Angiotensin II Blood Serum Levels in Piglets, after Intra-Dermal or Intra-Muscular Vaccination against PRRSV.

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces apoptosis in different organs. Angiotensin II (Ang II) is the main effector of the renin-angiotensin system and participates in apoptosis. Thus, this study aimed to investigate changes in piglet serum Ang II levels following intradermal (ID) and intramuscular (IM) vaccination with a commercial PRRS modified live virus (MLV) vaccine. The trial was conducted in a commercial pig farm, including 104 piglets which were randomly allocated to four groups: Group A-Porcilis PRRS ID, Group B-Porcilis PRRS IM, Group C-Diluvac ID and Group D-Diluvac IM. The study piglets were either vaccinated or injected at 2 weeks of age and they were tested by qRT-PCR for PRRSV and by ELISA for Ang II. The results indicated differences in viremia of tested piglets at 7 weeks of age, while piglets at 10 weeks of age were all found qRT-PCR positive for PRRSV. In addition, significant differences were noticed in Ang II in 7-week-old piglets. In conclusion, the present study provides evidence that ID vaccination induces less tissue damage, based on the lower measurements of Ang II in the serum of ID vaccinated piglets.

Coordinated activation of TGF-ß and BMP pathways promotes autophagy and limits liver injury after acetaminophen intoxication.

Ligands of the transforming growth factor-ß (TGF-ß) superfamily, including TGF-ßs, activins, and bone morphogenetic proteins (BMPs), have been implicated in hepatic development, homeostasis, and pathophysiology. We explored the mechanisms by which hepatocytes decode and integrate injury-induced signaling from TGF-ßs and activins (TGF-ß/Activin) and BMPs. We mapped the spatiotemporal patterns of pathway activation during liver injury induced by acetaminophen (APAP) in dual reporter mice carrying a fluorescent reporter of TGF-ß/Activin signaling and a fluorescent reporter of BMP signaling. APAP intoxication induced the expression of both reporters in a zone of cells near areas of tissue damage, which showed an increase in autophagy and demarcated the borders between healthy and injured tissues. Inhibition of TGF-ß superfamily signaling by overexpressing the inhibitor Smad7 exacerbated acute liver histopathology but eventually accelerated tissue recovery. Transcriptomic analysis identified autophagy as a process stimulated by TGF-ß1 and BMP4 in hepatocytes, with Trp53inp2, which encodes a rate-limiting factor for autophagy initiation, as the most highly induced autophagy-related gene. Collectively, these findings illustrate the functional interconnectivity of the TGF-ß superfamily signaling system, implicate the coordinated activation of TGF-ß/Activin and BMP pathways in balancing tissue reparatory and regenerative processes upon APAP-induced hepatotoxicity, and highlight opportunities and potential risks associated with targeting this signaling system for treating hepatic diseases.

Kidney biopsy findings in vancomycin-induced acute kidney injury: a pooled analysis.

BACKGROUND: Acute kidney injury represents a major adverse effect of vancomycin administration. The aim of the present study is to accumulate all biopsy-proven cases of vancomycin nephrotoxicity and assess the association of histopathological features with renal prognosis. METHODS: Medline, Scopus, CENTRAL, Web of Science, and Clinicaltrials.gov were systematically searched from inception to 29 September 2020. All case reports/series providing individual data of patients with biopsy-proven vancomycin nephrotoxicity were held eligible. A time-to-event analysis was performed evaluating the effects of histological diagnosis on renal recovery. RESULTS: Overall, 18 studies were included, comprising 21 patients. Acute tubulointerstitial nephritis was the predominant pattern in 9 patients and was associated with a significantly higher risk of permanent renal dysfunction (HR: 5.08, 95% CI: [1.05-24.50)] compared to acute tubular necrosis. Tubulitis and eosinophilic infiltration were the most common histopathological findings, while interstitial fibrosis was linked to significantly worse renal prognosis (HR: 5.55, 95% CI: 1.13-27.27). Immunofluorescence and electron microscopy features were non-specific. Obstruction by tubular casts composed of vancomycin aggregates and uromodulin has been identified as a new mechanism of nephrotoxicity. CONCLUSIONS: Acute tubular necrosis and tubulointerstitial nephritis represent the main histological patterns of vancomycin-induced acute kidney injury. The presence of fibrosis in the context of interstitial inflammation may be linked to lower recovery rates and worse long-term renal outcomes. A novel cast nephropathy obstructive mechanism has been suggested, necessitating further confirmation. Large-scale studies should define the exact indications of kidney biopsy in cases with suspected vancomycin nephrotoxicity.

Comparative efficacy of fixed-dose statin and antihypertensive agent combinations: A network meta-analysis of randomized controlled trials.

BACKGROUND: The concurrent administration of statins and antihypertensive agents has been associated with improved cardiovascular outcomes, although the optimal fixed-dose combination remains unclear. This meta-analysis aims to compare the blood pressure and lipid-lowering effects of various statin and antihypertensive drug combinations. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 20 March 2021. Randomized controlled trials evaluating the effects of statin-antihypertensive agent combinations on systolic blood pressure or serum lipids were held eligible. A random-effects frequentist model was applied to provide estimates of mean difference of percentage change. RESULTS: Overall, 18 studies were included, comprising 4450 patients. Compared to statin monotherapy no significant difference in the percentage change of low-density lipoprotein cholesterol was achieved by adding any antihypertensive agent. Compared to amlodipine monotherapy, the addition of moderate-intensity statin resulted in a significantly greater percentage reduction of systolic blood pressure (-2.22%, 95% confidence intervals: [-3.82 to -0.62]). Combined high-intensity statin and amlodipine lead to significant increase of high-density lipoprotein cholesterol (8.34%, 95% confidence intervals: [0.73 to 15.95]), while effective triglyceride reduction was achieved by adding amlodipine and telmisartan to high-intensity statin (-14.68%, 95% confidence intervals: [-28.48 to -0.89]). No significant difference of adverse effects was observed. CONCLUSION: The present network meta-analysis suggests that the administration of fixed-dose combinations of statins and antihypertensive agents is safe and effective in reducing blood pressure and serum lipids. The optimal dosing strategy to prevent cardiovascular events remains to be determined.

The Effect of TISSEELTM on Confined Bowel Perforation: An Experimental Study.

OBJECTIVE: During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was to investigate the feasibility of TISSEELTM versus the conventional suture placement technique on confined bowel lesions in rats. METHODS: Twenty-four Sprague-Dawley rats underwent confined bowel perforation and were divided into three groups: the SUTURE group (sutures were used), the SUTURE + TISSEELTM group (sutures and TISSEELTM were utilized), and the TISSEELTM group (only TISSEELTM was used). Blinded histopathologic analysis followed animal sacrifice. RESULTS: The median weight of the rats was 526 ± 50 g. A single animal had hematochezia on the first postoperative day. Cessation of bleeding at the perforation margin was indicated intraoperatively after TISSEELTM application. Animals in the TISSEELTM group presented less intraperitoneal adhesions and lower hemorrhagic infiltration compared to animals of the two other groups. In addition, animals in the TISSEELTM group showed thrombus formation at the bowel perforation site compared to animals of the two other groups (p = 0.042). Histopathologic analysis demonstrated reduced inflammatory reaction (p = 0.003), diminished fibrosis (p = 0.001), and better tissue regeneration (p = 0.000) in the TISSEELTM group compared to the other two groups. CONCLUSION: Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.

Possible Roles of Vitamin D in Bone Grafting.

Bone grafting is one of the most commonly used options to treat large bone defects. Evidence has shown that vitamin D may affect osseointegration, a major component for successful bone grafting. In vitro studies have proved that implants coated with activated vitamin D stimulate bone production and reduce bone resorption around implants. Animal studies have noticed that oral administration of vitamin D may stimulate bone formation as well as strengthen and support the interaction between bone and implants. Vitamin D insufficiency may affect negatively the cortical peri-implant bone formation, suggesting a negative effect in graft incorporation. Few clinical studies have observed that vitamin D administration enhanced graft incorporation and bone formation, while severe vitamin D deficiency is associated with failed implant osseointegration. Even though there are encouraging results of vitamin D supplementation on graft incorporation in animal studies, the use of vitamin D as an adjuvant in bone grafting procedures cannot be fully supported at the moment. However, there is theoretical support in the use of vitamin D after surgery and the use of bone grafts to support the bone structure, relieve pain and increase graft absorption. Further experimental and clinical studies are required to support the administration of vitamin D and its analogues in such cases.

The Effect of Prenatal Food Restriction on Brain Proteome in Appropriately Grown and Growth Restricted Male Wistar Rats.

BACKGROUND: Fetal growth restriction (FGR) has been associated with a higher risk of developing adverse perinatal outcomes and distinct neurodevelopmental and neurobehavioral disorders. The aim of the present study was to investigate the impact of prenatal food restriction on the brain proteome in both FGR and appropriately grown rats and to identify potential pathways connecting maternal malnutrition with altered brain development. METHODS: Ten time-dated pregnant Wistar rats were housed individually at their 12th day of gestation. On the 15th day of gestation, the rats were randomly divided into two groups, namely the food restricted one (n = 6) and the control group (n = 4). From days 15 to 21 the control group had unlimited access to food and the food restricted group was given half the amount of food that was on average consumed by the control group, based on measurements taken place the day before. On the 21st day of gestation, all rats delivered spontaneously and after birth all newborn pups of the food restricted group were weighed and matched as appropriately grown (non-FGR) or growth restricted (FGR) and brain tissues were immediately collected. A multiplex experiment was performed analyzing brain tissues from 4 FGR, 4 non-FGR, and 3 control male offspring. Differentially expressed proteins (DEPs) were subjected to bioinformatics analysis in order to identify over-represented processes. RESULTS: Proteomic analysis resulted in the profiling of 3,964 proteins. Gene ontology analysis of the common DEPs using DAVID (https://david.ncifcrf.gov/) showed significant enrichment for terms related to cellular morphology, learning, memory and positive regulation of NF-kappaB signaling. Ingenuity Pathway Analysis showed significant induction of inflammation in FGR pups, whereas significant induction of cell migration and cell spreading were observed in non-FGR pups. CONCLUSION: This study demonstrated that in both FGR and non-FGR neonates, a range of adaptive neurodevelopmental processes takes place, which may result in altered cellular morphology, chronic stress, poor memory and learning outcomes. Furthermore, this study highlighted that not only FGR, but also appropriately grown pups, which have been exposed to prenatal food deprivation may be at increased risk for impaired cognitive and developmental outcomes.

Regulation of Long Non-Coding RNAs by Statins in Atherosclerosis.

Despite increased public health awareness, atherosclerosis remains a leading cause of mortality worldwide. Significant variations in response to statin treatment have been noted among different populations suggesting that the efficacy of statins may be altered by both genetic and environmental factors. The existing literature suggests that certain long noncoding RNAs (lncRNAs) might be up- or downregulated among patients with atherosclerosis. LncRNA may act on multiple levels (cholesterol homeostasis, vascular inflammation, and plaque destabilization) and exert atheroprotective or atherogenic effects. To date, only a few studies have investigated the interplay between statins and lncRNAs known to be implicated in atherosclerosis. The current review characterizes the role of lncRNAs in atherosclerosis and summarizes the available evidence related to the effect of statins in regulating lncRNAs.

Markers of endothelial dysfunction and arterial stiffness in patients with early-stage autosomal dominant polycystic kidney disease: A meta-analysis.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is characterised by increased rates of cardiovascular complications leading to significant morbidity and mortality. This meta-analysis aims to evaluate whether the disease is linked to endothelial dysfunction and arterial stiffness during its early stages. METHODS: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov and Google Scholar databases comparing ADPKD patients with preserved renal function to healthy controls were included. The outcomes of interest were brachial flow-mediated dilatation, carotid-femoral pulse wave velocity, augmentation index, carotid intima-media thickness and central systolic blood pressure, plasma ADMA or homocysteine levels. Standardised mean differences (SMDs) were estimated by a random-effects model in R-3.6.3. RESULTS: A total of 27 studies were included, comprising 1967 individuals. ADPKD was linked to significantly lower flow-mediated dilatation (SMD: -1.44, 95% CI: [-2.35, -0.53]) and higher pulse wave velocity (SMD: 1.44, 95% CI: [0.22, 2.66]) and carotid intima-media thickness (SMD: 1.02, 95% CI: [0.57, 1.47]). No significant associations were noted regarding augmentation index (SMD: 0.62, 95% CI: [-0.19, 1.43]) and central systolic blood pressure (SMD: 1.84, 95% CI: [-0.12, 3.80]). Plasma homocysteine was significantly higher in ADPKD (SMD: 0.81, 95% CI: [0.16, 1.45]), while no difference was calculated for ADMA levels (SMD: 1.14, 95% CI: [-0.25, 2.53]). CONCLUSIONS: Early-stage ADPKD patients present increased vascular stiffness and endothelial dysfunction, as reflected by low flow-mediated dilatation and elevated values of pulse wave velocity, carotid intima-media thickness and plasma homocysteine. The exact effects of early arterial stiffness on long-term outcomes remain to be elucidated.

Intrathoracic schwannoma originating from intrathoracic vagus nerve.

In differential diagnosis of posterior mediastinal mass should be included the intrathoracic vagus nerve tumor. Surgical excision of intrathoracic vagus nerve schwannoma is associated with a low recurrence rate and excellent long-term results.

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice.

The aim of this study was to determine the cognitive and behavioral effects of extra virgin olive oil total phenolic content (TPC) and Sideritis (SID) extracts in female mice, and identify the associated neurochemical changes in the hippocampus and the prefrontal cortex. All animals received intraperitoneal low or high doses of TPC, SID or vehicle treatment for 7 days and were subjected to the Open Field (OF), Novel Object Recognition (NOR) and Tail Suspension Test (TST). The prefrontal cortex and hippocampus were dissected for analysis of neurotransmitters and aminoacids with high performance liquid chromatography with electrochemical detection (HPLC-ED). Both TPC doses enhanced vertical activity and center entries in the OF, which could indicate an anxiolytic-like effect. In addition, TPC enhanced non-spatial working memory and, in high doses, exerted antidepressant effects. On the other hand, high SID doses remarkably decreased the animals' overall activity. Locomotor and exploratory activities were closely associated with cortical increases in serotonin turnover induced by both treatments. Cognitive performance was linked to glutamate level changes. Furthermore, TPC reduced cortical taurine levels, while SID reduced cortical aspartate levels. TPC seems to have promising cognitive, anxiolytic and antidepressant effects, whereas SID has sedative effects in high doses. Both extracts act in the brain, but their specific actions and properties merit further exploration.

Blood Plasma Resistin and Atrial Fibrillation in Patients With Cardiovascular Disease.

BACKGROUND: Atrial fibrillation (AF) affects quality of life and prognosis of patients with cardiovascular disease. Resistin plays an important role in inflammatory response to internal and external factors. The aim of this study is to evaluate the association between resistin and permanent AF (PAF) in patients with cardiovascular disease. METHODS: In our study, we included 146 patients with cardiovascular disease. Plasma resistin concentrations and demographic characteristics of patients were recorded. The patients were divided in two groups: 118 patients without a history of PAF (NonAF group), and 28 patients with a history of PAF (AF group). Association of resistin with PAF and other variables was examined by parametric and non-parametric tests, and multivariable linear and univariable logistic regression analysis. RESULTS: No differences of demographic characteristics (gender, age and body mass index (BMI)) between two groups were observed (P > 0.05). Higher median levels of resistin were observed in group AF than in group NonAF (6.90 ng/mL vs. 5.83 ng/mL, P = 0.03). Multivariate linear regression analysis (adjusted to gender, age, BMI, hypertension, diabetes mellitus, coronary artery disease, and mitral valve disease) showed that resistin was associated with PAF (ß = 0.79, 95% confidence interval (CI): 0.08 to 1.51, P = 0.03). CONCLUSIONS: Our analysis showed that plasma resistin was associated with PAF, and resistin concentration was higher in patients with AF compared to those without AF.

Metabolic Response of Adult Male Offspring Rats to Prenatal Caffeine Exposure.

Caffeine is the most widely consumed psychoactive substance, with recommendations from health associations and regulatory bodies for limiting caffeine consumption during pregnancy being increasingly common. Prenatal exposure to caffeine has been shown to increase the risk of developing abnormalities in lipid metabolism in adult life. We further investigated the effect of prenatal caffeine exposure (PCE) (20 mg/kg of body weight) on the metabolic "reserve" of male Sprague Dawley offspring fed on a high fructose diet in adult life. Male adult PCE offspring were assigned to four groups; Nw and Nf: offspring of control mothers (N group of mothers), having received tap water or high fructose water respectively; Cw and Cf: offspring exposed to caffeine during gestation (C group of mothers) and receiving tap water or a high fructose water solution, respectively. Cf rats presented increased serum triglyceride level, as well as raised systolic and diastolic blood pressure levels, together with extensive renal tissue oedema in adulthood, compared to the other groups (p<0.05 for all comparisons). These findings show further evidence for potential detrimental metabolic effects of prenatal caffeine exposure during adulthood in this animal model.

Current challenges in the diagnosis and treatment of cardiac myxoma.

Cardiac myxoma is the most common benign cardiac tumor. It is located in the left atrium and typically arises from the foramen ovale in approximately 75% of the general patient population, in the right atrium in 23%, and in the ventricles in only 2%. Symptoms depend on its size, mobility, and relation to surrounding cardiac structures. Neurological complications resulting from cardiac myxoma are seen in 20% to 25% of patients. Molecular genetic studies show that the condition can be inherited in Carney complex due to mutations of the PRKAR1A gene. Cardiac myxoma resection is a cardiac surgery with a low complication rate and the 30­day mortality of up to 10%. Recurrence may be observed months or years after surgery, and its rate is approximately 5%. Long­term follow­up with transthoracic echocardiography is needed in all patients after tumor resection. This review summarizes the available data on cardiac myxoma and, in particular, issues relating to diagnosis and treatment.

Efficacy and safety of colistin loading dose: a meta-analysis.

OBJECTIVES: Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model. RESULTS: Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10-1.39] but not clinical (RR = 1.04, 95% CI = 0.87-1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90-1.91) and mortality (RR = 1.03, 95% CI = 0.82-1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias. CONCLUSIONS: Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.

The Effect of TISSEEL® on Colorectal Anastomosis Healing Process in a Diabetic Animal Experimental Model.

BACKGROUND/AIM: Diabetes mellitus is an established risk factor of colorectal anastomosis failure. The purpose of the present study was to evaluate the effect of TISSEEL® in anastomotic healing. MATERIALS AND METHODS: Forty male, Sprague-Dawley rats were used. Diabetes was induced in half of them by intraperitoneal injection of Streptozotocin, 60 mg/kg. One week after the injection, animals were operated and a 1 cm segment was removed and an end-to-end hand sewn anastomosis was performed. TISSEEL® was applied in each group (diabetic, non-diabetic) following randomization. RESULTS: The pathology analysis revealed improved tissue remodeling in the TISSEEL® group, both for the normoglycemic and the diabetic group. Specifically, the extent of inflammation was decreased (p<0.001), whereas fibroblast and collagen formation were improved (p=0.040 and p=0.008). Neovascularization was also improved (p=0.047). CONCLUSION: Application of TISSEEL® on colorectal anastomoses improves healing in rats that suffer from severe hyperglycemia.

Association of postoperative fluid overload with adverse outcomes after congenital heart surgery: a systematic review and dose-response meta-analysis.

BACKGROUND: Pediatric cardiac surgery is commonly associated with acute kidney injury (AKI) and significant fluid retention, which complicate postoperative management and lead to increased rates of morbidity. This meta-analysis aimed to accumulate current literature evidence and evaluate the correlation of fluid overload degree with adverse outcome in patients undergoing congenital heart surgery. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar were systematically searched from inception. All studies reporting the effects of fluid overload on postoperative clinical outcomes were selected. A dose-response meta-analytic method using restricted cubic splines was implemented in R-3.6.1. RESULTS: Twelve studies were included, with a total of 3111 pediatric patients. Qualitative synthesis indicated that fluid overload was linked to significantly higher risk of mortality, AKI, prolonged hospital, and intensive care unit (ICU) stay, as well as with increased duration of mechanical ventilation, inotrope need, and infection rate. Meta-analysis demonstrated a linear correlation between fluid overload and the risk of mortality (χ2 = 6.22, p value = 0.01) and AKI (χ2 = 35.84, p value < 0.001), while a positive curvilinear relationship was estimated for the outcomes of hospital (χ2 = 18.84, p value = 0.0001) and ICU stay (χ2 = 63.69, p value = 0.0001). CONCLUSIONS: The present meta-analysis supports that postoperative fluid overload is significantly linked to elevated risk of prolonged hospital stay, AKI development, and mortality in pediatric patients undergoing cardiac surgery. These findings warrant replication by future prospective studies, which should define the optimal cutoff values and assess the effectiveness of therapeutic strategies to limit fluid overload in the postoperative setting.

Dimethylarginines in acute myocardial infarction: Association with lifestyle, sociodemographic, and somatometric factors.

BACKGROUND: Recent findings associate asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) with the prognosis of acute myocardial infarction (AMI). The purpose of the current study was to associate patients' lifestyle, sociodemographic, and somatometric characteristics with the time course of ADMA and SDMA concentrations in the serum of AMI patients. PATIENTS AND METHODS: In the serum of 66 AMI patients, ADMA, SDMA, troponin T, and C-reactive protein (CRP) were measured upon hospital admission (<24 h) and on the 3rd day following. Lifestyle, sociodemographic, and somatometric characteristics were obtained through a questionnaire, filled on patient discharge. RESULTS: ADMA concentrations on the 1st day positively correlated with daily reported hours of sleep (+0.497, P < 0.001) and delivery or eating out frequency (+0.285, P = 0.02), whereas it negatively correlated with reported physical condition (-0.304, P = 0.013). A personal history of hypertension indicated higher 1st-day ADMA concentration (1.818 vs 1.568, P = 0.042). Age positively correlated with 1st-day SDMA (+0.320, P = 0.009). All of the biomarker concentrations were reduced on the 3rd day measurements (P < 0.001). Self-reported lifetime minimum BMI positively correlated with either absolute (r = +0.366, P = 0.009) or percentage (r = +0.262, P = 0.045) ADMA reduction. A daily sleep in 5-8-h range was inversely correlated with percentage (-0.410, P = 0.001) or absolute (r = -0.369, P = 0.002) SDMA reduction. CONCLUSIONS: Modifiable factors such as BMI, eating habits, physical condition, and sleep seem to affect the baseline levels or time course of ADMA and SDMA in AMI patients. Changes in these factors may affect AMI prognosis by altering dimethylarginine levels.

Predictors of tolvaptan short-term response in patients with refractory ascites: A meta-analysis.

BACKGROUND AND AIM: Tolvaptan represents an oral V2 -receptor antagonist, which has been suggested as a promising add-on diuretic treatment for refractory ascites. The present meta-analysis aims to accumulate current evidence and identify which clinical and laboratory factors are linked to short-term response to tolvaptan therapy. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception. All observational studies reporting the correlation of patients' characteristics with tolvaptan response were selected. RESULTS: Tolvaptan response was associated with significantly higher baseline body weight (mean difference: 4.59 kg, 95% confidence interval [CI]: [3.58, 5.61]), presence of hepatitis C (odds ratio: 1.59 95% CI: [1.18, 2.14]), lower blood urea nitrogen (BUN) (mean difference: -6.88 mg/dL, 95% CI: [-8.13, -5.63]), lower serum creatinine (mean difference: -0.17 mg/dL, 95% CI: [-0.30, -0.05]), lower C-reactive protein (mean difference: -1.43 mg/dL, 95% CI: [-2.52, -0.35]), and higher sodium levels (mean difference: 1.00 mEq/L, 95% CI: [0.45, 1.55]). The outcomes of bodyweight, hepatitis C, BUN, and C-reactive protein remain significant independently of response definition and risk of bias. CONCLUSIONS: The present findings suggest bodyweight, BUN, C-reactive protein, and hepatitis C as potential predictive factors of tolvaptan short-term response in patients with refractory ascites. Future studies are needed to introduce cut-off values and construct an optimal combined screening model.

Fibrin sealants as an adequate treatment alternative to traditional suturing for confined bowel lesions: A hypothesis for future experimental research.

Bowel perforation is a rare, but serious complication of laparoscopic surgery with a mortality rate that reaches 20%. There are several risk factors that could predispose to bowel perforation, but the surgeon's experience and the difficulty of each case play the most important role. Delayed bowel injuries happen due to conduction of electrical energy through the abdominal cavity, and in the majority of cases require reoperation. Early bowel injuries are caused by thermal injury of an electrosurgical instrument or during the insertion of the laparoscopic instruments inside the peritoneal cavity. Such injuries are recognized during the operation and are usually fixed by placing sutures. TISSEEL™ is a fibrin sealant with various applications in several surgical specialties, that simulates the latter stages of the coagulation cascade, and could be used as an alternative treatment for confined bowel perforations during laparoscopy. The efficacy of fibrin sealants in closing bowel gaps has been tested in some experimental models as well as its adequacy in enhancing bowel anastomoses performed with sutures. In addition, there is scarce evidence that fibrin sealants enhance the healing process after bowel enclosure either combined to suturing or not, which is supported by an experimental pilot study, that was conducted by our study group. The present study tries to combine all the available data in order to propose an effective alternative treatment for confined bowel injuries or controversial cases, that happen during laparoscopic surgery. In that way, every surgeon could face them even without huge expertise, conversions to open surgery would diminish and the disadvantages of suturing would disappear. Future experimental studies should be designed in the terms of extensive comparison of the two methods, with the purpose of this comparison to be tested in humans in the future.