Survival benefit of pancreatic enzyme replacement therapy in patients undergoing treatment of pancreatic neuroendocrine tumours.

BACKGROUND: Treatment with somatostatin analogues (SSAs) or pancreaticoduodenectomy frequently causes malnutrition-inducing pancreatic exocrine insufficiency. This single-centre retrospective cohort study aimed to establish whether pancreatic enzyme replacement therapy (PERT) improves survival or nutritional status in SSA or pancreaticoduodenectomy-treated patients with pancreatic neuroendocrine tumours (pNETs). METHODS: SSA and/or pancreaticoduodenectomy-treated patients with pNETs, diagnosed between 2009 and 2019, (n = 77) were retrospectively identified from departmental databases. Data was sourced from clinical records. Overall survival and percentage monthly weight changes were compared between PERT-treated (n = 45) and non-PERT-treated (n = 32) patients. RESULTS: PERT-treated patients experienced significantly greater median monthly weight gain (+0.01% vs -0.10%, p = 0.038) and 5-year survival (81% vs 51%, p = 0.007). PERT was not, however, independently associated with survival (Hazard ratio 0.47, 95% CI 0.14-1.62, p = 0.232). Considering SSA-treated patients (n = 50) only, PERT-treated patients (n = 24) showed numerically but non-significantly improved monthly weight gain (+0.04% vs -0.18%, p = 0.139) and median survival (55.5, 95% CI 10.2-100.7 vs 42.4, 95% CI 11.7-73.2 months, p = 0.082). CONCLUSION: PERT may improve survival and nutrition in SSA and pancreaticoduodenectomy-treated patients with pNETs, however, low patient numbers precluded the reliable mitigation of confounding in this study. A further multi-centre study is required to define the benefits of PERT in this population.

COVID-19 vaccination attitudes and uptake: A sociocultural perspective focusing on parents and peers.

The global fight against the COVID-19 pandemic has underscored the critical importance of widespread vaccination to mitigate the impact of the virus on public health. The current study aimed to investigate which social influences might be most important for predicting attitudes towards COVID-19 vaccination and vaccine uptake among young students in the UK. We focused on the cultural evolution and social transmission aspects, i.e., parent-to-child versus peer-to-peer, of attitudes and vaccine uptake during the COVID-19 pandemic. A sample of 192 UK students (aged 18 to 35 years old) filled in an online survey including measures for attitudes towards COVID-19 vaccination and vaccine uptake and/or intention, age, and gender. Participants were also asked about their mother's, father's, and best friend's attitudes towards COVID-19 vaccination and vaccine uptake. Finally, they provided a subjective measure of the quality relationship with their parents. Overall, our results suggest that both parents and very close friends are important agents in understanding the students' attitudes towards COVID-19 vaccination and vaccine uptake. More specifically, our findings suggest the mother's vaccine uptake as the most salient predictor of students' attitudes towards COVID-19 vaccination and vaccine uptake, particularly when the students report having a positive relationship with their parents. In cases where students' experience negative relationship with their parents, the best friend's vaccine uptake may supersede the mother's influence. Despite these nuances, a general trend emerges from our data suggesting that vaccine uptake could be primarily guided by vertical transmission (i.e., parent to child). Our results have the potential to influence public health strategies, communication campaigns, and targeted interventions to enhance vaccination uptake. Identifying key social predictors can enable policymakers and health authorities to tailor vaccination promotion efforts towards mothers' and peers' vaccine uptake to increase overall positive attitudes and vaccine uptake among young people.

Casting a Wider NET: Pancreatic Exocrine Insufficiency Induced by Somatostatin Analogues among Patients with Neuroendocrine Tumours?

Somatostatin-analogues (SSAs) are a first-line treatment of unresectable neuroendocrine tumours (NETs). However, SSAs inhibit pancreatic secretions, which could lead to pancreatic exocrine insufficiency (PEI). PEI is known to be detrimental to patient quality of life and nutritional status. This study aimed to evaluate the effect of SSAs on pancreatic exocrine function in patients with NETs, using the 13C-mixed triglyceride breath test (13C-MTGT). Exocrine function was assessed using the 13C-MTGT at baseline and after a third SSA injection (two months). A quotient of 13CO2/12CO2 was measured by mass spectrometry, and the cumulative percent dose recovered at 6 h (cPDR) is reported. The secondary endpoints investigated were change in weight, HbA1C, and vitamin D levels. Ten patients completed the study. Exocrine function reduced in all patients (n = 10) following SSA therapy (median reduction from baseline: -23.4% (range: -42.1-0.5%, p = 0.005)). vitamin D levels decreased in all but one patient (median decrease from baseline: -26.5%, (-44.7-10%; p = 0.038)), and median HbA1C levels increased by 8.0% (0-59.3%; p = 0.008). Change in weight was not significant (median decrease from baseline: -0.21% (-4.5-3.5%, p = 1.000)). SSA therapy has a consistent impact on exocrine function from early in the treatment course, but the long-term clinical effects of this remain to be defined. Further studies are required to determine the clinical relevance of this observation and optimise the management of PEI in this cohort.

Prolonged cyclin-dependent kinase inhibition results in septin perturbations during return to growth and mitosis.

We investigated how Saccharomyces cerevisiae coordinate polarization, budding, and anaphase during a unique developmental program called return to growth (RTG) in which cells in meiosis return to mitosis upon nutrient shift. Cells reentering mitosis from prophase I deviate from the normal cell cycle by budding in G2 instead of G1. We found that cells do not maintain the bipolar budding pattern, a characteristic of diploid cells. Furthermore, strict temporal regulation of M-phase cyclin-dependent kinase (CDK; M-CDK) is important for polarity establishment and morphogenesis. Cells with premature M-CDK activity caused by loss of checkpoint kinase Swe1 failed to polarize and underwent anaphase without budding. Mutants with increased Swe1-dependent M-CDK inhibition showed additional or more penetrant phenotypes in RTG than mitosis, including elongated buds, multiple buds, spindle mispositioning, and septin perturbation. Surprisingly, the enhanced and additional phenotypes were not exclusive to RTG but also occurred with prolonged Swe1-dependent CDK inhibition in mitosis. Our analysis reveals that prolonged activation of the Swe1-dependent checkpoint can be detrimental instead of beneficial.