NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients

AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.

Bioengineered dermal substitutes for periocular defects

Bioengineered materials are used as a substitute in many fields of medicine,especially in plastic surgery and in burns.In ophthalmic plastic surgery they can be used for covering large tissue defects or as a tarsal plate substitute,in cases when it is not possible to use conventional surgical techniques.We have searched PubMed and Web of Science scientific databases.We can generally categorize skin substitutes by the type of tissue used-we distinguish autografts,allografts,and xenografts.There are also completely synthetic substitutes.The aim of our article was to summarize the current state of knowledge and to sum up all the clinical applications of bioengineered materials in the periocular region.There are only a few scientific articles about this topic and lack of prospective randomized studies aimed on use of bioengineered materials in periocular region.Nevertheless,there are many articles describing successful case reports or case reports series.According to literature,bioengineered materials are the most commonly used in big traumas or large surgical defects,especially in oculoplastic tumour surgery.Bioengineered dermal substitutes are not frequently used in the periocular region.Dermal substitutes are useful,when it is not possible to close the defect with any other conventional surgical technique.

Molecular biology of pancreatic cancer

In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syn- dromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancre- atic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations （somatic point mutations and allelic losses） affect onco- genes and tumor-suppressor genes within RAS, AK-I- and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle （SMAD/DPC, CDKN2A/p16） and apoptosis （TP53）. Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer

AIM： To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS： Endoscopic ultrasound （EUS）-guided fine needle aspiration cytology （FNA） was performed on 101 consecutive patients （63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis） with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis （CGCE） and single-strand conformation polymorphism （SSCP） techniques. In addition, allelic losses of tumor suppressor genes p16 （INK4, CDKN2A） and DPC4 （MADH4, SMAD4） were detected by monitoring the loss of heterozygosity （LOH） at 9p and 18q, respectively. RESULTS： Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations （P 〈 0.001）, 24% and 90% for p53 mutations （NS）, 13% and 100% for p16 mutations （NS）, 85% and 64% for aUelic losses at 9p （P 〈 0.001） and 78% and 57% for allelic losses at 18q （P 〈 0.05）. When tests for different molecular markers were combined, the best results were obtained with K-ras ＋ LOH at 9p （92% and 64%, P 〈 0.001）, K-ras ＋ LOH at 18q （92% and 57%, P 〈 0.001）, and K-ras ＋ LOH 9q ＋ LOH 18q （96% and 43%, P 〈 0.001）. When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION： EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.

Promising new treatment targets in patients with fibrosing lung disorders

The processes of lung fibrogenesis and fibrotic healing are common to a number of conditions with different etiologies. The lungs are the only affected organ in some cases, whereas in others, several organ systems are involved. Therapeutic options can be discussed from various perspectives. In this review, we address the localization of therapeutic targets with regard to cell compartments, including secreted ligands, cell surface, plasma membrane-cytosol interplay, cytosol and nucleus. Complex approach using stem cell therapy is also discussed. As the prognosis of patients with these disorders remains grim, treatment combinations targeting different molecules within the cell should sometimes be considered. It is reasonable to assume that blocking specific pathways will more likely lead to disease stabilization, while stem cell-based treatments could potentially restore lung architecture. Gene therapy could be a candidate for preventive care in families with proven specific gene polymorphisms and documented familial lung fibrosis. Chronobiology, that takes into account effect of circadian rhythm on cell biology, has demonstrated that timed drug administration can improve treatment outcomes. However, the specificrecommendations for optimal approaches are still under debate. A multifaceted approach to interstitial lung disorders, including cooperation between those doing basic research and clinical doctors as well as tailoring research and treatment strategies toward(until now) unmet medical needs, could improve our understanding of the diseases and, above all, provide benefits for our patients.

Treatment of congenital ptosis

Congenital ptosis is an abnormally low position of the upper eyelid,with respect to the visual axis in the primary gaze.It can be present at birth or manifest itself during the first year of life and can be bilateral or unilateral.Additionally,it may be an isolated finding or part of a constellation of signs of a specific syndrome or systemic associations.Depending on how much it interferes with the visual axis,it may be considered as a functional or a cosmetic condition.In childhood,functional ptosis can lead to deprivation amblyopia and astigmatism and needs to be treated.However,even mild ptosis with normal vision can lead to psychosocial problems and correction is also advised,albeit on a less urgent basis.Although,patching and glasses can be prescribed to treat the amblyopia,the mainstay of management is surgical.There are several types of surgical procedure available depending on the severity and etiology of the droopy eyelid.The first part of this paper will review the different categories of congenital ptosis,including more common associated syndromes.The latter part will briefly cover the different surgical approaches,with emphasis on how to choose the correct condition.In spite of many complex factors inherent to the treatment of congenital ptosis,the overall outcomes are quite satisfactory,and most surgeons feel that ptosis management can be both challenging and rewarding at the same time.

比较子宫肌瘤栓塞术与肌瘤切除术在欲保留生育能力妇女的疗效差异:一项随机对照试验的初步结果

Objective: To compare the clinical results of surgical and endovascular treatment of uterine myomas in young women. Study design: In a university-affiliated, tertiary care center a prospective trial was conducted. Sixty-three women, wishing to retain fertility, with intramural fibroid(s) larger than 4 cm, were randomly selected either for uterine artery embolization or myomectomy. Invasiveness, efficacy, and complications of both procedures were compared. Results: Thirty embolizations and 33 myomectomies (15 laparoscopic, 18 open) were performed. The mean follow-up was 17 months. In embolized patients, there was a significantly shorter procedure length (p < 0.0001), hospital stay (p < 0.001) and disability period (p < 0.0001), lower CRP (p < 0.001) and higher hemoglobin (p < 0.0001) concentrations the 2nd day after procedure. But there was a higher incidence of reinterventions (p < 0.01) and a lower rate of total symptomatic relief (p < 0.1). The groups did not significantly differ in: technical success rate, febrile morbidity, FSH levels 6 months after the procedure, and complication rates. Conclusions: Although the reproductive outcomes of uterine artery embolization and myomectomy cannot be evaluated at the moment, our first results indicate that both methods are clinically successful in the majority of cases and are not connected with significant number of serious complications.