Enhanced antimicrobial efficacy of chlorhexidine-encapsulated halloysite nanotubes incorporated in presurgical orthopedic appliances: an in vitro, controlled study.

AIMS AND OBJECTIVE: Presurgical infant's orthopedic appliances (PSIOs) play an increasingly crucial role in the interdisciplinary management of neonatal CLP, aiming to improve and maintain adequate nasolabial aesthetics, followed by primary lip/nasal surgery in both unilateral and bilateral CLP cases. The use of PSIOs in cleft lip and palate patients can lead to contamination with oral microflora, acting as a potential reservoir for infectious microorganisms. Acrylic surfaces might provide retention niches for microorganisms to adhere, and inhabit, which is difficult to control in immunocompromised patients, thus predisposing them to increased infection risks. The objective of this multi-assay in vitro study was to investigate the effects of incorporating chlorhexidine-loaded halloysite nanotubes (CHX-HNTs) fillers on the morphological, cytotoxic, release, and antimicrobial characteristics of self-cured acrylic polymethyl methacrylate (PMMA) material used in pre-surgical orthopedic appliances. METHODS: Disk-shaped PMMA specimens were prepared with varying proportions of CHX-HNTs. A control group without any addition served as a reference, and four experimental samples contained a range of different concentrations of CHX-HNTs (1.0, 1.5, 3, and 4.5 wt%). The antimicrobial efficacy was assessed using an agar diffusion test against common reference microorganisms: Candida albicans, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus agalactiae. Cytotoxicity was examined using the L929 cell line (mouse fibroblasts) through a (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, MTT) cell viability assay. The release kinetics of CHX were monitored using UV-spectral measurements. The statistical analysis used a one-way ANOVA followed by Tukey's post hoc test. RESULTS: The integration of CHX-HNTs in PMMA exhibited a substantial dose-dependent antifungal and antibacterial effect against microorganisms at tested mass fractions (1.0 to 4.5 wt%). CHX release was sustained for up to 60 days, supporting prolonged antimicrobial activity. Furthermore, no significant cytotoxicity was determined in the L929 fibroblast cell line (control), indicating the biocompatibility of the CHX-HNTs-enhanced PMMA. CONCLUSION: Incorporating CHX-HNTs in PMMA successfully enhanced its antimicrobial properties, providing sustained CHX release and superior antimicrobial efficacy. These findings demonstrate the potential of antimicrobial nanoparticles in dental therapies to improve therapeutic outcomes. However, rigorous further clinical trials and observational studies are warranted to validate the practical application, safety, and efficacy. CLINICAL RELEVANCE: This study has the potential to make a major impact on the health of infants born with cleft lip and palate by helping to reduce the prevalence of infectious illnesses. The incorporation of CHX-HNTs into PMMA-based appliances is a novel promising preventive approach to reduce microbial infections.

Oral side effects of COVID-19 vaccines in 32 European countries: Analysis of EudraVigilance reports.

The recent reports of oral side effects (SEs) following COVID-19 vaccination warrant further investigation into their prevalence, severity, and aetiology. This study was conducted to synthesize the first-ever population-level evidence about oral SEs of COVID-19 vaccines in Europe. The European Union Drug Regulating Authorities Pharmacovigilance (EudraVigilance) database was accessed in August 2022 to extract summary data of all potential oral SEs reported after COVID-19 vaccination. The data were reported descriptively and cross-tabulated to facilitate sub-group analysis per vaccine type, sex, and age group. Dysgeusia was the most commonly reported oral SE (0.381 case per each 100 received reports), followed by oral paraesthesia (0.315%), ageusia (0.296%), lip swelling (0.243%), dry mouth (0.215%), oral hypoaesthesia (0.210%), swollen tongue (0.207%), and taste disorder (0.173%). Females had significantly (Sig. < 0.001) a higher prevalence of all most common (top 20) oral SEs, except for salivary hypersecretion, which was equally prevalent among females and males. The present study revealed a low prevalence of oral SEs, with taste-related, other sensory and anaphylactic SEs being the most common SEs in Europe, similar to what was found earlier among the US population. Future studies should explore the potential risk factors of oral sensory and anaphylactic SEs to verify whether they are causally linked to COVID-19 vaccines.

Is Periodontitis Associated with Age-Related Cognitive Impairment? The Systematic Review, Confounders Assessment and Meta-Analysis of Clinical Studies.

It has been suggested that molecular pathological mechanisms responsible for periodontitis can be linked with biochemical alterations in neurodegenerative disorders. Hypothetically, chronic systemic inflammation as a response to periodontitis plays a role in the etiology of cognitive impairment. This study aimed to determine whether periodontitis (PDS) is a risk factor for age-related cognitive impairment (ACI) based on evidence of clinical studies. A comprehensive, structured systematic review of existing data adhering to the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) guidelines was carried out. Five electronic databases, PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched for key terms published in peer-reviewed journals until January 2021. The Newcastle-Ottawa scale was used to assess the quality of studies and risk of bias. The primary and residual confounders were explored and evaluated. A meta-analysis synthesizing quantitative data was carried out using a random-effects model. Seventeen clinical studies were identified, including 14 cohort, one cross-sectional, and two case-control studies. Study samples ranged from 85 to 262,349 subjects, with follow-up between 2 and 32 years, and age above 45 years, except for two studies. The findings of studies suggesting the PDS-ACI relationship revealed substantial differences in design and methods. A noticeable variation related to the treatment of confounders was observed. Quality assessment unveiled a moderate quality of evidence and risk of bias. The subgroups meta-analysis and pooled sensitivity analysis of results from seven eligible studies demonstrated overall that the presence of PDS is associated with an increased risk of incidence of cognitive impairment (OR = 1.36, 95% CI 1.03-1.79), particularly dementia (OR = 1.39, 95% CI 1.02-1.88) and Alzheimer's disease (OR = 1.03 95% CI 0.98-1.07)). However, a considerable heterogeneity of synthesized data (I2 = 96%) and potential publication bias might affect obtained results. While there is a moderate statistical association between periodontitis and dementia, as well as Alzheimer's disease, the risk of bias in the evidence prevents conclusions being drawn about the role of periodontitis as a risk factor for age-related cognitive impairment.

The impact of coronavirus infectious disease 19 (COVID-19) on oral health.

Health services across the world face an unprecedented situation as a result of a global COVID-19 outbreak. Urgent joined research efforts regarding the SARS-COV-2 rapid tests, accurate diagnosis, especially early recognition, and effective treatment of life-threatening complications would be highly desirable for humanity and medical workforce all over the world that try to combat a current global pandemic threat. Due to indirect complex effect, intensified COVID-19 therapies and multi-drug treatment, it is believed that some oral conditions could be aggravated by COVID-19 disease, particularly those with autoimmune aetiology, linked to compromised immune system or long-term pharmacotherapy.

Atypical oral candidiasis in a psoriatic patient during targeted immunotherapy with an interleukin 17 inhibitor (secukinumab).

BACKGROUND: Secukinumab is a human monoclonal antibody immunoglobulin that neutralises interleukin (IL)-17A, and as such, is effective in the treatment of psoriasis. However, as IL-17A is essential in protection against fungal infections, patients treated with this drug may develop candidiasis. This report presents a case of atypical oral candidiasis occurring during targeted drug immunotherapy with an interleukin 17 (IL-17) inhibitor (secukinumab), with the aim of emphasisinge the necessity of periodical oral health assessment and monitoring. It provides a rational clinical approach to therapeutic protocol in the treatment of side effects associated with novel medications for autoimmune diseases. CASE PRESENTATION: Symptomatic tongue lesions were observed in a 50-year-old female patient on a monthly systemic treatment of 300 mg of secukinumab, which appeared after 60 days of using the medication. Two inconclusive biopsies and an unsuccessful application of oral corticosteroids made the diagnostic process challenging. Papillae on the back of the tongue were atrophied, forming a well-defined erythema and white non-detachable plaques on the lateral border of the tongue. Cytopathological and histopathological exam results were compatible with a diagnosis of oral candidiasis. Topical antifungal medication led to subsequent regression of the tongue lesions. During asymptomatic period and follow up for 7 months, a reduced monthly dose 150 mg of secukinumab was administered. CONCLUSIONS: Patients undergoing treatment with IL-17 blockers, such as secukinumab, should be carefully monitored in order to avoid oral side effects resulting from the use of this medication.

Dental Care Provision during Coronavirus Disease 2019 (COVID-19) Pandemic: The Importance of Continuous Support for Vulnerable Patients.

As a result of the ongoing 2019 coronavirus disease (COVID-19) pandemic, the medical and dental services across the world have to tackle unprecedented situations, providing essential care and professional support. The global health care crisis caused directly by the vast number of severe COVID-19 cases, and indirectly by reduced access to health care, as well as by limited secondary care provision, had a major impact on specialist services, and subsequently the deterioration of medical and dental conditions, particularly in vulnerable persons. In particular, at present, special care dentistry seems to play a unique role, dealing with a wide range of patients with underlying medical conditions and co-morbidities, phobic individuals, and persons with learning/physical disabilities. The effective adaptation of health services to the current new reality, based on an empathetic approach and recent guidelines, would allow us to maintain an adequate care provision, minimizing the long-term impact of the pandemic.

Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells.

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-ß-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 µM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 µM and 50 µM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.

The Role of General Anaesthesia in Special Care & Paediatric Dentistry; Inclusion Criteria and Clinical Indications.

Dental practitioners dealing with children and individuals with special needs can be supported by the provision of general anaesthesia for the most challenging patients in situations where other options are insufficient. The availability of general anaesthesia will further the aim of extending access to the widest range of dental care to the greatest number of patients regardless of disability, age or phobia. The objective is to ensure patients have a pain-free and healthy mouth, and any necessary treatment in the most appropriate setting related to their specific needs. A strictly individual and holistic approach is required when evaluating the risk versus benefit of proceeding with general anaesthesia for delivery of dental treatment particularly for children and special needs individuals. It is vitally important to consider and address all relevant factors specific to this particular group of patients including assessment of capacity, validity of consent, and any specific medical, social and behavioural issues. The other sedation modalities must be always taken into consideration. This article emphasises the crucial decision-making role of dentists in the referral process for dental treatment under general anaesthesia and the need for multidisciplinary co-operation between dental practitioners, community and hospital services.

Is Propofol Safe For Food Allergy Patients? A Review of the Evidence.

Allergic cross-reactivity between propofol and food is frequently considered as a risk factor for perioperative allergic hypersensitivity reactions and anaphylaxis during dental anaesthesia and sedation. Better understanding of of this cross-reactivity is important to providing safe care. There are, however, conflicting assumptions about anaphylactic reactions to propofol in patients reporting allergy to certain type of the food. Egg and/or soya allergy are often cited as contraindications to propofol administration but the evidence remains unclear. The main goal of this article is to review the available advice and evidence about the cross-reactivity between propofol and foods. A literature search was undertaken. The current published evidence does not elucidate that propofol allergy and food allergies are linked directly, but this drug should be used with caution in atopic patients with allergies to egg and/or soya bean oil. Clinical audit projects may gather data on anaphylactic events during anaesthesia and may aid the profession in this dilemma.

Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine.

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle's medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 µg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 µg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50) after 48 h was estimated at 5.19 µg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs.

Catechin Hydrate Augments the Antibacterial Action of Selected Antibiotics against Staphylococcus aureus Clinical Strains.

Synergistic effects between commonly used antibiotics and natural substances may be an alternative to conventional antibacterial therapies. The objective of the presented study was to assess the in vitro antibacterial activity of catechin hydrate (CH) and evaluate the interactions of CH with selected antibiotics using Staphylococcus aureus clinical and reference strains. CH displayed diverse activity towards examined S. aureus strains, with minimal inhibitory concentrations (MICs) ranging from 256 to 2048 µg/mL. The interaction between CH and antibiotics was assessed by an E-test. The most significant synergistic effects were noticed for CH in combination with clindamycin and erythromycin. For cefoxitin and vancomycin a decrease of MIC values in the presence of CH was also observed, but it did not reach statistical significance. The obtained results demonstrate that CH shows antimicrobial activity against Staphylococcus aureus clinical strains. What is more, we proved a synergistic effect of CH with erythromycin and clindamycin.

Inhibition of Oral Streptococci Growth Induced by the Complementary Action of Berberine Chloride and Antibacterial Compounds.

Synergistic interactions between natural bioactive compounds from medicinal plants and antibiotics may exhibit therapeutic benefits, acting against oral cariogenic and opportunistic pathogens. The aim of the presented work was to assess the antibacterial activity of berberine chloride (BECl) in light of the effect exerted by common antibiotics on selected reference strains of oral streptococci (OST), and to evaluate the magnitude of interactions. Three representative oral microorganisms were investigated: Streptococcus mutans ATCC 25175 (SM), S. sanguinis ATCC 10556 (SS), S. oralis ATCC 9811 (SO) and microdilution tests, along with disc diffusion assays were applied. Here, we report that growth (viability) of all oral streptococci was reduced by exposure to BECl and was dependent primarily on exposure/ incubation time. A minimum inhibitory concentrations (MIC) of BECl against OST ranged from 512 µg/mL (SS) to 1024 µg/mL (SM, SO). The most noticeable antibacterial effects were observed for S. sanguinis (MIC 512 µg/mL) and the most significant synergistic action was found for the combinations BECl-penicillin, BECl-clindamycin and BECl-erythromycin. The S. oralis reflects the highest MBC value as assessed by the AlamarBlue assay (2058 µg/mL). The synergy between berberine and common antibiotics demonstrates its potential use as a novel antibacterial tool for opportunistic infections and also provides a rational basis for the use of berberine as an oral hygiene measure.

Caffeic Acid phenethyl ester and ethanol extract of propolis induce the complementary cytotoxic effect on triple-negative breast cancer cell lines.

Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells' susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL-1 for MDA-MB-23 cells and 33.68 µg∙mL-1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

Caffeic acid reduces the viability and migration rate of oral carcinoma cells (SCC-25) exposed to low concentrations of ethanol.

Alcohol increases the risk of carcinoma originated from oral epithelium, but the biological effects of ultra-low doses of ethanol on existing carcinoma cells in combination with natural substances are still unclear. A role for ethanol (EtOH), taken in small amounts as an ingredient of some beverages or mouthwashes to change the growth behavior of established squamous cell carcinoma, has still not been examined sufficiently. We designed an in vitro study to determine the effect of caffeic acid (CFA) on viability and migration ability of malignant oral epithelial keratinocytes, exposed to ultra-low concentrations (maximum 100 mmol/L) EtOH. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide) and LDH (lactate dehydrogenase) assays were used to assess the cytotoxic effect of EtOH/CFA and the viability of squamous carcinoma SCC-25 cells (ATCC CRL-1628, mobile part of the tongue). Tested EtOH concentrations were: 2.5, 5, 10, 25, 50, and 100 mmol/L, along with an equal CFA concentration of 50 µmol/L. Carcinoma cells' migration was investigated by monolayer "wound" healing assay. We demonstrated that very low concentrations of EtOH ranging between 2.5 and 10 mmol/L may induce the viability of oral squamous cell carcinoma cells, while the results following addition of CFA reveal an antagonistic effect, attenuating pro-proliferative EtOH activity. The migration rate of oral squamous carcinoma cells can be significantly inhibited by the biological activity of caffeic acid.

Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro.

Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

The accuracy and retention of presurgical infant orthopaedics constructed from different polymer materials: A comparative study.

Objectives: This laboratory-based study aimed to evaluate and compare the accuracy and retention of moulding plates when used as pre-surgical orthopaedic appliances (PSIOs) for infants with cleft lip and/or palate (CL/P). Methods: Ten moulding plates were fabricated from three different materials (total sample size: 30), including polymethyl methacrylate (PMMA), a hard clear aligner (PET-G polymer), and a dual-layered hard and soft clear aligner (mixed PET-G/EVA) on ten three-dimensional (3D) printed working models. Accuracy was evaluated by measuring the virtual gap between the data acquired from the moulding plate and the working model after the optical scanning at each of the designated 36 points for each plate. Exocad software was used to facilitate all virtual alignments and measurements. Retention was measured using a digital gauge that quantified the traction force required to separate the plates from the retention test cast (a soft resin printed cast). Results: PET-G plates exhibited the best fit with the working cast, with overall adaptations of 0.146 ± 0.012 for PET-G, 0.250 ± 0.073 for PET-G/EVA, and 0.294 ± 0.113 for PMMA. For region-specific misfit, PET-G plates exhibited superior accuracy across all regions, with mean discrepancies of 0.16 ± 0.08 mm, 0.15 ± 0.061 mm, and 0.12 ± 0.128 mm in the anterior, middle, and posterior regions, respectively. Retention for PET-G was significantly higher than the other materials, with a mean of 3.34 N ± 0.487, as opposed to 1.65 N ± 0.331for PMMA and 1.27 N ± 0.239 for PET-G/EVA (P < 0.05). Conclusions: Moulding plates constructed from PET-G exhibited a better fit and higher retention than those made from PET-G/EVA and PMMA. Clinical significance: Collectively, our findings suggest that the selection of PET-G for PSIO appliances could have clinical significance by potentially improving treatment outcomes in infants with CL/P.

Caregivers' Experience with Lip Taping as a Presurgical Orthopedic Treatment for Cleft Lip and Palate Defects.

BACKGROUND: This study aimed to assess caregivers' experiences and perceptions of applying lip taping as presurgical orthopedic therapy (PSO) for infants with a cleft lip and palate. METHODS: A retrospective survey was conducted, inviting parents to respond to a series of structured questions between September 2022 and June 2023. The questionnaire focused on evaluating parents' experience with lip taping, a crucial component of PSO. Descriptive statistics and the Chi-square test were employed to analyze relationships between categorical variables. RESULTS: Of the 157 participants, overall, 122 completed the survey, forming the dataset for analysis. A majority (90.0%) reported sufficient experience in using lip taping and no major difficulties with lip taping application. Caregivers with higher education levels exhibited a significantly positive correlation (p = 0.015). Additionally, 93.4% confirmed the efficacy of lip taping for premaxillary segment retraction, with this outcome being correlated with caregivers' knowledge and education (p = 0.008). Interestingly, caregivers' age also demonstrated a substantial association (p = 0.020). CONCLUSIONS: While a vast majority expressed positive experiences with lip taping as a presurgical treatment, continuous, tailored education on cleft lip and palate is imperative. This education should be directed towards caregivers and individuals offering direct support to parents of children with CLP, ensuring optimal care and preparation for surgical treatment.

Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: An umbrella review of systematic reviews.

BACKGROUND: Stem cell therapy (SCT) has emerged as a potential therapeutic avenue, with various cell types being explored for their efficacy in treating DCM. However, the safety and efficacy of these therapies have been the subject of numerous systematic reviews. This umbrella review aims to consolidate the existing evidence on stem cell interventions for DCM, providing a comprehensive overview of the current research landscape. METHODS: This review was conducted following the JBI and PRISMA guidelines. Systematic reviews and meta-analyses of randomized controlled trials (RCTs) evaluating the safety and efficacy of SCT for DCM were included. Outcomes such as 6MWT, LVEDD, LVEF, MACE, NYHA, and QoL, among others, were considered. A literature search was executed across databases like PubMed, Embase, Web of Science, and Cochrane Database up to October 07, 2023. The quality of the included reviews was assessed using the JBI Checklist for Systematic Reviews and Research Syntheses. Data synthesis was carried out in both narrative and tabular formats, with the GRADE criteria guiding the determination of evidence certainty. RESULTS: Nine systematic reviews met the inclusion criteria. LVEF found to be significantly improved with SCT. LVEDD and LVEDV assessments yielded mixed results, with some reviews observing significant changes. LVESV showed consistent reductions across multiple studies. BNP concentrations post-interventions were explored in several studies, with mixed findings. Health-related quality of life (HRQL) showed varied results, with some studies noting improvements and others finding no significant differences. NYHA classifications and 6-MWT results indicated potential benefits from stem cell treatments. SCT was observed to be generally safe. The certainty of evidence was low or very low for most of outcomes. CONCLUSION: SCT showed has shown promise in treating DCM, with many studies highlighting its safety and potential benefits. Nonetheless, the existing data has its limitations due to biases in the RCTs studies. To truly establish the benefits of SCT for DCM, future high quality RCTS, are crucial.