Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO.

Background: Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods: Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results: NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion: This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.

Incomprehensible treatment of retinoblastoma with high doses of vitamin C.

PURPOSES: To inform about a case of neglected retinoblastoma that was left untreated for more than 3 years by parents. During this time period the local finding worsened from endophytic retinoblastoma group B according IIRC (ABC classification) to extraorbital propagation. BACKGROUND: Retinoblastoma is the most common intraocular tumor in childhood, that occurs approximately in 1 : 15-20 000 births worldwide. In European region cases of extraocular propagation are very infrequent. Extraorbital propagation is extremely rare in middle and high income countries. METHODS: We report the preoperative ophthalmological findings, MRI imaging, treatment methods and postoperative results of this case. RESULTS: After initial dose of six courses of chemotherapy patient underwent surgery (orbital exenteration). In postoperative period patient received two more courses of chemotherapy. In spite of progressed stage of the disease, we obtained good results with our therapy. CONCLUSIONS: We suppose that good treatment results, in spite of extraordinary long lag interval and hopeless pretreatment condition, caused by alternative therapy with high doses vitamin C and no protein intake, were caused by therapeutic naïve retinoblastoma with an absence of RB1 gene mutation (Fig. 6, Ref. 7).

Why is it necessary to examine retina when the patient suffers from aplastic anemia?

PURPOSES: To inform about a case of Revesz syndrome (RS) with initial ophthalmological symptomatology of severe proliferative vitreoretinopathy of the left eye (LE). After the aplastic anemia had developed, RS was established. The exudative retinopathy was successfully treated with photocoagulation on the right eye (RE). BACKGROUND: RS is characterized by fatal bone marrow failure, exudative retinopathy, neuroradiographic abnormalities, neurodevelopmental delay and skin abnormalities. Non-treated exudative retinopathy leads to blindness. METHODS: We report ophthalmological findings as follows: fundus photography and fluorescein angiography (FA) acquired by examinations under general anesthesia in patient with RS. Results of genetic tests helped to establish the diagnosis. RESULTS: Two­year old Caucasian male was examined due to total retinal detachment on LE and signs of chorioretinal scarring on RE. In preoperative screening, thrombocytopenia was detected; later, severe pancytopenia developed. Considering the hematological findings and clinical appearance, we suspected RS, which was confirmed by genetic tests. We found a pathogenic mutation in gene TINF2 (variant c.865C>T;p.Pro289Ser) in a mosaic state with autosomal dominant mode of inheritance. This mutation has not been described in RS yet. Blind LE was enucleated because of dolorous neovascular glaucoma. FA of RE shows excessive areas of capillary nonperfusion with vascular abnormalities and exudation. After the photocoagulation, the visual acuity (VA) on RE remains 0.9 at the age of 7 years. CONCLUSIONS: RS is an extremely rare condition.  The initial symptomatology could be ophthalmological or hematological. The positive finding of TINF2 gene mutation helped in establishing the correct diagnosis. The ischemic retinopathy was successfully treated by photocoagulation (Fig. 6, Ref. 6). Text in PDF www.elis.sk.

Use of Corneal Topography in Pediatric Ophthalmology.

AIM: To introduce the topic of pediatric keratoconus, highlighting the importance of routine corneal topography and tomography in children and adolescents from predisposed groups. To attempt to ensure the early detection of keratoconus and its subclinical form, enabling early treatment, which brings better expected postoperative results.  Material and methods: Using the corneal tomograph Pentacam AXL we examined children and adolescents with astigmatism equal or greater than  2 diopters (in at least one eye) and patients with at least one risk factor such as eye rubbing in the case of allergic pathologies, positive family history of keratoconus or certain forms of retinal dystrophy. In total, we included 231 eyes (116 patients), of which 54 were girls and 62 were boys. RESULTS: The Belin-Ambrósio deviation index parameter was evaluated, in which we classified a total of 41 eyes as subclinical keratoconus and 12 eyes as clinical keratoconus. Next, the corneal maps were evaluated individually, in which we included a total of 15 eyes as subclinical keratoconus and 6 eyes as clinical keratoconus. In our group, compared to the control group, subclinical and clinical keratoconus occurred most often in the group of patients with astigmatism and in the group of so-called "eye rubbers". After individual evaluation, keratoconus occurred more frequently in boys than in girls in our cohort. CONCLUSION: Most patients with keratoconus are diagnosed when there is a deterioration of visual acuity and changes on the anterior surface of  the cornea. Corneal topography and tomography allows us to monitor the initial changes on the posterior surface of the cornea, and helps us to detect the subclinical form of keratoconus and the possibility of its early treatment. Therefore, it is important to determine which groups are at risk and groups in which corneal topography and tomography should be performed routinely.

LATE CHOROIDAL NEOVASCULAR COMPLICATIONS IN A PATIENT TREATED FOR RETINOBLASTOMA. A CASE REPORT.

AIM: Case report of choroidal neovascularization (CNV) detection in patient who was treated for bilateral retinoblastoma in early childhood. MATERIAL AND METHODS: Patient at 1.5 years of age treated for endophytic retinoblastoma stage 4 (according to the Reese-Ellsworth classification) bilaterally, with a positive mutation in the Rb1 gene. After undergoing bilateral retinal laser treatment and 6 cycles of systemic chemotherapy, the tumor remained inactive without other complications. At the age of 14, the boy developed visual impairment in his left eye with metamorphosis. Based on a local finding and other auxiliary examinations, he was diagnosed with CNV in the macular area at the interface of the tumor scar and the healthy retina of the left eye. RESULTS: After three applications of anti-VEGF (antibodies blocking vascular endothelial growth factor) substance intravitreally (bevacizumab 1.2 mg), there was a reduction in CNV and also an improvement in visual function.

[The prevalence of anemia and its impact on hospitalization mortality in patients with acute heart failure]. / Prevalence anémie a vliv na hospitalizacní mortalitu pacientu prijatých pro akutní srdecní selhání.

AIM OF STUDY: To evaluate the influence of entry hemoglobin level on the hospitalization mortality of the patients admitted with AHF caused by 4 major etiologies--acute coronary syndrome with ST elevation (STEMI, n = 325) and without ST elevation (nonSTEMI, n = 210), decompensated chronic ischaemic heart disease (IHD, n = 206) and dilated cardiomyopathy (CMP, n = 88). RESULTS: We analyzed 1,253 consecutive 1st-time hospitalizations of AHF patients of whom 1,212 had their entry hemoglobin known. Out of these, 829 subjects were of STEMI (1), nonSTEMI (2), IHD (3) and CMP (4) etiology and were included in further analyses. We devided these patients into subgroups according to hemoglobin levels: I--no anemia, II--minor and III--severe anemia. The hospitalization mortality in subgroups (I-II-III) of each etiology was 16.9-24.5-35.3% (1); 12.4-9.8-35.7% (2); 9.0-9.7-18.2% (3); 1.5-21.4-33.3% (4); all etiologies together 12.4-15.0-28.8%, total rate 14.1%. Univariate analysis (chi2) showed significant differencies in hospitalization mortality depending on etiology and hemoglobin level but not type of failure (de novo/decompensation). Other parametres (comorbidities, laboratory and hemodynamic values, medication at entry) had a very variable impact on mortality throughout etiologies and hemoglobin subgroups. CONCLUSION: The presence of anemia increases hospitalization mortality of patients with acute heart failure. The relation between hemoglobin level and mortality seems to be linear, we did not observe "U shape" type of relation. It is necessary to distinguish etiologies of AHF as well as consider effects of laboratory and anamnestic variables when interpreting the results.

Recommendations for the Management of Uveitis Associated With Juvenile Idiopathic Arthritis: The Czech and Slovak adaptation of SHARE Initiative.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.

EFFECT OF MULTIPLE VARIABLES ON THE REFRACTIVE ERROR AFTER CATARACT SURGERY.

PURPOSE: To analyze refractive results after cataract surgery in relation to used type of monofocal intraocular lens, calculation formula, to age, gender and laterality. SETTINGS: Department of Ophthalmology, Comenius University and University hospital in Bratislava, Slovakia Methods: We analyzed 173 eyes (118 patients) after uneventful cataract surgery. We calculated prediction error (PE) and mean absolute error (MAE) of postoperative refraction. RESULTS AND CONCLUSION: We found no statistically significant differences in PE and MAE in relation to types of used IOL, calculation formulas, gender, age or laterality. Key words: Optical biometry, monofocal IOL, IOL calculation, refractive error.

Marshall and stickler syndrome in one family.

The authors present the ocular finding in a patient sent to the Department of Paediatric Ophthalmology at the Children's University Hospital - Faculty of Medicine, Comenius University in Bratislava at the age of 3 months, with congenital glaucoma in her right eye and bilateral high myopia. The family anamnesis of the patient shows repeated occurrence of stunted growth, myopia, facial dysmorphia and cataract. The child's mother had high myopia, the mother's brother underwent cataract surgery, the child's grandmother and her sisters and the child's great grandmother had high myopia and glaucoma, and probably underwent cataract surgery at a young age. The child's mother and grandmother underwent a genetic examination, with a conclusion of Marshall syndrome. Within the framework of neonatal screening, poor cortical auditory evoked potential, a defect of the interventricular septum and bifid uvula were diagnosed in the child. With regard to the overall finding in the patient and the genetic family history, we suspected Marshall syndrome. A genetic examination determined Stickler syndrome type 1 with the presence of mutation in the COL2A gene (variant c.2710C >T (p.Arg904Cys,rs121912882)). Due to high intraocular pressure with the impossibility of compensation by medication, bilateral trabuculectomy was performed on the patient. At present the patient has intraocular pressure compensated with adjuvant medicamentous therapy. With regard to high myopia and pronounced degenerative changes on the periphery of the retina in the sense of lattice degeneration, preventive cryopexy of the retinal periphery is planned. A molecular genetic analysis helped diagnose the pathology as Stickler syndrome type 1, which manifested phenotype symptoms of Marshall syndrome or Stickler syndrome type 2. Key words: Marshall syndrome, Stickler syndrome, mid-facial dysmorfism, myopia, glaucoma, cataract.

Ophthalmological finding in a patient with lowe syndrome.

The authors present the ophthamological finding in a patient who at the age of 4.5 months was admitted due to a finding of total bilateral congenital cataract. The patient was observed by a neurologist for central hypotonia and mental retardation. Upon a complex examination of the patient, suspicion of Lowe syndrome was stated, which was confirmed by a metabolic examination and also by genetic tests. Upon an examination of the family, a genetic defect (mutation of OCRL1 gene) was confirmed also in the mother of the patient. A mild subcapsular opacification was present in the mother, beneath the posterior capsule. The patient was operated on for bilateral congenital cataract. Upon an examination under general anaesthesia, trabeculodysgenesis was diagnosed. Intraocular pressure remains within the norm. The patient is now aged 8 years, regularly monitored with regard to metabolic compensation, and by a neurologist and ophthalmologist, with satisfactory visual functions. Early diagnosis of the Lowe syndrome was determined on the basis of a complex examination of the patient within the framework of etiological diagnosis of bilateral congenital cataract. Key words: Lowe syndrome, oculo - cerebro - renal syndrome, congenital cataract, glaucoma, nystagmus.

[Retinopathy of prematurity - therapy. Part 2]. / Retinopatia prematúrnych detí - terapia II. cast

Retinopathy of prematurity (ROP) is a disease that affects immature vasculature in the eyes of premature babies that potentially leads to blindness. Authors describe revised indications for the treatment of ROP, standard treatment - peripheral retinal ablation by laser photocoagulation and the cryotherapy using off label treatment-intravitreal anti-VEGF injection. Key words: retinopathy of prematurity, indications, laser photocoagulation, cryotherapy, intravitreal anti-VEGF therapy.

[Screening retinopathy of prematurity (ROP)]. / Skríning retinopatie prematúrnych detí (ROP).

Retinopathy of prematurity (ROP) is abnormal blood vessel development in the retina of the eye in a premature infant that potentially leads to blindness. The guidelines present the timing of initial examination and subsequent reexamination intervals for screening and treating ROP. Key words: retinopathy of prematurity, screening, timing of the examination.

[Vogt-Koyanagi-Harada syndrome in children - a case report]. / Vogt-Koyanagi-Harada syndróm v detskom veku.

Vogt-Koyanagi-Harada (VKH) syndrome is a multisystemic disease characterized by granulomatous panuveitis with exsudative retinal detachment and often associated with neurological and skin symptomatology. In the paper is presented a rare case of probably VHK syndrome in 11-year old caucasian race boy in which was found the bilateral granulomatous panuveitis with exsudative retinal detachment without other systemic symptomatology with typical clinical characteristics and course. Systemic corticosteroid therapy in a patient gradually improved the state, which was then complicated by the occurrence of juxtapapillary subretinal neovascular membrane on both eyes. The following administration of intravitreal injection anti-VEGF (bevacizumab) was modified visual acuity and reduced neovascular membrane. Key words: Vogt-Koyanagi-Harada syndrome, children, juxtapapillary choroidal neovascular membrane, anti-VEGF, bevacizumab.

[Benefit of paint diode laser coagulation in the treatment of ROP]. / Prínos konfluujúcej (paint)-- diôdlaserkoagulácie v liecbe retinopatie nezrelýh detí.

PURPOSE: Authors compare results of ROP treatment with a single spot diodlasercoagulation (DLC) versus paint--DLC. METHODS: A retrospective chart review of patients with threshold retinopathy of prematurity treated between 2001-2010 was conducted. A single spot DLC was used from January 2001 to May 2008. In this group (SI) there were 338 patients (671 eyes) with ROP. In the second group (S II) since June 2008 to June 2010 we have used the paint DLC in 158 patients (316 eyes). Authors compare the need for reoperations to achieve regression of ROP in both groups. Rate of progression, frequency of retreatment, complications and structural outcomes were evaluated. RESULTS: In SI was retreatment only with DLC necessary in 43 eyes (6.4%). Additional cryotherapy was used in 22 eyes (3.3%). A scleral buckling was used in 107 eyes (15.9%). In S II was retreatment with DLC used in 4 eyes (1.3%), the additional cryotherapy in 6 eyes (1.9%) and the scleral buckling in 11 eyes (3.5%). CONCLUSION: According to our outcomes we have found out the paint DLC mode is more effective than the single spot DLC in the ROP treatment.

Relationship between high aortic pulse pressure and extension of coronary atherosclerosis in males.

A high pulse pressure (PP) is a marker of increased artery stiffness and represents a well-established independent predictor for cardiovascular morbidity and mortality. The objective of the research was to determine whether invasively measured central aortic PP was related to the presence and severity of coronary artery disease. In total 1075 consecutive stable male patients undergoing diagnostic coronary angiography with a preserved left ventricular function were included. Diseased coronary vessel (DCV) was defined by the presence of >50 % stenosis. Men were divided into 3 groups according to the increased value of PP. The average PP in the tertiles was 47.8+/-7.1 vs. 67.0+/-4.9 vs. 91.3+/-12.8 mm Hg (p<0.01). The significant differences of DCV was found among tertiles (1.51+/-1.11 vs 1.80+/-1.04 vs. 1.99+/-0.98 DCV, p<0.01). Aortic PP together with age and hyperlipoproteinemia were found as factors with an independent relationship to DCV according to multivariate linear regression. In conclusions the increased value of aortic PP in the male population is independently connected with more severe atherosclerosis evaluated by the significant number of DCV.