Infected Implants Research Articles

Optimising Titanium Implant Stability and Infection Resistance through Iron Nanoparticle Coatings: A Preclinical Investigation

Optimising Titanium Implant Stability and Infection Resistance through Iron Nanoparticle Coatings: A Preclinical Investigation

Perioperative antibiotic prophylaxis in implant breast reconstruction

Implant infection is the most common and serious complication in implant-based breast reconstruction. To prevent infection, many surgeons have adopted a perioperative antibiotic prophylaxis regimen for managing patients. However, there has been considerable debate regarding the duration of antibiotic prophylaxis. After reading this article, plastic surgeons should manage their patients with an understanding of the evidence supporting perioperative antibiotic prophylaxis.

Glucose-gated nanocoating endowing polyetheretherketone implants for enzymatic gas therapy to boost infectious diabetic osseointegration

The hyperglycemic micromilieu surrounding implants in diabetic patients leads to high failure rate of implantation and implant-associated infection. Carbon monoxide (CO) has been reported to combat infections; however, its on-demand liberation and the elucidation of the underlying antibacterial mechanism remain challenging. To address this issue, we develop a multipurpose orthopedic implant comprising polyetheretherketone, glucose oxidase (GOx), and manganese carbonyl nanocrystals (MnCO), serving as a glucose-gated nanocoating for enzymatic gas therapy to improve infectious diabetic osseointegration. The GOx acts as a glucose-actuated gate responsive to hyperglycemia, thereby delivering CO in situ triggered by the GOx-driven Fenton-like reaction of MnCO nanocrystals. The released CO considerably prevents bacterial multiplication by penetrating the membrane, binding to cytochrome bo3, and interfering with the respiratory chain in vitro. Furthermore, the engineered implant displays desired antibacterial properties and enhances osseointegration in vivo. Collectively, the orthopedic nanocoating implant is capable of delivering glucose-gated enzymatic gas therapy, promising for treating infectious diabetic bone defects.

Risk of orthopaedic implant infection during bacteraemia.

Orthopaedic implant material can get infected via haematogenous spread from a distant source at any point after implantation. The sources of haematogenous orthopaedic implant infections have been studied only for prosthetic joints. The most common source of infection has varied, but it can be, for example from the skin and soft tissues, cardiovascular system and dental infections. The risk for developing a periprosthetic joint infection (PJI) during bacteraemia is dependent on the pathogen: it is highest for Staphylococcus aureus and beta-haemolytic streptococci, but low for gram-negative bacteria. The risk for developing a (PJI) during Staphylococcus aureus bacteraemia (SAB) has varied between 12 and 41%; the risk for developing an infection in any orthopaedic implant in the extremities during SAB is probably almost the same as for prosthetic joints, but data are very limited. The risk of developing an infection in spinal implants during bacteraemia is not known, as it has not been studied. Especially in the case of SAB, infected orthopaedic implants are usually symptomatic, so asymptomatic implants do not routinely require further diagnostic work-up, such as synovial fluid aspiration.

Inhibitory effects of chlorhexidine-loaded calcium carbonate nanoparticles against dental implant infections

This study aimed to design sustained released biodegradable calcium carbonate nanoparticles loaded with chlorhexidine (CHX-loaded NPs) and to investigate the early osteogenic differentiation and antimicrobial effects on the important bacteria involved in infections of dental implants. The microemulsion method was used to prepare the calcium carbonate nanoparticles loaded with chlorhexidine. The prepared nanoparticles were characterized using conventional methods. The release pattern determination and the biodegradation test were performed for the prepared nanoparticles. For the early osteogenic differentiation test of the prepared nanoparticles, alkaline phosphatase (ALP) activity was detected in human dental pulp stem cells (HDPSCs). The antimicrobial effects of the nanoparticles were evaluated against Escherichia coli, Streptococcus mutans, Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The sizes of free calcium carbonate nanoparticles and CHX-loaded NPs were 105 ± 1.63 and 118 ± 1.47 nm and their zeta potentials were − 27 and − 36, respectively. A 50% degradation of nanoparticles was achieved after 100 days. These nanoparticles showed a two-stage sustained release pattern in vitro. Microscopic images revealed that the morphology of free calcium carbonate nanoparticles primarily took on a spherical calcite form, while CHX-loaded NPs predominantly exhibited a cauliflower-like vaterite polymorph. The nanoparticles increased the activity of ALP in cells in two weeks significantly (p < 0.05). Antimicrobial and antibiofilm results showed an efficient effect of the prepared nanoparticle against the studied bacteria. Calcium carbonate nanoparticles are an efficient multifunctional vector for chlorhexidine and can be used as a bioactive antibacterial agent against various oral microorganisms to prevent implant infections.

Exploring Drug Resistance: Microbial Profiles, Antibiotic Sensitivity, and Biofilm Development in Orthopedic Implant Infections.

Background With the advent of and rise in antibiotic resistance globally, especially in postoperative patients, studying the antibiogram and associated factors is the need of the hour. The present study was undertaken to document the microbiological profile in postoperative orthopedic patients with the infected implant in situ and to observe the antibiotic susceptibility patterns of isolated organisms in such infections. Methods This study was conducted in the Department of Microbiology of a tertiary care hospital for six months after obtaining institutional ethical approval. A total of 236 samples from patients with orthopedic implant infections were received during the study period, out of which 53 samples with positive culture isolate were further analyzed for microbiological profile including biofilm production. All observations and demographics were recorded and analyzed using SPSS software version 21.0(IBM Corp., Armonk, NY, USA) and represented in the form of graphs, data, and tables. Results and conclusion The study showed a culture positivity rate of 53 (23%) out of 236 samples, in which gram-negative isolates 36 (68%)were more than gram-positive isolates 17 (32%). The most common isolate was staphylococcus aureus 17 (32%) of which the majority were MRSA 13 (76%), followed by Escherichia coli 9 (17%) and Klebsiella pneumoniae 9 (17%). Out of the 53 isolates, 20 were biofilm producers. Biofilm-producing isolates were more resistant to tested routine antibiotics compared to non-biofilm. This study could represent the initial interdisciplinary effort in an ongoing process to better understand and manage orthopedic implant infections at the hospital, specifically focusing on infections related to orthopedic devices.

Organisms Causing Postoperative Implant Infection in Orthopedic Patients Presenting at a Tertiary Care Hospital.

Introduction Infections pose a significant challenge in orthopedics related to implant failure. In orthopedic surgeries, surgical site infections (SSIs) extend the patient's hospital stay by an average of two weeks and also increase morbidity, double hospitalization rates, and triple the financial burden on the patient. This study aims to determine the common organism in patients with postoperative implant infections presenting at a tertiary care hospital. Methods A cross-sectional study was conducted in the Department of Orthopedic Surgery at JPMC Karachi over a six-month period, from November 24, 2022, to May 25, 2023. All patients of both genders aged 18-65 years presenting with postoperative implant infection within six hours of the development of symptoms were enrolled. Baseline demographic details and clinical histories were recorded at the time of presentation. A swab for culture and sensitivity was taken from the implant site using a sterile swab stick in patients with confirmed or suspected infections. Results Of 196 patients, the mean age of the patients was 48.47±5.19 years. Gender distribution showed that 49% of patients were females and 51% were males. The mean duration of surgery was 1.71±0.49 hours (100 minutes approximately);Klebsiella species 26% and Staphylococcus aureus25.5% were the most common organisms isolated from infected surgical wounds, followed by Pseudomonas species in 32 patients (16.3%), Acinetobacter species in 27 patients (13.8%), Escherichia Coliin 23 patients (11.7%), and coagulase-negativeStaphylococcusin 13 patients (6.6%). Conclusion In our cohort, Staphylococcus species and Klebsiella species were the most common pathogens isolated from postoperative implant infections. The rise in Klebsiella species suggests that changes in prophylactic antibiotic practices may have contributed to this trend. Therefore, there is an urgent need to reassess current prophylactic strategies in light of the increasing incidence of infections caused by gram-negative bacteria.

Amino Acid Functionalized SrTiO3 Nanoarrays with Enhanced Osseointegration Through Programmed Rapid Biofilm Elimination and Angiogenesis Controlled by NIR-Driven Gas Therapy.

Bacterial biofilm formation is closely associated with persistent infections of medical implants, which can lead to implantation failure. Additionally, the reconstruction of the vascular network is crucial for achieving efficient osseointegration. Herein, an anti-biofilm nanoplatform based on L-arginine (LA)/new indocyanine green (NICG) that is anchored to strontim titanium oxide (SrTiO3) nano-arrays on a titanium (Ti) substrate by introducing polydopamine (PDA) serving as the interlayer is designed and successfully fabricated. Near-infrared light (NIR) is used to excite NICG, generating reactive oxygen species (ROS) that react with LA to release nitric oxide (NO) molecules. Utilizing the concentration-dependent effect of NO, high power density NIR irradiation applied during the early stage after implantation to release a high concentration of NO, which synergized with the photothermal effect of PDA to eliminate bacterial biofilm. Subsequently, the irradiation power density can be finely down-regulated to reduce the NO concentration in subsequent treatment for accelerating the reconstruction of blood vessels. Meanwhile, SrTiO3 nano-arrays improve the hydrophilicity of the implant surface and slowly release strontium (Sr) ions for continuously optimizing the osteogenic microenvironment. Effective biofilm elimination and revascularization alongside the continuous optimization of the osteogenic microenvironment can significantly enhance the osseointegration of the functionalized Ti implant in in vivo animal experiments.

Piezoelectric-Enhanced Nanocatalysts Trigger Neutrophil N1 Polarization against Bacterial Biofilm by Disrupting Redox Homeostasis.

Strategies of manipulating redox signaling molecules to inhibit or activate immune signals have revolutionized therapeutics involving reactive oxygen species (ROS). However, certain diseases with dual resistance barriers to the attacks by both ROS and immune cells, such as bacterial biofilm infections of medical implants, are difficult to eradicate by a single exogenous oxidative stimulus due to the diversity and complexity of the redox species involved. Here, this work demonstrates that metal-organic framework (MOF) nanoparticles capable of disrupting the bacterial ROS-defense system can dismantle bacterial redox resistance and induce potent antimicrobial immune responses in a mouse model of surgical implant infection by simultaneously modulating redox homeostasis and initiating neutrophil N1 polarization in the infection microenvironment. Mechanistically, the piezoelectrically enhanced MOF triggers ROS production by tilting the band structure and acts synergistically with the aurintricarboxylic acid loaded within the MOF, which inhibits the activity of the cystathionine γ-cleaving enzyme. This leads to biofilm structure disruption and antigen exposure through homeostatic imbalance and synergistic activation of neutrophil N1 polarization signals. Thus, this study provides an alternative but promising strategy for the treatment of antibiotic-resistant biofilm infections.

Engineering Coatings Inspired by Cell Membrane Thermal Dynamics to Enhance Photothermal Therapy and Osteogenesis for Implant Infections.

Photothermal therapy (PTT) encounters challenges of rapid thermal loss and potential tissue damage. In response, we propose a Heat-Boost and Lock implant coating strategy inspired by the thermal adaptation of biological membranes, enabling precise local photothermal utilization. This coating incorporates a poly(tannic acid) (pTA) bridging layer on implants, facilitating stable layer-by-layer integration of a black phosphorus (BP) photothermal layer and a top cell membrane Heat-Boost and Lock layer. The cell membrane layer significantly curtails photothermal loss (extending the heat retention by 17.62%) and stores energy within its phospholipid bilayer, boosting photothermal effects near implants (achieving a temperature increasement of 275%). Theoretical analysis indicates that these local heat preservation properties of the cell membrane arise from its low thermal conductivity and phase-change properties. In a Staphylococcus aureus-infected bone implant model, our coating demonstrates precise antibacterial action around implants (reach an antibacterial ratio of 99.52%). The synergetic locking function of cell membrane and pTA delays BP biodegradation, ensuring favorable photothermal stability and long-term osteo-inductive performance (increasing the bone volume fraction by 53.45%). Beyond providing an endogenic biointerface, this strategy extends the application of cell membrane in local thermal management, offering possibilities for effective and safe PTT modalities.

Bacteriological spectrum of infections in orthopaedic implants and their antibiotic susceptibility pattern

Bacteriological spectrum of infections in orthopaedic implants and their antibiotic susceptibility pattern

Implant-based Breast Reconstruction Salvage with Negative Pressure Wound Therapy with Instillation: An Evaluation of Outcomes.

Implant infection is problematic in breast reconstruction. Traditionally, infected tissue expanders (TE)/implants are removed for several months before replacement, resulting in breast reconstruction delay. Salvage involving device removal, negative pressure wound therapy with instillation and dwell (NPWTi-d) placement, and early staged TE/implant replacement within a few days has been described. The purpose of this study was to compare outcomes of the NPWTi-d salvage pathway with traditional implant removal. A retrospective review was performed on patients who underwent implant-based reconstruction and developed TE/implant infection/exposure requiring removal. Patients were divided into two groups. Group 1 had TE/implant removal, NPWTi-d placement, and TE/implant replacement 1-4 days later. Group 2 (control) underwent standard TE/implant removal and no NPWTi-d. Reinfection after TE/implant salvage, TE/implant-free days, and time to final reconstruction were assessed. The study included 47 patients (76 TE/implants) in group 1 (13 patients, 16 TE/implants) and group 2 (34 patients, 60 TE/implants). The success rate (no surgical-site infection within 90 days) of implant salvage was 81.3% in group 1. No group 1 patients abandoned completing reconstruction after TE/implant loss versus 38.2% (13 of 34) in group 2 (P = 0.0094). Mean implant-free days was 2.5 ± 1.2 in group 1 versus 134.6 ± 78.5 in group 2 (P = 0.0001). The interval to final implant-based reconstruction was 69.0 ± 69.7 days in group 1 versus 225.6 ± 93.6 days in group 2 (P = 0.0001). A breast implant salvage pathway with infected device removal, NPWTi-d placement, and early TE/implant replacement was successful in 81.3%. Patients experienced 132 less implant-free days and faster time to final reconstruction.

NIR responsive scaffold with multistep shape memory and photothermal-chemodynamic properties for complex tissue defects repair and antibacterial therapy

Complex tissue damage accompanying with bacterial infection challenges healthcare systems globally. Conventional tissue engineering scaffolds normally generate secondary implantation trauma, mismatched regeneration and infection risks. Herein, we developed an easily implanted scaffold with multistep shape memory and photothermal-chemodynamic properties to exactly match repair requirements of each part from the tissue defect by adjusting its morphology as needed meanwhile inhibiting bacterial infection on demand. Specifically, a thermal-induced shape memory scaffold was prepared using hydroxyethyl methacrylate and polyethylene glycol diacrylate, which was further combined with the photothermal agent iron tannate (FeTA) to produce NIR light-induced shape memory property. By varying ingredients ratios in each segment, this scaffold could perform a stepwise recovery under different NIR periods. This process facilitated implantation after shape fixing to avoid trauma caused by conventional methods and gradually filled irregular defects under NIR to perform suitable tissue regeneration. Moreover, FeTA also catalyzed Fenton reaction at bacterial infections with abundant H2O2, which produced excess ROS for chemodynamic antibacterial therapy. As expected, bacteriostatic rate was further enhanced by additional photothermal therapy under NIR. The in vitro and vivo results showed that our scaffold was able to perform high efficacy in both antibiosis, inflammation reduction and wound healing acceleration, indicating a promising candidate for the regeneration of complex tissue damage with bacterial infection.

Casein phosphopeptide/antimicrobial peptide co-modified SrTiO3 nanotubes for prevention of bacterial infections and repair of bone defects

Endowing titanium surfaces with multifunctional properties can reduce implant-related infections and enhance osseointegration. In this study, titanium dioxide nanotubes with strontium doping (STN) were first created on the titanium surface using anodic oxidation and hydrothermal synthesis techniques. Next, casein phosphopeptide (CCP) and an antimicrobial peptide (HHC36) were loaded into the STN with the aid of vacuum physical adsorption (STN-CP-H), giving the titanium surface a dual function of "antimicrobial-osteogenic". The surface of STN-CP-H has a suitable roughness and good hydrophilicity, which is conducive to osteoblasts. STN-CP-H had a 99 % antibacterial rate against S. aureus and E. coli and effectively prevented the growth of bacterial biofilm. Meanwhile, the antibacterial mechanism of STN-CP-H was initially explored with the help of transcriptome sequencing technology. STN-CP-H could greatly increase osteoblast adhesion, proliferation, and expression of osteogenic markers (alkaline phosphatase, runt-related transcription) when CCP and Sr worked together synergistically. In vivo, the STN-CP-H coating could effectively promote new osteogenesis around titanium implant bone and had no toxic effects on heart, liver, spleen, lung and kidney tissues. A potential anti-infection bone healing material, STN-CP-H bifunctional coating developed in this work efficiently inhibited bacterial infection of titanium implants and encouraged early osseointegration.

Emerging Strategies to Prevent Bacterial Infections on Titanium-Based Implants.

Titanium and titanium alloys remain the gold standard for dental and orthopedic implants. These materials are heavily used because of their bioinert nature, robust mechanical properties, and seamless integration with bone. However, implant-associated infections (IAIs) remain one of the leading causes of implant failure. Eradicating an IAI can be difficult since bacteria can form biofilms on the medical implant, protecting the bacterial cells against systemic antibiotics and the host's immune system. If the infection is not treated promptly and aggressively, device failure is inevitable, leading to costly multi-step revision surgeries. To circumvent this dire situation, scientists and engineers continue to develop novel strategies to protect the surface of medical implants from bacteria. In this review, details on emerging strategies to prevent infection in titanium implants are reported. These strategies include anti-adhesion properties provided by polymers, superhydrophobic, superhydrophilic, and liquid-infused surface coatings, as well as strategies and coatings employed to lyse the bacteria. Additionally, commercially available technologies and those under preclinical trials are examined while discussing current and future trends.

On-demand bactericidal and self-adaptive antifouling hydrogels for self-healing and lubricant coatings of catheters

Catheter-related infections are one of the most common nosocomial infections with increasing morbidity and mortality, and robust antibacterial or antifouling catheter coatings remain great challenges for long-term implantation. Herein, multifunctional hydrogel coatings were developed to provide persistent and self-adaptive antifouling and antibacterial effects with self-healing and lubricant capabilities. Polyvinyl alcohol (PVA) with β-cyclodextrin (β-CD) grafts (PVA-Cd) and 4-arm polyethylene glycol (PEG) with adamantane and quaternary ammonium compound (QAC) terminals (QA-PEG-Ad) were crosslinked through host-guest recognitions between adamantane and β-CD moieties to acquire PVEQ coatings. In response to bacterial infections, QACs exhibit reversible transformation between zwitterions (pH 7.4) and cationic lactones (pH 5.5) to generate on-demand bactericidal effect. Highly hydrophilic PEG/PVA backbones and zwitterionic QACs build a lubricate surface and decrease the friction coefficient 10 times compared with that of bare catheters. The antifouling hydrated layer significantly inhibits blood protein adsorption and platelet activation and reveals negligible hemolysis and cytotoxicity. The dynamic host-guest crosslinking achieves full self-healing of cracks in PVEQ hydrogels, and the mechanical profiles were recovered to over 90 % after rejuvenating the broken hydrogels, exhibiting a long-term stability after mechanical stretching, twisting, knotting and compression. After subcutaneous implantation and local bacterial infection, the retrieved PVEQ-coated catheters display no tissue adhesion and 3 log folds lower bacterial number than that of bare catheters. PVEQ coatings effectively prevent the repeated bacterial infections and there are few inflammatory reactions in the surrounding tissue, while substantial lymphoid infiltration and inflammatory cell aggregation occur in muscle tissues around the bare catheter. Thus, this study demonstrates a catheter coating strategy by on-demand bactericidal, self-adaptive antifouling, self-healing and lubricant hydrogels to address medical devices-related infections. Statement of significanceIt is estimated over two billion peripheral intravenous catheters are annually used in hospitals around the world, and catheter-associated infection has become a great clinical challenge with rapidly rising morbidity and mortality. Surface coating is considered a promising approach, but substantial challenges remain in the development of coatings that simultaneously satisfy both anti-fouling and antibacterial attributes. Even more, few attempts have been made to design mechanically robust coatings and reversible antibacterial or antifouling capabilities, which are critical for long-term medical implants. To address these challenges, we propose a concise strategy to develop hydrogel coatings from commercially available poly(ethylene glycol) and polyvinyl alcohol. In addition to self-healing and lubricant capabilities, the reversible conversion between zwitterionic and cationic lactones of quaternary ammonium compounds enables on-demand bactericidal and self-adaptive antifouling effects.

Ultrasound-Activated Probiotics Vesicles Coating for Titanium Implant Infections Through Bacterial Cuproptosis-Like Death and Immunoregulation.

Implant-associated infections (IAIs) are the main cause of prosthetic implant failure. Bacterial biofilms prevent antibiotic penetration, and the unique metabolic conditions in hypoxic biofilm microenvironment may limit the efficacy of conventional antibiotic treatment. Escaping survival bacteria may not be continually eradicated, resulting in the recurrence of IAIs. Herein, a sonosensitive metal-organic framework of Cu-TCPP (tetrakis(4-carboxyphenyl) porphyrin) nanosheets and tinidazole doped probiotic-derived membrane vesicles (OMVs) with high-penetration sonodynamic therapy (SDT), bacterial metabolic state interference, and bacterial cuproptosis-like death to eradicate IAIs is proposed. The Cu-TCPP can convert O2 to toxic 1O2 through SDT in the normoxic conditions, enhancing the hypoxic microenvironment and activating the antibacterial activity of tinidazole. The released Cu(II) under ultrasound can be converted to Cu(I) by exogenous poly(tannic acid) (pTA) and endogenous glutathione. The disruption of the bacterial membrane by SDT can enhance the Cu(I) transporter activity. Transcriptomics indicate that the SDT-enhanced Cu(I) overload and hypoxia-activated therapy hinder the tricarboxylic acid cycle (TCA), leading to bacterial cuproptosis-like death. Moreover, the OMVs-activated therapy can polarize macrophages to a M2-like phenotype and facilitate bone repair. The sonodynamic biofilm microenvironment modulation strategy, whereby the hypoxia-enhanced microenvironment is potentiated to synergize SDT with OMVs-activated therapy, provides an effective strategy for antibacterial and osteogenesis performance.

PET/CT Recognition of Costal Cartilage Infection After Breast Implant Surgery.

Postoperative infection of breast implants can lead to implant removal and other complications. This study aimed to investigate the presence of costal cartilage infection following breast implant surgery and the diagnostic role of PET/CT in identifying this rare complication. A retrospective study included 16 patients with persistent infections after breast implant removal surgery. Patients underwent PET/CT scans before surgery, and surgical plans were made based on PET/CT findings. Surgical procedures were guided by PET/CT, and specimens were collected for pathological examination and microbiological culture. Follow-up assessments were performed at 1, 3, and 12 months postoperatively. Among the 16 patients, 11 were diagnosed with costal cartilage infection, whereas 5 had subcutaneous soft tissue infections. PET/CT accurately identified costal cartilage infection in all cases and localized the infected costal cartilage in the majority of cases. Microbiological culture results showed various pathogens. All patients were cured with one or staged surgery. Costal cartilage infection following breast implant surgery is a significant concern. PET/CT plays a crucial role in the accurate diagnosis and localization of infected costal cartilage, aiding in appropriate surgical management. Patients should be closely monitored for the possibility of costal cartilage infection when experiencing persistent symptoms after breast implant surgery.

The corrosion resistance, biocompatibility and antibacterial properties of the silver-doped dicalcium phosphate dihydrate coating on the surface of the additively manufactured NiTi alloy

Additive manufacturing (AM) of NiTi alloys has attracted significant attention for its exceptional forming precision and suitability for processing complex medical implant structures. However, challenges such as the excessive release of Ni2+, bioinertness, and insufficient antibacterial ability have emerged as primary factors impeding the application of NiTi alloy in the medical field. To address these issues, the silver-doped dicalcium phosphate dihydrate (Ag-DCPD) coating is electrochemically deposited on the LPBF-NiTi alloy surface for the first time. The study investigates the effects of varying Ag doping content (2 %, 4 %, and 6 %) on morphology, corrosion resistance, biomineralization, and long-term stability of DCPD coating using scanning electron microscopy (SEM), electrochemical analysis, and immersion tests. Results show that the 4Ag-DCPD coating exhibits the most uniform and dense surface morphology, excellent corrosion resistance, and biomineralization. The corrosion current density (Icorr) is two orders of magnitude lower than that of the LPBF-NiTi alloy matrix (from 1.1 × 10−6 to 1.4 × 10−8), and a dense hydroxyapatite (HA) layer forms after immersion testing. In vitro cell experiments indicate that the 4Ag-DCPD coating maintains high cell viability, favorable cell morphology, and excellent biocompatibility. Additionally, the 4Ag-DCPD coating demonstrates effective antibacterial activity against Escherichia coli (79.75 %) and Staphylococcus aureus (69.33 %), which reduces the risk of implantation infection. Overall, the 4Ag-DCPD coated LPBF-NiTi alloy shows promising clinical application potential as a medical implant.

Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial

BackgroundInsertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.MethodsDRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.ConclusionWe present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.Trial registrationClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.