CONTEXT: SB16 is a proposed biosimilar to reference denosumab (DEN; brand name: Prolia). OBJECTIVE: This phase 3 randomized, double-blind, multicenter study evaluated the biosimilarity of SB16 to DEN in women with postmenopausal osteoporosis (NCT04664959). DESIGN: The study included 457 postmenopausal osteoporosis patients who had a lumbar spine or total hip T-score between -2.5 and -4. Patients were randomized in a 1:1 ratio to receive either 60 mg of SB16 or DEN subcutaneously at month 0 and month 6. At month 12, patients were rerandomized to continue with the assigned treatment or switch from DEN to SB16 up to month 18. This report includes results up to month 12. METHODS: The primary endpoint was the percent change from baseline in lumbar spine bone mineral density (BMD) at month 12. Secondary endpoints including the percent change from baseline in BMD of the lumbar spine (except for month 12), total hip, and femoral neck; pharmacokinetic, pharmacodynamic (serum C-telopeptide of type I collagen, and procollagen type I N-terminal propeptide), safety, and immunogenicity profiles were measured up to month 12. RESULTS: The least-squares mean differences in percent change from baseline in lumbar spine BMD at month 12 were 0.33% (90% CI, -0.25 to 0.91) in the full analysis set and 0.39% (95% CI, -0.36 to 1.13) in the per-protocol set; both within the predefined equivalence margin. The secondary endpoints were comparable between the 2 treatment groups. CONCLUSION: The reported efficacy, pharmacokinetic, pharmacodynamic, safety, and immunogenicity data support the biosimilarity of SB16 to DEN.

• MeSH
• Lumbar Vertebrae drug effects   diagnostic imaging   MeSH
• Biosimilar Pharmaceuticals * therapeutic use   pharmacokinetics   administration & dosage   adverse effects   MeSH
• Denosumab * therapeutic use   pharmacokinetics   adverse effects   administration & dosage   MeSH
• Double-Blind Method MeSH
• Bone Density Conservation Agents * therapeutic use   pharmacokinetics   administration & dosage   adverse effects   MeSH
• Bone Density drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Osteoporosis, Postmenopausal * drug therapy   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

PURPOSE: This study aimed to evaluate the relationship between on- and off-water performance tests in canoe slalom. METHODS: A total of 34 elite canoe slalom athletes, who competed in one of the following categories, namely K1 men (K1M, n = 9), K1 women (K1W, n = 8), C1 men (C1M, n = 9), or C1 women (C1W, n = 8), volunteered for the study. On-water testing consisted of two flat water tests: sprints with turns to both sides (SBS; 2 × 15 m shuttle sprints) and an all-out shuttle test (12 × 15 AOT; 12 × 15 m shuttle sprints). Off-water testing included anthropometric analyses, power output in bench press, pull measurement, and 3 × 200 m performance on a kayak ergometer. Each athlete completed testing over two consecutive days. RESULTS: The results showed a significant relationship between the on-water tests (SBS/AOT) and body weight (kg, r = 0.472/0.478), body fat (%, r = 0.451/0.445), Pmax bench press (W, r = 0.748/0.705), Pmax bench pull (W, r = 0.704/0.693), relative Pmax bench press (W/kg, r = 0.735/0.663), relative Pmax in bench pull (W/kg, r = 0.727/0.700), ergo best 200 m (s, r = 0.851/0.884), ergo best mean 200 m (W, r = 0.902/0.922), and ergo 3 × 200 m total time (s, r = 0.842/0.884), determined using the Pearson correlation coefficient. CONCLUSION: Based on the identified relationships, we recommend regular monitoring of the physical fitness levels of canoe slalom athletes using the described off-water tests. These tests can help identify the strengths and weaknesses of athletes, enabling coaches to optimize the training process.

• Publication type
• Journal Article MeSH

Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and in clinical practice, Lp(a) is mainly used to (re)define CV risk, particularly in individuals at borderline CV risk and people with a family history of premature coronary heart disease, according to various guidelines. Specific Lp(a)-targeted antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) agents have been developed to produce substantial Lp(a) reductions via the inhibition of apo(a) synthesis in the liver. These drugs are conjugated to N-acetylgalactosamine (GalNAc) to ensure their binding to asialoglycoproteins, which are specifically expressed on the surface of the hepatocytes. Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use. The present narrative review summarizes the available clinical data on the efficacy and safety of these investigational Lp(a)-lowering therapies, as reported in phase 1 and 2 trials. The effects of these drugs on other [aside from Lp(a)] lipid parameters are also discussed. The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units).

• Publication type
• Journal Article MeSH
• Review MeSH

Background: Abiraterone acetate is an androgen-receptor pathway inhibitor commonly used for treatment of metastatic prostate cancer. The levels of androgens during treatment with abiraterone acetate with prednisone (AAP) are lower than those achieved by androgen-deprivation therapy only, potentially resulting in a high risk of skeletal muscle loss. Methods: The cohort included 43 patients treated with AAP for metastatic hormone-sensitive prostate cancer or metastatic castration-resistant prostate cancer. To detect and quantify sarcopenia, we utilized standard computer tomography (CT) imaging. Skeletal muscle mass index (SMI) was evaluated by assessing two adjacent axial sections at the level of the L3 vertebra. Results: Sarcopenia at the time of AAP initiation was present in 72.1% of patients. Body mass index (BMI) was inversely associated with the presence of sarcopenia at the time of AAP initiation. There was a statistically significant decrease in SMI over AAP treatment. Age > 75 years and the absence of previous radiotherapy were associated with a higher rate of SMI decrease during AAP therapy. Overall and progression-free survival was not significantly associated with SMI decrease during AAP therapy. Conclusions: SMI decline occurs during AAP treatment for mHSPC and mCRPC, and is more pronounced in patients over 75 years old and those without previous local treatment. There was no statistically significant association between survival outcomes and SMI decline during AAP therapy.

• Publication type
• Journal Article MeSH

Publikace se zaměřuje na radiační onkologii a na možnosti radioterapie nádorových nemocí. Určeno odborné veřejnosti.

• MeSH
• Neoplasms radiotherapy   MeSH
• Radiation Oncology MeSH
• Radiotherapy MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• onkologie
• radiologie, nukleární medicína a zobrazovací metody
• NML Publication type
• kolektivní monografie

Identifying biological markers to guide treatment decisions in first-episode psychosis (FEP) is essential for improving patient outcomes. This longitudinal study investigated DNA methylation (DNAm) patterns and DNAm-derived cell-type proportions (CTP) in blood and associated them with response to risperidone treatment, a second-generation antipsychotic drug, in antipsychotic-naïve FEP patients. We also explored longitudinal changes in DNAm associated with risperidone treatment. We profiled DNAm in 114 individuals before (anFEP) and after two months of risperidone treatment using microarrays. The main results were compared with 115 healthy controls and validated in an independent cohort of subjects with schizophrenia (n = 26) with one-month follow-up data. We identified 302 differentially methylated positions (DMPs) associated with treatment response, measured by changes in the Positive and Negative Syndrome Scale score, of which 16 were validated in the independent cohort. Sixteen differentially methylated regions (DMRs) were associated with response, with one (in SIPA1L3) being validated. A decrease in B-cell proportions was correlated with symptom improvement in both cohorts. Additionally, four DMPs associated with risperidone treatment were identified: two related to the psychotic state and two specifically to risperidone treatment. DNAm-derived CTP showed alterations in anFEP compared with controls, particularly in the neutrophil-to-lymphocyte ratio, which normalized after treatment. These findings suggest that DNAm, particularly in B-cells, may be a promising marker for monitoring response to risperidone treatment in schizophrenia. Our longitudinal study revealed novel and known genes that may be regulated by risperidone and could be used as response markers to improve prognosis in schizophrenia and FEP.

• MeSH
• Antipsychotic Agents * therapeutic use   MeSH
• Adult MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• DNA Methylation * drug effects   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Psychotic Disorders * drug therapy   genetics   blood   MeSH
• Risperidone * therapeutic use   pharmacology   MeSH
• Schizophrenia * drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Epilepsy in children is often associated with impaired quality of life, lower academic achievement, and reduced academic self-concept, as well as an increased risk of depression and anxiety. This study aims to evaluate the possible impact of comorbidities, such as learning disabilities (LD) and attention deficit hyperactivity disorder (ADHD), on these variables. METHODS: A total of 104 children with epilepsy (CWE) aged 8-15 years, attending mainstream schools, participated in the study. Of these, 45 were diagnosed with LD and/or ADHD. Participants completed the CHEQOL-25 questionnaire to assess quality of life (QoL), the SPAS questionnaire to evaluate academic self-concept, as well as inventories measuring depressive and anxiety symptoms. The data were analyzed to identify differences between subgroups with and without LD/ADHD using a two-sample t-test. Additionally, correlation analysis was conducted to identify other relevant variables influencing QoL, academic self-concept, and depressive and anxiety symptoms. RESULTS: QoL and academic self-concept were significantly poorer in CWE with LD/ADHD compared to those without comorbidities. QoL showed statistically significant associations with depressive and anxiety symptoms, and academic self-concept. While depressive symptoms levels in CWE without comorbidities align with those in the general population, CWE with LD/ADHD showed an increased association with depressive symptoms. Although anxiety symptoms were relatively strongly associated with depressive symptoms, their prevalence remains broadly comparable to that of children without epilepsy, regardless of the presence of LD/ADHD. CONCLUSION: CWE with LD/ADHD and their families may benefit from focused attention, including targeted counseling and therapeutic interventions. However, specific interventional studies are recommended, based on child-specific findings.

• MeSH
• Depression epidemiology   psychology   MeSH
• Child MeSH
• Mental Health * MeSH
• Epilepsy * psychology   epidemiology   complications   MeSH
• Attention Deficit Disorder with Hyperactivity epidemiology   psychology   MeSH
• Comorbidity MeSH
• Quality of Life * psychology   MeSH
• Humans MeSH
• Adolescent MeSH
• Learning Disabilities * epidemiology   psychology   MeSH
• Surveys and Questionnaires MeSH
• Self Concept * MeSH
• Anxiety epidemiology   psychology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Arrested or protracted labor in nulliparous women caused by insufficient uterine contractility is a common problem in obstetrics, for which few management guidelines exist. The European Association of Perinatal Medicine nominated an expert panel, consisting of specialists in obstetrics and gynecology and midwives representing their respective professional national societies in nine European countries and patient representatives. The panel developed an evidence-based guideline for clinical practice supported by the Knowledge Institute of the Dutch Association of Medical Specialists. Five priority clinical questions (PICOs) were identified on nulliparous women, at term, with a singleton fetus, in cephalic presentation, and the diagnosis of arrested or protracted labor. For each question relevant outcome measures were defined as well as a minimal clinically important difference for each of them. Five literature searches were performed by an information specialist and articles were selected independently by two panel members. The GRADE methodology was used to write evidence summaries, considerations, and recommendations. The draft guideline was sent out for review to scientific societies involved in perinatal care in 20 European countries. Comments were answered, and the guideline was revised accordingly. The following procedures should be offered to women: 1) Amniotomy alone may be considered. 2) Women should be informed that there is no scientific evidence regarding the beneficial effects of immediate (<1 h) or delayed administration of oxytocin, although the first option may reduce the duration of labor. A joint decision is recommended, based on clinical judgment, and women's values and preferences. 3) A low-dose oxytocin regimen for labor augmentation should be considered. 4) Amniotomy should be considered before the administration of oxytocin infusion during the first stage of spontaneous labor. 5) Oxytocin augmentation for at least four hours with adequate uterine contractions should be considered, before an operative delivery is proposed, provided that fetal and maternal conditions are adequate.

• MeSH
• Amniotomy MeSH
• Dystocia * therapy   diagnosis   MeSH
• Obstetric Labor Complications * therapy   diagnosis   MeSH
• Humans MeSH
• Oxytocin administration & dosage   MeSH
• Parity MeSH
• Labor, Obstetric MeSH
• Pregnancy MeSH
• Oxytocics administration & dosage   MeSH
• Delivery, Obstetric MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH

BACKGROUND: Bordetella pertussis isolates which do not express some of acellular pertussis vaccine (aPv) antigens, e.g. pertactin (PRN), have been increasingly reported in countries using aPvs. In Finland, primary pertussis vaccination with whole-cell vaccine was replaced by aPv containing pertussis toxin (PT) and filamentous hemagglutinin (FHA) in 2005 and then by aPv containing PT, FHA, and PRN in 2009. We aimed to study alterations in the expression of FHA, PRN, and PT, three antigens included in aPvs and adenylate cyclase toxin (ACT) not included in current aPvs, among Finnish isolates collected during 1991-2020. METHODS: Of 904 isolates collected by the Finnish Reference Laboratory for Pertussis during 1991-2020, 302 were randomly included. An adapted, monoclonal antibody based, antigen expression ELISA, including the culture of B. pertussis in Stainer-Scholte medium, was performed to quantify the expression of ACT, FHA, PRN, and PT of each isolate. ACT activity was also measured for 16 isolates. Arbitrary units were used for comparing levels of each antigen expression of isolates grouped in every five years. FINDINGS: Following the implementation of aPv in 2005, B. pertussis isolates exhibited a 1.75-fold increase for FHA (p < 0.001) and a 1.5-fold increase for ACT (p < 0.0041) expression until 2020. No FHA or ACT deficient isolates were detected. As the number of PRN deficient isolates has significantly increased with the time, the amount of PRN produced by the positive isolates has also started to decrease, especially after the use of aPv containing PRN. During this period, fluctuations in PT expression were observed. INTERPRETATION: The study demonstrated that in response to aPv-induced selection pressure, different types of selection of B. pertussis has occurred. For FHA and ACT, a steady increase in their production is observed, whereas the frequency of PRN deficient isolates is increased with time.

• MeSH
• Vaccines, Acellular immunology   MeSH
• Adenylate Cyclase Toxin immunology   MeSH
• Antigens, Bacterial * immunology   MeSH
• Adhesins, Bacterial MeSH
• Bordetella pertussis * immunology   isolation & purification   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Virulence Factors, Bordetella immunology   MeSH
• Humans MeSH
• Whooping Cough * prevention & control   immunology   microbiology   MeSH
• Pertussis Vaccine * immunology   administration & dosage   MeSH
• Pertussis Toxin immunology   MeSH
• Bacterial Outer Membrane Proteins immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Finland MeSH

BACKGROUND: Cancer patients are particularly vulnerable during the COVID-19 pandemic. Vaccinations are essential in controlling the pandemic. However, due to their exclusion from clinical trials for COVID-19 vaccines, there is limited data on the vaccines' effectiveness and safety for this group. OBJECTIVES: We evaluated humoral (anti-S antibody) and cellular (T-cell) immune response in patients with solid cancer on systemic anticancer treatment versus healthy controls prime-vaccinated by the BNT162b2 COVID-19 mRNA vaccine. METHODS: CoVigi was the phase IV prospective open-label non-randomized multicentric clinical trial evaluating anti-S and anti-N SARS-CoV-2 antibodies and SARS-CoV-2-specific T-cell response by IFN-γ-release assay in several time points during the prime COVID-19 mRNA vaccination (prior to the first vaccine dose, prior to the second dose, at 4-8 weeks, at 3 months, and 6 months after vaccination). Immune response was analyzed in the context of previous SARS-CoV-2 infection and anticancer therapy (chemotherapy (CT) + monoclonal antibodies (mAb), mAb, immune checkpoint inhibitors, tyrosine kinase inhibitors, and curative radiotherapy). RESULTS: Among 204 patients with solid cancer and 73 healthy controls, 65% of SARS-CoV-2-naïve patients with cancer developed anti-S antibodies after the first vaccine dose, rising to 92% after the second dose. By 6 months, all BNT162b2-vaccinated patients with solid cancer developed antibody response. Patients treated with CT showed impaired both humoral and cellular immune response to BNT162b2 vaccination. Antibody levels in SARS-CoV-2-recovered patients were comparable to healthy controls. T-cell response peaked after the second dose of BNT162b2 and was not significantly impaired in solid cancer patients except those treated with CT. CONCLUSION: Immune response to BNT162b2 COVID-19 mRNA vaccine is substantially shaped by pre-vaccination COVID-19 infection. All patients with solid cancer on active anticancer therapy exhibited seroconversion after COVID-19 vaccination, although the extent of both humoral and cell immune response was substantially hampered in those treated by CT. TRIAL REGISTRATION: EudraCT No. 2021-000566-14 (registration date February 17, 2021).

• Publication type
• Journal Article MeSH