Monitoring radiofrequency renal lesions in real time using contrast-enhanced ultrasonography: a porcine model

BACKGROUND AND PURPOSE: Ablation by cold (cryoablation) or radiofrequency energy (RFA), has been popularized for the treatment of small renal tumors. Regrettably, there currently is no reliable method of radiologically monitoring the propagation of RF lesions in real time. Ultrasonography enhanced by gas-filled microbubble contrast agents allows depiction of regions of tissue perfusion and has been described as a useful adjunct in diagnosing renal pseudotumors, improving prostate biopsy results, and confirming successful ablation of liver tumors. We hypothesized that contrast-enhanced ultrasonography (CEUS) would allow us to define, in real time, areas of cell death secondary to RFA and thus determine successful treatment. MATERIALS AND METHODS: Five female swine underwent initial laparoscopic exploration and creation of ipsilateral upper- and lower-pole renal RFA lesions. Lesion size was measured with standard gray-scale, Doppler, and microbubble CEUS. After 2 weeks, an identical procedure was performed on the contralateral kidney, including repeat sonographic measurements on the first kidney. All swine were then immediately sacrificed, and both kidneys (20 lesions) were harvested for pathologic analysis (hematoxylin-eosin and nicotinamide adenine dinucleotide stains). Radiographic lesion size was then compared with the gross and microscopic findings. RESULTS: The RFA lesions could not be imaged accurately in real time with standard gray-scale or Doppler sonography. However, microbubble CEUS was able to monitor parenchymal blood flow and, thus, the lesions (no blood flow) in real time. Hypoechoic lesions (no bubble enhancement) imaged during contrast sonography corresponded with regions of cell death as demonstrated on pathologic analysis. CONCLUSIONS: Microbubble CEUS is can monitor RFA lesions in real time. This novel imaging modality should allow more effective renal tumor ablation.     

Investigation of the Mg-HCO(3)(-)-ATPase activity of thyroid tissue cells under various pathologies

Abstract Distribution of the Mg(2+) -dependent, HCO(3)(-) -stimulated ATPase (HCO(3)(-) -ATPase) was investigated in sub-cellular fractions of the tissue of the human thyroid gland. It was found that especially high enzymatic activity is characteristic of mitochondria and the endoplasmic reticulum. Correlation between various pathologies of the thyroid and HCO(3)(-) -ATPase activity was demonstrated. The activity was evaluated using the difference between active and passive ATPase. During development of the various pathologies, the sub-cellular fractions of the gland showed uneven alterations of HCO(3)(-)-ATPase activity. Intriguingly, the enzyme kinetic parameters are also changed, i.e. in the different pathologies both enzyme activity and its affinity towards bicarbonate ions are altered. This raises the question whether pathology is caused by, or results in, changes in the enzyme at the molecular level.     

Drug Repurposing from an Academic Perspective

Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the "valley of death" by bridging basic to clinical sciences.     

Viruses in cancers among the immunosuppressed

Most cancer forms known to be caused by viruses are increased among the immunosuppressed, but several cancer forms without established viral etiology are also increased, notably nonmelanoma skin carcinoma (NMSC). We followed all 13,429 solid organ transplantation patients in Sweden for cancer occurrence after transplantation. We requested these tumor specimens and sequenced the first 89 specimens received (62 NMSCs, 27 other cancers). The sequences were analyzed for viruses based on two bioinformatics algorithms (paracel‐blast (sensitive for detection of known viruses) and hidden Markov model (HMM; sensitive for distantly related viruses)). Among the 62 NMSCs, the virus family detected in the largest proportion of specimens was Mimiviridae (9/62 NMSCs). The majority of the virus‐related reads belonged to Papillomaviridae. The HMM analysis identified 86 additional previously not described viral contigs related to 11 virus families, with reads related to Mimiviridae being the most common (detected in 28/62 NMSCs) with the most prevalent contig (Mimivirus SE906, 1937 bp) detected in 17/62 NMSCs. Among the 27 other cancers, viral sequences were detected in only 5 specimens by blast analysis, compared to in all 27 specimens by HMM (Mimiviridae, Poxviridae, Phycodnaviridae and virus‐related sequences yet unclassified to any family). 99% of the virus reads belonged to a single previously not described sequence (Mimivirus SE996, 911 bp). A multitude of viruses is readily detectable in specimens with cancers occurring among the immunosuppressed, with sequences related to Mimiviridae being the most prevalent. Further research would be needed to elucidate the biological significance of the viruses.     

Association of Pre-Admission Statin Use With Reduced In-Hospital Mortality in COVID-19

BackgroundCoronavirus disease-19 (COVID-19) infection is associated with an uncontrolled systemic inflammatory response. Statins, given their anti-inflammatory properties, may reduce the associated morbidity and mortality. This study aimed to determine the association between statin use prior to hospitalization and in-hospital mortality in COVID-19 patients.MethodsIn this retrospective study, clinical data were collected from the electronic medical records of patients admitted to the hospital with confirmed COVID-19 infection from March 1, 2020 to April 24, 2020. A multivariate regression analysis was performed to study the association of pre-admission statin use with in-hospital mortality.ResultsOf 255 patients, 116 (45.5%) patients were on statins prior to admission and 139 (54.5%) were not. The statin group had a higher proportion of end stage renal disease (ESRD) (13.8% vs. 2.9%, p = 0.001), diabetes mellitus (63.8% vs. 35.2%, p<0.001), hypertension (87.9% vs. 61.1%, p < 0.001) and coronary artery disease (CAD) (33.6% vs. 5%, p < 0.001). On multivariate analysis, we found a statistically significant decrease in the odds of in-hospital mortality in patients on statins before admission (OR 0.14, 95% CI 0.03- 0.61, p = 0.008). In the subgroup analysis, statins were associated with a decrease in mortality in those with CAD (OR 0.02, 95% CI 0.0003–0.92 p = 0.045) and those without CAD (OR 0.05, 95% CI 0.005–0.43, p = 0.007).ConclusionsOur study suggests that statins are associated with reduced in-hospital mortality among patients with COVID-19, regardless of CAD status. More comprehensive epidemiological and molecular studies are needed to establish the role of statins in COVID-19.     

Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton

Although much evidence suggests that the plasma membrane of eukaryotic cells is not homogenous, the precise architecture of this important structure has not been clear. Here we use transmission electron microscopy of plasma membrane sheets and specific probes to show that most or all plasma membrane-associated proteins are clustered in cholesterol-enriched domains ("islands") that are separated by "protein-free" and cholesterol-low membrane. These islands are further divided into subregions, as shown by the localization of "raft" and "non-raft" markers to specific areas. Abundant actin staining and inhibitor studies show that these structures are connected to the cytoskeleton and at least partially depend on it for their formation and/or maintenance.