ECOG performance status 0 or 1 and symptom classification do not improve the ability to predict renal cell carcinoma-specific survival

ObjectivesWe tested and compared the improvement in prognostic ability related to the consideration of either ECOG performance status (ECOGPS) and/or symptom classification (S-CLASS) in renal cell carcinoma specific mortality (RCC-SM) predictions.MethodsUnivariate and multivariate Cox regression analyses targeted RCC-SM in 2570 RCC patients treated with either partial or radical nephrectomy. The increment in predictive accuracy related to the addition of either ECOGPS, S-CLASS or both was quantified using Harrell’s concordance index.ResultsFollow-up ranged from 0.1 to 23 years (median 3.2) and 610 patients (23.7%) died of RCC. In multivariable analyses, ECOGPS and S-CLASS represented independent predictors of RCC-SM. The addition of ECOGPS to established RCC-SM predictors increased the predictive accuracy by 0.3% (p = 0.8) versus 0.6% (p = 0.5) for S-CLASS versus 0.6% (p = 0.5) for both.ConclusionsNeither ECOGPS nor S-CLASS improves the ability to predict RCC-SM. Therefore, these variables may be safely omitted when RCC-SM risk is quantified.     

The effect of medical therapy and islet cell transplantation on diabetic nephropathy: an interim report

BACKGROUND: The effect of islet cell transplantation (ICT) on renal function in type 1 diabetes is uncertain and some recent studies report a significant decline in estimated glomerular filtration rate (GFR) and worsening of albuminuria. METHODS: We are conducting a prospective crossover study comparing medical treatment with islet transplantation on the progression of diabetic complications, including renal function. The primary endpoint is change in GFR measured by Tc-diethylenetriaminepentaacetate with secondary endpoints including estimated GFR and albumin excretion. RESULTS: We have followed 21 patients after islet transplantation a median of 29 months (range 13-45) and compared their results with medically treated patients followed a median 29.5 months (range 13-56). There is no difference in the rate of decline in measured GFR between medically treated patients (-0.35+/-0.89; 95% CI: -0.57 to -0.13 mL/min/month/1.73 m) and those after ICT (-0.31+/-1.18; 95% CI: -0.61 to -0.01) and neither is significantly different from that expected for the general population. The rate of decline in our estimated GFR results is lower than that reported in other studies and we did not find any worsening of albuminuria. CONCLUSIONS: We do not find evidence of worsening of renal function after islet transplantation compared with medically treated patients.     

Biochemical resolving power of fluorescence lifetime imaging: untangling the roles of the instrument response function and photon-statistics

A deeper understanding of spatial resolution has led to innovations in microscopy and the disruption of biomedical research, as with super-resolution microscopy. To foster similar advances in time-resolved and spectral imaging, we have previously introduced the concept of ‘biochemical resolving power’ in fluorescence microscopy. Here, we apply those concepts to investigate how the instrument response function (IRF), sampling conditions, and photon-statistics limit the biochemical resolution of fluorescence lifetime microscopy. Using Fisher information analysis and Monte Carlo simulations, we reveal the complex dependencies between photon-statistics and the IRF, permitting us to quantify resolution limits that have been poorly understood (e.g., the minimum resolvable decay time for a given width of the IRF and photon-statistics) or previously underappreciated (e.g., optimization of the IRF for biochemical detection). With this work, we unravel common misunderstandings on the role of the IRF and provide theoretical insights with significant practical implications on the design and use of time-resolved instrumentation.     

Platelet count and preoperative haemoglobin do not significantly increase the performance of established predictors of renal cell carcinoma-specific mortality

OBJECTIVE: Anaemia and/or thrombocytosis were identified as independent predictors of poor survival in renal cell carcinoma (RCC). We tested the extent to which these markers worsen the prognosis in these patients. METHODS: Analyses targeted 1828 patients with renal cell carcinoma. Univariable, multivariable, and predictive accuracy analyses addressed RCC-specific mortality (RCC-SM). RESULTS: In univariable and multivariable analyses, both platelet count and preoperative haemoglobin level were statistically significant predictors of RCC-SM. However, neither platelet count nor preoperative haemoglobin level increased the combined multivariable accuracy of established RCC-SM (predictive accuracy gain=0.3%) predictors. CONCLUSIONS: Patients who present with severe anaemia or elevated platelets are at no higher risk of RCC-SM than that related to their stage, grade, histologic subtype, and Eastern Cooperative Oncology Group-Performance Status.     

Activation of interleukin-2 receptor alpha expression by extracellular HTLV-I Tax1 protein: a potential role in HTLV-I pathogenesis.

The Tax1 protein of human T cell leukemia/lymphoma virus type I (HTLV-I) has been shown to stimulate the proliferation of human lymphocytes. Here we report that lymphocyte proliferation can be induced at extracellular Tax1 concentrations as low as 25 pM. The proliferative response induced by extracellular Tax1 is accompanied by an activation of endogenous interleukin-2 receptor alpha-chain (IL-2R alpha) expression in human lymphocytes. Functional activation of IL-2R alpha expression in peripheral blood lymphocytes treated with Tax1 was demonstrated using an [125I]IL-2-binding assay. In addition, an enzyme-linked immunosorbent assay demonstrated that soluble IL-2R alpha in the medium of IL-2- and Tax1-treated cells was over 13-fold greater than in the medium of control treated cells. Overexpression of IL-2R alpha is a common clinical feature of some patients with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myopathy (TSP/HAM). The ability of extracellular Tax1 protein to activate expression of IL-2R alpha in both infected and uninfected lymphocytes may contribute to the abnormal lymphocyte proliferation observed in both ATL and TSP/HAM.     

Transient viral load increases in HIV-infected children in the U.K. and Ireland: what do they mean?

OBJECTIVES: To investigate transient increases in viral load during sustained suppression in children in the UK and Ireland Collaborative HIV Paediatric Study (CHIPS). DESIGN: Cohort of HIV-infected children from 39 centres. METHODS: Transient viraemia was defined as > or =1 detectable viral loads (> or =50 copies/ml) between two undetectable values (<50 copies/ml) <280 days apart, during a period of sustained viral suppression (from a confirmed level of <50 copies/ml until the last undetectectable measurement before antiretroviral therapy change or until a confirmed level of >50 copies/ml). RESULTS: Of 595 children initiating HAART without previous treatment, 347 (58%) achieved sustained suppression. Of these, 78 (23%) experienced 109 episodes of transient viraemia (median 134 copies/ml); 92 (84%) had levels of <1000 copies/ml (maximum 39,839). Transient viraemia was more common during second-line therapy (25/100 child-years [CY]) and following a previous episode (19/100 CY) compared with first-line therapy without a previous episode (11/100 CY). Rates decreased with age at HAART initiation (incidence rate ratio [IRR] 0.95 per year older; P = 0.05), but were higher in those suppressed for longer (IRR 1.63 in those suppressed for 21 year versus <1 year; P = 0.03). CD4+ and CD8+ T-cell counts were similar before and after transient viraemia. Of detectable viral loads during periods of suppression 44% were transient increases rather than virological failure: experiencing transient viraemia did not increase subsequent virological failure (P = 0.20). CONCLUSIONS: Transient viraemia is relatively common among children on HAART, occurring more frequently in those starting HAART at younger ages, on second-line therapy and after longer suppression. It does not appear to affect CD4+ or CD8+ T-cell counts or the risk of subsequent virological failure. Natural variation, assay effects and adherence might all have a role.     

Sequence analysis of Vietnamese P[6] rotavirus strains suggests evidence of interspecies transmission

Nucleotide and amino acid sequences of the VP8* gene of five Vietnamese P[6] rotavirus strains detected from hospitalized patients with acute gastroenteritis were analyzed and compared with other human and porcine P[6] rotaviruses. It is of interest that these strains had greatest identity with two Italian porcine rotavirus strains, 134/04-10 and 134/04-11. To our knowledge, these five Vietnamese rotaviruses are the rare P[6] rotavirus strains belonging to lineage I that cluster into sublineage Ic with porcine rotaviruses, and not into sublineage Ia, as other human P[6] rotaviruses have done so far. Sequence analysis of the VP7 gene of these P[6] rotavirus strains was also performed. The results showed that the Vietnamese G9P[6] strain had high similarity with other human G9 rotaviruses, confirming a human-animal reassortant virus, whereas other three G4P[6] strains had best identity with porcine G4 rotavirus strains, suggesting interspecies transmission of rotavirus between porcine and humans. This result provides the important data on molecular characteristics of Vietnamese rotaviruses, and highlights interspecies transmission events of rotaviruses in Vietnam as well as in Asia.