The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or ...not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.
The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on ...morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis.
We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 10
cells/kg or 4 × 10
cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity.
One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-β in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity.
Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.
This study aimed to measure the toxicity resulting from collagenase administration to the peritoneal cavity in a pig model as a preliminary step to break down the stroma surrounding tumors.
Eight ...pigs were treated with 2 different collagenase concentrations previously tested in rats by our group. Time and temperature were controlled using a peritoneal lavage system (PRS System, Combat Medical Ltd.) identical to that used in human surgeries through hyperthermic intraperitoneal chemotherapy (HIPEC); 2 additional pigs were treated with peritoneal lavage only. Samples of blood and peritoneal fluid were collected pre-treatment, immediately after treatment, and 24 h postoperatively. In addition, histological studies and blood collagenase levels were measured.
No complications were observed during the surgeries. Intraoperative images evidenced the release of peritoneal tissue during collagenase treatment. After surgery, the animals showed no signs of pain. Diet and mobility were normal at 4 h postoperatively, and there were no significant differences in hematologic or biochemical parameters. Quantification of MMP1 and MMP2 in all samples as measured by absorbance showed no differences in blood collagenase levels between pre-treatment, post-treatment, and 24 h postoperatively. None of the animals treated with collagenase showed peritoneal adhesions during the second surgery. Histologically, peritoneal organs and serous structures did not show any microscopic alterations associated with collagenase treatment in any group.
Lavage of the peritoneal cavity with doses of up to 100,000 collagen digestion units/animal for 30 min is safe and removes connective tissue from the peritoneal cavity.
Information on temporal trends can identify groups of people at risk for any particular condition; however information on temporal trends on migraine headache at population levels is scarce. Our aim ...was to estimate the time trends in the prevalence of migraine from 2003 to 2012 in Spain.
A population-based national study was conducted. We analyzed data using individualized information taken from national surveys conducted in 2003/4, 2006/7, 2009/10 and 2011/12. A total of 94,158 Spanish adults participated. We considered the presence of self-rated and diagnosed migraine, and we analyzed socio-demographic features, lifestyle habits, self-rated health status, and comorbid diseases using logistic regressions.
The prevalence of migraine increased from 6.54% in 2003 to 9.69% in 2012 with significant time trends (adj. OR 1.65; 95%CI 1.50-1.81). The probability of women of suffering migraine was 3 times higher than for men (adj.OR 3.08; 2.82-3.37). There was a declining trend in migraine prevalence as age increased (adj.OR 0.42; 0.35-0.51). Demographic variables associated with migraine were lower educational level (adj.OR 1.32; 1.13-1.54) and not being an immigrant (adj.OR 1.37; 1.15-1.64). A worse self-reported health status was related to higher prevalence of migraine (adj.OR 2.83; 2.59-3.09). The prevalence of migraine also increased as the number of comorbid conditions increased (adj.OR 2.42; 2.05-2.86).
The prevalence of migraine has increased in the first decade of the 21st century in Spain. Migraine was associated with being female, mid-age, low educational level, not being an immigrant, worse self-rated health status and presence of comorbid conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity is a pandemic disease associated to severe health problems. Management is usually multimodal, but many patients eventually need surgery to reduce weight. Many guidelines recommend endoscopy ...prior to surgery. This study reviews a series of patients undergoing sleeve gastrectomy to see whether endoscopy performance and histopathological findings influence surgery outcome.
Retrospective series of patients undergoing sleeve gastrectomy as bariatric procedure at a single institution. We have reviewed the demographic data, the associated pathologies, endoscopic findings prior to surgery, histopathological findings in the surgical resection specimen and postoperative complication rate.
259 patients fulfilled criteria for the study. Over 70% were women and the mean age was 46.9 (SD 9.8). Preoperative endoscopy was performed in 28.9% of the patients and biopsy only in 19.3%. Helicobacter pylori was detected in 28% of the patients undergoing endoscopy (either in the biopsy or the urease test) and eradicated before surgery in all the patients. Helicobacter pylori was present in 9.7% of the surgical resection specimens and its presence was significantly associated with the development of postoperative complications, mostly staple line leaks (p = 0.01).
Our study confirms that Helicobacter infection is significantly associated with postoperative complications after sleeve gastrectomy. It is therefore important to detect its presence and eradicate it before surgery.
During the nineties it was described, as an original finding, the existence of afferent amyelinic nerve endings in animal dorsal root ganglia (DRG) caused by diverse experimental lesions. These works ...do not take into account the historical studies carried out by Ehrlich (1886), Ramón y Cajal (1890) and Dogiel (1885) among others. Ramón y Cajal (1899) confirmed the existence of these nerve endings naming them after their discoverer as "Dogiel's arborisations". Ramón y Cajal claims that these endings originate from fibres of sympathetic nature, something supported by later authors devoted to this topic. In any case, the same authors remarked already a possible relationship with pathological phenomena, nonetheless always referring to the frequent occasions in which the same images appeared in healthy animals. In this work we review the bibliography about the classically named "Terminal Dogiel's nests" which in modern literature have been referred to as sprouting of sympathetic axons in dorsal root ganglia likely related with sympathetically maintained pain. Furthermore, we present the finding, not described up to date, of multiple afferent amyelinic nervous endings related with the "Terminal Dogiel's nests" observed in different DRG from young adult healthy rabbits.
Objectives
To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other ...metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up.
Methods
n
= 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control.
Results
The presence of T2D increased the likelihood of higher levels of depressive symptoms (
χ
2
= 15.84,
p
= 0.001). Polynomial contrast revealed a positive linear relationship (
χ
2
= 13.49,
p
= 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-
χ
2
= 24.06,
df
= 3,
p
< .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up.
Conclusions
This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short–medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
Abstract
Introduction
Pathogenic mutations in FLNC and DSP are a common cause of arrhythmogenic left ventricular cardiomyopathy and "arrhythmic dilated cardiomyopathy". We aimed to study demographic ...and clinical differences amongst these carriers.
Purpose
1. To study the prevalence of malignant ventricular arrhythmias in DSP and FLNC mutation carriers in the studies and reports published in the literature.
2. To analyse the effect of age, left ventricular ejection fraction (LVEF), and sex on ventricular arrhythmias in both groups.
Methods
A systematic review of the human studies published in Medline and EMBASE until September 2022 was carried out. "Desmoplakin Mutations", "Filamin Mutations", "Arrhythmogenic Cardiomyopathy" and "Dilated Cardiomyopathy" were the keywords included in the search queries. Studies, family reports, and registries reporting on individual data of pathogenic or likely pathogenic mutation carriers were selected for analysis.
Results
Twenty-four articles published between 2002 and 2020 were selected from a total of 430 entries. 171 DSP carriers (from 16 studies) and 169 FLNC carriers (from 7 studies) were included in the analysis. Mean age was similar in both groups: 39.45±19.23 years in DSP vs 42.02±16.27 in the FLNC group (p:0.201). The proportion of females was higher among DSP carriers than that found among FLNC carriers: 101 (59%) vs 76 (45%), p: 0.012. Non-missense mutations were more frequent in both groups: 98 DSP carriers (57%) and 157 FLNC carriers (97%). LVEF was slightly more depressed amongst FLNC carriers: 47.75±14.94% vs 52.37±14.64%, p:0.014.
A total of 81 major arrhythmic events (sudden death, ventricular fibrillation, sustained ventricular tachycardia were reported. The LVEF of the male patients that had suffered a major event was similar in both groups (39.13±18.20% in DSP vs 39.03±12.24% in FLNC, p:0.987). On the contrary, LVEF was significantly lower in female carriers of DSP mutations (32.33±15.65% in DSP vs 47.60±15.88% in FLNC, p:0.050).
Male carriers show a worse prognosis than their female counterparts (log-rank 0.005) (Figure). The difference was not significant after adjusting for LVEF and type of mutation (missense vs non-missense). LVEF (HR 0.94 per percentage unit (0.91-0.96), p <0.001) and non-missense mutations (HR 0.21 (0.07-0.66), p:0.008) were inversely associated with adverse outcomes in DSP carriers in a multivariate analysis. LVEF was also associated with a better outcome in FLNC carriers (HR 0.97 (0.95-0.99), p: 0.019.
Conclusion
Moderate systolic dysfunction is a risk factor for malignant arrhythmias amongst DSP and FLNC mutation carriers. Female FLNC carriers with mild systolic dysfunction are at risk for sustained ventricular arrhythmias. Missense DSP mutations are associated with poor arrhythmic prognosis.Sex differences in survival
The purpose of this study was to assess the effects of the addition of Nitroglycerin or Nicorandil to University of Wisconsin solution in long-term myocardial preservation. In a model of heterotopic ...heart transplantation in pigs, the donor heart was preserved for 24 hours by means of continuous perfusion in this solution, in the presence or absence of these drugs. During this period, the oxygenation and pH of the solution were measured, as were lactate concentrations and enzyme release. At regular intervals following reperfusion we measured the concentrations of enzymes, antioxidants, glutathione peroxidase, glutathione reductase, malondialdehyde, endothelin and nitrite, and, two hours later, samples of both ventricles were taken for a morphological study. In the treated groups there was a higher lactate production during preservation and, during reperfusion, the signs of contracture and the elevation of enzyme levels were more marked than in the untreated groups. In contrast, the glutathione reductase concentrations did not decrease during the first phase of reperfusion and were directly correlated with those of antioxidants, endothelin levels increased less than in the untreated groups and, in the case of nitroglycerin, the nitrite concentration was significantly greater than in the remaining groups. We conclude that nitroglycerin and nicorandil improved the oxidative state and endothelial function and did not produce substantial morphological changes, but increased cell necrosis and contracture, possibly due to the duration of ischemia.
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