Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Therapeutic regimens for the treatment of toxoplasmosis are not standardized. Treatment strategy mainly at the end of the second and the beginning of the third trimester, especially in cases of negative prenatal diagnosis, is the least uniform. In some situations, the choice of treatment may be ambiguous, and adverse drug reactions of the therapy should be taken into consideration. METHODS: Adverse drug reactions of anti-toxoplasma therapy with spiramycin (n = 77) versus pyrimethamine/sulfadiazine (n = 35) were compared in 112 pregnant women. RESULTS: Up to 36.6% of women reported adverse reactions to the treatment overall (n = 41). Out of those 38.9% (n = 30) were treated with spiramycin and 31.4% (n = 11) with pyrimethamine/sulfadiazine. Toxic allergic reactions were the only indication for discontinuation of treatment in 8.9% of patients (n = 10), where 9.1% (n = 7) were reported in spiramycin and 8.6% (n = 3) in pyrimethamine/sulfadiazine cohort. Neurotoxic complications (acral paraesthesia) were significantly more frequent during the therapy with spiramycine in 19.5% (n = 15) compared to no cases in pyrimethamine/sulfadiazine group (p = .003). Other adverse drug reactions, such as gastrointestinal discomfort, nephrotoxicity, vaginal discomfort were reported, but the differences between the cohorts were not significant. CONCLUSIONS: The superiority of one of the therapeutic regimens was not statistically demonstrated, since the differences in overall toxicity or incidence of toxic allergic reactions between the cohorts were not confirmed (p = .53 and p = 1.00, respectively). However, although the isolated neurotoxicity of spiramycin was the only significant adverse reaction demonstrated in this study, pyrimethamine/sulfadiazine therapy should be preferred, because it is known to be more effective and with limited adverse reactions.
- MeSH
- alergie * farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- kongenitální toxoplazmóza * farmakoterapie MeSH
- lidé MeSH
- nežádoucí účinky léčiv * MeSH
- plod MeSH
- pyrimethamin škodlivé účinky MeSH
- spiramycin * škodlivé účinky MeSH
- sulfadiazin škodlivé účinky MeSH
- těhotenství MeSH
- toxoplazmóza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions ́ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.
- MeSH
- epidurální analgezie * MeSH
- kolorektální nádory * chirurgie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- morfin MeSH
- multicentrické studie jako téma MeSH
- nádorové cirkulující buňky * MeSH
- opioidní analgetika terapeutické užití MeSH
- prospektivní studie MeSH
- randomizované kontrolované studie jako téma MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- protokol klinické studie MeSH
Nákaza virem SARS-CoV-2 probíhá ve většině případů asymptomaticky nebo jen s mírnými respiračními příznaky. U pacientů s rizikovými faktory, mezi které patří zejména vysoký věk, obezita, kardiovaskulární choroby a imunosuprese, může dojít v důsledku rozvoje cytokinové bouře k závažnému průběhu onemocnění. COVID-19 je spojován se zvýšeným rizikem krvácivých a tromboembolických komplikací. Mezi nejčastější místa krvácení patří gastrointestinální trakt a CNS. Jednou z příčin ruptury cévní stěny a následného krvácení při COVID-19 může být dysfunkce poškozeného endotelu. Virové infekce jsou jedny z nejsilnějších spouštěčů autoimunitních onemocnění. Jednou z možných příčin hemoragické CMP je virem indukovaná akutní vaskulitida.
Most cases of SARS-CoV-2 infection are asymptomatic or have only mild respiratory symptoms. Patients with risk factors, including but not limited to advanced age, obesity, cardiovascular disease and immunosuppression, may develop a severe course of disease due to the development of a cytokine storm. COVID-19 is associated with an increased risk of bleeding and thromboembolic complications, with the gastrointestinal tract and CNS being among the most frequent sites of bleeding. One of the causes of vessel wall rupture and subsequent bleeding in COVID-19 may be dysfunction of the damaged endothelium. Viral infections are one of the most potent triggers of autoimmune diseases. One of the possible causes of haemorrhagic CMP is virus-induced acute vasculitis.
- MeSH
- autoimunitní nemoci etiologie MeSH
- cerebrální krvácení etiologie MeSH
- cévní mozková příhoda * diagnóza etiologie terapie MeSH
- COVID-19 * komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- vaskulitida etiologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
BACKGROUND: The diagnosis of SARS-CoV-2 is almost exclusively performed by PCR or antigen detection. The detection of specific antibodies has not yet been considered in official diagnostic guidelines as major laboratory evidence for a case definition. The aim the present study is to analyze antibody responses in outpatient and inpatient cohorts of COVID-19 patients in the Czech Republic over a 12-month period, and assess the potential of antibodies as a diagnostic tool. METHODS: A total of 644 patients was enrolled in the prospective study. IgA, IgM and IgG antibody levels, as well as virus neutralization titers, were analyzed over a 12-month period. RESULTS: Our study showed low antibody positivity levels at the admission. However, at 2 weeks after infection, 98.75% and 95.00% of hospitalized patients were IgA and IgG positive, respectively. Even in the outpatient cohort characterized by milder disease courses, the IgG antibody response was still sustained at 9 and 12 months. The data show a high correlation between the IgG levels and virus neutralization titers (VNTs). Samples from later time-points showed positive antibody responses after vaccination in both cohorts characterized by high IgG levels and VNT over 1:640. The samples from unvaccinated persons indicated a relatively high level of reinfection at 6.87%. CONCLUSIONS: Our results show that the detection of antibodies against the SARS-CoV-2 shows an increasing sensitivity from week 2 after infection and remains highly positive over the 12-month period. The levels of IgG antibodies correlate significantly with the VNTs. This suggests that the serological data may be a valuable tool in the diagnosis of SARS-CoV-2 infection.
- MeSH
- COVID-19 * diagnóza epidemiologie MeSH
- lidé MeSH
- prospektivní studie MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- tvorba protilátek * MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival of only 21%. Reliable prognostic and/or predictive biomarkers are needed to improve NSCLC patient stratification, particularly in curative disease stages. Since the endogenous cannabinoid system is involved in both carcinogenesis and anticancer immune defense, we hypothesized that tumor tissue expression of cannabinoid 1 and 2 receptors (CB1 and CB2) may affect survival. METHODS: Tumor tissue samples collected from 100 NSCLC patients undergoing radical surgery were analyzed for CB1 and CB2 gene and protein expression using the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The gene and protein expression data were correlated with disease stage, histology, tumor grading, application of chemotherapy, and survival. Additional paired tumor and normal tissue samples of 10 NSCLC patients were analyzed independently for comparative analysis of CB1 and CB2 gene expression. RESULTS: Patients with tumors expressing the CB2 gene had significantly longer overall survival (OS) (P<0.001), cancer specific survival (CSS) (P=0.002), and disease-free survival (DFS) (P<0.001). They also presented with fewer lymph node metastases at the time of surgery (P=0.011). A multivariate analysis identified CB2 tumor tissue gene expression as a positive prognostic factor for CSS [hazard ratio (HR) =0.274; P=0.013] and DFS (HR =0.322; P=0.009), and increased CSS. High CB2 gene and protein expression were detected in 79.6% and 31.5% of the tested tumor tissue samples, respectively. Neither CB1 gene nor CB1 or CB2 protein expression affected survival. When comparing paired tumor and tumor-free lung tissue samples, we observed reduced CB1 (P=0.008) and CB1 (P=0.056) gene expression in tumor tissues. CONCLUSIONS: In NSCLC patients undergoing radical surgery, expression of the CB1 and CB2 receptor genes is significantly decreased in neoplastic versus tumor-free lung tissue. CB2 tumor tissue gene expression is strongly associated with longer survival (OS, CSS, DFS) and fewer lymph node metastases at the time of surgery. More studies are needed to evaluate its role as a biomarker in NSCLC and to investigate the potential use of CB2 modulators to treat or prevent lung cancers.
- Publikační typ
- časopisecké články MeSH
Pandemie COVID-19 zasáhla v roce 2020 celý svět. Na konci dubna 2021 podle Světové zdravotnické organizace (WHO) prodělalo na celém světě COVID-19 140 332 386 lidí, z toho je evidováno 3 004 088 úmrtí. Je proto předmětem intenzivních výzkumů nejen v oblasti medicíny, ale vzhledem k významnému ovlivnění života protiepidemickými opatřeními se na toto téma diskutuje i z pohledu vzdělávání, ekonomiky a mezi širokou laickou veřejností. Původcem onemocnění je koronavirus SARS-CoV-2, který je zařazen do čeledi Coronaviridae a patří k dalším šesti dosud objeveným koronavirům, které způsobují také respirační onemocnění lidí. Asociace mezi virovými onemocněními a autoimunitními chorobami je dobře známá, přestože přesné mechanismy zatím zůstávají nejasné. V literatuře se začínají objevovat práce, které dokumentují vznik autoimunitního onemocnění i v důsledku nákazy SARS-CoV-2. Mimo neurologických a revmatologických komplikací jsou hlášeny i případy nově diagnostikovaného diabetes mellitus 1. typu. Ve Fakultní nemocnici v Hradci Králové jsme v letech 2020 a 2021 zaznamenali celkem 4 mladé pacienty, u nichž byl nově zjištěn diabetes. Podíl COVID-19 na vzniku diabetu je vzhledem ke klinické souslednosti možný.
The COVID-19 pandemic in 2020 affected the whole world. According to the World Health Organization (WHO), more than 140 million people worldwide have been infected and over 3 million people have died. COVID-19 has affected medicine, education, economics and social life. COVID-19 is caused by the SARS-CoV-2 coronavirus. It belongs to the family Coronaviridae. Six other coronaviruses are known to cause respiratory disease in man. The association between viral diseases and autoimmune diseases is well known, although the exact mechanisms remain unclear. Even the SARS-CoV-2 coronavirus can cause various autoimmune disorders, including type 1 diabetes mellitus. At the University Hospital in Hradec Kralove, we diagnosed new-onset diabetes mellitus in four young patients.
- MeSH
- autoimunitní nemoci epidemiologie virologie MeSH
- COVID-19 imunologie komplikace MeSH
- diabetes mellitus 1. typu * epidemiologie imunologie MeSH
- dítě MeSH
- lidé MeSH
- mladý dospělý MeSH
- SARS-CoV-2 imunologie růst a vývoj účinky léků MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
We stratified post-COVID patients into four newly established clinical groups based on the presence or absence of at least one subjective respiratory symptom and at least one objective sign of pulmonary involvement. Nearly half of outpatients and one third of hospitalized post-COVID patients had objective signs of pulmonary involvement without accompanying subjective respiratory symptoms three months after diagnosis.
- MeSH
- COVID-19 * komplikace epidemiologie patologie MeSH
- hospitalizace MeSH
- lidé MeSH
- plíce patofyziologie MeSH
- prospektivní studie MeSH
- SARS-CoV-2 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
