Search

Introduction: Cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) regimen activity was assessed in a single institution phase II trial (PACT-19) on pancreatic ductal adenocarcinoma (PDAC). The PACT-31 study explored the external validity of PACT-19 results., Materials and Methods: Patients aged ≥18 and ≤75 years with KPS ≥70, and PDAC diagnosis receiving PAXG in the participating institutions were eligible and categorized as follows: A) PACT-19; B) PACT-31-HSR; C) PACT-31-non-HSR. With a sample of 175 patients, assuming a target 1-year overall survival of 60 % for metastatic and of 80 % for non-metastatic patients, the trial will be considered successful with the 1-year OS falling into the 95 % CI., Results: Data from 68 PACT-19 and 168 PACT-31 patients were retrieved. After 124 events, 1yOS was 52.5 % (95 %CI: 44.6-60.4 %) for metastatic and 80.5 % (95 %CI: 71.9-89.1 %) for non-metastatic patients. Survival overlapped between PACT-19 and PACT-31-HSR (median 17.6 and 17.4 months, p = 0.21) and was significantly shorter in PACT-31-non-HSR (median 11.3 months; p = 0.03). Differences of dose-intensity, use of maintenance therapy, and treatment after progression between PACT-31-HSR and non-HSR were evidenced., Discussion: PACT-19 results have external validity. The outcome difference between HSR and non-HSR centers endorses the need of creating a hub-and-spoke network aimed at sharing the expertise on rare-diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer., Methods: A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020., Results: Overall, 253 publications were identified. Subgroup analyses were reported in 217 (86%) publications. A statistically significant association of presence of subgroup analysis with study sponsor was observed: subgroup analyses were reported in 157 (94%) for-profit trials compared with 60 (70%) non-profit trials (P < 0.001). Description of the methodology of subgroup analysis was completely lacking in 82 trials (38%), only cited without methodological details in 100 trials (46%) and fully described in 35 trials (16%). Forest plot of subgroup analyses for the primary endpoint was available in 195 publications (77%). Among publications with reported forest plots, the median number of subgroups for primary endpoint was 19 (range 6-78). Out of the 217 publications with subgroup analyses, authors discuss the heterogeneity of treatment effect among different subgroups in 173 publications (80%), although a formal test for interaction for subgroup analysis of primary endpoint was reported for at least one variable only in 60 publications (28%). Correction for multiplicity was explicitly carried out only in nine trials (4%)., Conclusions: The very high prevalence of subgroup analyses in published papers, together with their methodological weaknesses, makes advisable an adequate education about their correct presentation and correct reading. More attention about proper planning and conduction of subgroup analysis should be paid not only by readers, but also by authors, journal editors and reviewers., Competing Interests: Disclosure The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: MDM reports personal fees from AstraZeneca, Pfizer, Novartis, Roche, Takeda, Janssen, Eisai, Astellas, Merck Sharp & Dohme (MSD), Boehringer Ingelheim, grants from Tesaro-GlaxoSmithKline, outside the submitted work. FP reports grants and personal fees from Bayer, AstraZeneca, Pierre Fabre, Roche, Incyte, MSD, Janssen Cilag, personal fees from Daichii Sankyo, Clovis, Bristol Myers Squibb, Astellas, Ipsen, Seagen, Eli Lilly, GlaxoSmithKline, grants from Tesaro, Pfizer, Exelixis, Aileron, outside the submitted work. MLR had a role as a consultant for Eli Lilly, AstraZeneca and MSD outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Three Bacillus strains isolated from honey samples and bee gut were pre-selected for their in vitro antimicrobial activity against Paenibacillus larvae and Ascosphaera apis, important honeybee pathogens. The analysis of their 16S rRNA sequences revealed that C4, M1 and G2III strains belong to the subtilis species. Surfactin synthesis was verified by IR spectroscopy and HPLC studies. Surfactin inhibited P. larvae but it failed to affect A. apis. Vegetative cells of P. larvae were affected as soon as they came in contact with the surfactin sample; two orders of magnitude less in log scale were recorded. Optimal surfactin production was observed in MEL medium, a broth with molasses as the only carbon source. Bacillus subtilis G2III strain exhibited the highest levels of surfactin synthesis in BHI and MEL broths: 1391AU/ml and 2782AU/ml, respectively. Since only A. apis inhibition was observed when cell suspensions were assayed, we suspect that there may be an antimycotic compound within cells. The co-production of surfactin and a fungicide by these strains might biologically control bee pathogens in apiculture.

Enterococcus faecium J96 was isolated from a healthy free-range chicken and it inhibited Salmonella Pullorum, in vitro, due to its lactic acid and bacteriocin production. In vivo assays were carried out with 30-h-old broiler chicks. The lactic acid bacteria (approximately 1 x 10(9) cells per chick) were orally administered as preventive and as therapeutic treatments. In the first case they were given to the chicks twice a day for 3 consecutive days. In the second case the lactic bacteria were administered in the same way after a 24-h challenge by Salmonella Pullorum (in both instances the salmonella dose was 1 x 10(5) cells per chick). Cecal contents, liver, and spleens were analyzed and liver and spleen fragments were also fixed in formaldehyde (pH 7.00) in order to determine salmonella translocation. The chickens that were preventively treated with E. faecium J96 survived the Salmonella Pullorum challenge. Those that were infected on the first day and then inoculated with lactic bacteria died 4 days later. Salmonellae were isolated from their livers and spleens. From these results we may conclude that E. faecium J96 can protect newly hatched chicks from Salmonella Pullorum infection but cannot act as a good therapeutic agent.

Production of antagonistic compounds was studied in a strain of Enterococcus faecium isolated from the intestinal tract of a free-ranging chicken. Production of lactic acid and a bacteriocin was observed in cultures of this bacterium, alone and in mixed culture fermentations with pathogenic Salmonella serotypes (i.e., Gallinarum, Pullorum, Enteritidis, and Typhimurium). Growth inhibition of these avian and human pathogens was observed after 4 h of incubation at 37 degrees C in CAm broth, a medium developed according to the nutrients present in chicken food. The antibacterial action was due to the combined effect of lactic acid and bacteriocin. Accumulation of these metabolites caused both a bacteriostatic and a bactericidal action against the gram-negative bacteria assayed.