APR (Italy)

Rectal-sparing strategies for locally advanced rectal cancer are gaining interest owing to favorable oncological results and reduced impact on functional outcomes. In patients managed with watch-and-wait or local excision after neoadjuvant chemoradiotherapy (nCRT), local regrowth occurs in approximately 15-30% of cases. Total mesorectal excision (TME) is the standard treatment for regrowth; however, local excision (LE) may be considered in selected cases to preserve rectal function. This narrative review evaluates clinical and oncological outcomes of patients undergoing LE for suspected regrowth. A narrative review of the literature was conducted using databases and search terms including "rectal cancer," "rectal sparing," and "local regrowth." Five retrospective studies were identified, encompassing a total of 159 patients. Treatment protocols, neoadjuvant regimens, and follow-up strategies varied across the studies. Histopathological findings revealed ypT ≥ 2 in 45.3% of cases. Reported overall survival (OS) was consistently above 94.5%, while 2-year locoregional recurrence-free survival ranged from 74% to 85%. Systemic recurrence occurred in 9.1% of patients. LE was associated with shorter operative time, reduced blood loss, and lower rates of Clavien-Dindo ≥ 3 complications. Local excision for regrowth may represent a feasible alternative to radical surgery in selected patients, particularly within specialized centers and under strict surveillance protocols. Further prospective studies are warranted to validate its long-term oncologic safety and functional outcomes.

An automated resource analysis technique is introduced, targeting a Call-By-Push-Value abstract machine, with memory prediction as a practical goal. The machine has a polymorphic and linear type system enhanced with a first-order logical fragment, which encodes both low-level operational semantics of resource manipulations and high-level synthesis of algorithmic complexity. Resource analysis must involve a diversity of static analysis, for escape, aliasing, algorithmic invariants, and more. Knowing this, we implement the Automated Amortized Resource Analysis framework (AARA) from scratch in our generic system. In this setting, access to resources is a state-passing effect which produces a compile-time approximation of runtime resource usage. We implemented type inference constraint generation for our calculus, accompanied with an elaboration of bounds for iterators on algebraic datatypes, for minimal ML-style programming languages with Call-by-Value and Call-By-Push-Value semantics. The closed-formed bounds are derived as multivariate polynomials over the integers. This now serves as a base for the development of an experimental toolkit for automated memory analysis of functional languages.

Abstract Bacterial isolates belonging to Pseudomonas syringae pv. actinidiae, the causal agent of kiwifruit bacterial canker, have been isolated, during 2021 and 2022, from Actinidia chinensis orchards of Central Italy planted with cultivars Hayward and Zespri G3®. A total of 23 isolates were obtained from twigs and leaves that showed the typical symptoms of bacterial canker, including leaf spotting and twig canker. All of them showed resistance to 1.2 mM copper sulphate added to mannitol–glutamate–yeast extract (MGY) medium. No other Pseudomonas syringae pv. actinidiae strains were isolated from the orchards. The P. s. pv. actinidiae strains that showed resistance to copper have the copA and copD genes that regulate the efflux of copper through the inner membrane and the copper sensor copS gene. They do not possess the cusABC complex that confers resistance to high concentration of copper. Representative copper‐resistant strains were proven pathogenic to kiwifruit plants upon artificial inoculation. This is the first record of copper‐resistant P. s. pv. actinidiae strains in Italy and, as far as we know, in Europe.

Multiple endocrine neoplasia type 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome, associated with a wide tumor spectrum but hallmarked by primary hyperparathyroidism, which represents the most common clinical feature, followed by pituitary (functional and non-functional) adenomas, and neuroendocrine tumors. MEN4 clinically overlaps MEN type 1 (MEN1) but differs from it for milder clinical features and an older patient's age at onset. The underlying mutated gene, CDKN1B, encodes the cell cycle regulator p27, implicated in cellular proliferation, motility and apoptosis. Given the paucity of MEN4 cases described in the literature, possible genotype-phenotype correlations have not been thoroughly assessed, and specific clinical recommendations are lacking. The present review provides an extensive overview of molecular genetics and clinical features of MEN4, with the aim of contributing to delineate peculiar strategies for clinical management, screening and follow-up of the last and least known MEN syndrome. A literature search was performed through online databases like MEDLINE and Scopus. MEN4 is much less common that MEN1, tend to present later in life with a more indolent course, although involving the same primary organs as MEN1. As a consequence, MEN4 patients might need specific diagnostic and therapeutic approaches and a different strategy for screening and follow-up. Further studies are needed to assess the real oncological risk of MEN4 carriers, and to establish a standardized screening protocol. Furthermore, a deeper understanding of molecular genetics of MEN4 is needed in order to explore p27 as a novel therapeutic target.

Noninvasive continuous positive airway pressure (NIV-CPAP) is effective in patients with hypoxemic respiratory failure. Building evidence during the COVID-19 emergency reported that around 50% of patients in Italy treated with NIV-CPAP avoided the need for invasive mechanical ventilation. Standard NIV-CPAP systems operate at high gas flow rates responsible for noise generation and inadequate humidification. Furthermore, open-configuration systems require a high concentration of oxygen to deliver the desired FiO2 . Concerns outlined the risk for aerosolization in the ambient air and the possible pressure drop in hospital supply pipes. A new NIV-CPAP system is proposed that includes automatic control of patient respiratory parameters. The system operates as a closed-loop breathing circuit that can be assembled, combining a sleep apnea machine with existing commercially available components. Analytical simulation of a breathing patient and simulation with a healthy volunteer at different FiO2 were performed. Inspired and expired oxygen fraction and inspired and expired carbon dioxide pressure were recorded at different CPAP levels with different oxygen delivery. Among the main findings, we report (a) a significant (up to 30-fold) reduction in oxygen feeding compared to standard open high flow NIV-CPAP systems, to assure the same FiO2 levels, and (b) a negligible production of the noise generated in ventilatory systems, and consequent minimization of patients' discomfort. The proposed NIV-CPAP circuit, reshaped in closed-loop configuration with the blower outside of the circuit, has the advantages of minimizing aerosol generation, environmental contamination, oxygen consumption, and noise to the patient. The system is easily adaptable and can be implemented using standard CPAP components.