Eradication Of Infection Research Articles

Different regimens for eradication of Helicobacter pylori infection in children: a randomized controlled trial.

As an empirical treatment for children with H. pylori infection, CTT is safe and provides the highest eradication rate. HT, ST, and CT might not be superior to TT. This study was registered at the Pan African Clinical Trials Registry, Cochrane South Africa, under the identifier PACTR202201686010590. Date of registration: 04 January 2022. • Triple therapy has been the standard eradication regimen for pediatric H. pylori infection. The efficacy of triple therapy has decreased in many countries due to increased antibiotic resistance. • This randomized controlled trial is the first to compare triple therapy, sequential therapy, hybrid therapy, concomitant therapy, and ciprofloxacin-based triple therapy for the eradication of pediatric H. pylori infection. Triple therapy exhibited the lowest eradication rate among the studied regimens, suggesting it may not be an adequate therapeutic option for infected children. Ciprofloxacin-based triple therapy appears to be a safe and effective therapeutic choice for pediatric H. pylori infection. Additionally, this study provides the first reported eradication rate of hybrid therapy in pediatric H. pylori infection.

Nucleus-Targeting Photosensitizers Enhance Neutrophil Extracellular Traps for Efficient Eradication of Multidrug-Resistant Bacterial Infections.

Neutrophil extracellular traps (NETs) are web-like complexes of DNA and proteins that are extruded by activated neutrophils and play critical roles as major components of the innate immune response against pathogen invasion. However, some microbes have developed strategies to evade NET attacks, leading to impaired immune defenses and persistent infections. In this study, an engineered neutrophil strategy for enhancing the antibacterial activity of NETs is developed. A nucleus-targeting photosensitizer (NCP) with strong reactive oxygen species production and a strong DNA-binding capacity is synthesized. NCP-loaded neutrophils are subsequently constructed via direct incubation of NCP with neutrophils, and the NCP is closely inserted into the nucleus DNA. Upon activation by bacteria-related toxins, NCP-coupled NETs can be released rapidly, actively trapping bacteria and providing a high local concentration of NCP around them. Both in vitro and in vivo results revealed that NCP-coupled NETs can effectively eradicate various multidrug-resistant bacteria and biofilms through photodynamic therapy, overcome bacterial immune evasion, and promote tissue recovery from severe wound infections. This design can significantly strengthen NET function, providing a non-antibiotic alternative platform for treating bacterial infectious diseases.

The Efficacy of Calcium Sulfate/Hydroxyapatite (CaS/HA) Gentamicin in Osteomyelitis Treatment: A Case Series

Background: Osteomyelitis is a challenging condition caused by infection and inflammation of the bone, presenting a significant economic burden to healthcare systems. Calcium sulfate/hydroxyapatite (CaS/HA) is a bone void filler composed of 60% calcium sulfate and 40% hydroxyapatite. This case series aimed to report the efficacy and infection-related outcomes of CaS/HA combined with Gentamicin (CaS/HA-G) in treating osteomyelitis. Methods: Patients aged 18 and older diagnosed with osteomyelitis requiring surgical intervention and treated with CaS/HA-G during their procedure were included in the study, with a median (Q1–Q3) = 10 (7–16)-month follow-up period of time. Data collected included demographic, surgical, and outcome information. Infection eradication was determined by the normalization of the C-reactive protein, erythrocyte sedimentation rate levels, or the absence of clinical infection symptoms. Results: The case series involved 21 patients (twelve male, nine female) with a mean (SD) age of 54.8 (16.6) years. Vancomycin or/and Tobramycin were used as an additional antibiotic in 17 patients. At the last follow-up, 20 out of 21 patients (95.2%) had eradicated the infection, with a median (Q1–Q3) eradication time of 128 (71.8–233.5) days. Conclusions: In conclusion, this study demonstrates that CaS/HA-G is effective in controlling osseous infection in osteomyelitis while acting as an absorbable bone void filler.

Microbial profile of diabetic foot osteomyelitis from the northwest of England

BackgroundOsteomyelitis of the diabetic foot is a common and challenging complication affecting patients with diabetic foot ulcers and infections. The complexity of these infections lies in their polymicrobial nature, high rates of persistence and recurrence. This study examined the microbiological profile of diabetic foot osteomyelitis from a teaching hospital in Northwest England and their resistance patterns to understand its impact on infection persistence and to direct effective treatment.MethodsA retrospective review of 105 patients who underwent surgical management for diabetic foot osteomyelitis between 2019 and 2024. We analysed three consecutive culture samples for each patient to assess for the microbiological profile and resistance patterns of these infections and to monitor infection recurrence and persistence rates.ResultsA total of 105 patients were identified. Infection eradication was noted in 42% of the cohort, infection persistence in 18%, and late infection recurrence in 40%. Polymicrobial growth was evident in 72% of our study sample. Gram-positive bacteria made up the majority of the bacterial isolates in all 3 culture samples, 74.81% in sample 1, 69.31% in sample 2, and 55.1% in sample 3. Staphylococcus aureus was the most prevalent gram-positive bacteria, at 52.38% in sample 1, 36.19% in sample 2, and 18.09% in sample 3, followed by Haemolytic Streptococcus, Enterococcus and Corynebacterium. The frequently identified gram-negative bacteria were Pseudomonas in sample 1 (7.61%), E. coli and Proteus in sample 2 (5,71%), Pseudomonas and Proteus in sample 3 (2.85%). Gram-positive bacteria were resistant to penicillin and macrolides with resistance of staphylococcus aureus to clarithromycin identified among all 3 culture samples. Gram-negative bacteria were most resistant to amoxicillin. Staphylococcus aureus was responsible for infection persistence in most of our cohort (12/19) 63.15%. Among those patients, Staphylococcus was resistant to clarithromycin in 6 of the cases. The 5-year mortality rate for our study sample was 32.38%.ConclusionThis study highlights the prevalence of polymicrobial growth and multi-drug resistant pathogens in the scope of diabetic foot osteomyelitis. It highlights the predominance of Staphylococcus aureus and its resistant strains among patients affected by diabetic foot osteomyelitis in Greater Manchester.

Multifunctional scaffolds of β-tricalcium phosphate/bioactive glass coated with zinc oxide and copper oxide nanoparticles

Incorporating nanoparticles into scaffolds with regenerative potential is a promissory strategy to provide them with antimicrobial activity. Bioceramics, such as β-tricalcium phosphate (β-TCP) and bioactive glasses (BGs), stand out among synthetic materials for bone regeneration. In this context, we report the incorporation of zinc oxide (ZnO) and copper oxide/copper nitrate (CuO/Cu2H3NO5) nanoparticles onto the surface of the β-TCP/BG scaffolds. This report addresses the physicochemical characterization of the scaffolds, their antimicrobial activity, and their response to MC3T3-E1 cells. Our findings show that the incorporation of both nanoparticles effectively inhibited S. aureus growth, including its biofilm formation. While the presence of the nanoparticles initially decreased MC3T3-E1 cell viability, cell proliferation improved with prolonged incubation. Overall, the β-TCP/BG_Zn and β-TCP/BG_Cu scaffolds showed an early antimicrobial response, aiding infection eradication, while also supporting cell proliferation over time.

Clinical and Radiographic Outcomes of a Long Cementless Monobloc Stem for Revision Total Hip Arthroplasty Due to Chronic Periprosthetic Infection

BackgroundA long cementless monobloc stem is widely used for aseptic loosening, with satisfactory five-to-ten-year outcomes reported. Nonetheless, related studies on chronic periprosthetic joint infection (PJI) are scant. This study evaluated the clinical and radiographic outcomes of the stem in two-stage revisions due to PJI. MethodsThis prospective multicenter cohort study consisted of patients from three medical centers who were enrolled in a single arm from January 2017 to May 2022. All patients were diagnosed with chronic PJI based on International Consensus Meeting (ICM) criteria and underwent two-stage revisions using a long monobloc cementless revision stem. Among 44 patients, 37 (12 women and 25 men) completed an average follow-up of 35.6 months (range, 14 to 75). The primary outcome was the stability of the stem; secondary outcomes included infection eradication, Harris hip score, leg length discrepancy, major complications, and isolated pathogens at intraoperative cultures. ResultsAt one year after revision, the infection-free prosthesis survival rate was 97.3% (95% CI [confidence interval]: 96.4 to 98.2%). At the last follow-up, the mean subsidence was 2.9 ± 2.1 mm (range, 0.8 to 4.8). Postoperative leg length discrepancy averaged −4.6 ± 4.9 mm (range, −16 to 0). The Engh score averaged 14.1 ± 6.9 (range, 0 to 22). The Harris hip score improved from a preoperative average of 35.7 ± 8.5 (range, 12 to 50) to 80.4 ± 9.3 (range, 58 to 92) at the 1-year postoperative follow-up (P < 0.01). ConclusionThe long cementless monobloc stem used in the current study presents a feasible option for two-stage revision in cases of chronic PJI. The bone ingrowth and stability could be observed within the short follow-up time.

Tracing the path of Quorum sensing molecules in cystic fibrosis mucus in a biomimetic in vitro permeability platform

P. aeruginosa employs specific quorum sensing (QS) mechanisms to orchestrate biofilm formation, enhancing resistance to host defences. In physiological conditions, QS molecules permeate the lung environment and cellular membrane to reach the cytoplasmic Aryl Hydrocarbon Receptor (AhR) that is pivotal for activating the immune response against infection. In pathological conditions like cystic fibrosis (CF) this interkingdom communication is altered, favouring P. aeruginosa persistence and chronic infection. Here, we aim to investigate the molecular journey of QS molecules from CF-like environments to the cytoplasm by quantifying via HPLC-MS the permeability of selected QS molecules (quinolones, lactones, and phenazines) through in vitro models of the two main biological lung barriers: CF-mucus and cellular membrane. While QS molecules not activating AhR exhibit intermediate permeability through the cellular membrane model (PAMPA) (1.0–4.0 × 10−6 cm/s), the AhR-activating molecule (pyocyanin) shows significantly higher permeability (8.6 ± 1.4 × 10−6 cm/s). Importantly, combining the CF mucus model with PAMPA induces a 50% decrease in pyocyanin permeability, indicating a strong mucus-shielding effect with pathological implications in infection eradication. This study underscores the importance of quantitatively describing the AhR-active bacterial molecules, even in vitro, to offer new perspectives for understanding P. aeruginosa virulence mechanisms and for proposing new antibacterial therapeutic approaches.

Biomimetic Electrodynamic Metal-Organic Framework Nanosponges for Augmented Treatment of Biofilm Infections.

Electrodynamic therapy (EDT) is a promising alternative approach for antibacterial therapy, as reactive oxygen species (ROS) are produced efficiently in response to an electric field without relying on endogenous H2O2 and O2. However, the inherent toxicity of metallic catalysts and numerous bacterial toxins during the therapeutic process still hinder its development. Herein, biomimetic metal-organic (MOF@EV) nanosponges composed of ginger-derived extracellular vesicles (EVs), and electrodynamic metal-organic frameworks (MOFs) are developed for the eradication of bacterial infections and the absorption of toxins. The prolonged circulation time of MOF@EV in vivo facilitates their accumulation at infection sites. More interestingly, MOF@EV can behave as nanosponges and effectively prevent host cells from binding to bacterial toxins, thereby reducing damage to cells. Subsequently, the MOF@EV nanosponges are discovered to work as electro-sensitizers, which is confirmed through both theoretical calculation and experimental verification. As a result, ROS is continuously produced under the electric field to achieve effective EDT-mediated bacterial eradication. Meanwhile, the treatment process of MOF@EV in vivo is visualized in mice infected with luciferase-expressing Staphylococcus aureus (S. aureus), and excellent biofilm eradication capacity and detoxification efficiency are demonstrated in a subcutaneous abscess model. This work provides a promising strategy for the treatment of bacterial infections.

Efficacy and safety of vonoprazan-based bismuth quadruple therapy for first-line Helicobacter pylori eradication: A large-scale, real-world study.

Vonoprazan (VPZ) has been shown to have superior acid-inhibitory effects compared to proton pump inhibitors (PPIs). However, there is a paucity of research examining the efficacy of vonoprazan-based bismuth quadruple therapy (VBQT) in the eradication of primary Helicobacter pylori infection. This study aimed to evaluate the effectiveness and safety of VBQT as a first-line treatment for H pylori eradication. This retrospective, real-world, single-arm study included consecutive treatment-naive patients who received VBQT (VPZ 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, bismuth potassium citrate 220 mg, all administered twice daily for 14 days) for H pylori eradication between March 1, 2021, and May 30, 2023. The study included both outpatients and inpatients. Eradication rates were assessed using 13C-urea breath tests or 14C-urea breath tests performed 4 to 6 weeks after treatment. The primary outcomes included eradication rates, adverse events, and treatment compliance. A total of 612 H pylori-infected patients were included in the study. The intention-to-treat (ITT), modified ITT (MITT), and per-protocol analyses showed H pylori eradication rates of 84.3% (95% CI: 812% to 87.1%), 95.9% (95% CI: 93.9% to 97.4%), and 96.4% (95% CI: 94.4% to 97.8%), respectively. In the ITT analysis, the adverse event rate was 12.7%, and the treatment compliance rate was 96.9%. In real-world practice, the VBQT regimen demonstrates excellent efficacy and favorable tolerability as a first-line therapy for H pylori eradication.

Fungal Shoulder Periprosthetic Infections: A Systematic Review.

Background: Data regarding fungal PJIs of the shoulder are scarce. The present systematic review aims to identify and evaluate all published shoulder fungal PJIs in an effort to better understand the diagnostic and therapeutic approach to these infections. Methods: A systematic review according to the PRISMA guidelines was conducted, locating all shoulder fungal PJIs. The initial search located 1435 articles. Data were collected on demographics, the causative fungus, antifungal treatment (AFT), surgical interventions, and infection outcomes. Results: After screening and implementation of the inclusion criteria, a total of 10 articles, including 10 cases, were eligible. The sample's mean age was 62.44 years. Diabetes mellitus was the most common comorbidity (30%), while 70% were immunocompromised. Candida spp. was the most common causative fungus (nine cases; 90%), while all cases were confirmed with cultures. In three cases (30%), there was bacterial co-infection. The mean duration of antifungal treatment (AFT) was 8.4 weeks, while the preferred agent was fluconazole (60% of cases), followed by amphotericin B (30%). Most cases (50%) underwent resection arthroplasty as part of the treatment, while two-stage revision arthroplasty was performed in 30%. Infection's eradication was reported in 90% of the studied cases. Conclusions: The diagnosis and management of fungal periprosthetic shoulder infections are particularly challenging and require a multidisciplinary approach. The combination of antifungal therapy and tailored surgical strategies is crucial, but further research is needed to refine treatment protocols and address the unique considerations in shoulder PJIs.

Hepatitis B infection: Evaluation of demographics and treatment of chronic hepatitis B infection in Northern-western Tanzania.

Chronic hepatitis B virus (HBV) infection is still a major public health problem. In response to the World Health Organization (WHO), Tanzania implemented immunization and treatment to achieve the eradication of HBV infection by 2030. To achieve this goal, frequent updates of demographic data, antiviral therapy eligibility, and uptake are essential. We therefore evaluated demographic data, antiviral therapy eligibility, and uptake among chronically HBV-infected patients attending at Bugando Medical Centre (BMC), Tanzania. A cross-sectional study enrolled 196 chronic HBV patients from April 23, 2023, to October 10, 2023, at BMC, where 100 and 96 patients were retrospectively and prospectively enrolled, respectively. Study's ethical clearance and permission were observed by the Catholic University of Health and Allied Sciences/Bugando Medical Centre research ethics and review committee and the Bugando Medical Centre management respectively. For all patients, socio-demographic data and whole blood samples were obtained. Full blood picture, alanine and aspartate amino transferases, and HBV viral load parameters were determined. Aspartate-Platelet Ratio Index (APRI) and Fibrosis Four (FIB-4) scores were calculated according to their respective formulas. Therapy eligibility and uptake were evaluated according to the 2015 WHO HBV prevention, treatment, and care guidelines. The data were summarized and analysed using STATA version 15. The median age for all patients was 39 [IQR: 32-47.5] years. Nearly all study patients, 99% (194/196), were older than 20 years old, with significant male dominance (73.5% [144/196] versus 26.5% [52/196]; p<0.0001). Anti-HBV antiviral therapy eligibility was 22.4%, while uptake was 6.8% (3/4), which was significantly lower than the WHO expectation of 80% (p <0.0001). Almost all chronically HBV-infected patients attending at BMC were older than 20 years old and were significantly dominated by males. Antiviral therapy uptake was remarkably lower than expected by the WHO towards combating HBV infection by 2030.

Effectiveness of zero dose HBV vaccine on prevention of HBV breakthrough infection among vaccinated Egyptian children

Hepatitis B virus (HBV) is a vaccine preventable disease. Sufficient post vaccination response is critical step to achieve infection eradication. Vaccine hypo-responsiveness is a major risk factor for HBV chronic infection. We aimed to evaluate the effectiveness of birth dose HBV vaccine in preventing perinatal HBV infection and to detect the rate of HBV surface antibody (HBs-Ab) seroconversion and its relation to interleukin-4 polymorphism (IL-4 PM) among a group of vaccinated Egyptian infants. This observational analytical study involved 77 infants aged 6 to 12 months who received 4 doses of HBV vaccine including a zero dose. We measured serum levels of HBV-DNA and hepatitis B surface antigen (HBsAg) as markers of infectivity, and the level of (HBsAb) to assess vaccine responsiveness. Cytokine gene analysis to detect IL-4 gene polymorphism and its association with vaccine un-responsiveness were investigated. We observed that none of the vaccinated infants acquired HBV infection. Of the included 77 infants, seroconversion against HBV was detected in 72 (93.5%), 28 (36.4%) had low response and 44 (57.1%) had high response. While 5 (6.5%) were non responders. There was significant association between IL-4 gene polymorphism and the poor seroconversion after HBV vaccination. (p=0.03). Furthermore, HBsAb titer was significantly lower in children who have IL-4 gene polymorphism (p=0.014). In conclusion, implementation of birth-dose HBV vaccination is effective for prevention of perinatal infection, but seroconversion rate may be insufficient to induce long term protection. IL-4 gene polymorphism is associated with poor response to HBV vaccine.

Electrically-driven drug delivery into deep cutaneous tissue by conductive microneedles for fungal infection eradication and protective immunity

Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.

Targeted recruitment of immune effector cells for rapid eradication of influenza virus infections

Despite much research, considerable data suggest that influenza virus remains a serious health problem because i) the effectiveness of current vaccines ranges only from 19% to 60%, ii) available therapies remain ineffective in advanced stages of disease, iii) death rates vary between 25,000 and 72,000/year in the United States, and iv) avian influenza strains are now being transmitted to dairy cattle that in turn are infecting humans. To address these concerns, we have developed zanDR, a bispecific small molecule that binds and inhibits viral neuraminidase expressed on both free virus and virus-infected cells and recruits naturally occurring anti-rhamnose and anti-dinitrophenyl (DNP) antibodies with rhamnose and DNP haptens. Because the neuraminidase inhibition replicates the chemotherapeutic mechanism of zanamivir and oseltamivir, while rhamnose and DNP recruit endogenous antibodies much like an anti-influenza vaccine, zanDR reproduces most of the functions of current methods of protection against influenza virus infections. Importantly, studies on cells in culture demonstrate that both of the above protective mechanisms remain highly functional in the zanDR conjugate, while studies in lethally infected mice with advanced-stage disease establish that a single intranasal dose of zanDR not only yields 100% protection but also reduces lung viral loads faster and ~1,000× more thoroughly than current antiviral therapies. Since zanDR also lowers secretion of proinflammatory cytokines and protects against virus-induced damage to the lungs better than current therapies, we suggest that combining an immunotherapy with a chemotherapy in single pharmacological agent constitutes a promising approach for treating the more challenging forms of influenza.

Modular component exchange has no advantage in Debridement, Antibiotics and Implant Retention (DAIR) for early onset hip and knee prosthetic joint infection.

Debridement, Antibiotics and Implant Retention (DAIR) has been the mainstay of treatment for early onset periprosthetic joint infection in spite of variable results. Modular component exchange is a widely recommended strategy to improve success rates with DAIR though very strong evidence to support its practice is still lacking. Eighty six patients underwent DAIR for early onset PJI following primary hip and knee arthroplasty were divided into two groups for this retrospective review. 45 patients (group 1) underwent DAIR with modular component exchange and 41 patients without exchange (group 2). We compared success rates based on infection eradication (primary outcome variable) and need for revision surgical procedures between these two groups. We also assessed differences in primary outcome based on type of arthroplasty, timing of DAIR and addition of local antibiotics. The overall success rate after DAIR was 71%. The outcome was similar in both groups (69% vs 74%, P = 0.66). The need for revision surgical procedures was 27% which was similar in both groups (P = 0.98) with 23% needing revision of prosthetic components. Type of arthroplasty (hip or knee) and addition of local antibiotics had no bearing on infection eradication after DAIR with or without modular component exchange. DAIR with in 45days of primary arthroplasty had significantly higher success rate compared to DAIR after 45days in both groups. We observed that modular component exchange did not improve infection eradication after DAIR for early onset PJI following hip and knee arthroplasty. Reasonable success rates can be expected after DAIR especially if the patient develops early clinical signs and the procedure is carried out as early as possible.

Encapsulation of Mentha aquatica methanol extract in alginate hydrogel promotes wound healing in a murine model of Pseudomonas aeruginosa burn infection

Burn injuries are the fourth most prevalent devastating form of trauma worldwide. Among the most extensively explored materials, composite dressings with alginate loaded with herbal extract can be mentioned. This research aimed to develop a sodium alginate (SA)-based hydrogel encapsulated with Mentha aquatica (MA) methanol extract and investigate its therapeutic efficacy in the infected burn mouse model. SEM, FTIR, in vitro extract release, HPLC, mechanical test, contact angle, swelling, degradability, and temperature response properties were used to analyze the hydrogel scaffold's physicochemical structure. Additionally, the antibacterial activity and MIC level of the extract, cell cytotoxicity, and macroscopic and microscopic analysis of the wound healing process were done using Masson's trichrome and hematoxylin-eosin staining. The physicochemical properties of the SA hydrogel encapsulated with MA extract were verified. The lowest inhibitory dose of the extract was determined to be 12.5 mg/ml. Application of SA/MA hydrogel to localized wounds of deep third-degree burns demonstrated faster tissue regeneration, collagen recovery, and eradication of bacterial infection. This research focused on the design and the preparation of a novel and effective biomaterials-based medical product, which has the potential to rehabilitate infected and injured skin tissue; therefore, it can be a promising candidate for wound dressing applications.

Effectiveness of long-term low-dose aspirin in the prevention of gastric cancer after Helicobacter pylori eradication: study design and rationale of Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT)

BackgroundIn addition to Helicobacter pylori (H. pylori) infection eradication, some medications, including aspirin, metformin, and statins, have been suggested to have protective effects against gastric cancer (GC) development in observational studies. We launched the Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT) to evaluate the effectiveness of long-term low-dose aspirin use for the prevention of development and mortality of GC after H. pylori eradication.Methods/designAGCPT is a prospective population-based double-blind, randomized clinical trial. The study sample was targeted at 21,000 participants aged from 35 to 70 years old, both sexes, in Ardabil, a province in northwest Iran with relatively high rates of GC incidence and mortality. All eligible participants were initially tested for H. pylori infection using a H. pylori stool antigen test. Participants with positive tests undergo H. pylori eradication by standard treatment regimens. All participants with a negative test and those with a positive test with a subsequent confirmed H. pylori eradication test were entered into the intervention phase. In the intervention phase, participants were allocated randomly into either the treatment (daily oral consumption of 81 mg enteric-coated aspirin tablets) arm or the control (placebo) arm using permuted balanced blocks. Subjects will be followed for an average period of 10 years to evaluate the incidence and mortality rates of GC.DiscussionIn addition to preventing other diseases like cardiovascular events, aspirin may prevent GC incidence and mortality. AGCPT will investigate the difference between the two study arms in the proportion of the cumulative incidence and mortality rates of GC. The study’s results may help policymakers and researchers update the strategies for GC prevention.Trial registrationThis trial with the registry name of “The effect of Low-dose Aspirin in the Prevention of Gastric Cancer” was registered in the Iranian Registry of Clinical Trials, IRCT.ir, under the identifier IRCT201105082032N3. Registered on April 21, 2017.

Fluorescent Microneedle‐Based Theranostic Patch for Naked‐Eye Monitoring and On‐Demand Photo‐Therapy of Bacterial Biofilm Infections

AbstractThe eradication of recalcitrant bacterial biofilm infections necessitates the development of speedy diagnostics and prompt therapeutics. However, constructing a portable versatile platform that enables in situ monitoring of biofilm infections accompanied by potent antibiofilm activity remains challenging. To address this conundrum, a microneedle theranostic patch (Mn: C/G@MN) is devised by incorporating an innovative biophotonic probe (manganese‐doped carbon dots, Mn: CDs) into methacrylated gelatin for visual monitoring of biofilm infection and on‐demand photo‐therapy. The Mn: C/G@MN patch penetrates the physical barrier of biofilms to track their acidic microenvironment, exhibiting a visualized fluorescence color change (from yellow to turquoise) to enable naked‐eye monitoring of biofilm infection. Furthermore, the Mn: C/G@MN patch can drastically eradicate biofilm on‐demand through the synergy of local hyperthermia and hydroxyl radical (•OH) storm under 808 nm near‐infrared light illumination, enabling the damaging of extracellular polymeric substances (EPS) matrix to disperse biofilms and subsequently kill detached bacteria. Both in vitro and in vivo findings authenticate that biofilm infection monitoring‐and‐treating can be achieved. Moreover, the versatile Mn: C/G@MN patch is conducive to suppressing inflammatory responses, expediting collagen deposition, stimulating angiogenesis, and accelerating biofilm‐infected wound healing. As envisaged, this work highlights the potential of such a versatile platform for application in integrated theranostics for biofilm infection.

MIP3α-Rel Mtb intranasal DNA vaccination induces reactive T-cell infiltration into the lungs in mice and macaques.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the leading cause of mortality due to a single infectious organism. While generally curable, TB requires a lengthy and complex antibiotic regimen, due in large part to bacteria that can shift to a persistent state in the presence of antibiotic pressure. Rel Mtb is the primary enzyme regulating the stringent response, which contributes to the metabolic shift of Mtb to a persistent state. Targeting Rel Mtb with a vaccine to eliminate persistent bacteria through the induction of Rel Mtb -specific T-cell immunity in combination with antibiotics to kill dividing bacteria has shown promise in model systems. In a mouse model of Mtb infection, a vaccine created by genetically fusing rel Mtb to the chemokine macrophage inflammatory protein 3α ( MIP3 α), a ligand for the CC chemokine receptor type 6 (CCR6) present on immature dendritic cells, has been shown to enhance T-cell responses and accelerate eradication of infection in mouse models compared to a vaccine lacking the chemokine component. In this study, immunogenicity studies in the mouse and rhesus macaque models provide evidence that intranasal administrations of the DNA form of the MipRel vaccine led to enhanced lung infiltration of T cells after a series of immunizations. Furthermore, despite similar T-cell immunity seen in PBMCs between MipRel and Rel vaccinations, lung and bronchoalveolar lavage cell samples are more enriched for cytokine-secreting T cells in MipRel groups compared to Rel groups. We conclude that intranasal immunization with a MIP-3α fusion vaccine represents a novel strategy for use of a simple DNA vaccine formulation to elicit T-cell immune responses within the respiratory tract. That this formulation is immunogenic in a non-human primate model historically viewed as poorly responsive to DNA vaccines indicates the potential for clinical application in the treatment of Mtb infection, with possible application to other respiratory pathogens. Future studies will further characterize the protective effect of this vaccination platform.

Use of intra-operative fluorescence imaging in periprosthetic joint infection: State of the art and future perspectives.

In periprosthetic joint infections (PJIs), the surgeon's role becomes pivotal in addressing the infection locally, necessitating the surgical removal of infected and necrotic tissue. Opportunity to enhance the visualization of infected tissue during surgery could represent a game-changing innovation. The aim of this narrative review is to delineate the application of intraoperative fluorescence imaging for targeting infected tissues in PJIs. A systematic review, adhering to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was carried out. The search included multiple online database; MEDLINE, Scopus, and Web of Science. For data extraction the following were evaluated: (i) diagnosis of musculoskeletal infection; (ii) use of intraoperative fluorescence imaging; (iii) infected or necrotic tissues as target. Initially, 116 studies were identified through online database searches and reference investigations. The search was narrowed down to a final list of 5 papers for in-depth analysis at the full-text level. Subsequently, 2 studies were included in the review. The study included a total of 13 patients, focusing on cases of fracture-related infections of the lower limbs. The primary and crucial role for orthopedic surgeons in PJIs is the surgical debridement and precise removal of necrotic and infected tissue. Technologies that enable clear and accurate visualization of the tissue to be removed can enhance the eradication of infections, thereby promoting healing. A promising avenue for the future involves the potential application of intraoperative fluorescence imaging in pursuit of this objective.