Etiology and therapy indication for cochlear implantation in children with single-sided deafness : Retrospective analysis.

OBJECTIVE: The characteristics of children with single-sided deafness (SSD) who become candidates for unilateral cochlear implantation (uCI) were identified. STUDY DESIGN: In all, 118 children with SSD presenting from 2013-2019 to a tertiary pediatric children's hospital were retrospectively assessed regarding candidacy for uCI. RESULTS: Of the 118 children, 103 had completed uCI candidacy assessment, while 15 were undergoing this assessment at the time of review. More than half of children did not go on to implantation (63/103, 61%), with the 2 main reasons being (1) half (31/63) did not meet candidacy criteria for implantation, most commonly due to cochlear nerve aplasia/hypoplasia (31/82 who were assessed with MRI, 38%) and (2) families (30/103; 29%) declined participation in the surgical arm of the trial. The most common etiologies of SSD in the 37/103 (36%) children who both met candidacy and consented to implantation were congenital cytomegalovirus (cCMV; 16/37, 43%), unknown (6/37, 16%), cochleovestibular anomaly and trauma (each 5/37, 14%). CONCLUSIONS: Many children with SSD who present for implant candidacy assessment do not ultimately receive uCI. Major factors contributing to noncandidacy are cochlear nerve aplasia and parental acceptance of the intervention. While approximately half of children with SSD in our cohort were candidates for implantation, only 1/3 of the total cohort proceeded with implantation with the main predictors of acceptability of this intervention being an etiology (i.e., cCMV) that carries risk of progressive deterioration in the better hearing ear or SSD that was sudden in onset. These findings provide important insight into this new population of cochlear implant users and the emerging acceptance of intervention in children with SSD.

Treatment outcomes of recurrent respiratory papillomatosis : Retrospective analysis of juvenile and adult cases.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease of viral etiology which is characterized by multiple, recurrent growth of papillomas in the aerodigestive tract. MATERIALS AND METHODS: The surgical outcomes and the recurrence rates of 106 patients with RRP of the larynx were analyzed. The patients were treated at the University of Magdeburg between 1983 and 2014. The surgical outcomes of conventional and laser surgery regarding time to relapse and complications were compared. In addition, the influence of the quadrivalent vaccine Gardasil® on the disease was analyzed in 10 patients. RESULTS: Children with RRP had a statistically significant greater number of surgeries throughout their lifetimes compared to adult patients. There were no differences between the adult (n = 79) and juvenile (n = 27) groups in the time to relapse and the number of surgeries/year. The time to relapse and number of procedures/year were not influenced by the various surgical methods. Complications after conventional and laser surgery were not statistically different between the two groups. Serious complications and the need for a tracheotomy were only reported after conventional surgery. In the 10 patients who were immunized with Gardasil®, a statistically significant lower number of surgeries/year after vaccination was achieved. CONCLUSION: RRP is a rare disease. Treatment requires experience and may be very difficult. The analysis of the course of the disease has shown that the treatment of choice is surgical excision with the CO2 laser combined with the quadrivalent or polyvalent vaccine. Consequent vaccination of both boys and girls has the potential to reduce the occurrence of RRP.

[Treatment outcomes of recurrent respiratory papillomatosis : Retrospective analysis of juvenile and adult cases. German version]. / Behandlungsergebnisse bei rezidivierender respiratorischer Papillomatose : Retrospektive Analyse juveniler und adulter Fälle.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease of viral etiology which is characterized by multiple, recurrent growth of papillomas in the aerodigestive tract. MATERIALS AND METHODS: The surgical outcomes and the recurrence rates of 106 patients with RRP of the larynx were analyzed. The patients were treated at the University of Magdeburg between 1983 and 2014. The surgical outcomes of conventional and laser surgery regarding time to relapse and complications were compared. In addition, the influence of the quadrivalent vaccine Gardasil® on the disease was analyzed in 10 patients. RESULTS: Children with RRP had a statistically significant greater number of surgeries throughout their lifetimes compared to adult patients. There were no differences between the adult (n = 79) and juvenile (n = 27) groups in the time to relapse and the number of surgeries/year. The time to relapse and number of procedures/year were not influenced by the various surgical methods. Complications after conventional and laser surgery were not statistically different between the two groups. Serious complications and the need for a tracheotomy were only reported after conventional surgery. In the 10 patients who were immunized with Gardasil®, a statistically significant lower number of surgeries/year after vaccination was achieved. CONCLUSION: RRP is a rare disease. Treatment requires experience and may be very difficult. The analysis of the course of the disease has shown that the treatment of choice is surgical excision with the CO2 laser combined with the quadrivalent or polyvalent vaccine. Consequent vaccination of both boys and girls has the potential to reduce the occurrence of RRP.

Multiparametric modeling of the ineffective efforts in assisted ventilation within an ICU.

In the context of assisted ventilation in ICU, it is of vital importance to keep a high synchronization between the patient's attempt to breath and the assisted ventilation event, so that the patient receives the ventilation support requested. In this work, experimental equipment is employed, which allows for unobtrusive and continuous monitoring of a multiple relevant bioparameters. These are meant to guide the medical professionals in appropriately adapting the treatment and fine-tune the ventilation. However, synchronization phenomena of different origin (neurological, mechanical, ventilation parameters) may occur, which vary among patients, and during the course of monitoring of a single patient, the timely recognition of which is challenging even for experts. The dynamics and complex causal relations among bioparameters and the ventilation synchronization are not well studied. The purpose of this work is to elaborate on a methodology toward modeling the ventilation synchronization failures based on the evolution of monitored bioparameters. Principal component analysis is employed for the transformation into a small number of features and the investigation of repeating patterns and clusters within measurements. Using these features, nonlinear prediction models based on support vector machines regression are explored, in terms of what past knowledge is required and what is the future horizon that can be predicted. The proposed model shows good correlation (over 0.74) with the actual outputs, constituting an encouraging step toward understanding of ICU ventilation dynamic phenomena.

Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study.

BACKGROUND: Sepsis emerges as the leading risk factor for acute kidney injury (AKI) development in critically ill patients. Much effort has been invested so far on early diagnosis of AKI using promising biomarkers. This study aimed to determine whether urine alpha1-microglobulin (α1m), a lipocaline member previously used as an indicator of proximal tubular dysfunction, can early predict the development of sepsis-associated AKI (SAAKI) in critically ill patients. METHODS: A prospective, observational study was conducted in a single center Intensive Care Unit (ICU). Patients with normal renal function admitted to the ICU followed for sepsis and AKI development. Urine α1m levels were analyzed in pooled samples from 24-hour urine collections on sepsis onset and at various time points thereafter. The diagnostic performance of urine α1m was assessed using thenonparametriccalculation of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Among 286 critically ill patients admitted to our ICU in a year, 45 patients with sepsis met the inclusion criteria. SAAKI developed in 16 septic patients (35.6%). Urine α1m levels were significantly elevated in all septic patients (average value of all samples on the day of sepsis: 46.02 ± 7.17 mg/l) and showed a trend to increase in patients who finally developed SAAKI. The AUC for SAAKI prediction according to α1m urine levels 24-hours before SAAKI onset was 0.739 (sensitivity 87.5%, specificity 62.07%, cutoff level 47.9 mg/l). Urine α1m 24-hours before SAAKI, serum creatinine on sepsis onset and Acute Physiology and Chronic Health Evaluation II (APACHE II) score on sepsis onset emerged as the most powerful independent predictors of SAAKI. The combination of these three parameters improved the AUC for SAAKI prediction to 0.944. CONCLUSION: Urine α1m levels might help in the early prediction of SAAKI development and may prove useful biomarker. The pathogenetic implications of α1m in sepsis and SAAKI need further investigation. Hippokratia 2014; 18 (3): 262-268.

Temperature multiscale entropy analysis: a promising marker for early prediction of mortality in septic patients.

A few studies estimating temperature complexity have found decreased Shannon entropy, during severe stress. In this study, we measured both Shannon and Tsallis entropy of temperature signals in a cohort of critically ill patients and compared these measures with the sequential organ failure assessment (SOFA) score, in terms of intensive care unit (ICU) mortality. Skin temperature was recorded in 21 mechanically ventilated patients, who developed sepsis and septic shock during the first 24 h of an ICU-acquired infection. Shannon and Tsallis entropies were calculated in wavelet-based decompositions of the temperature signal. Statistically significant differences of entropy features were tested between survivors and non-survivors and classification models were built, for predicting final outcome. Significantly reduced Tsallis and Shannon entropies were found in non-survivors (seven patients, 33%) as compared to survivors. Wavelet measurements of both entropy metrics were found to predict ICU mortality better than SOFA, according to a combination of area under the curve, sensitivity and specificity values. Both entropies exhibited similar prognostic accuracy. Combination of SOFA and entropy presented improved the outcome of univariate models. We suggest that reduced wavelet Shannon and Tsallis entropies of temperature signals may complement SOFA in mortality prediction, during the first 24 h of an ICU-acquired infection.

Early embryonic lethality in genetically engineered mice: diagnosis and phenotypic analysis.

Embryonic lethality is a common phenotype that occurs in mice that are homozygous for genetically engineered mutations. These phenotypes highlight the time and place that a gene is first required during embryogenesis. Early embryonic lethality (ie, before and up to mid-gestation) can be straightforward to analyze because the stage at which death occurs suggests why an embryo has failed. Here we summarize general strategies for analyzing early embryonic lethal phenotypes in genetically engineered mouse mutants.

Oscillating LDL accumulation in normal human aortic arch - shear dependent endothelium.

OBJECTIVE: Abnormal mass transfer of blood components to the arterial walls initiates atherosclerosis. Understating the role of mass transfer within the arterial walls requires quantitative analysis. The oscillating lipid accumulation in the aortic wall is examined in the normal human aortic arch with shear dependent endothelium properties. METHODS: A semi-permeable nature of the arterial wall computational model, applied in the normal human aortic arch under unsteady normal flow and mass conditions, is incorporated with hydraulic conductivity and permeability treated as wall shear stress dependent. The coupling of fluid dynamics and solute dynamics at the endothelium was achieved by the Kedem-Katchalsky equation. A typical aortic arch blood flow waveform at resting conditions and lasting 800 msec is applied. RESULTS: With constant values of water infiltration and endothelial permeability the surface vertex average normalized luminal concentration is 4.25 % higher than that at the entrance. With shear dependent values the surface vertex average normalized luminal concentration is 7.3 % higher than at the entrance. The luminal surface concentration at the arterial wall is flow-dependent with local variations due to geometric features. Concave sides of the aortic arch exhibit, relatively to the convex ones, elevated low density lipoprotein at all time steps. CONCLUSIONS: The degree of elevation in luminal surface LDL concentration is mostly affected from the water infiltration velocity at the vessel wall. Shear dependent endothelial values must be taken into account whenever fluid and mass flow within the arterial system is incorporated.

Influence of oscillating flow on LDL transport and wall shear stress in the normal aortic arch.

Lipid accumulation in the aortic wall is an important factor in the development of atherosclerosis. The Low Density Lipoprotein (LDL) at the surface of the endothelium in relation to Wall Shear Stress (WSS) in the normal human aortic arch under unsteady, normal flow and mass conditions was computationally analysed. Concave sides of the aortic arch exhibit, relatively to the convex ones, elevated LDL levels at the surface of the endothelium for all time steps. At the peak systolic velocity, the LDL level reaches a value 23.0% higher than that at entrance in the ascending-descending aorta region. The corresponding LDL levels at the surface of the endothelium for the near minimum entrance velocity instant reaches 26.0%. During the cardiac cycle, the highest area averaged normalized LDL taken up as compared to the lowest one is 0.69%. WSS plays an important role in the lipid accumulation. Low WSS regions are exposed to high LDL levels at the surface of the endothelium. Regions of elevated LDL levels do not necessarily co-locate to the sites of lowest WSS. The near wall paths of the velocities might be the most important factor for the elevated LDL levels at the surface of the endothelium.

The oocyte population is not renewed in transplanted or irradiated adult ovaries.

BACKGROUND: According to conventional theory, the oocyte population is not renewed in mammalian ovaries after birth. A new hypothesis proposes that oocytes are generated continuously from haematopoietic progenitor cells. There is, however, no evidence that they can ovulate, although they may partially restore fertility by organizing 'helper follicles'. The hypothesis that follicles can form de novo in adult ovaries has been tested in a transplant model. METHODS: Ovaries from adult mice were transplanted under the kidney capsule or into the ovarian bursa of histocompatible, transgenic CAG::H2B-EGFP host animals. Some donors were sterilized before transplantation by X-irradiation to ensure 'empty niches' were available for repopulation. The phenotype of follicular oocytes at 2, 4 and 8 weeks post-transplantation was scored by epifluorescence. RESULTS: A total of 819 oocytes were examined in 30 ovarian grafts. None expressed green fluorescence, as would be predicted if they had formed de novo from germ cell progenitors in the systemic circulation of the host. Furthermore, small follicles eliminated by irradiation were not replaced in transplanted ovaries, and the few growing follicles present were apparently survivors of the original population. CONCLUSIONS: No evidence was found to support the hypothesis that progenitor cells from extra-ovarian sources can repopulate the adult ovary. The findings are consistent with the conventional view that a limited number of oocytes are formed before birth and declines with age. The study did not, however, rule out the possibility that germline stem cells may reside in the adult ovary.

The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment.

Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity.

Effect of a policy for restriction of selected classes of antibiotics on antimicrobial drug cost and resistance.

Based on the instructions of the National Organization of Pharmaceutical Agents (Greece) from July 1, 2003, quinolones, 3( rd )and 4(th )generation cephalosporins, carbapenems, monobactams, glycopeptides, oxazolidinones, and streptogramins were considered as "restricted" antibiotics that could be used only with the approval of an Infectious Disease specialist. We analyzed the effect of the policy on the consumption and cost of antibiotics as a group and of specific classes, adjusted for the patient load, as well as on the antimicrobial resistance of isolated bacteria. We analyzed 5 trimesters (2 prior and 3 after the implementation of the new policy). A 20% and 16% reduction in adjusted consumption [in daily defined doses (DDDs)] and cost, respectively, of the restricted antibiotics was accomplished during the first trimester after implementation of the new policy. However, this was accompanied by a 36% and 56% increase in adjusted consumption and cost, respectively, of unrestricted antibiotics. A logistic regression model that we performed showed that the new policy had an independent positive effect on the in vitro antimicrobial susceptibility of Pseudomonas aeruginosa (p=0.051) but not of Acinetobacter baumannii and Escherichia coli isolates. Our data suggest that there are considerable limitations to the programs aiming to reduce the consumption of restricted antibiotics through the approval of their use by specialists, at least in some settings.

T-box genes in development: from hydra to humans.

The T-box gene family was uncovered less than a decade ago but has been recognized as important in controlling many and varied aspects of development in metazoans from hydra to humans. Extensive screening and database searching has revealed several subfamilies of genes with orthologs in species as diverse as Caenorhabditis elegans and humans. The defining feature of the family is a conserved sequence coding for a DNA-binding motif known as the T-box, named after the first-discovered T-box gene, T or Brachyury. Although several T-box proteins have been shown to function as transcriptional regulators, to date only a handful of downstream target genes have been discovered. Similarly, little is known about regulation of the T-box genes themselves. Although not limited to the embryo, expression of T-box genes is characteristically seen in dynamic and highly specific patterns in many tissues and organs during embryogenesis and organogenesis. The essential role of several T-box genes has been demonstrated by the developmental phenotypes of mutant animals.

DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.

The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human disorder, usually associated with deletions of chromosome 22q11. The genetic basis for the wide range of developmental anomalies in the heart, glands and facial structures has been elusive. We have investigated the potential role of one candidate gene, Tbx1, which encodes a transcription factor of the T-box family, by producing a null mutation in mice. We found that mice heterozygous for the mutation had a high incidence of cardiac outflow tract anomalies, thus modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1-/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae and cleft palate. On the basis of this phenotype in mice, we propose that TBX1 in humans is a key gene in the etiology of DGS/VCFS.

The stem cells of early embryos.

Cells resident in an organism that possess the dual capacity for self-renewal and differentiation into a spectrum of subtypes are referred to as stem cells. In the past decade, basic research performed on stem cells has shed light on the molecular pathways operating in vivo which can be harnessed in vitro for the establishment of cell lines mirroring the stem cells in the organism. The attractiveness of stem cells as in vitro models of organotypic differentiation and their potential application in a clinical context holds great promise and is only beginning to be exploited. Stem cells can be broadly grouped into two categories based on their origin from either the embryonic or the adult. Only the early embryo possesses truly pluripotent cells that can give rise to all the cell types present in the embryo proper and adult. The adult, on the other hand, possesses specialized, tissue- or organ-specific stem cell types, which can give rise to the differentiated cell types of that specific organ and have in some instances been shown to transdifferentiate. However, no stem cell obtained from an adult organism has yet been shown to exhibit developmental potential matching the breadth of that of stem cells obtained from embryos. This review focuses on the different types of stem cells that are resident in early stage mammalian embryos, detailing their derivation and propagation in addition to highlighting their developmental potential and opportunities for future applications.

Mapping and expression analysis of the mouse ortholog of Xenopus Eomesodermin.

The T-box gene family has been conserved throughout metazoan evolution. The genes code for putative transcription factors which share a uniquely defining DNA binding domain, known as the T-box ([Bollag et al., 1994]). They are implicated in the control of diverse developmental processes by their highly specific expression patterns throughout gastrulation and organogenesis in mouse and other species ([Chapman et al., 1996]) ([Gibson-Brown et al., 1998]), and by mutations in T-box genes that have profound developmental effects ([Papaioannou, 1997]; [Chapman and Papaioannou, 1998]; [Papaioannou and Silver, 1998]). In this report, we describe the mapping and expression pattern of the mouse ortholog of a gene, Eomesodermin, first identified in Xenopus ([Ryan et al., 1996]). The mouse gene was previously reported ([Wattler et al., 1998]) under the name MmEomes. The gene maps to mouse chromosome 9 in a region syntenic with human chromosome 3p. Mouse eomesodermin is expressed in the trophoblast of the blastocyst and in its derivative, the chorionic ectoderm. At gastrulation, eomesodermin is expressed in the primitive streak and embryonic mesoderm as well, but this expression disappears prior to the end of gastrulation. Later, eomesodermin is expressed in the developing forebrain, in a pattern largely overlapping a closely related T-box gene, Tbr1 ([Bulfone et al., 1995]), and is also seen in a localized area of each limb.