Effectiveness of a Balanced Nine-Strain Synbiotic in Primary-Care Irritable Bowel Syndrome Patients-A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial.

The aim of the study was to characterize effects of a multi-strain synbiotic in patients with moderate to severe irritable bowel syndrome (IBS) of all stool form types. A total of 202 adult IBS patients were randomized (1:1) and after a four-week treatment-free run-in phase and were treated either with the synbiotic or a placebo for 12 weeks. The primary endpoints were the assessment of the severity of IBS symptoms (IBS-SSS) and the improvement of IBS global symptoms (IBS-GIS). Secondary endpoints comprised adequate relief (IBS-AR scale), stool form type (Bristol Stool Form Scale), bowel movements, severity of abdominal pain and bloating, stool pressure, feeling of incomplete stool evacuation, and adverse events. A total of 201 patients completed the study. Synbiotic treatment, in comparison to placebo, significantly improved IBS-SSS and IBS-GIS scores. At the end of the treatment, 70% of patients in the synbiotic group achieved adequate relief. After 12 weeks of treatment, the secondary endpoints were favorably differentiated in the synbiotic group when compared with the placebo group. Two patients in the synbiotic group reported transient adverse events (headache). The results indicate that treatment of IBS patients with the synbiotic significantly improved all major symptoms of IBS and was well-tolerated. The ClinicalTrials.gov registration was NCT05731232.

Endovascular carotid revascularization under open-chest extracorporeal circulation combined with cardiac surgery in unstable patients at increased risk of carotid-related stroke: SIMultaneous urgent cardiac surgery and MicroNet-covered stent carotid revascularization in extreme-risk patients-SIMGUARD Study.

BACKGROUND: In patients at urgent need for cardiac surgery coexisting with increased-stroke-risk carotid stenosis, any staged intervention increases the risk of complications from the primarily unaddressed pathology. In this challenging cohort, we assessed safety and feasibility of endovascular carotid revascularization under open-chest extracorporeal circulation (ECC) combined with cardiac surgery (hybrid-room true simultaneous treatment). METHODS: Per-protocol (PP), after general anesthesia induction, chest-opening and ECC stand-by installation, carotid stenting (CAS) was performed (femoral/radial or direct carotid access) with ad-hoc/on-hand switch to ECC cardiac surgery. RESULTS: Over 78 months, 60 patients (70.7±6.9years, 85% male, all American Society of Anesthesiology grade IV) were enrolled. All were at increased carotid-related stroke risk (ipsilateral recent stroke/transient ischemick attack, asymptomatic cerebral infarct, increased-risk lesion morphology, bilateral severe stenosis). Majority of study procedures involved CAS+coronary bypass surgery or CAS+valve replacement±coronary bypass. 45 (75%) patients were PP- and 15 (25%) not-PP (NPP-) managed (context therapy). CAS was 100% neuroprotected (transient flow reversal-64.4%, filters-35.6%) and employed micronet-covered plaque-sequestrating stents with routine post-dilatation optimization/embedding. 4 deaths (6.7%) and 7 strokes (11.7%) occurred by 30-days. Despite CAS+surgery performed on aspirin and unfractionated heparin-only (delayed clopidogrel-loading), no thrombosis occurred in the stented arteries, and 30-days stent patency was 100%. NPP-management significantly increased the risk of death/ipsilateral stroke (OR 38.5; P<0.001) and death/any stroke (OR 12.3; P=0.002) by 30-days. CONCLUSIONS: In cardiac unstable patients at increased carotid-related stroke risk who require urgent cardiac surgery, simultaneous cardiac surgery and CAS with micronet-covered stent lesion sequestration is feasible and safe and shows efficacy in minimizing stroke risk. Larger-scale, multicentric evaluation is warranted. (SIMGUARD NCT04973579).

Supporting the diagnosis of infantile colic by a point of care measurement of fecal calprotectin.

Background: Infantile colic (IC) is a condition characterized by extensive crying which affects about 20% of all infants during their first months of life. Most pediatricians diagnose IC only based on their clinical experience. Aim: Investigating if a measurement of fecal calprotectin can support the diagnosis of IC. Methods: The crying behavior of newborns was assessed using the Wessel's criteria. Fecal calprotectin levels were measured in non-colicky and colicky babies using a standard test that can be used at the time and place of patient care (point of care (PoC) measurement). Results: Colicky babies were found to have significantly elevated fecal calprotectin levels. Calprotectin levels were not influenced by gender, type of feeding, gestation age or birth weight. However, significantly elevated fecal calprotectin levels were found in cesarean section born babies. Fecal calprotectin ≥100 µg/g correlated with a colicky status of an infant while those <100 µg/g indicated a non-colicky status the error margin was 11.2 and 13.2%, respectively. Combining data of fecal calprotectin with information about the type of delivery made it possible to determine the colicky status in vaginally-born infants with fecal calprotectin ≥100 µg/g with an accuracy of 97.8%. As elevated fecal calprotectin levels in cesarean-born infants can be caused by IC, but also by the disturbed gut microbiota commonly found in these babies, the accuracy of diagnosing the colicky status of a cesarean-born infant with calprotectin levels ≥100 µg/g was less accurate (accuracy rate of 76.5%). Conclusion: Data from the study suggest that measuring fecal calprotectin should be considered by pediatricians to support the diagnosis of IC.The study was registered at ClinicalTrials.gov under NCT04666324.

Factors Determining Effective Probiotic Activity: Evaluation of Survival and Antibacterial Activity of Selected Probiotic Products Using an "In Vitro" Study.

There are many different probiotic products on the market. Are they all equally effective? What criteria should a probiotic formulation meet to provide the most benefit to the patient? The current research aims to evaluate the parameters that influence the effectiveness of market probiotic products. These properties are critical for restoring eubiosis in patients with drug-induced dysbiosis or other pathological conditions, which could be caused by stress, wrong eating. Methods: The disintegration time of probiotic capsules in hydrochloric acid was investigated using a disintegration testing device. The survival rate of probiotic preparations in hydrochloric acid at pH 2 and in a 0.4% bile solution was then evaluated. For this purpose, the number of bacteria before and after incubation in the respective solutions was determined using the plate method. Inhibition of gastrointestinal pathogens by the probiotic products was determined using the Strus bar graph method. The highest survival rate of probiotic bacteria at low pH is shown by preparations produced in the form of acid-resistant capsules. Conclusions: The most important factor determining the good survival of bacterial strains under conditions simulating the gastrointestinal tract is the type of capsule used for their production and storage. The best antimicrobial activity against most common human gastrointestinal pathogens such as Eschericha coli, Shigella, Salmonella spp., Clostridioides difficile (the largest inhibition zones) are shown by probiotic products with the greatest diversity of bacterial strains.

Long-term survival following postoperative myocardial infraction after coronary artery bypass surgery.

BACKGROUND: Postoperative myocardial infraction (MI) is a serious complication among patients undergoing Coronary Artery Bypass Grafting (CABG). Data on the impact of postoperative MI on patients undergoing CABG, specifically with respect to their long term outcomes are sparse. METHODS: We retrospectively analyzed all patients who underwent isolated CABG between January 2014 and December 2016 and identified those who fulfilled the definition of the type 5MI following CABG according to the Fourth Universal Definition of Myocardial Infarction. RESULTS: A total of 4,642 CABG patients were identified, of whom 141 (3.04%) were diagnosed with postoperative MI. The mean follow-up time was 5.1±2.07 years (range, 4.4-6.9 years). Postoperative MI was more common in patients with recent acute coronary syndrome, when compared to stable angina (22.8% vs. 31.9%; P=0.011) and in those with non-elective versus planned surgery (28.4% vs. 18.4%; P=0.003). Postoperative MI after CABG was associated with an increased rate of postoperative complications, including cardiac tamponade and re exploration for bleeding. Mortality after postoperative MI was higher at short-term follow-up (up to one year) and long-term follow-up (up to five years). The risk factors for postoperative MI after CABG were incomplete revascularization (IR) [OR (95% CI): 2.25 (1.59-3.12), P=0.001], non-elective surgery [OR (95% CI): 1.68 (1.10-2.54), P=0.015] and female gender [OR (95% CI): 1.48 (1.01-2.18), P=0.045]. CONCLUSIONS: PMI after CABG is associated with reduced short- and long-term survival. The main risk factors for postoperative MI are IR, female gender, and non-elective surgery.

Nine-Strain Bacterial Synbiotic Improves Crying and Lowers Fecal Calprotectin in Colicky Babies-An Open-Label Randomized Study.

The aim of this study (ClinicalTrials.gov registration NCT04666324) was to determine the effects of a nine-strain synbiotic and simethicone on the duration of crying and the gut inflammation marker calprotectin in colicky babies aged 3-6 weeks, diagnosed using the Wessel criteria. The open-label study comprised a control group of non-colicky babies (n = 20) and two parallel treatment groups (each n = 50) to which colicky babies were randomly and equally assigned to receive the multi-strain synbiotic or simethicone orally for 28 days. Primary outcome measures were the change in daily crying duration and the level of fecal calprotectin on days 1 and 28 of the study. Administration of the synbiotic resulted in a rechange of crying duration of -7.18 min/day of treatment, while simethicone had a significantly smaller effect (-5.74 min/day). Fecal calprotectin levels in colicky babies were significantly elevated compared to those in non-colicky babies. Treatment with the nine-strain synbiotic resulted in a significant lowering of fecal calprotectin at the end of the study, while no such effect was found for simethicone. No adverse effects were reported. Study results confirm earlier findings of crying duration reductions in colicky babies by the synbiotic, an effect that might be linked to its anti-inflammatory properties.

Hybrid techniques for myocardial regeneration: state of the art and future perspectives.

Myocardium has a limited proliferative capacity, and adult hearts are considered incapable of regenerating after injury. A significant loss in the viable myocardium eventually diminishes the heart's ability to contract synchronously, leading to heart failure. Despite the development in interventional and pharmacological treatment for ischemic heart disease and heart failure, there is a significant number of highly symptomatic patients. For these individuals, treatments that stimulate myocardial regeneration can offer alleviation of dyspnea and angina and improvement in quality of life. Stem cells are known to promote neovascularization and endothelial repair. Various stem cell lines have been investigated over the years to establish those with the highest potential to differentiate into cardiomyocytes, including bone marrow-derived mononuclear cells, mesenchymal stromal cells, CD34+, CD133+, endothelial progenitor cells, and adipose-derived mesenchymal stromal cells. Stem cell studies were based on several delivery pathways: infusion into coronary vessels, direct injection into the injured region of the myocardium, and delivery within the novel bioengineered scaffolds. Acellular materials have also been investigated over the years. They demonstrate the therapeutic potential to promote angiogenesis and release of growth factors to improve the restoration of critical components of the extracellular matrix. This review summarizes hybrid cardiac regeneration treatments that combine novel bioengineering techniques with delivery approaches that cardiac surgeons can provide.

Bilateral internal thoracic artery use in two-vessel disease does not increase the perioperative risk-A propensity score matched analysis.

BACKGROUND: Bilateral internal thoracic arteries (BITA) are uncommonly used in the every-day practice due to safety concerns and technical challenges with Y-grafts. We hypothesized that in-situ BITA use during coronary artery by-pass grafting (CABG) for two vessel disease is equally safe to standard strategy with left internal thoracic artery-left anterior descending artery revascularization and venous graft to other target vessels. METHODS: A propensity score matched analysis was used to compare elective on-pump CABG patients who received in-situ BITA (BITA-group), versus left internal thoracic artery graft to the left anterior descending artery plus vein (SITA-group). Primary end points were 30-days all-cause-mortality, major adverse cardiac events and incidents and deep sternal wound infections. RESULTS: A total of 50 matched pairs (c-statistics 0.769) were selected from patients operated on between January 2015 and April 2020 using BITA (n = 50) and SITA (n = 2170). There were no inter-group differences in demographics and basic clinical characteristics. The total operation time was longer in the BITA-group (4.0 vs 3.6 hours; p = 0.004). The rate of complete revascularization was similar, as was median aortic cross-clamp time, median extracorporeal circulation time, rate of re-explorations for bleeding, deep sternal wound infections or length of stay. One patient died in BITA group, 3 days after surgery, from a non-cardiac cause. After 36 months, the survival rate was 98% for BITA-group and 96% for controls (log-rank, p = 0.577). CONCLUSIONS: In-situ use of BITA during coronary revascularization for two-vessel disease is as safe and effective, as use of single ITA and vein graft. In-situ strategy abolishes allows to avoid the technically demanding composite graft configuration.

Early postoperative hemodynamic instability after heart transplantation - incidence and metabolic indicators.

BACKGROUND: Primary graft dysfunction (PGD) is the main cause of death in the first 30 days after heart transplantation (HTX), accounting for approximately 40% of mortality. The study's primary aim was to assess the incidence of PGD, following the International Society for Heart and Lung Transplantation consensus, and to compare it with the incidence of significant postoperative hypotension despite administration of high-dose inotropes and vasoconstrictors. The secondary aim of the study was to determine changes in biochemical markers that accompany the phenomenon. METHODS: Forty-five patients who underwent HTX between 2010 and 2015 were enrolled in this study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Hemodynamic instability was defined as significant postoperative hypotension (mean arterial pressure (MAP) < 60 mmHg) combined with a high inotrope score (> 10). Data for long-term mortality were obtained from the population registration office. RESULTS: PGD incidence was relatively low (17.8%); however, hemodynamic instability was common (40%). Among unstable patients, MAP was insufficient for end-organ perfusion (51.4 ± 9.5 mmHg) but no decrease in left ventricular function was observed (cardiac index, 2.65 ± 0.6 l/min/m2; left ventricular ejection fraction, 52.9 ± 15.5%). Within this group, mean systemic vascular resistance index (961 ± 288 dyn*s*m2/cm5) was low despite receiving high doses of vasoactive agent (norepinephrine 0.21 (0.06-0.27) µg/kg/min during first 24 h postoperatively and 0.21 (0.01-0.27) µg/kg/min during next 24 h postoperatively). After HTX, serum lactate levels were initially significantly higher in patients with hemodynamic instability (p = 0.002); however, impaired lactate clearance was not observed (p = 0.366), and lactate levels normalized within the first 24 h postoperatively. Postoperative hemodynamic instability altered the long-term outcome and increased 5-year mortality after HTX (p = 0.034). CONCLUSIONS: Hemodynamic instability is a more common phenomenon than PGD. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients.

The Role of Deep Hypothermia in Cardiac Surgery.

Hypothermia is defined as a decrease in body core temperature to below 35 °C. In cardiac surgery, four stages of hypothermia are distinguished: mild, moderate, deep, and profound. The organ protection offered by deep hypothermia (DH) enables safe circulatory arrest as a prerequisite to carrying out cardiac surgical intervention. In adult cardiac surgery, DH is mainly used in aortic arch surgery, surgical treatment of pulmonary embolism, and acute type-A aortic dissection interventions. In surgery treating congenital defects, DH is used to assist aortic arch reconstructions, hypoplastic left heart syndrome interventions, and for multi-stage treatment of infants with a single heart ventricle during the neonatal period. However, it should be noted that a safe duration of circulatory arrest in DH for the central nervous system is 30 to 40 min at most and should not be exceeded to prevent severe neurological adverse events. Personalized therapy for the patient and adequate blood temperature monitoring, glycemia, hematocrit, pH, and cerebral oxygenation is a prerequisite and indispensable part of DH.

Inhibition of Quinolone- and Multi-Drug-Resistant Clostridioides Difficile Strains by Multi Strain Synbiotics-An Option for Diarrhea Management in Nursing Facilities.

Diarrhea is a common problem in nursing homes. A survey among nursing facilities in Poland was used to characterize diarrhea outbreaks, the burden caused for residents and caregivers and the employed measures. Survey results confirmed that diarrhea is a common problem in nursing homes and in most cases affects groups of residents. The related burden is high or very high for 27% of residents and 40% of caregivers. In 80% of nursing facilities pro or synbiotics are part of the measures used to manage diarrhea. Administration of these kinds of products has been suggested for the management of diarrhea, especially in cases caused by Clostridioides (C.) difficile. C. difficile is one of many potential causes for diarrhea, but is of particular concern for nursing homes because it is responsible for a large proportion of diarrhea outbreaks and is often caused by multi-drug resistant strains. In vitro inhibition of a quinolone-resistant and a multi-drug resistant C. difficile strain was used to evaluate the growth inhibitory effects of commonly used products containing probiotic microorganisms. Growth of both strains was best inhibited by multi-strain synbiotic preparations. These findings suggest that multi-strain synbiotics can be considered as an interventional option for diarrhea caused by C. difficile.

Functional Recovery after Intramyocardial Injection of Adipose-Derived Stromal Cells Assessed by Cardiac Magnetic Resonance Imaging.

AIMS: A major clinical concern is the continuous increase in the number of patients diagnosed with advanced coronary artery disease, ischemic heart failure, and refractory angina, and one of the most promising treatment options for these conditions is stem cell-based therapy. The aim of this study was to assess the functional improvement following intramyocardial injection of adipose-derived stromal cells, using cardiac magnetic resonance. METHODS AND RESULTS: Thirteen patients with ischemic heart failure, reduced left ventricular ejection fraction, refractory angina, and who have been disqualified from any form of direct revascularization were enrolled in the study with transthoracic autologous adipose-derived stromal cell implantation. All patients underwent cardiac magnetic resonance prior to the procedure and after 12 months of follow-up. A significant increase in stroke volume (83.1 ± 8.5 mL vs 93.8 ± 13.8 mL, p = 0.025) and stroke volume index (43.3 ± 7.6 mL/m2 vs 48.7 ± 9.1 mL/m2, p = 0.019), a statistical trend toward an increase in left ventricle ejection fraction (36.7 ± 13.2 vs 39.7 ± 14.9, p = 0.052), and cardiac output improvement (5.0 ± 0.7 vs 5.5 ± 0.9, p = 0.073) was observed in the patient postprocedure. Enhanced relative regional thickening was noted in the segments with adipose-derived stromal cell implantation. CONCLUSIONS: Intramyocardial adipose-derived stromal cell implantation is a promising therapeutic option for selected, symptomatic patients with ischemic heart failure, who have preserved myocardial viability despite being unsuitable for direct revascularization.

Infantile Colic-The Perspective of German and Polish Pediatricians in 2020.

The objective of the study was to characterize how infantile colic is perceived and managed by German and Polish pediatricians. Data in both countries were collected by using a paper questionnaire with seven questions and predefined and free text fields for the answers. Answers from 160 German and 133 Polish pediatricians were collected. The average of the occurrence rates estimated by both responder groups were at the higher end of published rates. The majority of pediatricians from both countries rated the parental burden caused by infantile colic to be high or very high. Pediatricians' awareness about the association between infantile colic and maternal depression and premature termination of breastfeeding is relatively well established in both countries. While more than 90% of German pediatricians stated knowledge of infantile colic being a major risk factor for shaken baby syndrome, this knowledge was only declared by half of the Polish responders. Pharmacological interventions, pro-/synbiotics or simethicone, are part of the treatment repertoire of nearly all responding pediatricians. In addition, non-pharmacological interventions (e.g., change of feeding, change of parental behavior) are also among the employed interventions. Results of this study will allow to better design and prioritize communication about infantile colic directed at pediatricians.

Hyaluronic Acid as a Component of Natural Polymer Blends for Biomedical Applications: A Review.

In this review, we provide a report on recent studies in the field of research on the blends of hyaluronic acid with other natural polymers, namely collagen and chitosan. Hyaluronic acid has attracted significant interest in biomedical and cosmetic applications due to its interesting properties. In recent years, blends of hyaluronic acid with other polymers have been studied for new materials development. New materials may show improved properties that are important in the biomedical applications and in cosmetic preparations. In this review paper, the structure, preparation, and properties of hyaluronic acid blends with collagen and chitosan have been discussed and examples of new materials based on such blends have been presented. A comparison of the currently available information in the field has been shown. Future aspects in the field of hyaluronic acid blends and their applications in the biomedical and cosmetic industry have also been mentioned.

In-Vitro Growth Inhibition of Bacterial Pathogens by Probiotics and a Synbiotic: Product Composition Matters.

A variety of activities potentially contribute to the beneficial effects of probiotic bacteria observed in humans. Among these is a direct inhibition of the growth of pathogenic bacteria in the gut. The present study characterizes head-to-head the in-vitro pathogen growth inhibition of clinically relevant infectious bacterial strains by different types of probiotics and a synbiotic. In-vitro growth inhibition of Escherichia (E.) coli EPEC, Shigella (Sh.) sonnei, Salmonella (S.) typhimurium, Klebsiella (K.) pneumoniae and Clostridioides (C.) difficile were determined. Investigated products were a yeast mono strain probiotic containing Saccharomyces (Sac.) boulardii, bacterial mono strain probiotics containing either Lactobacillus (L.) rhamnosus GG or L. reuteri DSM 17938, a multi strain probiotic containing three L. rhamnosus strains (E/N, Oxy, Pen), and a multi strain synbiotic containing nine different probiotic bacterial strains and the prebiotic fructooligosaccharides (FOS). Inhibition of pathogens was moderate by Sac. boulardii and L. rhamnosus GG, medium by L. reuteri DSM 17938 and the L. rhamnosus E/N, Oxy, Pen mixture and strong by the multi strain synbiotic. Head-to-head in-vitro pathogen growth inhibition experiments can be used to differentiate products from different categories containing probiotic microorganisms and can support the selection process of products for further clinical evaluation.