PD-1 receptor outside the main paradigm: tumour-intrinsic role and clinical implications for checkpoint blockade.

Blocking the inhibitory receptor PD-1 on antitumour T lymphocytes is the main rationale underlying the clinical successes of cancer immunotherapies with checkpoint inhibitor (CI) antibodies (Abs). Besides this main paradigm, there is recent evidence of unconventional and "ectopic" signalling pathways of PD-1, found to be expressed not only by lymphocytes but also by peculiar subsets of cancer cells. Several groups reported on the tumour-intrinsic role of PD-1 in multiple settings, including melanoma, hepatocellular, thyroid, lung, pancreatic and colorectal cancer. Its functional activity appears intriguing but is not yet conclusively clarified. The initial studies are, in fact, supporting either a pro-tumourigenic role involved in chemoresistance and disease relapse or, oppositely, tumour-suppressive functions. The implications connected to the therapeutic administration of PD-1 blocking Abs are, of course, potentially relevant, respectively inferring an anti-tumour activity contrasting PD-1+ tumourigenic cells or a pro-tumoural effect by tackling PD-1 tumour suppressive signalling. The progressive exploration and consideration of this new paradigm of tumour-intrinsic PD-1 signalling may improve the interpretation of the observed clinical effects by anti-PD-1 Abs, likely resulting from multiple cumulative activities, and might provide important bases for dedicated clinical studies that take into account such composite roles of PD-1.

Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: a retrospective, multicenter, real-world study.

BACKGROUND: Despite its proven activity as third-line treatment in gastrointestinal stromal tumors (GIST), regorafenib can present a poor tolerability profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract regorafenib-related adverse events and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of regorafenib in patients with metastatic GIST, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off). PATIENTS AND METHODS: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify patients with GIST who had received regorafenib from February 2013 to January 2021. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons. RESULTS: Of a total of 152 patients with GIST, 49 were treated with standard dose, while 103 received personalized schedules. At a median follow-up of 36.5 months, median progression-free survival was 5.6 months [95% confidence interval (CI) 3.73-11.0 months] versus 9.7 months (95% CI 7.9-14.5 months) in the standard-dose and the personalized schedule groups, respectively [hazard ratio (HR) 0.51; 95% CI 0.34-0.75; P = 0.00052]. Median overall survival was 16.6 months (95% CI 14.1-21.8 months) versus 20.5 months (95% CI 15.0-25.4 months), respectively (HR 0.75; 95% CI 0.49-1.22; P = 0.16). CONCLUSIONS: Regorafenib-personalized schedules are commonly adopted in daily clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Therefore, regorafenib treatment optimization in patients with GIST may represent the best strategy to maximize long-term therapy.

[Classification of the instrument of assessment of children between 0 and 3 years of age]. / Classificazione degli strumenti di valutazione per bambini da 0-3 anni.

One of the difficulties described in epidemiological studies about psychopathology in children 0-3 years of age appears during the assessment phase. In fact, the assessment of indicators of particular difficulties in children is hampered by the rapid processes of transformation of behavior that cross all areas of child development. The aim of this article was to provide an overview as complete as possible of all instruments used in the assessment phase of children 0-3 years. The literature shows a number of tools for evaluation and diagnosis of psychopathology that have been divided into four categories: mental development tests, interviews with parents, questionnaires and rating scales, evaluation of the parent-child assessment of specific diagnostic entities. The main features of each instrument are described.

[The role of angiography in cryptogenic submesocolic digestive tract bleeding]. / Ruolo dell'angiografia nelle emorragie digestive sottomesocoliche criptogenetiche.

Three cases of chronic gastrointestinal bleeding are described; the Authors emphasize the important role of mesenteric arteriography in establishing site and nature of bleeding. The review of international literature shows a success rate between 41 and 73% of cases studied with this method after negativity of other diagnostic procedures.

[Some methodological aspects of the study of internal migration: the Italian experience, 1969-1979]. / Alcuni aspetti metodologici nello studio delle migrazioni interne. L'esperienza italiana 1969-1979

PIP: A mover-stayer model is used to analyze internal migration among the regions of Italy between 1969 and 1979. Opportunity hypotheses concerning the transition matrices and the behavior of nonmigrants are used to identify some patterns of migration that can serve as a basis for forecasting future migration trends. (summary in ENG, FRE)^ieng

[Portacaval anastomosis with a bypass of lyophilized dura mater. Experimental research in young dogs]. / Anastomosi porta-cava con by-pass di dura madre liofilizzata. Ricerche sperimentali in cani di giovaneetà.

A review of the relevant literature is followed by an account of the use of freeze-dried dura mater prostheses in the construction of porta-cava anastomoses in young dogs. Results of an experiment showed that involution of the dura mater in the new passage between the porta and the cava was followed by the establishment of connective tissue only, and later by the appearance of smooth muscle. The conclusion is drawn that this material gives satisfactory results and is ripe for further development, using various modalities.

[Sequential renal scintiscanning with 99mTc calcium gluconate. Possibilities and limitations]. / La scintigrafia renale sequenziale con tecnezio 99m calcio gluconato. Possibilità e limiti.

The methods used in the study of the kidney are discussed and sequential scintiscanning is suggested as a means of supplementing purely morphological data with morpho-functional data. An account of the modalities employed with a variety of radio-compounds and reasons are proffered for the choice of 99mTc calcium gluconate. Results obtained with this method are described. These include the acquisition of information concerning the function and shape of the renal parenchyma and urinary tracts. Organic classification of the results will be dealt with in a later paper. It is felt that the method proposed is a valuable diagnostic aid with interesting possibilities in the study of diseases of the urinary apparatus.