Cannabidiol can affect morphology, morphometry, enzymatic and microbial activity of rabbit digestive system

The present research aimed to evaluate the effects of the continuative dietary administration of a hemp oil extract containing cannabinoids (cannabidiol, CBD) on the macroscopic morphology, morphometry, and enzymatic activity of different intestinal tracts as well as on the production of short-chain fatty acids (SCFAs) in the cecum of growing rabbits. The research was performed on 16 rabbits randomly selected from 2 experimental groups (8 per group). In detail, 42 sixty-day-old New Zealand White × California rabbits (sex ratio 1:1, average weight 1621.3 ± 46.2 g) were homogeneously divided into 2 groups (21 animals/group), namely control and CBD. Both groups were fed the same commercial diet, but the CBD one was supplemented with 0.1 mL of hemp extract in coconut-based oil corresponding to 10 mg of CBD/animal/d. Up to 92 d of age (for 27 d), individual live weight and feed intake were measured weekly. At 92 d of age, 8 rabbits/group (sex ratio 1:1) were moved to a specialized slaughterhouse, and the gastrointestinal tract was separated from the carcass. Samples from 8 rabbits per dietary treatment were used for the histomorphological analysis of small and large intestines. In addition, duodenum, jejunum, ileum, and cecum were processed for enzymatic analysis. The caecal contents were used for the SCFAs determination. The administration of CBD did not affect feed intake and the final rabbits’ whole body weight (P > 0.05), but some changes were detected in the gastrointestinal tract of the animals. CBD seemed to interfere with protein digestion, with a significantly lower activity of the enzymes related to peptides in the small intestine and a consequent increase of the fermentative activity of caecal microbiota. This effect, in combination with a general decrease of fermentative activity in the caecal content of rabbits submitted to CBD treatment, was responsible for a change in the SCFA proportion mainly regarding the reduction of butyrate production (P < 0.01) that resulted significant higher in CTR group compared to CBD. This last result is very important for intestinal health. Such fermentation activity modification was coupled with changes in the relative abundance of goblet cells in the colon. Overall, our findings suggest that a relatively long-term administration of CBD may affect digestion in rabbits, in particular at enzymatic and fermentative levels

Gastric Cancer Stem Cells: A Glimpse on Metabolic Reprogramming

Gastric cancer (GC) is one of the most widespread causes of cancer-related death worldwide. Recently, emerging implied that gastric cancer stem cells (GCSCs) play an important role in the initiation and progression of GC. This subpopulation comprises cells with several features, such as self-renewal capability, high proliferating rate, and ability to modify their metabolic program, which allow them to resist current anticancer therapies. Metabolic pathway intermediates play a pivotal role in regulating cell differentiation both in tumorigenesis and during normal development. Thus, the dysregulation of both anabolic and catabolic pathways constitutes a significant opportunity to target GCSCs in order to eradicate the tumor progression. In this review, we discuss the current knowledge about metabolic phenotype that supports GCSC proliferation and we overview the compounds that selectively target metabolic intermediates of CSCs that can be used as a strategy in cancer therapy

Mirrors Can Affect Growth Rate, Blood Profile, Carcass and Meat Traits and Caecal Microbial Activity of Rabbits Reared in a “Small Group” Free-Range System

The aim of this work was to propose a model of free-range raising for rabbit able to maximize the animal welfare and at the same time the productive performances through the use of mirrors. A total of 81 rabbits were allocated into free-range areas and divided into three groups (nine replicates per group): in the first group (face to face, F2F), the rabbits of each replicate could see each other. In the second group (blind) each replicate was isolated from the others; in the third group (mirrors), the replicates were divided as for the Blind group but two mirrors were placed in a corner of the perimeter. The blind group rabbits showed the lowest final weight (p < 0.05), while rabbits from the mirrors groups showed the best FCR and net dressing out values. The blind group showed the highest production of total short chain fatty acids, acetate (p < 0.05) and propionate (p < 0.01). The F2F rabbits showed higher levels of creatine phosphokinase and lactate dehydrogenase and lower values of blood glucose than those of the other groups, due to the higher locomotion activity. The use of mirrors can improve rabbit’s growth performance and carcass traits by lowering the rabbit’s locomotion activity in comparison to the other tested systems

Low-voltage area ablation in addition to pulmonary vein isolation in patients with atrial fibrillation: a systematic review and meta-analysis

Background: Low-voltage area (LVA) ablation, in addition to pulmonary vein isolation (PVI), has been proposed as a new strategy in patients with atrial fibrillation (AF), but clinical trials have shown conflicting results. We performed a systematic review and meta-analysis to assess the impact of LVA ablation in patient undergoing AF ablation (PROSPERO-registered CRD42024537696). Methods: Randomized clinical trials investigating the role of LVA ablation in addition to PVI in patients with AF were searched on PubMed, Embase, and the Cochrane Library from inception to 22 April 2024. Primary outcome was atrial arrhythmia recurrence after the first AF ablation procedure. Secondary endpoints included procedure time, fluoroscopy time, and procedure-related complication rate. Sensitivity analysis including only patients with LVA demonstration at mapping and multiple subgroups analyses were also performed. Results: 1547 patients from 7 studies were included. LVA ablation in addition to PVI reduced atrial arrhythmia recurrence (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52-0.81, p &lt; 0.001) with a number needed to treat to prevent recurrence of 10. No difference in procedure time (mean difference [MD] -5.32 min, 95% CI -19.01-8.46 min, p = 0.45), fluoroscopy time (MD -1.10 min, 95% CI -2.48-0.28 min, p = 0.12) and complication rate (OR 0.81, 95% CI 0.40-1.61, p = 0.54) was observed. Consistent results were demonstrated when considering only patients with LVA during mapping and in prespecified subgroups for AF type (paroxysmal vs. persistent), multicentric vs. monocentric trial, and ablation strategy in control group. Conclusions: In patients with AF, ablation of LVAs in addition to PVI reduces atrial arrhythmia recurrence without a significant increase in procedure time, fluoroscopy time, or complication rate

Pancreatic fistula after a pancreaticoduodenectomy for ductal adenocarcinoma and its association with morbidity: a multicentre study of the French Surgical Association

AbstractBackgroundsA pancreatic fistula (PF) is the most relevant complication after a pancreaticoduodenectomy (PD). This retrospective multicentric study attempts to elucidate the risk factors and complications of a PF in a large cohort of patients undergoing a PD for ductal adenocarcinoma.MethodsUsing a survey tool, clinical data of 1325 patients undergoing a PD for ductal adenocarcinoma at 37 institutions, between January 2004 and December 2009, were collected. Peri-operative risk factors associated with PF and its association with morbidity and mortality were assessed. Morbidity and PF were graded according to the ISGPF (International Study group for pancreatic fistula) definition and the Dindo–Clavien classification.ResultsOverall PF, mortality, morbidity and relaparotomy rates were 14.3%, 3.8%, 54.4% and 11.7%, respectively. PF occurred more frequently after a pancreaticojejunostomy (PJ) compared with a pancreaticogastrostomy (PG) (16.8% vs. 10.4%; P = 0.0012). Independent risk factors for PF by multivariate analysis were absence of pre-operative diabetes (P = 0.0014), PJ reconstruction (P = 0.0035), soft pancreatic parenchyma (P < 0.0001) and low-volume centre (P = 0.0286). Clinically relevant PF (grade B and C) and severe complications (Dindo–Clavien grade IIIB, IV, V) were significantly more frequent after PJ than PG (71.6% vs. 28.3%; P = 0.030 and 24.8% vs. 19.1%; P = 0.015, respectively). Overall mortality and relaparotomy rates were similar after PG and PJ.ConclusionsA soft pancreatic parenchyma, the absence of pre-operative diabetes, PJ and low-volume centre are independent risk factors for PF after PD for ductal adenocarcinoma. A significantly higher incidence and clinical severity of PF are associated with PJ

Neutrophil/lymphocyte ratio: a potential biomarker in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors

IntroductionLiterature has shown that there is a correlation between increased circulatory inflammatory factors and negative prognosis, which can be evaluated through the using the neutrophil and lymphocyte ratio (NLR). The aim of this research is to investigate the predictive and prognostic role of the NLR in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, treated with immunotherapy, and its correlation to the overall survival (OS), progression free survival (PFS) and objective response rate (ORR).MethodsThis multicentric study coordinated by the Oncology Unit of University of Campania “Luigi Vanvitelli”, retrospectively analyzed data from 135 patients diagnosed with R/M HNSCC from 13 Italian oncological centers.ResultsTwo groups were made using the median NLR value of 4.2. 71 patients (52.6%) had NLR&gt;4 and 64 patients (47.4%) had NLR&lt;=4. Mean OS of patients with NLR&gt;4 was significantly shorter than that of patients with NLR&lt;=4 (23.1 vs 37.4 months, p= 0.002). Univariable analysis showed a statistically significant correlation between OS and NLR value (p=0.002), and between OS and ECOG (p=0.022). Median PFS stratified by NLR value, was statistically significant: 6.5 vs 20 months in patients with NLR&gt;4 and NLR&lt;=4, respectively (p= 0.013O). ORR in the general population was 32.6%. NLR-stratified ORR confirmed the unfavorable prognostic role of high NLR: 20% if NLR&lt;=4, and 12.5% if NLR&gt;4.DiscussionBasal NLR value lower than the cut-off of 4 is independently associated with better OS, PFS and ORR in patients with R/M HNSCC treated with immunotherapy, in first- or second- line

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case-control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46-0.95], p\u2009=\u20090.0281), PFS (HR 0.65 [95% CI 0.48-0.89]; p\u2009=\u20090.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p\u2009=\u20090.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of\u2009 65\u20091 somatic DDR gene mutation was 20% and 24.5% (p\u2009=\u20090.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p\u2009=\u20090.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking.METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines.RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ).CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.</p

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking.METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines.RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ).CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.</p

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI