Partial cricotracheal resection in children weighing less than 10 kilograms.

OBJECTIVES: To assess the long-term outcome, safety, and efficacy of partial cricotracheal resection (PCTR) for subglottic stenosis in a group of children and infants weighing less than 10 kg at the time of the surgery. STUDY DESIGN: Historical cohort study. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: Thirty-six children weighing less than 10 kg at the time of the surgery were compared to a group of 65 children who weighed more than 10 kg. The Kaplan Meier method and Cox regression were carried out to detect differences in decannulation time and rates and to examine the influence of various parameters (i.e., comorbidities, type of surgery, and complications requiring revision surgery) at the time of decannulation. Evaluation of the long-term outcome was based on questionnaires assessing breathing, voice, and swallowing. RESULTS: Decannulation rate was 92 percent (33/36) for the group of children weighing less than 10 kg. No significant differences were found between the two body weight groups with respect to the aforementioned covariates. The median follow-up period was nine years (range, 1-23 yrs). Questionnaire responses revealed completely normal breathing and swallowing in 72 percent and 90 percent of the children, respectively. Seventy-one percent of the patients considered their voice to be rough or weak. CONCLUSION: PCTR in infants and children weighing less than 10 kg is a safe and efficient technique with similar long-term results when compared to results seen in older and heavier children.

Reflections on Partial Least Squares Path Modeling

The purpose of the present article is to take stock of a recent exchange in Organizational Research Methods between critics (Rönkkö & Evermann, 2013) and proponents (Henseler et al., 2014) of partial least squares path modeling (PLS-PM). The two target articles were centered around six principal issues, namely whether PLS-PM: (1) can be truly characterized as a technique for structural equation modeling (SEM); (2) is able to correct for measurement error; (3) can be used to validate measurement models; (4) accommodates small sample sizes; (5) is able to provide null hypothesis tests for path coefficients; and (6) can be employed in an exploratory, model-building fashion. We summarize and elaborate further on the key arguments underlying the exchange, drawing from the broader methodological and statistical literature in order to offer additional thoughts concerning the utility of PLS-PM and ways in which the technique might be improved. We conclude with recommendations as to whether and how PLS-PM serves as a viable contender to SEM approaches for estimating and evaluating theoretical models.

Partial Cricotracheal Resection in Children: Potential Pitfalls and Avoidance of Complications.

OBJECTIVES: To delineate the various factors contributing to failure or delay in decannulation after partial cricotracheal resection (PCTR) in children. STUDY DESIGN: Case series. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: A retrospective case review of 100 children who underwent PCTR between 1978 and 2008 for severe subglottic stenosis using an ongoing database. RESULTS: Ninety of 100 (90%) patients were decannulated. Six patients needed secondary tracheostomy. The results of the preoperative evaluation showed grade II stenosis in four patients, grade III in 64 patients, and grade IV in 32 patients. The overall decannulation rate was 100 percent in grade II, 95 percent in grade III, and 78 percent in grade IV stenosis. Fourteen (14%) patients required revision open surgery. The most common cause of revision surgery was posterior glottic stenosis. Partial anastomotic dehiscence was seen in four patients. Delayed decannulation (>1 year) occurred in nine patients. Overall mortality rate in the whole series was 6 percent. No deaths were directly related to the surgery. No iatrogenic recurrent laryngeal nerve injury was present in the entire series. CONCLUSION: Comorbidities and associated syndromes should be addressed before PCTR is planned to improve the final postoperative outcome in terms of decannulation. Perioperative morbidity due to anastomotic dehiscence, to a certain extent, can be avoided by intraoperative judgment in the selection of double-stage surgery when more than five tracheal rings need to be resected. Subglottic stenosis with glottic involvement continues to pose a difficult challenge to pediatric otolaryngologists, often necessitating revision procedures.

Rib fractures at postmortem computed tomography (PMCT) validated against the autopsy

To evaluate the sensitivity of postmortem computed tomography (PMCT) in rib fracture detection validated against autopsy. Fifty-one forensic cases underwent a postmortem CT prior to forensic autopsy. Two image readers (radiologist and forensic pathologist) assessed high resolution CT data sets for rib fractures. Correct recognition rates (CRR), sensitivity and specificity values were calculated over all observations as well as individually for every rib and region. Additionally, for partial rib fractures the sensitivity of autopsy was calculated vice versa. 3876 entries in each study protocol (autopsy, PMCT radiologist and PMCT forensic pathologist) were investigated. A total of 690 fractures (autopsy), 491 (PMCT and radiologist) and 559 (PMCT and forensic pathologist) were detected. The CRR was 0.85. Sensitivity and specificity of PMCT for rib fracture detection were 0.63 (0.58 radiologist, 0.68 forensic pathologist) and 0.97 (both readers 0.97), respectively. Low CRR and sensitivity values were obtained for antero-lateral fractures. Partial rib fractures were better detected by PMCT. PMCT has a rather low sensitivity for rib fracture detection when validated against autopsy and indicates that clinical CT may also demonstrate a reasonable number of false negatives. Partial rib fractures often remain undetected at autopsy.

Symptomatic complex partial status epilepticus manifesting as utilization behavior of a mobile phone.

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions.

After antigenic challenge, naive T lymphocytes enter a program of proliferation and differentiation during the course of which they acquire effector functions and may ultimately become memory cells. In humans, the pathways of effector and memory T-cell differentiation remain poorly defined. Here we describe the properties of 2 CD8+ T-lymphocyte subsets, RA+CCR7-27+28+ and RA+CCR7-27+28-, in human peripheral blood. These cells display phenotypic and functional features that are intermediate between naive and effector T cells. Like naive T lymphocytes, both subsets show relatively long telomeres. However, unlike the naive population, these T cells exhibit reduced levels of T-cell receptor excision circles (TRECs), indicating they have undergone additional rounds of in vivo cell division. Furthermore, we show that they also share effector-type properties. At equivalent in vivo replicative history, the 2 subsets express high levels of Fas/CD95 and CD11a, as well as increasing levels of effector mediators such as granzyme B, perforin, interferon gamma, and tumor necrosis factor alpha. Both display partial ex vivo cytolytic activity and can be found among cytomegalovirus-specific cytolytic T cells. Taken together, our data point to the presence of T cells with intermediate effector-like functions and suggest that these subsets consist of T lymphocytes that are evolving toward a more differentiated effector or effector-memory stage.

A treatment planning method for sequentially combining radiopharmaceutical therapy and external radiation therapy.

PURPOSE: Effective cancer treatment generally requires combination therapy. The combination of external beam therapy (XRT) with radiopharmaceutical therapy (RPT) requires accurate three-dimensional dose calculations to avoid toxicity and evaluate efficacy. We have developed and tested a treatment planning method, using the patient-specific three-dimensional dosimetry package 3D-RD, for sequentially combined RPT/XRT therapy designed to limit toxicity to organs at risk. METHODS AND MATERIALS: The biologic effective dose (BED) was used to translate voxelized RPT absorbed dose (D(RPT)) values into a normalized total dose (or equivalent 2-Gy-fraction XRT absorbed dose), NTD(RPT) map. The BED was calculated numerically using an algorithmic approach, which enabled a more accurate calculation of BED and NTD(RPT). A treatment plan from the combined Samarium-153 and external beam was designed that would deliver a tumoricidal dose while delivering no more than 50 Gy of NTD(sum) to the spinal cord of a patient with a paraspinal tumor. RESULTS: The average voxel NTD(RPT) to tumor from RPT was 22.6 Gy (range, 1-85 Gy); the maximum spinal cord voxel NTD(RPT) from RPT was 6.8 Gy. The combined therapy NTD(sum) to tumor was 71.5 Gy (range, 40-135 Gy) for a maximum voxel spinal cord NTD(sum) equal to the maximum tolerated dose of 50 Gy. CONCLUSIONS: A method that enables real-time treatment planning of combined RPT-XRT has been developed. By implementing a more generalized conversion between the dose values from the two modalities and an activity-based treatment of partial volume effects, the reliability of combination therapy treatment planning has been expanded.

Formation of a direct arterial blood supply to the anterior pituitary gland following complete or partial interruption of the hypophyseal portal vessels

If regions of the anterior pituitary gland received systemic blood via a direct arterial blood supply these regions would escape hypothalamic regulation and thus be a sequela in endocrine disorders. Since, in the untreated rat, all of the blood supply to the anterior pituitary gland is via the hypophyseal portal vessels, we hypothesized that partial interruption of the portal vessels could provoke the establishment of a direct arterial blood supply (arteriogenesis). We utilized the injection of polystyrene microspheres (15 or 9 micron diameter) into the left ventricle of the heart to test this hypothesis. Microspheres are trapped in the first capillary plexus they reach since they are too large to traverse the capillaries. No microspheres reached the anterior pituitary gland of control rats, a finding consistent with the fact that the anterior pituitary gland receives all of its blood supply via the hypophyseal portal blood vessels. Microspheres were observed in the primary portal capillary plexus in the infundibulum (median eminence), infundibular stalk (pituitary stalk), and infundibular process (pars nervosa), the first capillary plexus which they reached. A lesion of the medial basal hypothalamus (MBH) which destroyed the long portal vessels did not result in arteriogenesis since few, if any, microspheres were observed in the anterior pituitary gland. We confirmed, using vascular casts, that these lesions resulted in the long-term destruction of the primary portal capillaries in the infundibulum and of the long portal vessels. In MBH-lesioned animals it appears that all of the blood supply of the anterior pituitary gland is via short portal vessels arising from the infundibular stem and process.(ABSTRACT TRUNCATED AT 250 WORDS)

A partial ordering of knots and links through diagrammatic unknotting

In this paper we de. ne a partial ordering of knots and links using a special property derived from their minimal diagrams. A link K' is called a predecessor of a link K if Cr(K') < Cr(K) and a diagram of K' can be obtained from a minimal diagram D of K by a single crossing change. In such a case, we say that K' < K. We investigate the sets of links that can be obtained by single crossing changes over all minimal diagrams of a given link. We show that these sets are specific for different links and permit partial ordering of all links. Some interesting results are presented and many questions are raised.

Partial cricotracheal resection for congenital subglottic stenosis in children: the effect of concomitant anomalies.

OBJECTIVE: To review the surgical outcomes of partial cricotracheal resection in children with severe congenital subglottic stenosis and define the effect of concomitant anomalies or syndromes affecting outcome. METHODS: Forty-one children with subglottic stenosis of congenital and mixed (acquired on congenital) etiologies who underwent partial cricotracheal resection were identified from a prospectively collected database. Children with congenital subglottic stenosis and concomitant anomalies/syndromes were compared to children with congenital subglottic stenosis with no syndromes or concomitant anomalies. Operation-specific decannulation rates and complication rates were the primary outcome measures. We performed a two-sample test of proportion using the STATA-10 software for categorical variables to detect differences in proportions. Significance was set at p value<0.05. RESULTS: Twenty-seven (66%) of 41 children had concomitant anomalies/syndromes and 14 (34%) had congenital subglottic stenosis without concomitant anomalies/syndromes. Four patients needed revision surgery in the concomitant anomaly group and two patients needed revision surgery in the non concomitant anomaly group before achieving decannulation. The operation-specific decannulation rate in the concomitant anomaly group was 85% and 86% in the non anomaly group. When compared to children without concomitant anomaly, children with concomitant anomalies were more likely to have delayed decannulation following partial cricotracheal resection. However, this difference was not found to be statistically significant. The complication and operation-specific decannulation rates after partial cricotracheal resection were comparable to children without concomitant anomalies. Mortality rate was 11% (three of 27 patients) in the group with associated congenital anomalies or syndromes. Two patients succumbed to the primary pathology and one patient died due to tracheostomy-tube obstruction. There was no post-operative death in the non anomaly group. CONCLUSION: Partial cricotracheal resection can be done safely and effectively in children with concomitant anomalies/syndromes to achieve decannulation. The post-operative course may be prolonged but the decannulation and the complication rates are comparable to those children with congenital subglottic stenosis without concomitant anomalies.

Tracing of the Rhône River, wastewater, and mixing within Lake Geneva : stable isotope compositions of water and dissolved inorganic carbon

This study presents an evaluation of the stable isotopic composition of water (hydrogen and oxygen) and dissolved inorganic carbon (DIC) of Lake Geneva, a deep, peri-alpine lake situated at the border between Switzerland and France. The research goal is to apply vertical and seasonal variations of the isotope compositions to evaluate mixing processes of pollutants, nutrients and oxygen. Depth profiles were sampled at different locations throughout Lake Geneva on a monthly and seasonal basis over the course of three years (2009-2011). The results of the oxygen isotopic composition indicate a Rhône River interflow, which can be traced for about 55 km throughout the lake during summer. The Rhône River interflow is 7 to 15 m thick and the molar fraction of Rhône water is estimated to amount up to 37 %. Calculated density of the water and measured isotopic compositions demonstrate that the interflow depth changes in conjunction with the density gradient in the water column during fall. Partial pressure of CO2 indicates that the epilimnion is taking up CO2 from the atmosphere between spring and fall. The epilimnion is most enriched in 13CDIC in September and a progressive depletion of 13CDIC can be observed in the metalimnion from spring to late fall. This stratification is dependent on the local density stratification and the results demonstrate that parameters, which are indicating photosynthesis, are not necessarily linked to δ13CDIC values. In addition, the amount of primary production shows a strong discrepancy between summer 2009 and 2010, but δ13CDIC values of the epilimnion and metalimnion do not indicate variations. In the hypolimnion of the deep lake δ13CDIC values are constant and the progressive depletion allows tracing remineralization processes. The combination of stable carbon and oxygen isotopic compositions allows furthermore tracing Rhône River water fractions, as well as wastewater, stormwater and anthropogenic induced carbon in the water column of the shallow Bay of Vidy. In combination with the results of measured micropollutants, the study underlines that concentrations of certain substances may be related to the Rhône River interflow and/or remineralization of particulate organic carbon. Water quality monitoring and research should therefore be extended to the metalimnion as well as sediment water interface.

Biases on the administered parenteral doses of an experimental drug during phase I clinical trials

Introduction: The pharmaceutical aspects of drug administration in clinical trials receive poor consideration compared with the important attention devoted to the analytical and mathematical aspects of biological sample exploitation. During PK calculations, many researchers merely use for dose the nominal amount declared, overlooking the noticeable biases that may result in the assessment of PK parameters. The aim of this work was to evaluate the biases related to doses injected of a biosimilar drug in 2 Phase I clinical trials. Patients (or Materials) and Methods: In trial A, 12 healthy volunteers received different doses of a biosimilar of interferon beta-1a by either subcutaneous (SC) or intravenous (IV) injection. The doses were prepared by partially emptying 0.5-mL syringes supplied by the manufacturer (drop count procedure). In trial B, 12 healthy volunteers received 3 different formulations of the drug by IV injection (biosimilar without albumin [HSA], biosimilar with HSA and original brand [Rebif®]) and 2 different formulations as multiple SC injections (biosimilar HSA-free and original brand). In both trials, the actual dose administered was calculated as: D = C·V - losses. The product titer C was assessed by ELISA. The volume administered IV was assessed by weighting. Losses were evaluated by in vitro experiments. Finally, the binding of 125I-interferon to HSA was evaluated by counting the free and HSA complexed molecule fractions separated by gel filtration. Results: Interferon was not significantly adsorbed onto the lines used for its IV administration. In trial A, the titer was very close to the one declared (96 ± 7%). In trial B, it differed significantly (156 ± 10% for biosimilar with/without HSA and 123 ± 5% for original formulation). In trial A, the dose actually administered showed a large variability. The real injected volume could be biased up to 75% compared with the theoretical volume (for the lower dose administered [ie, 0.03 mL]). This was mainly attributed to a partial re-aspiration of the drug solution before withdrawing the syringe needle. A strict procedure was therefore applied in trial B to avoid these inaccuracies. Finally, in trial B, 125I-Interferon beta-1a binding to HSA appeared time dependent and slow, reaching 50% after 16-hour incubation, which is close to steady state reported for the comparator Rebif®. Conclusion: These practical examples (especially biases on actual titer and volume injected) illustrate that actual dose assessment deserves attention to ensure accuracy for estimates of clearance and distribution volume in the scientific literature and for registration purposes, especially for bioequivalence studies.

Partial protection and intrathecal invasion of CD8(+) T cells in acute canine distemper virus infection.

Initial non-inflammatory demyelination in canine distemper virus infection (CDV) develops against a background of severe immunosuppression and is therefore, thought to be virus-induced. However, recently we found a marked invasion of T cells throughout the central nervous system (CNS) in dogs with acute distemper despite drastic damage to the immune system. In the present study, this apparent paradox was further investigated by immunophenotyping of lymphocytes, following experimental CDV challenge in vaccinated and non-vaccinated dogs. In contrast to CDV infected, unprotected dogs, vaccinated dogs did not become immunosuppressed and exhibited a strong antiviral immune response following challenge with virulent CDV. In unprotected dogs rapid and drastic lymphopenia was initially due to depletion of T cells. In peripheral blood, CD4(+) T cells were more sensitive and depleted earlier and for a longer time than CD8(+) cells which recovered soon. In the cerebrospinal fluid (CSF) we could observe an increase in the T cell to B cell and CD8(+) to CD4(+) ratios. Thus, partial protection of the CD8(+) cell population could explain why part of the immune function in acute distemper is preserved. As found earlier, T cells invaded the CNS parenchyma in these dogs but also in the protected challenged dogs, which did not develop any CNS disease at all. Since markers of T cell activation were upregulated in both groups of animals, this phenomenon could in part be related to non-specific penetration of activated T cells through the blood brain barrier. However, in diseased animals much larger numbers of T cells were found in the CNS than in the protected dogs, suggesting that massive invasion of T cells in the brain requires CDV expression in the CNS.