Objective: The aim of our study was to evaluate results of chemotherapy regimens and analyse prognostics factors in children with relapse of osteosarcoma. Patients and methods: From 2000–2007, we treated 57 patients with non metastatic osteosarcoma, median age 15,5 years (range 3–18). 29 pts relapsed. 26 pts with osteosarcoma relapse were treated, and 3 pts with OS relapse refused the treatment. In 24 pts pulmonary metastases were detected (7 solitary), while 2 pts had local relapse of disease. Disease free interval (DFI) was more than 1 year in 12 patients. Surgery was performed in 20 pts (17 thoracotomy, 3 amputation). Chemotherapy regimens administered were: HD IFO-VP16 (11 pts), HDMth/IFO-VP16 (6 pts), HDMth/Carbo-VP16 (9 pts). Results : During 8–116 months follow up period (Me=32 mts), disease free suvival rate was 33.12%. There was no significant difference in survival in relation to the type of chemotherapy regimen applied.Prognostic factors that influenced survival were: presence of a solitary metastasis (p= 0.026), local relapse of disease (p= 0.002), completeness of resection (p=0.043) and DFIlonger than 1 year (p= 0.039). Conclusion: The use of aggressive multimodal therapy (surgery/chemotherapy) and evaluation of prognostic factors are necessary for successful treatment in patients with osteosarcoma relapse. Chemotherapy regimen HD IFO-VP16 had better initial tumore response, but in longer follow up the survival rate was similar to other chemotherapy groups

From a cohort of 110 idiopathic clubfeet, 26 feet in 18 children requiring surgery for severe relapse have been studied. Surgery was comprised of a lateral column shortening procedure (Lichtblau) plus or minus a plantarmedial release. Surgery was staged to avoid wound complications. Pre-operatively, feet were prospectively categorised into one of four grades according to a system reported by Dimeglio. Children were reviewed on two subsequent occasions. At review, feet were again graded. In addition, appearance and functional outcome was analysed and included an assessment of gait, activity and functional limitation. Three children were lost to follow-up, leaving 22 feet in seven male and eight female patients available for review. The mean age at surgery was 43 months (23–82). The mean time from surgery to first and second reviews was 35 and 56 months, respectively. There was a significant improvement in grading at first review compared to pre-operative grading (Wilcoxon signed ranks test). Although there remained a significant improvement in grading at second review compared to the preoperative grading, there was a significant reduction in the number of feet in which grading had improved when compared to first review. There was no significant change in function between the two post-operative reviews (Chi-square tests), with the majority of children experiencing little functional limitation. There were no wound complications. Relapse surgery, involving a lateral column shortening procedure for severe clubfoot, results in a significant initial improvement when assessed using a grading system. This improvement in grading subsequently decreases over time. However, the functional outcome in such cases remains favourable

Only few patients with osteosarcoma relapse with solitary skeletal lesions as only sign of recurrence. We used the COSS database to learn more about these rare occurrences. This report covers all patients with high-grade osteosarcoma of the limbs or axial skeleton registered into the COSS database between 1980 and 2003 who developed 1st recurrences as solitary osseous lesions distant from the primary tumour before 01/2005. Patient-, tumour-, and treatment-related variables and outcomes were evaluated. 38 patients (27 male, 11 female) developed solitary osseous recurrences a median of 2.1 years (range:.5 – 14.3) from primary diagnosis. Primary sites had been limbs in 36 and axial in 2, relapses involved axial sites (24), limbs (10), or craniofacial bones (4). Treatment for osseous recurrence included surgery in 28 patients, radiotherapy in 10, and chemotherapy in 27. After a median follow-up of 1.9 years (range:.1–21.2) from 1st recurrence for all 38 patients and 5.5 years (.3–21.2) for 16 survivors (10 of these in continuous 2nd surgical remission), 2- & 5-year overall and event-free survival probabilities were 55% & 34% and 34% & 27%, respectively. A long interval to recurrence (> 1.5 years) predicted for better outcomes (p< .01). For those 21 patients achieving a 2nd complete surgical remission, 2- & 5-year overall and event-free survival probabilities were 81% & 61% and 52% & 49%, respectively, while only 1/17 patients failing to achieve a 2nd complete surgical remission survived beyond 5 years (p< .001) after additional radiotherapy. 14/16 survivors had also received 2nd-line chemotherapy. 1st solitary skeletal recurrences of osteosarcoma seem to have a favourable outcome provided treatment includes complete surgery as part of multimodal therapy. Some presumed bone metastases may rather represent second primary osteosarcomas. The COSS studies that form the basis of this report were supported by Deutsche Krebshilfe

The Ponseti method is the gold standard treatment for clubfoot. It begins in early infancy with weekly serial casting for up to 3 months. Globally, a commonly reported barrier to accessing clubfoot treatment is increased distance patients must travel for intervention. This study aims to evaluate the impact of the distance traveled by families to the hospital on the treatment course and outcomes for idiopathic clubfoot. No prior studies in Canada have examined this potential barrier. This is a retrospective cohort study of patients managed at a single urban tertiary care center for idiopathic clubfoot deformity. All patients were enrolled in the Pediatric Clubfoot Research Registry between 2003 and April 2021. Inclusion criteria consisted of patients presenting at after percutaneous Achilles tenotomy. Postal codes were used to determine distance from patients’ home address to the hospital. Patients were divided into three groups based on distance traveled to hospital: those living within the city, within the Greater Metro Area (GMA) and outside of the GMA (non-GMA). The primary outcome evaluated was occurrence of deformity relapse and secondary outcomes included need for surgery, treatment interruptions/missed appointments, and complications with bracing or casting. A total of 320 patients met inclusion criteria. Of these, 32.8% lived in the city, 41% in the GMA and 26% outside of the GMA. The average travel distance to the treatment centre in each group was 13.3km, 49.5km and 264km, respectively. Over 22% of patients travelled over 100km, with the furthest patient travelling 831km. The average age of presentation was 0.91 months for patients living in the city, 1.15 months for those within the GMA and 1.33 months for patients outside of the GMA. The mean number of total casts applied was similar with 7.1, 7.8 and 7.3 casts in the city, GMA and non-GMA groups, respectively. At least one two or more-week gap was identified between serial casting appointments in 49% of patients outside the GMA, compared to 27% (GMA) and 24% (city). Relapse occurred in at least one foot in 40% of non-GMA patients, versus 27% (GMA) and 24% (city), with a mean age at first relapse of 50.3 months in non-GMA patients, 42.4 months in GMA and 35.7 months in city-dwelling patients. 12% of the non-GMA group, 6.8% of the GMA group and 5.7% of the city group underwent surgery, with a mean age at time of initial surgery of 79 months, 67 months and 76 months, respectively. Complications, such as pressure sores, casts slips and soiled casts, occurred in 35% (non-GMA), 32% (GMA) and 24% (city) of patients. These findings suggest that greater travel distance for clubfoot management is associated with more missed appointments, increased risk of relapse and treatment complications. Distance to a treatment center is a modifiable barrier. Improving access to clubfoot care by establishing clinics in more remote communities may improve clinical outcomes and significantly decrease the burdens of travel on patients and families

Background. Exebacase, an antistaphylococcal lysin in Phase 3 of development as a treatment for S. aureus bacteremia/right-sided endocarditis has demonstrated antibiofilm activity in vitro and has previously been used as salvage therapy in four patients with relapsing multidrug-resistant (MDR) S. epidermidis knee prosthetic joint infection (PJI) using a procedure called LysinDAIR (administration of the lysin during the performance of an arthroscopic DAIR). Materials/methods. We performed a single center, exploratory, open-label prospective study using the LysinDAIR procedure in patients with chronic (inoculation >3 months prior to treatment) coagulase-negative staphylococci (CNS) PJI of the knee with two different clinical presentations and treatment paradigms. Cohort A: first episode of CNS knee PJI, for whom the LysinDAIR was followed by clindamycin + levofloxacin planned to be prescribed for three months and then stopped; and Cohort B: relapsing episodes of MDR CNS knee PJI for whom the LysinDAIR was followed by primary antimicrobial therapy for three months, followed by suppressive antimicrobial therapy (SAT). Exebacae susceptibility testing was performed before treatment for each patient. In agreement with the French Health authority, exebacase (2 to 3.5 total mg in 30–50 ml (∼0.067 – 0.075 mg/m) was administered directly into the joint during arthroscopy. Results. Eight patients were treated. Exebacase administration was well tolerated by all patients and no serious adverse drug reactions to exebacase were reported. In cohort A (n=4), patients had susceptible S. epidermidis PJI, a painful joint effusion without fistula and without loosening, and received three months of levofloxacin + clindamycin (one patient received an alternative regimen following antibiotic adverse events) and then antibiotics were stopped. During a follow-up of 14, 19, 26 and 36 months, no relapse, no recurrence of the joint effusion and no loosening occurred. In cohort B (n=4), patients had MDR CNS, clinical signs of septic arthritis with a joint effusion without fistula and without loosening and received daptomycin + linezolid or doxycycline. One patient died from COVID-19 at week 4. SAT (tedizolide, n=2; doxycycline, n=1) was then prescribed to other patients. One experienced an infection relapse involving S. caprae under tedizolid therapy at six months. The two other patients continue to do well under SAT 8 and 12 months after the LysinDAIR procedure. Conclusions. The LysinDAIR procedure is a minimally invasive procedure, which has been shown to be easy-to-perform, safe, and has the potential for use as initial treatment or salvage therapy in patients with CNS chronic knee PJI

Osteochondromas are benign chondrogenic lesions arising on the external surface of the bone with aberrant cartilage (exostosis) from the perichondral ring that may contain a marrow cavity also. In a few cases, depending on the anatomical site affected, different degrees of edema, redness, paresthesia, or paresis can take place due to simple contact or friction. Also, depending on their closeness to neurovascular structures, the procedure of excision becomes crucial to avoid recurrence. We report a unique case of recurrent osteochondroma of the proximal humerus enclosing the brachial artery which makes for an important case and procedure to ensure that no relapse occurs. We report a unique case of a 13-year-old female who had presented with a history of pain and recurrent swelling for 5 years. The swelling size was 4.4 cm x 3.7 cm x 4 cm with a previous history of swelling at the same site operated in 2018. CT reports were suggestive of a large well defined broad-based exophytic diaphyseal lesion in the medial side of the proximal humerus extending posteriorly. Another similar morphological lesion measuring approximately 9 mm x 7 mm was noted involving the posterior humeral shaft. The minimal distance between the lesion and the brachial artery was 2 mm just anterior to the posterio-medial growth. Two intervals were made, first between the tumor and the neurovascular bundle and the other between the anterior tumor and brachial artery followed by exostosis and cauterization of the base. Proper curettage and excision of the tumor was done after dissecting and removing the soft tissue, blood vessels, and nerves so that there were very less chances of relapse. Post-operative X-ray was done and post 6 months of follow-up, there were no changes, and no relapse was observed. Thus, when presented with a case of recurrent osteochondroma of the proximal humerus, osteochondroma could also be in proximity to important vasculature as in this case enclosing the brachial artery. Thus, proper curettage and excision should be done in such cases to avoid recurrence

Specific brace-fitting complications in idiopathic congenital talipes equinovarus (CTEV) have been rarely described in published series, and usually focus on non-compliance. Our primary aim was to compare the rate of persistent pressure sores in patients fitted with Markell boots and Mitchell boots. Our additional aims were to describe the frequency of other brace fitting complications and identify age trends in these complications. A retrospective analysis of medical files of 247 idiopathic CTEV patients born between 01/01/2010 - 01/01/2021 was performed. Data was collected using a REDCap database. Pressure sores of sufficient severity for clinician to recommend time out of brace occurred in 22.9% of Mitchell boot and 12.6% of Markell boot patients (X. 2. =6.9, p=0.009). The overall rate of bracing complications was 51.4%. 33.2% of parents admitted to bracing non-compliance and 31.2% of patients required re-casting during the bracing period for relapse. For patients with a minimum follow-up of age 6 years, 44.2% required tibialis anterior tendon transfer. Parents admitting to non-compliance were significantly more likely to have a child who required tibialis anterior tendon transfer (X. 2. =5.71, p=0.017). Overall rate of capsular release (posteromedial release or posterior release) was 2.0%. Neither medium nor longterm results of Ponseti treatment in the Australian and New Zealand clubfoot have been published. Globally, few publications describe specific bracing complications in clubfoot, despite this being a notable challenge for clinicians and families. Recurrent pressure sores is a persistent complication with the Mitchell boots for patients in our center. In our population of Australian clubfoot patients, tibialis anterior tendon transfer for relapse is common, consistent with the upper limit of tibialis anterior tendon transfer rates reported globally

Aims. To identify the minimum set of outcomes that should be collected in clinical practice and reported in research related to the care of children with idiopathic congenital talipes equinovarus (CTEV). Methods. A list of outcome measurement tools (OMTs) was obtained from the literature through a systematic review. Further outcomes were collected from patients and families through a questionnaire and interview process. The combined list, as well as the appropriate follow-up timepoint, was rated for importance in a two-round Delphi process that included an international group of orthopaedic surgeons, physiotherapists, nurse practitioners, patients, and families. Outcomes that reached no consensus during the Delphi process were further discussed and scored for inclusion/exclusion in a final consensus meeting involving international stakeholder representatives of practitioners, families, and patient charities. Results. In total, 39 OMTs were included from the systematic review. Two additional OMTs were identified from the interviews and questionnaires, and four were added after round one Delphi. Overall, 22 OMTs reached ‘consensus in’ during the Delphi and two reached ‘consensus out’; 21 OMTs reached ‘no consensus’ and were included in the final consensus meeting. In all, 21 participants attended the consensus meeting, including a wide diversity of clubfoot practitioners, parent/patient representative, and an independent chair. A total of 21 outcomes were discussed and voted upon; six were voted ‘in’ and 15 were voted ‘out’. The final COS document includes nine OMTs and two existing outcome scores with a total of 31 outcome parameters to be collected after a minimum follow-up of five years. It incorporates static and dynamic clinical findings, patient-reported outcome measures, and a definition of CTEV relapse. Conclusion. We have defined a minimum set of outcomes to draw comparisons between centres and studies in the treatment of CTEV. With the use of these outcomes, we hope to allow more meaningful research and a better clinical management of CTEV. Cite this article: Bone Jt Open 2022;3(1):98–106

Sarcomas generally metastasize to the lung, while extra-pulmonary metastases are rare. However, they may occur more frequently in certain histological sub-types. Bone metastases from bone and soft tissue sarcomas account for a significant number of extra-pulmonary disease. Resection of lung metastases is widely accepted as therapeutic option to improve the survival of oligometastatic patients but there is currently no literature supporting curative surgical management of sarcoma bone metastases. Most are treated on a case-by-case basis, following multidisciplinary tumour boards recommendations. One study reported some success in controlling bone metastases using radiofrequency ablation. Our goal was to assess the impact of curative resection of bone metastases from soft tissue and bone sarcomas on oncologic outcomes. Extensive review of literature was done to evaluate epidemiological and outcomes of bone metastases in sarcoma. We examined our prospective database for all cases of bone metastases from sarcoma treated with surgical resection between 1990 and 2016. Epidemiology, pathology, metastatic status upon diagnosis, type of secondary relapses and their treatments were recorded. Overall survival and disease-free survival were calculated and compared to literature. Thirty-five patients were included (18 men, 17 women) with a mean age of 46 years. Fifteen were soft tissue (STS) and 20 were bone (BS) sarcomas. Most STS were fibrosarcomas, leiomyosarcomas or UPS while chondrosarcomas and osteosarcomas were the most frequent BS. Nine (60%) STS were grade 3, 4 (27%) grade 2 and one grade 1 (3%). Eight (23%) were metastatic upon diagnosis (6 lungs, 3 bone). Treatment of the primary tumour included wide excision with reconstruction and (neo)-adjuvant therapies as required. Margins were negative in 32 cases and micro-positive in 3 cases. Amputation occurred in 6 (17%) cases. Primary lung metastases were treated by thoracotomy and primary bone metastases by wide excision. First relapse occurred in bone in 19 cases (54%), lungs and bone in 7 cases, 5 in lungs and 4 in soft-tissues. Lung metastases were treated by thoracotomy and chemotherapy in 3 cases, chemotherapy alone in the remaining cases. Bone metastases were treated by wide resection-reconstruction in 24 cases, extensive curettage in 4. Soft tissue relapses were re-excised in 4 patients. Two amputations were required. All margins were negative except for the 4 treated by curettage. Fourteen second relapses occurred in bone, 7 were radically-excised and 2 curetted. At last follow-up, 6 patients were alive (overall survival of 17%), with a mean survival of 57 months, a median overall survival of 42.5 months and a median disease-free survival (DFS) of 17 months. Overall survival was 17%, compared to an 11% 10-year survival previously reported in metastatic sarcomas. Median disease-free survival was better in this study, compared to 10 months in literature, so as median OS (42.5 months vs 15). Three patients were alive with no evidence of disease. DFS, OS and median survival seemed to be improved by bone metastases wide excision and even if several recurrences occur, curative surgery with adjuvant therapies should be considered

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Background. Neglected clubfoot in this series is defined as untreated equino-cavo-adducto-varus in older children, or adults. Relapsed clubfoot is the residual deformity that remains after single or multiple surgical interventions. Severe neglected clubfoot rarely exists today in developed countries, except in some emigrants from low- and middle-income countries. Acute surgical management with corrective mid-foot osteotomy and elongation of the Achilles tendon has excellent functional outcome. Objective. To assess the functional outcome of acute correction of neglected Talipes-quino-varus deformity in adults. Methods. This is cross sectional, hospital–based study that took place in Khartoum, Sudan. Forty patients were included in this study. Midfoot osteotomy and elongation of the Achilles tendon were performed to all patients. Data was collected using a questionnaire and the functional outcome has been assessed using the American Orthopaedic Foot and Ankle Society Score (AOFAS). This score was measured before surgery and one years after surgery. Results. The mean age was 19.9±4.7 years. Males were 25 (62.5%) and females were 15 (37.5%). The mean preoperative AOFAS score was 37.7±7.1 (poor). This score improved to 80.7±13.7 (good to excellent), two years after surgery. However, this indicates significant change in the functional outcome after the operation (P value < 0.05). Excellent post-operative functional outcome was found among patients aged 18 – 23 years 18 (50%) P. value: 0.021. The majority of patients 36(90%) were fully satisfied with the operation, 2(5%) partially satisfied and 2(5%) were unsatisfied. Conclusion. Acute correction of neglected and relapsed TEV with elongation of the Achilles tendon and single midfoot osteotomy has excellent functional outcome as assessed by AOFAS Score. The satisfaction with this procedure is impressive. The younger age population showed better outcomes with this procedure

Aim. As the number of performed total hip arthroplasties (THA) and total knee arthroplasties (TKA) has increased over the years, revision surgeries are expected to increase as well. Revision surgeries are associated with a longer operating room time, prolonged length of stay (LOS), and more frequent complications. Postoperative hematomas are a major reason for wound healing disturbances and periprosthetic joint infections (PJI). We aimed to systematically assess the use and safety of a microporous polysaccharide hemosphere (MPH) in revision THA and TKA. We focused on the risk reduction of further revision surgeries in case of wound healing disorders and hematoma, transfusion of packed red blood cells (PRBC), loss of hemoglobin (hb) and mean LOS following the use of MPH. Method. Our prospective study includes 89 patients who underwent revision surgery after THA and TKA with application of MPH and were compared to 102 patients who did not receive MPH and underwent revision surgery after THA and TKA. Five grams of MPH. 1. were applied periarticular before fascia closure and to the subcutaneous soft tissue. The follow-up was conducted in daily clinical visits during the inpatient stay and three months postoperatively in our outpatient clinic. Repeated revision surgery was performed in case of prolonged secretion (>10 days) or clinical suspicion of infection. After matching the cohorts the outcomes were statistically analyzed using paired methods. Results. A significantly lower odds ratio for repeat revisions was found for the MPH cohort (OR=0.312; 95%-CI 0.090, 0.893; p=0.027). Differences between pre- and postoperative hb levels, LOS and transfusions of PRBC did not reach significance. No intra- or postoperative complications to MPH occurred. Moreover, no infection relapse occurred after applying MPH. Conclusions. Routine use of MPH in revision arthroplasty management after TKA and THA appears to be safe and an effective way to support hemostasis, with no observed adverse events related to MPH use. There were noticeably less hematomas and revision surgeries in the MPH group. 1. Arista BD, Franklin Lakes, NJ, USA

Introduction. Recurrence in CTEV is not uncommon and as the child becomes older the foot in question is often stiffer and less amenable to the more traditional serial casting Ponseti method. Treatment of these recurrent CTEV feet with external fixators has been previously documented. We aim to present the Sheffield technique of an external circular frame with adjunctive hindfoot and midfoot osteotomies to correct relapsed CTEV and their associated Roye (outcome) scores. Materials and Methods. Retrospective analysis of patient records from 1999 to 2019 were performed for those undergoing frame correction of CTEV. Patients were included if there was adjunctive foot osteotomies in the setting of CTEV frame correction and willingness to partake in retrospective Roye outcome scoring. The Roye score was sent out in the mail to parents asking for scoring of the current level of symptoms. Results. 160 patients were contacted for Roye score evaluation. We successfully collected outcome data for 46 feet in 39 patients. 27 (69%) patients had idiopathic CTEV. Average age at fixator application 12.6 years (range 7–18). Mean length of follow up 10.6 years (1 – 20). 76% of patients were either very (22%) or somewhat (54%) satisfied with the status of their foot. The largest negative score was 61% of parents found difficulty in finding shoes to fit their child's feet after treatment. 39% of patients had significant persistent pain associated with their feet but 67% were not at all (26%) or only somewhat (41%) limited in their walking ability. Conclusions. We have demonstrated short to mid term follow up for relapsed CTEV treated via external fixation. The Roye score has demonstrated a large proportion of patients are overall satisfied with their outcome with the most common complaints being difficulties in finding shoes to fit and persistent pain on strenuous activity

Aim. Antimicrobial peptides occur naturally in our intrinsic immune system. PLG0206 is a novel, engineered, 24-amino acid peptide which has broad-spectrum antimicrobial activity, including in biofilm and against multi-drug resistant pathogens (1,2). This is the first clinical study to evaluate the safety and tolerability of PLG0206 when administered via an irrigation solution in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA) during debridement, antibiotics, and implant retention (DAIR). Secondary objectives were to evaluate pharmacokinetics (PK), biomarkers and initial clinical efficacy at one year post-DAIR procedure. Method. This prospective, multicenter, open-label, interventional study assessed two dose levels of PLG0206. Fourteen patients underwent revision for PJI after TKA. At the end of debridement, they received a single intra-articular irrigation of PLG0206 into the wound cavity lasting 15 minutes at concentrations of 3 mg/mL (n=7) or 10 mg/mL (n=7). Patients received post-operative care and intravenous/oral antimicrobial therapy as per their institutional guidelines. Patients were monitored for safety and signs of relapse or persistent infection for 12 months post study drug administration and PK and blood biomarkers were assessed. Results. All patients completed their final study assessment at Day 365. Over the 1-year follow-up, only one recurrence (7%) was noted at Day 169 in the low-dose cohort. Following dosing, nine patients (64.3%) had limited systemic exposure; maximum plasma concentration occurred 1-hour post-administration and declined rapidly to undetectable levels by 24 hours following treatment in all patients. The incidence of drug related treatment-emergent adverse events (TEAEs) was low. Two patients, both in the higher dose cohort, experienced a transient drug related TEAE; one of hypertransaminasaemia and one of neuralgia. Both events were moderate in severity and resolved within two weeks of onset. Conclusions. A single 15-minute irrigation of PLG0206 into the wound cavity of patients undergoing a DAIR procedure for PJI following TKA, is safe and well tolerated by patients. This new antimicrobial peptide offers a promising therapeutic option in musculoskeletal infection. The initial clinical efficacy is encouraging but now needs to be investigated in a much larger clinical trial

Aim. Decubitus ulcers are found in approximately 4.7% of hospitalized patients, with a higher prevalence (up to 30%) among those with spinal cord injuries. These ulcers are often associated with hip septic arthritis and/or osteomyelitis involving the femur. Girdlestone resection arthroplasty is a surgical technique used to remove affected proximal femur and acetabular tissues, resulting in a substantial defect. The vastus lateralis flap has been employed as an effective option for managing this dead space. The aim of this study was to evaluate the long-term outcomes of this procedure in a consecutive series of patients. Method. A retrospective single-center study was conducted from October 2012 to December 2022, involving 7 patients with spinal cord injuries affected by chronic severe septic hip arthritis and/or femoral head septic necrosis as a consequence of decubitus ulcers over trochanter area. All patients underwent treatment using a multidisciplinary approach by the same surgical team (orthopedic and plastic surgeons) along with infectious disease specialists. The treatment consisted of a one-stage procedure combining Girdlestone resection arthroplasty with unilateral vastus lateralis flap reconstruction, alongside targeted antibiotic therapy. Complications and postoperative outcomes were assessed and recorded. The mean follow-up period was 8 years (range 2-12). Results. Of the 7 patients, 5 were male and 2 were female, with a mean age of 50.3 years at the time of surgery. Minor wound dehiscence occurred in 28.6% of the flap sites, and 2 patients required additional revisional procedures—one for hematoma and the other for bleeding. There were no instances of flap failure, and complete wound healing was achieved in an average of 32 days (range 20-41), with the ability to load over the hip area. No cases of infection recurrence or relapse were observed. Conclusions. An aggressive surgical approach is strongly recommended for managing chronic hip septic arthritis or proximal femur osteomyelitis in patients with spinal cord injuries. A single-stage procedure combining Girdlestone resection arthroplasty with immediate vastus lateralis muscle flap reconstruction proves to be an effective strategy for dead space management and localized antibiotic delivery through the vastus muscle, giving reliable soft tissue coverage around the proximal femur to avoid the recurrence of pressure ulcers. The implementation of a standardized multidisciplinary protocol contributes significantly to the success of reconstruction efforts

Aim. Antibiotics have limited activity in the treatment of multidrug-resistant or chronic biofilm-associated infections, in particular when implants cannot be removed. Lytic bacteriophages can rapidly and selectively kill bacteria, and can be combined with antibiotics. However, clinical experience in patients with surgical infections is limited. We investigated the outcome and safety of local application of bacteriophages in addition to antimicrobial therapy. Method. 8 patients (2 female and 6 male) with complex orthopedic and cardiovascular infections were included, in whom standard treatment was not feasible or impossible. The treatment was performed in agreement with the Article 37 of the Declaration of Helsinki. Commercial or individually prepared bacteriophages were provided by ELIAVA Institute in Tbilisi, Georgia. Bacteriophages were applied during surgery and continued through drains placed during surgery three times per day for the following 5–14 days. Follow-up ranged from 1 to 28 months. Results. Median age was 57 years, range 33–75 years. Two patients were diagnosed with a persistent knee arthrodesis infection, one chronic periprosthetic joint infection (PJI), one cardiovascular implantable electronic device (CIED) infection and four patients with left ventricular assist device (LVAD) infection. The isolated pathogens were multi-drug-resistant Pseudomonas aeruginosa (n=3), methicillin-sensitive Staphylococcus aureus (n=4), methicillin-resistant Staphylococcus aureus (MRSA) (n=1) and methicillin-resistant Staphylococcus epidermidis (MRSE) (n=1). 4 infections were polymicrobial. 5 patients underwent surgical debridement with retention of the implant, 1 patient with PJI underwent the exchange of the prosthesis and one patient with LVAD infection was treated conservatively. All patients received intravenous and oral antibiotic therapy and local application of bacteriophages. At follow-up of 12 month, 5 patients were without signs or symptoms of infection, whereas in one patient with LVAD infection, a relapse was observed with emergence of phage-resistant Pseudomonas aeruginosa. In this patient, no surgical revision was performed. Conclusions. Bacteriophage therapy may represent a valid additional approach, when standard antimicrobial and surgical treatment is not possible or feasible, including in difficult-to-treat infections. In our case series, 5 of 6 patients were infection free after 1 year. Further studies need to address the optimal bacteriophage administration route, concentration, duration of treatment and combination with antimicrobials

Aim. dalbavancin, a lipo-glycopeptide antibiotic effective against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus), allows extended dosing interval due to its peculiar pharmacokinetics. Despite being registered for treatment of acute skin infections, off-label use has shown promise in various settings, particularly in osteo-articular infections. This study aims to assess dalbavancin's pharmacological efficacy and its safety and clinical success in patients treated according to personalized schedules guided by Therapeutic Drug Monitoring (TDM), particularly in long-term therapies. Methods. non-interventional, retrospective, single-center pharmacological study. We included adult patients with at least one dalbavancin TDM determination from July 1, 2022 to February 1, 2024 and treated with outpatient parenteral antimicrobial therapy. We recorded dalbavancin trough concentration (Cmin) and its peak concentration (Cmax) and employed log-linear regression models to predict the timing of dalbavancin dosing, aiming to sustain Cmin levels above 4 or 8.04 mg/L, according to recent literature. Data regarding index infections, patients’ characteristics, outcomes, and adverse events were also collected. Results. we included 32 patients, whose clinical and microbiological characteristics are depicted in Table 1. Regarding the primary outcome, 132/134 (98.5%) trough concentration was >4 mg/L, while 112/134 (83.6%) was >8.04 mg/L. For the secondary outcomes, 2/32 patients experienced an adverse event correlated to dalbavancin: (i) exanthema one week after the start of therapy and (ii) exanthema, conjunctivitis, angioedema, and nausea one month after the start of therapy. Moreover, we observed 4/32 clinical unsuccess (one failure during treatment, one relapse after the end of therapy, one switch to another antibiotic, and one isolation of non-susceptible microorganism). Conclusions. a TDM-based approach with the use of a log-linear regression model allows a more precise timing of dalbavancin administration by maintaining sufficient concentration of circulating drugs. This approach is promising for infections requiring a long-term treatment, such as orthopedic infection where source control is not possible. For any tables or figures, please contact the authors directly

Aim. Antimicrobial suppression has shown to significantly improve treatment success of streptococcal periprosthetic joint infection (PJI) compared to 12-week standard antimicrobial therapy, however, only short-term follow-up was investigated. In this study we assessed the impact of suppression on the long-term outcome of streptococcal PJI. Method. Consecutive patients with streptococcal PJI (defined by EBJIS criteria) treated 2009–2021 were prospectively included and allocated into standard and suppression (> 6 months) treatment group. Infection-free survival was assessed with Kaplan-Meier-method and compared between the groups with log rank test. Rates of infection-free, streptococcal infection-free and relapse-free status as well as tolerability of suppression were assessed. Results. Sixty-three PJI episodes (36 knee, 26 hip and one shoulder prosthesis) of patients with a median age of 70 (35–87) years were included. Twenty-seven (43%) were females. Predominant pathogens were S. agalactiae (n=20), S. dysgalactiae (n=18) and S. mitis/oralis (n=13). The main surgical procedures used were two-stage exchange (n=35) and prosthesis retention (n=21). Standard 12-week treatment was administered in 33 patients and suppression in 30 patients, of whom 10 had ongoing suppression and 20 had discontinued antibiotics at time of follow-up. Used oral antibiotics for suppression were amoxicillin (n=29), doxycycline (n=5) and clindamycin (n=2); 6 patients changed antibiotic substance due to side effects. The median follow-up time was 3.9 (0.3–13.3) years. Infection-free survival after 7.5 years was 38% with standard treatment and 62% with suppression (p=0.038). Of all failures, 52% (14/27) were due to streptococci. Suppression was effective in preventing streptococcal infection for the duration of antimicrobial treatment, however, after discontinuation relapses or new infections due to streptococci occurred in 5/20 (25%) patients and infection with any Streptococcus spp. was observed in 9/19 (47%) failures with standard treatment, 5/6 (83%) failures after discontinuing suppression and none during suppression. All failures in patients with ongoing suppression were caused by gram-negative rods. Conclusion. At long-term follow-up, the success rate was superior with suppression compared to standard treatment. Most failures after stopping suppression were caused by streptococci, whereas failures under suppression were caused by aerobic gram-negative rods

Aim. infected segmental bone defect (ISBD) is frequent in developing countries. The aim of this study was to assess the efficacy of the Masquelet technique in the treatment of ISBD in a low-resource setting. Patients and Method. We performed a prospective cohort study during the period from 2018 to 2022. Patients with infected bone defect of long bones were included. Management protocol consisted of two stages in all patients. The first stage consisted in debridement, tissues biopsy for microbiological culture, stabilization with external fixator and defect filling with gentamicin cement spacer. The second stage consisted of reconstruction using a cancellous bone autograft alone, or a mixture of autograft with allograft (demineralized bone matrix + tricalcium phosphate) and 1 gram of vancomycin powder. All patients were followed-up for at least one year. The results were assessed based on both objective (clinical and radiographic evaluation) and subjective (limb function and patient satisfaction) criteria. Main outcomes were bone union, reoperation and failure rates, union time, and limb function. Results. We included 31 patients in this study (80.6% men), with a median age of 35 [9 – 80] years. The tibia was affected in 12 cases and the femur in 15 cases. The median size of bone defect was 4 [1.5 – 12] cm. The most prevalent microorganisms were Klebsiella pneumoniae and Staphylococcus aureus. The mean interval between both stages was 14 (8 – 36) weeks and the median follow-up period after the second stage was 20 [12-62] months. External fixation was used in both stages in 25(80%) cases. Bone union was achieved in 26 (83.8%) patients of whom 24 without recurrence of infection, over a median time of 9 [6 – 16] months. All patients with a mixed graft (allograft and autograft) impregnated with local antibiotics achieved bone union. Two patients needed reoperation for relapse of infection between both stages, and subsequently achieved bone union without recurrence of infection. There were three cases of failure related to persistent infection or insufficient fixation stability in the second stage. Conclusions. Masquelet technique is a reliable procedure that can be safely performed in limited resources settings with satisfactory results. The mixture of autograft and allograft when available, all mixed with vancomycin seems to give promising results

Decreasing the chance of local relapse or infection after surgical excision of bone metastases is a main goals in orthopedic oncology. Indeed, bone metastases have high incidence rate (up to 75%) and important cross-relations with infection and bone regeneration. Even in patients with advanced cancer, bone gaps resulting from tumor excision must be filled with bone substitutes. Functionalization of these substitutes with antitumor and antibacterial compounds could constitute a promising approach to overcome infection and tumor at one same time. Here, for the first time, we propose the use of nanostructured zinc-bone apatite coatings having antitumor and antimicrobial efficacy. The coatings are obtained by Ionized Jet Deposition from composite targets of zinc and bovine-derived bone apatite. Antibacterial and antibiofilm efficacy of the coatings is demonstrated in vitro against S. Aureus and E. Coli. Anti-tumor efficacy is investigated against MDA- MB-231 cells and biocompatibility is assessed on L929 and MSCs. A microfluidic based approach is used to select the optimal concentration of zinc to be used to obtain antitumor efficacy and avoid cytotoxicity, exploiting a custom gradient generator microfluidic device, specifically designed for the experiments. Then, coatings capable of releasing the desired amount of active compounds are manufactured. Films morphology, composition and ion-release are studies by FEG- SEM/EDS, XRD and ICP. Efficacy and biocompatibility of the coatings are verified by investigating MDA, MSCs and L929 viability and morphology by Alamar Blue, Live/Dead Assay and FEG-SEM at different timepoints. Statistical analysis is performed by SPSS/PC + Statistics TM 25.0 software, one-way ANOVA and post-hoc Sheffe? test. Data are reported as Mean ± standard Deviation at a significance level of p <0.05. Results and Discussion. Coatings have a nanostructured surface morphology and a composition mimicking the target. They permit sustained zinc release for over 14 days in medium. Thanks to these characteristics, they show high antibacterial ability (inhibition of bacteria viability and adhesion to substrate) against both the gram + and gram – strain. The gradient generator microfluidic device permits a fine selection of the concentration of zinc to be used, with many potential perspectives for the design of biomaterials. For the first time, we show that zinc and zinc-based coatings have a selective efficacy against MDA cells. Upon mixing with bone apatite, the efficacy is maintained and cytotoxicity is avoided. For the first time, new antibacterial metal-based films are proposed for addressing bone metastases and infection at one same time. At the same time, a new approach is proposed for the design of the coatings, based on a microfluidic approach. We demonstrated the efficacy of Zn against the MDA-MB-231 cells, characterized for their ability to form bone metastases in vivo, and the possibility to use nanostructured metallic coatings against bone tumors. At the same time, we show that the gradient-generator approach is promising for the design of antitumor biomaterials. Efficacy of Zn films must be verified in vivo, but the dual-efficacy coatings appear promising for orthopedic applications