BACKGROUND AND OBJECTIVE: While active surveillance (AS) is an alternative to surgical interventions in patients with small renal masses (SRMs), evidence regarding its oncological efficacy is still debated. We aimed to evaluate oncological outcomes for patients with SRMs who underwent AS in comparison to surgical interventions. METHODS: In April 2024, PubMed, Scopus, and Web of Science were queried for comparative studies evaluating AS in patients with SRMs (PROSPERO: CRD42024530299). The primary outcomes were overall (OS) and cancer-specific survival (CSS). A random-effects model was used for quantitative analysis. KEY FINDINGS AND LIMITATIONS: We identified eight eligible studies (three prospective, four retrospective, and one study based on Surveillance, Epidemiology and End Results [SEER] data) involving 4947 patients. Pooling of data with the SEER data set revealed significantly higher OS rates for patients receiving surgical interventions (hazard ratio [HR] 0.73; p = 0.007), especially partial nephrectomy (PN; HR 0.62; p < 0.001). However, in a sensitivity analysis excluding the SEER data set there was no significant difference in OS between AS and surgical interventions overall (HR 0.84; p = 0.3), but the PN subgroup had longer OS than the AS group (HR 0.6; p = 0.002). Only the study based on the SEER data set showed a significant difference in CSS. The main limitations include selection bias in retrospective studies, and classification of interventions in the SEER database study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients treated with AS had similar OS to those who underwent surgery or ablation, although caution is needed in interpreting the data owing to the potential for selection bias and variability in AS protocols. Our review reinforces the need for personalized shared decision-making to identify patients with SRMs who are most likely to benefit from AS. PATIENT SUMMARY: For well-selected patients with a small kidney mass suspicious for cancer, active surveillance seems to be a safe alternative to surgery, with similar overall survival. However, the evidence is still limited and more studies are needed to help in identifying the best candidates for active surveillance.
- MeSH
- Ablation Techniques methods MeSH
- Humans MeSH
- Kidney Neoplasms * surgery mortality pathology MeSH
- Nephrectomy * methods MeSH
- Watchful Waiting * MeSH
- Tumor Burden MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Comparative Study MeSH
- Systematic Review MeSH
A new group of potent histone deacetylase inhibitors (HDACis) capable of inhibiting cell growth and affecting cell-cycle progression in Tohoku Hospital Pediatrics-1 (THP-1) monocytic leukaemia cells was synthesized. The inhibitors belong to a series of hydroxamic acid derivatives. We designed and synthesized a series of 22 N-hydroxycinnamamide derivatives, out of which 20 are new compounds. These compounds contain various substituted anilides as the surface recognition moiety (SRM), a p-hydroxycinnamate linker, and hydroxamic acids as the zinc-binding group (ZBG). The whole series of synthesized hydroxamic acids inhibited THP-1 cell proliferation. Compounds 7d and 7p, which belong to the category of derivatives with the most potent antiproliferative properties, exert a similar effect on cell-cycle progression as vorinostat and induce apoptosis in THP-1 cells. Furthermore, compounds 7d and 7p were demonstrated to inhibit HDAC class I and II in THP-1 cells with comparable potency to vorinostat and increase acetylation of histones H2a, H2b, H3, and H4. Molecular modelling was used to predict the probable binding mode of the studied HDACis in class I and II histone deacetylases in terms of Zn2+ ion chelation by the hydroxamate group.
- MeSH
- Apoptosis * drug effects MeSH
- Cell Cycle drug effects MeSH
- Histone Deacetylases metabolism MeSH
- Histone Deacetylase Inhibitors * pharmacology chemical synthesis chemistry MeSH
- Hydroxamic Acids * pharmacology chemical synthesis chemistry MeSH
- Coumaric Acids * pharmacology chemistry chemical synthesis MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents * pharmacology chemical synthesis chemistry MeSH
- Drug Screening Assays, Antitumor MeSH
- Molecular Docking Simulation MeSH
- THP-1 Cells MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions, to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score. METHODS: RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test and Cochrane-Q test respectively, including the comparison of palmar vs. dorsal regions (chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response means (SRM)/linear regression. Analyses were also performed separately for early and established RA. RESULTS: A total of 435 patients (N = 138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p ≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (p < 0.001) and the palmar side of the finger joints by PD (p < 0.001) were more frequently pathologic. The reduced US7 score (GS/PD: palmar MCP2, dorsal wrist, EDC and ECU, only PD: dorsal MCP2) showed therapy response (SRM 0.433) after 6 months and retained 76% of the full US7 score's information. No major differences between the groups of early and established RA could be detected. CONCLUSIONS: The wrist, MCP2, EDC, and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.
- MeSH
- Humans MeSH
- Adolescent MeSH
- Arthritis, Rheumatoid * diagnostic imaging drug therapy pathology MeSH
- Tendons diagnostic imaging MeSH
- Severity of Illness Index MeSH
- Synovitis * pathology MeSH
- Ultrasonography MeSH
- Wrist MeSH
- Wrist Joint diagnostic imaging pathology MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
The aim of this study was to provide evidence for the hypothesis that estimated glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be determined for all elderly type 2 diabetes mellitus (T2DM) patients based on eGFRcys upward and downward reclassification rate for hypothetical metformin dose reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m2 . A total of 265 consecutive T2DM elderly patients (age range 65-91 years) from outpatient diabetic clinic were included in the study. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines for metformin dosing were strictly followed. Estimated glomerular filtration rate from serum creatinine (eGFRcrea) led to results of metformin eligibility. Each of the results of eGFRcrea-based eligibility was further compared to eGFRcys-based eligibility. Creatinine was measured by enzymatic method standardized against international reference material SRM 967. Cystatin C was determined by method traceable to DA ERM 471 international standard. eGFRcrea and eGFRcys were calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. A downward reclassification rate was higher than upward reclassification rate (31 vs 3, respectively; P < 0.0001). The median (IQR) eGFRcrea was higher than eGFRcys (73 (58-85) vs 63 (50-75) mL/min/1.73 m2 , respectively; P < 0.0001). eGFRcys reclassified significant proportion of patients with T2DM from metformin eligible CKD stages to less or non-eligible stages. The downward reclassification was more frequent in patients older than 80 years (P < 0.01). Cystatin C-based eGFR selects more complicated patients, where lower doses of metformin are possibly advisable. We recommend calculating both eGFRcrea and eGFRcys for metformin dosing in elderly patients with T2DM.
- MeSH
- Renal Insufficiency, Chronic blood physiopathology MeSH
- Cystatin C blood MeSH
- Diabetes Mellitus, Type 2 blood drug therapy physiopathology MeSH
- Glomerular Filtration Rate physiology MeSH
- Hypoglycemic Agents administration & dosage MeSH
- Creatinine blood MeSH
- Humans MeSH
- Metformin administration & dosage MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Age Factors MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
INTRODUCTION: Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5-33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM. METHOD: Adult patients (n = 158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n = 15). All participants underwent MRI with DWI sequence included. RESULTS: Mean ADC values of solid RCC (1.65 ± 0.38 × 10-3 mm2/s) were lower than healthy renal parenchyma (2.47 ± 0.12 × 10-3 mm2/s, p < 0.05). There was no difference between mean ADC values of ccRCC, pRCC and chRCC (1.82 ± 0.22 × 10-3 vs 1.61 ± 0.07 × 10-3 vs 1.46 ± 0.09 × 10-3 mm2/s, respectively, p = ns). An inverse relationship between mean ADC values and Fuhrman grade of nuclear atypia of solid ccRCCs was observed: grade I-1.92 ± 0.11 × 10-3 mm2/s, grade II-1.84 ± 0.14 × 10-3 mm2/s, grade III-1.79 ± 0.10 × 10-3 mm2/s, grade IV-1.72 ± 0.06 × 10-3 mm2/s. This was significant (p < 0.05) only between tumors of I and IV grades. Significant difference (p < 0.05) between mean ADC values of solid RCCs, benign renal tumors and renal cysts was observed (1.65 ± 0.38 × 10-3 vs 2.23 ± 0.18 × 10-3 vs 3.15 ± 0.51 × 10-3 mm2/s, respectively). In addition, there was a significant difference (p < 0.05) in mean ADC values between benign cysts and cystic RCC (3.36 ± 0.35 × 10-3 vs 2.83 ± 0.21 × 10-3 mm2/s, respectively). CONCLUSION: ADC maps with b values of 0 and 800 s/mm2 can be used as an imaging biomarker, to differentiate benign SRM from malignant SRM. Using ADC value threshold of 1.75 × 10-3 mm2/s allows to differentiate solid RCC from solid benign kidney tumors with 91% sensitivity and 89% specificity; ADC value threshold of 2.96 × 10-3 mm2/s distinguishes cystic RCC from benign renal cysts with 90% sensitivity and 88% specificity. However, the possibility of differentiation between ccRCC histologic subtypes and grades, utilizing ADC values, is limited.
- MeSH
- Kidney Diseases, Cystic diagnosis MeSH
- Diagnosis, Differential MeSH
- Diffusion Magnetic Resonance Imaging methods MeSH
- Adult MeSH
- Carcinoma, Renal Cell * diagnosis pathology surgery MeSH
- Organ Sparing Treatments methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Kidney Neoplasms * diagnosis pathology surgery MeSH
- Nephrectomy methods MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Cell phones and other communication devices have become the primary source of socialization, especially among adolescents. The aim of the study was to assess the levels of radiated radiofrequency (RF) power (1788.5 MHz, max. 30 V/m) around the head of adolescents. The measurements were performed in 2016 at the Department of Medical Biophysics of Jessenius Faculty of Medicine in Martin. The sample group consisted of 44 adolescents of Viliam Pauliny-Toth, Grammar School in Martin. To measure the performance levels of electromagnetic fields (EMF), we used selective radiation meter NARDA SRM 3006 (9 kHz–6 GHz) with the function of a spectrum analyzer. The average values of power were recorded in eight positions around the head with six minutes exposure length of each of them. Every adolescent filled out a short questionnaire on personal perception of the effects of RF radiation on the body after the exposure. The statistical evaluation showed a significant decrease in the intensity of power on the left side of the adolescent’s head compared to the right side (p < 0.01–0.001), which confirmed different degrees of absorption by the head tissues. The highest level of absorption was measured at temporal area of the head connecting both ears. Shortterm exposure to RF radiation did not cause strong adverse health effects in adolescents, however in a few cases tachycardia, drowsiness, headache, fatigue and restlessness appeared. It is necessary to pay more attention to the examination of the relationship between exposure to RF EMF and the potential adverse health reactions mainly in adolescents.
- MeSH
- Electromagnetic Fields * adverse effects MeSH
- Head radiation effects MeSH
- Humans MeSH
- Adolescent MeSH
- Cell Phone MeSH
- Surveys and Questionnaires MeSH
- Radio Waves classification adverse effects MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Targeted mass spectrometry-based proteomics approaches enable the simultaneous and reproducible quantification of multiple protein analytes across numerous conditions in biology and clinical studies. These approaches involve e.g. selected reaction monitoring (SRM) typically conducted on a triple quadrupole mass spectrometer, its high-resolution variant named pseudo-SRM (p-SRM), carried out in a quadrupole coupled with an TOF analyzer (qTOF), and "sequential window acquisition of all theoretical spectra" (SWATH). Here we compared these methods in terms of signal-to-noise ratio (S/N), coefficient of variance (CV), fold change (FC), limit of detection and quantitation (LOD, LOQ). We have shown the highest S/N for p-SRM mode, followed by SRM and SWATH, demonstrating a trade-off between sensitivity and level of multiplexing for SRM, p-SRM, and SWATH. SRM was more sensitive than p-SRM based on determining their LOD and LOQ. Although SWATH has the worst S/N, it enables peptide multiplexing with post-acquisition definition of the targets, leading to better proteome coverage. FC between breast tumors of different clinical-pathological characteristics were highly correlated (R2 >0.97) across three methods and consistent with the previous study on 96 tumor tissues. Our technical note presented here, therefore, confirmed that outputs of all the three methods were biologically relevant and highly applicable to cancer research.
- MeSH
- Mass Spectrometry instrumentation methods MeSH
- Humans MeSH
- Limit of Detection MeSH
- Neoplasms chemistry metabolism MeSH
- Signal-To-Noise Ratio MeSH
- Proteins analysis MeSH
- Proteomics methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Spontaneous preterm birth significantly contributes to the overall neonatal morbidity associated with preterm deliveries. Nearly 50% of cases are associated with microbial invasion of the amniotic cavity followed by an inflammatory response. Robust diagnostic tools for neonates jeopardized by infection and inflammation may thus decrease the overall neonatal morbidity substantially. Amniotic fluid retrieved during labor retains fetal and pregnancy-related protein fingerprint and its sampling does not place any unwanted stress on women. Using exploratory and targeted methods we analyzed proteomes of amniotic fluid sampled at the end of spontaneous preterm labor prior to delivery from women with and without infection and inflammation. Exploratory data indicated several amniotic fluid proteins to be associated with infectious-inflammatory complications in spontaneous preterm birth. LC-SRM analysis subsequently verified statistically significant changes in lipocalin-1 (P = 0.047 and AUC = 0.67, P = 0.046), glycodelin (P = 0.013 and AUC = 0.73, P = 0.013), and nicotinamide phosphoribosyltransferase (P = 0.018 and AUC = 0.71, P = 0.01).
- MeSH
- Adult MeSH
- Pregnancy Complications, Infectious genetics pathology MeSH
- Humans MeSH
- Peptide Mapping MeSH
- Peripartum Period genetics MeSH
- Amniotic Fluid metabolism MeSH
- Premature Birth genetics pathology MeSH
- Proteome genetics MeSH
- Pregnancy MeSH
- Inflammation complications genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Cíl: Porovnat stanovení celkového bilirubinu metodou přímé spektrofotometrie v plné žilní krvi a metodou Jendrassik-Gróf v séru žilní krve u 437 novorozenců narozených v Krajské nemocnici T. Bati ve Zlíně (KNTB). Typ studie: retrospektivní průřezová. Metody: Přímá spektrofotometrie plné žilní krve na analyzátoru ABL 835 firmy Radiometer a spektrofotometrické stanovení v séru žilní krve metodou Jendrassik-Gróf na analyzátoru Architect firmy Abbott. Obě metody mají metrologickou návaznost měření na referenční materiál NIST SRM 916a. Výsledky: Medián (mezikvartilové rozpětí) sérového bilirubinu byl 228 μmol/l (186-263), medián (mezikvartilové rozpětí) bilirubinu v plné krvi byl 237 μmol/l (192-287). Wilcoxonův párový test prokázal mezi mediány statisticky významný rozdíl (p<0,0001). Blandův-Altmanův rozdílový graf a Passing Bablokova regrese ukazují, že především v oblasti koncentrací nad 280 μmol/l měří přímá spektrofotometrie celkového bilirubinu v plné žilní krvi vyšší výsledky než stanovení v séru žilní krve (p<0,0001). Závěr: Při koncentraci bilirubinu nad 280 μmol/l měří přímá spektrofotometrie v plné žilní krvi výrazně vyšší výsledky než stanovení v séru (p<0,0001). Hodnoty nad 280 μmol/l je tedy nutné potvrdit měřením v séru žilní krve v biochemické laboratoři.
Aim: The aim of the study is to compare determination of total bilirubin by direct spectrophotometric method in whole venous blood and by indirect Jendrassik-Gróf method in venous serum in 437 newborns born in Tomas Bata hospital in Zlin. Design: retrospective cross section design. Methods: Determination of total bilirubin by direct spectrophotometric method in whole venous blood was performed on Radiometer ABL 835 analyzer. Determination of total bilirubin in venous serum by indirect Jendrassik-Gróf was performed on Abbott Architect analyzer. Both methods are metrologically traceable to reference material NIST SRM 916a. Results: The median (interquartile range) of serum venous bilirubin was 228 μmol/L (186-263). The median of venous whole blood total bilirubin was 237 μmol/L (192-287). The significant difference between medians was found (p<0,0001). Bland- Altman plot and Passing-Bablok regression show that direct spectrophotometric method of whole venous blood gave higher results than Jendrassik-Gróf test in venous serum mainly in the concentration range above 280 μmol/l (p<0,0001). Conclusions: Direct spectrophotometric results of total bilirubin in whole venous blood in the concentration range above 280 umol/l should be confirmed by indirect serum determination in clinical biochemistry laboratory.
- MeSH
- Bilirubin * analysis diagnostic use blood MeSH
- Blood Chemical Analysis methods utilization MeSH
- Hemolysis MeSH
- Infant, Newborn MeSH
- Jaundice, Neonatal * diagnosis MeSH
- Cross-Sectional Studies MeSH
- Reference Standards MeSH
- Retrospective Studies MeSH
- Spectrophotometry * methods instrumentation utilization MeSH
- Check Tag
- Infant, Newborn MeSH
- Publication type
- Comparative Study MeSH
Vývoj diagnostických a terapeutických přístupů v onkologii vyžaduje, kromě jiného, citlivé kvantitativní přístupy pro stanovení proteinů souvisejících s nádorovými procesy v klinických vzorcích. V tomto článku jsou představeny nové kvantitativní metody cílené proteomiky. Hlavní potenciál metod monitorování vybraných reakcí (SRM) a pseudo‑SRM spočívá v kvantifikaci předem vybraných proteinů ve větších souborech vzorků s vysokou citlivostí a selektivitou, čímž představují alternativu ke stávajícím imunochemickým přístupům. Potenciál HRM a SWATH spočívá naopak v získávání digitálních proteomických fingerprintů, z nichž je následně možné extrahovat kvantitativní proteomická data na podobném principu jako u SRM. Článek představuje aplikace uvedených metod v řadě studií z oblasti onkologického výzkumu, kde byly použity ke stanovení a validaci stávajících i nově navrhovaných proteinových biomarkerů a při studiu jejich úlohy v mechanizmu vzniku a vývoje nádorů.
Development of novel diagnostic and therapeutic approaches in cancer research requires sensitive and quantitative assays for determination of cancer‑associated proteins in clinical samples. Novel quantitative targeted proteomic approaches are overviewed in this communication. A major advantage of selected reaction monitoring (SRM) and pseudo-SRM lies in the selective and sensitive quantification of selected proteins in large sample sets. As such, they represent an alternative to immunochemical approaches. On the other hand, the potential of HRM and SWATH lies in recording of digital fingerprints, which enable post‑acquisition quantitative proteomic data mining on a similar basis to SRM. This article shows applications of targeted proteomics in a number of cancer research studies where they were used for quantification and validation of current or potential protein biomarkers and to study their role in cancer development and progression. Key words: proteomics – selected reaction monitoring – oncology – SWATH – biomarkers – molecular diagnostics This work was supported by the project of Czech Science Foundation No. 14-19250S, by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) and by MH CZ – DRO (MMCI, 00209805) and BBMRI_CZ (LM2010004). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers. Submitted: 3. 2. 2014 Accepted: 26. 3. 2014
