Lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib in treatment of advanced renal cell carcinoma (aRCC) in the phase 3 CLEAR study. We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib plus pembrolizumab versus sunitinib, at the final overall survival analysis time point of CLEAR (cutoff: July 31, 2022). Treatment-naïve adults with aRCC were randomized to: lenvatinib (20 mg PO QD in 21-day cycles) plus pembrolizumab (n = 355; 200 mg IV Q3W); lenvatinib plus everolimus (not reported here); or sunitinib (n = 357; 50 mg PO QD; 4 weeks on/2 weeks off). The most common (lenvatinib plus pembrolizumab; sunitinib, respectively) metastatic site was lung (71.0%; 63.9%), followed by lymph node (45.6%; 43.7%), bone (22.5%; 24.9%), and liver (17.7%; 19.6%). Across treatment arms, ≥65% had two or more metastatic organs/sites involved, >80% of patients had nontarget lesions, and ~45% had baseline sums of diameters of target lesions ≥60 mm. Lenvatinib plus pembrolizumab demonstrated greater progression-free survival, objective response rate, and duration of response versus sunitinib across evaluable subgroups regardless of site or size of baseline metastasis or number of metastatic sites at baseline. Overall survival generally trended to favor lenvatinib plus pembrolizumab versus sunitinib; and tumor shrinkage was greater across sites (lung, lymph node, liver, and bone) for patients in the lenvatinib-plus-pembrolizumab arm versus the sunitinib arm. These results further support lenvatinib plus pembrolizumab as a standard-of-care in patients with aRCC regardless of site or size of baseline metastasis or the number of metastatic sites.

• MeSH
• chinoliny * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• fenylmočovinové sloučeniny * aplikace a dávkování   terapeutické užití   MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   terapeutické užití   MeSH
• karcinom z renálních buněk * farmakoterapie   patologie   mortalita   sekundární   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory ledvin * farmakoterapie   patologie   mortalita   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sunitinib * aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Chronic intestinal inflammation significantly contributes to the development of colorectal cancer and remains a pertinent clinical challenge, necessitating novel therapeutic approaches. Indole-based microbial metabolite mimics Felix Kopp Kortagere 6 (FKK6), which is a ligand and agonist of the pregnane X receptor (PXR), was recently demonstrated to have PXR-dependent anti-inflammatory and protective effects in a mouse model of dextran sodium sulfate (DSS)-induced acute colitis. Here, we examined the therapeutic potential of FKK6 in a mouse model (C57BL/6 FVB humanized PXR mice) of colitis-associated colon cancer (CAC) induced by azoxymethane and DSS. FKK6 (2 mg/kg) displayed substantial antitumor activity, as revealed by reduced size and number of colon tumors, improved colon histopathology, and decreased expression of tumor markers (c-MYC, β-catenin, Ki-67, and cyclin D) in the colon. In addition, we carried out a chronic toxicity (30 days) assessment of FKK6 (1 mg/kg and 2 mg/kg) in C57BL/6 mice. Histological examination of tissues, biochemical blood analyses, and immunohistochemical staining for Ki-67 and γ-H2AX showed no difference between FKK6-treated and control mice. Comparative metabolomic analyses in mice exposed for 5 days to DSS and administered with FKK6 (0.4 mg/kg) revealed no significant effects on several classes of metabolites in the mouse fecal metabolome. Ames and micronucleus tests showed no genotoxic and mutagenic potential of FKK6 in vitro. In conclusion, anticancer effects of FKK6 in azoxymethane/DSS-induced CAC, together with FKK6 safety data from in vitro tests and in vivo chronic toxicity study, and comparative metabolomic study, are supportive of the potential therapeutic use of FKK6 in the treatment of CAC. SIGNIFICANCE STATEMENT: Microbial metabolite mimicry proposes that chemical mimics of microbial metabolites that serve to protect hosts against aberrant inflammation in the gut could serve as a new paradigm for the development of drugs targeting inflammatory bowel disease if, like the parent metabolite, is devoid of toxicity but more potent against the microbial metabolite receptor. We identified a chemical mimic of Felix Kopp Kortagere 6, and we propose that Felix Kopp Kortagere 6 is devoid of toxicity yet significantly reduces tumor formation in an azoxymethane-dextran sodium sulfate model of murine colitis-induced colon cancer.

• MeSH
• azoxymethan toxicita   MeSH
• chronická nemoc MeSH
• indoly farmakologie   terapeutické užití   MeSH
• kolitida farmakoterapie   chemicky indukované   metabolismus   patologie   MeSH
• kolorektální nádory * farmakoterapie   metabolismus   patologie   MeSH
• modely nemocí na zvířatech * MeSH
• molekulární mimikry MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• nádory asociované s kolitidou patologie   farmakoterapie   metabolismus   MeSH
• síran dextranu toxicita   MeSH
• zánět farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• aortální stenóza * chirurgie   komplikace   MeSH
• chirurgická náhrada chlopně metody   MeSH
• frakční průtoková rezerva myokardu * MeSH
• koronární angioplastika * metody   MeSH
• koronární bypass * metody   MeSH
• lidé MeSH
• nemoci koronárních tepen * chirurgie   komplikace   terapie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• MeSH
• antiflogistika farmakologie   chemie   MeSH
• dexamethason * farmakologie   chemie   analogy a deriváty   MeSH
• játra * účinky léků   metabolismus   MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• myši MeSH
• nanokuličky * chemie   MeSH
• nosiče léků chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hand and foot osteosarcoma represents ~1% of all diagnosed cases of osteosarcoma. The rarity of osteosarcoma of the hand and foot leads to frequent misdiagnosis, delayed diagnosis or incorrect treatments, which can lead to fatal consequences. Typically, salvaging the affected limb is the treatment of choice, and with the use of chemotherapy, 60-65% of patients with osteosarcoma can be treated without amputation. Due to its rarity, misdiagnosis and treatment delays are common, yet detailed reviews and analyses of such cases are limited. The present retrospective cohort study aimed to review and analyze cases of osteosarcoma located in the hand and foot. From January 2007 to January 2019, 11 patients were treated at the Masaryk Memorial Cancer Institute Sarcoma Center (Brno, Czechia), 5 cases affected the hand and 6 affected the foot. A total of 6 male patients and 5 female patients, with a mean age of 30.9±16.74 years, were diagnosed with hand or foot osteosarcoma. The mean follow-up period was 90.36±66.14 months. The mean tumor size detected during diagnosis was 4.29±1.81 cm. Osteoblastic osteosarcoma was the most common histopathological type, accounting for 4 cases (33.4%). A majority of the osteosarcomas were identified as high grade (81.8%). A total of 5 patients experienced misdiagnoses following their initial biopsy, with 2 patients initially receiving treatment outside the Masaryk Memorial Cancer Institute Sarcoma Center. The most frequently encountered misdiagnosis was giant-cell tumor of the bone. A total of 3 patients underwent limb amputation and 2 patients developed lung metastasis and succumbed to the disease. The disease-free survival period and overall survival rate were calculated using Kaplan-Meier survival analysis. The mean disease-free survival period was 82.83±60.05 months, while the overall survival rate was 72%, with a mean survival time of 90.36±56.73 months. In summary, an examination of a case series involving 11 patients diagnosed with osteosarcoma of the hand and foot was conducted. The treatment approach, clinical characteristics and patient outcomes were described. A total of four case studies of patients with osteosarcoma in the hand or foot were presented. Misdiagnosis of this disease may result in the inappropriate treatment being administered to patients, therefore, the correct and rapid diagnosis of disease is necessary for effective treatment of hand and foot osteosarcomas.

• Publikační typ
• časopisecké články MeSH

OBJECTIVES: To determine the safety and oncological advantages of en bloc resection of bladder tumour (ERBT) vs conventional transurethral resection of bladder tumour (cTURBT) in terms of resection quality, staging quality, and safety. PATIENTS AND METHODS: We conducted a single-blinded randomised controlled trial at seven European hospitals with the following inclusion criteria: first diagnosis of non-muscle-invasive bladder cancer, no singular carcinoma in situ, and tumour size >4.3 mm. Patients were randomised intraoperatively in a 1:1 ratio to either the ERBT or cTURBT group. Outcome analysis was performed using the chi-square test, t-test, and multivariate regression analysis. RESULTS: A total of 97 patients were randomised into the study (cTURBT = 40, ERBT = 57). A switch to cTURBT was necessary in two patients (3.5%) and 11.5% of the screened patients were preoperatively excluded for ERBT. There was no difference in the specimen presence of detrusor muscle with 73.7% in cTURBT and 67.3% in ERBT specimens (P = 0.69). There were no significant differences in mean operative time (ERBT 27.6 vs cTURBT 25.4 min, P = 0.450) or mean resection time (ERBT 16.3 vs cTURBT 15.5 min, P = 0.732). Overall the complication rate did not differ significantly (ERBT 18.2% vs cTURBT 7.5%, P = 0.142). Bladder perforations occurred significantly more often in the ERBT group (ERBT seven vs cTURBT none, P = 0.020). R0 status was reported more often after ERBT, whilst a second resection was significantly less frequent after ERBT (P = 0.018). Recurrence rates were comparable for both techniques after 6 months of follow-up. CONCLUSION: The feasibility of ERBT is higher than previously reported. Whereas other perioperative and safety parameters are comparable to cTURBT, bladder perforations occurred significantly more often in the ERBT group and raised safety concerns. This is why this trial was terminated.

• MeSH
• cystektomie * metody   škodlivé účinky   MeSH
• jednoduchá slepá metoda MeSH
• karcinom z přechodných buněk chirurgie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transuretrální resekce močového měchýře MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.

• MeSH
• Aspirin * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• extracelulární vezikuly * metabolismus   účinky léků   MeSH
• inhibitory agregace trombocytů * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inhibitory faktoru Xa * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci * krev   prevence a kontrola   farmakoterapie   MeSH
• kombinovaná farmakoterapie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• prospektivní studie MeSH
• proteomika metody   MeSH
• rivaroxaban * aplikace a dávkování   MeSH
• senioři MeSH
• trombóza krev   prevence a kontrola   farmakoterapie   MeSH
• výsledek terapie MeSH
• zánět krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Feruloyl esterases (FAEs) are a crucial component of the hemicellulose-degrading enzyme family that facilitates the degradation of lignocellulose while releasing hydroxycinnamic acids such as ferulic acid with high added value. Currently, the low enzyme yield of FAEs is one of the primary factors limiting its application. Therefore, in this paper, we optimized the fermentation conditions for the expression of FAE BpFaeT132C-D143C with excellent thermal stability in Escherichia coli by experimental design. Firstly, we explored the effects of 11 factors such as medium type, isopropyl-β-D-thiogalactopyranoside (IPTG) concentration, and inoculum size on BpFaeT132C-D143C activity separately by the single factor design. Then, the significance of the effects of seven factors, such as post-induction temperature, shaker rotational speed, and inoculum size on BpFaeT132C-D143C activity, was analyzed by Plackett-Burman design. We identified the main factors affecting the fermentation conditions of E. coli expressing BpFaeT132C-D143C as post-induction temperature, pre-induction period, and post-induction period. Finally, we used the steepest ascent path design and response surface method to optimize the levels of these three factors further. Under the optimal conditions, the activity of BpFaeT132C-D143C was 3.58 U/ml, which was a significant 6.6-fold increase compared to the pre-optimization (0.47 U/ml), demonstrating the effectiveness of this optimization process. Moreover, BpFaeT132C-D143C activity was 1.52 U/ml in a 3-l fermenter under the abovementioned optimal conditions. It was determined that the expression of BpFaeT132C-D143C in E. coli was predominantly intracellular in the cytoplasm. This study lays the foundation for further research on BpFaeT132C-D143C in degrading agricultural waste transformation applications.

• MeSH
• Escherichia coli * genetika   metabolismus   enzymologie   MeSH
• fermentace * MeSH
• isopropylthiogalaktosid metabolismus   MeSH
• karboxylesterhydrolasy * genetika   metabolismus   chemie   biosyntéza   MeSH
• kultivační média chemie   MeSH
• kyseliny kumarové metabolismus   MeSH
• lignin MeSH
• rekombinantní proteiny genetika   metabolismus   biosyntéza   chemie   MeSH
• stabilita enzymů MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH

Farmakogenetické (PGx) vyšetření představuje slibný nástroj pro optimalizaci psychiatrické farmakoterapie. Svým potenciálem může přispět ke zvýšení její účinnosti a snížení rizika vzniku nežádoucích účinků. Ekonomická limitace v podobě vyšší ceny vyšetření vyžaduje cílenější výběr pacientů, tento přístup však v praxi zatím chybí. Za tím účelem byl klinickými farmaceutkami v Psychiatrické nemocnici Bohnice vyvinut skórovací systém CYPRI (CYP pharmacogenetic risk score) identifikující pacienty, kteří by mohli mít z PGx vyšetření největší prospěch. Cílem pilotní studie bylo pak zhodnotit účinnost a efektivitu skórovacího systému CYPRI při výběru pacientů pro PGx vyšetření v kontextu následně uskutečněných a klinicky významných změn v jejich medikaci. Do pilotní studie, která probíhala mezi lednem 2024 a březnem 2025, bylo zařazeno 23 pacientů (průměrný věk 38 let, 74 % mužů). Vzorek zahrnoval hospitalizované pacienty s širokým spektrem psychiatrických diagnóz, včetně schizofrenie, bipolární a schizoafektivní poruchy, deprese i úzkostných poruch. Pacienti, u kterých bylo PGx indikováno lékařem a/nebo klinickým farmaceutem a kteří v CYPRI skórovali alespoň jedním bodem, podstoupili po souhlasu PGx vyšetření. Následně u nich byla provedena analýza dopadu výsledku tohoto vyšetření na úpravy v medikaci. Byla zjištěna statisticky významná korelace (t = 2,733; p = 0,0063) mezi hodnotami CYPRI skóre a následnými klinicky významnými změnami v medikaci. Pacienti s vysokým CYPRI skóre (> 3) také vyžadovali statisticky významně více úprav medikace a monitorace než pacienti s nízkým skóre (≤ 3) (p < 0,05). Tyto výsledky potvrzují, že CYPRI skóre by mohlo v budoucnu sloužit jako strukturovaný a nákladově efektivní nástroj pro výběr vhodných kandidátů na PGx vyšetření, zejména v oboru psychiatrie. Širší použití CYPRI skóre v praxi prozatím limituje, i přes slibné výsledky z pilotní studie, relativně malá velikost vzorku. Pro potvrzení těchto výstupů je zapotřebí další výzkum na větších kohortách.

Pharmacogenetic (PGx) testing is a promising tool for optimizing psychiatric pharmacotherapy by improving its effectiveness and reducing the risk of adverse effects. However, its higher cost necessitates a more selective approach to patient screening, which is currently lacking in clinical practice. To address this gap, clinical pharmacists at Bohnice Psychiatric Hospital developed a CYPRI (CYP Pharmacogenetic Risk Score) scoring system to identify patients who would benefit the most from PGx testing. This pilot study aimed to assess the effectiveness and efficiency of the CYPRI scoring system in selecting patients for PGx testing, focusing on clinically significant medication adjustments that followed. Our study was conducted from January 2024 to March 2025 and included 23 hospitalized patients (mean age: 38 years; 74% male) with a range of psychiatric diagnoses, including schizophrenia, bipolar disorder, schizoaffective disorder, depression, and anxiety disorders. Pharmacogenetic testing was offered to patients following an initial indication by a psychiatrist and/or clinical pharmacist, provided they scored at least one point on the CYPRI scale. Upon providing an informed consent, they underwent the PGx testing. The resulting impact on medication adjustments was analyzed. A statistically significant correlation was found between the CYPRI scores and clinically significant medication changes (t = 2.733; p = 0.0063). Additionally, patients with high CYPRI scores (> 3) required significantly more medication adjustments and monitoring than those with low scores (≤ 3) (p < 0.05). These findings suggest that the CYPRI score could serve as a structured and cost-effective tool for identifying suitable candidates for PGx testing, especially in psychiatry. Despite these promising results, the relatively small sample size remains a limitation for the broader implementation of the CYPRI score. Further research with larger cohorts is needed to validate these findings.

This study aimed to determine the effect of complex training (CT) on post-activation performance enhancement (PAPE) effect magnitude, 5- and 30-m linear sprint, 5-0-5 change-of-direction (COD), back squat (BS) and hip thrust (HT) one-repetition maximum [1RM], and jumping performance (countermovement jump [CMJ], drop jump [DJ], and broad jump [BJ]). The PAPE effect was elicited before and after each intervention by 3 BS repetitions at 90% 1RM and verified by CMJ performance. Twenty-four soccer players were randomly and equally assigned to 6 weeks of either medium (MED; [65-70%1RM]) or high-intensity (HIGH; [80-85%1RM]) CT performed twice a week. The HIGH group significantly improved their 5-m time (p < 0.001; effect size [ES] = 1.91), 30-m time (p = 0.001; ES = 0.66), BS 1RM (p = 0.019; ES = 0.19) and HT 1RM (p = 0.035; ES = 0.26), BJ length (p = 0.012; ES = 0.62) and DJ height (p = 0.002; ES = 0.57) from pre- to post-intervention. The MED group significantly improved their 5-m time (p = 0.004; ES = 0.52), BS 1RM (p = 0.019; ES = 0.36) and BJ length (p = 0.012; ES = 0.7). Significantly shorter 5-m sprint time (p = 0.001; ES = 1.63) and greater DJ height percentage increase (p < 0.001; ES = 1.81) were found in the HIGH group compared to the MED group. Moreover, a significant main effect of the group, indicating a higher PAPE response in the MED group compared to the HIGH group for CMJ peak power output, was observed at both pre- and post-CT intervention (p = 0.045; η2 = 0.171). Six weeks of either medium or high-intensity CT could be used to enhance jumping performance, linear speed and lower-body maximum strength among soccer players. Superior improvements in acceleration and DJ might be expected after high-intensity CT than medium intensity. Medium-intensity CT can improve PAPE response.

• Publikační typ
• časopisecké články MeSH