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

Brain abscess due to Klebsiella pneumoniae in a liver-transplanted child.

Brain abscesses are a rare, severe complication of orthotopic liver transplantation (OLT). They are almost exclusively due to fungi, Nocardia, or Toxoplasma, and usually occur within months of surgery. Here we report the case of an adolescent who developed a brain abscess due to Klebsiella pneumoniae 11.5 years after OLT. Fever was absent and laboratory parameters were not indicative of infectious disease, and therefore the diagnosis of a central nervous system neoplasm was considered. Subsequent magnetic resonance imaging and spectroscopy led to a diagnosis of a brain abscess, and to prompt appropriate antibiotic treatment. This case shows that K. pneumoniae may cause a brain abscess long after liver transplantation. The appearance of neurological symptoms should alert clinicians to consider a brain abscess even in the absence of overt clinical/laboratory signs of inflammation, which may be blunted by chronic immunosuppression

Brain abscess due to Klebsiella pneumoniae in a liver-transplanted child

Brain abscesses are a rare, severe complication of orthotopic liver transplantation (OLT). They are almost exclusively due to fungi, Nocardia, or Toxoplasma, and usually occur within months of surgery. Here we report the case of an adolescent who developed a brain abscess due to Klebsiella pneumoniae 11.5 years after OLT. Fever was absent and laboratory parameters were not indicative of infectious disease, and therefore the diagnosis of a central nervous system neoplasm was considered. Subsequent magnetic resonance imaging and spectroscopy led to a diagnosis of a brain abscess, and to prompt appropriate antibiotic treatment. This case shows that K. pneumoniae may cause a brain abscess long after liver transplantation. The appearance of neurological symptoms should alert clinicians to consider a brain abscess even in the absence of overt clinical/laboratory signs of inflammation, which may be blunted by chronic immunosuppression