Dramatic increase in antimicrobial resistance in ESKAPE clinical isolates over the 2010-2020 decade in India.

RATIONALE AND OBJECTIVES: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) constitute a threat to humans worldwide. India is now the most populous country. The goal was to investigate the evolution of the rates of antimicrobial resistance in ESKAPE pathogens across India over the 2010-20 decade. METHODS: The data (89 studies) were retrieved from the Medline PubMed repository using specific keywords. RESULTS: The study of 20 177 ESKAPE isolates showed that A. baumannii isolates were the most represented (35.9%, n = 7238), followed by P. aeruginosa (25.3%, n = 5113), K. pneumoniae (19.5%, n = 3934), S. aureus (16.3%, n = 3286), E. faecium (2.6%, n = 517) and Enterobacter spp. (0.4%, n = 89). A notable increase in the resistance rates to antimicrobial agents occurred over the 2010-20 decade. The most important levels of resistance were observed in 2016-20 for A. baumannii (90% of resistance to the amoxicillin-clavulanate combination) and K. pneumoniae (81.6% of resistance to gentamycin). The rise in ß-lactamase activities was correlated with an increase in the positivity of Gram-negative isolates for ß-lactamase genes. CONCLUSIONS: This review highlighted that, in contrast to developed countries that kept resistance levels under control, a considerable increase in resistance to various classes of antibiotics occurred in ESKAPE pathogens in India over the 2010-2020 decade.

Two to Five-Year Outcomes of Total Ankle Arthroplasty with the Infinity Fixed-Bearing Implant: A Concise Follow-up of a Previous Report.

LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Knowledge and Attitude toward Antibiotic Use and Identification of Financially Feasible Options to Curb the Spread of Antibiotics in Environment.

A survey on antibiotic literacy in terms of the use and abuse of antibiotics to track and understand antibiotic consumption is crucial to optimize the use of antibiotics and minimizing antimicrobial resistance (AMR). Purposive random sampling, using the snow-ball questionnaire technique, was adopted to ensure that the respondents distributed across India, coming from rural and urban settings, were adolescents as well as adults and had completed at least the higher secondary school level of education. Respondents were divided into five subcategories. The questionnaire was distributed between April 2021 and July 2021, during the second COVID-19 wave in India. The survey questionnaire included 34 questions, comprising multiple-choice and 5-point Likert scale-type questions. This study composed of 972 respondents. Most respondents considered antibiotics safe and frequently failed to discriminate between the symptoms of bacterial and viral infections, most often leading to self-prescription. About 34% of the rural participants and 50% of the urban participants considered antibiotic resistance a serious health concern. Antibiotic prescriptions by the medical or paramedical practitioner were largely empirical. At least 95% of participants acknowledged having heard about antibiotics; nearly 20% of antibiotic consumption came from nonprescription users, while 30% had not completed their antibiotic therapy for a variety of reasons. Sixty-two percent consumed antibiotics to treat cold and flu symptoms. Results from the survey suggest the presence of a crucial gap between the respondents' perception of antibiotics and levels of information regarding antibiotic use and misuse. The present study may serve as a benchmark that strongly recommends a financially feasible policy, which includes educating society regarding the spread of AMR and its severe consequences by incorporating AMR into the curriculum at the levels of senior secondary school and higher education.

Co-existence of Extended Spectrum ß-Lactamase and carbapenemase-producing genes from Diarrheagenic Enteric pathogens isolated in a tertiary care hospital.

Multiple drug resistance (MDR) among bacterial pathogens is a growing concern that clinicians are facing worldwide. Diarrhea among infants is frequent and is caused by various bacterial and viral infectious agents. Two hundred and twelve stool specimens were collected from pediatric patients from a rural quaternary hospital in Barshi, Sholapur, India, between March and December 2017. Total 180 specimens were positive for various bacterial pathogens, while the remaining 32 diarrhea cases may have been caused by a viral or uncultured bacterial pathogen. Identification of the bacterium and its antibiotic susceptibility were primarily carried out with VITEK-2. Distribution of diarrhea-causing bacteria among the 180 samples was as follows: 61.11% (110) Escherichia coli, 30.55% (55) Klebsiella pneumoniae, 4.44% (8) Proteus mirabilis, 2.22% (4) Shigella spp. 1.11% (2) Morganella morganii and 0.55% (1) each for Enterobacter cloacae and Citrobacter koseri. There was a co-existence of multiple genetic traits conferring extreme drug resistance (XDR) status to 19 isolates, 17 of which were determined to be E. coli and one each of E. cloacae and C. koseri. Antibiotype determination using VITEK-2 and polymerase chain reaction (PCR) amplification of the genetic traits indicated the co-existence of blaTEM and blaCTX-M15 isolates in all 19 isolates, with the exception of E. cloacae. Results showed that 10 out of 19 strains expressed the AmpC cephalosporinase blaCMY-2 gene, whereas metallo-carbapenemase was expressed in four isolates. Distribution of blaNDM-11 and acquired penicillinase blaSHV-1 resistance among 180 clinical isolates is discussed in the light of ESBL traits. This is the first report from the rural part of Maharashtra India showing that as many as 10.55% of the pathogenic strains were XDR, a step ahead of MDR.

Total Ankle Replacement Versus Arthrodesis for End-Stage Ankle Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF). OBJECTIVE: To determine which treatment is superior in terms of clinical scores and adverse events. DESIGN: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307). SETTING: 17 National Health Service trusts across the United Kingdom. PATIENTS: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure. INTERVENTION: Patients were randomly assigned to TAR or AF surgical treatment. MEASUREMENTS: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible. RESULTS: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9]). LIMITATION: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques. CONCLUSION: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Heath Technology Assessment Programme.

Green Synthesis of Silver Nanoparticles Using the Tridax procumbens Plant Extract and Screening of Its Antimicrobial and Anticancer Activities.

In this study, we report the green synthesis of silver nanoparticles (AgNPs) using the aqueous leaf extract of Tridax procumbens (TNP), which acts as the source of the reducing and capping agent. The distinctive absorption at 370 nm suggested synthesis of TNPs, which was confirmed by TEM, with a size in the range of 11.1 nm to 45.4 nm and a spherical shape, having a face-centered cubic structure, analyzed by XRD, and a Zeta potential of -20.7 mV, which indicated a moderate stability of TNP. The FTIR analysis revealed the presence of amines and hydroxyl groups with fluoro compounds over the TNPs. The HRLC-MS analysis of TNPs suggested the presence of a major capping agent such as fosinopril and reducing agents such as peptides (Gln Gly Ala, Ser Pro Asn, and Leu Met), terpenoids (lupanyl acid, tiamulin), polyphenol (peucenin), and alkaloids (8',10'-dihydroxydihydroergotamine, carteolol). The synthesized silver nanoparticles exhibited antimicrobial activity against multidrug-resistant (MDR) clinical isolates (Escherichia coli, Shigella spp., Aeromonas spp., Pseudomonas aeruginosa, and Candida tropicalis) and had anticancer activity against A459 (IC50 42.70 µg/ml). The extraction of partially purified aqueous leaf extracts by silica gel column chromatography followed by HPLC to synthesize silver nanoparticles (TNP11) and analyzed by HRLC-MS suggested that dipeptides were involved in the reduction of Ag+ to Ag0. Overall, the results showed that the green silver nanoparticles of T. procumbens could be safe, as they are endowed with potential antimicrobial activity against MDR clinical isolates and human lung carcinoma cells.

Osteochondral Lesions of the Ankle Treated with Bone Marrow Concentrate with Hyaluronan and Fibrin: A Single-Centre Study.

Osteochondral defects of the ankle (OCD) are being increasingly identified as a clinically significant consequence of injury to the ankle, with the potential to lead to osteoarthritis if left untreated. The aim of this retrospective cohort study was to evaluate a single-stage treatment of OCD, based on bone marrow aspirate (BMA) centrifuged to produce bone marrow concentrate (BMC). In a dual syringe, the concentrate was mixed with thrombin in one syringe, whereas hyaluronan and fibrinogen were mixed in a second syringe. The two mixtures were then injected and combined into the prepared defect. Clinical outcome and quality of life scores (MOXFQ and EQ-5D) were collected at baseline and yearly thereafter. Multilevel models were used to analyse the pattern of scores over time. Ninety-four patients were treated between 2015 and 2020. The means of each of the three components of the MOXFQ significantly improved between baseline and 1 year (p < 0.001 for each component), with no further change from year 1 to year 3. The EQ-5D index also improved significantly from baseline to 1 year, with no evidence for further change. Our results strongly indicate that this BMC treatment is safe for, and well tolerated by, patients with OCD of the ankle as both primary treatment and those who have failed primary treatment. This technique provides a safe, efficacious alternative to currently employed cartilage repair techniques, with favourable outcomes and a low complication rate at 36 months.

The management of talar osteochondral lesions - Current concepts.

Osteochondral lesions of the talus (OLTs) are a common complication following trauma, involving both the articular cartilage and the underlying subchondral bone, with variable aetiologies and often presenting with non-specific symptoms. Diagnosis of OLTs requires a combination of clinical assessment and imaging and despite many different treatment options, there is no generalised consensus regarding which option is the most effective. Left untreated, OLTs risk progressing to osteoarthritis. Acute non-displaced OLTs can be treated non-operatively. However, OLTs refractory to non-surgical care for three to six months may be suitable for surgical care. In these cases, conservative treatments are often unsuccessful, particularly for larger and more severe defects and so the majority require surgical intervention. Although bone marrow stimulation techniques remain the "gold standard" for lesions <150 mm2, there still requires a need for better long term clinical data and cost-benefit analyses compared with other treatment options. Biological attempts at either regenerating or replacing the articular cartilage are however demonstrating some promising results, but each with their own advantages and disadvantages. In this review, we summarise the clinical management of OLTs and present the current concepts of different treatment regimes.

Design and psychometric testing of a new patient-reported outcome measure for ankle treatment.

BACKGROUND: Several outcome scores are used to assess the outcome of ankle surgery, but many are not validated and there is currently no 'gold-standard'. Consequently, there is demand to develop a new 'gold-standard' score to assess ankle surgery. The study aim was to review existing scores to develop and validate a new patient-reported outcome measure (PROM) to assess the outcome of operative ankle surgery. METHODS: The questionnaire items covered three areas: pain, symptoms and activity. The scale was reviewed by a patient group, resulting in the Oswestry Ankle score (Os-Ankle). The Os-Ankle was validated using a cohort of 206 patients at both pre-operative and post-operative stages of ankle surgery. Patients provided two other outcome scores, the scores currently used at our centre: the Manchester-Oxford Foot Questionnaire (MOxFQ) and the Veterans Rand-12 (VR-12). Factor analysis and Rasch were determined to assess the psychometric testing and design of the Os-Ankle score. A follow up paper assesses the validity of the Os-Ankle against two existing scores. RESULTS: Results of the factor and Rasch analysis suggested that 12-items should be removed. The remaining 18-items fitted the Rasch model well, suggesting good internal consistency. CONCLUSION: A new ankle PROM, the Os-Ankle, was successfully developed and demonstrated good psychometric testing. The Os-Ankle evaluates pain, symptoms and activities and results in a single score. The Os-Ankle has been validated in our follow up paper, and is ready to be implemented by ankle clinicians to monitor clinical outcomes. With the publication of two back to back papers, it will allow for further engage with other clinicians and other centres. LEVEL OF EVIDENCE: Level II, prospective comparative study.

A new "tension side" locking plate for Hallux Valgus: A prospective multicentre case series.

BACKGROUND: Proximal osteotomy of the first metatarsal is often indicated for Hallux Valgus correction. Previously recognised complications however, include transfer metatarsalgia, first metatarsophalangeal joint stiffness, problems with fixation and prominence of metalware. METHODS: We report on one year follow up of an international prospective series between June 2009 and October 2012 involving three centres, including 91 feet (58 patients) that underwent proximal osteotomy, using a new locking plate applied to the plantar surface of the metatarsal. RESULTS: Mean Hallux Valgus angle improved from 27.9 (±13.1)° to 12.4 (±8.2)° while mean Intermetatarsal angle improved from 12.5 (±8.4) to 7.1 (±3.4) and there was a statistically significant improvement in both mean AOFAS-HMI score 54.2 (±13.9) to 94.0 (±9.5) and Visual Analogue Pain Scale 4.7 (±1.5) to 0.6 (±1.3). 70% of patients were back at their preoperative employment at five weeks. Mean surgical time was 56min and the plate was generally well tolerated. There were five implant related complications. CONCLUSIONS: Locked fixation from the tension side of the construct encourages early weight bearing with a low risk of implant prominence. Our radiological, functional and clinical parameters are comparable with similar series and we therefore recommend this technique.

Cell cultured chondrocyte implantation and scaffold techniques for osteochondral talar lesions.

Cell cultured techniques have gained interest and popularity in osteochondral defects because, unlike bone marrow stimulation methods, where fibrocartilage fills the defect, they allow for the regeneration of "hyaline-like cartilage" with better stiffness, resilience, and wear characteristics. Osteochondral defects in the ankle are a rare but challenging problem to treat in young active patients. If left alone, they can cause pain and reduced function and risk progressive degenerative changes in the joint. Clinical results of cell cultured and scaffold technology in the ankle, although still limited by small studies and midterm follow-up, are certainly encouraging.

Anatomic description of the distal tibia: implications for internal fixation.

Fracture fixation using minimally invasive plating techniques around the distal tibia are well described, although there are a number of potential hazards and complications. Our study provides an anatomical description of the distal tibia and its relations to surrounding structures. Twenty magnetic resonance imaging scans of the distal tibia were analyzed in the coronal, sagittal, and axial planes. Measurements were taken by 2 observers on 2 occasions of the distance of anterior structures from the tibial cortex as well as dimensional parameters. The mean dimensions of the distal tibia at the level of the plafond were 39 mm medial-lateral and 36 mm anteroposterior. The anterior neurovascular bundle was found to be a mean of 3 mm from the anterior tibial cortex with the anterior tendinous structures located <6 mm. The intraclass correlation coefficient for the first observer was 0.8 and for the second observer was 0.78 with an interclass correlation coefficient of 0.8. This demonstrated excellent interobserver and intraobserver reliability. This study presents the first magnetic resonance imaging-based anatomical description of the distal tibia. It showed that key anatomical structures are in very close proximity to the distal tibia, and this is important to consider when treating fractures in this region with internal fixation.

Are old running shoes detrimental to your feet? A pedobarographic study.

BACKGROUND: Footwear characteristics have been implicated in fatigue and foot pain. The recommended time for changing running shoes is every 500 miles. The aim of our study was to assess and compare plantar peak pressures and pressure time integrals in new and old running shoes. FINDINGS: This was a prospective study involving 11 healthy female volunteers with no previous foot and ankle problems. New running shoes were provided to the participants. Plantar pressures were measured using the Novel Pedar system while walking with new and participants' personal old running shoes. Plantar pressures were measured in nine areas of the feet. Demographic data, age of old running shoes, Body Mass Index (BMI), peak pressures and pressure-time integral were acquired. The right and left feet were selected at random and assessed separately. Statistical analysis was done using the paired t test to compare measurements between old and new running shoes.The mean peak pressures were higher in new running shoes (330.5 ± 79.6 kiloPascals kPa) when compared to used old running shoes (304 ± 58.1 kPa) (p = 0.01). The pressure-time integral was significantly higher in the new running shoes (110 ± 28.3 kPa s) compared to used old running shoes (100.7 ± 24.0 kPa s) (p = 0.01). CONCLUSION: Plantar pressure measurements in general were higher in new running shoes. This could be due to the lack of flexibility in new running shoes. The risk of injury to the foot and ankle would appear to be higher if running shoes are changed frequently. We recommend breaking into new running shoes slowly using them for mild physical activity.

Avulsion fracture of the medial malleolus following posterior tibialis tendon dislocation: a case report.

Dislocation of the posterior tibialis tendon as an isolated injury is rare. The diagnosis is often delayed due to its rarity and the need for various second line imaging modalities. We present a case of a dislocated posterior tibialis tendon that resulted in an avulsion type fracture of the medial malleolus. The fracture was openly reduced and internally fixed with inter-fragmentary screws. The patient was asymptomatic at 1 year follow-up.

Tenosynovial osteochondromatosis of the flexor hallucis longus tendon.

We present a case of tenosynovial osteochondromatosis affecting the flexor hallucis longus tendon in a 29-year-old male with chronic ankle pain. Clinical examination was normal. Plain radiographs and MRI revealed multiple calcified lesions. These were removed surgically and histological analysis confirmed the diagnosis. This condition is rare, particularly in the foot and ankle. This is the first reported case of such a lesion with an absence of any clinically palpable nodules and highlights the need for a high index of suspicion and the need for imaging.

Retained blackthorn causing peroneal tendonitis: a case report.

We present the first reported case of peroneal tenosynovitis secondary to a retained blackthorn in a patient with a 4 months history of persistent pain and swelling around her lateral malleolus following a penetrating injury. Ultrasonography reported considerable subcutaneous fluid but no identifiable foreign body. Magnetic resonance imaging confirmed peroneal sheath synovitis with a possible retained foreign body posteriorly. Surgical exploration revealed marked synovitis and chronic inflammation of the peroneal sheath with the tip of a blackthorn deep to peroneus longus. This case illustrates the many ways in which penetrating blackthorn injuries may present. In particular it highlights the need for a high index of suspicion for retained foreign material and the need for further imaging and surgical exploration when symptoms do not resolve.

The effect of newer anti-rheumatic drugs on osteogenic cell proliferation: an in-vitro study.

BACKGROUND: Disease modifying anti-rheumatic drugs (DMARDs) may interfere with bone healing. Previous studies give conflicting advice regarding discontinuation of these drugs in the peri-operative setting. No consensus exists in current practice especially with the newer DMARDs such as Leflunomide, Etanercept, and Infliximab. The aim of this study was to assess the in-vitro effect of these drugs alone and in relevant clinical combinations on Osteoblast activity. METHODS: Osteoblasts were cultured from femoral heads obtained from five young otherwise healthy patients undergoing total hip replacement. The cells were cultured using techniques that have been previously described. A full factorial design was used to set up the experiment on samples obtained from the five donors. Normal therapeutic concentrations of the various DMARDs were added alone and in combination to the media. The cell proliferation was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multilevel regression analysis was used to estimate which drugs or combination of drugs significantly affected cell proliferation. RESULTS: Infliximab and Leflunomide had an overall significant inhibitory effect (p < 0.05). Dexamethasone had a small stimulatory effect that was however strongly donor-dependent. The cox-2 inhibitor Etoricoxib was found to negate or increase the action of two other drugs (Leflunomide and Dexamethasone). Methotrexate and Etanercept had no discernable donor-dependant or donor-independent effect on osteoblast proliferation. CONCLUSION: Our study indicates that in-vitro osteoblast proliferation can be inhibited by the presence of certain DMARDs. Combinations of drugs had an influence and could negate the action of a drug on osteoblast proliferation. The response to drugs may be donor-dependent.

Biomechanical characteristics of three staples commonly used in foot surgery.

BACKGROUND: Bone staples are an accepted method of fixation in foot surgery. They reduce operating time and trauma in surgical procedures. A variety of memory staples are available but their properties compared to standard staples are not known. We carried out a study comparing two popular types of memory staples and a standard stainless steel staple. METHODS: Standardized bone models of metatarsals made from Tufnol tubes were osteotomized and stabilised using one of three types of bone staples, two types of memory staple (Memory staple and heat-activated Memoclip) or a standard stainless steel staple (Richards). Constructs were loaded in bending and torsion on a material testing machine. The moment and torque to achieve 10 degree of bending or torsion and permanent angulation of the osteotomized bones were assessed. RESULTS: The Richards staple was found to provide a four times larger resistance to bending and torsion than the two memory staples. However, it was permanently deformed after bending. The Memory and Memoclip staples were equal in their stiffness. In addition, angulation of bones fixed with the Memoclip was elastic, preventing any permanent deformation. CONCLUSION: The Richards staple was stiffer, although the permanent deformation of this staple is a disadvantage. Memoclip staples exhibit lower but adequate stiffnesss when compared to the standard Richards staple and are not permanently deformed after bending. The Memoclip staples were easier to handle. The results will enable surgeons to determine the optimal staple for foot and ankle procedures.

A comparison of radiation exposure with the conventional versus mini C arm in orthopedic extremity surgery.

BACKGROUND: The mini C arm is a mobile fluoroscopic device for use on extremities. It has been reported that this type of device has several advantages over a conventional C arm, the most important of which is a decreased level of radiation scatter to the surgeon. METHODS: This was a case control study. The radiation dose to the surgeon was calculated from the radiation exposure time and distance from the x-ray emitter. Cases using the mini C arm were compared with operation-matched controls that had the identical procedure performed with a conventional C arm. RESULTS: The mini C arm caused statistically less radiation scatter to the surgeon, but there was no statistically significant difference in the radiation exposure to the patient. This was despite a significantly larger number of exposures with the mini C arm for each operation type. CONCLUSIONS: The mini C arm should be used in preference to the conventional C arm for extremity surgery, if both are available.