Radiotherapy and radiosensitivity syndromes in DNA repair gene mutations.

BACKGROUND: Ionizing radiation DNA damage is the main mechanism of radiotherapy (RT) action and the outcome of treatment and healthy tissue toxicity is influenced by a number of external and internal factors, including mutations in DNA damage recognition and repair. Disorders of DNA repair may result in increased sensitivity to cancer treatment. PURPOSE: The mechanism of DNA repair and an overview of genetic syndromes with mutations in genes involved in DNA repair clarify the accelerated carcinogenesis and increased radiosensitivity in RT cancers. Most radiosensitivity syndromes are autosomal recessively inherited; examples are ataxia teleangiectasia, Nijmegen breakage syndrome, xeroderma pigmentosum, Cockayne syndrome, Bloom syndrome and Werner syndrome. CONCLUSION: Radiotherapy is contraindicated in most homozygous patients with recessive radiosensitivity syndromes. Asymptomatic heterozygotes may have an increased risk of tumor incidence and a small part of them slightly increased risk of RT intolerance; however, this does not limit RT treatment. The high risk of secondary malignancies after radiotherapy is a contraindication to adjuvant RT in Li-Fraumeni syndrome.

Sarcopenia in Metastatic Colorectal Carcinoma.

Sarcopenia is the loss of skeletal muscle mass (SMM) and is associated with decreased muscle strength and/or decreased physical performance. Sarcopenia in patients with malignancies is a multifactorial problem, caused by chronic inflammation associated with malignancies, aging, nutritional deficiency, inactivity, and antineoplastic treatment. Sarcopenia is present in approximately 30-60% of patients with metastatic colorectal cancer (mCRC). It is an objective, measurable predictor of survival and systemic toxicity. The detection and quantification of sarcopenia in routine clinical practice does not require any particular test beyond routine imaging. Initial results show that regimens used to treat mCRC can have differential effect on skeletal mass. SMM tends to decrease during intensive regimens. Conversely, SMM tends to increase during low-intensity maintenance therapy or in patients with stable disease. The status of the underlying disease is another determinant of muscle mass changes, and SMM decreases during disease progression. Third-line therapy with regorafenib, a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor, results in more skeletal muscle loss than trifluridine/tipiracil chemotherapy, which may have consequences for the survival or quality of life of patients. Larger prospective studies are needed to elucidate the importance of SMM changes during mCRC treatment. TB received fees for lectures and consultations related to the treatment of colorectal cancer from Merck, Amgen, Eli Lilly, Servier, Roche, Sanofi and Bayer. JH declares she has no potencional conflict of interest. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 15. 9. 2019 Accepted: 25. 10. 2019.

Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome.

Recently, the genetic cause of several syndromic forms of glycemia dysregulation has been described. One of them, MEHMO syndrome, is a rare X-linked syndrome recently linked to the EIF2S3 gene mutations. MEHMO is characterized by Mental retardation, Epilepsy, Hypogonadism/hypogenitalism, Microcephaly, and Obesity. Moreover, patients with MEHMO had also diabetes and endocrine phenotype, but detailed information is missing. We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene. Both probands had a neonatal hypoglycemia, early onset insulin-dependent diabetes, and hypopituitarism due to dysregulation and gradual decline of peptide hormone secretion. Based on the clinical course in our two probands and also in previously published patients, neonatal hypoglycemia followed by early-onset diabetes and hypopituitarism may be a consistent part of the MEHMO phenotype.

ß-blockers in the treatment of periocular infantile capillary haemangioma.

Infantile capillary haemangioma (IH) is the most common congenital vascular tumor of childhood and infancy. Although the majority of these lesions regress spontaneously, many of children with IH particularly in the periocular or orbital region need treatment. Ocular indications for treatment include obstruction of the visual axis or high degrees of astigmatism causing amblyopia, exposure keratopathy secondary to proptosis or compressive optic neuropathy. Our purpose was to assess the effectiveness and tolerance of beta-blockers (BB), propranolol and metoprolol, in the treatment of these lesions. We performed a retrospective review of 21 infant patients with periocular or/and orbital IH. The mode of treatment for 13 patients was with the non-selective ß blocker propranolol (PR) and 8 patients were treated with the ß1 selective blocker metoprolol (ME). We analysed the changes in IH lesion size, colour and thickness after the treatment with ß-blockers, the onset and the period of their action, recurrence of IH and adverse effects of the treatment. The effectiveness of metoprolol to propranolol was compared as well as their use in combination with systemic steroids. In the first month of the treatment with beta-blockers, significant regression of the IH was observed in all patients. During the following months of treatment the regression was not rapid and after 6 to 12 months the lesions remained stationary. The final result of the treatment of 15 patients (71.4%) was deemed excellent while the treatment of 5 patients (23.8%) was deemed good. A single patient (4.7%) had only fair response to the therapy. During the whole series no serious life-threatening adverse effects were observed. The usage of beta-blockers, both propranolol and metoprolol, in the therapy of orbital and periocular capillary infantile haemangioma seems to be very effective in reduction of the tumor and had only rare, minimum adverse effects. These facts favour beta-blockers as the first line treatment of children with IH.

Prevention of neural tube defects by folic acid - awareness among women of childbearing age in Slovakia.

BACKGROUND: Folic acid deficiency plays a central role in the aetiology of many congenital anomalies including neural tube defects. Protective effect of folic acid on embryo may be acquired only if taken periconceptionally. OBJECTIVES: The aim of the study was to investigate the awareness about folic acid among women of childbearing age in Bratislava, Slovakia. METHODS: There were 130 respondents involved in the research (106 pregnant women, 24 female students of medical faculty). Using questionnaire we acquired following data: pregnancy details, interest in diet before and during pregnancy, recommendations regarding nutrition and supplementation pre- and post-conception, knowledge about folic and other acid in 2004 and 2009. RESULTS: More than half of the respondents knew the sources of folic acid. The interest in the nutrition facts of the food dropped from 91 % to 58.5 %. The number of pregnant women advised about correct nutrition and folic acid supplementation before and during pregnancy increased from 16 % to 37 %. Planning the next gravidity with folic acid supplementation became greater than 21 % (38 % in 2009). Nevertheless, only 46 % of these women believed that proper food content with folic acid may prevent congenital anomalies. In a group of students planning to take folic acid periconceptionally the number raised up to 62.5 %. CONCLUSION: The results revealed low knowledge about the effect of folic acid on developing embryo among women of childbearing age. Effective intervention programs are needed with the aim to improve periconceptional intake of folic acid in 2004 and 2009. The results in both periods show low knowledge about this essential vitamin (Tab. 1, Fig. 8, Ref. 31).

[Contemporary possibilities of intraocular pressure measurement]. / Soucasné moznosti merení nitroocního tlaku.

Authors introduced current possibilities of measuring intraocular pressure (IOP). A list of available methods of monitoring IOP is published; contact measurement method IOP directly on the cornea, but also over upper lid, methodology of minimal contact and non-contact measurement. Following contact methods are described; former measurements of IOP by impression Schiotz tonometer and the current methodology applanation. So far as the gold standard measurement Goldmann applanation tonometer (GAT) is considered, another methodology with applanation measurements are compared: Pascal dynamic contoured tonometer (DCT ), BioResonator - resonant applanation tonometer (ART ), digital applanation tonometer Tonopen and last hit: continuous measurement of IOP by Sensimed Triggerfish. Orientation and rapid assessment is palpation pressure control over the lid and measuring by tonometer Diaton. Rebound tonometer (RBT) iCare belongs to measurements with minimal contact, no need anesthetic drops and fluorescein, therefore a self - home version of IOP measurements (Icare ONE) is developed. Non-contact measurement of IOP by different pneumotonometers is popular for screening assessment of IOP. Reichert Ocular Response Analyzer (ORA) is a non-contact applanation IOP measurement and reveals additional properties of the cornea. In the discussion of a range methodology is evaluated, the experience of other authors and their own experience is compared. For monitoring of patients is necessary to select the most suitable methodology, measure repeatedly and accurately to allow long-term monitoring of intraocular pressure.

[Epidemiology of neural tube defects]. / Epidemiológia defektov neurálnej rúry.

INTRODUCTION: Neural tube defects represent group of congenital diseases with relatively high incidence in population. Authors assess world and Slovak literature and statistical facts about the epidemiology of NTD and compare them with their own results of retrospective study performed in Children's Hospital, Bratislava. MATERIALS AND METHODS: List of patients consists of 250 children (106 boys, 144 girls): X-ray images showing lumbo-sacral part of vertebral column were evaluated retrospectively (X-ray of native abdomen, urological tract or skeleton). Authors assessed presence or non-presence of spina bifida on images, without relation to age, gender or diagnosis of patients. RESULTS: From the total number of 250 radiograms, 72 findings were positive (36 boys and 36 girls), 160 images were negative, 18 were unsuitable for evaluation due to low image quality. The highest diagnostic capture was from urological images - 40% of all positive findings. Incidence of spina bifida in Children's Hospital concluded from X-ray images is quite high - 28.8%. CONCLUSION: According to the data from National Centre of Health Statistics the incidence of open caudal neural tube defects in Slovakia is under 5 per 10 000 live-born children at present time. However the occurrence of occult spina bifida is not known exactly. The high rate of spina bifida presented herein (28%) can be caused by relatively low number of evaluated radiograms. Also the fact that children were not only healthy ones and data were obtained from the western part of Slovakia as well. In conclusion we can say that after accidental finding of caudal neural tube defect consecutive diagnostics should be performed in clinical positive cases - genetics, MRI and consultation with specialists to decide for the optimal follow up of the patient.

Antibody response to chlamydiae in children with asthma and respiratory illness.

No relation between the occurrence of antibodies to chlamydial agents and asthma in children was found. In asthmatic children, the antibodies to Chlamydia trachomatis occurred in 3.1% and to Chlamydophila pneumoniae in 22.7%, whereas in a control group of children without asthma or other allergic disease in 2.3% and 24.0%, respectively. The occurrence of antibodies of IgA and IgG classes to C. pneumoniae was also very similar; its rise was age-dependent. On the other hand, in the group of children in a pre-school age with respiratory tract infection, anti-chlamydial antibodies were demonstrated significantly more often (18.5% of IgG antibodies to C. trachomatis, 20.0% of IgM antibodies to both C. trachomatis and C. pneumoniae) than in those suffering from other, non-respiratory illness (3.9% of the former and 5.9% of the latter antibodies). However, in these children, we did not succeed in detection of C. trachomatis in conjunctival and nasopharyngeal smears by PCR. Nevertheless, chlamydial agents (C. trachomatis in infants, C. pneumoniae in pre-school children) should be taken into consideration in a differential diagnosis of respiratory tract inflammation.

[Later age diaphragmatic hernia]. / Diafragmatická hernia manifestovaná v neskorsom veku.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is usually diagnosed antenatally or through the neonatal period at present. It is also used to treat and manage CDH in this date. However in rare cases CDH could be presented after finished neonatal period with non-specific and misleading symptoms. The aim of our presentation is to analyze the patients with late - presenting and diagnosed CDH. METHODS: During period 1996-2006 we operated on 54 children with CDH, 12 of them with late - presenting CDH, age variance was 9 months and 6 years. The spectrum of symptoms was from asymptomatic CDH (2 patients), mild respiratory (4 patients) and gastrointestinal symptoms (4 patients), combination of respiratory and gastrointestinal symptoms (2 patients) and finally the symptomatology of bowel incarceration (2 patients). RESULTS: Seven children presented with another associated malformations (m. Down, congenital heart failure, hydrocephalus, anorectal atresia). All 12 patients were operated on with a good results. The operation was composed of reposition of the herniated part of gastrointestinal tract (without need of resection) and diaphragmatic plastic. Two patients were reoperated on - once because of diaphragmatic relaxation and the second one due to consecutive heart operation. CONCLUSION: Congenital diaphragmatic hernia could be presented with chronic and non-specific respiratory or gastrointestinal symptoms. Time to time, presentation of diaphragmatic hernia as "acute abdomen" could be seen. The operation is indicated, also in asymptomatic patients as a prevention of life-threating events.

Correlation of Disc Damage Likelihood Scale, visual field, and Heidelberg Retina Tomograph II in patients with glaucoma.

PURPOSE: To correlate the analysis of the optic nerve head (ONH) obtained with Disc Damage Likelihood Scale (DDLS), Heidelberg Retina Tomograph II (HRT II), and visual field (VF) parameters (Aulhorn scale, mean deviation [MD], and pattern standard deviation [PSD]) in patients with glaucoma. METHODS: Sixty-five eyes were evaluated using the DDLS classification. Fifty-seven eyes had stable primary open-angle glaucoma (POAG) and eight eyes were normal (control group). Classification of the ONH was performed using the HRT II, with Moorfields Regression Analysis (MRA) and Cup Shape Measure (CSM) indexes. The VF was examined by Full Threshold test (30-2) using the Humphrey Field Analyzer (HFA) perimeter and evaluated by three METHODS: Aulhorn's scale of 0 to 6, and two global indices, MD and PSD. RESULTS: The amount of ONH damage as estimated by the DDLS correlated well with topographic damage determined by HRT II (r=0.923 with MRA and r=0.807 with CSM) and with visual field loss as measured by the MD (r=-0.792) and PSD (r=0.718) of the HFA and Aulhorn field staging system (r=0.849). CONCLUSIONS: This study shows that evaluation of the ONH using the DDLS provides information that correlates well with VF and with data obtained from HRT II.

[Macular area in glaucoma patients]. / Makulární oblast u pacientu s glaukomem.

PURPOSE: To evaluate the possible use of HRT II and OCT 3 for detection and monitoring of glaucoma changes in the macular area. METHODS: In the retrospective study 65 eyes (13 healthy and 52 with primary open angle glaucoma) of 36 patients have been monitored. All patients underwent complete ophthalmologic examination including visual acuity testing, biomicroscopy of fundus, computer perimetry, HRT II and eleven patients were examined using OCT 3. The visual field has been tested on HFA (Humphrey Field Analyzer) using the full threshold test 30-2. Foveolar sensitivity and foveolar sensitivity compared to the age have been evaluated. The optic nerve head has been examined and subsequently evaluated using HRT II. The retinal nerve fiber layer (t-RNFL) and Cup Shape Measurement (t-CSM) in the temporal area have been monitored. The macula has been examined on OCT 3. Foveolar thickness, inner and outer macular thickness, average macular thickness and aggregate macular volume have been monitored. RESULTS: Decrease of the visual acuity and foveolar sensitivity have been registered with the deterioration of the visual field. Further general decrease of the value of t-RNFL and increase of the t-CSM index have been registered from the results of the HRT II examinations. This corresponds to decrease of the nerve fibers and excavation deepening in the temporal area. Average macular thickness and total macular volume examined on OCT 3 demonstrate aggregate decrease of values with the progressive changes in the visual field. CONCLUSION: With the progressive visual field changes with the open angle glaucoma patients occurs also deterioration of finding in the macular area. Changes discovered using the subjective examination and expressed as a slight decrease of the visual acuity as well as decrease of the foveolar sensitivity on HFA can be objectively proved using HRT II and OCT 3.

[Clinical preoperative study and results of trabeculectomy after 2 years]. / Klinická predoperacní vysetrení a výsledky trabekulektomie po dvou letech.

PURPOSE: To determine whether preoperative anatomical and functional results have an influence on the postoperative decrease in intraocular pressure (IOP) and therapy two years after trabeculectomy (TE). METHODS: In a retrospective study 40 patients (80 eyes) with primary open angle glaucoma were followed. They underwent TE with two releasable sutures on both eyes performed by the same method and the same surgeon. The preoperative and postoperative levels of IOP (as measured by the Goldmann tonometer) and therapy (according to target pressure) were compared with preoperative gonioscopy (Shaffer's scale 0-4), the excavation of the optic nerve (c/d ratio) and preoperative results of the visual field (threshold tests and Aulhorn's classification 0-V). RESULTS: The preoperative size of the angle of the anterior chamber has no expressive influence on the postoperative decrease in IOP (p = 0.079), there is an even smaller influence on decrease on therapy (p = 0.619). As well the preoperative excavation of the optic disc had no influence on the postoperative decrease in IOP (p = 0.179) and therapy (p = 0.467). There is an analogy with the visual fields; preoperative changes had no influence on the postoperative decreasee IOP (p = 0.502) and therapy (p = 0.247). CONCLUSION: Preoperative anatomical and functional status had no the influence on the success of TE.

[Long-term experience with glaucoma silicone implants in a multicenter study]. / Dlouhodobé zkusenosti s glaukomovým silikonovým implantátem (GSI) v multicentrické studii.

PURPOSE: To evaluate the experience with a glaucoma implant in complicated glaucoma, designed in collaboration with the Institute of Polymers in Prague. METHODS: In a multicentric retrospective study 91 eyes of 86 patients with otherwise uncontrollable glaucoma underwent GSI implantation in four departments. The implant of medical silicone consists of a tube with an internal diameter of 0.4 mm, connected to a round lens-shaped episcleral plate 169 mm2, covering the tube orifice from above. The indications were infantile glaucoma (14 eyes), traumatic glaucoma (14 eyes), various secondary glaucomas in 12, primary open-angle glaucoma in 11, neovascular and after PPV in 10 eyes each, usually after unsuccessful previous surgery. RESULTS: The average follow-up time was 20.5 months (SD +/- 19.5). Postoperative intraocular pressure at the last control was 6-22 mmHg in 56 eyes (50.95%). Life table analysis showed a cumulative probability of 494% (at least qualified success). Long-term hypotony was seen in 6 eyes. CONCLUSIONS: The GSI is comparable with similar tube shunts but is much less expensive. In vitro experiments are planned to improve the construction of the implant and its results.

[A pediatrician's views on the treatment of extensive hemangiomas in childhood]. / Pohlad pediatra na liecbu rozsiahlych hemangiómov v detskom veku.

Haemangiomas are the most frequent tumours of child age. They are found in 10-12% of infants. The authors summarize contemporary knowledge of the treatment of haemangiomas as well as their own experience with their treatment. They follow-up 18 children with haemangiomas at different sites, incl. ten with extensive haemangiomas. The latter were treated conservatively with prednisone and interferon alpha.

[Immediate and late intraocular pressure levels after trabeculectomy with releasable sutures] ]. / Casná a pozdní hladina nitroocního tlaku po trabekulektomii s povolitelnými stehy.

PURPOSE: To evaluate the level of IOP and clinical status the first day after trabeculectomy (TE) with releasable sutures (RS), to follow up the extraction of RS in correlation with early and late postoperative level of IOP. METHODS: In a retrospective study, 40 patients with open angle glaucoma were followed. They underwent TE with two RS on both eyes. RESULTS: Hypotony (IOP less than 6 mmHg) was noted in 15 eyes (19%) the first day after the operation, shallow anterior chamber in 5 (6%). An IOP level higher than 20 mmHg was found in 11 eyes (13%) one day after surgery. No RS were extracted in the first group of 26 eyes. The early mean IOP was 10.15 +/- 7.1 mmHg the 1st day after surgery. IOP increased to a mean level of 15.3 +/- 3.8 mmHg two years after TE, 65% of eyes were without glaucoma therapy. One RS was extracted in the second group of 28 eyes. The early mean level of IOP was 10.7 +/- 6.5 mmHg, the late level 13.9 +/- 3.7 mmHg. The target pressure was maintained in 68% of the eyes without additional glaucoma therapy. The third group had 26 eyes and two RS were extracted after TE. The early mean level of IOP was 14.7 +/- 6.9 mmHg, the mean level of IOP was 15.8 +/- 3.9 mmHg two years after surgery, 39% of eyes were without glaucoma therapy. CONCLUSION: A level of IOP the first day after the operation, lower than 6 mmHg or higher than 20 mmHg, must not be an indicator for failure of the surgery. Observing the level of IOP 3-5 days after surgery determines whether the RS is to be removed or not. The use of RS prevents short-term complications and the extraction of RS during the postoperative period can positively influence the evaluation of filtration.

[Monitoring intraocular pressure and therapy after trabeculectomy in both eyes during a 2-year period]. / Sledování nitroocního tlaku a lécby po dobu dvou let po trabekulektomii na obou ocích.

PURPOSE: To evaluate the level of intraocular pressure (IOP) and glaucoma therapy during two years after trabeculectomy (TE) with two releasable sutures (RS) on the first and the second operated eye. METHODS: In a retrospective study, preoperative and postoperative IOP and glaucoma therapy in 40 patients with open angle glaucoma, were evaluated. Patients underwent standardized TE with two RS on both eyes performed by the same surgeon. The first (worse) eye was operated on an average of three years after the diagnosis of glaucoma, and after 8.2 +/- 6.9 months the second (better) eye was operated on. RESULTS: TE with RS significantly decreased the level of IOP (p < 0.0001) and therapy (p < 0.0001) during a two year follow up period. There was no significant difference in IOP (p = 0.226) and glaucoma therapy (p = 0.086) between the first and the second operated eye. IOP was stabilised within 2-3 months after surgery for most patients, however glaucoma therapy was added for some to keep the target pressure. After one year IOP and therapy were stable for all patients. CONCLUSION: There is no difference between the first-worse and the second-better operated eye regarding IOP and glaucoma therapy during a two year period.

[Frequency of removal of releasable sutures after trabeculectomy]. / Frekvence extrakce povolitelných stehu po trabekulektomii.

PURPOSE: To find out the frequency and time of extraction of releasable sutures (RS) in the first and second operated eye. METHODS: In a retrospective study, 40 patients with primary open glaucoma were followed. Patients underwent trabeculectomy with two RS on both eyes. The trabeculectomy was performed by the same surgeon and by the identical method. RESULTS: It was not necessary to remove RS postoperatively in 30% of the first operated eyes and in 35% of the second operated eyes. One RS was removed in 37.5% of the first and 32.5% of the second eyes. Two RS were removed equally in 32.5% of both eyes. The differences of RS extraction on the first and on the second eye were not significant (p = 0.76). The extraction time was similar in both eyes, too. CONCLUSION: There is no difference between the first and second operated eye regarding the frequency and time of extraction RS.

[An unusual case of gastroschisis combined with dysganglionosis]. / Neobvyklý prípad gastroschízy kombinovanej s dysganglionózou.

Authors describe a child with gastroschisis, which was associated with dysganglionosis. Therapy required an uncommon surgical treatment in connection with a long term parenteral and enteral nutrition.