Members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily share an intracytoplasmic Toll-IL-1 receptor (TIR) domain, which mediates recruitment of the interleukin-1 receptor-associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood and fibroblast cells did not activate nuclear factor kappaB and mitogen-activated protein kinase (MAPK) and failed to induce downstream cytokines in response to any of the known ligands of TIR-bearing receptors. The otherwise healthy children developed infections caused by pyogenic bacteria. These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms.

The receptors for interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma activate components of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, leading to the formation of at least two transcription factor complexes. STAT1 interacts with STAT2 and p48/IRF-9 to form the transcription factor IFN-stimulated gene factor 3 (ISGF3). STAT1 dimers form gamma-activated factor (GAF). ISGF3 is induced mainly by IFN-alpha/beta, and GAF by IFN-gamma, although both factors can be activated by both types of IFN. Individuals with mutations in either chain of the IFN-gamma receptor (IFN-gammaR) are susceptible to infection with mycobacteria. A heterozygous STAT1 mutation that impairs GAF but not ISGF3 activation has been found in other individuals with mycobacterial disease. No individuals with deleterious mutations in the IFN-alpha/beta signaling pathway have been described. We report here two unrelated infants homozygous with respect to mutated STAT1 alleles. Neither IFN-alpha/beta nor IFN-gamma activated STAT1-containing transcription factors. Like individuals with IFN-gammaR deficiency, both infants suffered from mycobacterial disease, but unlike individuals with IFN-gammaR deficiency, both died of viral disease. Viral multiplication was not inhibited by recombinant IFN-alpha/beta in cell lines from the two individuals. Inherited impairment of the STAT1-dependent response to human IFN-alpha/beta thus results in susceptibility to viral disease.

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BACKGROUNDSince the medical record is the major source of health information, it is necessary to maintain accurate, comprehensive and properly coded patient data. We reviewed 300 medical records from patients at King Faisal Specialist Hospital and Research Center, representing four departments (medicine, surgery, pediatrics and obstetrics and gynecology).METHODSThe records were audited following the guidelines of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for accuracy and completeness of documentation and coding of primary and secondary diagnoses and procedures performed.RESULTSOf 1051 items abstracted, 876 (83.3%) were accurately documented, 41 (3.9%) were inaccurately documented, and 134 (12.7%) were not documented. Of the items abstracted, 736 (70%) were assigned a correct code, 110 (10.5%) were assigned an incorrect code, and 205 (19.5%) were not coded. More items classified as accurately documented were coded correctly (71.1%) than items inaccurately documented (49.7%) (P<0.0001). The difference in comprehensiveness of documentation, which reflects physician performance, was not statistically significant among the four departments (P value <0.234). The difference in the accuracy of coding, which reflects coder performance, was statistically significant (P value < 0.036).CONCLUSIONSOnly 60% of the audited records met the benchmark for good quality medical records with regards to documentation and coding. A positive correlation between the accurate documentation and correct coding was noted, which supports the conclusion that high quality documentation enhances coding accuracy. These data, although encouraging, suggest room for improvement, which can be achieved through the collaboration of clinicians, who have extensive clinical experience, and coding professionals, who have comprehensive classification system expertise.

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