Evolution of the Management of Brain Metastases: A Bibliometric Analysis.

A systematic review of the published literature was conducted to analyze the management evolution of brain metastases from different cancers. Using the keywords "brain metastasis", "brain metastases", "CNS metastasis", "CNS metastases", "phase III" AND/OR "Randomized Controlled Trial" (RCT), relevant articles were searched for on the SCOPUS database. A total of 1986 articles were retrieved, published over a 45-year period (1977-2022). Relevant articles were defined as clinical studies describing the treatment or prevention of brain metastases from any cancer. Articles on imaging, quality of life, cognitive impairment after treatment, or primary brain tumors were excluded. After a secondary analysis, reviewing the abstracts and/or full texts, 724 articles were found to be relevant. Publications significantly increased in the last 10 years. A total of 252 articles (34.8%) were published in 12 core journals, receiving 50% of the citations. The number of publications in Frontiers in Oncology, BMC Cancer, and Radiotherapy and Oncology have increased considerably over the last few years. There were 111 randomized controlled trials, 128 review articles, and 63 meta-analyses. Most randomized trials reported on brain metastases management from unselected tumors (49), lung cancer (47), or breast cancer (11). In the last 5 years (2017 to 2022), management of brain metastasis has moved on from WBRT, the use of chemotherapy, and radio-sensitization to three directions. First, Radiosurgery or Radiotherapy (SRS/SRT), or hippocampal-sparing WBRT is employed to reduce radiation toxicity. Second, it has moved to the use of novel agents, such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) and third, to the use of molecularly directed therapy such as TKIs, in asymptomatic low volume metastasis, obviating the need for WBRT.

Redo Aortic Surgery in a Patient with a Large Arachnoid Cyst and Myelodysplasia.

A 70-year-old man was referred for redo root and ascending aortic surgery. Preoperative investigations depicted a large arachnoid cyst occupying the left frontotemporal region and myelodysplasia with persistent thrombocytopenia. We describe successful operative management of this patient in the context of such rare intracranial pathology.

Dysregulation and oncogenic activities of ubiquitin specific peptidase 2a in the pathogenesis of hepatocellular carcinoma.

Ubiquitin specific peptidase 2a (USP2a) plays critical roles in protein degradation and other cellular activities. Currently, our understanding on USP2a dysregulation in subjects with hepatocellular carcinoma (HCC) and its roles in HCC pathogenesis is limited. In this study, we found that USP2a mRNA and protein levels were significantly upregulated in HCC tumors from both human and mice. USP2a overexpression in HepG2 and Huh 7 cells significantly increased cell proliferation while inhibition of USP2a activity by chemical inhibitor or stable knockout of USP2 by CRISPR markedly reduced cell proliferation. In addition, USP2a overexpression significantly augmented the resistance while knockout of USP2a markedly increased the susceptibility of HepG2 cells to bile acid-induced apoptosis and necrosis. Consistent with the oncogenic activities detected in vitro, overexpression of USP2a promoted de novo HCC development in mice with significantly increased tumor occurrence rates, tumor sizes and liver/body ratios. Further investigations with unbiased co-immunoprecipitation (Co-IP)-coupled proteomic analysis and Western blot identified novel USP2a target proteins involved in cell proliferation, apoptosis, and tumorigenesis. Analysis of those USP2a target proteins revealed that USP2a's oncogenic activities are mediated through multiple pathways, including modulating protein folding and assembling through regulating protein chaperones/co-chaperones HSPA1A, DNAJA1 and TCP1, promoting DNA replication and transcription through regulating RUVBL1, PCNA and TARDBP, and altering mitochondrial apoptotic pathway through regulating VDAC2. Indeed, those newly identified USP2a target proteins were markedly dysregulated in HCC tumors. In summary, USP2a was upregulated in HCC subjects and acted as an oncogene in the pathogenesis of HCC through multiple downstream pathways. The findings provided molecular and pathogenesis bases for developing interventions to treat HCC by targeting USP2a or its downstream pathways.

Correction: Hashmi et al. Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats. Biomolecules 2021, 11, 1549.

In the published publication [...].

Dysregulation and activities of ubiquitin specific peptidase 2b in the pathogenesis of hepatocellular carcinoma.

Ubiquitin specific peptidase-2 (USP2) plays important roles in a myriad of cellular activities through deubiquitinating target proteins and its implications in various diseases, especially cancers, are starting to emerge. Our current understanding on USP2 expression in subjects with hepatocellular carcinoma (HCC) and its roles in the pathogenesis of HCC is limited. In this study, we found that USP2 protein and mRNA levels were significantly dysregulated in HCC tumor (HCC-T) when compared to adjacent non-tumor (HCC-NT) or normal liver tissues from both human and mouse HCC model. Among the USP2 isoforms, USP2b was the predominant isoform in the normal liver and markedly down-regulated in HCC-T tissues in both human and mice. Data from overexpression, chemical inhibition and knockout studies consistently demonstrated that USP2b promoted cell proliferation, colony formation and wound healing in HepG2 and Huh 7 cells. On the other hand, USP2b exhibited proapoptotic and pronecrtotic activities through enhancing bile acid-induced apoptosis and necrosis in both HepG2 and Huh 7 cells. Unbiased proteomic analysis of USP2-knockout (KO) and parental HepG2 cells resulted in identification of USP2-regulated downstream target proteins involved in cell proliferation, apoptosis, and tumorigenesis, including serine/threonine kinase 4 (STK4), epidermal growth factor receptor (EGFR), dipeptidyl peptidase 4 (DPP4) and fatty acid binding protein 1 (FABP1). In conclusion, USP2b expression was dysregulated in subjects with HCC and contributed to the pathogenesis of HCC by promoting cell proliferation and exerting proapoptotic and pronecrotic activities. The findings provide the molecular basis for developing therapies for HCC through modulating USP2b expression or activities.

Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats.

Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.

A Narrative Review on the Phytochemistry, Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine.

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant's extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.

A systematic review of risk prediction models for perioperative mortality after thoracic surgery.

OBJECTIVES: Guidelines advocate that patients being considered for thoracic surgery should undergo a comprehensive preoperative risk assessment. Multiple risk prediction models to estimate the risk of mortality after thoracic surgery have been developed, but their quality and performance has not been reviewed in a systematic way. The objective was to systematically review these models and critically appraise their performance. METHODS: The Cochrane Library and the MEDLINE database were searched for articles published between 1990 and 2019. Studies that developed or validated a model predicting perioperative mortality after thoracic surgery were included. Data were extracted based on the checklist for critical appraisal and data extraction for systematic reviews of prediction modelling studies. RESULTS: A total of 31 studies describing 22 different risk prediction models were identified. There were 20 models developed specifically for thoracic surgery with two developed in other surgical specialties. A total of 57 different predictors were included across the identified models. Age, sex and pneumonectomy were the most frequently included predictors in 19, 13 and 11 models, respectively. Model performance based on either discrimination or calibration was inadequate for all externally validated models. The most recent data included in validation studies were from 2018. Risk of bias (assessed using Prediction model Risk Of Bias ASsessment Tool) was high for all except two models. CONCLUSIONS: Despite multiple risk prediction models being developed to predict perioperative mortality after thoracic surgery, none could be described as appropriate for contemporary thoracic surgery. Contemporary validation of available models or new model development is required to ensure that appropriate estimates of operative risk are available for contemporary thoracic surgical practice.

Dysregulation of bile acids increases the risk for preterm birth in pregnant women.

Preterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB.

The role of thoracic surgery in extracorporeal membrane oxygenation services.

Background Recent evidence surrounding the use of venovenous extracorporeal membrane oxygenation in treating acute respiratory failure has led to the expansion of extracorporeal membrane oxygenation services worldwide. The high rate of complications related to venovenous extracorporeal membrane oxygenation often requires intervention by specialist thoracic surgeons. This study aimed to investigate the role of specialist thoracic surgeons within the multidisciplinary team managing these high-risk patients. Methods We retrospectively reviewed 90 patients who received venovenous extracorporeal membrane oxygenation at our tertiary referral center between December 2011 and May 2015. Four patients who underwent lung transplantation were excluded. Results We found that 29.1% (25/86) of patients on venovenous extracorporeal membrane oxygenation had undergone a thoracic intervention. A total of 82 interventions were performed: 11 thoracotomies, 49 chest drains, 13 rigid bronchoscopies, 4 flexible bronchoscopies, 4 temporary endobronchial blockers, and 1 sternotomy. Of the 11 thoracotomies, 3 were reexplorations. Survival to discharge for patients who underwent thoracic surgical interventions was 72% (18/25). Conclusions Our experience has demonstrated that a large proportion of patients receiving venovenous extracorporeal membrane oxygenation require a thoracic intervention, many of which are major intraoperative procedures. Patients on venovenous extracorporeal membrane oxygenation have benefited from rapid on-site access to thoracic surgical services to manage these challenging life-threatening complications.

Observer performance using virtual pathology slides: impact of LCD color reproduction accuracy.

The use of color LCDs in medical imaging is growing as more clinical specialties use digital images as a resource in diagnosis and treatment decisions. Telemedicine applications such as telepathology, teledermatology, and teleophthalmology rely heavily on color images. However, standard methods for calibrating, characterizing, and profiling color displays do not exist, resulting in inconsistent presentation. To address this, we developed a calibration, characterization, and profiling protocol for color-critical medical imaging applications. Physical characterization of displays calibrated with and without the protocol revealed high color reproduction accuracy with the protocol. The present study assessed the impact of this protocol on observer performance. A set of 250 breast biopsy virtual slide regions of interest (half malignant, half benign) were shown to six pathologists, once using the calibration protocol and once using the same display in its "native" off-the-shelf uncalibrated state. Diagnostic accuracy and time to render a decision were measured. In terms of ROC performance, Az (area under the curve) calibrated = 0.8570 and Az uncalibrated = 0.8488. No statistically significant difference (p = 0.4112) was observed. In terms of interpretation speed, mean calibrated = 4.895 s; mean uncalibrated = 6.304 s which is statistically significant (p = 0.0460). Early results suggest a slight advantage diagnostically for a properly calibrated and color-managed display and a significant potential advantage in terms of improved workflow. Future work should be conducted using different types of color images that may be more dependent on accurate color rendering and a wider range of LCDs with varying characteristics.