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.

Patterned Electrospinning: A Method of Generating Defined Fibrous Constructs Influencing Cell Adhesion and Retention.

A critical component of tissue engineering is the ability to functionally replace native tissue stroma. Electrospinning is a technique capable of forming fibrous constructs with a high surface area for increased cell-material interaction and enhanced biocompatibility. However, physical and biological properties of electrospun scaffolds are limited by design controllability on a macroscale. We developed a methodology for generating electrospun scaffolds with defined patterns and topographic features to influence physical properties and biological interactions. Five unique design electrospinning target collectors were fabricated to allow for generation of defined polymeric scaffold patterns including lines, sinusoids, squares, zigzags, and solid. Poly(lactic-co-glycolic) acid was electrospun under identical conditions utilizing these varied targets, and constructs generated were examined as to their physical configuration, mechanical and chemical properties, and their ability to foster vascular smooth muscle cell adhesion and retention at 24 h. Modifying collector designs led to significant differences in fiber target coverage ranging from 300 mm2 for solid (100% of the target area) to 217.8 mm2 for lines (72.6% of the target area). Measured fiber excess, residual open area, and contact angle (hydrophobicity) followed the same trend as fiber target coverage with respect to the collector pattern: lines > sinusoids > squares > zigzags > solid. Similarly, the line design allowed for the greatest cell adhesion and retention (258 ± 31 cells), whereas solid exhibited the lowest (150 ± 15 cells); p < 0.05. There was a strong direct correlation of cell adhesion to construct residual open area (R2 = 0.94), normalized fiber excess (R2 = 0.99), and fiber grammage (R2 = 0.72), with an inverse relationship to fiber target coverage (R2 = 0.94). Our results demonstrate the ability to utilize patterned collectors for modifying macroscopic and microscopic electrospun scaffold features, which directly impact cell adhesion and retention, offering translational utility for designing specific tissue constructs.

Design Effect of Metallic (Durable) and Polymeric (Resorbable) Stents on Blood Flow and Platelet Activation.

Bioresorbable vascular scaffolds (BVS) provide transient vessel support for occluded coronary arteries while resorbing over time, potentially allowing vessel restoration approximating the native, healthy state. Clinical trials indicate that the Absorb BVS (Abbott Vascular, Santa Clara, CA) performance was similar to that of the Xience metallic drug-eluting stent (DES), with low long-term complications rates. However, when under-deployed in very small vessels (diameter < 2.25 mm), the thrombosis rate of BVS was higher, possibly due to the effect of strut thickness on the hemodynamics (157 µm BVS vs. 81 µm DES). This study aims to determine the influence of BVS design in vessels of varying diameter on the potential platelet activation. Sixteen computational fluid dynamics models of vessels of varying diameter (1.8-3.0 mm), strut thickness (81-157 µm), and BVS/DES designs were compared. Platelet stress accumulation (SA), a metric for the activation potential, was calculated along platelet flow trajectories and their probability distribution was compared. The models were consistent with clinical observations, indicating that devices deployed in very small vessels exhibited increased probability for platelet activity as compared to the same devices deployed in nominal sized vessels. Deployment, although with residual stenosis, increased probability for higher SA than in similar diameter straight vessels. Reducing BVS struts thickness while maintaining their pattern improved performance closer to that of DES. Our findings highlight the importance of appropriate vessel sizing and deployment technique for BVS, and may help designing future BVS with thinner struts, ultimately improving performance in very small vessels.

Synthesis and preclinical evaluation of bactericidal agent isolated from soil bacterium (Streptomyces): a novel diagnostic technique to enhance anticancer efficacy through radiosynthesis.

OBJECTIVES: Dactinomycin is a well-known antitumor-antibiotic drug isolated from soil bacterium Streptomyces, which exhibits broad-spectrum pharmacological and biochemical effects. In this study, dactinomycin was successfully labeled with technetium-99m for early diagnosis of bacterial infection and to discriminate it from acute inflammation. MATERIALS AND METHODS: Various labeling parameters such as pH, ligand concentration, reducing agent, and stabilizing agent were investigated. Radio-TLC technique was used to calculate percent radiochemical purity of radiopharmaceutical. Characterization studies were carried out using electrophoresis and radio-high-performance liquid chromatography techniques. Furthermore, saline and serum stability studies were performed to investigate biocompatibility. Biodistribution and scintigraphy studies were performed in infected and inflamed animal models to discriminate between bacterial infections (Escherichia coli and Staphylococcus aureus) and acute inflammations (heat-killed S. aureus). RESULTS: The results demonstrated that the highest radiochemical purity of at least 95% was achieved using 100-500 µg ligand and 3-8 µg SnCl2·2H2O as reducing agent at 4-9 pH. Technetium-99m-dactinomycin (Tc-DTN) was observed clearly bounded to the infection site having target/nontarget ratio 2.96±0.64 at 30 min after administration, which increased to 5.21±1.03 at 4 h after administration. Further accumulation was seen in heart, lungs, liver, stomach, kidneys, spleen, and intestine. An in-vitro cell-binding study was also performed, which showed high binding affinity of Tc-DTN with S. aureus-induced infectious lesions. CONCLUSION: Tc-DTN can easily be synthesized using standardized optimization conditions. The radiopharmaceutical has the highest accumulation potential at targeted site induced by S. aureus without any prominent in-vivo cytotoxicity. Tc-DTN may be used as a potential diagnostic agent to locate S. aureus-induced infection lesions at an early stage. Tc-DTN can successfully discriminate between infection and inflammatory models which cannot be achieved from other radiopharmaceuticals developed in the past few decades.

Thickness of buccal bone in the mandible and its clinical significance in mono-cortical screws placement. A CBCT analysis.

The aim of this study was to determine the safest length of monocortical screws that can be inserted for the treatment of mandibular fractures following Champy's technique. Fifty cone-beam computed tomography (CBCT) scans of hemi-mandibles were studied. Linear measurements were taken from the buccal cortical plate to the tooth apex, from the canine to the second premolar, and from the buccal cortical plate to the tooth apex and the inferior alveolar canal in the molar area. The minimum values of the horizontal distances both at the level of the apex and the inferior alveolar canal at the second molar were found to be 4 mm, which is greater than those of the first molar. At the canine, first premolar and second premolars, the minimum values of the horizontal distances at the level of the apex was found to be 2 mm, 2.33 mm and 2 mm, respectively. Stabilizing miniplates using 4 mm screws both at the level of the apex and the inferior alveolar canal is safe in the second molar area, anterior to this, there is a risk of injury to tooth root and inferior alveolar nerve.

Anti-Platelet Therapy for Acute Coronary Syndrome: A Review of Currently Available Agents and What the Future Holds.

Dual anti-platelet therapy remains a cornerstone in the management of patients suffering from acute coronary syndromes (ACS). The combination of aspirin and clopidogrel has been shown to result in significant reductions in cardiovascular end points including recurrent infarction and death in several randomised control trial of patients with ACS. However, many patients still experience ischaemic events on the combination of aspirin and clopidogrel. Aspirin is a relatively weak anti platelet agent. Clopidogrel is a pro drug that required activation by hepatic metabolism and hence its onset of action is delayed; there is genetic variation in the clinical response to the drug, the platelet inhibition is irreversible and no intravenous form is available. Consequently new anti-platelet agents have been developed to address the short falls of this combination therapy. This paper discusses existing anti-platelet regimes and focuses on novel antiplatelet agents that are currently under clinical evaluation.

Endovascular repair of common celiomesenteric trunk stenosis.

A common celiomesenteric trunk (CMT) is one of the several anatomic variations in the mesenteric circulation and occurs when the celiac and superior mesenteric arteries originate from a single common trunk. Because of its rarity, few lesions of the CMT have been reported. We herein present a case of atherosclerotic stenosis of the CMT of an 81-year-old female who presented with symptoms of mesenteric angina. To our knowledge, this represents the first reported case of endovascular treatment of CMT stenosis.

Prophylactic inferior vena cava (IVC) filter placement may increase the relative risk of deep venous thrombosis after acute spinal cord injury.

BACKGROUND: To determine whether the prophylactic placement of an inferior vena cava (IVC) filter after acute spinal cord injury (SCI) causes an increased incidence of deep venous thrombosis (DVT). METHODS: A retrospective chart review was conducted employing charts from patients admitted to the SCI service of one inpatient rehabilitation center for 2 consecutive years. One hundred fourteen subjects met inclusion criteria, namely an acute SCI, length of rehabilitation stay greater than 7 days, and level of injury between C3 and L3. Subjects were classified into two groups: those who received a prophylactic IVC filter during their acute stay and those that did not. The occurrence of DVT during initial rehabilitation was the primary outcome measure. Other demographic and medical information including the occurrence of pulmonary embolism were also collected. RESULTS: Of the 114 subjects, two were excluded because of DVT occurring before rehabilitation admission. Of the remainder, 54 (47%) had prophylactic IVC filters placed. Of those with filters, 11 (20.4%) experienced a DVT during their rehabilitation stay. Of the 58 without filters, only three (5.2%) experienced a DVT during rehabilitation (p = 0.021, Fisher's exact test). Confounding factors included the Injury Severity Score and possibly the cause of injury and presence of long bone fracture. Only one individual experienced pulmonary embolism during rehabilitation hospitalization, and that was in a person with a prophylactic IVC filter. CONCLUSIONS: The presence of prophylactic IVC filters in acute SCI patients may actually increase the risk of DVT, which has its own associated morbidities and costs.

Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women.

UNLABELLED: One-year treatment of osteoporotic postmenopausal women with transdermal estrogen resulted in significant decreases in bone marrow adipocyte volume and prevented increases in adipocyte number as compared to placebo-treated controls. Estrogen treatment also prevented increases in mean adipocyte size over 1 year. INTRODUCTION: Aging is associated not only with bone loss but also with increases in bone marrow adipocytes. Since osteoblasts and adipocytes are derived from a common precursor, it is possible that with aging, there is a preferential "switch" in commitment of this precursor to the adipocyte over the osteoblast lineage. We tested the hypothesis that the apparent "age-related" increase in marrow adipocytes is due, at least in part, to estrogen (E) deficiency. METHODS: Reanalysis of bone biopsies from a randomized, placebo-controlled trial involving 56 postmenopausal osteoporotic women (mean age, 64 years) treated either with placebo (PL, n = 27) or transdermal estradiol (0.1 mg/d, n = 29) for 1 year. RESULTS: Adipocyte volume/tissue volume (AV/TV) and adipocyte number (Ad#) increased (by 20%, P < 0.05) in the PL group, but were unchanged (Ad#) or decreased (AV/TV, by -24%, P < 0.001) in the E group. E treatment also prevented increases in mean adipocyte size over 1 year. CONCLUSIONS: These findings represent the first in vivo demonstration in humans that not only ongoing bone loss, but also the increase in bone marrow adipocyte number and size in postmenopausal osteoporotic women may be due, at least in part, to E deficiency.

Therapy considerations in drug-eluting stents.

Approximately 12 million Americans have coronary artery disease, and almost one in five deaths in the United States can be attributed to this disease. In addition, 1.2 million Americans undergo cardiac catheterization and over one-half million receive a percutaneous coronary intervention such as balloon angioplasty, atherectomy, or stent implantation annually. This article will provide an overview of (1) atherosclerosis, the progressive disease which can lead to thrombotic events and/or the development of hemodynamically significant coronary artery lesions; (2) restenosis, the reappearance of significant lesions after coronary interventions such as stent placement; and (3) drug-eluting stents, the devices which, by using appropriate polymers to elute the appropriate drug with the appropriate pharmacokinetics, have almost completely eliminated restenosis.

Ketoconazole treatment of gonadotropin independent precocious puberty in girls with McCune-Albright syndrome: a preliminary report.

McCune-Albright syndrome (MAS) in girls is characterized by gonadotropin independent precocious puberty (GIPP). This form of GIPP is resistant to therapy with GnRH analogues. As an alternative treatment, we successfully used ketoconazole 200 mg t.i.d. orally in two girls with MAS, GIPP and advanced bone age Ketoconazole led to rapid control of GIPP with cessation of menses and regression of pubertal signs in both patients. Ketoconazole was temporarily interrupted in one patient due to pruritus but later restarted without problem. After 1 year of therapy both patients have remained free of menses, progression of puberty and other side effects. Repeat sonography on ketoconazole revealed continued presence of ovarian cysts. Our preliminary experience indicates the safety and effectiveness of ketoconazole as a therapy for GIPP with potential advantages over previously used modes of treatment. Longer use of ketoconazole to suppress GIPP is required to determine whether this therapy can prolong linear growth with enhancement of final height.

Human ARHGDIG, a GDP-dissociation inhibitor for Rho proteins: genomic structure, sequence, expression analysis, and mapping to chromosome 16p13.3.

GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activity of GTPases. We recently reported the identification of a new GDI for the Rho-related GTPases named RhoGDIgamma. This gene is now designated ARHGDIG by HUGO. Here, in a detailed analysis of tissue expression of ARHGDIG, we observe high levels in the entire brain, with regional variations. The mRNA is also present at high levels in kidney and pancreas and at moderate levels in spinal cord, stomach, and pituitary gland. In other tissues examined, the mRNA levels are very low (lung, trachea, small intestine, colon, placenta) or undetectable. RT-PCR analysis of total RNA isolated from exocrine pancreas and islets shows that the gene is expressed in both tissues. We also report the genomic structure of ARHGDIG. The gene spans over 4 kb and is organized into six exons and five introns. The upstream region lacks a canonical TATA box and contains several putative binding sites for ubiquitous and tissue-specific factors active in central nervous system development. Using FISH, we have mapped the gene to chromosome band 16p13.3. This band is rich in deletion mutants of genes involved in several human diseases, notably polycystic kidney disease, alpha-thalassemia, tuberous sclerosis, mental retardation, and cancer. The promoter structure and the chromosomal location of RhoGDIgamma suggest its importance and underscore the need for further investigation into its biology.