- MeSH
- bronchopulmonální dysplazie diagnóza komplikace MeSH
- farmakoterapie klasifikace MeSH
- kardiovaskulární nemoci diagnóza klasifikace patofyziologie MeSH
- kazuistiky jako téma MeSH
- lidé MeSH
- novorozenci extrémně nezralí MeSH
- novorozenec MeSH
- růstová retardace plodu diagnóza MeSH
- šok * diagnóza etiologie farmakoterapie klasifikace MeSH
- terlipresin * farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years. STUDY DESIGN, SIZE, DURATION: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy. LIMITATIONS, REASONS FOR CAUTION: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited. WIDER IMPLICATIONS OF THE FINDINGS: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
- MeSH
- analýza spermatu MeSH
- azoospermie farmakoterapie MeSH
- cyklofosfamid * terapeutické užití MeSH
- dakarbazin terapeutické užití MeSH
- dítě MeSH
- doxorubicin terapeutické užití škodlivé účinky MeSH
- etoposid terapeutické užití aplikace a dávkování MeSH
- folikuly stimulující hormon krev MeSH
- Hodgkinova nemoc * farmakoterapie MeSH
- inhibiny krev MeSH
- lidé MeSH
- mladiství MeSH
- motilita spermií účinky léků MeSH
- oligospermie farmakoterapie MeSH
- počet spermií MeSH
- prednison terapeutické užití aplikace a dávkování MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- vinkristin terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.
- MeSH
- adiponektin metabolismus krev MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus MeSH
- faktor 2 související s NF-E2 metabolismus MeSH
- folikuly stimulující hormon krev MeSH
- GABA metabolismus MeSH
- hormon uvolňující gonadotropiny metabolismus MeSH
- hypothalamus * metabolismus účinky léků patologie MeSH
- inzulinová rezistence MeSH
- krysa rodu rattus MeSH
- leptin krev metabolismus MeSH
- letrozol farmakologie MeSH
- luteinizační hormon krev MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar * MeSH
- pyroptóza * účinky léků MeSH
- syndrom polycystických ovarií * chemicky indukované metabolismus farmakoterapie patologie MeSH
- testosteron krev MeSH
- triglyceridy krev metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
V tomto článku sa venujeme endokrinne sprostredkovanej osteoporóze spôsobenej poruchami sekrécie rastového hormónu (RH); nedostatku rastového hormónu u dospelých a akromegálii. RH a inzulínu podobný rastový faktor-1 (IGF-1) stimulujú lineárny rast kostí prostredníctvom komplexných hormonálnych interakcií a aktivujú epifýzové prechondrocyty. GH prostredníctvom receptorového aktivátora jadrového faktora-kappaB (RANK), jeho ligandu (RANK-L) a osteoprotegerínového systému stimuluje produkciu osteoprotegerínu a jeho akumuláciu v kostnej matrici. Nesprávna funkcia tohto mechanizmu môže viesť k špecifickému poškodeniu kostí. Primárnym problémom kostného postihnutia pri poruchách sekrécie rastového hormónu je riziko osteoporotických fraktúr, preto je dôležité posúdiť kvalitu kosti, ktorá lepšie odráža skutočnú predispozíciu pacienta na fraktúru. Metódou odhadu kvality kostí z DXA skenov bedrovej chrbtice je trabekulárne kostné skóre (TBS). Pri akromegálii TBS lepšie definuje riziko zlomeniny, pretože BMD je normálna alebo dokonca zvýšená. TBS pomáha sledovať efekt liečby rastovým hormónom a vitamínom D. Napriek týmto zisteniam by sa TBS nemal používať samostatne, ale je potrebné komplexné zváženie všetkých rizikových faktorov zlomenín, BMD a markerov kostného obratu.
In this article, we address endocrine-mediated osteoporosis caused by disorders of growth hormone (GH) secretion; growth hormone deficiency in adults and acromegaly. GH and insulin-like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activate epiphyseal prechondrocytes. GH stimulates the production of osteoprotegerin and its accumulation in the bone matrix through the receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L) and the osteoprotegerin system. Incorrect function of this mechanism can lead to specific bone damage. The primary problem of bone involvement in disorders of GH secretion is the risk of osteoporotic fractures, so it is important to assess the quality of the bone, which better reflects the actual predisposition of the patient to fracture. The method for estimating bone quality from DXA scans of the lumbar spine is the trabecular bone score (TBS). In acromegaly, TBS better defines fracture risk because BMD is normal or even elevated. TBS helps to monitor the effect of treatment with growth hormone and vitamin D. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and markers of bone turnover is required.
- Klíčová slova
- trabekulární kostní skóre,
- MeSH
- absorpční fotometrie metody MeSH
- akromegalie diagnóza komplikace MeSH
- insulinu podobný růstový faktor I nedostatek MeSH
- kostní denzita * účinky léků MeSH
- lidé MeSH
- osteoporotické fraktury etiologie prevence a kontrola MeSH
- osteoporóza etiologie MeSH
- růstový hormon * nedostatek terapeutické užití MeSH
- vitamin D terapeutické užití MeSH
- Check Tag
- lidé MeSH
INTRODUCTION: The SALL4 gene encodes a transcription factor that is essential for early embryonic cellular differentiation of the epiblast and primitive endoderm. It is required for the development of neural tissue, kidney, heart, and limbs. Pathogenic SALL4 variants cause Duane-radial ray syndrome (Okihiro syndrome), acro-renal-ocular syndrome, and Holt-Oram syndrome. We report a family with vertical transmission of a SALL4 pathogenic variant leading to radial hypoplasia and kidney dystopia in several generations with additional growth hormone deficiency (GHD) in the proband. CASE PRESENTATION: Our male proband was born at the 39th week of gestation. He was born small for gestational age (SGA; birth weight 2,550 g, -2.2 SDS; length 47 cm, -2.0 SDS). He had bilateral asymmetrical radial ray malformation (consisting of radial hypoplasia, ulnar flexure, and bilateral aplasia of the thumb) and pelvic kidney dystopia, but no cardiac malformations, clubfoot, ocular coloboma, or Duane anomaly. He was examined for progressive short stature at the age of 3.9 years, where his IGF-1 was 68 μg/L (-1.0 SD), and growth hormone (GH) after stimulation 6.2 μg/L. Other pituitary hormones were normal. A brain CT revealed normal morphology of the cerebral midline and the pituitary. He had a dental anomaly - a central mandibular ectopic canine. MRI could not be done due to the presence of metal after multiple corrective plastic surgeries of his hands. His mother's and father's heights are 152.3 cm (-2.4 SD) and 177.8 cm (-0.4 SD), respectively. His father has a milder malformation of the forearm. The affected paternal grandfather (height 164 cm; -2.3 SD) has a radial ray defect with missing opposition of the thumb. The family reports a similar phenotype of radial dysplasia in the paternal grandfather's mother. The proband started GH therapy at age 6.5 years when his height was 109 cm (-2.8 SDS) and he experienced catch-up growth as expected in GHD. Puberty started spontaneously at the age of 12.5 years. At age 13, his height was 158.7 cm (-0.2 SDS). Whole-exome sequencing revealed a nonsense variant in the SALL4 gene c.1717C>T (p.Arg573Ter) in the proband, his father, and paternal grandfather. CONCLUSION: This is the first observation of a patient with a congenital upper limb defect due to a pathogenic SALL4 variant who has isolated GHD with no apparent cerebral or facial midline anomaly and has been successfully treated with growth hormone.
- MeSH
- dospělí MeSH
- Duaneův retrakční syndrom * genetika patologie MeSH
- fenotyp MeSH
- horní končetina patologie MeSH
- hypopituitarismus * genetika MeSH
- ledviny patologie MeSH
- lidé MeSH
- lidský růstový hormon * MeSH
- předškolní dítě MeSH
- transkripční faktory genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- kazuistiky MeSH
Jodové zásobení těhotných a kojících žen je klíčové pro zdraví plodu a novorozence, zejména pro správnou funkci štítné žlázy. Nedostatečná jodová saturace může vést k závažným následkům, včetně trvalého poškození zdraví dítěte. V České republice využíváme pro monitoring jodového zásobení novorozenců neonatální TSH získané v rámci celoplošného novorozeneckého screeningu kongenitální hypotyreózy. Výsledky monitoringu byly až do nedávné doby příznivé (do roku 2018 v Čechách a do roku 2022 na Moravě), nicméně v posledních letech se zvyšuje procentuální zastoupení novorozenců se zvýšeným TSH, což naznačuje prohlubující se jodový deficit této křehké populace. Jednou z příčin může být nedostatečná jodová suplementace těhotných žen nad rámec běžného alimentárního příjmu (tj. 150–200 μg jodu denně) a snížení konzumace mléka, mléčných produktů, vajec a soli s jodem. Česká republika se nyní opět musí zaměřit na tuto rizikovou populaci stran prohlubujícího se jodového deficitu. Důležité je zaměřit se především na osvětové aktivity a zajistit adekvátní suplementaci jodu již v období těhotenství.
The iodine supply of pregnant and lactating women is crucial for the health of the fetus and newborn, especially for the proper function of the thyroid gland. Inadequate iodine saturation can lead to serious consequences, including permanent health damage to the child. In the Czech Republic, we use neonatal TSH obtained within the Nationwide Newborn Screening Program for Congenital Hypothyroidism to monitor the iodine supply of newborns. The monitoring results were favorable until recently (until 2018 in Bohemia and until 2022 in Moravia); however, in recent years, there has been an increase in the percentage of newborns with elevated TSH, indicating a deepening iodine deficiency in this vulnerable population. One of the reasons may be inadequate iodine supplementation of pregnant women beyond the normal dietary intake (i.e., 150–200 μg of iodine per day) and a decrease in the consumption of dairy, eggs and iodized salt. The Czech Republic must now focus again on this at-risk population regarding the deepening iodine deficiency. It is important to focus primarily on educational activities and ensure adequate iodine supplementation during pregnancy.
- MeSH
- jod * metabolismus nedostatek terapeutické užití MeSH
- kongenitální hypotyreóza diagnóza etiologie MeSH
- lidé MeSH
- novorozenec MeSH
- novorozenecký screening MeSH
- těhotenství MeSH
- thyreotropin krev MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
Desmopresin acetát je syntetickým analogem antidiuretického hormonu. Jeho indikací je léčba centrálního diabetu insipidu, primární enuresis nocturna u pacientů starších pěti let s normální koncentrační schopností ledvin a terapie nykturie dospělých. Bezpečnost a účinnost léčiva jsou dlouhodobě známy, což prokazuje i jeho zařazení do aktuálních doporučených postupů.
Desmopressin acetate is a synthetic analogue of anti‐diuretic hormone. It is indicated in central diabetes insipidus, primary nocturnal enuresis in patients older than 5 years of age with normal kidney concentrating ability, and in nycturia affecting adults. The safety and effectiveness of this drug have been known for a long time, which is reflected by its position in the current guidelines.
- MeSH
- antidiuretika farmakologie terapeutické užití MeSH
- centrální diabetes insipidus diagnóza farmakoterapie MeSH
- desmopresin * aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé MeSH
- nežádoucí účinky léčiv klasifikace MeSH
- noční enuréza farmakoterapie MeSH
- nykturie farmakoterapie MeSH
- těhotné ženy MeSH
- vasopresiny agonisté terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- lidé MeSH
- nemoci štítné žlázy diagnóza MeSH
- thyreotropin * analýza MeSH
- virové nemoci MeSH
- Check Tag
- lidé MeSH
Obavy pacientů z vyšetření a ošetření jsou nedílnou součástí praxe většiny nejen zubních lékařů. Se strachem z ošetření zubním lékařem se potýká až 75 % vyspělé populace. Nepřekonatelným strachem (odontofobií) se všemi sociálními, zdravotními a ekonomickými důsledky zanedbané zubní péče pak trpí kolem 10 % lidí. Toto sdělení přibližuje možnosti léčby dentální fobie. Prvním předpokladem pro zdárné ošetření je podání lokální anestezie. Mírnější formy odontofobie můžeme zvládnout pomocí nefarmakologických metod, jako jsou vlídné vystupování, odvedení pozornosti, vhodné přístrojové vybavení apod. Těžší případy navíc řešíme pomocí farmakoterapie; například je možno použít benzodiazepiny, oxid dusný, dle moderních postupů i oxytocin.
Patients ́ fear of examination and treatment is an integral part of the most physicians ́ routine not only a dentist ́s one. Up to 75% of the population are afraid of being treated by a dentist. About 10% of people suffer from an overwhelming fear (odontophobia) with all the social, health and economical consequences of a neglected dental care. This review article offers an overview of the treatment options of dental phobia. The first prerequisite for a successful treatment is the application of local anesthesia. Milder forms of odontophobia can be managed with non-pharmacological methods, such as a gentle attitude, diversion of attention, and appropriate technical equipment. In addition, more difficult cases are controlled with pharmacotherapy; for example, it is possible to use benzodiazepines, nitrous oxide, and according to modern guidelines, even oxytocin.
