Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

BACKGROUND: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer. METHODS: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors. Clinical data and treatment outcomes were assessed by using retrospective medical chart reviews in every participating center. Study endpoints were: overall response rate (ORR), 6-month progression-free survival (PFS), and grade ≥3 immune-related adverse events. RESULTS: From August 2016 to October 2022, 31 patients with SOT (98% kidney) and solid tumors were identified (36.0% lung cancer, 19.4% melanoma, 13.0% genitourinary cancer, 6.5% gastrointestinal cancer). Programmed death-ligand 1 expression was positive in 29% of tumors. Median age was 61 years, 69% were males, and 71% received ICB as first-line treatment. In the whole cohort the ORR was 45.2%, with a 6-month PFS of 56.8%. In the lung cancer cohort, the ORR was 45.5%, with a 6-month PFS of 32.7%, and median overall survival of 4.6 months. The grade 3 immune-related adverse events rate leading to ICB discontinuation was 12.9%. Allograft rejection rate was 25.8%, and risk of rejection was similar regardless of the type of ICB strategy (monotherapy or combination, 28% versus 33%, P = 1.0) or response to ICB treatment. CONCLUSIONS: ICB could be considered a feasible option for SOT recipients with some advanced solid malignancies and no alternative therapeutic options. Due to the risk of allograft rejection, multidisciplinary teams should be involved before ICB therapy.

[Implication of bronchopulmonary cancer patients in thoracic oncology]. / Implication des patients atteints d'un cancer broncho-pulmonaire en oncologie thoracique.

Changed relationships between patient and health care provider have given patients a greater role in their care. Nowadays, they have the opportunity to be involved in decision-making regarding any diagnostic, therapeutic or monitoring intervention related to their disease. Access to international scientific data through the web, the activity of different patient associations, and the information given by their referring physician can enrich their knowledge about their disease and its possible treatments. In addition to the objective criteria usually assessed, the role currently assumed by patient associations in clinical research helps to identify their expectations. In addition, a number of new tools allow the thoracic oncologist to better understand patients' wishes. Health authorities' use of patient-reported outcomes and patients' use of digital applications contribute to improved survival without any deleterious impact on quality of life. Web applications designed to monitor a patient's toxicities during treatment are now commercially available. To meet our patients' expectations, we are called upon to incorporate these different digital tools into our daily practice.

Quels malades peuvent et doivent aller en réanimation ?: Which patients can and should go to intensive care?

When a lung cancer patient develops an organ failure, the intensity of the care should be decided taking into account patient's wishes and his plan of carekeeping, in mind that the objective of an intensive care unit (ICU) admission is to allow the patient to be discharged from ICU and hospital with an acceptable quality of life. But the physician in charge of the patient at the time of acute disease often does not have these information. It is therefore essential that the referring oncologist had an early discussion with the patient to inform him and collect his opinion. These information have to be noted in the patient's medical chart. The prognostic criteria of lung cancer patients admitted in ICU are related to the patient's characteristics, the cancer's characteristics and the severity of acute disease. In order that a decision of ICU admission is in accordance with the patient's therapeutic project, a close discussion between the oncologist and the intensivist is essential, especially in this period of SARS-CoV2 pandemy.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Parallel streams for the relay of vibrissal information through thalamic barreloids.

This study investigated the organization of a vibrissal pathway that arises from the interpolar division of the spinal trigeminal complex (SP5i), transits through the ventral posterior medial nucleus (VPM), and innervates the somatosensory cortical areas in the rat. Using Fluoro-Gold and biotinylated dextran amine, respectively, as retrograde and anterograde tracers, the following organization plan was disclosed. The SP5i projection arises from a population of small-sized neurons that selectively innervate the ventral lateral part of VPM. In cytochrome oxidase-stained material, this region does not display any barreloid arrangement, but Fluoro-Gold injections in single barrel columns labeled rods of cells that extend caudally into the ventral lateral division of VPM. Thus, on the basis of retrograde labeling, barreloids were divided into core and tail compartments, which correspond to the rod segments running across the dorsal and ventral lateral parts of VPM, respectively. Double-labeling experiments revealed that SP5i afferents innervate the tail of barreloids. The anterograde labeling of thalamocortical axons show that most "core cells" project to a single barrel column, whereas some "tail cells" give rise to branching axons that innervate the second somatosensory area and the dysgranular zone of the barrel field. Injections that straddled the transition zone between the core and tail regions disclosed cells projecting to a single barrel column and to the surrounding dysgranular zone. These results suggest that the projection of "barreloids cells" to the granular and/or dysgranular zones relates to the class of prethalamic input(s) they receive.

Transient inhibition of RU 486 antiglucocorticoid action by dexamethasone.

RU 486 antagonizes both progesterone and glucocorticoids at the receptor level. To study the duration of RU 486 antiglucocorticoid activity on corticotropic function and to establish the means of overcoming it with dexamethasone, plasma corticolipotropic hormones and cortisol were measured in 10 healthy male patients during the 3 days after intake, at 2200 h, of a single 400-mg dose of RU 486, alone or combined with a single dexamethasone dose (1, 2, or 4 mg) given at 2400 h. On the first day after RU 486 alone, ACTH, lipotropin, and cortisol plasma levels were significantly higher than basal values. The 1-mg dose of dexamethasone totally abolished the stimulatory effect of RU 486, and higher doses of dexamethasone (2 and 4 mg) further depressed hormone levels. During the succeeding days, antiglucocorticoid activity of RU 486 alone was still present 34 h after administration, while on the third day all hormone levels returned to normal. After the combined administration, the RU 486 effect reappeared as early as the first day with the 1-mg dose of dexamethasone, while it was delayed until the third day with the higher doses. These results showed that a single 400-mg dose of RU 486 induced a response that lasted at least 34 h. Thus, a dose-dependent competition between RU 486 and dexamethasone was demonstrated. However, the suppressive effect of dexamethasone was only transient, after which the antiglucocorticoid activity of RU 486 reappeared.