Quantitative implications of the updated EARL 2019 PET-CT performance standards

Purpose Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET-CT studies were used to derive four image datasets-the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23-30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data

Quantitative implications of the updated EARL 2019 PET-CT performance standards

Purpose Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET-CT studies were used to derive four image datasets-the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23-30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data

Physiochemical property space distribution among human metabolites, drugs and toxins

<p>Abstract</p> <p>Background</p> <p>The current approach to screen for drug-like molecules is to sieve for molecules with biochemical properties suitable for desirable pharmacokinetics and reduced toxicity, using predominantly biophysical properties of chemical compounds, based on empirical rules such as Lipinski's "rule of five" (Ro5). For over a decade, Ro5 has been applied to combinatorial compounds, drugs and ligands, in the search for suitable lead compounds. Unfortunately, till date, a clear distinction between drugs and non-drugs has not been achieved. The current trend is to seek out drugs which show metabolite-likeness. In identifying similar physicochemical characteristics, compounds have usually been clustered based on some characteristic, to reduce the search space presented by large molecular datasets. This paper examines the similarity of current drug molecules with human metabolites and toxins, using a range of computed molecular descriptors as well as the effect of comparison to clustered data compared to searches against complete datasets.</p> <p>Results</p> <p>We have carried out statistical and substructure functional group analyses of three datasets, namely human metabolites, drugs and toxin molecules. The distributions of various molecular descriptors were investigated. Our analyses show that, although the three groups are distinct, present-day drugs are closer to toxin molecules than to metabolites. Furthermore, these distributions are quite similar for both clustered data as well as complete or unclustered datasets.</p> <p>Conclusion</p> <p>The property space occupied by metabolites is dissimilar to that of drugs or toxin molecules, with current drugs showing greater similarity to toxins than to metabolites. Additionally, empirical rules like Ro5 can be refined to identify drugs or drug-like molecules that are clearly distinct from toxic compounds and more metabolite-like. The inclusion of human metabolites in this study provides a deeper insight into metabolite/drug/toxin-like properties and will also prove to be valuable in the prediction or optimization of small molecules as ligands for therapeutic applications.</p

M1a prostate cancer:Results of a Dutch multidisciplinary consensus meeting

ObjectivesTo determine the consensus of a Dutch multidisciplinary expert panel on the diagnostic evaluation and treatment of de novo and recurrent metastatic prostate cancer (PCa) limited to non-regional lymph nodes (M1a) in daily clinical practice.Materials and methodsThe panel consisted of 37 Dutch specialists from disciplines involved in the management of M1a PCa (urology, medical and radiation oncology, radiology, and nuclear medicine). We used a modified Delphi method consisting of two voting rounds and a consensus meeting (video conference). Consensus (good agreement) was defined as the situation in which ≥ 75% of the panelists chose the same option.ResultsConsensus existed for 57% of the items. The panel agreed that prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) is the most appropriate standard imaging modality to identify de novo (100%) and recurrent (97%) M1a PCa. Androgen deprivation therapy (ADT) combined with radiotherapy to the prostate ± the M1a lesion(s) was most frequently considered an option for de novo M1a PCa. For M1a as recurrent disease, ADT alone, deferring treatment, or local radiotherapy to the M1a lesion(s) were judged to be the most important treatment options. However, no specific indications for treatment choice in relation to disease characteristics could be formulated.ConclusionsThe Dutch consensus panel preferred PSMA-PET/CT as the standard diagnostic modality to detect M1a PCa. Although potential treatment options were identified, explicit recommendations could not be formulated. This might (partly) be explained by the absence of high-level clinical evidence in this subset of patients. Further research is, therefore, strongly encouraged

Oligometastatic Prostate Cancer:Results of a Dutch Multidisciplinary Consensus Meeting

Background: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. Objective: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. Design, setting, and participants: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. Outcome measurements and statistical analysis: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. Results and limitations: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. Conclusions: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. Patient summary: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation. A multidisciplinary panel reached consensus that oligometastatic prostate cancer (OMPC) is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should provide insight into the biology and clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC

Endoscopic treatment of perforated ulcer

Cu introducerea în anul 1976 a agenţilor anti H2, s-a micşorat evident numărul cazurilor de tratament chirurgical adresate ulcerului uo enal sau stomacal. Necatând la aceasta, incidenţa complicaţiilor asociate cu maladie ulceroase, în special perforaţia, practic nu s-a schimbat. Din 1990. când Mouret a descris în primieră suturarea laparoscopică a ulcerului duodenal perforat şi Nathanson. care a e ectuat primul tratament cu succes al ulcerului peptic perforat, metoda laparoscopică a devenit o procedură folosită pe larg. Primele cazuri de tratament laparoscopic al ulcerului perforat în Moldova au fost efectuate în 1997. Studiul prezentat se bazează pe analiza a 54 cazuri de ulcer perforat (48 barbaţi şi 6 femei), spitalizaţi în secţiile de chirurgie a Centrul Naţional Practico-Știinţific in Medicina de Urgenţă cu vârsta medie 25, 16 ani (15-60 ani). Analiza clinică confirmă: tratamentul laparoscopic este .o metoda eficientă de tratament, reduce durata de spitalizare a pacientului, există o reluare rapidă a tranzitului intestinal, iar complicaţiile postoperatorie sunt reduse.With the introduction of H2 receptor antagonist in 1976 there is a significant reduction of elective surgical cases carried out for duodenal and gastric ulcers. However the incidence of complications associated with peptic ulcer disease particularly perforation has not changed appreciably. Since 1990 when Mouret reported the first laparoscopic sutureless repair for a perforated duodenal ulcer and Nathanson the first successful laparoscopic suture repair for perforated peptic ulcer, laparoscopic approach became a widespread procedure. The first cases of treatment laparoscopic of perforated ulcer in Moldova were performed in 1997. The study is based on the analysis of 54 cases of perforated ulcer (48 men and 6 women), hospitalized in the surgical department of the Republican Emergency Hospital, mean age 25, 16 (limits 16 - 60 years). The performed clinical analysis attests that laparoscopic treatment is a safe and efficient method, it reduces the hospitalizing period and has a low rate of complications

Eficacitatea tratamentului cu «Sumamed» a infecţiei sexual transmisibile la pacienţii cu uretroprostatită cronică

Summary To study the efficacy of Sumamed in patients presenting with chronic urethroprostatitis due to sexually transmitted infections. 78 patients with chronic urethroprostatitis were observed out of which 48 had infection with C. trachomatis and 19 had U. urealyticum while 11 patients had combined infections. Sumamed as single drug therapy was administered to 31 patients and as a combined therapy with Ofloxacin in 47 patients. Sumamed was found to be effective in 89,9% patients infected C. trachomatis and in 83,4% patients with U. urealyticum. The efficacy of Sumamed increased markedly on combined therapy with ofloxacin - showing 100% effect in those with U. urealyticum infections and 93,2% patients with C. Trachomatis. Clinical symtems were attenuated in all patients with effective treatment but only 47,3%patients treated with only Sumamed and 73,6 % patients treated with combined therapy were assymptomatic after complete treatment. While the normalization of expressed prostatic scretions were fou nd in 35.4% and in 60.8% patients respectively. Conclusion: Sumamed is quite effective in treatment of Sexually transmitted infections and the efficacy of the treatment increases on combined therapy with Ofloxacin .The pretreatment with usually not recommended antibiotics for sexually transmitted infection reduces the efficacy

A systems chemical biology study of malate synthase and isocitrate lyase inhibition in Mycobacterium tuberculosis during active and NRP growth

The ability of Mycobacterium tuberculosis (Mtb) to survive in low oxygen environments enables the bacterium to persist in a latent state within host tissues. In vitro studies of Mtb growth have identified changes in isocitrate lyase (ICL) and malate synthase (MS) that enable bacterial persistent under low oxygen and other environmentally limiting conditions. Systems chemical biology (SCB) enables us to evaluate the effects of small molecule inhibitors not only on the reaction catalyzed by malate synthase and isocitrate lyase, but the effect on the complete tricarboxylic acid cycle (TCA) by taking into account complex network relationships within that system

Synthesis and characterization of ZnO nanopowder by non-basic

Nanocrystalline ZnO particles were prepared from methanolic solutions of zinc acetate dihydrate without using base such as NaOH or LiOH through a colloid process carried out at a low temperature of 60 o C. The precipitate obtained after 12-72h contained ZnO, covered with polymeric species of zinc hydroxo acetate. The reaction course was studied by mass spectrometry means. To complete the hydrolysis process, up to pure ZnO, it was necessarily to reflux the white precipitate separate from methanolic solution, in water at 80 o C. We found that reaction time in the presence of methanol primarily influenced the size of the particles, while the reaction time in the presence of water mainly influenced the ZnO purity