Evaluation of PD1 and PD-L1 expression in high-grade sarcomas of the limbs in the adults: possible implications of immunotherapy.

Sarcomas are a heterogeneous group of rare tumours. Improvements in immunotherapy and the important role of PD1 and PD-L1 expression in advancement and prognosis have opened new fields of research for the treatment of these neoplasia. We evaluated the immunohistochemistry of PD1 and PD-L1 expression in 60 adults' patients affected by high-grade sarcomas of the limbs. PD1 expression was 65% while PD-L1 was 68.3%. PD-L1 expression seems to correlate to Ki67 in liposarcomas, fibrosarcoma's and pleomorphic sarcomas, while it does not show any correlation to chondrosarcomas, while in rhabdomyosarcomas there is a correlation but, given the small sample size, it was not possible to perform a statistic analysis. Our study shows positivity among the different subgroups of positive PD1 lymphocytes infiltration and PD-L1 expression in high-grade sarcomas of the limbs.

Effect of metabolic and antioxidant supplementation on sperm parameters in oligo-astheno-teratozoospermia, with and without varicocele: A double-blind placebo-controlled study.

Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow-up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.

[Antiestrogen therapy in the treatment of breast neoplasms]. / La terapia antiestrogenica nel trattamento del carcinoma della mammella.

During recent years the development of hormone therapy for the treatment breast neoplasms has seen, in addition to classic aspecific antiestrogens (AE) like tamoxifen (TAM) and to a lesser extent toremifen, a major development of new molecules divided into two groups: the first is the so-called selective estrogen receptor modulators (SERMs), the most important of which is Raloxifen, which mediate estrogen-agonist effects in some tissues and estrogen-antagonist effects in others; the second group includes the aromatase inhibitors (AI), important enzymes for peripheral estrogen conversion. Some studies compare or associate classic AE with the new SERMs and AI, both in adjuvant therapy and in treatment for advanced forms. Other trials assess the anti-osteoporotic activity of some SERMs which present concomitant inhibitory activity on the breast and endometrium.

[Consent to transfusion of blood and hemoderivatives]. / Consenso alle trasfusioni di sangue ed emoderivati.

The transfusion of blood or hemoderivatives is a medical procedure that necessarily involves the possibility of danger or damage, given that, even with maximum prudence, diligence and expertise, it is impossible to avoid severe risks of infections, transfusional reactions, alloimmunisation, undesired immunomodulating effects, etc. Article 19 of Ministerial Decree 15/01/1991 makes it obligatory to obtain informed consent , understood as the free expression of the acceptance of treatment provided after being fully informed of the nature, possibility, risks and collateral effects of the procedure. Consent to blood transfusion can only be given by a person with full mental faculties, whereas transfusion treatment can be proposed for a minor, for a prisoner or for a person who is temporarily incapacitated by their physical conditions. The authors examine a number of problems regarding the following questions: what happens if consent is withheld? What can happen if consent is not requested or if the transfusion is performed when consent has been denied? In conclusion, it is difficult to offer operating schemes that are easy to apply: much depends on the patient's conditions, his reactions, his concerns, his trust in the doctor and the latter's communication skills.

[A new organizational model of hospitals and law]. / Il nuovo modello organizzativo degli ospedali e la giustizia.

One of the more important legislative news in Italy is the company management of the National Health Care. The Health Care System has a long time budget and a yearly time budget, which allow to achieve some objectives identified inside an organizing system, based on Departments and their Directors. Another point is the competitivity among public/public and public/private structures. The problem of the penal responsibility of the medical doctor and staff is discussed.

Effects of adenosine receptor agonists on efferent renal nerve activity in anesthetized rats.

The aim of this study was to investigate the effects of A1 and A2 adenosine-receptor activation on the sympathetic nervous system. The effects on efferent renal nerve activity of selective A1 (CCPA; 2-chloro-N-6-cyclopentyladenosine) and A2 (2HE-NECA; 2-hexynyl-5'-N-ethylcarboxamidoadenosine) adenosine-receptor agonists were studied in anesthetized rats either with intact baroreflexes (intact rats) or with bilateral sinoaortic denervation and vagotomy (denervated rats). After a control period of 5 min, A1 or A2 agonist or vehicle were intravenously infused for 8 min in separate groups of intact or denervated rats, in which arterial pressure and heart rate were continuously recorded. CCPA (5.0 microg/kg/min) and 2HE-NECA (0.7 microg/kg/min) were selected to obtain comparable blood pressure changes over the period of observation. Arterial pressure significantly and equally decreased during the A1 (-41 +/- 8%), and A2 (-35 +/- 5%) agonist administration. Heart rate significantly decreased during A1 agonist infusion, but it did not change during A2 agonist administration. Bilateral sinoaortic denervation and vagotomy did not modify the hemodynamic responses to both drugs. The A1 and A2 administration caused a large and significant increase in efferent renal nerve activity (+66 +/- 22% and +76 +/- 15%, respectively), and this effect was entirely abolished in denervated rats. A linear relation with a significant negative slope between changes in arterial pressure and changes in neural discharge was observed for each treatment. The comparison of the regression slopes showed that the reflex increase of efferent sympathetic activity caused by the administration of both agonists was significantly smaller than the increment induced by equipotent hypotensive dose of sodium nitroprusside (10 microg/kg). These data show that the selective activation of A1 and A2 receptors elicits a reflex increase in efferent renal nerve activity. This neural activation is smaller as compared with the effect of equihypotensive doses of sodium nitroprusside, thus indicating a blunting effect of both adenosine agonists on baroreceptor sensitivity.

Influence of diabetic treatment regimens on vitamin D metabolism in elderly patients.

The influence of diabetic treatment regimens on vitamin D metabolism and on bone mineral content has been explored in 41 elderly patients with normal renal and hepatic functions. The data obtained suggest that oral treatment with hypoglycemic compounds exerts a negative influence on vitamin D metabolism. It is possible that the reduction of 25-OH-hydroxy-vitamin D levels depends on a high conversion rate to the active 1,25-dihydroxy-vitamin D, as a consequence of parathormone-stimulated increase of 1-alpha-hydroxylase activity. On the other hand, no differences in bone mineral densities were observed in correlation with the diabetic treatment regimens. Therefore, oral treatment with hypoglycemic compounds can only be associated with an accelerated vitamin D metabolism.

Hysteroscopic retrieval of occult IUD.

PIP: The direct view of the uterine cavity offered by hysteroscopy can provide valuable information about the position of an IUD, its condition, and its relationship with other formations, thereby facilitating its removal. The diagnostic and therapeutic reliability of this technique was analyzed in 8 women with occult IUDs. Involved were 3 Nova T IUDs, 2 Gravigards, 2 Minigravigards, and 1 Progestasert device. 1 patient had undergone unsuccessful curettage for removal of the IUD; none of the other women had experienced any surgical manipulation prior to the hysteroscopy. The surgery consisted of 4 steps: 1) distention of the uterine cavity by insufflation of carbon dioxide, 2) hysteroscopic location of the IUD, 3) sighted grasping of the IUD or IUD segment with forceps, and 4) removal of the device together with the hysteroscope under dynamic vision. Hysteroscopic location and removal were successful in all 8 patients, with no complications. Hysteroscopy is thus recommended as an alternative retrieval technique, especially in cases when it is necessary to assess the deterioration and possible myometrial penetration of the IUD or the inflammation of the uterine cavity.^ieng