Idealism is the core of the Pratyabhijñã philosophy: the main goal of Utpaladeva (fl. c. 925-950 AD) and of his commentator Abhinavagupta (fl. c. 975-1025 AD) is to establish that nothing exists ...outside of consciousness. In the course of their demonstration, these Śaiva philosophers endeavour to distinguish their idealism from that of a rival system, the Buddhist Vijñānavāda. This article aims at examining the concept of otherness (paratva) as it is presented in the Pratyabhijñā philosophy in contrast with that of the Vijñānavādins'. Although, according to the Pratyabhijñā, the other subjects are not ultimately real since all subjects are nothing but limited manifestations of a single absolute subject, the fact that we are aware of their existence in the practical world has to be accounted for. The Vijñānavādins explain it by arguing the we infer the others' existence. The Pratyabhijñā philosophers, while refuting their opponents' reasoning as it is expounded in Dharmakīrti's Santānāntarasiddhi, develop a particulary original analysis of our awareness of the others, stating that this awareness is neither a perception (pratyakṣa) nor an inference (anumāna), but rather a guess (ūha) in which we sense the others' freedom (svātantrya).
A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated ...by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.
PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.
We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range IQR) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio HR = 2.02 95% confidence interval {CI } = 1.23-3.31) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 95% CI = 1.58-6.22) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 95% CI = 1.60-6.56 for KS; HR = 5.28 95% CI = 2.17-12.83 for NHL).
Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
Summary
Background
Several phase I trials are currently evaluating new antiangiogenic compounds. While hypertension and proteinuria have been largely reported as a class side effect of these agents, ...data on renal function i.e. the glomerular filtration rate (GFR) in patients (pts) treated with new antiangiogenic compounds in phase I trials are much scarcer.
Patients and methods
Between November 2005 and March 2008, we identified 72 pts with solid tumors who had been included in four Phase I trials testing antiangiogenic or related compounds. Thirty-two pts had received a pan-HER/VEGFR inhibitor (A), 29 had received a vascular-disrupting agent (B) and 11 had received a pan-VEGFR inhibitor in combination with CPT11 (C). For each patient, we retrospectively analyzed the serum creatinine level (SCr), Cr clearance (CrCl) calculated by both the Cockcroft and Gault and aMDRD equations at baseline, during treatment and at the end of treatment. Acute renal failure (ARF) was defined as a decrease of >25% in CrCl, and severe renal failure (SRF) as a decrease of >50% in CrCl. Chronic renal failure (CRF) was defined according to the KDOQI-KDIGO classification. Renal dysfunction was defined as Cl <60 ml/min with a normal Cr level (<125 μmol/l).
Results
Each pt had received an average of 4 cycles of treatment (1 to 12). During treatment, the incidence of ARF ranged from 40.2% to 44.4% (
A
= 11/32,
B
= 19/29,
C
= 2/11). Seven to 9.7% of these cases were severe (
A
= 1/32,
B
= 6/29,
C
= 0/11). Moreover, 26.4 to 27.7% of the pts had exhibited persistent renal insufficiency at the end of the study (
A
= 5/32,
B
= 15/29,
C
= 0/11). From the start till the end of treatment, ARF had been documented in 20.8% to 22.2% of the pts. The average reduction in clearance was 9.8 to 11.6 ml/min/1.73 m2 between baseline and the end of treatment.
Conclusion
The incidence of renal toxicity in phase I pts treated with antiangiogenic compounds was much higher than expected. Simple screening of Cr levels appears to be insufficient and careful nephrologic monitoring at baseline and during treatment should be implemented in early clinical trials assessing the risk/benefit ratio of new antiangiogenic compounds.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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