Effect of cement volume on biomechanical response of a spine segment treated with a PEEK polymer implant: a finite element comparative study with vertebroplasty.

In the current study, a 3D finite element study was performed to investigate the biomechanical response of an osteoporotic spine segment treated with a novel transpedicular implant (V-STRUT©, Hyprevention, France) made of PEEK (polyetheretherketone) material combined with either injections of 2, 3, 4, 5 and 6 cc of cement. The objective was to assess numerically the biomechanical performance of the implant in combination with different doses of the injected bone cement and to compare its performance with the gold standard vertebroplasty (VP) technique. A female (69 yo) was selected and a 3D finite element model of an osteoporotic spine segment was built based on a Computed Tomography (CT) scan performed from T12 to L2 with corresponding intervertebral discs and ligaments. A heterogeneous distribution of bone material properties was assigned to the bone using grey scale levels. Bilateral ellipsoid geometries of the inserted cement were retained for the V-STRUT and VP models based on experimental observation performed on different patients treated with the V-STRUT device. The current study demonstrated an optimal dose of 4 cc of bilaterally injected cement for the V-STRUT and VP techniques to restore the treated segment and confirmed that the V-STRUT device in combination with bone cement is superior to VP alone in establishing the normal stiffness and in reducing the applied stress to the immediately adjacent vertebral levels.

Surgical and Percutaneous Image-guided Therapies of Abdominal Wall Endometriosis: a Systematic Review of Current Evidence.

OBJECTIVE: Despite various surgical and non-surgical strategies for abdominal wall endometriosis, the lack of definitive guidance on optimal treatment choice leads to clinical uncertainty. This review scrutinizes the safety and efficacy of abdominal wall endometriosis treatments to aid in decision-making. DATA SOURCES: We performed a systematic literature review of PubMed, Embase and Cochrane Library databases from 1947 until December 2023. METHODS OF STUDY SELECTION: A comprehensive literature search identified studies that assessed both surgical and nonsurgical interventions, including high-intensity focused ultrasound (HIFU), cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). This review is registered in NIHR-PROSPERO (CRD 42023494969). Local tumor control (LTC), local pain relief (LPR) and adverse events (AE) were recorded. TABULATION, INTEGRATION, AND RESULTS: This review included 51 articles among 831 identified. All study designs were considered eligible for inclusion. A total of 2,674 patients are included: 2,219 patients (83%) undergoing surgery, and 455 (17%) undergoing percutaneous interventions (342 HIFU, 103 cryoablation, 1 RFA, 9 MWA). Follow-up length was 18 months in median, ranging from 1 to 235 months. Overall LTC rates ranged from 86% to 100%. Surgical interventions consistently demonstrated the highest rate of LTC with a median rate of 100%, and LPR with a median rate of 98.2% (95% confidence interval [CI]: 93.9-97.7). HIFU showed median LTC and LPR rates, respectively of 95.65% (95% CI, 87.7-99.9) and 76.1% (95% CI, 61.8-90.4); and cryoablation of 85.7% (95% CI, 66.0-99.9) and 79.2% (95% CI, 67.4-91.03). Minor AE were reported after surgery in 17.5% of patients (225/1284) including 15.9% (199/1284) of mesh implantation; 76.4% (239/313) after HIFU; and 8.7 % (9/103) after cryoablation. Severe AE were reported in 25 patients in the surgery group and 1 in the percutaneous group. CONCLUSION: The safety profile and efficacy of nonsurgical interventions support their clinical utility for management of abdominal wall endometriosis.

[Resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogenic addictions: BRAF and ALK]. / Résistance aux anti-EGFR via l'acquisition successive et cumulée de deux nouvelles addictions oncogénique BRAF et ALK.

Targeted therapies are the standard first-line treatment for metastatic lung adenocarcinoma with certain molecular abnormalities. These abnormalities are particularly common in Southeast Asia and French Polynesia. A 51-year-old Tahitian female non-smoker was diagnosed in 2018 with stage IV lung adenocarcinoma harboring a p.L858R EGFR mutation. She received gefitinib as first-line treatment. Due to locoregional progression and the presence of a resistance mutation (p.T790M of EFGR), she received osimertinib as second-line treatment, after which chemotherapy was proposed as 3rd-line treatment. An additional biopsy detected not only the previously known EGFR mutation, but also a BRAF p.V600E mutation. Following disease progression during chemotherapy, the patient received targeted therapies combining dabrafenib, trametinib and osimertinib. Due to a dissociated response after four months of treatment, a 5th line of paclitaxel bevacizumab was initiated. Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed. As the response was once again dissociated, a final line was proposed before stopping active treatments due to their toxicity and overall deterioration in the patient's state of health. This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.

Embolization of Middle Meningeal Arteries for Symptomatic Subacute Subdural Hematoma in Patients with Cancer.

PURPOSE: The purpose of this study was to evaluate the technical and clinical success of middle meningeal artery (MMA) embolization performed for symptomatic subacute subdural hematoma (SDH) in patients with cancer. METHODS: This study retrospectively included 23 consecutive patients (12 men, 11 women; median age 61 years, interquartile range: 55.5-75.5) who underwent 34 MMA angiograms for symptomatic SDH in 2022 and 2023. Median SDH thickness was 10.5 mm (7-12). Median platelet count was 117 K/mcL (54.5-218). 10 patients (43.5%, 10/23) had hematologic malignancies, seven patients (30.4%, 7/23) had surgery. Fluoroscopy time (FT), reference dose (RD), and kerma area product (Kap) were analyzed. Adverse events and outcomes were recorded. RESULTS: The median imaging and clinical follow-up were 65 days (36.5-190.5) and 163 days (86-274), respectively. The technical success rate was 91.2% (31/34) as three MMA were not identified in two patients. Median procedure duration was 61 min (55.5-75.5). Median FT was 21.6 min (15.5-31.8); median RD was 158 mGy (96-256); and median Kap was 32.9 Gy.cm2 (20.4-45.1). No further intervention was needed. For 16 patients, SDH resolved after in median 59.5 days (50-90). For seven patients, SDH remained visible on the last imaging follow-up performed at 24 days in median (6.5-36.5). No predictive factor of failure was identified. The adverse event rate was 1/23 (4.3%). Eight patients (34.8%, 8/23) died during follow-up from progression of cancer. CONCLUSION: MMA embolization of symptomatic SDH in patients with cancer appears safe and is associated with improvement in clinical symptoms.

Detection of florfenicol resistance in opportunistic Acinetobacter spp. infections in rural Thailand.

Florfenicol (Ff) is an antimicrobial agent belonging to the class amphenicol used for the treatment of bacterial infections in livestock, poultry, and aquaculture (animal farming). It inhibits protein synthesis. Ff is an analog of chloramphenicol, an amphenicol compound on the WHO essential medicine list that is used for the treatment of human infections. Due to the extensive usage of Ff in animal farming, zoonotic pathogens have developed resistance to this antimicrobial agent. There are numerous reports of resistance genes from organisms infecting or colonizing animals found in human pathogens, suggesting a possible exchange of genetic materials. One of these genes is floR, a gene that encodes for an efflux pump that removes Ff from bacterial cells, conferring resistance against amphenicol, and is often associated with mobile genetic elements and other resistant determinants. In this study, we analyzed bacterial isolates recovered in rural Thailand from patients and environmental samples collected for disease monitoring. Whole genome sequencing was carried out for all the samples collected. Speciation and genome annotation was performed revealing the presence of the floR gene in the bacterial genome. The minimum inhibitory concentration (MIC) was determined for Ff and chloramphenicol. Chromosomal and phylogenetic analyses were performed to investigate the acquisition pattern of the floR gene. The presence of a conserved floR gene in unrelated Acinetobacter spp. isolated from human bacterial infections and environmental samples was observed, suggesting multiple and independent inter-species genetic exchange of drug-resistant determinants. The floR was found to be in the variable region containing various mobile genetic elements and other antibiotic resistance determinants; however, no evidence of HGT could be found. The floR gene identified in this study is chromosomal for all isolates. The study highlights a plausible impact of antimicrobials used in veterinary settings on human health. Ff shares cross-resistance with chloramphenicol, which is still in use in several countries. Furthermore, by selecting for floR-resistance genes, we may be selecting for and facilitating the zoonotic and reverse zoonotic exchange of other flanking resistance markers between human and animal pathogens or commensals with detrimental public health consequences.

Safety and efficacy of cryoablation of Soft-Tissue tumors.

OBJECTIVES: To assess the safety and efficacy of percutaneous cryoablation (CA) of soft-tissue tumors (desmoid tumors (DT), vascular malformations (VM), and abdominal wall endometriosis (AWE)). METHODS: This systematic review of studies published before January 2024 encompassed a detailed analysis of CA techniques and technical aspects for the treatment of soft-tissue tumors. Data concerning CA efficacy, complication rates, and other relevant metrics was extracted and included for analysis. RESULTS: The analysis included 27 studies totaling 554 CA procedures. For DT (13 studies, 393 sessions), CA showed an average pain reduction of 79 ± 17% (range: 57-100) and a lesion volume decrease of 71.5 ± 9.8% (range: 44-97). VM (4 studies, 58 sessions) had a 100% technical success rate and an average pain reduction of 72 ± 25% (range: 63-85). The average pain reduction for AWE (6 studies, 103 sessions) was 82 ± 13% (range: 62-100). Overall, the complication rate for CA was low, with minor adverse events (AE) in about 20% of patients and major events in less than 5% of patients. CONCLUSION: Showing substantial efficacy in pain reduction and lesion volume decrease, as well as low incidence of severe AE, CA presents as a highly effective and safe alternative for the treatment of soft-tissue tumors. ADVANCES IN KNOWLEDGE: CA is effective and safe in treating soft-tissue tumors, particularly DT, VM, and AWE.

Percutaneous Lung Biopsies With Robotic Systems: A Systematic Review of Available Clinical Solutions.

Objectives: This systematic review aims to assess existing research concerning the use of robotic systems to execute percutaneous lung biopsy. Methods: A systematic review was performed and identified 4 studies involving robotic systems used for lung biopsy. Outcomes assessed were operation time, radiation dose to patients and operators, technical success rate, diagnostic yield, and complication rate. Results: One hundred and thirteen robot-guided percutaneous lung biopsies were included. Technical success and diagnostic yield were close to 100%, comparable to manual procedures. Technical accuracy, illustrated by needle positioning, showed less frequent needle adjustments in robotic guidance than in manual guidance (P < .001): 2.7 ± 2.6 (range 1-4) versus 6 ± 4 (range 2-12). Procedure time ranged from comparable to reduced by 35% on average (20.1 ± 11.3 minutes vs 31.4 ± 10.2 minutes, P = .001) compared to manual procedures. Patient irradiation ranged from comparable to reduced by an average of 40% (324 ± 114.5 mGy vs 541.2 ± 446.8 mGy, P = .001). There was no significant difference in reported complications between manual biopsy and biopsies that utilized robotic guidance. Conclusion: Robotic systems demonstrate promising results for percutaneous lung biopsy. These devices provide adequate accuracy in probe placement and could both reduce procedural duration and mitigate radiation exposure to patients and practitioners. However, this review underscores the need for larger, controlled trials to validate and extend these findings.

A novel mitochondrial DNA variant in MT-ND6: m.14430A>C p.(Trp82Gly) identified in a patient with Leigh syndrome and complex I deficiency.

Leigh syndrome is a severe progressive mitochondrial disorder mainly affecting children under the age of 5 years. It is caused by pathogenic variants in any one of more than 75 known genes in the nuclear or mitochondrial genomes. A 19-week-old male infant presented with lactic acidosis and encephalopathy following a 2-week history of irritability, neuroregression and poor weight gain. He was hypotonic with pathological reflexes, impaired vision, and nystagmus. Brain MRI showed extensive bilateral symmetrical T2 hyperintense lesions in basal ganglia, thalami, and brainstem. Metabolic workup showed elevated serum alanine, and heavy lactic aciduria with increased ketones, fumarate, malate, and alpha-ketoglutarate as well as reduced succinate on urine organic acid analysis. Lactic acidemia persisted, with only a marginally elevated lactate:pyruvate ratio (16.46, ref. 0-10). He demised at age 7 months due to respiratory failure. Exome sequencing followed by virtual gene panel analysis for pyruvate metabolism and mitochondrial defects could not identify any nuclear cause for Leigh syndrome. Mitochondrial DNA (mtDNA) genome sequencing revealed 88% heteroplasmy for a novel variant, NC_012920.1(MT-ND6):m.14430A>C p.(Trp82Gly), in blood DNA. This variant was absent from the unaffected mother's blood, fibroblast, and urine DNA, and detected at a level of 5% in her muscle DNA. Mitochondrial respiratory chain analysis revealed markedly reduced mitochondrial complex I activity in patient fibroblasts (34% of parent and control cells), and reduced NADH-linked respirometry (less than half of parental and control cells), while complex II driven respirometry remained intact. The combined clinical, genetic, and biochemical findings suggest that the novel MT-ND6 variant is the likely cause of Leigh syndrome in this patient. The mitochondrial ND6 protein is a subunit of complex I. An interesting finding was the absence of a significantly elevated lactate:pyruvate ratio in the presence of severe lactatemia, which directed initial diagnostic efforts towards excluding a pyruvate metabolism defect. This case highlights the value of a multidisciplinary approach and complete genetic workup to diagnosing mitochondrial disorders in South African patients.

Spatio-temporal spread of artemisinin resistance in Southeast Asia.

Current malaria elimination targets must withstand a colossal challenge-resistance to the current gold standard antimalarial drug, namely artemisinin derivatives. If artemisinin resistance significantly expands to Africa or India, cases and malaria-related deaths are set to increase substantially. Spatial information on the changing levels of artemisinin resistance in Southeast Asia is therefore critical for health organisations to prioritise malaria control measures, but available data on artemisinin resistance are sparse. We use a comprehensive database from the WorldWide Antimalarial Resistance Network on the prevalence of non-synonymous mutations in the Kelch 13 (K13) gene, which are known to be associated with artemisinin resistance, and a Bayesian geostatistical model to produce spatio-temporal predictions of artemisinin resistance. Our maps of estimated prevalence show an expansion of the K13 mutation across the Greater Mekong Subregion from 2000 to 2022. Moreover, the period between 2010 and 2015 demonstrated the most spatial change across the region. Our model and maps provide important insights into the spatial and temporal trends of artemisinin resistance in a way that is not possible using data alone, thereby enabling improved spatial decision support systems on an unprecedented fine-scale spatial resolution. By predicting for the first time spatio-temporal patterns and extents of artemisinin resistance at the subcontinent level, this study provides critical information for supporting malaria elimination goals in Southeast Asia.

Interventional Oncology: 2024 Update.

Interventional Oncology (IO) stands at the forefront of transformative cancer care, leveraging advanced imaging technologies and innovative interventions. This narrative review explores recent developments within IO, highlighting its potential impact facilitated by artificial intelligence (AI), personalized medicine and imaging innovations. The integration of AI in IO holds promise for accelerating tumour detection and characterization, guiding treatment strategies and refining predictive models. Imaging modalities, including functional MRI, PET and cone beam CT are reshaping imaging and precision. Navigation, fusion imaging, augmented reality and robotics have the potential to revolutionize procedural guidance and offer unparalleled accuracy. New developments are observed in embolization and ablative therapies. The pivotal role of genomics in treatment planning, targeted therapies and biomarkers for treatment response prediction underscore the personalization of IO. Quality of life assessment, minimizing side effects and long-term survivorship care emphasize patient-centred outcomes after IO treatment. The evolving landscape of IO training programs, simulation technologies and workforce competence ensures the field's adaptability. Despite barriers to adoption, synergy between interventional radiologists' proficiency and technological advancements hold promise in cancer care.

Long-term outcomes after percutaneous cryoablation of abdominal wall endometriosis.

OBJECTIVE: To retrospectively evaluate the long-term outcomes after percutaneous cryoablation of abdominal wall endometriosis (AWE). METHOD: The Institutional Review Board approved this retrospective observational review of 40 consecutive patients, of a median age of 37 years (interquartile range [IQR] 32-40 years), presenting with a total of 52 symptomatic AWE nodules. All patients underwent cryoablation between January 2013 and May 2022 with a minimum follow-up period of 12 months. Outcomes were assessed using a visual analog scale (VAS) that measured pain, as well as by magnetic resonance imaging (MRI). The pain-free survival rates were derived using the Kaplan-Meier estimator. Adverse events were analyzed and graded using the classification system of the Cardiovascular and Interventional Radiological Society of Europe. RESULTS: The median follow-up time was 40.5 months (IQR 26.5-47.2 months). The median VAS score before cryoablation was 8 (IQR 7-9). Complete relief of symptoms was documented in 80% (32/40) of patients at 3 months after initial cryoablation and correlated with the absence of residual endometriosis nodules on MRI. The median pain-free survival rates were 89.2% [95% CI, 70.1-96.4%] at 36 months and 76.8% [95% CI, 55.3-83.8%] after 60 months. No patient or lesion characteristics were found to be prognostic of failure. No major adverse events or side effects were reported in long term. CONCLUSION: Cryoablation safely and effectively afforded long-term pain relief for patients with AWE nodules. CLINICAL RELEVANCE STATEMENT: AWE cryoablation was found to be safe and effective in the long-term. KEY POINTS: • Cryoablation is highly effective with 80% of patients experiencing complete relief of AWE symptoms after a single procedure. • Cryoablation is safe without long-term adverse events or side effects. • The median pain-free survival rates are 89.2% at 36 months and 76.8% at 60 months.

Comparison of a Patient-Mounted Needle-Driving Robotic System versus Single-Rotation CT Fluoroscopy to Perform CT-Guided Percutaneous Lung Biopsies.

PURPOSE: To compare the effectiveness of percutaneous lung biopsy using a patient-mounted needle-driving robotic system with that using a manual insertion of needles under computed tomography (CT) fluoroscopy guidance. MATERIALS AND METHODS: In this institutional review board approved study, the cohort consisted of a series of patients who underwent lung biopsies following the intention-to-treat protocol from September 2022 to September 2023 using robot (n = 15) or manual insertion under single-rotation CT fluoroscopy (n = 66). Patient and procedure characteristics were recorded as well as outcomes. RESULTS: Although age, body mass index, and skin-to-target distance were not statistically different, target size varied (median, 8 mm [interquartile range, 6.5-9.5 mm] for robot vs 12 mm [8-18 mm] for single-rotation CT fluoroscopy; P = .001). No statistical differences were observed in technical success (86.7% [13/15] vs 89.4% [59/66], P = .673), Grade 3 adverse event (AE) (6.7% [1/15] vs 12.1% [8/66], P = .298), procedural time (28 minutes [22-32 minutes] vs 19 minutes [14.3-30.5 minutes], P = .086), and patient radiation dose (3.9 mSv [3.2-5.6 mSv] vs 4.6 mSv [3.3-7.5 mSv], P = .398). In robot-assisted cases, the median angle out of gantry plane was 10° (6.5°-16°), although it was null (0°-5°) for single-rotation CT fluoroscopy (P = .001). CONCLUSIONS: Robot-assisted and single-rotation CT fluoroscopy-guided percutaneous lung biopsies were similar in terms of technical success, diagnostic yield, procedural time, AEs, and radiation dose, although robot allowed for out-of-gantry plane navigation along the needle axis.

Response to comment on 'The clinical pharmacology of tafenoquine in the radical cure of Plasmodium vivax malaria: An individual patient data meta-analysis'.

In our recent paper on the clinical pharmacology of tafenoquine (Watson et al., 2022), we used all available individual patient pharmacometric data from the tafenoquine pre-registration clinical efficacy trials to characterise the determinants of anti-relapse efficacy in tropical vivax malaria. We concluded that the currently recommended dose of tafenoquine (300 mg in adults, average dose of 5 mg/kg) is insufficient for cure in all adults, and a 50% increase to 450 mg (7.5 mg/kg) would halve the risk of vivax recurrence by four months. We recommended that clinical trials of higher doses should be carried out to assess their safety and tolerability. Sharma and colleagues at the pharmaceutical company GSK defend the currently recommended adult dose of 300 mg as the optimum balance between radical curative efficacy and haemolytic toxicity (Sharma et al., 2024). We contend that the relative haemolytic risks of the 300 mg and 450 mg doses have not been sufficiently well characterised to justify this opinion. In contrast, we provided evidence that the currently recommended 300 mg dose results in sub-maximal efficacy, and that prospective clinical trials of higher doses are warranted to assess their risks and benefits.

Online searches for hepatocellular carcinoma drugs mirror prescription trends across specialties and changes in guideline recommendations.

Background & aims: The treatment options for systemically progressed hepatocellular carcinoma (HCC) have significantly expanded in recent years. In this study, we aimed to evaluate the potential of Google searches as a reflection of prescription rates for HCC drugs in the United States (US). Methods: We conducted an in-depth analysis of US prescription data obtained from the IQVIA National Prescription Audit (NPA) and corresponding Google Trends data from January 2017 to December 2022. We focused on drugs used in the first line and second or later treatment lines for HCC, collecting data on their prescriptions and search rates. Search volumes were collected as aggregated search queries for both generic drugs and their respective brand names. Results: During the study period from Q1 2017 to Q4 2022, monthly prescriptions for drugs used in HCC treatment showed an 173% increase (from 1253 to 3422). Conversely online searches increased by 3.5% (from 173 to 179 per 10 million searches). Notably, strong correlations were observed between search interest and prescriptions for newer drugs, which indicates increasing usage, while older drugs with declining usage displayed limited correlation. Our findings suggest a growing role of non-physician professions in managing systemically progressed HCC within the US healthcare system, although oncologists remained primarily responsible for drug prescriptions. Conclusions: In conclusion, online search monitoring can offer the potential to reflect prescription trends specifically related to the treatment of HCC. This approach provides a swift and accessible means of evaluating the evolving landscape of HCC treatment.

Polyetheretherketone Polymer Transpedicular Vertebral System to Treat Vertebral Compression Fracture: A Multicentre Pilot Study of Feasibility and Safety.

OBJECTIVES: To prospectively evaluate the feasibility and safety of a polyetheretherketone (PEEK) polymer transpedicular vertebral system to treat vertebral compression fracture (VCF). METHODS: Nine consecutive patients (4 men and 5 women; median age 59 [interquartile range: 58-64 years]) were included. The procedure duration, length of hospital stay, and complications were reported. Visual analog scale (VAS) and the Oswestry disability index (ODI) for pain and disability were assessed before and at 2, 6, and 12-month after the procedure. RESULTS: The procedure was technically feasible in all patients. The median procedural time was 64 minutes [45-94]. Only minor adverse events were reported (5 clinically asymptomatic cement leakages) but no severe complications. No post procedural adjacent fracture was reported during follow-up (median: 193 days [147-279]). The median VAS score decreased from 55 mm [50-70] before the procedure to 25 mm [5-30] at 2-month (P = .0003) and 30 mm [15-40] at 6-month follow-up (P = .14). The median ODI decreased from 23% [19-26] before the procedure to 12% [10-14] at 2-month (P = .03) and 12% [9-20] at 6-month follow-up (P = .47). CONCLUSIONS: Percutaneous transpedicular fixation of VCF by PEEK implants appears feasible and safe.

Directional microwave ablation in spine: experimental assessment of computational modeling.

BACKGROUND: Despite the theoretical advantages of treating metastatic bone disease with microwave ablation (MWA), there are few reports characterizing microwave absorption and bioheat transfer in bone. This report describes a computational modeling-based approach to simulate directional microwave ablation (dMWA) in spine, supported by ex vivo and pilot in vivo experiments in porcine vertebral bodies. MATERIALS AND METHODS: A 3D computational model of microwave ablation within porcine vertebral bodies was developed. Ex vivo porcine vertebra experiments using a dMWA applicator measured temperatures approximately 10.1 mm radially from the applicator in the direction of MW radiation (T1) and approximately 2.4 mm in the contra-lateral direction (T2). Histologic assessment of ablated ex vivo tissue was conducted and experimental results compared to simulations. Pilot in vivo experiments in porcine vertebral bodies assessed ablation zones histologically and with CT and MRI. RESULTS: Experimental T1 and T2 temperatures were within 3-7% and 11-33% of simulated temperature values. Visible ablation zones, as indicated by grayed tissue, were smaller than those typical in other soft tissues. Posthumous MRI images of in vivo ablations showed hyperintensity. In vivo experiments illustrated the technical feasibility of creating directional microwave ablation zones in porcine vertebral body. CONCLUSION: Computational models and experimental studies illustrate the feasibility of controlled dMWA in bone tissue.