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3D printing injectable microbeads using a composite liposomal ink for local treatment of peritoneal diseases.
Get PDFThe peritoneal cavity offers an attractive administration route for challenging-to-treat diseases, such as peritoneal carcinomatosis, post-surgical adhesions, and peritoneal fibrosis. Achieving a uniform and prolonged drug distribution throughout the entire peritoneal space, though, is difficult due to high clearance rates, among others. To address such an unmet clinical need, alternative drug delivery approaches providing sustained drug release, reduced clearance rates, and a patient-centric strategy are required. Here, we describe the development of a 3D-printed composite platform for the sustained release of the tyrosine kinase inhibitor gefitinib (GEF), a small molecule drug with therapeutic applications for peritoneal metastasis and post-surgical adhesions. We present a robust method for the production of biodegradable liposome-loaded hydrogel microbeads that can overcome the pharmacokinetic limitations of small molecules with fast clearance rates, a current bottleneck for the intraperitoneal (IP) administration of these therapeutics. By means of an electromagnetic droplet printhead, we 3D printed microbeads employing an alginate-based ink loaded with GEF-containing multilamellar vesicles (MLVs). The sustained release of GEF from microbeads was demonstrated. In vitro studies on an immortalized human hepatic cancer cell line (Huh-7) proved concentration-dependent cell death. These findings demonstrate the potential of 3D-printed alginate microbeads containing liposomes for delivering small drug compounds into the peritoneum, overcoming previous limitations of IP drug delivery
Apnoeic oxygenation during paediatric tracheal intubation: a systematic review and meta-analysis
Get PDFAbstract
Background
Supplemental oxygen administration by apnoeic oxygenation during laryngoscopy for tracheal intubation is intended to prolong safe apnoea time, reduce the risk of hypoxaemia, and increase the success rate of first-attempt tracheal intubation under general anaesthesia. This systematic review examined the efficacy and effectiveness of apnoeic oxygenation during tracheal intubation in children.
Methods
This systematic review and meta-analysis included randomised controlled trials and non-randomised studies in paediatric patients requiring tracheal intubation, evaluating apnoeic oxygenation by any method compared with patients without apnoeic oxygenation. Searched databases were MEDLINE, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), Scopus, and Web of Science from inception to March 22, 2023. Data extraction and risk of bias assessment followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) recommendation.
Results
After initial selection of 40 708 articles, 15 studies summarising 9802 children were included (10 randomised controlled trials, four pre-post studies, one prospective observational study) published between 1988 and 2023. Eight randomised controlled trials were included for meta-analysis (n=1070 children; 803 from operating theatres, 267 from neonatal intensive care units). Apnoeic oxygenation increased intubation first-pass success with no physiological instability (risk ratio [RR] 1.27, 95% confidence interval [CI] 1.03–1.57, P=0.04, I2=0), higher oxygen saturation during intubation (mean difference 3.6%, 95% CI 0.8–6.5%, P=0.02, I2=63%), and decreased incidence of hypoxaemia (RR 0.24, 95% CI 0.17–0.33, P<0.01, I2=51%) compared with no supplementary oxygen administration.
Conclusion
This systematic review with meta-analysis confirms that apnoeic oxygenation during tracheal intubation of children significantly increases first-pass intubation success rate. Furthermore, apnoeic oxygenation enables stable physiological conditions by maintaining oxygen saturation within the normal range.
Clinical trial registration
Protocol registered prospectively on PROSPERO (registration number: CRD42022369000) on December 2, 2022
Effects of combustible cigarettes and electronic nicotine delivery systems on the development and progression of chronic lung inflammation in mice.
No full textINTRODUCTION
Although detrimental effects of combustible cigarettes (CCs) on the progression of lung inflammatory diseases are well known, changes in electronic nicotine delivery systems (ENDS)-exposed lung-infiltrated immune cells are still unrevealed.
METHODS
The analysis of blood gas parameters, descriptive and quantitative histology of lung tissues, determination of serum cytokines, intracellular staining and flow cytometry analysis of lung-infiltrated immune cells were used to determine the differences in the extent of lung injury and inflammation between mice from experimental (CC and ENDS-exposed animals) and control group (Air-exposed mice).
RESULTS
Continuous exposition to either CCs or ENDS induced severe systemic inflammatory response, increased activation of NLRP3 inflammasome in neutrophils and macrophages and enhanced dendritic cell-dependent activation of Th1 and Th17 cells in the lungs. ENDS induced less severe immune response than CCs. Serum concentrations of inflammatory cytokines were significantly lower in the samples of ENDS-exposed mice. Compared to CCs, ENDS recruited lower number of circulating leukocytes in injured lungs and had less capacity to induce CD14/TLR-2-dependent activation of NLRP3 inflammasome in lung-infiltrated neutrophils and macrophages. ENDS-primed dendritic cells had reduced capacity for the generation of Th1 and Th17 cell-driven lung inflammation. Accordingly, extensive immune cell-driven lung injury resulted in severe respiratory dysfunction in CCs-exposed mice, while ENDS caused moderate respiratory dysfunction in experimental animals.
CONCLUSIONS
Continuous exposition to either CCs or ENDS induced immune cell-driven lung damage in mice. ENDS triggered immune response which was less potent than inflammatory response elicited by CCs and, therefore, caused less severe lung injury and inflammation.
IMPLICATIONS
This is the first study that compared the effects of CCs and ENDS on lung-infiltrated immune cells. Although both CCs and ENDS elicited systemic inflammatory response, immune cell-driven lung injury and inflammation were less severe in ENDS-exposed than in CC-exposed animals. Continuous exposition to ENDS-sourced aerosols was less harmful for respiratory function of experimental animals than CC-derived smoke
Ten years of injectable platelet-rich fibrin.
Get PDFThe use of platelet-rich fibrin (PRF) has seen widespread advantages over platelet-rich plasma (PRP) in many fields of medicine. However, until 2014, PRF remained clinically available only in its solid clotted form. Modifications to centrifugation protocols and tube technology have led to the development of a liquid injectable version of PRF (i-PRF). This narrative review takes a look back at the technological developments made throughout the past decade and further elaborates on their future clinical applications. Topics covered include improvements in isolation techniques and protocols, ways to further concentrate i-PRF, and the clinical impact and relevance of cooling i-PRF. Next, various uses of i-PRF are discussed, including its use in regenerative periodontology, implantology, endodontics, temporomandibular joint injections, and orthodontic tooth movement. Furthermore, various indications in medicine are also covered, including its use in sports injuries and osteoarthritis of various joints, treatment of diabetic ulcers/wound care, and facial esthetics and hair regrowth. Finally, future applications are discussed, mainly its use as a drug delivery vehicle for small biomolecules, such as growth factors, antibiotics, exosomes, and other medications that may benefit from the controlled and gradual release of biomolecules over time
The Legal and Ethical Framework Governing Body Donation in Europe - 2nd update on Current Practice.
Get PDFBACKGROUND
In 2008, members of the TEPARG provided first insights into the legal and ethical framework governing body donation in Europe. In 2012, a first update followed. This paper is now the second update on this topic and tries to extend the available information to many mor European contries.
METHODS
For this second update, we have asked authors from all European countries to contribute their national perspectives. By this inquiry, we got many contributions compiled in this paper. When we did not get a personal contribution, one of us (EB) searched the internet for relevant information.
RESULTS
Perspectives on the legal and ethical framework governing body donation in Europe.
CONCLUSIONS
We still see that a clear and rigorous legal framework is still unavailable in several countries. We found national regulations in 18 out of 39 countries; two others have at least federal laws. Several countries accept not only donated bodies but also utilise unclaimed bodies. These findings can guide policymakers in reviewing and updating existing laws and regulations related to body donation and anatomical studies
Fetal Assessment in Pregnancy (Indication and Methodology for Fetal Monitoring in a low-risk Population). Guideline of the DGGG, DEGUM, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/089, February 2023).
No full textPURPOSE
The aim of this guideline was to find evidence on whether carrying out Doppler examinations and CTGs in low-risk cohorts of pregnant women improves outcomes.
METHODS
First, a systematic search for guidelines was carried out. Identified guidelines were evaluated using the DELPHI instrument of the AWMF. Three guidelines were found to be suitable to evaluate CTG. Two DEGUM best practice guidelines were judged suitable to describe the methods. All studies on this issue were additionally analyzed using 8 PICO questions. A structured consensus of the participating professional societies was achieved using a nominal group process and a structured consensus conference moderated by an independent moderator.
RECOMMENDATIONS
No antepartum Doppler sonography examinations should be carried out in low-risk cohorts in the context of antenatal care. No antepartum CTG should be carried out in low-risk cohorts. NOTE: The guideline will be published simultaneously in the official journals of both professional societies (i. e., Geburtshilfe und Frauenheilkunde for the DGGG and Ultraschall in der Medizin/European Journal of Ultrasound for the DEGUM)
Inflammation in acute myocardial infarction: the good, the bad and the ugly.
Get PDFConvergent experimental and clinical evidence have established the pathophysiological importance of pro-inflammatory pathways in coronary artery disease. Notably, the interest in treating inflammation in patients suffering acute myocardial infarction (AMI) is now expanding from its chronic aspects to the acute setting. Few large outcome trials have proven the benefits of anti-inflammatory therapies on cardiovascular outcomes by targeting the residual inflammatory risk (RIR), i.e. the smouldering ember of low-grade inflammation persisting in the late phase after AMI. However, these studies have also taught us about potential risks of anti-inflammatory therapy after AMI, particularly related to impaired host defence. Recently, numerous smaller-scale trials have addressed the concept of targeting a deleterious flare of excessive inflammation in the early phase after AMI. Targeting different pathways and implementing various treatment regimens, those trials have met with varied degrees of success. Promising results have come from those studies intervening early on the interleukin-1 and -6 pathways. Taking lessons from such past research may inform an optimized approach to target post-AMI inflammation, tailored to spare 'The Good' (repair and defence) while treating 'The Bad' (smouldering RIR) and capturing 'The Ugly' (flaming early burst of excess inflammation in the acute phase). Key constituents of such a strategy may read as follows: select patients with large pro-inflammatory burden (i.e. large AMI); initiate treatment early (e.g. ≤12 h post-AMI); implement a precisely targeted anti-inflammatory agent; follow through with a tapering treatment regimen. This approach warrants testing in rigorous clinical trials
Rhegmatogenous retinal detachment in choroidal melanoma: clinical features and surgical outcomes.
No full textPURPOSE
To describe the clinical features, prognostic factors, safety and rate of success of surgery and visual outcomes in patients with rhegmatogenous retinal detachment (RRD) and choroidal melanoma (CM).
METHODS
A retrospective, observational case-series of 21 patients with rhegmatogenous retinal detachment or combined tractional-rhegmatogenous retinal detachment in patients with choroidal melanoma over a period of 20 years.
RESULTS
Nineteen patients were included in the final analysis. The mean elevation of CM was 4.0 mm and the mean largest diameter was 11.0 mm. RRD occurred after the CM treatment in 14 eyes at a mean interval of 44.2 months. The RRD was macula-on RRD in 6 eyes, there was posterior vitreous detachment (PVD) in 15 and PVR in 7 eyes. BCVA at presentation was 0.71 logMAR and final was 1.5 logMAR (p = 0.01). The primary surgical success rate was 59%. No intraocular or extraocular tumour dissemination occurred. Mean follow-up was 66 months.
CONCLUSION
RRD in patients with CM is uncommon but requires multidisciplinary management. Anatomical results are favourable but visual outcomes are poor due to a combination of factors related to melanoma treatment, macular retinal detachment and PVR. Vitrectomy as a surgical intervention for RRD in treated CM appears to be safe in terms tumour dissemination
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