Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program.

SOLAR-1 and BYLieve trials documented the efficacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CA-mutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients. We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP) opened to PIK3CA-mutant HR+/HER2- ABC patients treated with alpelisib and fulvestrant. Primary endpoint was PFS by local investigators using RECIST1.1. Eleven centers provided individual data on 233 consecutive patients. Patients had received a median number of 4 (range: 1-16) prior systemic treatments for ABC, including CDK4/6 inhibitor, chemotherapy, fulvestrant and everolimus in 227 (97.4%), 180 (77.3%), 175 (75.1%) and 131 (56.2%) patients, respectively. After a median follow-up of 7.1 months and 168 events, median PFS was 5.3 months (95% CI: 4.7-6.0). Among 186 evaluable patients, CBR at 6 months was 45.3% (95% CI: 37.8-52.8). In multivariable analysis, characteristics significantly associated with a shorter PFS were age < 60 years (HR = 1.5, 95% CI = 1.1-2.1), >5 lines of prior treatments (HR = 1.4, 95% CI = 1.0-2.0) and the C420R PI3KCA mutation (HR = 4.1, 95% CI = 1.3-13.6). N = 91 (39.1%) patients discontinued alpelisib due to adverse events. To our knowledge, this is the largest real-life assessment of alpelisib efficacy. Despite heavy pre-treatments, patients derived a clinically relevant benefit from alpelisib and fulvestrant.

Heavy metals in four fish species from the French coast of the Eastern English Channel and Southern Bight of the North Sea.

Shallow coastal waters act as nurseries for various fish species and have been recognized as essential fish habitat. We studied heavy metal concentrations in four fish species (plaice, dab, flounder and cod) as an indicator of large-scale habitat quality. The study took place along the French coasts between the Eastern English Channel and the Southern Bight of the North Sea. All species show different concentrations of measured metals (e.g., Cd, Cu, Mn and Pb) in liver but not in muscle. The highest concentrations are found for the flounder and the lowest for cod which is consistent with their habitat and diet. Although our results do not highlight levels of appreciable pollution within the study area, inter-site differences are mainly observed in the muscle tissues and are generally in agreement with the known environmental data (e.g., anthropogenic pressure). However, in the Bay of Seine, one of the most contaminated estuaries in Europe, metal concentrations are in the same range or even lower than those found in fish collected from areas distant from any anthropogenic pressures. At one site, the comparisons of the Cd, Cu and Pb concentrations between healthy and diseased dabs have been carried out on the muscle and liver tissues. The results of this preliminary study show a relationship between metal concentrations and the pathological status of the fish. The use of fish health as indicator of habitat quality is discussed.

Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation.

Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluate the effect of single and multiple donor-specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty-five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowel transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 x 10(6) cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 10(6) cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 10(6) cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 10(6) cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100% in 0.5 mg/kg and 42.1% in 1 mg/kg FK506 groups). On day 30, 58.3% of bone-marrow-infused animals and 66.6% of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12% after transplant and were significantly higher in bone-marrow-infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short-course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation.

[Nutritional and disease diagnosis in institutionalized children. Day care center Elisio Teixeira Leite, Perus, SP 1993]. / Diagnóstico nutricional e de saúde de crianças institucionalizadas - creche Elísio Teixeira Leite, Perus, SP, 1993.

As a part of one survey about health conditions in institutionalized children, the nutritional status were evaluated. Data were obtained through antropometric assessment in a sample of 111 pre-school children matriculated in a small official day-care center in Perus-SP. According to Gomez, 50.0% of all that children were classified as malnourished, 23.4% of them in the I degree; 22.4% in II degree and only 4.3% in III degree. Taking into account the Waterlow's classification there was a highest frequency of cronic-actual malnutrition (30.8%) concentrated in children between 12-48 months of age. Additionally, these children presented highest incidence of infective-respiratory and intestinal diseases. These evidences lead on to the improvement of the follow-up of children growth and food consumption, specially that under 24 meses, to attempt for an early identification of malnutrition, thus increasing the chance of nutritional recuperation.