Cranioplasty infection in porous hydroxyapatite: Potential antibacterial properties

Introduction: Intensive research is dedicated to the development of novel biomaterials and medical devices to be used as grafts in reconstructive surgery, with the purpose of enhancing their therapeutic effectiveness, safety, and durability. A variety of biomaterials, from autologous bone to polymethylmetacrylate, polyether ether ketone, titanium, and calcium-based ceramics are used in cranioplasty. Porous hydroxyapatite (PHA) is reported as a possible material for bone reconstruction, with good signs of biocompatibility, osteoconductive and osteointegrative properties. In the present paper we studied the possible antibacterial properties of PHA in a laboratory test in order to provide a possible overview of the occurrence of post-operative infections in PHA cranioplasty. Method: The test method has been designed to evaluate the potential antimicrobial activity of specimens under dynamic contact conditions to overcome difficulties in ensuring contact of inoculum to the specimen surface. The test was conducted using Staphylococcus aureus ATCC6538 as a bacterial strain. Results: Two experimental sets were performed to evaluate the antimicrobial properties of the specimens against two different Staphylococcus aureus concentrations. The first preliminary test (a) verified the antibacterial property at 0, 1, 2, and 4 h of contact time; the second confirmatory test (b) was repeated to verify the antibacterial property at 0, 4, 8 h. In the first experiment, after the first hour of contact, the bacterial inoculum was reduced by 7.96% compared to "inoculum only," which increased to 26.11% at the second hour, and up to 52.33% after 4 h. In the second experiment, the confirmation test showed that bacterial growth reaches maximum inhibition after 4 h of contact. At 4 h, there was a higher bacterial reduction of 72.93%, which decreased at 8 h (36.45%). Conclusion: Analyzing the growth trend of viable microorganisms under Dynamic Contact Conditions it can be seen that PHA cranioplasty appears to inhibit exponential growth by inducing bacterial stasis in the early hours of contact, reaching a maximum reduction within 4 h, in this adopted experimental condition

Intraoperative imaging O-Arm™ in secondary surgical correction of post-traumatic orbital fractures

Abstract Purpose To determine the safety and efficacy of O-Arm™ intraoperative imaging in maxillofacial surgery of post-traumatic orbital fractures. In order to ensure correct placement of titanium plate, immediately after fixing, viewable, in the axial, sagittal and coronal images. Methods The authors evaluated 5 consecutive adult patients with orbital fractures who required a reoperation involving displacement of titanium mesh between January and December 2015. The displacement or incorrect positioning of titanium mesh was detected at post-operative CT scan or clinical neurological findings. Intraoperative O-Arm™ imaging was used for our patients who underwent secondary maxillofacial orbital fracture surgery due to the failure of first surgical approach. Results An eyelid incision was performed in order to obtain maximal exposure and minimizing cosmetic defects. Any previous fixation device was skeletonized and removed, any improperly reduced fracture was mobilized, reduced and refixated with 1.5 mm plates, screws and titanium mesh. The intra-operative O-Arm™ imaging technique was used at the end of the procedures. In 4 cases it confirmed the appropriateness of the newly obtained reconstruction, in 1 case a first scan showed a suboptimal result and the devices were correctly repositioned, guided by the O-Arm™ images. Conclusions Intraoperative O-Arm™ assisted craniofacial reconstruction surgery improves the assessment of neurovascular structure decompression, skeletal fragment identification, fixation procedures and for the correct re-establishment of facial symmetry in orbital floor fractures

Growth and rupture of an intracranial aneurysm: the role of wall aneurysmal enhancement and CD68+

IntroductionIntracranial aneurysms occur in 3%–5% of the general population. While the precise biological mechanisms underlying the formation, growth, and sudden rupture of intracranial aneurysms remain partially unknown, recent research has shed light on the potential role of inflammation in aneurysm development and rupture. In addition, there are ongoing investigations exploring the feasibility of employing new drug therapies for controlling the risk factors associated with aneurysms. CD68, a glycosylated glycoprotein and the human homolog of macrosialin, is prominently expressed in monocyte/macrophages within inflamed tissues and has shown potential application in oncology. An observational study was conducted with the aim of comparing the histological characteristics of aneurysm walls with preoperative MRI scans, specifically focusing on CD68 activity.MethodAn observational pilot study was conducted to investigate the histological characteristics of the aneurysm wall that could be potentially associated with aneurysm growth and rupture. A total of 22 patients diagnosed with ruptured and unruptured intracranial aneurysms who had undergone conventional clipping between January 2017 and December 2022 were included in the study.ResultsA histopathological analysis of the aneurysm wall was performed in all patients, particularly focusing on the presence of CD68. A preoperative MRI with gadolinium was conducted in 10 patients with unruptured aneurysms and six patients with ruptured aneurysms. An emergency clipping was performed in the remaining six patients. The results showed that CD68 positivity and wall enhancement were significantly associated with intracranial aneurysm wall degeneration, growth, and rupture.ConclusionThe histological and radiological inflammatory findings observed in the wall of cerebral aneurysms, as well as the CD68 positivity, are significantly associated with the risk of intracranial aneurysm growth and rupture. This study highlights the crucial importance of considering clinical and medical data when making treatment decisions for intracranial aneurysms. Furthermore, it emphasizes the relevance of evaluating wall enhancement in MRI scans as part of the diagnostic and prognostic process

Enhancing Safety in Regional Anesthesia: Guidelines from the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI)

Background Regional anesthesia techniques have become integral to modern perioperative care, offering enhanced pain management and recovery outcomes. However, their application in patients with specific conditions, such as anticoagulation therapy or preexisting comorbidities, raises concerns regarding safety and efficacy. Current guidelines addressing these issues are fragmented, necessitating comprehensive, evidence-based recommendations. Methods A multidisciplinary panel of experts in anesthesiology and pain management was convened under the auspices of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI). The guidelines presented herein were developed according to the GRADE system (Grading of Recommendations of Assessment Development and Evaluations), in compliance with the methodological manual for the production of clinical practice guidelines published by the National Center for Clinical Excellence, Quality, and Safety of Care, Italian National Institute of Health. Results The guidelines encompass recommendations on neuraxial blocks in anticoagulated patients, the dual guidance use in peripheral nerve blocks, the role of sterile field preparation, and post-procedural monitoring. Evidence from meta-analyses and large-scale observational studies supported most recommendations, though limitations in study heterogeneity were noted. Conclusions These guidelines provide a structured framework for clinicians to enhance patient safety and procedural efficacy in regional anesthesia. Further research is encouraged to address identified gaps, particularly regarding specific patient subgroups and novel regional anesthesia techniques

Adverse fetal and perinatal outcomes associated with Zika virus infection during pregnancy: an individual participant data meta-analysis

Background: Zika virus (ZIKV) infection during pregnancy is associated with an increased risk of congenital malformations. The prevalence of short and long-term consequences, however, remains uncertain due to heterogeneity across studies. Individual Participant Data Meta-Analysis (IPD-MA) offers an alternative approach to provide more precise and generalisable estimates through data harmonisation across studies, allowing for standardised definitions and exploration of heterogeneity. This project was undertaken to estimate absolute and relative risks of adverse outcomes for individuals with ZIKV infection during pregnancy. Methods: IPD-MA studies and their datasets were identified through a systematic search conducted in 2018 with the following criteria: observational longitudinal or surveillance-based studies investigating ZIKV during pregnancy or at birth, measured fetal, infant, or child outcomes, and included at least 10 participants. Here we used IPD data shared by March 2022 from 18 studies from international health organisations and research networks, comprising 24 unique datasets, in 11 countries. Datasets were harmonised with standardised definitions, using variables related to pregnant individuals, methods used for ZIKV diagnoses, fetal characteristics and outcomes, and pooled for analysis. Frequentist and Bayesian regression methods were applied to estimate outcome prevalence and evaluate the association between maternal ZIKV infection and fetal loss, microcephaly and congenital zika syndrome as primary outcomes. Findings: Data including 9568 pregnant individuals and 9608 newborns, were harmonised. The risk of severe primary microcephaly was significantly higher in ZIKV-positive pregnancies (1.5%, CI 0.8%–2.7%) compared to ZIKV-negative ones (0.3%, CI 0.1%–1.0%), with a relative risk of 4.5 (CI 1.5–13.3) in the one-stage meta-analysis. While some risk estimates were consistent between Bayesian and Frequentist methods, estimates for other outcomes varied, underscoring the influence of both the analytical approach and the definition of ZIKV on the associations. Interpretation: Our findings align with previously published meta-analyses and indicate an added burden to adverse pregnancy outcomes with higher prevalence compared to pre-epidemic population-based average values. Future research should focus on additional outcomes with clear definitions of maternal infection. Women of reproductive age should be informed about the risks of Zika infection during pregnancy to support reproductive planning. Funding: This project was supported by the Wellcome Trust grant number 206532/Z/17/Z, the WHO Health Emergencies Programme Global Arbovirus Initiative, and the WHO Department of Sexual and Reproductive Health and Research, including the Human Reproduction Special Programme (HRP)

Minimizing Entropy for Training and Quantization (METaQ): A Novel Algorithm for Neural Network Training and Compression

A neural network compression strategy is developed during the training phase by adding a regularization term $\phi(w)$ to the loss function, in order to minimize the entropy of the network weights. $\phi(w)$ results from a nondifferentiable optimization problem that is computationally very complex to solve. However, fortunately, to train the network, it is not necessary to explicitly find $\phi(w)$; instead, it is sufficient to provide its (sub)gradient to standard machine learning tools (such as PyTorch) to guide the training towards a low entropy weight configuration (in addition to achieving good accuracy). This subgradient can be computed using the optimal Lagrange multipliers $\beta^*$ associated with the set of constraints involving the weights $w$ in the problem that defines $\phi(w)$. In this work, we will develop a procedure to determine $\beta^*$ by applying Lagrangian relaxation and optimization techniques, also developing ad hoc methods for certain sub-problems when necessary for efficiency reasons. Once a trained network with low entropy is obtained, the compression strategy culminates in the quantization of the weights. The task of encoding the weights is implemented via well-known compression algorithms that come arbitrarily close to the entropy. The introduction of the term $\phi(w)$ appropriately modeled for the function to be optimized during training is what makes this work innovative. The tests were conducted using the LeNet-5 network on the MNIST dataset, although the strategy is also applicable to larger networks. The achieved results show a $29\times$ compression of LeNet-5 (Compression Ratio 3.43\%) with an accuracy of 99.01\%, making METaQ a strategy comparable to state-of-the-art NN-compression algorithms. The project's source code is freely available at: https://github.com/cardiaa/METa

From Reparative Surgery to Regenerative Surgery: State of the Art of Porous Hydroxyapatite in Cranioplasty

Decompressive craniectomy is one of the most common neurosurgical procedures, usually performed after neuropathological disorders, such as traumatic brain injury (TBI), but also vascular accidents (strokes), erosive tumours, infections and other congenital abnormalities. This procedure is usually followed by the reconstruction of the cranial vault, which is also known as cranioplasty (CP). The gold-standard material for the reconstruction process is the autologous bone of the patient. However, this is not always a feasible option for all patients. Several heterologous materials have been created in the last decades to overcome such limitation. One of the most prominent materials that started to be used in CP is porous hydroxyapatite. PHA is a bioceramic material from the calcium phosphate family. It is already widely used in other medical specialties and only recently in neurosurgery. In this narrative review of the literature, we summarize the evidence on the use of PHA for cranial reconstruction, highlighting the clinical properties and limitations. We also explain how this material contributed to changing the concept of cranial reconstruction from reparative to regenerative surgery

Management accounting systems in venture capital-backed start-up companies

Management Accounting Systems (MAS) can help start-up companies to manage resource allocation and satisfy investors’ information needs. This study helps to investigate the main features of MAS adopted by Italian venture capital-backed startup companies. Also, the study aims to analyse how venture capitalists monitor their investment through management accounting. Thirty semi-structured interviews were carried out to gather information from a corporate and an investor perspective. Our results show that both start-up companies and investors consider MAS as useful to make conscious and target-oriented decisions. MAS are used by investors to monitor the investee’s performance and contribute in aligning goals’ time horizon. In addition, MAS help investors to develop a cooperative relationship with start-up companies and to provide business advices. This study contributes to the agency-theory debate by showing that MAS help not only to reduce information asymmetries but also to foster a dialogue and to benefit from investors’ human capital

From Reparative Surgery to Regenerative Surgery: State of the Art of Porous Hydroxyapatite in Cranioplasty

Decompressive craniectomy is one of the most common neurosurgical procedures, usually performed after neuropathological disorders, such as traumatic brain injury (TBI), but also vascular accidents (strokes), erosive tumours, infections and other congenital abnormalities. This procedure is usually followed by the reconstruction of the cranial vault, which is also known as cranioplasty (CP). The gold-standard material for the reconstruction process is the autologous bone of the patient. However, this is not always a feasible option for all patients. Several heterologous materials have been created in the last decades to overcome such limitation. One of the most prominent materials that started to be used in CP is porous hydroxyapatite. PHA is a bioceramic material from the calcium phosphate family. It is already widely used in other medical specialties and only recently in neurosurgery. In this narrative review of the literature, we summarize the evidence on the use of PHA for cranial reconstruction, highlighting the clinical properties and limitations. We also explain how this material contributed to changing the concept of cranial reconstruction from reparative to regenerative surgery.</jats:p