Peroral Treatment Research Articles

Postoperative recovery in peroral versus intravenous antibiotic treatment following laparoscopic appendectomy for complicated appendicitis: a substudy of a cluster randomized cluster crossover non-inferiority study.

Acute appendicitis is the most common cause of abdominal pain requiring surgery, usually managed with laparoscopic appendectomy. In Denmark, the standard postoperative treatment for complicated cases involves intravenous antibiotics. This study compares peroral versus intravenous antibiotics in the context of fast-track surgery and Enhanced Recovery After Surgery (ERAS) protocols. Our objective is to evaluate the impact of peroral versus intravenous antibiotics on patient-reported outcomes following laparoscopic appendectomy for complicated appendicitis. This was a sub-study within a broader Danish cluster-randomized non-inferiority trial conducted at Zealand University Hospital, focusing on adult patients undergoing laparoscopic appendectomy for complicated appendicitis. Participants were randomized into two groups: one receiving a three-day course of peroral antibiotics and the other intravenous antibiotics after surgery. Recovery quality was assessed on the third postoperative day using the Quality of Recovery-15 (QoR-15) questionnaire. The study included 54 patients, 23 in the peroral and 31 in the intravenous groups. The peroral group reported significantly better recovery outcomes, with higher QoR-15 scores (mean difference of 12 points, p < 0.001). They also experienced shorter hospital stays, averaging 47 h less than the intravenous group (p < 0.001). No significant differences between the groups were observed in readmissions or severe postoperative complications. Peroral antibiotic administration after laparoscopic appendectomy for complicated appendicitis significantly improves patient recovery and reduces hospital stay compared to intravenous antibiotics. These results advocate a potential shift towards peroral antibiotic use in postoperative care, aligning with ERAS principles. ClinicalTrials.gov NCT04803422.

Peroral cholangioscopy-guided diagnosis and treatment of Clonorchis sinensis liver flukes.

Peroral cholangioscopy-guided diagnosis and treatment of Clonorchis sinensis liver flukes.

Effects of Chrysin and Chrysin-7-sulfate on Ochratoxin A-Albumin Interactions and on the Plasma and Kidney Levels of the Mycotoxin in Rats.

The nephrotoxic mycotoxin ochratoxin A (OTA) is a common food contaminant. OTA binds to the Sudlow's Site I region of serum albumin with very high affinity, resulting in its slow elimination. The displacement of OTA from albumin may be beneficial due to the faster excretion of the mycotoxin, while it may also lead to the increased tissue uptake of OTA. Furthermore, it is challenging to displace the mycotoxin from albumin even with high-affinity Site I ligands. In this study, we tested the impacts of Site I and Heme site ligands on OTA-albumin interactions by applying fluorescence spectroscopic, ultracentrifugation, and modeling studies. Chrysin-7-sulfate (C7S) strongly displaced OTA from both human and rat albumins; therefore, the impacts of C7S (single intravenous administration) and the parent flavonoid chrysin (repeated peroral treatment) were examined on the plasma and kidney levels of OTA in rats. Chrysin barely influenced the concentrations of mycotoxin in plasma and kidneys. In the first few hours, C7S significantly decreased the plasma levels of OTA compared to the control animals; while after 24 h, only minor differences were noticed. Our study highlights the superior displacing ability of C7S vs OTA regarding human and rat albumins.

Changes in Dickkopf-1, but Not Sclerostin, in Gingival Crevicular Fluid Are Associated with Peroral Statin Treatment in Patients with Periodontitis.

Background and Objectives: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling. The aim of this study was to determine the levels of SOST and DKK-1 in periodontal patients with and without peroral statins treatment in their therapy. Materials and Methods: A total of 79 patients with diagnosed periodontitis were divided into two groups: 39 patients on statin therapy (SP group) and 40 patients without statin therapy as a control group (P group). The periodontal clinical examination probing (pocket) depth (PD) and gingival recession (GR) were measured, and approximal plaque was detected, while vertical and horizontal bone resorption was measured using a panoramic radiograph image. Clinical attachment loss (CAL) values were calculated using PD and GR values. Gingival crevicular fluid (GCF) was collected and used for measuring SOST and DKK-1 levels. A questionnaire was used to assess lifestyle habits and statin intake. Patients' medical records were used to obtain biochemical parameters. Results: There was no significant difference in sclerostin concentration between the SP and P group. DKK-1 values were significantly higher in the SP group compared to the control group (p = 0.04). Also, PD (p = 0.001) and GR (p = 0.03) were significantly higher in the SP group. The level of DKK-1 had a positive relationship with the PD, the greater the PD, the higher the level of DKK-1 (Rho = 0.350), while there was no significant association with other parameters. Conclusions: Peroral statins in periodontal patients are associated with GCF levels of DKK-1 but not with sclerostin levels.

BAMLET administration via drinking water inhibits intestinal tumor development and promotes long-term health

Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) can act as a peroral treatment for colorectal cancer. ApcMin/+ mice, which carry mutations relevant to hereditary and sporadic human colorectal cancer, that received BAMLET in the drinking water showed long-term protection against tumor development and decreased expression of tumor growth-, migration-, metastasis- and angiogenesis-related genes. BAMLET treatment via drinking water inhibited the Wnt/β-catenin and PD-1 signaling pathways and prolonged survival without evidence of toxicity. Systemic disease in the lungs, livers, spleens, and kidneys, which accompanied tumor progression, was inhibited by BAMLET treatment. The metabolic response to BAMLET included carbohydrate and lipid metabolism, which were inhibited in tumor prone ApcMin/+ mice and weakly regulated in C57BL/6 mice, suggesting potential health benefits of peroral BAMLET administration in addition to the potent antitumor effects. Together, these findings suggest that BAMLET administration in the drinking water maintains antitumor pressure by removing emergent cancer cells and reprogramming gene expression in intestinal and extra-intestinal tissues.

A144 ZENKER’S PERORAL ENDOSCOPIC MYOTOMY (Z-POEM) OUTCOMES IN TREATMENT OF ZENKER’S DIVERTICULUM: A RETROSPECTIVE CASE SERIES

Abstract Background Zenker’s diverticulum (ZD) is an outpouching of tissue in an area of the posterior hypopharynx called the Killian triangle. ZD is associated with dysphagia, regurgitation, cough and recurrent aspirations. Open surgical repair has been the traditional treatment approach but has high morbidity (0-40%) and mortality (0-9.5%). Endoscopic intervention with septotomy is a less invasive approach with lower complications and shorter recovery times. However, technical success rates range between 56.4-100%, and recurrences occur in 0-32% of patients. Recent studies have shown promising results for peroral endoscopic myotomy treatment of ZD (Z-POEM), although data is limited. Aims In this first Canadian case series, we assess the safety and efficacy of Z-POEM, a novel approach for managing ZD. Methods This is a retrospective case series of all patients who underwent Z-POEM for ZD at Kingston Health Sciences center between July 2021-2023. Data collected included patient demographics, symptoms [Kothari Haber Score (KHS)] pre and post Z-POEM, ZD size and prior treatments. Technical outcomes were also analyzed including the procedure time and the Z-POEM Difficulty Score (ZPDS), which ranges from 0-3 based on maneuverability, fibrosis, and oozing. Clinical success was defined as complete or near-complete resolution of symptoms (i.e. KHS ampersand:003C2), and recurrence was defined as KHS of 3 or more. Lastly, we recorded adverse events and hospital length of stay. Results This case series included 9 patients (6 males and 3 females). The mean age ± standard deviation (SD) was 66.1 ± 10.64 years. One patient had two separate Z-POEM procedures and those were analyzed separately (total sample size = 10). The mean duration of symptoms before the procedure was 31.2 ± 10.12 months and the mean size of ZD was 2.25 ± 1.10 cm. Two patients had prior treatments before their Z-POEM procedure. The median preprocedural KHS was 6 (range 3-10) with dysphagia being the most commonly reported symptom in 80% of patients. In terms of technical outcomes, the mean procedural time was 32.3 ± 13.21 mins, and the median ZPDS score was 2. Most patients required 4-6 clips, with one patient requiring 11 clips for closure. No adverse events or periprocedural complications were reported. 9/10 patients (90%) were discharged one day after the procedure, and one patient required a longer stay (4 days) for observation. Clinical success was achieved in 8/10 patients (80%) of patients with a KHS score of 0 at mean 12 months follow-up. The remaining two patients (20%) had a KHS score of 3 at follow-up suggesting some persistent symptoms. Conclusions Z-POEM is safe and effective in management of ZD with high technical and clinical success rates in the short-term. Larger-scale studies are required to determine the long-term clinical efficacy of Z-POEM in treatment of ZD. Funding Agencies None

Acute Pancreatitis following Percutaneous Electrohydraulic Lithotripsy.

The gold-standard treatment of acute calculous cholecystitis is cholecystectomy. For patients not suitable for surgery, endoscopic or percutaneous techniques can be used for gallbladder decompression. The national percutaneous cholecystostomy rates have increased by 567% from 1994 to 2009*. Some of these patients are still not surgical candidates after the acute cholecystitis episode has resolved. Hence, it is crucial to have a management plan in place for such patients. There are several peroral endoscopic treatment options available, including ultrasound-guided transmural drainage, lithotripsy, and transpapillary stenting**. Furthermore, due to the advent of percutaneous biliary endoscopes, interventional radiology (IR) can now perform percutaneous lithotripsy and gallstone removal followed by cystic duct stenting. This method aims to internalize gallbladder drainage without the need for a long-term external cholecystostomy tube. Acute pancreatitis is a rare complication that can arise following interventions involving the biliary and cystic ducts. Acute pancreatitis can occur after retrograde ampullary manipulation during endoscopic retrograde cholangiopancreatography. However, this can sometimes happen after percutaneous antegrade interventions performed by IR. In this report, we will examine a rare complication that occurred in a patient with acute calculous cholecystitis: acute pancreatitis following percutaneous electrohydraulic lithotripsy with cystic duct stenting performed by IR.

PS-B10-1: DIFFERENT MECHANISMS OF BLOOD PRESSURE REDUCTION INDUCED BY CHRONIC PERORAL OR INTRACEREBROVENTRICULAR CLONIDINE ADMINISTRATION IN SALT-DEPENDENT OR ANGIOTENSIN II-DEPENDENT HYPERTENSION

Objective: The agonists of alpha2-adrenergic receptors are known to lower blood pressure (BP) through a reduction of brain sympathetic outflow but their chronic antihypertensive effects in rats with low-renin or high-renin forms of experimental hypertension were not studied yet. Moreover, there is no comparison of mechanisms underlying BP reduction elicited by chronic peroral (PO) or intracerebroventricular (ICV) clonidine treatment. Design and Methods: Adult male Dahl S rats fed 4% NaCl diet and Ren-2 transgenic rats were treated with clonidine administered either in the drinking fluid (0.5 mg/kg/day PO) or via the infusion into the lateral brain ventricle (0.1 mg/kg/day ICV) for 4 weeks. Basal BP as well as the contributions of renin-angiotensin system or sympathetic nervous system (acute BP responses to intravenous injection of either captopril 10 mg/kg or pentolinium 5 mg/kg) to BP maintenance were determined in conscious cannulated rats at the end of the study. Results: Both peroral and intracerebroventricular clonidine treatment lowered BP to the same extent in either rat model. However, in both models chronic clonidine treatment reduced sympathetic BP component only in rats treated intracerebroventricularly but not perorally treated animals. In contrast, peroral clonidine treatment reduced angiotensin-dependent vasoconstriction in Ren- transgenic rats, whereas it lowered residual BP in Dahl rats. Conclusions: Our results indicate different mechanisms of antihypertensive action of clonidine depending on the route of its administration - central or systemical

Case report Liraglutid and insuline resistance

Weight reduction in patients with cardiovascular (CV) diseases and concurrent overweight or obesity brings a fundamental improvement in health and prognosis of such diseases, a proven reduction in mortality and morbidity, and is associated with a reduction in pharmacotherapy and the number of hospitalizations, therefore, it is also economically effective. With the current growing trend in population, obesity also becomes a population risk factor that is more significant than smoking, and a leading cause of preventable diseases. From this point of view, the availability of a new effective anti-obesity medication is very welcome, in particular, liraglutide elegantly interferes with the physiological mechanisms regulating food intake. In addition, it reduces the risk of developing diabetes and has anti- atherogenic effects. At the obese diabetic 2 type patients on insulin treatment often resistance develops and in spite of high insuline dosage inadequate control of glucose and HbA1c levels are obvious. We present the extreme case on this topic down: May 2013: first examination dated in our database of cardiology care dept. for out patients, 65 years old man, weight 144 kg, height 178 cm, waist circumferrence 143cm. His history: arterial hypertension since 1993, diabetes 2 type since 2008 on peroral treatment, paroxysmal atrial fibrilation since March 2013, diameter of the left atrium 50mm on ECHO, invasive coronarography negat. Therapy: telmisartan, metoprolol, nitrendipin, warfarin, propafenon, digoxin, spironolacton, statin. November 2013: effect of therapeutic lifestyle changes: regular sinus rhythm, weight 133kg, waist circumferrence 134cm, spironolacton substituted by eplerenon (asymetric gynecomastia), digoxin ex May 2014: weight 126kg, September 2014: atrial fibrilation, propafenon substituted by flekainid, then atrial flutter, switch from flekainid to amiodaron and digoxin, warfarin substituted by apixaban February 2015: sinus rhythm , weight 129kg December 2015: weight 140kg, BP 170/90 mmHg, atrial flutter with a-v blockage 4:1, ankle oedema on both sides, Hb 115g/l, urinary acid 499umol/l, creatinin 119 umol/l, added allopurinol, urapidil, furosemid May 2017: intensification of the diabetes treatment, added insulin application, dosage escalation during the next years, on ECHO: left atriium diameter 52mm, left ventricle diameter 62mm, systolic function of the left ventricle preserved, moderate mitral and tricuspidal regurgitation December 2017: sinus bradycardia 46/min, amiodaron and digoxin ex, sick sinus syndrom brady-tachycardia form, hepatomegaly July 2018: bariatric procedure contraindicated by surgeon because of age and health status December 2018: creatinin 169umol/l, urinary acid 652umol/l October 2019: weight 158 kg, hospitalisation for heart failúre, confirmed by increased NT- BNP level, therapeutic changes from sartan to ARNI, from warfarin to apixaban, increased furosemid dosage. February 2021: weight 159kg, O2 peripheral saturation 93%, start of partial fasting (8:16) May 2021: signifficant dyspnoe, NYHA III, ECHO: left atrium diameter 56mm, left ventricle diameter 70mm, EF of the left ventricle 0,50, E/A 0,7 March 2022: attempt to implantate permanent cardiostimulation device unsuccesfull because of anatomic venous abnormalities. Brain MRI: postischemic frontal area defect right side Creatinin 220 umol/l, kalium 5,4 mmol/l, Hb 121 g/l, diabetic nephropathy. Weight 160kg. Added iron supplement. In spite of high insulin dosage (Humalog 3x20 units and basal 2x50 units) 160 units per day the glucose level were around 20mmol/l July 2022: weight 161 kg, starting of liraglutid daily application of 0,6mg s.c., dosage escalation every week to 1,2, 2,4, 3,0 mg. October 2022: hunger feeling was signifficantly reduced, eating of smaller portions, without craving between main time schedule of eating. Weight reduced to 151kg during first 3 months of liraglutid application (cca minus 100g per day), insulin dosage was reduced to 60 units daily (Humalog ex, basal insulin reduced to 60 units) what was accompanied by signifficant glucose level reduction to around 8 mmol/l. Creatinin level was 166 umol/l, acidum uricum level was 323 umol/l. January 2023: weight 157kg, fat content 50%, water content 40%. ECHO: left ventricle diameter 60mm, EF 0,5, left atrium diameter 54mm, tricuspidal regurgitation not detected, E/A 0,7. creatinin 128 umol/l , kalium 4,5 mmol/l.

Cannabidiol Decreases Intestinal Inflammation in the Ovariectomized Murine Model of Postmenopause.

Cannabidiol (CBD) (25 mg/kg peroral) treatment was shown to improve metabolic outcomes in ovariectomized (OVX) mice deficient in 17β-estradiol (E2). Herein, CBD effects on intestinal and hepatic bile acids (BAs) and inflammation were investigated. Following RNA sequencing of colon tissues from vehicle (VEH)- or CBD-treated sham surgery (SS) or OVX mice (n = 4 per group), differentially expressed genes (DEGs) were sorted in ShinyGO. Inflammatory response and bile secretion pathways were further analyzed. Colon content and hepatic BAs were quantified by LC-MS (n = 8-10 samples/group). Gut organoids were treated with CBD (100, 250, 500 µM) with or without TNFα and lipopolysaccharide (LPS) followed by mRNA extraction and qPCR to assess CBD-induced changes to inflammatory markers. The expression of 78 out of 114 inflammatory response pathway genes were reduced in CBD-treated OVX mice relative to vehicle (VEH)-treated OVX mice. In contrast, 63 of 111 inflammatory response pathway genes were increased in CBD-treated sham surgery (SS) mice compared to VEH-treated SS group and 71 of 121 genes were increased due to ovariectomy. CBD did not alter BA profiles in colon content or liver. CBD repressed Tnf and Nos2 expression in intestinal organoids in a dose-dependent manner. In conclusion, CBD suppressed colonic inflammatory gene expression in E2-deficient mice but was pro-inflammatory in E2-sufficient mice suggesting CBD activity in the intestine is E2-dependent.

Studies of the Specific Activity of Aerosolized Isoniazid against Tuberculosis in a Mouse Model.

The aerosol inhalation delivery of isoniazid in mice was investigated, and the specific activity of the aerosol form of isoniazid was studied with the mouse model of tuberculosis infection, the M. tuberculosis H37Rv strain. Aerosol delivery was performed using a laminar-flow horizontal nucleation chamber. The inhalation dose was measured in real-time mode using a diffusion aerosol spectrometer. The mean particle diameter was 0.6 ± 0.03 μm, and the inhalation dose was 5-9 mg/kg. Pharmacokinetic measurements were carried out in nose-only and whole-body chambers. Isoniazid concentration in blood serum and its mass in the lungs were measured as a function of time using high-performance liquid chromatography. Studies of the specific activity of aerosolized isoniazid reveal that treatment with the aerosol lead to the complete recovery of the experimental tuberculosis infection as early as after 28 days after the start of inhalation treatment, while in the animals from the group receiving isoniazid per-orally, sole revivable tuberculosis mycobacteria were detected. Histologic examinations show that only a few macrophagal (nonspecific) granulomas without mycobacteria were detected in the spleen after per-oral and aerosol treatment, the number of granulomas on the 28th day being three times smaller in the latter case. The results show that the developed technique of isoniazid aerosol inhalation may have clinical potential.

Long-term impact of persistent vegetations at 6 month followup after treatment of infective endocarditis: a substudy of the Partial Oral vs Intravenous Antibiotic Treatment of Endocarditis (POET) tria

Abstract Background Our knowledge of changes in vegetation size throughout the course of infective endocarditis (IE) and the impact of persistent vegetations on mortality or embolization after completed antibiotic treatment is sparse. No study has previously investigated the prevalence or clinical impact of persistent vegetations on transthoracic echocardiography (TTE) at 6-months follow-up after ended IE treatment. Purpose To investigate the association between persistent vegetations at the 6-months TTE after treatment for IE and long-term prognosis as assessed in the POET trial. Methods The POET trial was a nationwide, multicenter RCT, randomizing 400 patients to either partial oral or intravenous (IV) antibiotic treatment of left-sided IE, after initial stabilization of infection using conventional IV therapy. A persistent vegetation was defined as a vegetation seen on 6-months follow-up TTE (4–7 months) after ended antibiotic treatment for IE. In the POET trial, primary outcome was defined as 1) all-cause mortality, 2) unplanned cardiac surgery, 3) embolic events or 4) relapse of bacteremia, in the 5-year follow-up period. Patients without TTE due to death or lack of available TTE were excluded. Results Out of 400 patients, 20 were excluded due to death during 6-months follow-up, and 201 were excluded due to unavailable TTE, leaving 179 TTEs for analysis. At 6-months follow-up, a persistent vegetation was seen in 30 patients (16.7%, 21 males (70%), mean age 69.6 years (SD 7.7)) (Table 1). Seventeen patients (56.7%) had a persistent vegetation on the aortic valve and 13 patients (43.3%) on the mitral valve. More patients without a persistent vegetation had undergone initial surgical treatment of IE than those with a vegetation (57.7 vs 23.3%, p=0.001). In all surgically treated patients with persistent vegetation at 6-months follow-up, the vegetation was found on another valve than the operated valve. The composite primary outcome from 6-months follow-up and until 5-year follow-up occurred in 8 patients (26.7%) with a persistent vegetation, compared to 38 patients (25.5%) (p=1.00) without. (Table 2) In patients randomized for peroral treatment, no significant difference in prevalence of persistent vegetation was found (15 patients (50%) with persistent vegetations vs. 74 patients (49.7%) without, p=1.00). Conclusion The occurrence of persistent vegetations at 6 months follow-up was 16.7%. There was no association between persistent vegetations at 6-months follow-up and the occurrence of the primary outcome after 5 years follow-up, suggesting that the risk associated with residual vegetations after end of antibiotic treatment is negligible after 6-months. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation

Epithelial Heat Shock Proteins Mediate the Protective Effects of Limosilactobacillus reuteri in Dextran Sulfate Sodium-Induced Colitis.

Defects in gut barrier function are implicated in gastrointestinal (GI) disorders like inflammatory bowel disease (IBD), as well as in systemic inflammation. With the increasing incidence of IBD worldwide, more attention should be paid to dietary interventions and therapeutics with the potential to boost the natural defense mechanisms of gut epithelial cells. The current study aimed to investigate the protective effects of Limosilactobacillus reuteri ATCC PTA 4659 in a colitis mouse model and delineate the mechanisms behind it. Wild-type mice were allocated to the control group; or given 3% dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis; or administered L. reuteri for 7 days as pretreatment; or for 14 days starting 7 days before subjecting to the DSS. Peroral treatment with L. reuteri improved colitis severity clinically and morphologically and reduced the colonic levels of Tumor necrosis factor-α (TNF-α) (Tnf), Interleukin 1-β (Il1β), and nterferon-γ (Ifng), the crucial pro-inflammatory cytokines in colitis onset. It also prevented the CD11b+Ly6G+ neutrophil recruitment and the skewed immune responses in mesenteric lymph nodes (MLNs) of CD11b+CD11c+ dendritic cell (DC) expansion and Foxp3+CD4+ T-cell reduction. Using 16S rRNA gene amplicon sequencing and RT-qPCR, we demonstrated a colitis-driven bacterial translocation to MLNs and gut microbiota dysbiosis that were in part counterbalanced by L. reuteri treatment. Moreover, the expression of barrier-preserving tight junction (TJ) proteins and cytoprotective heat shock protein (HSP) 70 and HSP25 was reduced by colitis but boosted by L. reuteri treatment. A shift in expression pattern was also observed with HSP70 in response to the pretreatment and with HSP25 in response to L. reuteri-DSS. In addition, the changes of HSPs were found to be correlated to bacterial load and epithelial cell proliferation. In conclusion, our results demonstrate that the human-derived L. reuteri strain 4659 confers protection in experimental colitis in young mice, while intestinal HSPs may mediate the probiotic effects by providing a supportive protein–protein network for the epithelium in health and colitis.

Genomic identification of streptococcal strains and relation to clinical characteristics. A substudy to The Partial Oral Treatment of Endocarditis (POET) Trial.

The Danish National Partial Oral Treatment of Endocarditis Trial (POET) demonstrated non-inferiority of partly peroral compared to intravenous antibiotic therapy for infective endocarditis (IE) caused by Streptococcus spp, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. Identifications by whole genome sequencing (WGS) of available streptococcal strains were related to clinical data. Sequences were obtained using Illumina technology (MiseqÒ) followed by core genome analysis and single-nucleotide polymorphism phylogeny examinations. Average nucleotide identification (ANI) calculated using the tool fastANI. Informations on +/- preexisting valve prosthesis, valve surgery and outcome related to obtained identifications. Streptococcal strains (n=123) from 117 patients were WGS examined. Twelve percent were pyogenic group strains and 88% belonged to viridans groups, mainly mitis and bovis groups. Phylogenetic trees were in accordance regarding species and subspecies identifications. High ANI percentages to type strains were found. Respectively 39, 60 and 16 IE cases involved mitral, aortic or both valves. IE caused by pyogenic group or mitis plus bovis group streptococci most frequent affected, respectively, mitral and aortic valves. Thirty-one patients (26%) had a preexisting prosthesis; notably, in 50% of bovis group IE cases. Fifty-six patients had valve surgery done during the current disease; 8% and 93% of patients having, respectively, pyogenic group and mitis group strains as causative agents. Of patients allocated to intravenous or intravenous followed by peroral antibiotic treatment, respectively 26 and 30 had valve surgery done during the current disease. Composite outcome (all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen) at five-year follow-up comprised in total 39 events. In conclusion, molecular examinations adds on substantially by detailing species and subspecies affiliations. A broad spectrum of streptococcal species and subspecies causing IE were identified with mitis- and bovis group strains dominating. Relating strain identifications to clinical data can assist in planning and treating confirmed/suspected IE patients. Adding WGS identification of streptococci in selected patients groups (e.g. IE) in order to expand number of cases characterized in detail seems ideal and advocates for centralized registration of results to reveal important clinical relations.

Peroral endoscopic myotomy treatment for symptomatic esophageal diverticulum: a systematic review and meta-analysis.

Peroral endoscopic myotomy (POEM) is a rapidly evolving technique for the treatment of esophageal diverticulum. The aim of this study was to perform a systematic review and meta-analysis of the literature focusing on POEM for symptomatic esophageal diverticula, including an in-depth evaluation of its efficacy, safety, and limitations. A comprehensive literature search was completed to identify articles that examined the efficacy and safety of POEM for esophageal diverticula. Heterogeneity among studies was assessed using the I2 statistic. Meta-regression and sensitivity analyses were performed to explore the sources of heterogeneity and assess potentially important covariates influencing the main outcomes. Primary endpoints such as rates of success, adverse events, and recurrences were evaluated. P values of ≤0.05 were considered statistically significant. Nine studies with a total of 153 patients were enrolled. Pooled technical success, clinical success, adverse events, and recurrence rates were 99% [95% confidence interval (CI), 97-100%; I2 = 0%), 94% (95% CI, 89-97%; I2 = 24%), 2% (95% CI, 0-6%, I2 = 0%), and 0% (95% CI, 0-1%; I2 = 0%), respectively. The pooled perforation rate was 6% (95% CI, 1-11%; I2 = 0%). Meta-regression analysis indicated that esophageal diverticula types and motility disorders were not associated with the clinical success rate (P > 0.05). POEM is a feasible, safe, and effective treatment for symptomatic esophageal diverticula, with low adverse events and recurrence rates.

A Rare Complication of Barium Swallow Test

Question: A 70-year-old man with gastroenteropancreatic neuroendocrine tumor of the duodenum underwent robotic subtotal stomach-preserving pancreatoduodenectomy (PD). During the surgery, retrocolic reconstruction for pancreaticojejunostomy and hepaticojejunostomy, as well as antecolic reconstruction for gastrojejunostomy, were performed. Surgical anatomy following these reconstructions is illustrated in Figure A. The patient’s postoperative follow-up was uneventful. Six months later, the patient underwent a barium swallow test for a medical checkup at another hospital. The examination found no significant findings in the stomach, but revealed reflux of the barium sulfate into the intrahepatic biliary trees through the afferent loop (Figure B). After the barium swallow test on that day, the patient was referred to our hospital. He complained only of fever, but did not demonstrate other symptoms. The laboratory findings showed the following unremarkable changes: white blood cell, 6920/μL; total bilirubin, 0.89 mg/dL; direct bilirubin, 0.25 mg/dL; aspartate transaminase 23 U/L; alanine aminotransferase, 22 U/L; and C-reactive protein, 0.76 mg/dL. The abdominal computed tomography revealed retained barium sulfate in the bilateral biliary system (Figure C). What is the treatment strategy for this patient? Look on page 402 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. Retained barium sulfate in the biliary system may cause hepatolithiasis because of progressive water absorption, leading to complications such as obstructive jaundice, cholangitis, and sepsis.1Walsham A. Larsen J. Adverse effects of barium sulfate in the biliary tract.Diagn Interv Radiol. 2008; 14: 94-96PubMed Google Scholar Despite the absence of guidelines for the treatment of barium-induced choleliths, evidence-based guidelines for hepatolithiasis after biliary reconstruction propose peroral endoscopic treatment as the first-line option, or percutaneous transhepatic biliary drainage (PTBD) as an alternative.2Tazuma S. Unno M. Igarashi Y. et al.Evidence-based clinical practice guidelines for cholelithiasis 2016.J Gastroenterol. 2017; 52: 276-300Crossref PubMed Scopus (71) Google Scholar However, endoscopic approaches using a double-balloon endoscope (DBE) could be less invasive and have several advantages in bilateral drainage as well as in the accurate evaluation for residual choleliths with peroral direct cholangioscopy.3Ishihara Y. Matsumoto K. Kato H. et al.Treatment outcomes, including risk factors of stone recurrence, for hepatolithiasis using balloon-assisted endoscopy in patients with hepaticojejunostomy (with video).Surg Endosc. 2020; 34: 1895-1902Google Scholar Therefore, urgent endoscopic intervention was attempted in this case. In facilities where DBEs are not available, PTBD should be considered. Using DBE, saline was injected into the biliary trees via a catheter through the hepaticojejunostomy, and barium sulfate lodged at the main bile duct was washed out (Figure D). An endoscopic nasobiliary drainage tube was placed, and further irrigation was conducted for 3 days. After confirmation of duct clearance by a computed tomography scan, the patient was discharged. The reflux of orally administered barium sulfate into the intrahepatic biliary system is a rare but complicated adverse effect of a barium swallow test. To date, several conditions, including spontaneous or postoperative fistula and choledochoenterostomy, have been reported to be associated with reflux.1Walsham A. Larsen J. Adverse effects of barium sulfate in the biliary tract.Diagn Interv Radiol. 2008; 14: 94-96PubMed Google Scholar However, to our knowledge, this report is the first of barium sulfate reflux into the intrahepatic biliary trees in a patient undergoing PD. Urgent endoscopic intervention was safe and effective to prevent barium-induced biliary complications. In conclusion, the present case demonstrated a rare complication of barium sulfate in the biliary system following biliary reconstruction. It suggests that barium swallow test following PD should be contraindicated. Therefore, in similar patients experiencing this rare adverse effect, urgent intervention with DBE or PTBD should be performed to avoid complex biliary complications.

Exploration of a transdermal nanoemulgel as an alternative therapy for postmenopausal osteoporosis

The study investigated the ability of a transdermal nanoemulgel formulation to enhance the bioavailability and anti-osteoporotic efficacy of raloxifene hydrochloride (RH) using recent techniques such as micro-CT, SEM-EDX analysis. The ex-vivo permeation, histopathology, SEM, DSC and CLSM studies were carried out to determine the mechanistics of permeation. The in-vivo pharmacokinetic and pharmacodynamic studies were performed after establishing osteoporosis model using ovariectomy surgery. The biocompatibility of the developed nanoemulgel was tested as per OECD TG 439 protocol. The permeation of RH enhanced by 13 fold compared to plain drug gel. DSC and SEM examination showed change in microstructure of the skin which is the foundation for improved permeation. The pharmacokinetic study suggested 26 fold improved bioavailability of RH compared to per-oral marketed treatment. The micro-CT study demonstrated 202% enhanced bone mineral density. Improved pharmacokinetic and pharmacodynamic performance supported our claim of a successful delivery system. Our formulation is proposed to be safe, patient compliant and therapeutically effective alternative to the available marketed product.

Zinc, brain, behavior

The purpose of the review was to analyze current notions about role of essential trace element zinc in brain activity and therefore in behavior. At the beginning of the review the basic data about zinc metabolism was described. The facts of zinc involvement into neurologic disorders and human cognition were represented. The results of the own investigation, devoted zinc peroral treatment and intrabrain microinjections influence on rats normal and pathological motor behavior were described. In particular, it is shown that zinc, depending on the dose and its mode of entry into the organism, can weaken and prevent the development of picrotoxin-induced neostriatal hyperkinesis (human Huntington horea analog), but it may aggravate hyperkinesis symptoms and even independently cause the motor stereotypy. On the basis of their own data and literary, it was suggested that neurons membranes structures are different sensitive to a certain zinc concentration and what does the specific way of behavior realization is ultimately depend.

Anti-Pathogenic and Immune-Modulatory Effects of Peroral Treatment with Cardamom Essential Oil in Acute Murine Campylobacteriosis.

Human infections with enteropathogenic Campylobacter jejuni (C. jejuni) including multi-drug resistant isolates are emerging worldwide. Antibiotics-independent approaches in the combat of campylobacteriosis are therefore highly desirable. Since the health-beneficial including anti-inflammatory and anti-infectious properties of cardamom have been acknowledged for long, we here addressed potential anti-pathogenic and immune-modulatory effects of this natural compound during acute campylobacteriosis. For this purpose, microbiota-depleted IL-10−/− mice were orally infected with C. jejuni strain 81–176 and subjected to cardamom essential oil (EO) via the drinking water starting on day 2 post-infection. Cardamom EO treatment resulted in lower intestinal pathogen loads and improved clinical outcome of mice as early as day 3 post-infection. Furthermore, when compared to mock controls, cardamom EO treated mice displayed less distinct macroscopic and microscopic inflammatory sequelae on day 6 post-infection that were paralleled by lower colonic numbers of macrophages, monocytes, and T cells and diminished pro-inflammatory mediator secretion not only in the intestinal tract, but also in extra-intestinal and, remarkably, systemic organs. In conclusion, our preclinical intervention study provides the first evidence that cardamom EO comprises a promising compound for the combat of acute campylobacteriosis and presumably prevention of post-infectious morbidities.

Resveratrol Alleviates Acute Campylobacter jejuni Induced Enterocolitis in a Preclinical Murine Intervention Study.

The polyphenolic compound resveratrol has been shown to exert health-beneficial properties. Given globally emerging Campylobacter infections in humans, we addressed potential anti-pathogenic, immuno-modulatory and intestinal epithelial barrier preserving properties of synthetic resveratrol in the present preclinical intervention study applying a murine acute campylobacteriosis model. Two days following peroral C. jejuni infection, secondary abiotic IL-10−/− mice were either subjected to resveratrol or placebo via the drinking water. Whereas placebo mice suffered from acute enterocolitis at day 6 post-infection, resveratrol treatment did not only lead to improved clinical conditions, but also to less pronounced colonic epithelial apoptosis as compared to placebo application. Furthermore, C. jejuni induced innate and adaptive immune cell responses were dampened in the large intestines upon resveratrol challenge and accompanied by less colonic nitric oxide secretion in the resveratrol versus the placebo cohort. Functional analyses revealed that resveratrol treatment could effectively rescue colonic epithelial barrier function in C. jejuni infected mice. Strikingly, the disease-alleviating effects of resveratrol could additionally be found in extra-intestinal and also systemic compartments at day 6 post-infection. For the first time, our current preclinical intervention study provides evidence that peroral resveratrol treatment exerts potent disease-alleviating effects during acute experimental campylobacteriosis.