Background
Incidence of positive surgical margins after curative gastrectomy ranges from 1% to 20%. It has been suggested that positive surgical margin is an adverse prognosis factor, with a higher ...local recurrence and worse overall survival (OS). However, the management of these patients remains unclear.
Methods
A total of 267 patients who underwent gastrectomy with curative intent between January 2010 and December 2018 in our centre were enrolled in this study. Post‐operative histological analysis revealed positive resection margins in 18 patients (8%). Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared.
Results
Patients with positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, whole stomach involved and poorly differentiated tumours. Local recurrence was described in 50% of cases with positive margins. The multivariate analysis demonstrated that the TNM stage was the only independent prognostic factor associated with recurrence. OS for positive margins at 1, 3 and 5 years was 75%, 57% and 26%, respectively. The median survival in patients with positive margins was 38.33 versus 81.17 months for R0 patients (p = 0.027). Multivariate analysis showed that age (hazard ratio HR 1.041, 95% confidence interval CI 1.02–1.07, sex (HR 2.00, 95% CI 1.22–3.30) and TNM stage (p < 0.001) were independent factors of OS.
Conclusion
Positive resection margin was an indication of advanced and more aggressive disease rather than an independent prognosis factor for OS or recurrence in gastric cancer.
Incidence of positive surgical margins after curative gastrectomy ranges from 1% to 20%, but the significance remains unclear. We analysed 267 patients who underwent a gastrectomy at our centre. After the analysis, R1 margins were an indication of advanced and more aggressive disease than an independent prognostic factor for overall survival or recurrence in gastric cancer.
Rationale
Opioid drugs indirectly activate dopamine (DA) neurons in the ventral tegmental area (VTA) through a disinhibition mechanism mediated by mu opioid receptors (MORs) present both on the GABA ...projection neurons located in the medial tegmental nucleus/tail of the VTA (RMTg/tVTA) and on the VTA GABA interneurons. It is well demonstrated that ethanol, like opioid drugs, provokes VTA DA neuron disinhibition by interacting (through its secondary metabolite, salsolinol) with MORs present in VTA GABA interneurons, but it is not known whether ethanol could disinhibit VTA DA neurons through the MORs present in the RMTg/tVTA.
Objectives
The objective of the present study was to determine whether ethanol, directly microinjected into the tVTA/RMTg, is also able to induce VTA DA neurons disinhibition.
Methods
Disinhibition of VTA DA neurons was indirectly assessed through the analysis of the motor activity of rats. Cannulae were placed into the tVTA/RMTg to perform microinjections of DAMGO (0.13 nmol), ethanol (150 or 300 nmol) or acetaldehyde (250 nmol) in animals pre-treated with either aCSF or the irreversible antagonist of MORs, beta-funaltrexamine (beta-FNA; 2.5 nmol). After injections, spontaneous activity was monitored for 30 min.
Results
Neither ethanol nor acetaldehyde directly administered into the RMTg/tVTA were able to increase the locomotor activity of rats at doses that, in previous studies performed in the posterior VTA, were effective in increasing motor activities. However, microinjections of 0.13 nmol of DAMGO into the tVTA/RMTg significantly increased the locomotor activity of rats. These activating effects were reduced by local pre-treatment of rats with beta-FNA (2.5 nmol).
Conclusions
The tVTA/RMTg does not appear to be a key brain region for the disinhibiting action of ethanol on VTA DA neurons. The absence of dopamine in the tVTA/RMTg extracellular medium, the lack of local ethanol metabolism or both could explain the present results.
despite significant medical and technological advances, the incidence of postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) is reported to be between 3-45 %. The main objective ...of this study was to analyze the early post-surgical risk factors for developing POPF after DP.
a retrospective observational study was performed on a prospective basis of patients undergoing DP in a tertiary hospital from January 2011 to December 2021. Sociodemographic, preoperative analytical, tumor-related and postoperative complications variables were analyzed.
of the 52 patients analyzed, 71.8 % of the sample had postoperative drains amylase elevation. However, 25.7 % of the total had grade-B and/or grade-C POPF. Univariate logistic regression with the variables studied showed the following as risk factors for B-C or clinically relevant POPF: amylase values in drainage at the 5th postoperative day (POD) (p = 0.097; 1.01 1-1.01), preoperative BMI (p = 0.015; 1.27 1.04-1.55) and C-reactive protein (CRP) value at the 3rd POD (p = 0.034; 1.01 1.01-1.02). The ROC curve of CRP value at the 3rd POD showed an area under the curve of 0.764 (95 % CI: 0.6-0.93) and the best cut-off point was 190 mg/l (sensitivity 89 % and specificity 67 %).
CRP value at the 3rd POD is a predictive factor for POPF after DP. Early detection of patients at risk of POPF based on these characteristics could have an impact on their postoperative management.
West Nile Virus (WNV) is a mosquito vector-borne zoonosis with an increasing incidence in Europe that has become a public health concern. In Spain, although local circulation has been known for ...decades, until 2020, when a large outbreak occurred, West Nile Virus cases were scarce and mostly occurred in southern Spain. Since then, there have been new cases every year and the pathogen has spread to new regions. Thus, monitoring of circulating variants and lineages plays a fundamental role in understanding WNV evolution, spread and dynamics. In this study, we sequenced WNV consensus genomes from mosquito pools captured in 2022 as part of a newly implemented surveillance program in southern Spain and compared it to other European, African and Spanish sequences. Characterization of WNV genomes in mosquitoes captured in 2022 reveals the co-circulation of two WNV lineage 1 variants, the one that caused the outbreak in 2020 and another variant that is closely related to variants reported in Spain in 2012, France in 2015, Italy in 2021-2022 and Senegal in 2012-2018. The geographic distribution of these variants indicates that WNV L1 dynamics in southern Europe include an alternating dominance of variants in some territories.
DNA knots are deleterious for living cells if not removed. Several theoretical and simulation approaches address the question of how topoisomerases select the intermolecular passages that ...preferentially lead to unknotting rather than to the knotting of randomly fluctuating DNA molecules, but the formation of knots in vivo remains poorly understood. DNA knots form in vivo in non-replicating and replicating molecules, and supercoiling as well as intertwining are thought to play a crucial role in both the formation and resolution of DNA knots by topoisomerase IV. To confirm this idea, we used two-dimensional agarose gel electrophoresis run with different concentrations of chloroquine to demonstrate that non-replicating pBR322 plasmids grown in a topoisomerase I-defective E. coli strain (RS2λ) were more negatively supercoiled than in a wild-type strain (W3110) and, concurrently, showed significantly fewer knots. In this way, using wild-type and E. coli mutant strains, we confirmed that one of the biological functions of DNA supercoiling is to reduce the formation of DNA knots.
To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, ...tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years,
p
= 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (
p
= 0.043) and tended to be lower than in the healthy group (
p
= 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination.
Key points:
• Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered.
• However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required.
• This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.
Aim
Anastomotic leakage (AL) following ileorectal (IRA) or ileosigmoid (ISA) anastomosis is associated with a high morbidity. The identification of potential risk factors for AL could change ...operative planning and reduce further complications. This study assesses the rate, potential risk factors and management of AL after total colectomy (TC) and subtotal colectomy (STC).
Methods
A nationwide, multicentre, retrospective cohort study involved 26 Spanish referral centres. It included TC and STC with IRA or ISA patients between January 2013 and December 2020. Clinical data, primary surgery and complications were collected. Univariate and multivariate analysis to identify risk factors for AL were performed. Management of Grade B–C AL and permanent stoma rate was assessed according to revisional surgeries.
Results
The study included 1074 patients, 433 ISA group (40.3%) and 641 IRA group (59.7%). The overall incidence of AL was 14.3% with no differences between IRA and ISA (14.2% and 14.5% respectively), P = 0.871. Male sex, ASA score and lower total preoperative proteins were identified as independent risk factors for global and Grade B–C AL. Diverting ileostomy did not protect against AL (P = 0.084). Clavien–Dindo ≥IIIA complication was found in 251 patients (23.3%). Stoma reversal was not possible in 85 patients (8.1%), being more frequent after anastomosis excision and terminal ileostomy in AL Grade C.
Conclusion
Total colectomy and STC with IRA or ISA are high‐risk procedures with an increased AL rate. Male sex, ASA score and lower preoperative protein level were associated with global AL and AL Grade B and C. A lower permanent stoma rate could be obtained when diverting ileostomy is performed in revision surgery.
Alcohol use disorders are chronic and highly relapsing disorders, thus alcoholic patients have a high rate of recidivism for drug use even after long periods of abstinence. The literature points to ...the potential usefulness of N‐acetylcysteine (NAC) in the management of several substance use disorders probably due to its capacity to restore brain homeostasis of the glutamate system disrupted in addiction. However, there is little evidence in the case of alcohol. The aim of this study was to explore the potential anti‐relapse efficacy of NAC using the alcohol deprivation effect (ADE) model in long‐term experienced rats. Two experiments were performed in male Wistar rats to: (a) test the efficacy of NAC to prevent relapse and (b) discriminate the best administration schedule (intermittent vs. continuous) for NAC. In the first experiment, animals were implanted with mini‐osmotic pumps delivering 0 or 1 mg/hr NAC during 14 days. In a second experiment, rats received 0, 60, or 100 mg/kg once daily by subcutaneous injection. The efficacy to prevent ADE was evaluated in both experiments. NAC subcutaneously administered, either by continuous infusion or by intermittent injections regimen, is able to block the ADE. The best results were obtained after using 60 mg/kg NAC dose. Our findings support the hypothesis that NAC may represent a valuable therapy in the management of alcohol relapse.
In this research, the potential anti‐relapse efficacy of N‐acetylcysteine (NAC), using the alcohol deprivation effect (ADE) model in long‐term experienced male Wistar rats, has been explored. Two different experiments were performed in order to: (a) test the efficacy of NAC to prevent relapse and (b) discriminate the best administration schedule (intermittent vs. continuous) for the drug. NAC subcutaneously administered, either by continuous infusion or by intermittent injections regimen, was able to block the ADE. The best results were obtained after using 60 mg/kg NAC dose under an intermittent regimen.
Rationale
Using a preclinical model based on the Alcohol Deprivation Effect (ADE), we have reported that N-Acetylcysteine (NAC) can prevent the relapse-like drinking behaviour in long-term ...ethanol-experienced male rats.
Objectives
To investigate if chronic ethanol intake and protracted abstinence affect several glutamate transporters and whether NAC, administered during the withdrawal period, could restore the ethanol-induced brain potential dysfunctions. Furthermore, the antioxidant and anti-inflammatory effects of NAC during abstinence in rats under the ADE paradigm were also explored.
Methods
The expression of GLT1, GLAST and xCT in nucleus accumbens (Nacc) and dorsal striatum (DS) of male Wistar was analysed after water and chronic ethanol intake. We used the model based on the ADE within another cohort of male Wistar rats. During the fourth abstinence period, rats were treated for 9 days with vehicle or NAC (60, 100 mg/kg; s.c.). The effects of NAC treatment on (i) glutamate transporters expression in the Nacc and DS, (ii) the oxidative status in the hippocampus (Hip) and amygdala (AMG) and (iii) some neuroinflammatory markers in prefrontal cortex (PFC) were tested.
Results
NAC chronic administration during protracted abstinence restored oxidative stress markers (GSSG and GGSH/GSH) in the Hip. Furthermore, NAC was able to normalize some neuroinflammation markers in PFC without normalizing the observed downregulation of GLT1 and GLAST in Nacc.
Conclusions
NAC restores brain oxidative stress and neuroinflammation that we previously observed after protracted ethanol abstinence in long-term ethanol-experienced male rats. This NAC effect could be a plausible mechanism for its anti-relapse effect. Also, brain oxidative stress and neuroinflammation could represent and identify plausible targets for searching new anti-relapse pharmacotherapies.
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