The interrelatedness of cognitive abilities in very preterm and full-term born children at 5.5 years of age: a psychometric network analysis approach.

BACKGROUND: Very preterm (VP) birth is associated with a considerable risk for cognitive impairment, putting children at a disadvantage in academic and everyday life. Despite lower cognitive ability on the group level, there are large individual differences among VP born children. Contemporary theories define intelligence as a network of reciprocally connected cognitive abilities. Therefore, intelligence was studied as a network of interrelated abilities to provide insight into interindividual differences. We described and compared the network of cognitive abilities, including strength of interrelations between and the relative importance of abilities, of VP and full-term (FT) born children and VP children with below-average and average-high intelligence at 5.5 years. METHODS: A total of 2,253 VP children from the EPIPAGE-2 cohort and 578 FT controls who participated in the 5.5-year-follow-up were eligible for inclusion. The WPPSI-IV was used to measure verbal comprehension, visuospatial abilities, fluid reasoning, working memory, and processing speed. Psychometric network analysis was applied to analyse the data. RESULTS: Cognitive abilities were densely and positively interconnected in all networks, but the strength of connections differed between networks. The cognitive network of VP children was more strongly interconnected than that of FT children. Furthermore, VP children with below average IQ had a more strongly connected network than VP children with average-high IQ. Contrary to our expectations, working memory had the least central role in all networks. CONCLUSIONS: In line with the ability differentiation hypothesis, children with higher levels of cognitive ability had a less interconnected and more specialised cognitive structure. Composite intelligence scores may therefore mask domain-specific deficits, particularly in children at risk for cognitive impairments (e.g., VP born children), even when general intelligence is unimpaired. In children with strongly and densely connected networks, domain-specific deficits may have a larger overall impact, resulting in lower intelligence levels.

Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview.

OBJECTIVE: The role of serrated polyps (SPs) as colorectal cancer precursor is increasingly recognised. However, the true prevalence SPs is largely unknown. We aimed to evaluate the detection rate of SPs subtypes as well as serrated polyposis syndrome (SPS) among European screening cohorts. METHODS: Prospectively collected screening cohorts of ≥1000 individuals were eligible for inclusion. Colonoscopies performed before 2009 and/or in individuals aged below 50 were excluded. Rate of SPs was assessed, categorised for histology, location and size. Age-sex-standardised number needed to screen (NNS) to detect SPs were calculated. Rate of SPS was assessed in cohorts with known colonoscopy follow-up data. Clinically relevant SPs (regarded as a separate entity) were defined as SPs ≥10 mm and/or SPs >5 mm in the proximal colon. RESULTS: Three faecal occult blood test (FOBT) screening cohorts and two primary colonoscopy screening cohorts (range 1.426-205.949 individuals) were included. Rate of SPs ranged between 15.1% and 27.2% (median 19.5%), of sessile serrated polyps between 2.2% and 4.8% (median 3.3%) and of clinically relevant SPs between 2.1% and 7.8% (median 4.6%). Rate of SPs was similar in FOBT-based cohorts as in colonoscopy screening cohorts. No apparent association between the rate of SP and gender or age was shown. Rate of SPS ranged from 0% to 0.5%, which increased to 0.4% to 0.8% after follow-up colonoscopy. CONCLUSIONS: The detection rate of SPs is variable among screening cohorts, and standards for reporting, detection and histopathological assessment should be established. The median rate, as found in this study, may contribute to define uniform minimum standards for males and females between 50 and 75 years of age.

International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

The spectrum of aseptic central nervous system infections in southern Germany - demographic, clinical and laboratory findings.

BACKGROUND AND PURPOSE: Aseptic infections of the central nervous system (CNS) are frequently observed in Germany. However, no study has systematically addressed the spectrum of aseptic CNS infections in Germany. METHODS: Data on 191 adult patients diagnosed from January 2007 to December 2014 with aseptic meningitis or encephalitis/meningoencephalitis at our hospital were collected by chart review and analyzed for demographic, clinical and laboratory findings. Patients were stratified according to the causative virus and findings were compared between groups. RESULTS: In our cohort, meningitis was caused in 36% by enterovirus (EV), 15% by herpes simplex virus (HSV), 12% by varicella zoster virus (VZV) and 5% by tick borne encephalitis (TBE). Encephalitis/meningoencephalitis was caused in 13% by HSV, 13% by VZV, and three out of 11 tested patients were positive for TBE. The highest incidence of EV infections was between 25 and 35 years and of HSV infections between 30 and 60 years. VZV infections had a bimodal distribution peaking below 30 and above 70 years. VZV and EV infections were more frequently observed during summer, whereas HSV infections showed no seasonal preference. Inflammatory changes in cerebrospinal fluid (CSF) were highest in HSV and lowest in EV infections. CONCLUSIONS: Polymerase chain reaction tests for HSV, VZV and EV in CSF and TBE serology determined the causative virus in over 60% of tested patients. The age of affected patients, seasonal distribution, disease course and inflammatory changes in CSF differ between groups of patients affected by the most common viral infections.

Gestational age at diagnosis of early-onset fetal growth restriction and impact on management and survival: a population-based cohort study.

OBJECTIVE: To investigate the impact of gestational age (GA) at diagnosis of fetal growth restriction (FGR) on obstetric management and rates of live birth and survival for very preterm infants with early-onset FGR. DESIGN: Population-based cohort study. SETTING: All maternity units in 25 French regions in 2011. POPULATION: Fetuses diagnosed with FGR before 28 weeks of gestation among singleton births between 22 and 31 weeks of gestation without severe congenital anomalies. METHODS: We studied the effects of GA at diagnosis on perinatal management and outcomes. We used multivariable regression to identify antenatal factors (maternal characteristics, ultrasound measurements and sex) associated with the probability of live birth. MAIN OUTCOMES MEASURES: Live birth and survival to discharge from neonatal care. RESULTS: A total of 436 of 3698 fetuses were diagnosed with FGR before 28 weeks (11.8%); 66.9% were live born and 54.4% survived to discharge. 50% were live born when diagnosis occurred before 25 weeks, 66% at 25 weeks and >90% at 26 and 27 weeks of gestation. In all, 94.1% of live births were by prelabour caesarean, principally for maternal indications before 26 weeks. Low GA at diagnosis, an estimated fetal weight or abdominal circumference below the third centile and male sex were adversely associated with live birth in adjusted models. CONCLUSION: Gestational age at FGR diagnosis had an impact on the probability of live birth and survival, after consideration of other perinatal characteristics. Investigations of the outcomes of births with early-onset FGR need to include stillbirths and information on the GA at which FGR is diagnosed. TWEETABLE ABSTRACT: Evaluations of active management of pregnancies with early onset growth restriction should include stillbirths.

Updated Next-to-Next-to-Leading-Order QCD Predictions for the Weak Radiative B-Meson Decays.

Weak radiative decays of the B mesons belong to the most important flavor changing processes that provide constraints on physics at the TeV scale. In the derivation of such constraints, accurate standard model predictions for the inclusive branching ratios play a crucial role. In the current Letter we present an update of these predictions, incorporating all our results for the O(α_{s}^{2}) and lower-order perturbative corrections that have been calculated after 2006. New estimates of nonperturbative effects are taken into account, too. For the CP- and isospin-averaged branching ratios, we find B_{sγ}=(3.36±0.23)×10^{-4} and B_{dγ}=(1.73_{-0.22}^{+0.12})×10^{-5}, for E_{γ}>1.6 GeV. Both results remain in agreement with the current experimental averages. Normalizing their sum to the inclusive semileptonic branching ratio, we obtain R_{γ}≡(B_{sγ}+B_{dγ})/B_{cℓν}=(3.31±0.22)×10^{-3}. A new bound from B_{sγ} on the charged Higgs boson mass in the two-Higgs-doublet-model II reads M_{H^{±}}>480 GeV at 95% C.L.

Prevalence and characteristics of women reporting poor mental health during pregnancy: Findings from the 2010 French National Perinatal Survey.

BACKGROUND: Self-rated mental health is a useful indicator to examine the positive dimension of mental health and psychological well-being. The primary objective of this study was to estimate the prevalence of poor self-rated mental health during pregnancy in a nationally representative population in France. The second objective was to assess the sociodemographic and medical characteristics associated with this condition and with a health professional's consultation for psychological problems. METHODS: The study was based on the 2010 French National Perinatal Survey, which included all singleton live births in French maternity units during a 1-week period (n=14,326 women). Self-rated mental health was assessed using the following single-item question: "During your pregnancy, how did you feel from a psychological point of view: good - fairly good - rather poor - poor?" Women were also asked if they had visited a healthcare professional for psychological problems. They were interviewed between delivery and discharge to collect information on mental health, sociodemographic and medical characteristics, the context of their pregnancy, and their prenatal care. RESULTS: Of the women interviewed, 8.9% [95% CI, 8.5-9.5%] reported poor self-rated mental health during pregnancy. Among them, 18.7% consulted a healthcare professional for psychological problems. Sociodemographic characteristics indicative of social disadvantage were associated with a higher-risk of poor self-rated mental health, and a social gradient was observed. However, more favorable social characteristics were associated with consultation with a healthcare professional for these psychological difficulties. The reaction to the discovery of pregnancy and prenatal care differed significantly depending on self-rated mental health. Women with poor mental health had more complicated pregnancies. CONCLUSION: This study showed strong associations between many socially disadvantaged characteristics and a positive dimension of mental health. The findings suggest that well-being measures such as self-rated mental health should be routinely assessed during pregnancy so that women can be offered more appropriate support.

Effect of temperature on calibration quality of structured-light three-dimensional scanners.

This paper presents the outcome of research into the effects of ambient temperature changes on structured-light three-dimensional (3D) scanners. The tests were conducted in a thermal chamber and consisted of a comparison of the 3D measurement of a special reference unit (made of a carbon composite) performed at different temperatures, with measurements performed at the calibration temperature. A contact measuring arm with temperature compensation was used as a reference. Based on the results of these experiments, we propose a method that allows us to extend the existing scanner calibration method by using a temperature-correction procedure that is based on linear and nonlinear mathematical models. An exemplary application of this procedure has shown that the range of temperatures in which scanner accuracy is within declared limits can be increased 11-fold.

Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline.

BACKGROUND AND AIM: This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for colonoscopy. METHODS: This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. RESULTS: The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4 L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2 L PEG plus ascorbate or of sodium picosulphate plus magnesium citrate may be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

Are children born after infertility treatment at increased risk of retinoblastoma?

BACKGROUND: Retinoblastoma (RB) is the most frequent eye tumour in children, with an incidence of 1 in 15-20,000 births. It accounts for 11% of all cancers in the first year of life. Except for the hereditary forms, its causes are not well-known. Studies have recently suggested an increased risk of RB among children born after IVF, but the relevant literature is sparse. We assessed the association between infertility treatment, subfertility and RB. METHODS: We included all children living in France diagnosed with RB between 1 January 2000 and 31 December 2006 at the Institut Curie, the national reference centre for RB diagnosis and treatment. We used multiple logistic regression to compare them with a national sample of births in France in 1998 and 2003 (n = 28 170). RESULTS: The study included 244 non-familial RB cases. The risk of RB increased with maternal age [adjusted odds ratio (adj OR) = 2.07, 95% confidence interval (CI) 1.33-3.22 at 35-39 years compared with younger than 25 years and adj OR = 2.42, 95% CI 1.22-4.81 at 40 years or older], but the associations with IVF (adj OR = 1.37, 95% CI 0.64-2.95) and ovarian stimulation or intrauterine insemination (adj OR = 1.35, 95% CI 0.77-2.38) were not statistically significant after adjustment for maternal age and tobacco use. Among women who had no infertility treatment, the risk of RB was significantly increased when time to pregnancy exceeded 24 months (adj OR = 2.02, 95% CI 1.17-3.48) compared with time to pregnancy ≤ 24 months. CONCLUSIONS: Our study did not observe a significantly increased risk of RB associated with infertility treatment, in particular with IVF. But we did find an increased risk for women for whom time to pregnancy exceeded 24 months.

The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer.

BACKGROUND AND STUDY AIM: While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. STUDY DESIGN: Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. CONCLUSIONS: The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.

The gaseous messenger carbon monoxide is released from the eye into the ophthalmic venous blood depending on the intensity of sunlight.

Circadian and seasonal rhythms in daylight affect many physiological processes. In the eye, energy of intense visible light not only initiates a well-studied neural reaction in the retina that modulates the secretory function of the hypothalamus and pineal gland, but also activates the heme oxygenase (HO) to produce carbon monoxide (CO). This study was designed to determine whether the concentration of carbon monoxide (CO) in the ophthalmic venous blood changes depending on the phase of the day and differing extremely light intensity seasons: summer and winter. The concentration of CO in the venous blood flowing out from the nasal cavity, where heme oxygenase (HO) is expressed, but no photoreceptors, was used as a control. Sixteen mature males of a wild boar and pig crossbreed were used for this study. Samples of ophthalmic and nasal venous blood and systemic arterial and venous blood were collected repeatedly for two consecutive days during the longest days of the summer and the shortest days of the winter. The concentrations of CO in blood samples was measured using a standard addition method. During the longest days of the summer the concentration of CO in ophthalmic venous blood averaged 3.32 ± 0.71 and 3.43 ± 0.8 nmol/ml in the morning and afternoon, respectively, and was significantly higher than in the night averaging 0.89 ± 0.12 nmol/ml (p<0.001). During the shortest day of the winter CO concentration in ophthalmic venous blood was 1.11 ± 0.10 and 1.13 ± 0.14 nmol/ml during the light and nocturnal phase, respectively, and did not differ between phases, but was lower than in the light phase of the summer (p<0.01). The CO concentration in the control nasal venous blood did not differ between seasons and day phases and was lower than in ophthalmic venous blood during the summer (p<0.01) and winter (p<0.05). The results indicate that the gaseous messenger carbon monoxide is released from the eye into the ophthalmic venous blood depending on the intensity of sunlight.

Prevalence of risk factors for foot ulceration in patients with end-stage renal disease on haemodialysis.

BACKGROUND: End-stage renal disease (ESRD) has been associated with foot ulceration and lower extremity amputation (LEA). However, the underlying risk factors for foot ulceration have received limited attention in this population. AIM: The aim of this study was to investigate the prevalence and type of risk factors for foot ulceration present in patients with ESRD on haemodialysis without the coexistence of diabetes mellitus (DM). METHODS: One hundred and ninety participants with ESRD and/or DM were recruited over a 6-week period. Participants were allocated into one of three groups: (i) ESRD without DM; (ii) DM without ESRD; and (iii) coexisting ESRD and DM. Participants were screened for the risk factors for foot ulceration. Statistical comparisons were made between the three groups for both the prevalence and type of risk factors using a Fisher's exact test. RESULTS: Risk factors for foot ulceration were found to be highly prevalent in the ESRD population. Participants with both ESRD and DM exhibited statistically significant differences in risk factor presentation for peripheral neuropathy (P= 0.033), vascular insufficiency (P= 0.001) and footwear (P= 0.037) in comparison with participants with DM alone. CONCLUSION: There are high prevalence rates of risk factors for foot ulceration in the ESRD population on haemodialysis and are comparable with those with DM. Individuals with coexisting ESRD and DM have an even greater risk for foot ulceration and LEA. This highlights the importance that regular foot screening, preventative education and treatment are necessary for patients with ESRD potentially to reduce the risk of foot ulcerations and LEAs.

Pre-pregnancy body mass index and weight gain during pregnancy: relations with gestational diabetes and hypertension, and birth outcomes.

To study the relationship between pre-pregnancy body mass index (BMI) and weight gain during pregnancy with pregnancy and birth outcomes, with a focus on gestational diabetes and hypertension and their role in the association with fetal growth. We studied 1,884 mothers and offspring from the Eden mother-child cohort. Weight before pregnancy (W1) and weight after delivery (W2) were collected and we calculated BMI and net gestational weight gain (netGWG = (W2 - W1)/(weeks of gestation)). Gestational diabetes, hypertension gestational age and birth weight were collected. We used multivariate linear or logistic models to study the association between BMI, netGWG and pregnancy and birth outcomes, adjusting for center, maternal age and height, parity and average number of cigarettes smoked per day during pregnancy. High BMI was more strongly related to the risk of giving birth to a large-for-gestational-age (LGA) baby than high netGWG (odds ratio OR [95% CI] of 3.23 [1.86-5.60] and 1.61 [0.91-2.85], respectively). However, after excluding mothers with gestational diabetes or hypertension the ORs for LGA, respectively weakened (OR 2.57 [1.29-5.13]) for obese women and strengthened for high netGWG (OR 2.08 [1.14-3.80]). Low in comparison to normal netGWG had an OR of 2.18 [1.20-3.99] for pre-term birth, which became stronger after accounting for blood pressure and glucose disorders (OR 2.70 [1.37-5.34]). Higher net gestational weight gain was significantly associated with an increased risk of LGA only after accounting for blood pressure and glucose disorders. High gestational weight gain should not be neglected in regard to risk of LGA in women without apparent risk factors.

Influence of fetal and parental factors on intrauterine growth measurements: results of the EDEN mother-child cohort.

OBJECTIVE: In small-for-gestational-age neonates, parental and fetal characteristics can be used to distinguish between constitutionally small size and growth restriction, which is associated with a higher risk of morbidity and mortality. The aim of this study was to quantify relationships of parental and fetal characteristics with fetal ultrasound measurements. METHODS: The EDEN mother-child cohort included 2002 pregnant women with singleton pregnancies attending one of two university hospitals. Data from two routine ultrasound examinations for fetal biometry were recorded, at 20-25 and 30-35 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW) were studied as a function of prepregnancy maternal body mass index (BMI), maternal height, paternal height, fetal sex and gestational age. RESULTS: Data were obtained at the first scan from 1833 women and at the second scan from 1752 women. Parental anthropometric characteristics were significantly associated with ultrasound measurements at both scans. Maternal BMI was more strongly associated with AC and EFW, whereas both maternal and paternal height were more strongly associated with FL. An association was also found between fetal sex and all ultrasound measurements other than FL. CONCLUSION: Maternal and paternal anthropometric characteristics are significantly associated with ultrasound measurements in mid to late pregnancy. These relationships provide support for the use of these characteristics in ultrasound fetal size reference charts.

Combined transoral and suprahyoid approach for oropharyngeal cancers: an alternative to mandibulotomy.

UNLABELLED: Surgical treatment of oropharyngeal tumours usually requires mandibular osteotomy. Using this technique allows a better exposure and an easier excision, but this approach often generates complications. Since 1995, we used a less aggressive surgical technique, with a suprahyoid pharyngotomy when the oral approach was not sufficient, thus sparing the mandible. OBJECTIVE: The purpose of this study is to evaluate this technical evolution, ensuring that mandibular preservation doesn't affect quality of exeresis, local control and survival, while allowing a lower complication rate. MATERIAL AND METHODS: All patients who have had a surgical treatment for an oropharyngeal carcinoma between 1995 and 2001 in our center were included in this study. RESULTS: Mandibular sparing was used for 55 patients; 19 patients underwent mandibulotomy. The surgical procedure's quality was classified as clear, close, or insufficient margins. All adjuvant treatments were noted, functional and carcinologic results were evaluated. No significant differences are found for exeresis quality and local control. There are less complications (p = 0.045) and less surgical revisions (p = 0.023) in the preservation group. Survival and functional results are better in the preservation group, but without significant difference. For oropharyngeal tumours, survival is dependent on tumoural aggressivity, on general condition and co-morbidity and on the development of a second tumour. Results in local control rate (83.7% at 1 year) are satisfying compared to literature. CONCLUSION: Mandibular preservation is an efficient and safe procedure, even for T3/T4 tumours. Most of oropharyngeal tumours can be removed without mandibulotomy. The suprahyoid approach provides a good exposure when oral approach is insufficient, thus avoiding mandibulotomy and its complications.

Machine-learning facilitates selection of a novel diagnostic panel of metabolites for the detection of heart failure.

The metabolic derangement is common in heart failure with reduced ejection fraction (HFrEF). The aim of the study was to check feasibility of the combined approach of untargeted metabolomics and machine learning to create a simple and potentially clinically useful diagnostic panel for HFrEF. The study included 67 chronic HFrEF patients (left ventricular ejection fraction-LVEF 24.3 ± 5.9%) and 39 controls without the disease. Fasting serum samples were fingerprinted by liquid chromatography-mass spectrometry. Feature selection based on random-forest models fitted to resampled data and followed by linear modelling, resulted in selection of eight metabolites (uric acid, two isomers of LPC 18:2, LPC 20:1, deoxycholic acid, docosahexaenoic acid and one unknown metabolite), demonstrating their predictive value in HFrEF. The accuracy of a model based on metabolites panel was comparable to BNP (0.85 vs 0.82), as verified on the test set. Selected metabolites correlated with clinical, echocardiographic and functional parameters. The combination of two innovative tools (metabolomics and machine-learning methods), both unrestrained by the gaps in the current knowledge, enables identification of a novel diagnostic panel. Its diagnostic value seems to be comparable to BNP. Large scale, multi-center studies using validated targeted methods are crucial to confirm clinical utility of proposed markers.

Production of mammastatin, a tissue-specific growth inhibitor, by normal human mammary cells.

The growth of human mammary cells may be regulated by a balance between growth stimulatory and growth inhibitory pathways. Polypeptides of 47 and 65 kilodaltons (mammastatin) were isolated from conditioned medium of normal human mammary cells. Monoclonal antibodies against mammastatin were generated that blocked its activity and were used for purification and further characterization of the protein. Mammastatin inhibited the growth of 5 transformed human mammary cell lines, but had no effect on the growth of 11 transformed human cell lines derived from nonmammary tissues. Mammastatin appeared to be a heat-labile protein distinct from transforming growth factor-beta (TGF-beta). By immunoperoxidase staining it was detected in cultured normal human mammary cells, but was decreased in transformed mammary cells.

Experience with autosomal dominant polycystic kidney disease in patients before and after renal transplantation: a 7-year observation.

OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of multiple cysts in both kidneys. Symptoms of the disease may arise either from the presence of cysts or from increasing loss of kidney function. First symptoms usually appear in the third decade of life: lumbar pain, urinary tract infections, arterial hypertension, or renal colic due to cyst rupture or coexistent nephrolithiasis. An early diagnosis, male gender, large kidneys by sonography, arterial hypertension, hematuria, and urinary tract infections are predictive factors of a faster progression of the disease. Our aim was to establish the indications for nephrectomy among symptomatic ADPKD patients before kidney transplantation and to assess the risks of posttransplantation complications among ADPKD patients without nephrectomy. PATIENTS AND METHODS: The observed group consisted of 183 patients with ADPKD among whom 50 (27.3%) underwent kidney transplantation during a 7-year observation period (2000-2007). Among those subjects were 3 groups: (I) nephrectomy preceding transplantation; (II) nephrectomy during kidney transplantation; and (III) without nephrectomy. RESULTS: Among group I before transplantation we observed: arterial hemorrhage, wound infections, and splenectomy 4 weeks after ADPKD nephrectomy; afterward we observed: urinary tract infections and contralateral cyst infection. Among group II we only observed 1 case of wound infection. Among group III we observed: ascending urinary tract infections, cyst infections, and cyst hemorrhage. Cyst hemorrhage and cyst infections led mainly to ADPKD kidney nephrectomy. During the observation time, 80.95% of grafts were functioning. CONCLUSIONS: Unilateral nephrectomy is a well-founded preliminary surgical treatment before kidney transplantation. Bilateral nephrectomy before or during transplantation eliminates ADPKD complications and does not significantly increase general complications. The greatest numbers of complications and of graft losses were observed among the group without pretransplantation nephrectomy.