Concentrations of free thyroxin and albumin in serum in severe nonthyroidal illness: assay artefacts and physiological influences

Free thyroxin (FT4) estimates by two immunoassays were compared with the concentrations of albumin in serum of apparently euthyroid subjects who either were (n = 99) or were not (n = 327) suffering from severe nonthyroidal illness (sNTI). In neither group was FT4 significantly correlated with albumin (P greater than 0.05), according to a "labeled antibody" radioassay (Amerlex-MAB). On amalgamating both groups, correlation with albumin was positive and significant (P less than 0.001). In the group with sNTI, both FT4 and albumin concentrations were decreased (mean FT4 to 77% and mean albumin to 61% of the respective reference means). For an analog radioimmunoassay (Amerlex-M), FT4 in all groups was significantly (P less than 0.001) correlated with albumin. Correlation coefficients were greater than with Amerlex-MAB for both sNTI and euthyroid groups, as well as for the joint panel. Mean FT4 in sNTI was only 44% of the reference mean. Lower radio-tracer "analog" values in sNTI are exaggerated by additional technical artefacts resulting from tracer binding to albumin.     

Control charts to identify adverse outcomes in elective colon resection

BackgroundControl charts have been proposed for the measurement of quality in surgical care.MethodsFor each of 181 study hospitals in the 2005 National Inpatient Sample of the Healthcare Cost and Utilization Project database, an average moving range control chart for risk-adjusted postoperative length of stay (RApoLOS) was created for patients discharged alive after elective colectomy. RApoLOS outliers using upper control limits of 2.0σ, 2.5σ, and 3.0σ were correlated to coded complications (CCs). Hospital costs were correlated to RApoLOS outliers and CCs.ResultsOf 13,118 live discharges, 902 (6.9%) were outliers using a 3.0σ upper control limit, 1,350 (10.3%) were 2.5σ outliers, and 2,053 (15.7%) were 2.0σ outliers. CCs were identified in 92.7% of 3.0σ outliers, in 81.3% of 2.5σ outliers, and 70.6% of 2.0σ outliers. Increased costs were associated with RApoLOS outliers and poorly with CCs.ConclusionsAverage moving range control charts for RApoLOS outliers are valid tools for measurement of surgical quality and costs.     

Sepsis, systemic inflammatory response, and multiple organ dysfunction: the mystery continues

Human sepsis is thought to be systemic inflammatory response syndrome (SIRS) that is activated by invasive infection. The multiple organ dysfunction syndrome (MODS) is the identified failure of critical organ function in patients that have sustained SIRS. Because SIRS and MODS are consequences of the excessive activation of inflammation, extensive research and numerous clinical trials have pursued treatments that would modify the inflammatory response. This presentation reviews the normal local mechanisms of inflammation and provides a theoretical framework for the transition of the inflammatory process to a systemic level. Clinical trials with biomodulators to block or inhibit inflammation have generally failed to improve the outcomes in patients with severe sepsis, septic shock, and MODS. The role of counter-inflammatory signaling and the newer concept of the cholinergic anti-inflammatory pathway are being investigated, and newer hypotheses are focusing upon the balancing of proinflammatory and counter-inflammatory mechanisms as important directions for newer therapies. It is concluded that failure to define novel and effective treatments reflects fundamental gaps in our understanding of inflammation and its regulation.     

Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas

Some subsets of pediatric sarcoma patients have very poor survival rates. We sought to determine the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in pediatric sarcoma populations with <25% predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round cell tumors received EPOCH-fludarabine induction, a cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo alloHSCT because of progressive disease with diminishing performance status during induction. All 23 alloHSCT recipients experienced rapid full-donor engraftment, with no peritransplantation mortality. Five of 23 alloHSCT recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years), including 3 of 7 (42%) transplanted without overt disease (median survival 14.5 versus 29.0 months from alloHSCT for patients transplanted with versus without overt disease, respectively). Among the 28 patients who progressed on the study, the median survival from date of progression was 1.9 months for the 7 who did not receive a transplant compared with 11.4 months for the 21 transplanted (P = .0003). We found prolonged survival after posttransplantation progression with several patients exhibiting indolent tumor growth. We also saw several patients with enhanced antitumor effects from posttransplantation chemotherapy (objective response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation EOCH); however, this was associated with increased toxicity. This largest reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in this population, and that patients undergoing alloHSCT without overt disease show higher survival rates than reported using standard therapies. Enhanced chemo- and radiosensitivity of tumors and normal tissues was observed posttransplantation.