Inter-Laboratory Concordance of Cerebrospinal Fluid and Serum Kappa Free Light Chain Measurements

The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen’s kappa coefficient (k) was used to measure agreement on positive (5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87–0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73–0.97)), while ICC decreased (to 0.81 (0.53–0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics

Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca²+ entry because of the critical roles played by Ca²+ in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (−)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling

Malignant hyperthermia associated with enflurane anesthesia.

Malignant hyperthermia is induced by potent inhalation anesthetics. Enflurane must be added to the list of those anesthetic agents (such as halothane and succinylcholine) that are associated with this condition. The patient in our study was a young woman with no history of prior exposure to general anesthetics, and no family history of complications following administration of anesthetics. The other possible causes of hyperthermia in the patient were investigated and eliminated, and the condition was finally associated with enflurane. Enflurane should not be used in patients with a family history of this rare but often lethal disorder

Trattamento con Nutrizione Enterale perdigiunale di un grave caso di esofagite da reflusso in un lattante con Sindrome di Pierre-Robin

A case of Pierre-Robin syndrome associated with gastroesophageal reflux and oesophagitis is described. The infant was firstly fed with a hydrolysed-casein formula by gastrostomy, but there was not any improvement of his clinical status, in spite of an appropriate nutrient intake. For this reason, a jejunal enteral feeding, with a semi-elemental formula and then with a hydrolysed-casein formula was started. During this nutritional treatment, the infant showed an adequate weight gain and after 52 days the weight increased from 2880 g to 4580 g

Juvenile erythrocytosis in children after liver transplantation: prevalence, risk factors and outcome

Most reports of post-transplant erythrocytosis have involved kidney recipients and, so far, there have been no large studies of onset of erythrocytosis after orthotopic liver transplantation (OLT) in children. We present a long-term survey of pediatric liver recipients, evaluating prevalence, outcome and the main potential causes of erythrocytosis, including a comprehensive mutational analysis of commonly related genes (mutations of HBB and HBA, JAK2, EPOR, VHL, EPAS1 and EGLN1). Between 2000 and 2015, 90 pediatric OLT recipients were observed for a median period of 8.7 years (range 1–20.4 [IQR 4.9–13.6] years). Five percent of the study population (4 males and 1 female) developed erythrocytosis at 8.5 years post OLT (range 4.1–14.9 [IQR 4.7–14.7]) at a median age of 16.6 years (range 8.2–18.8 [IQR 11.7–17.7]). Erythrocytosis-free survival after OLT was 98.6% at 5 years, 95% at 10 years, and 85% at 15 years, with an incidence rate of 6/1000 person-years. No cardiovascular events or thrombosis were reported. No germinal mutation could be clearly related to the development of erythrocytosis. One patient, with high erythropoietin levels and acquired multiple bilateral renal cysts, developed clinical hyper-viscosity symptoms, and was treated with serial phlebotomies. In conclusion, this prospective longitudinal study showed that erythrocytosis is a rare complication occurring several years after OLT, typically during adolescence. Erythrocytosis was non-progressive and manageable. Its pathogenesis is still not completely understood, although male gender, pubertal age, and renal cysts probably play a role

Clinical Utility of Electrophysiological Evaluation in Crigler-Najjar Syndrome

We evaluated the neurological and neurophysiological features in ten patients with genetically characterized Crigler-Najjar (CN) syndrome: four with typical type I CN had undergone orthotopic liver transplantation (OLT); six had type II CN, and three of them developed severe hyperbilirubinemia with a limited response to phenobarbital leading to an intermediate phenotype I/II. Clinical neurological and multimodal electrophysiological evaluations [electroencephalogram (EEG), visual (VEPs), motor (MEPs) and brainstem auditory (BAEPs) evoked potentials] were performed. Neurological examinations showed mild hand tremor in four patients (one pre-OLT and one post-OLT type I, two type I/II). EEG revealed high voltage paroxysmal discharges in four patients (three type I/II, and one type I with a marked improvement after OLT). VEPs showed P100 wave increased latency in five patients (three type I, and two type I/II considered for OLT evaluation). MEPs showed prolonged central motor conduction time in five patients (two type I; one type I/II; two type II). Only EEG and VEPs findings showed a correlation with high bilirubin levels. BAEPs were normal. In conclusion, VEPs and EEG contribute to identify and monitor bilirubin neurotoxic effects, and may play a decisional role in some cases of severe hyperbilirubinemia without overt neurologic damage

Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease.

Various lines of evidence suggest that malfunctioning of the gut-liver axis contributes to hepatic damage of rodents and humans with nonalcoholic fatty liver disease. We evaluated the effects of short-term probiotic treatment in children with obesity-related liver disease who were noncompliant with lifestyle interventions.Twenty obese children (age 10.7 ± 2.1 years) with persisting hypertransaminasemia and ultrasonographic (US) bright liver were enrolled in this double-blind, placebo-controlled pilot study. At baseline, patients underwent clinical and laboratory anthropometric evaluation, measurement of the US hepatorenal ratio, standard liver function tests, oral glucose tolerance test, serum tumor necrosis factor-alpha, the glucose hydrogen breath test, and evaluation of serum antibodies to antipeptidoglycan-polysaccharide polymers. After exclusion of causes of liver disease other than obesity, patients received either probiotic Lactobacillus rhamnosus strain GG (12 billion CFU/day) or placebo for 8 weeks.Multivariate analysis after probiotic treatment revealed a significant decrease in alanine aminotransferase (average variation vs placebo P = 0.03) and in antipeptidoglycan-polysaccharide antibodies (average variation vs placebo P = 0.03) irrespective of changes in BMI z score and visceral fat. Tumor necrosis factor-alpha, and US bright liver parameters remained fairly stable.Probiotic L rhamnosus strain GG warrants consideration as a therapeutic tool to treat hypertransaminasemia in hepatopathic obese children noncompliant with lifestyle interventions