Joint Model-Order and Robust DoA Estimation for Underwater Sensor Arrays.

The direction-of-arrival (DoA) estimation algorithms have a fundamental role in target bearing estimation by sensor array systems. Recently, compressive sensing (CS)-based sparse reconstruction techniques have been investigated for DoA estimation due to their superior performance relative to the conventional DoA estimation methods, for a limited number of measurement snapshots. In many underwater deployment scenarios, the acoustic sensor arrays must perform DoA estimation in the presence of several practical problems such as unknown source number, faulty sensors, low values of the received signal-to-noise ratio (SNR), and access to a limited number of measurement snapshots. In the literature, CS-based DoA estimation has been investigated for the individual occurrence of some of these errors but the estimation under joint occurrence of these errors has not been studied. This work investigates the CS-based robust DoA estimation to account for the joint impact of faulty sensors and low SNR conditions experienced by a uniform linear array of underwater acoustic sensors. Most importantly, the proposed CS-based DoA estimation technique does not require a priori knowledge of the source order, which is replaced in the modified stopping criterion of the reconstruction algorithm by taking into account the faulty sensors and the received SNR. Using Monte Carlo techniques, the DoA estimation performance of the proposed method is comprehensively evaluated in relation to other techniques.

The role of surgical transcatheter valve implantation for the treatment of severe mitral annular calcification.

With a rise in the aging population, mitral annular calcification is increasingly encountered with an incidence of 10% in over 70 years old. This with increasing patient comorbidities presents a technical challenge due to the risk of atrioventricular disruption which is associated with high operative mortality of up to 75%. We describe two cases of severe mitral disease with marked annular calcification successfully treated with a balloon expandable transcatheter valve which was deployed on cardiopulmonary bypass via a trans-atrial approach.

Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury.

BACKGROUND: Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects. METHODS: We investigated the in vitro effects of GSK1995057 on human pulmonary microvascular endothelial cells (HMVEC-L) and then assessed the effects of pretreatment with nebulised GSK1995057 in a non-human primate model of acute lung injury. We then tested translation to humans by investigating the effects of a single nebulised dose of GSK1995057 in healthy humans (n=37) in a randomised controlled clinical trial in which subjects were subsequently exposed to inhaled endotoxin. RESULTS: Selective inhibition of TNFR1 signalling potently inhibited cytokine and neutrophil adhesion molecule expression in activated HMVEC-L monolayers in vitro (P<0.01 and P<0.001, respectively), and also significantly attenuated inflammation and signs of lung injury in non-human primates (P<0.01 in all cases). In a randomised, placebo-controlled trial of nebulised GSK1995057 in 37 healthy humans challenged with a low dose of inhaled endotoxin, treatment with GSK1995057 attenuated pulmonary neutrophilia, inflammatory cytokine release (P<0.01 in all cases) and signs of endothelial injury (P<0.05) in bronchoalveolar lavage and serum samples. CONCLUSION: These data support the potential for pulmonary delivery of a selective TNFR1 dAb as a novel therapeutic approach for the prevention of acute respiratory distress syndrome. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01587807.

Characterisation of eppin function: expression and activity in the lung.

Eppin is a serine protease inhibitor expressed in male reproductive tissues.The aim of this study was to investigate the localisation and regulation of eppin expression in myeloid and epithelial cell lines, and explore its potential role as a multifunctional host defence protein.Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with acute respiratory distress syndrome and cystic fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with Toll-like receptor agonists, cytokines and hormone receptor agonists. However, upregulated expression and secretion of eppin was observed following treatment of monocytes with epidermal growth factor. Incubation of recombinant eppin with monocytic cells resulted in significant inhibition of lipopolysaccharide-induced chemokine production. Furthermore, eppin inhibited lipopolysaccharide-induced NF-κB activation by a mechanism which involved accumulation of phosphorylated IκBα. In an in vivo model of lung inflammation induced by lipopolysaccharide, eppin administration resulted in decreased recruitment of neutrophils to the lung with a concomitant reduction in the levels of the neutrophil chemokine macrophage inflammatory protein-2.Overall, these results suggest a role for eppin outside of the reproductive tract and that eppin may have a role in the innate immune response in the lung.

Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation.

RATIONALE: Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. OBJECTIVE: To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. METHODS: We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 µg LPS inhalation (n=30). MEASUREMENTS AND MAIN RESULTS: After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 µg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1ß (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). CONCLUSIONS: Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products.

A role for whey acidic protein four-disulfide-core 12 (WFDC12) in the regulation of the inflammatory response in the lung.

INTRODUCTION: Secretory leucocyte protease inhibitor and elafin are members of the whey acidic protein (WAP), or WAP four disulfide-core (WFDC), family of proteins and have multiple contributions to innate defence including inhibition of neutrophil serine proteases and inhibition of the inflammatory response to lipopolysaccharide (LPS). This study aimed to explore potential activities of WFDC12, a previously uncharacterised WFDC protein expressed in the lung. METHODS: Recombinant expression and purification of WFDC12 were optimised in Escherichia coli. Antiprotease, antibacterial and immunomodulatory activities of recombinant WFDC12 were evaluated and levels of endogenous WFDC12 protein were characterised by immunostaining and ELISA. RESULTS: Recombinant WFDC12 inhibited cathepsin G, but not elastase or proteinase-3 activity. Monocytic cells pretreated with recombinant WFDC12 before LPS stimulation produced significantly lower levels of the pro-inflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared with cells stimulated with LPS alone. Recombinant WFDC12 became conjugated to fibronectin in a transglutaminase-mediated reaction and retained antiprotease activity. In vivo WFDC12 expression was confirmed by immunostaining of human lung tissue sections. WFDC12 levels in human bronchoalveolar lavage fluid from healthy and lung-injured patients were quantitatively compared, showing WFDC12 to be elevated in both patients with acute respiratory distress syndrome and healthy subjects treated with LPS, relative to healthy controls. CONCLUSIONS: Together, these results suggest a role for this lesser known WFDC protein in the regulation of lung inflammation.

Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high mortality and long-term morbidity. To date there is no effective pharmacological therapy. Aspirin therapy has recently been shown to reduce the risk of developing ARDS, but the effect of aspirin on established ARDS is unknown. METHODS: In a single large regional medical and surgical ICU between December 2010 and July 2012, all patients with ARDS were prospectively identified and demographic, clinical, and laboratory variables were recorded retrospectively. Aspirin usage, both pre-hospital and during intensive care unit (ICU) stay, was included. The primary outcome was ICU mortality. We used univariate and multivariate logistic regression analyses to assess the impact of these variables on ICU mortality. RESULTS: In total, 202 patients with ARDS were included; 56 (28%) of these received aspirin either pre-hospital, in the ICU, or both. Using multivariate logistic regression analysis, aspirin therapy, given either before or during hospital stay, was associated with a reduction in ICU mortality (odds ratio (OR) 0.38 (0.15 to 0.96) P = 0.04). Additional factors that predicted ICU mortality for patients with ARDS were vasopressor use (OR 2.09 (1.05 to 4.18) P = 0.04) and APACHE II score (OR 1.07 (1.02 to 1.13) P = 0.01). There was no effect upon ICU length of stay or hospital mortality. CONCLUSION: Aspirin therapy was associated with a reduced risk of ICU mortality. These data are the first to demonstrate a potential protective role for aspirin in patients with ARDS. Clinical trials to evaluate the role of aspirin as a pharmacological intervention for ARDS are needed.

Telesimulation Training for Endoscopic Mitral Valve Surgery: An Air-Pilot Training Concept for Distance Training.

OBJECTIVE: The aim of this study was to validate and assess the feasibility and impact of telesimulation training on surgical skills using a portable mitral valve telesimulator. METHODS: A telesimulation course composed of 3 online modules was designed based on backwards chaining, preassessment and postassessment, performance feedback, hands-on training on a telesimulator, and the theoretical content. A fully 3-dimensional-printed and transportable telesimulator was developed and sent out to the participants with instruments that were needed. Feedback about the platform was obtained from participants to validate its value as a training tool. Theoretical and technical assessments were carried out before and after the course. Technical assessments were based on the accuracy and time taken to place sutures at the anterior and posterior mitral annulus. RESULTS: In total, 11 practicing cardiac surgeons from Oceania, Asia, Europe, and North America completed the course. Theoretical preassessment and postassessment showed that participants scored significantly higher on postassessment (mean 87.5% vs 68.1%, P < 0.004). The participant evaluation scores of the simulator as a tool for endoscopic mitral valve surgery was 4 to 5 out of 5. There was a significant improvement in the speed (median 14.5 vs 39.5 s, P < 0.005) and the accuracy to place sutures in the mitral valve annulus following course completion (P < 0.001). CONCLUSIONS: Here we validated the educational value of a novel telesimulation platform and validated the feasibility to teach participants at a distance the knowledge and skills for endoscopic mitral valve surgery. Future studies will be required to validate the improvement in skills during surgery.

Comparative in-vivo bond failure rate of orthodontic brackets when bracket base is treated with micro-abrasive blasting vs. acid etching: eighteen month randomized control trial and scanning electron microscope study.

Background: The aim of this study was threefold. Firstly, it aimed to introduce and detail a novel method for chemically etching the bases of stainless-steel orthodontic brackets. Secondly, the study sought to investigate the structural alterations within the brackets' microstructure following chemical etching compared to those with sandblasted bases, using electron microscopy analysis. Lastly, the study aimed to evaluate and compare the long-term durability and survivability of orthodontic brackets with chemically etched bases versus those with sandblasted bases, both bonded using the conventional acid etch technique with Transbond XT adhesive, over an 18-month follow-up period. Methods: The study was a randomized clinical control trial with triple blinding and split-mouth study design and consisted of two groups. The brackets in the sandblasted group were prepared by sandblasting the intaglio surface of the base of the bracket with 50 µm SiO2 particles. Hydrofluoric acid was used to roughen the base in the acid-etched group. The bases of the brackets were viewed under an electron microscope to analyze the topographical changes. Results: A total of 5,803 brackets (3,006 acid-etch, 2,797 sandblasted) in 310 patients were bonded, in a split-mouth design by the same operator. The patients were followed for 18 months. The failure rate of 2.59% and 2.7% was noted in an acid-etched and sandblasted group, respectively. There was a close approximation of curves in the Kaplan-Meier plot, and the survival distribution of the two groups in the log-rank (Mantel-Cox) test was insignificant; x2 = 0.062 (P value = 0.804). Conclusion: Acid etching if the bases of the brackets can be used as an alternative to sandblasting furthermore acid etching can be performed on the chair side.

An international survey-based assessment of minimally invasive mitral valve surgery.

OBJECTIVES: Minimally invasive mitral valve surgery (MIMVS) has been shown to be safe and feasible however its adoption has lagged globally. The international consortium is lacking a set of guidelines that are specific to MIMVS. The aim of this study was to capture the practices of MIMVS in different centres. METHODS: A survey was constructed containing 52 multiple-choice and open-ended questions about various aspects of MIMVS. The survey was sent to centres that routinely and frequently perform MIMVS. All surgeons provided informed consent for participating in the survey and publication of data. RESULTS: The survey was sent to 75 known surgeons from whom 32 (42%) completed the survey. All survey responders performed >25 MIMVS cases annually. Twenty (68%) of the surgeons thought that simulation training, MIMVS fellowship and proctorship are all essential prior to commencing an MIMVS program. Eleven (34%) of the surgeons stated that 50-100 MIMVS cases are required to overcome the learning curve, followed by 6 (18%) who said 21-30 cases should suffice. Eighteen (62%) of the surgeons had adopted a fully endoscopic approach for their MIMVS, followed by 15 (51%) surgeons who had performed cases via endoscopic-assisted strategies, 5 (17%) surgeons had conducted the operation under direct visualization and 6 (20%) surgeons had used a robot for their MIMVS. CONCLUSIONS: The study highlights a marked variability on training and approach to MIMVS. Consensus guidelines should be established to allow standardization of MIMVS.

Structure of multidisciplinary heart teams, a survey-based heart team study.

OBJECTIVES: Multidisciplinary approach is well established in various disciplines, with evidence highlighting improved patient outcomes. The objective of this survey was to determine the real-world practice of heart teams across Europe. METHODS: The survey was drafted after a consensus opinion from the authors. The survey was sent to cardiac surgeons and cardiologists identified through electronic search. The survey link and the information sheet were sent through email followed by survey completion reminders. The survey responses were cumulated and analysed. RESULTS: Among 2188 invited clinicians, 220 clinicians from 26 countries took part in the survey (response rate 10%). The completion rate for the survey questions was 85%. A total of 140 (64%) were cardiac surgeons and 80 (36%) were cardiologists. The heart team meeting frequency was weekly according to 104 (55%) respondents. This was conducted face to face according to 139 (73%) of the responses. Eighty-seven (56%) of the respondents reported 10-20% of patients undergoing percutaneous coronary intervention were discussed at the heart team meeting. Seventy-nine (47%) respondents had ad hoc percutaneous coronary intervention institutional guidelines. Fifty-four (32%) respondents reported an audit process for the heart team decisions. CONCLUSIONS: This survey suggests that there is marked variability in the infra-structure and execution of heart teams in different institutions. The results of the survey suggest a need to formulate guidelines on the composition and execution of heart teams which may result in an increase in transparency of decision-making within different institutions in reporting and comparing outcomes.

Mitral valve repair in papillary muscle rupture.

Papillary muscle rupture (PMR) is a significant mechanical complication following myocardial infarction (MI), a condition associated with a high mortality. It results in severe mitral valve regurgitation (MR), often accompanied by cardiogenic shock and pulmonary edema, requiring both emergent medical treatment and surgical intervention. Surgical treatment includes either chordal sparing mitral valve replacement or mitral valve repair, which is associated with a high mortality. Mitral valve repair is believed to be superior to mitral valve replacement with respect to improving left ventricular function, albeit with risk of repair failure and resulting in increased cross clamp times. Concomitant coronary revascularization may improve both short- and long-term outcomes after surgery. With advances in medical innovations in the field of transcatheter devices, these devices may serve as a bridge to recovery or treatment in the setting of acute MR due to PMR. However, long-term data will be required to establish the non-inferiority of one treatment modality over the other. Management of these patients should be guided by a dedicated mitral heart team.

Suture map for endoscopic mitral valve replacement.

Mitral valve replacement using an endoscopic approach is an advanced skilled procedure. The purpose of creating the suture map for mitral valve replacement is to allow placement of sutures with the least tissue manipulation. The suture map serves as a guide for training purposes and for surgeons who are at an early stage of endoscopic surgery.

Suture map for endoscopic tricuspid valve repair.

Minimally invasive tricuspid surgery using a complete endoscopic approach has a steep learning curve. The purpose of creating the suture map is to allow placement of sutures with minimal tissue handling and to improve operating efficiency. This process is useful for surgeons who are just beginning to learn minimally invasive surgery and are at an early stage of their endoscopic surgical career.

The incidence of medication-related osteonecrosis of the jaw following tooth extraction in patients prescribed oral bisphosphonates.

Aims To determine the incidence of medication-related osteonecrosis of the jaw in patients prescribed oral bisphosphonate medication following dental extraction in a dedicated clinic within the Department of Oral Surgery of King's College Hospital. The effect of factors such as sex, duration of therapy, medical comorbidities and site of extraction, which have previously been reported to significantly affect the risk of developing osteonecrosis of the jaw, was also examined.Materials and methods Data were gathered from the dental records of patients who had extractions over an eight-year period and were included in this retrospective study. Patients with previous or current exposure to intravenous bisphosphonates, denosumab, novel-targeted chemotherapies used in the oncology setting or radiotherapy to the head and neck were excluded from this study.Results The incidence of medication-related osteonecrosis of the jaw following tooth extraction in this group of 652 was 0.8%. A significantly increased risk of developing medication-related osteonecrosis of the jaw was evident in patients prescribed oral bisphosphonates for four years or more (p = 0.02), with an incidence in this group of 1.6%.Conclusion This study demonstrates that, following dental extraction, patients who are prescribed oral bisphosphonates are at risk of developing medication-related osteonecrosis of the jaw and that this risk increases significantly when the patient has been taking the bisphosphonate for four years or more.

Open transcatheter valve implantation for mitral annular calcification: One-year outcomes.

BACKGROUND: Transcatheter mitral valve implantation (TMVI) for native mitral valve pathology with severe mitral annular calcification has emerged as an alternative treatment option to conventional mitral valve surgery. The objective of this study was to evaluate patients who were referred for TMVI with severe mitral annular calcification and their procedural outcomes. METHODS: Retrospective analysis of patients from 2017 to 2020 referred for TMVI was carried out. Demographic characteristic details; surgical strategy; perioperative complications; and hospital stay, including 30-day and 1-year mortality, were analyzed. RESULTS: Eleven patients were referred for consideration of TMVI. The 8 patients who underwent TMVI had a median age of 74 years (range, 57-80 years), the median Society of Thoracic Surgeons score was 4.6 (range, 2.4-10.9), and European System for Cardiac Operative Risk Evaluation II score was 5.2% (2%-10.1%). The median cardiopulmonary bypass time and crossclamp times were 170 minutes (range, 150-248 minutes) and 152 minutes (range, 118-214 minutes), respectively. The median hospital stay was 29 days (range, 2-40 days). Thirty-day in hospital mortality was 12%, whereas 1-year mortality was 25%. There was symptomatic improvement with downgrade of New York Heart Association functional class from III or IV to I or II. The 3 patients who were turned down had a median age of 73 years, median Society of Thoracic Surgeons score was 13.4, and median European System for Cardiac Operative Risk Evaluation II score was 5.72%. They were alive at 12 months follow-up from the date of surgical assessment; however, all with New York Heart Association functional class III or IV symptoms. CONCLUSIONS: We describe a series demonstrating the technical consideration and capability of transatrial TMVI to treat mitral annular calcification and native mitral valve disease. Our results are favorable when compared with TMVI global registry data for transseptal or transapical approach.

Role of preoperative blood markers as prognostic factors for lung cancer surgery.

OBJECTIVE: This study was undertaken to assess the potential value of preoperative blood components as prognostic markers of outcome after lung cancer resection, and hence their potential to aid in the selection of patients for curative surgery. METHODS: This was a single-center study on 313 patients who underwent surgery for non-small-cell lung cancer from 2006 to 2008. Data were analyzed retrospectively from a prospectively maintained thoracic database. Preoperative blood results including plasma fibrinogen levels, serum C-reactive protein, hemoglobin concentration, and platelet count were included in the analysis. RESULTS: The mean age was 75 years, and 40% of the patients were females. The most common resection was lobectomy in 68% of patients, followed by pneumonectomy, wedge resection, and segmentectomy in 18%, 10%, and 1.6%, respectively. Patients with abnormal C-reactive protein, fibrinogen, and hemoglobin levels had a worse overall survival. Large tumor size and nodal metastasis on clinical staging was also associated with poor survival. However, on Cox regression analysis, plasma fibrinogen and nodal metastasis were the only independent predictors of survival after lung resection. CONCLUSIONS: Among the different blood markers, elevated preoperative plasma fibrinogen was an independent marker of reduced survival in patients with resected non-small-cell lung cancer, and its value in selecting patients who may benefit from surgery needs further investigation.

A Porcine Ex Vivo Lung Perfusion Model To Investigate Bacterial Pathogenesis.

The use of animal infection models is essential to understand microbial pathogenesis and to develop and test treatments. Insects and two-dimensional (2D) and 3D tissue models are increasingly being used as surrogates for mammalian models. However, there are concerns about whether these models recapitulate the complexity of host-pathogen interactions. In this study, we developed the ex vivo lung perfusion (EVLP) model of infection using porcine lungs to investigate Klebsiella pneumoniae-triggered pneumonia as a model of respiratory infections. The porcine EVLP model recapitulates features of K. pneumoniae-induced pneumonia lung injury. This model is also useful to assess the pathogenic potential of K. pneumoniae, as we observed that the attenuated Klebsiella capsule mutant strain caused less pathological tissue damage with a concomitant decrease in the bacterial burden compared to that in lungs infected with the wild type. The porcine EVLP model allows assessment of inflammatory responses following infection; similar to the case with the mouse pneumonia model, we observed an increase of il-10 in the lungs infected with the wild type and an increase of ifn-γ in lungs infected with the capsule mutant. This model also allows monitoring of phenotypes at the single-cell level. Wild-type K. pneumoniae skews macrophages toward an M2-like state. In vitro experiments probing pig bone marrow-derived macrophages uncovered the role for the M2 transcriptional factor STAT6 and that Klebsiella-induced il-10 expression is controlled by p38 and extracellular signal-regulated kinase (ERK). Klebsiella-induced macrophage polarization is dependent on the capsule. Together, the findings of this study support the utility of the EVLP model using pig lungs as a platform to investigate the infection biology of respiratory pathogens.IMPORTANCE The implementation of infection models that approximate human disease is essential to understand infections and for testing new therapies before they enter into clinical stages. Rodents are used in most preclinical studies, although the differences between mice and humans have fueled the conclusion that murine studies are unreliable predictors of human outcomes. In this study, we have developed a whole-lung porcine model of infection using the ex vivo lung perfusion (EVLP) system established to recondition human lungs for transplant. As a proof of principle, we provide evidence demonstrating that infection of the porcine EVLP with the human pathogen Klebsiella pneumoniae recapitulates the known features of Klebsiella-triggered pneumonia. Moreover, our data revealed that the porcine EVLP model is useful to reveal features of the virulence of K. pneumoniae, including the manipulation of immune cells. Together, the findings of this study support the utility of the EVLP model using pig lungs as a surrogate host for assessing respiratory infections.

Microsurgical Reconstruction of the Jaws Using Vascularised Free Flap Technique in Patients with Medication-Related Osteonecrosis: A Systematic Review.

BACKGROUND: Osteonecrosis of the jaw (ONJ) has been reported to be associated with patients receiving primarily bisphosphonate (BP) therapies. However, lately it has been documented that other medications, such as RANK ligand inhibitor (denosumab) and antiangiogenic drug, can cause ONJ. Micro-osseous-vascular reconstruction of the jaws in patients affected by medication-related osteonecrosis of the jaw represents a viable option of treatment for patients affected by stage III of the disease. However, there are still considerable doubts about the success of this procedure in the short, medium, and long term. MATERIAL AND METHODS: A multidatabase (PubMed/MEDLINE, EMBASE, and CENTRAL) systematic search was performed. Any type of studies considering human patients treated with antiresorptive and antiangiogenic drugs was considered. The aim of the research is to primarily understand the success rate of micro-osseous-vascular reconstruction in the short, medium, and long period of time. This review has also the goal of better understanding any perioperative and postoperative complications resulting from the use of the reconstruction techniques. RESULTS: Eighteen studies resulted eligible for the study. Fibula free flap is the most commonly utilised vascularised free flap reconstruction technique (80.76%). Ten out of eighteen studies reported no complications. Recurrence of osteonecrosis was registered in five cases (6.41%) after free flap reconstruction. The overall free flap success rate was 96.16%. CONCLUSIONS: Based on the limited data available in literature (Level 4 of the Oxford Evidence-based medicine scale), micro-osseous-vascular reconstruction of the jaws represents a valid treatment in patients with bisphosphonate-related osteonecrosis at stage III of the disease. However, additional data based on a larger cohort of patients are necessary to justify this type of intervention in patient affected by MRONJ.