Background and Objectives: Various publications have compared outcomes among open (OPDs), laparoscopic (LPDs), and robotic pancreaticoduodenectomies (RPDs); however, the number of randomized controlled trials (RCTs) remains limited. This study aims to conduct a systematic review and analyze the outcomes between these approaches from randomized controlled trials. Materials and Methods: We performed a systematic literature search across PubMed/MedLine, Cochrane Library, ClinicalTrials.gov, and Google Scholar to identify relevant RCTs. The systematic review was conducted using the reporting items for systematic reviews and network meta-analyses guidelines (PRISMA-NMA) and registered in Prospero (CRD420251024475). For statistical analysis R software (version 4.3.2) was used. Results: Eight RCTs involving 1416 patients (706 OPDs, 600 LPDs, 110 RPDs) were included. LPD had a significantly longer operative time than OPD, while RPD showed no significant difference compared to OPD. Blood loss was reduced in both minimally invasive approaches. LPD showed a higher R0 resection rate and lower pancreatic fistula rate, whereas RPD had the lowest mortality. No significant differences were observed in major complications, reoperation, or readmission. LPD shortened hospital stay; RPD showed no difference. Conclusions: Although open pancreaticoduodenectomy remains a well-established standard, both laparoscopic and robotic approaches offer safe alternatives with distinct advantages. LPD is associated with shorter hospital stay and lower pancreatic fistula rates, whereas RPD demonstrates the lowest mortality. The lack of direct randomized comparisons between LPD and RPD highlights the need for further head-to-head trials.

The renin-angiotensin system (RAS) is an important regulator of functions in various systems, including the brain. A classic pathophysiological consequence of RAS imbalance is hypertension, but the system is also involved in the control of behaviour and the development of neurodegenerative diseases and psychiatric disorders. Angiotensin-converting enzyme type 2 (ACE2) is an important member of the protective arm of the RAS. We hypothesized that ACE2 blockade may alter the systemic balance controlling brain functions. The present study aimed to characterize the effect of systemic acute ACE2 blockade on some behavioural parameters and nociception in mice. Experiments were performed on male ICR mice treated acutely with the selective ACE2 inhibitor MLN-4760. We used a battery of behavioural tests: the “Elevated Plus Maze” for anxiety behaviour, the “Open Field” for exploratory behaviour, the “Hot Plate”, and formalin tests for thermal and chemical nociception, respectively. The results showed that acute treatment with the ACE2 inhibitor MLN reduces normal anxiety-like behaviour in a novel environment, as expressed by increased time spent in the open arms of the Elevated Plus Maze and increased distance in the central area of the Open Field Test. Short-term blockade of ACE2 produced antinociception in the acute thermal test and the inflammatory second phase of the formalin test. In summary, we can conclude that ACE2 is involved in the regulation of complex brain functions, such as motivational behaviour and pain perception.

Alzheimer's disease (AD), a form of dementia, presents a global concern. This study investigates the connection between hypertension and AD and the effects of the peptide novokinin (NVK), an AT2 receptor agonist in spontaneously hypertensive rats (SHRs). The brain's renin-angiotensin system (RAS) influences cognitive and emotional processes, suggesting potential intersections with AD. Streptozotocin (STZ), administered intracerebroventricularly (ICV), is used as a model of late-onset Alzheimer's disease. This model reveals a memory impairment associated with an insulin-resistant brain state, marked by neuroinflammatory processes contributing to cognitive deficits, oxidative stress, and reduced cerebral energy metabolism. NVK is an angiotensin AT2 receptor agonist, studied for its potential neuroprotective role. Female SHRs were used to investigate the effects of STZ-ICV (twice) and chronic NVK-ICV. NVK was administered for 14 days ICV using osmotic minipumps (ALZET®). The control group exhibited strain-typical increased exploratory activity, reduced anxiety in new environments, and impaired spatial memory, as expected for SHRs. The STZ-ICV negative control group showed signs of impaired memory and object recognition. In the `Open Field’ test, STZ-treated groups with and without NVK-ICV displayed heightened exploratory behaviour. Data from the `Elevated plus maze' test showed decreased anxiety in the STZ-ICV group while combining STZ and NVK normalized the anxiety behaviour. In the `T-maze' test, STZ-ICV-treated rats made fewer correct decisions. The STZ+NVK group exhibited enhanced spatial memory and improved anxiety-like behaviour in novel environments, potentially attributable to the proposed neuroprotective effects of NVK. These findings emphasize the association of RAS in the progression of AD and the potential protective role of the brain's AT2 receptors in this type of dementia.