Crohn's disease is a chronic immune-mediated intestinal inflammation targeted against a yet incompletely defined subset of commensal gut microbiota and occurs on the background of a genetic predisposition under the influence of environmental factors. Genome-wide association studies have identified about 70 genetic risk loci associated with Crohn's disease. The greatest risk for Crohn's disease represent polymorphisms affecting the CARD15 gene encoding nucleotide-binding oligomerization domain 2 (NOD2) which is an intracellular sensor for muramyl dipeptide, a peptidoglycan constituent of bacterial cell wall. The accumulated evidence suggests that gut microbiota represent an essential, perhaps a central factor in the induction and maintaining of Crohn's disease where dysregulation of normal co-evolved homeostatic relationships between intestinal microbiota and host mucosal immune system leads to intestinal inflammation. Taken together, these findings identify Crohn's disease as a syndrome of overlapping phenotypes that involves variable influences of genetic and environmental factors. A deeper understanding of different genetic abnormalities underlying Crohn's disease together with the identification of beneficial and harmful components of gut microbiota and their interactions are essential conditions for the categorization of Crohn's disease patients, which enable us to design more effective, preferably causative, individually tailored therapy. and L. Hrnčířová, J. Krejsek, I. Šplíchal, T. Hrnčíř
Denosumab is a human monoclonal antibody representing a novel therapy of osteoporosis. Contrary to always other antiosteoporotic drugs, it is not contraindicated in advanced chronic kidney disease, as its pharmacokinetic does not differ from patients with normal kidney function. However, published case reports in chronic kidney disease (CKD) patients stopped the therapy after single dose because of hypocalcemia. We present a case of successful treatment of osteoporosis in a young hemodialysis patient with repeated denosumab doses. and Sylvie Dusilová Sulková, Jiří Horáček, Roman Šafránek, Petr Gorun, Ondřej Viklický, Vladimír Palička
Ovarian cancer is the fifth most common malignancy in the world's female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits. and O. Kubeček, M. Bláha, D. Diaz-Garcia, S. Filip
Diagnosis of nerve agent intoxication is based on anamnestic data, clinical signs and laboratory examination. For acute poisoning, cholinesterase activity in the blood (erythrocyte AChE, plasma/serum BuChE) is sensitive, simple and most frequent laboratory examination performed in biochemical laboratories. Specialized examinations to precise treatment (reactivation test) or to make retrospective diagnosis (fluoride induced reactivation etc.) can be conducted. Other sophisticated methods are available, too. and J. Bajgar
Low-grade myofibroblastic sarcoma (LGMS) is a very rare, atypical myofibroblastic tumor with fibromatosis-like features with predilection mostly in head and neck region. LGMS occurs primarily in adult patients with a slight male predominance. Only few cases of LGMS affecting the larynx have been reported in literature to this date. We describe a case of low-grade myofibroblastic sarcoma of the larynx in a 40-year-old male patient. The clinicopathological characteristics, immunohistochemical findings and treatment are discussed. and P. Kordač, D. H. Nikolov, K. Smatanová, D. Kalfeřt
High grade gliomas are some of the deadliest human tumours. Conventional treatments such as surgery, radiotherapy and chemotherapy have only a limited effect. Nowadays, resection is the common treatment of choice and although new approaches, such as perioperative magnetic resonance imaging or fluorescent microscopy have been developed, the survival rate of diagnosed patients is still very low. The inefficacy of conventional methods has led to the development of new strategies and the significant progress of nanotechnology in recent years. These platforms can be used either as novel imaging tools or to improve anticancer drug delivery into tumours while minimizing its distribution and toxicity in healthy tissues. Amongst the new nanotechnology platforms used for delivery into the brain tissue are: polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of small molecular weight drugs as well as macromolecules - proteins, peptides and genes. The unique properties of these nanoparticles, such as surface charge, particle size, composition and ability to modify their surface with tissue recognition ligands and antibodies, improve their biodistribution and pharmacokinetics. All of the above mentioned characteristics make of nanoplatforms a very suitable tool for its use in targeted, personalized medicine, where they could possibly carry large doses of therapeutic agents specifically into malignant cells while avoiding healthy cells. This review poses new possibilities in the large field of nanotechnology with special interest in the treatment of high grade brain tumours. and P. Krůpa, S. Řehák, D. Diaz-Garcia, S. Filip
The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit. and A. Paulík, J. Grim, S. Filip
Interventions of paediatric obstructive sleep apnea syndrome are complex, varied and multidisciplinary. The goal of the treatment is to restore optimal breathing during the night and to relieve associated symptoms. Evidence suggests that the surgical intervention with removal of the tonsils and adenoids will lead to significant improvements in the most incomplicated cases, as recently reported from a meta-analysis. However, post-operative persistence of this syndrome in paediatric population is more frequent than expected, which supports the idea of the complexity of this syndrome. Adenotomy alone may not be sufficient in children with OSAS, because it does not address oropharyngeal obstruction secondary to tonsillar hyperplasia. Continuous positive airway pressure can effectively treat this syndrome in selected groups of children, improving both nocturnal and daytime symptoms, but poor adherence is a limiting factor. For this reason, CPAP is not recommended as first-line therapy for OSAS when adenotonsillectomy is an option. It is now being investigated the incorporation of nonsurgical approaches for milder forms and for residual OSAS after surgical intervention. Althought adeno-tonsillar hypertrophy is the most common for OSAS in children; obesity is emerging as an equally important etiological factor. Therefore an intensive weight reduction program and adequate sleep hygiene are also important lifestyle changes that may be very effective in mitigating the symptoms of this syndrome. Pharmacological therapy (leukotriene antagonists, topical nasal steroids) is usually use for mild forms of OSAS and in children with associated allergic diseases. Special orthodontic treatment and oropharyngeal exercises are a relatively new and promising alternative therapeutic modality used in selected groups of children with OSAS. and A. Šujanská, P. Ďurdík, J. Rabasco, O. Vitelli, N. Pietropaoli, M. P. Villa
Charcot foot neuropathic osteoarthropathy is a disorder affecting the soft tissues, joints, and bones of the foot and ankle. The disease is triggered in a susceptible individual through a process of uncontrolled inflammation leading to osteolysis, progressive fractures and articular malpositioning due to joint subluxations and dislocations. The progression of the chronic deformity with a collapsed plantar arch leads to plantar ulcerations because of increased pressure on the plantar osseous prominences and decreased plantar sensation. Subsequent deep soft tissue infection and osteomyelitis may result in amputation. The Charcot foot in diabetes represents an important diagnostic and therapeutic challenge in clinical practice. Conservative treatment remains the standard of the care for most patients with neuropathic disorder. Offloading the foot and immobilization based on individual merit are essential and are the most important recommendations in the active acute stage of the Charcot foot. Surgical realignment with stabilization is recommended in severe progressive neuropathic deformities consisting of a collapsed plantar arch with a rocker-bottom foot deformity. and P. Sponer, T. Kucera, J. Brtková, J. Srot
Gastrointestinal lipomas are usually asymptomatic, detected incidentally. However, they can cause severe symptoms such as obstruction, invagination, and bleeding. The transsection of an infarcted or large lipoma by needle sphincterotome (needle knife) and/or snare polypectomy of the upper part of the tumour is an option for the endoscopy treatment of giant infarcted lipomas. Cutting a top of lipoma (unroofing technique) allowed flow out of adipose tissue from the lipoma. and M. Kopáčová, S. Rejchrt, J. Bureš