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Drugs in R&D Jul 2024Atorvastatin is a drug widely used to prevent cardiovascular and cerebrovascular diseases. Current observational studies suggest that atorvastatin may be associated with...
BACKGROUND AND OBJECTIVE
Atorvastatin is a drug widely used to prevent cardiovascular and cerebrovascular diseases. Current observational studies suggest that atorvastatin may be associated with cognitive dysfunction (especially memory loss). However, some studies have suggested that dyslipidemia may be an important factor in cognitive dysfunction. The purpose of this study was to perform a pharmacovigilance analysis using real-world data from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) to assess whether memory loss is an adverse effect of atorvastatin and to further clarify its causality through Mendelian randomization (MR).
METHODS
We extracted real-world data from the FAERS database (Quarter 1 2004 to Quarter 1 2023). Disproportionality analysis methods and measures of association such as the reporting odds ratio (OR), proportional reporting ratio, Bayesian confidence interval progressive neural network, and polynomial Gamma Poisson distribution reduction were used to assess whether memory loss was an adverse effect of atorvastatin. In addition, we used MR to evaluate causality in depth.
RESULTS
In the pharmacovigilance analysis of atorvastatin, we extracted four datasets of clinical symptoms associated with memory loss from the FAERS database [Amnesia (n = 1196), Memory impairment (n = 840), Transient global amnesia (n = 38), and Retrograde amnesia (n = 9)]. The reporting OR, proportional reporting ratio, Bayesian confidence interval progressive neural network, and Gamma Poisson distribution reduction all showed positive results for amnesia, transient global amnesia, and retrograde amnesia, while the reporting OR and Bayesian confidence interval progressive neural network also showed positive results for memory disorders. Thus, memory loss was a frequent side effect of atorvastatin. The MR analyses were used to further evaluate the association between statins and memory loss. The results of the MR analysis (statins and memory loss) are as follows: Ivw (mre) (β = 0.11 [OR = 1.11], P = 0.01 < 0.05) and the OR and β directions of MR-Egger and weighted mode were the same. The results of the MR analysis (statins and mitochondrial DNA copy number) are as follows: Ivw(mre) (β = -0.03 [OR = 0.96], P < 0.01) and the OR and β direction of MR-Egger and weighted mode are the same. The results of the MR analysis (DNA copy number and memory loss) are as follows: Ivw(β = - 0.06 [OR = 0.94], P = 0.04 < 0.05) and the OR and β direction of MR-Egger and weighted mode were the same. The pleiotropy test did not find horizontal diversity in our results.
CONCLUSIONS
This study suggests that memory loss is a notable adverse event associated with atorvastatin and provides evidence indicating a potential causal relationship between atorvastatin and memory loss. We also found that statins may further affect memory by affecting mitochondrial function. Therefore, in the clinical use of atorvastatin, it is important to carefully monitor the changes in cognitive function of patients. Second, a pharmacovigilance analysis combined with MR was used in this study to provide a new approach for the study of adverse drug reactions. This comprehensive analysis method helps to evaluate the safety of drugs and the risk of adverse reactions more comprehensively and provides doctors with a more accurate clinical decision-making basis.
PubMed: 38963511
DOI: 10.1007/s40268-024-00474-6 -
European Journal of Clinical... Jul 2024Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to... (Review)
Review
BACKGROUND AND OBJECTIVE
Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting.
METHODS
We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis.
RESULTS
A total of 74 studies with 23,119 participants were included. After 12 months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively.
CONCLUSION
The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.
PubMed: 38963453
DOI: 10.1007/s00228-024-03720-7 -
Journal of Neurology Jul 2024Pompe disease is caused by a rare biallelic mutation in the GAA gene resulting in acid α-glucosidase deficiency and glycogen accumulation.
INTRODUCTION
Pompe disease is caused by a rare biallelic mutation in the GAA gene resulting in acid α-glucosidase deficiency and glycogen accumulation.
AIM
We analyzed hospital admissions associated with the administration of Myozyme®, utilizing the French hospital discharge database, known in France as the Programme de Médicalisation des Systèmes d'Information (PMSI), which comprehensively captures all hospital activity within the country.
METHODS
In this observational study, we examined hospitalization records from April 4, 2012, to December 31, 2019, within the PMSI database, focusing on admissions where Myozyme® was administered. We particularly investigated the incidence of critical care admissions and adverse events (AEs) related to Myozyme®.
RESULTS
From 2012 to 2019, approximately 26,714 hospital stays involving Myozyme® administration were recorded for 239 patients. Most (96.6%) of these were outpatient stays, with only 3.2% in critical care. Furthermore, hospitalizations without critical care needs increased from 96% in 2012 to 99% in 2019. Of the patients receiving at least one infusion, 997 critical care admissions were recorded, with 781 (78.3%) occurring concurrent with or the day after the Myozyme® treatment without directly correlating to adverse effects of enzyme therapy.
CONCLUSIONS
The analysis of the French hospital discharge database indicated that Myozyme® was associated with a low incidence of AEs and complications in a hospital context, supporting the consideration of its safe use in home-infusion settings.
PubMed: 38963441
DOI: 10.1007/s00415-024-12543-6 -
The International Journal of... Jul 2024In recent years, exercise has been increasingly recognised as an effective and promising non-pharmacological intervention to improve physical function in patients with...
In recent years, exercise has been increasingly recognised as an effective and promising non-pharmacological intervention to improve physical function in patients with Parkinson's disease (PD). Cardiorespiratory fitness (CRF) is an objective measure of a person's ability to perform aerobic exercise. Therefore, it is necessary to evaluate the CRF of patients with PD.However, the CRF of Chinese patients with PD is deficient.This study is to evaluate cardiorespiratory fitness in patients with early to mid-stage PD by cardiopulmonary exercise test(CPET) on a stationary cycle ergometer; :To compare the differences in each index of the CPET between the two groups of subjects; general data such as disease duration, medication use and exercise habits were also collected.:1)Finally, 36 PD patients and 12 healthy controls successfully completed the CPET without any adverse events.2)The V'Opeak, Metspeak, RERpeak, MVVpeak, Wpeak, HRpeak, HRpeak/pre,percentage of HRR-1 min decay > 12 bpm,SBPpeak in the PD group were lower than those in the control group(p < 0.05,each). Detailed data:V'O2peak(15.7 ± 4.5vs21.5 ± 3.6ml/kg/min,p < 0.01),Metspeak(4.5 ± 1.3 vs 6.1 ± 1.0,p < 0.01),RERpeak(1.04 ± 0.10 vs 1.15 ± 0.10,p = 0.001),MVVpeak(37.22 ± 11.58 vs 53.00 ± 16.85L/min,p = 0.009),Wpeak(49.17 ± 29.72vs49.17 ± 29.72W,p < 0.01),HRpeak(111.08 ± 16.67 vs111.08 ± 16.67bpm,p < 0.01),HRpeak/pre(71.19 ± 10.06 vs96.00 ± 21.13,p = 0.002),percentage of HRR-1min decay > 12bpm(33.3% vs 100%,p < 0.01),SBP(155.81 ± 31.83 vs 175.83 ± 17.84mmHg,p = 0.01).3)Divided PD patients into high V'Opeak group(V'Opeak ≥ 15 mL/kg/min) and low V'Opeak group(V'Opeak < 15 mL/kg/min). The age of patients, Hoehn-Yahr grade and incidence of symptom fluctuation in high V'Opeak group were lower(p < 0.05,respectively),percentage of males and percentage of HRR-1 min decay > 12 bpm were higher(p < 0.05,respectively);p < 0.05 is considered a statistically significant difference.Detailed data:age of patients(61.05 ± 6.93vs68.57 ± 7.99years,p = 0.005),Hoehn-Yahr grade(1.75 ± 0.48 vs 2.18 ± 0.64,p = 0.028),incidence of symptom fluctuation(59.1 vs 92.9%,p = 0.03),percentage of males(77.7 vs 42.9%,p = 0.041),percentage of HRR-1 min decay > 12 bpm(50 vs 7.1%,p = 0.008). :CPET were safe to perform and the cardiorespiratory fitness is significantly reduced in patients with early and middle stage Parkinson's disease.Patients with PD presented blunted HR and SBP responses to exercise test. Females, older age, fluctuating symptoms, high H-Y staging, and higher ADL may be associated with lower oxygen uptake.
PubMed: 38963402
DOI: 10.1080/00207454.2024.2377140 -
Dermatitis : Contact, Atopic,... Jul 2024Herbal medicine is widely used for dermatological diseases, particularly atopic dermatitis. This study aims to systematically review existing literature on the efficacy... (Review)
Review
Herbal medicine is widely used for dermatological diseases, particularly atopic dermatitis. This study aims to systematically review existing literature on the efficacy of both topical and systemic herbal interventions for atopic dermatitis across various age groups. Conducting a comprehensive search on MEDLINE/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (Central) until April 12, 2023, only randomized controlled trials (RCTs) were included. The review is reported following the PRISMA guidelines and was conducted in accordance to Cochrane recommendations. Two authors independently extracted details, including demographics, medication, control/placebo groups, outcomes, adverse events, and results, with quality assessment using the Cochrane risk of bias tool 2.0. A meta-analysis, utilizing the random-effects model, was conducted, and publication bias was assessed through funnel plot inspection. The quality of evidence adhered to GRADE working group recommendations. The primary focus was evaluating atopic dermatitis or pruritus severity. The review encompassed 51 RCTs (3763 participants). Of these, 31 RCTs explored 19 distinct herbs and five complex remedies, whereas 20 RCTs (1088 participants) specifically investigated evening primrose oil (EPO). Herbs such as sunflower, licorice, figs, coconut, EPO, indigo naturalis, licorice, mauve, St. John's wort, and a combination of aloe vera and olive oil were found to have evidence of efficacy in the local treatment of atopic dermatitis. A meta-analysis on systemic used EPO, involving 13 RCTs, found no significant difference in atopic dermatitis severity compared with placebo (SMD: 0.14; 95% CI [-0.45; 0.73], 13 RCTs). In conclusion, this review provides a nuanced perspective on herbal substance efficacy for atopic dermatitis. While the EPO meta-analysis failed to show a discernible benefit beyond placebo, individual herbal preparations showed promising results in RCTs included in this review. Nevertheless, larger, methodologically rigorous studies are essential to establish evidence for herbal remedies in atopic dermatitis treatment.
PubMed: 38963342
DOI: 10.1089/derm.2024.0132 -
Journal of Cellular and Molecular... Jul 2024Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of... (Review)
Review
Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)-based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab-based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune-related adverse event (irAE) associated with Ab-based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life-threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro-inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab-based novel cancer immunotherapeutics, namely immune checkpoint (IC)-targeting Abs, bispecific Abs (BsAbs) and Ab-drug-conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab-based biotherapeutics as an approach to support and refine clinical translation.
Topics: Humans; Neoplasms; Antibodies, Bispecific; Immunotherapy; Animals; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
PubMed: 38963257
DOI: 10.1111/jcmm.18470 -
The Cochrane Database of Systematic... Jul 2024An inguinal hernia occurs when part of the intestine protrudes through the abdominal muscles. In adults, this common condition is much more likely in men than in women.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An inguinal hernia occurs when part of the intestine protrudes through the abdominal muscles. In adults, this common condition is much more likely in men than in women. Inguinal hernia can be monitored by 'watchful waiting', but if symptoms persist or worsen, surgery is usually required, which can be open or laparoscopic. Laparoscopic (keyhole) repair of inguinal hernias in adults is generally performed using either the transabdominal preperitoneal (TAPP) or the totally extraperitoneal (TEP) method. Both methods include the use of mesh placed in front of the peritoneal lining of the abdominal wall, but for the TAPP technique, the abdominal cavity needs to be entered to place the mesh, and for the TEP technique, the whole procedure is done on the outside of the peritoneal lining of the abdominall wall. Whether one method is superior to the other has not been established, and there is debate about their relative benefits and harms. An advantage of TEP is its avoidance of the abdominal cavity; the downside is that it requires a steeper learning curve for clinicians. TAPP is considered simpler and makes it possible to inspect the contralateral side, but TAPP may have a higher risk of visceral injury compared to TEP. This is an update of a Cochrane review first published in 2005.
OBJECTIVES
To compare the benefits and harms of laparoscopic TAPP technique versus laparoscopic TEP technique for inguinal hernia repair in adults.
SEARCH METHODS
On 25 October 2022, the authors searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); and Ovid Embase, for published randomised controlled trials. To identify studies in progress, we searched ClinicalTrials.gov and the WHO International Clinical Trial Registry Platform (ICTRP).
SELECTION CRITERIA
All prospective randomised, quasi-randomised, and cluster-randomised trials that compared the laparoscopic TAPP technique with the laparoscopic TEP technique for inguinal hernia repair in adults were eligible for inclusion. We included studies that involved a mix of different types of groin hernia if we could extract data for the inguinal hernias. Studies may have also included a group of participants receiving hernia repair by open surgery, but these groups were not included in our review.
DATA COLLECTION AND ANALYSIS
Both review authors independently evaluated trial eligibility, extracted data from included studies, and assessed the risk of bias in the included studies. The review's primary outcomes were serious adverse events, chronic pain (persisting for at least six months after surgery), and hernia recurrence. We also assessed a variety of secondary outcomes at perioperative, early postoperative, and late postoperative time points. We performed statistical analyses using the random-effects model, and expressed the results as odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with their respective 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for key outcomes as high, moderate, low or very low.
MAIN RESULTS
We included 23 studies in this review update, which randomised 1156 people to TAPP and 1110 people to TEP, all requiring repair of inguinal hernias. Study sample sizes varied from 40 to 316 participants. The vast majority of study participants were male. We judged most studies to be at 'high' or 'unclear' risk of bias. Our judgements of the certainty of the evidence were low or very low for all outcomes we assessed. There may be little to no difference between TAPP and TEP laparoscopic techniques for serious adverse events (0.4% versus 0.7%; OR 0.58, 95% CI 0.15 to 2.32, P = 0.45, I = 0%; 19 studies, 1735 participants; low certainty of evidence); and hernia recurrence (1.2% versus 1.1%; OR 1.14, 95% CI 0.49 to 2.62, P = 0.97, I = 0%; 17 studies, 1712 participants; low certainty of evidence). The evidence is very uncertain about the effects of TAPP versus TEP techniques on chronic pain (OR 0.62, 95% CI 0.20 to 1.97, P = 0.68, I = 0%; 6 studies, 860 participants; very low certainty of evidence). In terms of secondary outcomes, the evidence is very uncertain for TAPP versus TEP techniques for perioperative visceral and vascular injury (15 studies, 1523 participants; very low certainty of evidence), and for haematoma or seroma during the early (≤ 30 days) postoperative phase (OR 0.86, 95% CI 0.54 to 1.37, P = 0.3861, I = 0%; 15 studies, 1423 participants; very low certainty of evidence). TEP technique may carry a higher risk of conversion to another hernia repair method (either TAPP technique or open surgery) when compared to TAPP (2.5% versus 0.7%; OR 0.28, 95% CI 0.09 to 0.84, P = 0.02, I = 0%; 13 studies, 1178 participants; low certainty of evidence). Only two studies (474 participants) reported quality of life in the late (> 30 days) postoperative phase; overall, there was an improvement in quality of life from the pre- to post-operative assessment, but the evidence suggests little to no difference between the techniques (low certainty of evidence).
AUTHORS' CONCLUSIONS
This review update found that there may be little to no difference between the TAPP and TEP techniques for serious adverse events, hernia recurrence, or chronic pain (low- to very-low-certainty evidence). Decisions about which method to use will most likely reflect surgeon and patient preference until high-certainty evidence becomes available. There may be a higher risk of needing to convert from TEP to TAPP or open surgery when compared to the risk of needing to convert from TAPP to open surgery (low-certainty evidence). If surgeons opt for TEP as their standard laparoscopic method, they could consider having a strategy for how to handle the potential need for conversion. This might include proficiency in the TAPP approach or having informed the patient about the risk of conversion to open surgery. For surgeons or surgical departments, the choice of a laparoscopic technique should involve shared decision-making with patients and their families or carers. Future research could focus on patient-reported outcomes, such as quality of life.
Topics: Humans; Hernia, Inguinal; Laparoscopy; Randomized Controlled Trials as Topic; Surgical Mesh; Male; Adult; Female; Herniorrhaphy; Operative Time; Peritoneum
PubMed: 38963034
DOI: 10.1002/14651858.CD004703.pub3 -
Epilepsia Open Jul 2024Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic... (Review)
Review
Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥2 years old and as add-on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early-line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4-29 years old in whom up to 14 ASMs had previously failed, to illustrate real-world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug-drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well-tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS. PLAIN LANGUAGE SUMMARY: Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox-Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors' everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine.
PubMed: 38962968
DOI: 10.1002/epi4.12998 -
Scandinavian Cardiovascular Journal :... Dec 2024. Temporary mechanical circulatory support (TMCS) has become a component in the therapeutic strategy for treatment of cardiogenic shock as a bridge-to-decision. TMCS can... (Comparative Study)
Comparative Study
. Temporary mechanical circulatory support (TMCS) has become a component in the therapeutic strategy for treatment of cardiogenic shock as a bridge-to-decision. TMCS can facilitate recovery of cardiopulmonary function, end-organ function, and potentially reduce the surgical risk of left ventricular assist device (LVAD) implantation. Despite the improvements of hemodynamics and end-organ function, post-LVAD operative morbidity might be increased in these high-risk patients. The aim of the study was to compare outcomes after Heartmate 3 (HM3) implantation in patients with and without TMCS prior to HM3 implant. In this retrospective cohort study of all HM3 patients in the period between November 2015 and October 2021, patients with and without prior TMCS were compared. Patients' demographics, baseline clinical characteristics, laboratory tests, intraoperative variables, postoperative outcomes, and adverse events were collected from patient records. The TMCS group showed an improvement in hemodynamics prior to LVAD implantation. Median TMCS duration was 19.5 (14-26) days. However, the TMCS group were more coagulopathic, had more wound infections, neurological complications, and more patients were on dialysis compared with patient without TMCS prior to HM3 implantation. Survival four years after HM3 implantation was 80 and 82% in the TMCS ( = 22) and non-TMCS group ( = 41), respectively. . Patients on TMCS had an acceptable short and long-term survival and comparable to patients receiving HM3 without prior TMCS. However, they had a more complicated postoperative course.
Topics: Humans; Heart-Assist Devices; Retrospective Studies; Male; Female; Middle Aged; Time Factors; Treatment Outcome; Hemodynamics; Shock, Cardiogenic; Risk Factors; Ventricular Function, Left; Adult; Recovery of Function; Heart Failure; Aged; Prosthesis Implantation; Risk Assessment; Prosthesis Design
PubMed: 38962929
DOI: 10.1080/14017431.2024.2353066 -
Advanced Science (Weinheim,... Jul 2024Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective...
Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.
PubMed: 38962911
DOI: 10.1002/advs.202402473