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Biosensors & Bioelectronics Jul 2023Current in-vitro 2D cultures and animal models present severe limitations in recapitulating human physiopathology with striking discrepancies in estimating drug efficacy... (Review)
Review
Current in-vitro 2D cultures and animal models present severe limitations in recapitulating human physiopathology with striking discrepancies in estimating drug efficacy and side effects when compared to human trials. For these reasons, microphysiological systems, organ-on-chip and multiorgans microdevices attracted considerable attention as novel tools for high-throughput and high-content research to achieve an improved understanding of diseases and to accelerate the drug development process towards more precise and eventually personalized standards. This review takes the form of a guide on this fast-growing field, providing useful introduction to major themes and indications for further readings. We start analyzing Organs-on-chips (OOC) technologies for testing the major drug administration routes: (1) oral/rectal route by intestine-on-a-chip, (2) inhalation by lung-on-a-chip, (3) transdermal by skin-on-a-chip and (4) intravenous through vascularization models, considering how drugs penetrate in the bloodstream and are conveyed to their targets. Then, we focus on OOC models for (other) specific organs and diseases: (1) neurodegenerative diseases with brain models and blood brain barriers, (2) tumor models including their vascularization, organoids/spheroids, engineering and screening of antitumor drugs, (3) liver/kidney on chips and multiorgan models for gastrointestinal diseases and metabolic assessment of drugs and (4) biomechanical systems recapitulating heart, muscles and bones structures and related diseases. Successively, we discuss technologies and materials for organ on chips, analyzing (1) microfluidic tools for organs-on-chips, (2) sensor integration for real-time monitoring, (3) materials and (4) cell lines for organs on chips. (Nano)delivery approaches for therapeutics and their on chip assessment are also described. Finally, we conclude with a critical discussion on current significance/relevance, trends, limitations, challenges and future prospects in terms of revolutionary impact on biomedical research, preclinical models and drug development.
Topics: Animals; Humans; Lab-On-A-Chip Devices; Biosensing Techniques; Drug Development; Microphysiological Systems; Liver
PubMed: 37060819
DOI: 10.1016/j.bios.2023.115271 -
Pediatric Neurology Jun 2020Dravet syndrome is a debilitating epileptic encephalopathy of childhood with few treatment options available in the United States before 2018. In the modern era, new... (Review)
Review
Dravet syndrome is a debilitating epileptic encephalopathy of childhood with few treatment options available in the United States before 2018. In the modern era, new genetic testing options will allow diagnosis closer to disease onset. Three new medicines-stiripentol, cannabidiol, and fenfluramine-have documented efficacy and safety as adjunctive therapies for treating pharmacoresistant Dravet syndrome. Early diagnosis resulting in earlier treatment with these and other medications may improve prognosis of long-term outcomes, including less severity of cognitive, motor, and behavioral impairments. New rescue medication formulations can now manage acute seizures and help prevent status epilepticus via intranasal, buccal, and intramuscular routes as opposed to rectal administration. Preventing status epilepticus and generalized tonic-clonic seizures could potentially lower the risk of sudden unexpected death in epilepsy. With this changing landscape in diagnostic and treatment options comes questions and controversies for the practicing clinician, especially as diagnostic techniques outpace clinical treatment strategies. Critical decision points include when to start treatment, what pharmacotherapy combinations to try first, which rescue medication to recommend, and how to advise parents on controversial topics (e.g., immunizations). Given that most patients require polypharmacy, clinicians must be cognizant of drug-drug interactions between new medicines, existing anti-epileptic drugs, and other medications to manage comorbidities and must have an understanding of available therapeutic drug monitoring strategies and pharmacokinetic parameters. This review places new diagnostic, treatment and acute care options into the modern era and provides an overview of the challenges and opportunities facing the pediatric epileptologist in this rapidly changing landscape.
Topics: Anticonvulsants; Cannabidiol; Child; Dioxolanes; Epilepsies, Myoclonic; Fenfluramine; Genetic Testing; Humans
PubMed: 32165031
DOI: 10.1016/j.pediatrneurol.2020.01.005 -
Endoscopy Feb 20201: ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before endoscopic retrograde cholangiopancreatography (ERCP) in...
PROPHYLAXIS
1: ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before endoscopic retrograde cholangiopancreatography (ERCP) in all patients without contraindications to nonsteroidal anti-inflammatory drug administration.Strong recommendation, moderate quality evidence. 2: ESGE recommends prophylactic pancreatic stenting in selected patients at high risk for post-ERCP pancreatitis (inadvertent guidewire insertion/opacification of the pancreatic duct, double-guidewire cannulation).Strong recommendation, moderate quality evidence. 3: ESGE suggests against routine endoscopic biliary sphincterotomy before the insertion of a single plastic stent or an uncovered/partially covered self-expandable metal stent for relief of biliary obstruction.Weak recommendation, moderate quality evidence. 4: ESGE recommends against the routine use of antibiotic prophylaxis before ERCP.Strong recommendation, moderate quality evidence. 5: ESGE suggests antibiotic prophylaxis before ERCP in the case of anticipated incomplete biliary drainage, for severely immunocompromised patients, and when performing cholangioscopy.Weak recommendation, moderate quality evidence. 6: ESGE suggests tests of coagulation are not routinely required prior to ERCP for patients who are not on anticoagulants and not jaundiced.Weak recommendation, low quality evidence.
TREATMENT
7: ESGE suggests against salvage pancreatic stenting in patients with post-ERCP pancreatitis.Weak recommendation, low quality evidence. 8: ESGE suggests temporary placement of a biliary fully covered self-expandable metal stent for post-sphincterotomy bleeding refractory to standard hemostatic modalities.Weak recommendation, low quality evidence. 9: ESGE suggests to evaluate patients with post-ERCP cholangitis by abdominal ultrasonography or computed tomography (CT) scan and, in the absence of improvement with conservative therapy, to consider repeat ERCP. A bile sample should be collected for microbiological examination during repeat ERCP.Weak recommendation, low quality evidence.
Topics: Cholangiopancreatography, Endoscopic Retrograde; Endoscopy, Gastrointestinal; Humans; Pancreatic Ducts; Self Expandable Metallic Stents; Sphincterotomy, Endoscopic
PubMed: 31863440
DOI: 10.1055/a-1075-4080 -
World Journal of Gastroenterology Sep 2019Anastomotic leak (AL) constitutes a significant issue in colorectal surgery, and its incidence has remained stable over the last years. The use of intra-abdominal drain... (Review)
Review
Anastomotic leak (AL) constitutes a significant issue in colorectal surgery, and its incidence has remained stable over the last years. The use of intra-abdominal drain or the use of mechanical bowel preparation alone have been proven to be useless in preventing AL and should be abandoned. The role or oral antibiotics preparation regimens should be clarified and compared to other routes of administration, such as the intravenous route or enema. In parallel, preoperative antibiotherapy should aim at targeting collagenase-inducing pathogens, as identified by the microbiome analysis. AL can be further reduced by fluorescence angiography, which leads to significant intraoperative changes in surgical strategies. Implementation of fluorescence angiography should be encouraged. Progress made in AL comprehension and prevention might probably allow reducing the rate of diverting stoma and conduct to a revision of its indications.
Topics: Anastomosis, Surgical; Anastomotic Leak; Anti-Bacterial Agents; Cathartics; Colon; Enema; Fluorescein Angiography; Gastrointestinal Microbiome; Humans; Incidence; Preoperative Care; Rectum; Surgical Wound Infection; Treatment Outcome
PubMed: 31558854
DOI: 10.3748/wjg.v25.i34.5017 -
Advanced Science (Weinheim,... Oct 2023Post-infectious irritable bowel syndrome (PI-IBS) occurs after acute infectious diarrhea, and dysbiosis can be involved in its pathogenesis. Here, the role of...
Post-infectious irritable bowel syndrome (PI-IBS) occurs after acute infectious diarrhea, and dysbiosis can be involved in its pathogenesis. Here, the role of chlorogenic acid (CGA) is investigated, a natural compound with several pharmacological properties, in alleviating PI-IBS in rats. It is elucidated that the gut microbiota plays a key role in PI-IBS pathogenesis and that rectal administration of CGA alleviated PI-IBS by modulating the gut microbiota and its metabolites. CGA supplementation significantly increased fecal Bacteroides acidifaciens abundance and glycine levels. Glycine structurally altered B. acidifaciens extracellular vesicles (EVs) and enriched functional proteins in the EVs; glycine-induced EVs alleviated PI-IBS by reducing inflammation and hypersensitivity of the intestinal viscera and maintaining mucosal barrier function. Moreover, B. acidifaciens EVs are enriched in the brain tissue. Thus, CGA mediates the mitigation of PI-IBS through the gut microbiota and its metabolites. This study proposes a novel mechanism of signal exchange between the gut microenvironment and the host.
Topics: Rats; Animals; Irritable Bowel Syndrome; Chlorogenic Acid; Gastrointestinal Microbiome; Inflammation; Glycine
PubMed: 37616338
DOI: 10.1002/advs.202302798 -
Epilepsy & Behavior : E&B Dec 2021Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a venous line may be difficult in children with seizures which would delay the initiation of treatment. Rectal drug administration can be socially awkward for patients and providers. Intranasal (IN) midazolam offers a valuable substitute that is easier and faster to administer.
OBJECTIVE
To assess the efficacy, safety, and acceptability of intranasal midazolam in children with acute seizure when compared to conventional IV or rectal benzodiazepine (BDZ).
METHODS
PubMed, google scholar, websites clinicaltrials.gov and the WHO-international clinical trials registry platform, were searched. Randomized controlled/prospective randomized trials comparing IN midazolam against IV/rectal BDZ in the treatment of acute seizures in pediatric patients were included in the meta-analysis.
RESULTS
Data of 10 studies were quantitatively analyzed. Intranasal midazolam (n = 169) when compared to IV/rectal BDZ (n = 161) has a shorter interval between hospital arrival and seizure cessation {(mean difference = -3.51; 95% CI [-6.84, -0.18]) P = 0.04}. Regarding time to seizure cessation after midazolam (n = 326) or BDZ (n = 322) administration, there is no significant difference between the two groups {(mean difference = -0.03; 95% CI [-1.30, 1.25]), P = 0.97} and both are equally effective for controlling acute seizures (odds ratio = 1.06; 95% CI [0.43, 2.63]; n = 737).
CONCLUSION
In children with acute seizures, IN midazolam is equally effective in aborting seizure and decreases the total time from hospital arrival and cessation of seizures, eventually leading to faster cessation of seizure as compared to IV/rectal BDZ.
Topics: Administration, Intranasal; Anticonvulsants; Benzodiazepines; Child; Diazepam; Humans; Midazolam; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus
PubMed: 34740090
DOI: 10.1016/j.yebeh.2021.108390 -
La Clinica Terapeutica 2019Post-Endoscopic Retrograde Cholangio-Pancreatography pancreatitis (PEP) is a relevant (1-4%) complication of biliopancreatic operative endoscopy. Rectal nonsteroidal... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Post-Endoscopic Retrograde Cholangio-Pancreatography pancreatitis (PEP) is a relevant (1-4%) complication of biliopancreatic operative endoscopy. Rectal nonsteroidal anti-inflammatory drugs (specifically, 100 mg of diclofenac) have shown promising prophylactic activity in PEP. The aim of our prospective study is to report whether prophylactic oral versus rectal suppository versus intramuscular diclofenac versus placebo are able to reduce the incidence and the severity of ERCP-induced pancreatitis.
MATERIALS AND METHODS
In this randomized, double-blinded, prospective study, 100 patients (49 male, 51 female), similar with regard to indication for ERCP, were enrolled between January 2016 and November 2017 to undergo ERCP in the Section of General and Thoracic Surgery of University Hospital of Palermo. They were randomized into five groups, respectively 20 patients with placebo by mouth; 20 patients with 50 mg diclofenac sodium enteric-coated capsules by mouth; 20 with 100 mg rectal suppository diclofenac, 20 with 75 mg/3 ml intramuscular diclofenac sodium, 20 with 75 mg/3 ml intramuscular diclofenac sodium and 20 with 75 mg/3 ml intravenous diclofenac. All drugs were administered 30 to 90 minutes before ERCP. All clinical data were collected one day before and 2, 12 and 24 hour after ERCP.
RESULT
Data were prospectively collected and to demonstrate the preventive effect of rectal diclofenac on PEP, a two-by-two table and chi-square test with Yates correction were used: the incidence of PEP was significantly lower (p < 0.001) in the rectal diclofenac group respect to other groups and, in the same way, the incidence of post-ERCP pain was significantly lower in the rectal diclofenac group than in the other groups (p = 0.001) and patients discharge was consequently earlier (p < 0.01).
CONCLUSION
100 mg dose rectal diclofenac administered 30-60 minutes before ERCP can effectively prevent PEP.
Topics: Acute Disease; Administration, Rectal; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Diclofenac; Double-Blind Method; Female; Humans; Male; Middle Aged; Pancreatitis; Prospective Studies; Treatment Outcome
PubMed: 31612188
DOI: 10.7417/CT.2019.2156 -
Current Opinion in Neurology Apr 2022The purpose of this review is to provide a succinct evaluation of the current rescue medications and action plans available to our patients with seizure clusters in the... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide a succinct evaluation of the current rescue medications and action plans available to our patients with seizure clusters in the outpatient setting.
RECENT FINDINGS
The main themes of the recent findings are that rescue medications and seizure action plans (SAPs) are underutilized, particularly in the adult population. The safety and efficacy of intranasal midazolam and intranasal diazepam is comparable with rectal diazepam for the treatment of seizure clusters. Additionally, this intranasal formulation has the benefit of a more socially acceptable route of administration and ease of use.
SUMMARY
The implication of these findings is a greater variety and awareness in the rescue medications available to our patients suffering from seizure clusters.
Topics: Administration, Intranasal; Adult; Anticonvulsants; Diazepam; Epilepsy; Humans; Seizures
PubMed: 35153281
DOI: 10.1097/WCO.0000000000001038 -
International Journal of Pharmaceutical... 2022Suppositories have not gained the level of acceptability, respect, and usage as most other dosage forms. Rectal administration is not often the first route of... (Review)
Review
Suppositories have not gained the level of acceptability, respect, and usage as most other dosage forms. Rectal administration is not often the first route of choice, but it becomes a good alternative when the oral route is inadvisable. Much work has been conducted in recent years on suppositories as a dosage form, as evidenced by the literature citations on suppository or suppositories. Although suppositories are not very popular as a mode of administering drugs, this dosage form will probably always have a place in medicine. Newer specialty suppository dosage forms have been developed to introduce drugs into the body, including the hollow-type suppository. Hollow-type suppositories have been investigated as a new dosage form that can be used for various purposes including but not limited to 1) enhancing the bioavailability of a drug, 2) slowing down or speeding up its onset of action, and 3) increasing or decreasing its duration of action. The flexibility of hollow-type suppositories may provide compounding pharmacists additional options for patients in the future. The purpose of this article is to provide a review of the characteristics and applications of hollow-type suppositories in both research and clinical situations.
Topics: Administration, Oral; Administration, Rectal; Biological Availability; Humans; Suppositories
PubMed: 35820136
DOI: No ID Found -
World Journal of Gastroenterology Aug 2019Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis...
BACKGROUND
Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis (PEP), since it has been considered to be the most common complication of ERCP. Although ERCP can lead various complications, it can also be avoided.AIMSTo study the published evidence and systematically review the literature on the prevention and treatment for PEP.
METHODS
A systematic literature review on the prevention of PEP was conducted using the electronic databases of ISI Web of Science, PubMed and Cochrane Library for relevant articles. The electronic search for the review was performed by using the search terms "Post endoscopic retrograde cholangiopancreatography pancreatitis" AND "prevention" through different criteria. The search was restricted to randomized controlled trials (RCTs) performed between January 2009 and February 2019. Duplicate studies were detected by using EndNote and deleted by the author. PRISMA checklist and flow diagram were adopted for evaluation and reporting. The reference lists of the selected papers were also scanned to find other relevant studies.
RESULTS
726 studies meeting the search criteria and 4 relevant articles found in the edited books about ERCP were identified. Duplicates and irrelevant studies were excluded by screening titles and abstracts and assessing full texts. 54 studies were evaluated for full text review. Prevention methods were categorized into three groups as (1) assessment of patient related factors; (2) pharmacoprevention; and (3) procedural techniques for prevention. Most of studies in the literature showed that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction, recurrent pancreatitis and history of previous PEP played a crucial role in posing high risks for PEP. 37 studies designed to assess the impact of 24 different pharmacologic agents to reduce the development of PEP delivered through various administration methods were reviewed. Nonsteroidal anti-inflammatory drugs are widely used to reduce risks for PEP. Rectal administration of indomethacin immediately prior to or after ERCP in all patients is recommended by European Society for Gastrointestinal Endoscopy guidelines to prevent the development of PEP. The majority of the studies reviewed revealed that rectally administered indomethacin had efficacy to prevent PEP. Results of the other studies on the other pharmacological interventions had both controversial and promising results. Thirteen studies conducted to evaluate the efficacy of 4 distinct procedural techniques to prevent the development of PEP were reviewed. Pancreatic Stent Placement has been frequently used in this sense and has potent and promising benefits in the prevention of PEP. Studies on the other procedural techniques have had inconsistent results.
CONCLUSION
Prevention of PEP involves multifactorial aspects, including assessment of patients with high risk factors for alternative therapeutic and diagnostic techniques, administration of pharmacological agents and procedural techniques with highly precise results in the literature.
Topics: Administration, Rectal; Anti-Inflammatory Agents; Biliary Tract Diseases; Catheterization; Cholangiopancreatography, Endoscopic Retrograde; Drainage; Humans; Pancreas; Pancreatitis; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Preoperative Care; Risk Assessment; Risk Factors; Somatostatin; Sphincter of Oddi; Stents
PubMed: 31413535
DOI: 10.3748/wjg.v25.i29.4019