A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.

Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans, the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for prevention, diagnosis, and treatment. We have previously introduced the use case for a new human model and identified M. ulcerans JKD8049 as a suitable challenge strain. Here, we present a provisional protocol for an initial study, for transparent peer review during the earliest stages of protocol development. Following simultaneous scientific peer review and community/stakeholder consultation of this provisional protocol, we aim to present a refined protocol for institutional review board (IRB) evaluation.

This paper describes a provisional clinical protocol for the pilot human challenge model of Mycobacterium ulcerans infection, which causes the skin disease 'Buruli ulcer' (BU). BU is typically painless and begins as a small area of redness or swelling, and is curable with antibiotics. If the diagnosis is delayed, it can result in large ulceration and disability. Side effects from antibiotics are common but rarely severe; nevertheless, preventative strategies, such as vaccination, are urgently needed. The overarching project, known as 'MuCHIM', aims to establish a safe and acceptable controlled human challenge model (CHIM) of this disease in healthy volunteers in Melbourne, Australia. This pilot protocol primarily aims to establish that it is safe and acceptable to participants, and secondarily to confirm successful establishment of infection and the infection rate amongst participants. We also aim to test less invasive diagnostic tests, assess immune responses to infection, to understand changes in the human microbiome during the trial, and explore microbiological characteristics of M. ulcerans infection. If this pilot is successful, we hope to test vaccines and other therapeutics using this model, which could blunt or reduce the rising incidence of this disease in Australia, while further informing vaccine development research.

Arteriovenous Shunts: Their Location and Role in Physiology, Pathology, and Tissue Transfer. A Preliminary Report in the Upper Limb.

Background: Tiny arteriovenous (AV) shunts of 10-150 µm (0.01-0.15 mm) are documented in the hands and feet. Larger shunts up to 0.5 mm (500 µm) have been discovered by the authors in the inner canthus and the human eye. This study seeks their possible existence in the upper limb. Methods: Radiographic lead oxide cadaver injection and dissection studies of 14 archival and six new upper limbs were examined. Results: AV shunts of 0.1-0.5 mm were discovered between the brachial, ulnar, and radial arteries and their venae comitantes and between their arterial perforators and the subcutaneous veins. Conclusion: This pilot study provides insight into the possible function of these large AV shunts associated with blood flow variation in temperature, blood pressure, tissue transfer, flap prefabrication, and flap necrosis.

A Novel Maternally Inherited GNAS Variant in a Family With Hyperphagia and Obesity: 3 Cases.

GNAS variants were recently described in 1% of patients not known to have pseudohypoparathyroidism/inactivating PTH/PTHrP signalling disorder 2 in the UK Genetics of Obesity Study. We describe a new missense GNAS variant, c.791A > C, p.(Asp264Thr), in a family with obesity, hyperphagia and mild PTH resistance. A 6-year-old female (body mass index +4.3 SD score [SDS], height +1.9 SDS) presented with hyperphagia and obesity from age 3 years. She had subtle brachydactyly, macrocephaly, and mildly delayed development. The 12-year-old brother (height +2.1 SDS, body mass index +2.9 SDS) had hyperphagia, obesity, mildly delayed development, and autism. He had subtle brachydactyly, as did the affected mother. We assessed the functional effect of the mutant, measuring cAMP production in cells transfected with wild type and mutant GNAS after ligand stimulation. Cells with the mutant GNAS showed impaired cAMP generation through melanocortin receptor 4, GH releasing hormone receptor, and PTH receptor. These cases demonstrate the clinical heterogeneity of monogenic disease, suggesting a need to test for PHP1A in children with obesity even without classical signs of PHP1A.

E-Scooter facial fractures: A comparative cohort study.

It was the aim of the study to analyze the distribution and pattern of facial fractures following e-scooter trauma. Prospective audit data of facial fractures were retrospectively collected to investigate the impact of e-scooter hire, specifically in the form of facial fractures associated with their use. Data collected included patient demographics, mode of injury, date of injury, facial bones involved, presence of soft tissue injury, and factors associated with injury, including intoxication and helmet use. A total of 849 patients were treated for facial fractures during the study period, of which 34 were attributed to e-scooter use. One-half of those injured riding e-scooters were intoxicated, and one-quarter were wearing helmets. There have been an increasing number of facial fractures associated with e-scooter use following the start of the shared e-scooter trial. Zygomaticomaxillary complex fractures were the most common pattern of facial fracture seen. Most patients required surgical management of their injuries. Policymakers should consider how to improve the enforcement of current regulations, given the healthcare cost associated with the management of these preventable injuries.

Cranioplasty is not required in the reconstruction of small combined scalp and calvarial defects.

BACKGROUND: Treatment of scalp malignancies may include the need for craniectomy. The decision to perform cranioplasty is not straightforward and is frequently subjective. The purpose of this study was to assess the clinical outcomes after reconstruction of complex scalp and calvarial defects by comparing patients with and without cranioplasty. METHODS: Retrospective review of the clinical records of a consecutive series of patients who underwent scalp soft tissue reconstruction after craniectomy for malignancy or osteoradionecrosis between 2014 and 2022 at Royal Melbourne Hospital was conducted. Demographics, previous treatments, surgical details, and post-operative complications were assessed. Traumatic injuries and decompressive craniectomies were excluded. Minimum follow-up of 6 months. RESULTS: Thirty-seven patients were included in the study. Indications for surgery included skin malignancies, osteoradionecrosis, or both. There was one reconstructive failure (in the non-cranioplasty group). Infection and metalware exposure were common complications in patients who underwent cranioplasty (38.5%). No patient developed neurological symptoms subsequent to craniectomy. One patient needed revision surgery due to esthetic reasons (cranioplasty group). Transposition flaps were associated with more complications and revision procedures. CONCLUSION: Combined scalp and calvarial defects pose a difficult reconstructive challenge. Stable soft tissue coverage is more reliably achieved with free flap reconstruction. Cranioplasty is not always mandatory and should be reserved for cases with a very large bony defect or when the defect is located in a cosmetically sensitive area.

Optimising Patient Outcomes in Tongue Cancer: A Multidisciplinary Approach.

A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

The impact of electric scooters in Melbourne: data from a major trauma service.

BACKGROUND: The proliferation of electric scooters globally has been associated with an increase in related injuries and consequent economic burden. This study aims to assess the injury patterns and the economic impact associated with electric scooter use in Melbourne, Australia. METHODS: A retrospective cohort study was conducted using hospital and registry data from January 2022 to January 2023. Data collected included demographic details, alcohol and helmet use, injury type and severity, operative treatment provided, and direct medical costs. The economic impact (in AUD) of the patient's emergency presentation and hospital admission was calculated. RESULTS: During the study period, 256 electric scooter related injuries were recorded, comprising 247 riders and nine pedestrians. The majority of patients were males (69%) with a median age of 29.5 (15-78). Alcohol use was reported by 34% and helmet use by 33%. Injuries most commonly affected the upper limb (53%) and head (50%), with abrasions (75%) and fractures (48%) being the most common type of injury sustained. The total hospital cost was $1 911 062, and the median cost was $1321.66 per patient (IQR: $479.37-$5096.65). CONCLUSION: Electric scooter usage, as observed through patient presentations to the Royal Melbourne Hospital, is associated with a considerable number of injuries, primarily among young males, and an ensuing substantial economic burden. The findings underscore the urgent need for improved safety measures to minimize electric scooter-related injuries and their clinical and economic repercussions.

Hippocampal Volume And Type 2 Diabetes Mellitus Without Comorbid Malady.

BACKGROUND: Evidence of type 2 diabetes mellitus (T2DM) associated with hippocampal atrophy is reported by researchers all around the globe. The majority of such studies were conducted among the geriatric and elderly populations with other substantial co-morbid diseases. Hence, the present study aims to evaluate the hippocampal volume of T2DM subjects below 60 years without any concomitant disorders and assess the declarative memory. MATERIALS AND METHODS: The cross-sectional observational study was conducted among the ethnic population of Manipur. A total of 17 T2DM subjects and 17 healthy controls, who are apparently healthy, matched by age, sex, and comparable education, were enrolled in the study. Magnetic Resonance Imaging (MRI) of high-resolution sagittal structural T1-weighted anatomical sequence was acquired using a three-dimension magnetization-prepared rapid-acquisition gradient echo (MPRAGE). The hippocampus volume was measured using the volBrain Automated MRI Brain Volumetry System. Declarative memory was estimated by the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: No statistically significant differences were found in hippocampal volume, and RAVLT scores between T2DM subjects, and healthy controls group (P > 0.05). CONCLUSIONS: The study data indicates that there is no particular hippocampal volume vulnerability in T2DM participants within the ethnic population of Manipur.

Antibiotic Prophylaxis Prescribing Practice in Head and Neck Tumor Resection and Free Flap Reconstruction.

BACKGROUND: Adherence to guidelines for antibiotic prophylaxis is often poor and is an important target for antimicrobial stewardship programs. Prescribing audits that suggested poor adherence to guidelines in a plastic surgery department led to a targeted education program to bring antibiotic prescriptions in line with hospital guidelines. We reviewed whether this intervention was associated with changed perioperative prescribing and altered surgical outcomes, including the rate of surgical site infections, specifically looking at clean-contaminated head and neck tumor resections with free flap reconstruction. METHODS: A retrospective cohort study was performed on 325 patients who underwent clean-contaminated head and neck tumor resection and free flap reconstruction from January 1, 2013, to February 19, 2019. Patients were divided into 2 groups, those before (pre-intervention) and after (postintervention) the education campaign. We analyzed patient demographic and disease characteristics, intraoperative and postoperative factors, and surgical outcomes. RESULTS: Patients pre-intervention were prescribed longer courses of prophylactic antibiotics (median [interquartile range], 9 [8] vs 1 [1]; P < .001), more topical chloramphenicol ointment (21.82% vs 0%; P < .001), and more oral nystatin (36.9% vs 12.2%; P < .001). Patients postintervention had higher rates of recipient infections (36.11% vs 17.06%; P < .001) and donor site infections (6.94% vs 1.19%; P = .006). CONCLUSIONS: Following the education campaign, patients were prescribed shorter courses of prophylactic antibiotics, more of the recommended cefazolin-metronidazole regimen, and fewer topical antibiotics. However, patients also had a higher rate of surgical site infections.

Risk factors for surgical site infection in free-flap reconstructive surgery for head and neck cancer: Retrospective Australian cohort study.

BACKGROUND: Surgical site infections (SSI) are common complications of free-flap reconstruction for head and neck cancer defects. This study aimed to identify risk factors for SSI following a significant change in local antibiotic prophylaxis practice. METHODS: A retrospective cohort study was conducted of 325 patients receiving free-flap reconstruction for head and neck cancer defects at a tertiary hospital in Melbourne, Australia between 2013 and 2019. Charts were queried for recipient SSI (primary outcome), donor SSI, other infections, antibiotic use, hospital length of stay, and mortality. RESULTS: Risk factors for SSI included female sex, T-classification, hardware insertion, clindamycin prophylaxis, and operative duration. There was a trend toward increased SSI with shorter ≤24 h prophylaxis (OR: 0.43). CONCLUSION: Antibiotic duration and type were associated with SSI. Complexity of surgery, T-classification, hardware use, and operative duration were also independently associated with SSI. A prospective trial is indicated to elicit optimal prophylactic antibiotic duration.

Quality-of-life outcomes after operative management of primary and secondary lymphoedema: a systematic review.

BACKGROUND: Lymphoedema is an incurable and progressive disease that affects not only physical function but overall quality of life. Surgical treatment options for the management of lymphoedema are being increasingly performed. This study aims to review post-operative health-related quality of life (HRQOL) following surgical treatment of lymphoedema. METHODS: A systematic search of the PubMed and Medline databases was performed from the date of their inception until September 2018 to evaluate HRQOL following different surgical options for the treatment of lymphoedema. RESULTS: One hundred and thirteen articles were identified. Twenty-one articles were included in the final review, comprising a total of 736 patients. HRQOL improvements appear to be sustained for at least 6-12 months post-operatively. In particular, major benefits were noted in the domains based around physical functioning. Patient satisfaction similarly mirrors HRQOL improvements, following an initial dip in the immediate post-operative period. CONCLUSION: All surgical treatment modalities for the management of lymphoedema confer significant HRQOL improvements across a diverse range of health domains, with this critical outcome of surgery an important pre-operative consideration. Recommendations for ongoing research are suggested.

Radiological assessment of facial fractures: a comparative study between surgeon and radiologist.

BACKGROUND: The authors aimed to examine the differences in CT facial bone interpretation by the faciomaxillary surgeon and the radiologist, in order to improve communication gaps and subsequently, the quality and consistency of patient care. METHODS: This study was conducted at a level I tertiary trauma centre. Patients with facial trauma who were referred to the faciomaxillary unit following a facial CT examination from August 2017 to September 2018 were eligible for inclusion. The inclusion period was extended to 5 years for panfacial trauma patients. All consecutive patients that fulfilled the study inclusion criteria for each type of injury were included in the study (a total of 120 patients assigned to the following six categories: orbits, skull and skull base, zygomaticomaxillary complex, Le Fort pattern, mandible and pan-facial fractures). Faciomaxillary surgeons, blinded to the radiology report, were asked to provide a verbal description of the fractures. The surgical interpretation was compared to the radiology report and further analysed. RESULTS: Of the 120 cases, the same fractures were reported in 43 cases (35.8%). Both types of specialists noted the predominant and clinically relevant fractures in 106 cases (88.3%). The reports did not match in 14 cases (11.7%) and different terminology was used in 76 cases (63.3%), with agreement in 25% (95% CI: 18-34%), partial agreement in 11.7% (95% CI: 5.9-17.4%) and no agreement in 63.3% (95% CI: 54.7-72.0%) cases. CONCLUSION: Radiologists and faciomaxillary surgeons frequently differ in their assessment of facial fractures.

Rationalizing post-operative prophylactic anticoagulation in reconstructive head and neck cancer patients: a review.

Microsurgical reconstructive head and neck cancer patients are at high risk of venous thromboembolism. The use of anticoagulation can reduce their risk; however, this also increases their bleeding risk. It is not clear whether the benefits of treatment outweigh the risks, and whether a specific post-operative anticoagulation regime is superior. The aim of this review is to evaluate the evidence pertaining to the risks and benefits of post-operative anticoagulation and to provide a rationale for its use in head and neck cancer patients receiving free flaps. The secondary aim was to determine the optimal post-operative anticoagulation regimen. A search was conducted in the PubMed and EMBASE databases identifying studies reporting venous thromboembolism rates in reconstructive head and neck cancer patients undergoing free flaps. These studies were reviewed for their eligibility. Outcomes measured were rates of venous thromboembolism, bleeding-related and microsurgical complications. A total of 306 studies were found from the search with another seven studies identified from citations of key articles. After assessment, nine studies were included. Venous thromboembolism rates ranged from 0.5% to 7% and the rates of bleeding-related complications ranged from 2.4% up to 29%. Anticoagulation appears to lower the risk of venous thromboembolism in this patient group, but also increases the bleeding risk. Risk stratification using the Caprini risk assessment model can help surgeons make decisions. For patients with cancer, low molecular weight heparin appears to be superior to heparin given twice daily but equal to heparin given three times daily and the bleeding risk of each medication appears similar.

Chest keloids: effect of surgical excision and adjuvant radiotherapy on recurrence, a systematic review and meta-analysis.

BACKGROUND: Chest keloids are a difficult sub-group of scars to treat, likely secondary to the high wound tension in the area that promotes excessive fibroblast proliferation and collagen deposition. Excision and adjuvant radiotherapy has been demonstrated as an efficacious treatment for keloids in general, but no meta-analysis exists to support the claims for chest keloids. This study aims to identify the rate of recurrence after surgical resection and radiotherapy on patients with chest keloids. METHODS: A search was performed using Embase, MEDLINE, Pubmed and Cochrane database on 22 December 2018 for terms 'radiotherapy', 'keloid' and 'chest'. Papers included met a prospectively designed inclusion criteria assessed by multiple investigators. RESULTS: Twelve studies, including 1 randomized controlled trial, were included for a total of 400 patients with a chest keloid scar managed with surgical excision and adjuvant radiotherapy. Overall pooled-estimate of recurrence rate was 22% (95% CI 12-32%). Meta-regression did not demonstrate a significant effect for method of wound closure, type of radiotherapy, radiotherapy dose (BED10 ) and study type. CONCLUSION: Excision and adjuvant radiotherapy represents an effective method of treatment for chest keloids, however sufficient prospective data, including randomized controlled trials, did not yet exist to support these findings. Further studies with sufficient sub-group analysis for keloid location are required to add to the pool of literature that can be added to this meta-analysis.

Virtual surgical planning in fibula free flap head and neck reconstruction: A systematic review and meta-analysis.

BACKGROUND: The traditional approach to head and neck reconstruction is considered challenging, requiring a subjective assessment of an often-complex defect followed by careful modelling of a bony flap to match this. The introduction of Virtual Surgical Planning (VSP) has provided the surgeon with a means to increase efficiency, precision and overall patient outcomes. This study aims to compare VSP and traditional head and neck reconstructions utilising fibula free flaps with regards surgical efficiency and patient outcomes. METHODS: A systematic search of the PubMed and Medline databases was performed from the date of their inception through to August 2018 to evaluate and compare VSP and non-VSP cohorts in the context of fibula free flap head and neck reconstruction. Primary comparative outcomes included operative and ischaemic time, with secondary outcomes including complications rates, measures of accuracy and financial benefits. RESULTS: One hundred and fifty-three articles were identified. Twenty-three articles were included in the review, comprising a total of 713 patients. VSP was associated with significantly decreased intraoperative time (Standardised Mean Difference -1.01; 95% CI -1.23 to 0.80; p = 0.000) and ischaemic time (Standardised Mean Difference -1.55; 95% CI -1.87 to -1.23, p = 0.002). VSP was also associated with reduced orthognathic deviation from an ideal outcome when compared to conventional techniques. No statistically significant differences in complication rates between conventional and VSP techniques were identified. CONCLUSION: The results of this meta-analysis suggests that VSP confers significant benefits with respect to improved orthognathic accuracy, ischaemic times and intraoperative times without any significant increase in complications. Recommendations for ongoing research are suggested.

Comparative osteoradionecrosis rates in bony reconstructions for head and neck malignancy.

BACKGROUND: Bony free flaps are used to reconstruct head and neck cancer defects. The most commonly used flaps are the free fibula flap and the deep circumflex iliac artery (DCIA) flap. Radiotherapy may be given post-operatively to prevent cancer recurrence. This radiotherapy can, however, destroy the bone; a complication termed osteoradionecrosis (ORN). Although there have been studies comparing free fibula and DCIA flaps in terms of success rates and complications, few have assessed the incidence of ORN in both groups. METHODS: A retrospective cohort study was conducted involving patients from Royal Melbourne Hospital and St Vincent's Hospital Melbourne who had either a free fibula or DCIA flap for head and neck cancer reconstruction in the past 10 years. Data collected included demographic, operative, and postoperative data. Analysis was performed using Statistical Package for Social Sciences and Microsoft Excel, utilising t-tests, chi-square tests and logistic regression analyses. RESULTS: A total of 154 patients were identified. Of these patients, 127 had free fibula flaps and 27 had free DCIA flaps. Twelve patients had ORN post-op, 10 had free fibula flaps, and 2 had free DCIA flaps. No statistically significant difference was found between the ORN rates in free fibula flaps and free DCIA flaps. CONCLUSION: Rates of ORN incidence should not be a major consideration in preoperative planning of free flaps for mandibular reconstruction as both fibula and DCIA free flaps are comparable.

Platelet activating factor: A potential biomarker in acute coronary syndrome?

Platelet activating factor (PAF) is a potent pro-inflammatory negotiator that shows distinct spectrum of biological and pharmacological effects. Importantly, it participates in a wide range of pathophysiological conditions. In cardiovascular system, PAF has been shown to have an important role in platelet and neutrophil aggregation, vascular permeability, microvascular leakage, thrombus formation, leukocyte adhesion to the endothelial cells, and initiation and progression of atherosclerosis. The purpose of this article was to review the PAF, a family of lipids that is associated with the pathology of coronary artery diseases due to their association with leading etiological mechanisms such as inflammation, endothelial dysfunction, oxidative and nitrosative stress, and platelet reactivity. This review further provides information about PAF and its potential role as a key contributor to the pathogenesis of cardiovascular disorders.

A quantitative, surface plasmon resonance-based approach to evaluating DNA binding by the c-Myc oncoprotein and its disruption by small molecule inhibitors.

The use of small molecules to interfere with protein-protein interactions has tremendous therapeutic appeal and is an area of intense interest. Numerous techniques exist to assess these interactions and their disruption. Many, however, require large amounts of protein, do not allow interactions to be followed in real time, are technically demanding or require large capital expenditures and high levels of expertise. Surface plasmon resonance (SPR) represents a convenient alternative to these techniques with virtually none of their disadvantages. We have devised an SPR-based method that allows the heterodimeric association between the c-Myc (Myc) oncoprotein and its obligate partner Max to be quantified in a manner that agrees well with values obtained by other methods. We have adapted it to examine the ability of previously validated small molecules to interfere with Myc-Max heterodimerization and DNA binding. These inhibitors comprised two distinct classes of molecules that inhibit DNA binding by preventing Myc-Max interaction or distorting pre-formed heterodimers and rendering them incapable of DNA binding. Our studies also point out several potential artifacts and pitfalls to be considered when attempting to employ similar SPR-based methods. This technique should be readily adaptable to the study of other protein-protein interactions and their disruption by small molecules.