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Journal of Clinical and Translational... Jul 2020Radiosurgery is employed for the treatment of brain metastases. The aim of this study is to evaluate the efficacy and tolerability of single-dose radiosurgery (SRS)...
BACKGROUND
Radiosurgery is employed for the treatment of brain metastases. The aim of this study is to evaluate the efficacy and tolerability of single-dose radiosurgery (SRS) compared to hypofractionated stereotactic radiotherapy (hFSRT).
MATERIALS AND METHODS
Between 2004 and 2018, we analyzed treatments of 97 patients with 135 brain metastases. Fifty-six patients were treated with SRS, and 41 patients were treated with hFSRT. Median dose was 16 Gy (12-20 Gy) for the SRS group and 30 Gy in 5-6 fractions for the hFSRT group. hFSRT was used for larger lesions and lesions located near critical structures. Kaplan-Meier curves were constructed for overall survival (OS) and local control (LC).
RESULTS
Median age was 64 years (range, 32-89 years). Median survival was 10 months (1-68 months). With a median follow-up of 10 months, no significant differences in OS between groups were found (=0.21). LC for all patients was 67%. Local progression-free survival (LPFS) at 6 months and 1 year was 71% and 60% for the SRS group, respectively, and 80% and 69% for the hFSRT group, respectively (=0.93). Although hFSRT was used for larger lesions and lesions in adverse locations, LPFS was not inferior compared to lesions treated with SRS. We observed acute toxicity grade 1-2 in 25 patients (25.8%). Late complications were observed in 11 patients (11.3%). Acute and late toxicity was similar in the SRS- and hFSRT-treated patients (=0.63 and =0.11, respectively). Brain recurrence occurred in 37.5% and 14.6% in the hFSRT and SRS group, respectively (=0.06).
CONCLUSIONS
Since patients treated with hFSRT exhibited similar survival and LPFS rates without differences in toxicity compared to those treated with SRS, hFSRT can be beneficial, particularly for patients with brain metastases.
RELEVANCE FOR PATIENTS
Hypofractionated schemes in stereotactic radiosurgery offers treatment alternatives to patients with large lesions or lesions near critical structures.
PubMed: 32875136
DOI: No ID Found -
Bulletin of the World Health... 1956Endemic syphilis and similar conditions are compared in this paper with yaws. Both are non-venereal and endemic, and they have very similar epidemiological...
Endemic syphilis and similar conditions are compared in this paper with yaws. Both are non-venereal and endemic, and they have very similar epidemiological characteristics. There is also considerable similarity in the clinical manifestations at the various stages of yaws and endemic syphilis, the differences that do appear being mainly due to different environmental and living conditions. No antigenic or immunogenic differences between syphilis and yaws have yet been demonstrated, and the sensitivity of both to penicillin is the same. Control measures for both diseases may be based on similar principles.The author considers the treponematoses to be closely related infections, and stresses the "unitarian" view put forward by various writers.
Topics: Environment; Humans; Penicillins; Pinta; Syphilis; Treponemal Infections; Yaws
PubMed: 13404469
DOI: No ID Found -
Nature Communications Oct 2017Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of...
Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (V ) and pyruvate carboxylase flux (V ) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of V and V fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-C]lactate and glucose tracer. PINTA measures V and V fluxes over a wide range of physiological conditions with minimal pyruvate cycling and detects increased hepatic V following treatment with a liver-targeted mitochondrial uncoupler. Finally, validation studies in humans demonstrate that the V /V ratio measured by PINTA is similar to that determined by in vivo NMR spectroscopy. This method will provide investigators with a relatively simple tool to non-invasively examine the role of altered hepatic mitochondrial metabolism.Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.
Topics: Acetates; Animals; Carbon Isotopes; Carbon-13 Magnetic Resonance Spectroscopy; Citrate (si)-Synthase; Gas Chromatography-Mass Spectrometry; Glutamic Acid; Humans; Lactic Acid; Liver; Magnetic Resonance Spectroscopy; Male; Mitochondria, Liver; Pyruvate Carboxylase; Pyruvic Acid; Rats
PubMed: 28986525
DOI: 10.1038/s41467-017-01143-w -
Technical Innovations & Patient Support... Sep 2023Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning...
INTRODUCTION
Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration.
MATERIAL AND METHODS
Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. μ, Ʃ, and σ values and margins were obtained.
RESULTS
Lateral displacements of less than 3 mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors μ, σ and Ʃ of the fusions with hepatic contour and bone reference in SI were 0.26 mm, 4 mm and 3 mm, and 0.8 mm, 5 mm and 3 mm respectively.
CONCLUSION
Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.
PubMed: 37744524
DOI: 10.1016/j.tipsro.2023.100215 -
Cancer Diagnosis & Prognosis 2023The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance...
BACKGROUND/AIM
The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation.
MATERIALS AND METHODS
After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared.
RESULTS
The median GTV volume on MRI was 2.4 cm (range=0.59-15.6 cm) compared to 3.5 cm (range=0.52-24.9 cm) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm, and 2.5 vs. 2.8 cm respectively).
CONCLUSION
In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.
PubMed: 37405211
DOI: 10.21873/cdp.10236 -
BJS Open Mar 2021In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP).
METHOD
This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes.
RESULTS
Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference -1.09; 95 per cent c.i. -5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, -0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively.
CONCLUSIONS
MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP.
Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cathartics; Colectomy; Elective Surgical Procedures; Female; Finland; Humans; Male; Metronidazole; Middle Aged; Neomycin; Preoperative Care; Single-Blind Method; Surgical Wound Infection
PubMed: 33839753
DOI: 10.1093/bjsopen/zrab011 -
Journal of Computational Biology : a... Apr 2015Identifying high-confidence candidate genes that are causative for disease phenotypes, from the large lists of variations produced by high-throughput genomics, can be...
Identifying high-confidence candidate genes that are causative for disease phenotypes, from the large lists of variations produced by high-throughput genomics, can be both time-consuming and costly. The development of novel computational approaches, utilizing existing biological knowledge for the prioritization of such candidate genes, can improve the efficiency and accuracy of the biomedical data analysis. It can also reduce the cost of such studies by avoiding experimental validations of irrelevant candidates. In this study, we address this challenge by proposing a novel gene prioritization approach that ranks promising candidate genes that are likely to be involved in a disease or phenotype under study. This algorithm is based on the modified conditional random field (CRF) model that simultaneously makes use of both gene annotations and gene interactions, while preserving their original representation. We validated our approach on two independent disease benchmark studies by ranking candidate genes using network and feature information. Our results showed both high area under the curve (AUC) value (0.86), and more importantly high partial AUC (pAUC) value (0.1296), and revealed higher accuracy and precision at the top predictions as compared with other well-performed gene prioritization tools, such as Endeavour (AUC-0.82, pAUC-0.083) and PINTA (AUC-0.76, pAUC-0.066). We were able to detect more target genes (9/18/19/27) on top positions (1/5/10/20) compared to Endeavour (3/11/14/23) and PINTA (6/10/13/18). To demonstrate its usability, we applied our method to a case study for the prediction of molecular mechanisms contributing to intellectual disability and autism. Our approach was able to correctly recover genes related to both disorders and provide suggestions for possible additional candidates based on their rankings and functional annotations.
Topics: Area Under Curve; Autism Spectrum Disorder; Gene Regulatory Networks; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Intellectual Disability; Models, Genetic; Molecular Sequence Annotation; Phenotype; ROC Curve
PubMed: 25844670
DOI: 10.1089/cmb.2015.0001 -
Bulletin of the World Health... 1961An attempt is made to explain along Darwinian lines the steps by which the treponematoses evolved and how they came to have their present distributions and...
An attempt is made to explain along Darwinian lines the steps by which the treponematoses evolved and how they came to have their present distributions and characteristics. The original ancestors of the treponemes would have been free-living organisms, but various forms of symbiosis with larger creatures would in time lead to the development of parasitism with varying degrees of pathogenicity. Modern man may have acquired his treponemes from his ungeneralized primate ancestors and taken them with him on his migrations over the world. Isolation of man in different continents, especially after the end of the Ice Age, would lead to speciation in both man and his parasites; this would account for the features of pinta in Central America. Ecological isolations would produce syphilis and yaws, the latter being successful in warm areas where no clothes were worn or overcrowding was gross, and syphilis being successful in colder climates but not in endemic yaws areas where so many people were immune by puberty.A syphilis organism has little chance of survival if it fails to infect the genitalia. This is perhaps the reason for congenital infections in that disease. The organotropic properties of syphilis treponemes may be the results of repeated passage through the foetus; the conditions for survival in the foetus are much different from those in the mother, so that organotropic rather than genitotropic strains would be selected.
Topics: Animals; Central America; Family; Humans; Infant, Newborn; Male; Pinta; Probability; Syphilis; Treponemal Infections; Yaws
PubMed: 13694226
DOI: No ID Found -
Acta Crystallographica. Section E,... Dec 2008In the title compound, [Mn(C(2)N(3))(NO(3))(C(24)H(16)N(6))(H(2)O)], the central manganese(II) ion is hepta-coordinated to a tridentate 2,3,5,6-tetra-2-pyridylpyrazine...
In the title compound, [Mn(C(2)N(3))(NO(3))(C(24)H(16)N(6))(H(2)O)], the central manganese(II) ion is hepta-coordinated to a tridentate 2,3,5,6-tetra-2-pyridylpyrazine ligand (tppz), a bidentate nitrate ligand, a terminal monodentate dicyanamide ligand (dca) and a water mol-ecule. The structure contains isolated neutral complexes, which are linked by O(water)-H⋯N hydrogen bonds generating chains along [010].
PubMed: 21581535
DOI: 10.1107/S1600536808041755 -
Toxicology and Applied Pharmacology Sep 2022Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated...
Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated Fibroblasts (CAFs) are the main producers and remodelers of the extracellular matrix (ECM), which is directly involved in drug resistance mechanisms. Primary Normal Fibroblasts (NFs) and CAFs and cell lines (fibroblasts and tumor cells), were used to generate ECM and to identify its role in the oxaliplatin and cetuximab chemoresistance processes of CRC cells mediated by SNAI1-expressing fibroblasts. Matrices generated by Snai1 KO MEFs (Knockout Mouse Embryonic Fibroblasts) confer less resistance on oxaliplatin and cetuximab than wild-type MEF-derived matrices. Similarly, matrices derived from CAFs cause greater survival of colorectal cancer cells than NF-derived matrices, in a similar way to Snai1 expression levels. In addition, Snail1 expression in fibroblasts regulates drug resistance and metabolism gene expression in tumor cells mediated by ECM. Finally, a series of 531 patients (TCGA) with CRC was used to assess the role of SNAI1 expression in patients' prognosis indicating an association between tumor SNAI1 expression and overall survival in colon cancer patients but not in rectal cancer patients. SNAI1 expression in CRC cancer patients, together with in vitro experimentation, suggests the possible use of SNAI1 expression in tumor-associated fibroblasts as a predictive biomarker of response to oxaliplatin and cetuximab treatments in patients with CRC.
Topics: Animals; Cell Line, Tumor; Cetuximab; Colorectal Neoplasms; Drug Resistance; Extracellular Matrix; Fibroblasts; Mice; Mice, Knockout; Oxaliplatin
PubMed: 35878797
DOI: 10.1016/j.taap.2022.116171