COVID-19: a plea to protect the older population

This is the final version. Available on open access from BMC via the DOI in this recor

The ethical plausibility of the ‘Right To Try’ laws

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.‘Right To Try’ (RTT) laws originated in the USA to allow terminally ill patients to request access to early stage experimental medical products directly from the producer, removing the oversight and approval of the Food and Drug Administration. These laws have received significant media attention and almost equally unanimous criticism by the bioethics, clinical and scientific communities. They touch indeed on complex issues such as the conflict between individual and public interest, and the public understanding of medical research and its regulation. The increased awareness around RTT laws means that healthcare providers directly involved in the management of patients with life-threatening conditions such as cancer, infective, or neurologic conditions will deal more frequently with patients’ requests of access to experimental medical products. This paper aims to assess the ethical plausibility of the RTT laws, and to suggest some possible ethical tools and considerations to address the main issues they touch.This paper was funded by the European School of Oncology

Supporting Supportive Care in Cancer: The ethical importance of promoting a holistic conception of quality of life

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordAdvances in anticancer therapies and increasing attention towards patient quality of life make Supportive Care in Cancer (SCC) a key aspect of excellence in oncological care. SCC promotes a holistic conception of quality of life encompassing clinical, ethical/existential, and spiritual dimensions. Despite the calls of international oncology societies empirical evidence shows that SCC has not yet been implemented. More efforts are needed given the clinical and ethical value of SCC not only for patients, but also for clinicians and hospitals. Drawing on different literature sources, we identify and discuss three important barriers to the implementation of SCC: 1) organisational – lack of adequate resources and infrastructures in over-stretched clinical environments, 2) professional- burnout of cancer clinicians; and 3) cultural – stigma towards death and dying. We add an ethical counselling framework to the SCC implementation toolkit- which, could offer a flexible and resource-light way of embedding SCC, addressing these barriers

Use of intensive rearing systems as back‐up for coastal lagoon aquaculture: an experience with eels, Anguilla anguilla L., in the Comacchio lagoons

. The possibility of using eels from intensive rearing ponds to restock natural basins has been investigated by comparing growth, survival and rate of yellow-to-silver metamorphosis of 'wild type' eels and of eels from an intensive rearing pond. A total of 2243 marked eels were released into a closed natural environment of 22ha; 1254 were wild type (average length 45·6 ± 9·0cm), and 989 from an intensive rearing pond, split by a mechanical grader in two groups. The first group was made of 617 well-growing eels (44·9 ± 3·0cm), the second one of 372 smaller eels (36·9 ± 4·3cm) which had not adapted to the artificial conditions. The starting size being equal the animals grew to the same extent; in some cases the animals previously adapted to the artificial pond grew better than the wild type. The rate of metamorphosis from yellow to silver eel was 28·4% for the wild type eels and 22% for the others, although the latter became mostly silver males. Survival of the wild type eels (starting with the 35-cm size class and covering the period from April to December) was calculated by mark-recapture at approximately 98·6%. For the eels previously well adapted to the intensive rearing pond it was only 85%, indicating some difficulty in competing in the natural environment. The good growth shown by the smaller eels, with a survival of about 90%, would seem to indicate that these animals might be effectively used for restocking purposes, thus favouring an integration between the intensive ponds and the extensive environments

Effect of body mass and physical activity at younger age on the risk of prostatic enlargement and erectile dysfunction : Results from the 2018 #Controllati survey

Objective: Overweight and low physical activity (PA) increase the risk of prostatic enlargement and erectile dysfunction (ED). Less clear is the role of these factors at young age on the lifelong risk. Materials and methods: During June 2018 the Italian Society of Urologists organized the month of Male Urologic Prevention "#Controllati". Men aged 18 years or more were invited to attend urologic centers for a visit and counselling about urologic/andrologic conditions. Each participating man underwent a physical examination and was asked about urologic symptoms, sexual activity and possible related problems. Results: We analyzed data from 2786 men, aged 55.1 years (SD 10.9, range 19-97). A total of 710 (25.5%) subjects had a diagnosis of prostatic enlargement and 632 (22.7%) of DE. Overweight/obese men were at increased risk of prostatic enlargement and ED with corresponding odds ratio (0R) in comparison with normal or underweight men, being respectively 1.18 (95% Confidence Interval (CI) 1.00-1.44) and 1.69 (95% CI 1.39-2.05). The OR of prostatic enlargement in comparison with men reporting at age 25 a BMI < 25.0 was 1.22 (95% CI 1.01-1.51) for men with a BMI at 25 years of age 65 25; the corresponding OR value for ED was 1.17 (0.92- 1.48). Considering total PA at diagnosis, the OR of prostatic enlargement in comparison with no or low PA, was 0.69 (95%CI 0.55-0.86) for men reporting moderate PA and 0.75 (95%CI 0.58-0.98) for those reporting intense PA. When we considered PA at 25 years of age, the OR of subsequent diagnosis of prostatic enlargement, in comparison with men reporting no/low PA at 25 years of age was 0.81 (95%CI 0.63-1.04) for men reporting moderate PA and 0.70 (95%CI 0.52-0.99) for those reporting intense PA. Conclusions: These findings underline the utility of encouraging healthy lifestyle habits among young men in order to reduce the subsequent risk of prostatic enlargement and ED

Effects of rapamycin on cultured hepatocyte proliferation and gene expression

Rapamycin, a potent immunosuppressive drug that disrupts normal signal‐transduction processes, inhibited hepatocyte proliferation without evidence of inherent cytotoxicity in rat hepatocytes cultured in conventional medium or in a medium enriched with epidermal growth factor. The antiproliferative effect was dose dependent, uninfluenced by the concentration of epidermal growth factor in the medium and long lasting after a brief exposure. The effect of rapamycin was unaltered by the concomitant presence of FK 506 in the medium, suggesting that different binding affinities of these two drugs or even a separate rapamycin binding site may exist. Hepatocytes harvested 12 and 24 hr after partial hepatectomy were progressively less responsive to the antiproliferative effect of rapamycin. The gene expression of transforming growth factor‐β was reduced under in vivo rapamycin treatment, but at the same time the gene expression of albumin and glyceraldehyde‐3‐phosphate dehydrogenase was unchanged or increased. The experiments confirm that rapamycin has inherent growth‐control qualities, and they strengthen the hypothesis that the recently defined immunophilin network is central to many aspects of cellular growth control. (HEPATOLOGY 1992;15:871–877). Copyright © 1992 American Association for the Study of Liver Disease

Fk506 “rescue” for resistant rejection of renal allografts under primary cyclosporine immunosuppression

Seventy-seven patients with ongoing acute rejection on initial CsA therapy were converted to FK506 to attempt graft salvage. Fifty-nine patients had undergone primary transplantation and 18 had been retransplanted; there were 52 cadaveric and 25 living-donor transplants. The indications for conversion to FK506 were ongoing, biopsy-confirmed rejection in all patients, including vascular rejection in 20. The median interval to rescue was 2 months (range 2 weeks to 36 months) after transplantation. Sixty-one of the 77 patients (79%) had already received one or more courses of an antilymphocyte preparation (OKT3: n=33; ALG or ATG: n=1; OKT3+ALG/ATG: n=27). Of the 77 patients, 57 (74%) have been successfully rescued and still have functioning grafts with a mean follow-up of 14 months, with a mean serum creatinine of 2.35±0.97 mg/dl. Eighteen patients were already dialysis-dependent at the time of conversion to FK506; of these, 9 (50%) were successfully salvaged and have a mean serum creatinine of 2.3 mg/dl. Of the 61 patients previously treated with antilymphocyte preparations, 48 (79%) were rescued. In those salvaged, prednisone doses have been lowered from 22.2±7.2 mg/day preconversion to 7.5±5.6 mg/day postconversion, and 12 patients are on FK506 monotherapy. In nondiabetics, mean serum glucose was 101.4±20.5 mg/dl preconversion and 93.2±22 postconversion (P=0.07), uric acid 7.3±2.3 and 7.1±1.5 mg/dl (P=0.53), and triglycerides 199.2±101.6 and 167.2±106.4 mg/dl (P=0.06). Cholesterol levels were significantly lower following FK conversion (207.7±46.5 mg/dl pre. vs. 188.3±39.7 post, P=0.007). FK506 is capable of salvaging renal allografts with ongoing acute rejection on CsA therapy, even when antilymphocyte preparations have been ineffective. © 1994 by Williams and Wilkins