Shape modelling reveals age-related knee bony shape changes in asymptomatic knees.

Osteoarthritis (OA) causes bony shape changes within the knee. Furthermore, the risk of developing OA increases with age. However, age alone does not cause OA. It is therefore important to understand the healthy age-related trajectories of knee shape before attributing these changes to OA. The aim of this study was to determine the association between bony knee shape and age using statistical-shape modelling (SSM). 96 participants received a CT scan of their knee. Three-dimensional models were created using manual segmentation. Separate SSM's for the distal femur and proximal tibia were created. Linear regression models were used to assess the association between age and femoral and tibial shape. Fourteen modes of the femoral and tibial SSM's captured 68% and 73% shape variation, respectively. Only femoral mode 3 and tibial mode 7 were associated with age. Increasing age was related to larger femoral bone volume and deepening of the femoral trochlear groove. Furthermore, increased age was associated with medial tibial plateau expansion. Aspects of bony femoral and tibial shape were significantly associated with aging, including femoral and tibial bone size, femoral trochlear groove, and medial tibial plateau area. Changes in knee morphology occur as a normal process of aging without osteoarthritis development. This may be a response to mechanical loading over time. Further research investigating the effect of these changes on loading in the knee may provide valuable information for knee health in older age.

Weightbearing versus non-weight bearing in geriatric distal femoral fractures: a systematic review and meta-analysis.

BACKGROUND: Demographics of patients who sustain geriatric distal femoral fractures (DFF) match those of patients with neck-of-femur fractures but have limited evidence with which to support post-operative weightbearing protocols. PURPOSE: This systematic review sought to identify any difference in outcomes for elderly patients with DFF who were allowed early versus delayed weightbearing postoperatively. METHODS: DATA SOURCES: PubMed, Medline, Embase and The Cochrane Library, reference lists of retrieved articles. STUDY SELECTION: English language papers published between January 2010 and February 2023 with AO-OTA type 33A, B and C femoral fractures as well as Lewis and Rorabeck Type I and II periprosthetic DFF surgically treated with either a lateral locking plate or retrograde intramedullary nail and an average patient age of ≥ 60 years. DATA EXTRACTION: Studies were assessed for inclusion by two authors and quality was assessed using the MINORS tool. DATA SYNTHESIS: Sixteen studies were included, Meta-analysis of non-union, malunion, infection, delayed union and implant complications was performed using Microsoft Excel and the MetaXL extension. The data on return to mobility were presented in narrative form. The analyses demonstrated no difference between the early and delayed weightbearing groups. CONCLUSIONS: There are no significant differences in complication rates between early versus delayed weightbearing after surgery for DFF in an elderly population. The study results are limited by high heterogeneity and low-quality studies. High quality, prospective studies are needed to determine the ideal postoperative weightbearing protocol. LEVEL OF EVIDENCE: Level III, Systematic Review and Meta-analysis of Level III studies. International Prospective Register of Systematic Reviews registration-Prospero CRD42022371460.

Intra-articular Vancomycin Reduces Prosthetic Infection in Primary Hip and Knee Arthroplasty.

Background: Intravenous antibiotic infusion has been the standard prophylaxis for total joint arthroplasty surgery. However, infection rates still occur at 1%-2% in many series. Single-dose intra-articular antibiotics (IAAs) present a safe and potentially more effective prophylactic regime in total joint arthroplasty. This study aimed to assess the outcomes of a single-dose IAA injection on PJI rates in a single surgeon series of hip and knee arthroplasty. Methods: We reviewed the data of all patients operated on for a primary hip or knee replacement from 2010 to 2021. From January 2018, 1 gm of vancomycin in 10 ml of saline was injected into every total joint replacement after fascial closure. A comparison was made with PJI referencing the Australian National Joint Replacement Registry data on revision for the 2 periods: 2010-2017 and 2018-2021. Results: During the period without IAA (2010-2017) for TKR, 6 of 489 (1.2%), and for THR, 5 of 694 (0.7%) had PJI requiring revision surgery. In the period with IAA (2018-2021) for TKR, 0 of 214 (0%, P = .11), and for THR, 1 of 517 (0.2%, P = .19) PJI required revision surgery, but the overall incidence of PJI for TKR and THR was significantly reduced (P = .03). Conclusions: A single dose of intra-articular vancomycin 1 gm injected into the total joint replacement following fascial closure reduced the incidence of deep PJI requiring a revision surgery in a single-surgeon series. These results demonstrate significant benefits to this technique which merit further larger trials.

Are Kinematics an Indicator of Outcome After Total Knee Arthroplasty?

BACKGROUND: A proportion of total knee arthroplasty (TKA) patients are dissatisfied postoperatively, particularly with their ability to perform higher-demand activities including deep-kneeling and step-up where kinematic parameters are more demanding. The purpose of this study was to examine the relationship between knee kinematics of step-up and deep-kneeling and patient-reported outcome measures following TKA. METHODS: Sixty-four patients were included at minimum 1-year follow-up. Participants performed a step-up and deep-kneeling task which was imaged via single-plane fluoroscopy. 3-dimensional prosthesis computer-aided design models were registered to the fluoroscopy, yielding in-vivo kinematic data. Associations between kinematics and patient-reported outcome measures, including Oxford Knee Score, American Knee Society Score, surgical satisfaction, and pain were assessed using log-transformed step-wise linear regressions. RESULTS: A higher total Oxford Knee Score was associated with more external rotation and more adduction at maximal flexion during kneeling and more external rotation and minimum flexion during step-up. Improved American Knee Society Score was associated with increased internal-external rotation during step-up. Improved surgical satisfaction was associated with greater maximum flexion and more external rotation at maximal flexion during deep-kneeling and more femoral internal rotation at terminal extension during step-up. An improved pain score was associated with greater maximum flexion and more femoral external rotation during deep-kneeling, as well as greater internal femoral rotation during step-up. CONCLUSION: The ability to move through full flexion/extension range and end-of-range rotation is important kinematic parameters that influence patient-reported outcome measures. Implant designs and postoperative rehabilitation should continue to focus on achieving these kinematic targets for enhanced outcomes after TKA.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

The use of intra-articular vancomycin is safe in primary hip and knee arthroplasty.

Background: The use of a single dose of intra-articular antibiotic (IAA) has been reported in reducing the rate of prosthetic joint injection after total hip and knee arthroplasty. We examine the safety of IAA in primary hip and knee replacement surgery and the blood levels and joint fluid levels of vancomycin utilising this technique. Methods: From August to October 2021, 68 patients undergoing primary total joint arthroplasty (THA & TKA) were given 1g vancomycin intra-articularly (IA)after closure of the fascia. All patients received 2g cefazolin intravenously (IV) 30 min prior to the procedure as is our standard prophylaxis, and 21 of the patients (IA + IV) were also administered an additional 1 gm vancomycin IV. Post-operative blood vancomycin, creatinine land eGFR level monitoring was performed d1 and d3. To determine the post-operative intra-articular vancomycin levels, surgical drain fluid was sampled at day 1 and 2, in 10 patients. Results: All patients had serum vancomycin levels measured on day 1 and 3. In the group where vancomycin was injected after fascial closure, the average blood vancomycin level day 1 was 5.2 µg/ml (range 2.0-10.9) and day 3 was <1.4 µg/ml. The average pre-op creatinine levels were 69.4 µmol/L (56.1-82.6) compared to 70.2 µmol/L (57.0-83.4) on day 1 and 66.1 µmol/L (52.6-79.6) on day 3, (p = 0.663). The average pre-op eGFR levels (ml/min/1.73 m2) were 82.2 (76.0-88.3) compared to 81.7 (75.6-87.8) on day 1 and 83.0 (76.8-89.2) on day 3 (p = 0.736). Samples of joint fluid aspirated from surgical drains on day 1 and day 2 showed average vancomycin levels of 224 µg/ml and 51 µg/ml respectively, significantly higher than the MIC for Staph aureus. Conclusions: The use of intra-articular vancomycin is safe in primary TJA, with no renal damage and delivers levels within the joint which are highly therapeutic for at least 48 h post injection.

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) in Canada: treatment update and the role of new IV antimicrobials.

INTRODUCTION: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) continue to be common infections causing significant morbidity and mortality worldwide. The timely initiation of empiric antimicrobial therapy is essential. In this paper, we provide a focused expert opinion on the current and potential empiric antimicrobial treatment options in HABP and VABP in Canada influenced by antimicrobial resistance impacting the use of older agents as well as available new intravenous (IV) antimicrobials. AREAS COVERED: The authors discuss treatment options for HABP and VABP in Canada. In addition, we focus on the potential role of new IV antimicrobials recently introduced to Canada. A literature search of HABP and VABP treatments was performed via PubMed (up to March 2023), using the following key words: monotherapy, combination therapy, aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins as well as amoxicillin/clavulanate, ceftobiprole, ceftolozane/tazobactam, dalbavancin, and fosfomycin. EXPERT OPINION: Empiric antimicrobial treatment for HABP and VABP in Canada continues to focus on both the severity of illness and the presence/absence of patient risk factors for antimicrobial resistance. The role of new IV antimicrobials in the empiric treatment for HABP and VABP depends on their antimicrobial activity and published data on efficacy and safety and influenced by Health Canada-approved indications.

Close Canine Contact: A Case of Infantile Pasteurella Meningitis.

This case report presents an interesting and rare cause of meningitis in young infants, Pasteurella multocida. Not only is the organism unusual but the well appearance of the infant made this diagnosis surprising. The 2021 American Academy of Pediatrics (AAP) clinical practice guidelines on well-appearing febrile infants brought a national guideline on the evaluation and management of fever in infants. However, providers should be aware that there is room for shared decision-making and that the guideline will miss a very small percentage of well-appearing infants with invasive bacterial infections.

Special Issue "Diagnosis and Treatment of Invasive Pulmonary Fungal Infections".

The Guest Editors Dr [...].

Part 2: mucormycosis: focus on therapy.

INTRODUCTION: Mucormycosis (MCR), a rare but life-threatening infection, occurs primarily in immunocompromised hosts. Mortality rates with invasive MCR are high (>30-50%), up to 90% with disseminated disease, but lower (10-30%) with localized cutaneous disease. Due to the rarity of MCR, randomized, controlled therapeutic trials are lacking. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy or in MCR cases refractory to or intolerant of LFAB. Early surgical debridement or excision plays important adjunctive roles in localized invasive disease. Control of hyperglycemia in diabetic patients, correction of neutropenia, and reduction of immunosuppressive therapy are critical for optimal survival. AREAS COVERED: The authors discuss various therapeutic options for mucormycosis. A literature search of mucormycosis therapies was performed via PubMed (up to December 2022), using the following keywords: invasive fungal infections; mold; mucormycosis; Mucorales; amphotericin B; isavuconazole; and posaconazole. EXPERT OPINION: Randomized, controlled therapeutic trials are lacking. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but oral triazoles (posaconazole and isavuconazole) may be effective as step-down therapy, in MCR cases refractory to or intolerant of LFAB. We encourage early surgical debridement or excision as adjunctive measures.

Part 1: Mucormycosis: prevalence, risk factors, clinical features, and diagnosis.

INTRODUCTION: Mucormycosis (MCR) is caused by filamentous molds within the Class Zygomycetes and Order Mucorales. Infections can result from inhalation of spores into the nares, oropharynx, or lungs, ingestion of contaminated food or water, or inoculation into disrupted skin or wounds. In developed countries, MCR occurs primarily in severely immunocompromised hosts. In contrast, in developing/low income countries, most cases of MCR occur in persons with poorly controlled diabetes mellitus and some cases in immunocompetent subjects following trauma. Mucormycosis exhibits a propensity to invade blood vessels, leading to thrombosis and infarction of tissue. Mortality rates associated with invasive MCR are high and can exceed 90% with disseminated disease. Mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM); (2) pulmonary; (3) cutaneous; (4) gastrointestinal or renal (5); disseminated; or (6) uncommon (focal) sites. AREAS COVERED: The authors discuss the prevalence, risk factors, and clinical features of mucormycosis. A literature search of mucormycosis was performed via PubMed (up to November 2022), using the key words: invasivefungal infections; mold; mucormycosis;Mucorales; Zyzomyces; Zygomycosis; Rhizopus, diagnosis. EXPERT OPINION: Mucormycosis occurs primarily in severely immunocompromised hosts. Mucormycosis can progress rapidly, and delay in initiating treatment by even a few days worsens outcomes.

Streptococcus pneumoniae serotyping and antimicrobial susceptibility: assessment for vaccine efficacy in Canada after the introduction of PCV13.

BACKGROUND: Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries. OBJECTIVES: To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines. METHODS: SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada-National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation. RESULTS: The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011-2020). CONCLUSIONS: The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.

Evidence for key individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis: A systematic review.

OBJECTIVE: To identify individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis. METHODS: MEDLINE, CINAHL, Scopus, Web of Science Core Collection and the Cochrane library were searched. Studies were included if they reported an association between baseline factors and change in pain or function following combined exercise therapy, osteoarthritis education, or weight management interventions for knee osteoarthritis. Risk of bias was assessed using Quality in Prognostic Factor Studies. Data was visualised and a narrative synthesis was conducted for key factors (age, sex, BMI, comorbidity, depression, and imaging severity). RESULTS: 32 studies were included. Being female compared to male was associated with 2-3 times the odds of a positive response. Older age was associated with reduced odds of a positive response. The effect size (less than 10% reduction) is unlikely to be clinically relevant. It was difficult to conclude whether BMI, comorbidity, depression and imaging severity were associated with pain and function outcomes following a combined first-line intervention for knee osteoarthritis. Low to very low certainty evidence was found for sex, BMI, depression, comorbidity and imaging severity and moderate certainty evidence for age. Varying study methods contributed to some difficulty in drawing clear conclusions. CONCLUSIONS: This systematic review found no clear evidence to suggest factors such as age, sex, BMI, OA severity and presence of depression or comorbidities are associated with the response to first-line interventions for knee OA. Current evidence indicates that some groups of people may respond equally to first-line interventions, such as those with or without comorbidities. First-line interventions consisting of exercise therapy, education, and weight loss for people with knee OA should be recommended irrespective of sex, age, obesity, comorbidity, depression and imaging findings.

Neuroblastoma Masquerading as a Septic Hip Infection in a Three-Year-Old.

Metastatic neuroblastoma to the bone and septic joint shares the same incidence in age and clinical symptomology. Here we discuss a three-year-old male who presented with anemia, persistent hip pain, and a refusal to bear weight. A thorough evaluation based on a broad differential diagnosis allowed for an expedient diagnosis of metastatic neuroblastoma. The timely diagnosis allowed for rapid enrolment in a children's oncology group (COG) clinical trial for advanced neuroblastoma. The patient tolerated the therapy without adverse events and remains in remission.

Statistical shape modelling reveals differences in hamstring morphology between professional rugby players and sprinters.

Hamstring morphology may play an important role in understanding the aetiology of hamstring injury. Currently, the methods available to capture detailed morphological data such as muscle shape have not been utilized for the hamstring muscles. The aim of this study was to examine the utility of statistical shape modelling (SSM) for describing and comparing hamstring muscle shape in rugby and sprinting athletes. Magnetic resonance images of both thighs of nine elite male rugby players and nine track and field sprinters were analysed. Images were converted to three-dimensional models enabling generation of four statistical shape models. Principal components describing the shape variation in the cohort were derived and evaluated. Six principal components were sufficient to discriminate differences in the shape of the hamstring muscles of rugby and sprinting athletes with 89% classification accuracy. Distinct shape features distinguishing rugby players from sprinters included size, curvature and axial torsion. These data demonstrate that SSM is useful for understanding hamstring muscle shape and that meaningful variation can be identified within a small sample. This method can be used in future research to enhance the anatomical specificity of musculoskeletal modelling and to understand the relationship between hamstring shape and injury.

A Five-Month-Old Boy With Hypotonia, Electrolyte Derangements, and Failure to Thrive.

Failure to thrive in the setting of profound hypotonia and multiple electrolyte derangements is a challenging constellation of findings that offers a broad differential diagnosis for providers to consider. Initial management should focus on the stabilization of the patient and correction of potential life-threatening electrolyte derangements. Once completed, the diagnosis should be sought, and in this case, many were considered and ultimately ruled out with thorough history and physical examination. Laboratory abnormalities revealed the final diagnosis of pseudohypoaldosteronism and connected the case. With proper treatment, our patient had a resolution of laboratory anomalies along with improved growth and tone.

Escalation of antimicrobial resistance among MRSA part 2: focus on infections and treatment.

INTRODUCTION: MRSA is associated with causing a variety of infections including skin and skin structure infections, catheter and device-related (e.g. central venous catheter, prosthetic heart valve) infections, infectious endocarditis, blood stream infections, bone, and joint infections (e.g. osteomyelitis, prosthetic joint, surgical site), central nervous system infections (e.g. meningitis, brain/spinal cord abscess, ventriculitis, hydrocephalus), respiratory tract infections (e.g. hospital-acquired pneumonia, ventilator-associated pneumonia), urinary tract infections, and gastrointestinal infections. The emergence and spread of multidrug resistant (MDR) MRSA clones has limited therapeutic options. Older agents such as vancomycin, linezolid and daptomycin and a variety of newer MRSA antimicrobials and combination therapy are available to treat serious MRSA infections. AREAS COVERED: The authors discuss infections caused by MRSA as well as common older and newer antimicrobials and combination therapy for MRSA infections. A literature search of MRSA was performed via PubMed (up to September 2022), using the keywords: antimicrobial resistance; ß-lactams; multidrug resistance, Staphylococcus aureus, vancomycin; glycolipopeptides. EXPERT OPINION: Innovation, discovery, and development of new and novel classes of antimicrobial agents are critical to expand effective therapeutic options. The authors encourage the judicious use of antimicrobials in accordance with antimicrobial stewardship programs along with infection-control measures to minimize the spread of MRSA.