Unilateral Lower Limb Amputations from Traumatic Events: A Systematic Review and Meta-Analysis

Background Limb amputations are one of the most devastating injuries for young people in traumatic settings. People with lower extremity loss face challenges in performing daily activities and managing life-long complications; thus, rehabilitation and prostheses are critical in improving the quality of life. This systematic review and meta-analysis aims to determine the outcomes of people who had unilateral transtibial and transfemoral amputations in terms of mobility, physical activity, prosthesis usage, and associated pain. Methods An in-depth search was conducted on the electronic databases of PubMed and Science Direct databases in September 2022 to find studies that investigated the health outcomes of traumatic unilateral leg amputees. Observational studies, clinical studies, comparative studies, and randomized controlled trials in the English language and within the last 10 years (2012-2022)  were thoroughly screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The quality of search results was checked by the Newcastle-Ottawa Scale (NOS). The current meta-analysis included four observational studies which comprised 563 patients, 352 transtibial, and 211 transfemoral amputations. RevMan 5.4 software was used to calculate risk ratios (RRs) with 95% confidence intervals (CI) to conduct this meta-analysis. Results The pooled effect estimate showed no statistically significant difference between transtibial and transfemoral amputees(RR = 1.15, 95% CI [0.93, 1.43], P = 0.21) in terms of physical activity. People who had transfemoral amputations used prostheses more frequently than those who had transtibial amputations(RR = 1.21,95% CI [1.09, 1.35], P = 0.0004). There was no statistical difference between the two groups who reported pain during prosthesis wearing (RR = 1.03, 95% CI [0.62, 1.73], P = 0.91). Conclusion People who used leg prostheses more frequently were associated with more independent mobility and adequate physical activity. Leg prostheses with better accommodation and mobility benefit people with traumatic unilateral transfemoral amputations

Knowledge about osteoporosis among healthy women attending a tertiary care hospital

INTRODUCTION: To determinate the knowledge on osteoporosis-risk factors and disease in three age groups of Pakistani women.METHODS: In this exploratory cross-sectional study, an osteoporosis knowledge assessment questionnaire (OKAT) was used to collect data and it was delivered through a face-to-face interview. Questions were asked about symptoms of osteoporosis, knowledge of risk factors, preventive factors and treatment. A convenience sample (n =320) comprising of three groups of healthy women aged 25-35 years, 36-45 years, and over 45 years was taken. The scoring range was 0 to 20. Among-group comparisions of means were analyzed by two-way ANOVA. To determine the overall influence of osteoporosis-risk factors, the multivariate analysis was used.RESULTS: The knowledge on osteoporosis in younger women was very poor compared to relatively older females. However, women belonging to higher socioeconomic status and better education had slightly more knowledge about osteoporosis compared to those with a low education level, regardless of age.CONCLUSION: The majority of women had modest knowledge on osteoporosis. Younger women were at increased risk for low bone mass and premature osteoporosis

Fusion of Bacterial Flagellin to a Dendritic Cell-Targeting αCD40 Antibody Construct Coupled With Viral or Leukemia-Specific Antigens Enhances Dendritic Cell Maturation and Activates Peptide-Responsive T Cells

Conventional dendritic cell (DC) vaccine strategies, in which DCs are loaded with antigens ex vivo, suffer biological issues such as impaired DC migration capacity and laborious GMP production procedures. In a promising alternative, antigens are targeted to DC-associated endocytic receptors in vivo with antibody–antigen conjugates co-administered with toll-like receptor (TLR) agonists as adjuvants. To combine the potential advantages of in vivo targeting of DCs with those of conjugated TLR agonists, we generated a multifunctional antibody construct integrating the DC-specific delivery of viral- or tumor-associated antigens and DC activation by TLR ligation in one molecule. We validated its functionality in vitro and determined if TLR ligation might improve the efficacy of such a molecule. In proof-of-principle studies, an αCD40 antibody containing a CMV pp65-derived peptide as an antigen domain (αCD40CMV) was genetically fused to the TLR5-binding D0/D1 domain of bacterial flagellin (αCD40.FlgCMV). The analysis of surface maturation markers on immature DCs revealed that fusion of flagellin to αCD40CMV highly increased DC maturation (3.4-fold elevation of CD80 expression compared to αCD40CMV alone) by specifically interacting with TLR5. Immature DCs loaded with αCD40.FlgCMV induced significantly higher CMVNLV-specific T cell activation and proliferation compared to αCD40CMV in co-culture experiments with allogeneic and autologous T cells (1.8-fold increase in % IFN-γ/TNF-α+ CD8+ T cells and 3.9-fold increase in % CMVNLV-specific dextramer+ CD8+ T cells). More importantly, we confirmed the beneficial effects of flagellin-dependent DC stimulation using a tumor-specific neoantigen as the antigen domain. Specifically, the acute myeloid leukemia (AML)-specific mutated NPM1 (mNPM1)-derived neoantigen CLAVEEVSL was delivered to DCs in the form of αCD40mNPM1 and αCD40.FlgmNPM1 antibody constructs, making this study the first to investigate mNPM1 in a DC vaccination context. Again, αCD40.FlgmNPM1-loaded DCs more potently activated allogeneic mNPM1CLA-specific T cells compared to αCD40mNPM1. These in vitro results confirmed the functionality of our multifunctional antibody construct and demonstrated that TLR5 ligation improved the efficacy of the molecule. Future mouse studies are required to examine the T cell-activating potential of αCD40.FlgmNPM1 after targeting of dendritic cells in vivo using AML xenograft models

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Protein-Polymer Functionalized Aqueous Ferrofluids Showing High T2 Relaxivity

Controlled size, shape and dispersibility of superparamagnetic iron oxide nanoparticles (SPIONs), has been achieved in a protein-polymer colloidal dispersion. Stable ferrofluid (FF) is synthesized in an aqueous medium of collagen, bovine serum albumin and poly(vinyl) alcohol that equilibrates with time, at ambient conditions, into an organized matrix with iron oxide particles sterically caged at defined sites. It mimics a biomineralization system; hence the process is termed biomimetics. Though the exact mechanism is not understood at this stage, we have established, with serial dilution of the protein-polymer solution that the SPIONs are formed inside the self-contained clusters of the two proteins and the polymer, which show a tendency to self assemble. More than the interparticle dipolar attractions of magnetic particles, electrostatic interactions play a role in cluster formation and collagen is responsible for the overall stability, supported by systematic dynamic light scattering data. The basic aim of this study was to increase magnetization of a previously synthesized ferrofluid without hampering stability, reducing the total macromolecular concentration. Thrice the magnetization was achieved and in addition, the synthesized FFs exhibited very high transverse relaxivity and showed good contrast in mice liver, in the in vivo studie

Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI?

INTRODUCTION Preoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re-excision surgery. METHOD Ninety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer. RESULTS MRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics. Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012). MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%). CONCLUSION This study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful in the preoperative diagnosis and evaluation of HG DCIS. Case by case discussion at MDT is crucial. Wider adaptation of MRI when indicated in the assessment of breast lesions with proper correlation to histology postoperatively is a key in improving our MRI interpretation skills, helping us to exploit the full scope of this useful tool

Left atrial myxoma with cardiogenic shock following a myocardial infarction: a case report

Abstract Background Myxomas are the most common primary cardiac tumor and typically originate in the left atrium. Atrial myxomas may present following complications of obstruction and emboli. If an atrial myxoma goes untreated, complications such as congestive heart failure, embolic stroke, and sudden death can occur. Case presentation A 58-year-old Caucasian male presented following a cardiac arrest. He was taken emergently to the cardiac catheterization lab and received two drug eluting stents. Following the procedure, he was found to have a left atrial mass that was intermittently obstructing the mitral valve on echocardiography. After leaving the cardiac catheterization lab, he was hypotensive and placed on multiple intravenous medications for hemodynamic support as well as an Impella device. Following medical optimization, he underwent one vessel coronary artery bypass graft as well as surgical excision of the left atrial mass, which pathology had shown to be an atrial myxoma. Conclusion This patient’s case of cardiogenic shock following revascularization was complicated by the identification of an atrial myxoma, which, when large enough, can obstruct blood flow through the mitral valve leading to acute mitral dynamic stenosis. This condition results in circulatory collapse due to obstruction of the left ventricle in diastole as the myxoma occludes the mitral valve