homolog 2 (EZH2) and promoted deacetylation of EZH2 which could bind to the promoter of Foxc1 and upregulate its expression to modulate inflammation. Moreover, our data demonstrated that MDL-811 not only ameliorated sickness behaviors in neuroinflammatory mice induced by LPS, but also markedly reduced the brain injury in ischemic stroke mice in addition to promoting long-term functional recovery. Importantly, MDL-811 also exhibited strong anti-inflammatory effects in human monocytes isolated from ischemic stroke patients, underlying an interesting translational perspective. Taken together, MDL-811 could be an alternative therapeutic candidate for ischemic stroke and other brain disorders associated with neuroinflammation.
Clinical outcomes of cancer patients with COVID-19: A systematic review and meta-analysis.
Authors: Maryam Alasfour, Salman Alawadi, Malak AlMojel, Philippos Apolinario Costa, Priscila Barreto Coelho, Thomas Plate, Soyeon Ahn, Gilberto Lopes
Journal: Journal of Clinical Oncology (2021)

e18600 Background: Patients with coronavirus disease 2019 (COVID-19) and cancer have worse clinical outcomes compared to those without cancer. Primary studies have examined this population, but most had small sample sizes and conflicting results. Prior meta-analyses exclude most US and European data or only examine mortality. The present meta-analysis evaluates the prevalence of several clinical outcomes in cancer patients with COVID-19, including new emerging data from Europe and the US. Methods: A systematic search of PubMED, medRxiv, JMIR and Embase by two independent investigators included peer-reviewed papers and preprints up to July 8, 2020. The primary outcome was mortality. Other outcomes were ICU and non-ICU admission, mild, moderate and severe complications, ARDS, invasive ventilation, stable, and clinically improved rates. Study quality was assessed through the Newcastle–Ottawa scale. Random effects model was used to derive prevalence rates, their 95% confidence intervals (CI) and 95% prediction intervals (PI). Results: Thirty-four studies (N = 4,371) were included in the analysis. The mortality prevalence rate was 25.2% (95% CI: 21.1–29.7; 95% PI: 9.8-51.1; I 2 = 85.4), with 11.9% ICU admissions (95% CI: 9.2-15.4; 95% PI: 4.3-28.9; I 2 = 77.8) and 25.2% clinically stable (95% CI: 21.1-29.7; 95% PI: 9.8-51.1; I 2 = 85.4). Furthermore, 42.5% developed severe complications (95% CI: 30.4-55.7; 95% PI: 8.2-85.9; I 2 = 94.3), with 22.7% developing ARDS (95% CI: 15.4-32.2; 95% PI: 5.8-58.6; I 2 = 82.4), and 11.3% needing invasive ventilation (95% CI: 6.7-18.4; 95% PI: 2.3-41.1; I 2 = 79.8). Post-follow up, 49% clinically improved (95% CI: 35.6-62.6; 95% PI: 9.8-89.4; I 2 = 92.5). All outcomes had large I 2 , suggesting high levels of heterogeneity among studies, and wide PIs indicating high variability within outcomes. Despite this variability, the mortality rate in cancer patients with COVID-19, even at the lower end of the PI (9.8%), is higher than the 2% mortality rate of the non-cancer with COVID-19 population, but not as high as what other meta-analyses conclude, which is around 25%. Conclusions: Patients with cancer who develop COVID-19 have a higher probability of mortality compared to the general population with COVID-19, but possibly not as high as previous studies have shown. A large proportion of them developed severe complications, but a larger proportion recovered. Prevalence of mortality and other outcomes published in prior meta-analyses did not report prediction intervals, which compromises the clinical utilization of such results.
How the nursing profession should adapt for a digital future
Authors: Richard G Booth, Gillian Strudwick, Susan McBride, Siobhán O’Connor, Ana Laura Solano López
Journal: BMJ (2021)

Digital technologies increasingly affect nursing globally.Examples include the growing presence of artificial intelligence (AI) and robotic systems; society's reliance on mobile, internet, and social media; and increasing dependence on telehealth and other virtual models of care, particularly in response to the covid-19 pandemic.Despite substantial advances to date, challenges in nursing's use of digital technology persist.A perennial concern is that nurses have generally not kept pace with rapid changes in digital technologies and their impact on society.This limits the potential benefits they bring to nursing practice and patient care.To respond to these challenges and prepare for the future, nursing must begin immediate transformation into a digitally enabled profession that can respond to the complex global challenges facing health systems and society.