30 years of ocular proton therapy, the Nice view.

PURPOSE: Radiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization. MATERAIAL AND METHODS: MEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991-2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (∼95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract). RESULTS: Although demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice. CONCLUSIONS: Some of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.

Hemofiltration for cytokine-driven illnesses: the mediator delivery hypothesis.

Hemofiltration is evolving as an adjunctive therapy for sepsis and other forms of systemic inflammation. Designed as a substitute for lost renal function, it is sometimes employed prior to the onset of renal failure to facilitate the nonspecific clearance of pro-inflammatory mediators. Prevailing theories suggest that hemofiltration attenuates the immune response when a threshold amount of excess cytokine is removed at the semi-permeable membrane. In this article we introduce an alternative hypothesis, in which hemofiltration exerts its effect by reinvigorating lymphatic flow and function. Crystalloid "replacement" solution, as much as 48 to 72 liters daily, is infused to restore intravascular volume lost through production of ultrafiltrate. Partial redistribution into interstitium and lymph mobilizes inflammatory mediators and other proteins, cellular byproducts, excessive ground matrix, fragments of apoptotic cells and free DNA. These substances are then metabolized, scavenged or cleared at multiple sites, including the reticuloendothelial system, liver, kidney, erythrocyte, and hemofilter.

Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. II. Classification and identification of urinary drug metabolites.

1. Five metabolites were isolated from the urine of dogs dosed with 3-(hydroxymethyl)-8-methoxy[4-14C]chromone. These were identified as 8-methoxychromone, 2-hydroxy-3-methoxyacetophenone, 3-(hydroxymethyl)-8-hydroxychromone, 8-hydroxychromone and 2,3-dihydroxyacetophenone. 2. These compounds were also present in the urine of rats treated with labelled drug, together with unchanged drug and two intermediate metabolites, 3-carboxy-8-methoxychromone and 3-(carboxymethyl)-8-hydroxychromone. 3. In addition to the unconjugated labelled compounds, glucuronides and sulphates were identified. 4. Quantitative data were obtained for all of the 20 labelled compounds in rat urine. 5. A scheme is presented for the biotransformation of 3-(hydroxymethyl)-8-methoxychromone in rats and dogs, and a mechanism for scission of the gamma-pyrone ring is suggested.