Paediatric spinal cord low-grade gliomas-evaluation and management of post-surgical residual disease.

PURPOSE: To assess the evaluation and management of post-surgical residual disease for low-grade intramedullary spinal cord tumours (IMSCT) in childhood. METHODS: A single-centre retrospective review of low-grade IMSCTs treated between 2000 and 2019. All surgeries were performed with intent of safe maximal resection guided by intra-operative neurophysiological monitoring (IONM). Pre- and post-operative MRIs were reviewed to assess the extent of resection (EOR), recorded as follows: gross total resection (GTR), near total resection (NTR), sub-total resection (STR) and partial resection (PR). Outcome measures were time to recurrence, need for and modality of additional therapy and ambulatory status at last follow-up. RESULTS: Thirty patients underwent surgery for IMSCT (median age 6.9 years). EOR was GTR = 8, NTR = 4, STR = 9, PR = 9. All patients were alive at last follow-up (median follow-up 73 months [IQR 93 months]). Eighteen patients (60%) remained radiologically stable. Twelve patients (40%) developed recurrence during surveillance. Progression free survival was significantly better in cases with GTR + NTR in comparison to either STR or PR (p = 0.039). 10/30 (33%) patients were treated with additional therapy. At last follow-up, 26/30 patients were independently mobile. CONCLUSION: Survival rates for low-grade IMSCT are excellent. Radical micro-surgical resection, guided by IONM provides effective means of balancing the objectives of maximal safe resection, functional outcome and tumour control. Whilst evidence of 'residual disease' was identified in over 2/3 of immediate post-operative MRI scans, additional treatment was required in only 1/3 of cases. Critical appraisal of post-operative imaging findings is required to better define 'residual disease'. Small volume residual disease (< 5%) does not compromise progression-free survival.

Lymphatic drainage map of the head and neck skin squamous cell carcinoma detected by sentinel lymph node biopsy.

OBJECTIVE: Squamous cell carcinoma of the skin often affects the scalp and neck region and has a potential for complex lymphatic metastases. The aim of this study was to examine the pattern of lymphatic drainage that would enable better insight and prediction of lymphatic metastasis of head and neck squamous cell carcinoma (HNSCC) in relation to the anatomical localization of the primary process. PATIENTS AND METHODS: A prospective analysis included 64 patients who underwent sentinel lymph node (SLN) biopsy. The biopsy was performed in patients with high-risk cutaneous head and neck squamous cell carcinoma between 2006 and 2010. RESULTS: SLNs in tumors of the forehead, temporal region, lateral cheek, and auricle were found in the cervical region at level II and parotid lymph nodes (p<0.001). In tumors of the nose, periorbital region, and postauricular tumors, SLNs were found in parotid lymph nodes (p<0.001), in tumors of the medial cheek in level I cervical lymph nodes and parotid lymph nodes (p=0.003). In tumors of the neck, SLNs were detected in the cervical region at level IV, whereas in tumors of the posterior scalp they were found in the occipital region (p<0.001). CONCLUSIONS: The results of SLN biopsy in high-risk cutaneous HNSCCs show the regularity of metastasis based on which a lymphatic drainage map can be constructed and thus potential metastatic sites depending on the primary tumor localization predicted.

Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

A comprehensive morphometric analysis of the frontal and zygomatic bone of the Zuttiyeh fossil from Israel.

The Zuttiyeh hominin craniofacial fossil was discovered in Israel in 1925. Radiometric dates and the archaeological context (Acheulo-Yabrudian) bracket the associated cave layers to between 200 and 500 ka (thousands of years ago), making it one of the earliest cranial fossils discovered in the Near East thus far. Its geographic position, at the corridor between Africa and Eurasia, in combination with its probable Middle Pleistocene date make it a crucial specimen for interpreting later human evolution. Since its discovery, qualitative descriptive and traditional morphometric methods have variously suggested affinities to Homo erectus (Zhoukoudian), Homo neanderthalensis (Tabun), and early Homo sapiens (Skhul and Qafzeh). To better determine the taxonomic affinities of the Zuttiyeh fossil, this study uses 3D semilandmark geometric morphometric techniques and multivariate statistical analyses to quantify the frontal and zygomatic region and compare it with other Middle to Late Pleistocene African and Eurasian hominins. Our results show that the frontal and zygomatic morphology of Zuttiyeh is most similar to Shanidar 5, a Near East Neanderthal, Arago 21, a European Middle Pleistocene hominin, and Skhul 5, an early H. sapiens. The shape differences between archaic hominins (i.e., Homo heidelbergensis and H. neanderthalensis) in this anatomical region are very subtle. We conclude that Zuttiyeh exhibits a generalized frontal and zygomatic morphology, possibly indicative of the population that gave rise to modern humans and Neanderthals. However, given that it most likely postdates the split between these two lineages, Zuttiyeh might also be an early representative of the Neanderthal lineage. Neanderthals largely retained this generalized overall morphology, whereas recent modern humans depart from this presumably ancestral morphology.

Application of probiotics in food products--challenges and new approaches.

The probiotic research conducted over the past 20 years has resulted in a valuable source of data related to health beneficial effects of probiotics. Nevertheless, documentation of probiotic benefits remains challenging, especially in functional foods that are designed for the generally healthy population that, however, regularly experiences episodes of 'suboptimal' health. In addition, in view of today's application of probiotics in an increasing variety of food matrixes, process optimization and product design need to take into account cell viability and probiotic function altogether. To meet this challenge, medium to high-throughput bioassays - based on the identification of active compounds and their mechanism of action - have to be developed and their predictive value established. Together with validated biomarkers for health and disease, this should help rationalize probiotic product development and associated health claim substantiation in human studies.

Study of valsartan interaction with micelles as a model system for biomembranes.

In this study, the interaction of valsartan (VAL), an angiotensin II receptor antagonist, with cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated. The effect of cationic micelles on spectroscopic and acid-base properties of VAL was carried out using UV spectrophotometry at physiological conditions (pH 7.4). The binding of VAL to CTAB micelles implied a shift in drug acidity constant (pK(a)(water)-pK(a)(micelle)=1.69) proving the great affinity of VAL dianion for the positively charged CTAB micelle surface. To quantify the degree of VAL/CTAB interaction, two constants were calculated by using mathematical models: micelle/water partition coefficient (K(x)) and drug/micelle binding constant (K(b)). The decrease of K(x) with VAL concentration, obtained by using pseudo-phase model, is consistent with an adsorption-like phenomenon. From the dependence of differential absorbance at lambda=295 nm on CTAB concentration, by using mathematical model that treats the solubilization of VAL dianion as its binding to specific sites in the micelles (Langmuir adsorption isotherm), the binding constant (K(b)=(2.50+/-0.49)x10(4)M(-1)) was obtained. Binding constant VAL/CTAB was also calculated using micellar liquid chromatography (MLC).

Coagulation status and the presence of postoperative deep vein thrombosis in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Venous thromboembolism is a relevant social and health care problem because of its high incidence among patients who undergo surgery (20-30% after general surgical operations and 50-75% after orthopedic procedures), its pulmonary embolism-related mortality rate, and its long-term sequelae (postthrombotic syndrome and ulceration), which may be disabling. This study aimed to determine the coagulation status and the presence of postoperative deep vein thrombosis (DVT) in patients undergoing laparoscopic (LC) and open cholecystectomy (OC). METHODS: Prospectively, 114 patients were randomized into two groups. group 1 (58 patients undergoing LC) and group 2 (56 patients who are undergoing OC). The coagulation parameters (prothrombin time [PT], partial thromboplastin time [PTT], D-dimer, prothrombin F1 + 2, antithrombin III, and factor VII) were monitored preoperatively and during the operation, then 24 and 72 h after the operation. The patients in both groups underwent color duplex scan examination preoperatively, then 3 and 7 days after surgery to establish the presence of DVT. None of the patients in either group received thrombosis prophylaxis. RESULTS: In the LC group, postoperative DVT developed in four patients (6.9%; in the calf veins of 3 patients and in the popliteal vein of 1 patient). In the OC group, nine patients (16.07%) had postoperative DVT (in the calf veins of 7 patients and in the popliteal and femoral veins of 2 patients). The plasma levels of monitored parameters in the patients of both groups were altered, but the difference between the groups was not statistically significant. For the patients in both groups who experienced DVT, only the decrease of factor VII had statistical significance (p < 0.05). CONCLUSIONS: The incidence of postoperative DVT among the patients who underwent OC was higher than among the patients who underwent LC (p < 0.05). The decrease in factor VII among the patients who underwent surgery could be a potentially useful parameter indicating the patients at high risk for developing DVT.

Analysis of catabolite control protein A-dependent repression in Staphylococcus xylosus by a genomic reporter gene system.

A single-copy reporter system for Staphylococcus xylosus has been developed, that uses a promoterless version of the endogenous beta-galactosidase gene lacH as a reporter gene and that allows integration of promoters cloned in front of lacH into the lactose utilization gene cluster by homologous recombination. The system was applied to analyze carbon catabolite repression of S. xylosus promoters by the catabolite control protein CcpA. To test if lacH is a suitable reporter gene, beta-galactosidase activities directed by two promoters known to be subject to CcpA regulation were measured. In these experiments, repression of the malRA maltose utilization operon promoter and autoregulation of the ccpA promoters were confirmed, proving the applicability of the system. Subsequently, putative CcpA operators, termed catabolite-responsive elements (cres), from promoter regions of several S. xylosus genes were tested for their ability to confer CcpA regulation upon a constitutive promoter, P(vegII). For that purpose, cre sequences were placed at position +3 or +4 within the transcribed region of P(vegII). Measurements of beta-galactosidase activities in the presence or absence of glucose yielded repression ratios between two- and eightfold. Inactivation of ccpA completely abolished glucose-dependent regulation. Therefore, the tested cres functioned as operator sites for CcpA. With promoters exclusively regulated by CcpA, signal transduction leading to CcpA activation in S. xylosus was examined. Glucose-dependent regulation was measured in a set of isogenic mutants showing defects in genes encoding glucose kinase GlkA, glucose uptake protein GlcU, and HPr kinase HPrK. GlkA and GlcU deficiency diminished glucose-dependent CcpA-mediated repression, but loss of HPr kinase activity abolished regulation. These results clearly show that HPr kinase provides the essential signal to activate CcpA in S. xylosus. Glucose uptake protein GlcU and glucose kinase GlkA participate in activation, but they are not able to trigger CcpA-mediated regulation independently from HPr kinase.

[Results of intensive therapy of meningococcal sepsis in children]. / Rezultati intenzivne terapije meningokokne sepse kod dece.

The authors report on the method, course and results of treatment of patients with meningococcal septicaemia. The two most common forms of meningococcal disease are meningococcal septicaemia (MS) and meningitis. Severe MS is a fulminant form of sepsis characterized by a rapidly spreading purpuric rash, haemodynamic instability and rapid progression to shock or death. The diganosis of MS was confirmed by isolation of NM in blood or cerebrospinal fluid, and/or positive solubile bacterial antigenes. However, in some children whose symptoms were consistent in MS (temperature and extensive purpura), no bacterial or soluble antigens were detected, particularly when they had been previours antibiotic treatment. Several scoring systems have been used to predict morbidity and mortility from MS. We selected the prognostic scor developed by Malley et al. Absolute neutrophil count less than 3 x 10(3)/mm3, platelet count less than 150 x 10(3)/mm3 and poor perfusion are indicators of poor prognosis. The presence of at least two of these indicators was associated with an 82% of risk of death. We reviewed the hospital records of 36 paediatric patients with acute meningococcal infection during a 5-year period. The age of our patients ranged from 2 months to 15 years (mean 4.4 yrs). Twenty seven (70%) of 36 children had MS and 11 (40.7%) had both MS and meningitis. Based on Malley scor, 13 (48.1%) patients had at least two predictors with > 82% of risk of lethal outcome. Four children (30.7%) died. Severe MS was diagnosed in 16 (59.2%) patients, who required mechanical ventilation (16; 59.2%), or continuous inotropic support and invasive measures of circulatory parametars (15; 55.5%). Shock treatment consisted of large volumes of crystalloid or colloid infusions thad ranged from 140 to 500 ml/kg/24 hrs (mean 215 ml/kg) Our results indicate that early controlled mechanical ventilations increase safety of large volume infusion with continuous invasive monitoring and inotropic stimulation, and may contribute to a greater survival of children with severe MS.

Pneumocystis carinii pneumonitis in haemophagocytic lymphohistiocytosis.

UNLABELLED: We report on a 10-y-old boy who developed Pneumocystis carinii pneumonitis (PCP) as the dominant symptom at the onset of haemophagocytic lymphohistiocytosis (HLH). PCP is a common infection in patients with combined primary immunodeficiencies or acquired immunodeficiency syndrome but it has rarely been observed at the onset of HLH. Typically, HLH presents as a febrile syndrome associated with cytopenia and hepatosplenomegaly. Repeated bone marrow aspirates, spleen or lymph node biopsies are sometimes required to reveal haemophagocytosis. Because of the significant immunosuppression during treatment of HLH, prophylaxis of PCP with co-trimoxazole is recommended. However, de-arranged immune response in HLH renders the patients susceptible to opportunistic infections, even before the introduction of immunosuppressants. CONCLUSION: We suggest that in patients with unclear respiratory symptoms, it is worth considering a differential diagnosis of HLH.

Characterization of an HPr kinase mutant of Staphylococcus xylosus.

The Staphylococcus xylosus gene hprK, encoding HPr kinase (HPrK), has been isolated from a genomic library. The HPrK enzyme, purified as a His(6) fusion protein, phosphorylated HPr, the phosphocarrier protein of the bacterial phosphotransferase system, at a serine residue in an ATP-dependent manner, and it also catalyzed the reverse reaction. Therefore, the enzyme constitutes a bifunctional HPr kinase/phosphatase. Insertional inactivation of the gene in the genome of S. xylosus resulted in the concomitant loss of both HPr kinase and His serine-phosphorylated-HPr phosphatase activities in cell extracts, strongly indicating that the HPrK enzyme is also responsible for both reactions in vivo. HPrK deficiency had a profound pleiotropic effect on the physiology of S. xylosus. The hprK mutant strain showed a severe growth defect in complex medium upon addition of glucose. Glucose uptake in glucose-grown cells was strongly enhanced compared with the wild type. Carbon catabolite repression of three tested enzyme activities by glucose, sucrose, and fructose was abolished. These results clearly demonstrate the prominent role of HPr kinase in global control to adjust catabolic capacities of S. xylosus according to the availability of preferred carbon sources.

Identification of a gene in Staphylococcus xylosus encoding a novel glucose uptake protein.

By transposon Tn917 mutagenesis, two mutants of Staphylococcus xylosus were isolated that showed higher levels of beta-galactosidase activity in the presence of glucose than the wild type. Both transposons integrated in a gene, designated glcU, encoding a protein involved in glucose uptake in S. xylosus, which is followed by a glucose dehydrogenase gene (gdh). Glucose-mediated repression of beta-galactosidase, alpha-glucosidase, and beta-glucuronidase activities was partially relieved in the mutant strains, while repression by sucrose or fructose remained as strong as in the wild type. In addition to the pleiotropic regulatory effect, integration of the transposons into glcU reduced glucose dehydrogenase activity, suggesting cotranscription of glcU and gdh. Insertional inactivation of the gdh gene and deletion of the glcU gene without affecting gdh expression showed that loss of GlcU function is exclusively responsible for the regulatory defect. Reduced glucose repression is most likely the consequence of impaired glucose uptake in the glcU mutant strains. With cloned glcU, an Escherichia coli mutant deficient in glucose transport could grow with glucose as sole carbon source, provided a functional glucose kinase was present. Therefore, glucose is internalized by glcU in nonphosphorylated form. A gene from Bacillus subtilis, ycxE, that is homologous to glcU, could substitute for glcU in the E. coli glucose growth experiments and restored glucose repression in the S. xylosus glcU mutants. Three more proteins with high levels of similarity to GlcU and YcxE are currently in the databases. It appears that these proteins constitute a novel family whose members are involved in bacterial transport processes. GlcU and YcxE are the first examples whose specificity, glucose, has been determined.

[Reference values of anthropometry parameters in school children and youths in Subotica]. / Referentne vrednosti antropometrijskih parametara skolske dece i omladine u Subotici.

Anthropometric measurements are most often used in order to evaluate the state of nourishment and gain insight into body growth and development of children and young people. The use of different criteria in everyday practical work causes very diversified results and at the same time presents a problem in early detection of certain disorders of growth, development and state of nourishment and in undertaking adequate dietetic and therapeutic treatments. In Subotica 18864 persons from 8-19 years of age were examined by transverse anthropometric measurements of height and weight. By statistical processing of results mean values, medians and percentiles of body height, body mass and the body mass index, BMI (kg/m2) were established. These reference values present a base for producing nomogram of growth, development and state of nourishment in children and young people in our area which could be applied in everyday work at clinics.

[Radiotherapy of esophageal cancer]. / Radioterapija karcinoma jednjaka.

In the Institute of Radiology in Belgrade, in 1960 to 1972 period, 115 patients with malignant tumors of eosophagus were treated only with radiation. Among them there were 89 men and 26 women. The tumors appeared most frequently in the seventh decade of life, and their localization did not have an essential influence on the course of the disease, respectively on the effects of medical treatment. Two of these patients survived 5 years, and 78 died in the course of the first year after radiation. Particularly we found improvement regarding the general condition and the better feeding possibilities (70 per cent of the cases). These patients spent their last days relatively well and in this we should see the significant of radiotherapy of these malignant tumors, because another choice of medical treatment and help does not exist for the present. From 1975 year we have been using the preoperative radiation in short courses in order to improve the surgical results.

[Importance of the determination of glucose-6-phosphate dehydrogenase in the diagnosis of congenital hemolytic anemias]. / Znacaj odredivanja glukozo-6-fosfat dehidrogenaze u dijagnostici urodenih hemoliznih anemija.

In the present paper, the enzyme activity of glucose-6-phosphate dehydrogenase (G-6-PD) was determined in blood haemolysate of 300 children, in the aim of differential diagnosis. In the studied group we found 2 children with markedly low activity of G-6-PD. The activity of enzyme in those patients ranged 0-37 mU/0,1 ml packed red cells. We investigated the activity of enzyme G-6-PD in the blood haemolysate of the parents and other relatives too. On that way we were able to establish that the mode of inheritance of defective enzyme activity was homozygote dominant, e.g. hemizygote recessive, respectively. Our study enabled us to discover the patients with inherited deficiency of erythrocytic G-6-PD in Belgrade.

[Treatment of acute lymphocytic leukemia in children with combination chemotherapy and irradiation of the central nervous system]. / Akutna limfocitna leukemija u dece lecene hemioterapijom i zracenjem centralnog nervnog sistema

From July 1972 until April 1975 51 children with acute lymphocytic leukemia had been treated with combination chemotherapy and central nervous system irradiation. First remission was induced in 46 patients. 13 patients died during the first and second year of treatment. Central nervous system leukemia developed only in 3 patients. In 9 patients chemotherapy had been stopped after 30 months of treatment. These results are very encouraging and we hope that majority of our patients will survive 5 years without relapse.