Aims. The aim of this study is to evaluate the surgical treatment with the best healing rate for patients with proximal femoral unicameral bone cysts (UBCs) after initial surgery, and to determine which procedure has the lowest adverse event burden during follow-up. Methods. This multicentre retrospective study was conducted in 20 tertiary paediatric hospitals in France, Belgium, and Switzerland, and included patients aged < 16 years admitted for UBC treatment in the proximal femur from January 1995 to December 2017. UBCs were divided into seven groups based on the index treatment, which included elastic stable intramedullary nail (ESIN) insertion with or without percutaneous injection or grafting, percutaneous injection alone, curettage and grafting alone, and insertion of other orthopaedic hardware with or without curettage. Results. A total of 201 patients were included in the study. The mean age at diagnosis was 8.7 years (SD 3.9); 77% (n = 156) were male. The mean follow-up was 9.4 years (SD 3.9). ESIN insertion without complementary procedure had a 67% UBC healing rate after the first operation (vs 30% with percutaneous injection alone (p = 0.027), 43% with curettage and grafting (p = 0.064), and 21% with insertion of other hardware combined with curettage (p < 0.001) or 36% alone (p = 0.014)). ESIN insertion with percutaneous injection presented a 79% healing rate, higher than percutaneous injection alone (p = 0.017), curettage and grafting (p = 0.028), and insertion of other hardware combined with curettage (p < 0.001) or alone (p = 0.014). Patients who underwent ESIN insertion with curettage had a 53% healing rate, higher than insertion of other hardware combined with curettage (p = 0.009). The overall rate of postoperative complications was 25% and did not differ between groups (p = 0.228). A total of 32 limb length discrepancies were identified. Conclusion. ESIN insertion, either alone or combined with percutaneous injection or curettage and grafting, may offer higher healing rates than other operative procedures. Limb length discrepancy remains a major concern, and might be partly explained by the cyst’s location and the consequence of surgery. Therefore, providing information about this risk is crucial. Cite this article: Bone Joint J 2024;106-B(5):508–514

In 79 consecutive patients with unicameral bone cysts we compared the results of aspiration and injection of bone marrow with those of aspiration and injection of steroid. All were treated by the same protocol. The only difference was the substance injected into the cysts. The mean radiological follow-up to detect activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a total of 27 injections of bone marrow and 65 a total of 99 injections of steroid. Repeated injections were required in 57% of patients after bone marrow had been used and in 49% after steroid. No complications were noted in either group. In this series no advantage could be shown for the use of autogenous injection of bone marrow compared with injection of steroid in the management of unicameral bone cysts

Aims. Preserving growth following limb-salvage surgery of the upper limb in children remains a challenge. Vascularized autografts may provide rapid biological incorporation with the potential for growth and longevity. In this study, we aimed to describe the outcomes following proximal humeral reconstruction with a vascularized fibular epiphyseal transfer in children with a primary sarcoma of bone. We also aimed to quantify the hypertrophy of the graft and the annual growth, and to determine the functional outcomes of the neoglenofibular joint. Patients and Methods. We retrospectively analyzed 11 patients who underwent this procedure for a primary bone tumour of the proximal humerus between 2004 and 2015. Six had Ewing’s sarcoma and five had osteosarcoma. Their mean age at the time of surgery was five years (two to eight). The mean follow-up was 5.2 years (1 to 12.2). Results. The overall survival at five and ten years was 91% (confidence interval (CI) 95% 75% to 100%). At the time of the final review, ten patients were alive. One with local recurrence and metastasis died one-year post-operatively. Complications included seven fractures, four transient nerve palsies, and two patients developed avascular necrosis of the graft. All the fractures presented within the first postoperative year and united with conservative management. One patient had two further operations for a slipped fibular epiphysis of the autograft, and a hemi-epiphysiodesis for lateral tibial physeal arrest. Hypertrophy and axial growth were evident in nine patients who did not have avascular necrosis of the graft. The mean hypertrophy index was 65% (55% to 82%), and the mean growth was 4.6 mm per annum (2.4 to 7.6) in these nine grafts. At final follow-up, the mean modified functional Musculoskeletal Tumour Society score was 77% (63% to 83%) and the mean Toronto Extremity Salvage Score (TESS) was 84% (65% to 94%). Conclusion. Vascularized fibular epiphyseal transfer preserves function and growth in young children following excision of the proximal humerus for a malignant bone tumour. Function compares favourably to other limb-salvage procedures in children. Longer term analysis is required to determine if this technique proves to be durable into adulthood. Cite this article: Bone Joint J 2018;100-B:535–41

Aim. To study the results of using recombinant human bone morphogenic protein-2 (rhBMP-2) to achieve bone union in children with complex orthopaedic problems including skeletal dysplasia, congenital limb deficiencies and complex trauma. Materials & Methods. Between November 2006 to April 2010, rhBMP-2 was used to achieve bone healing in a total of 19 children. The indications were delayed union or non-union in 16 long bones where previous surgeries had failed and 4 posterior spinal fusions. All children had underlying complex orthopaedic problems predisposing them to delayed bone healing. The average age at the time of surgery was 13 years and 8 months (Range: From 4 years to 19 years and 4 months). There were 7 boys and 12 girls. Results. Average follow-up period was 9.6 months (Range: From 3 months to 2 years and 2 months). Out of the 16 long bone non-unions treated with rhBMP-2, 13 united without further interventions but 3 required further intervention. The average time for clinical union was 10 weeks (Range: from 6 weeks to 18 weeks). The average time for radiological union was 15 weeks (Range: from 7 weeks to 27 weeks). Two children who underwent instrumented posterior spinal fusion and two children who underwent uninstrumented spinal fusion achieved radiologically evident spinal fusion at an average of 16 weeks. No local or systemic complications attributable to BMP were noted in any of the children. Conclusions. rhBMP-2 can be used successfully to achieve bone healing in long bone nonunion and delayed union and posterior spinal fusion in children with complex orthopaedic problems including skeletal dysplasia, congenital limb deficiencies and complex trauma. Its use in children has shown no unwanted effects in the short term. Significance. rhBMP-2 has been approved by Food and Drug Administration (FDA) as a bone graft substitute in adults. Its use in adults has been widely reported but there are only a few case reports of its use in children. This study shows that rhBMP-2 can be safely

Permanent growth arrest of the longer bone is an option in the treatment of minor leg-length discrepancies. The use of a tension band plating technique to produce a temporary epiphysiodesis is appealing as it avoids the need for accurate timing of the procedure in relation to remaining growth. We performed an animal study to establish if control of growth in a long bone is possible with tension band plating. Animals (pigs) were randomised to temporary epiphysiodesis on either the right or left tibia. Implants were removed after ten weeks. Both tibiae were examined using MRI at baseline, and after ten and 15 weeks. The median interphyseal distance was significantly shorter on the treated tibiae after both ten weeks (p = 0.04) and 15 weeks (p = 0.04). On T. 1. -weighted images the metaphyseal water content was significantly reduced after ten weeks on the treated side (p = 0.04) but returned to values comparable with the untreated side at 15 weeks (p = 0.14). Return of growth was observed in all animals after removal of implants. Temporary epiphysiodesis can be obtained using tension band plating. The technique is not yet in common clinical practice but might avoid the need for the accurate timing of epiphysiodesis. Cite this article: Bone Joint J 2013;95-B:855–60

Forearm fractures in children have a tendency to displace in a cast leading to malunion with reduced functional and cosmetic results. In order to identify risk factors for displacement, a total of 247 conservatively treated fractures of the forearm in 246 children with a mean age of 7.3 years (. sd. 3.2; 0.9 to 14.9) were included in a prospective multicentre study. Multivariate logistic regression analyses were performed to assess risk factors for displacement of reduced or non-reduced fractures in the cast. Displacement occurred in 73 patients (29.6%), of which 65 (89.0%) were in above-elbow casts. The mean time between the injury and displacement was 22.7 days (0 to 59). The independent factors found to significantly increase the risk of displacement were a fracture of the non-dominant arm (p = 0.024), a complete fracture (p = 0.040), a fracture with translation of the ulna on lateral radiographs (p = 0.014) and shortening of the fracture (p = 0.019). Fractures of both forearm bones in children have a strong tendency to displace even in an above-elbow cast. Severe fractures of the non-dominant arm are at highest risk for displacement. Radiographs at set times during treatment might identify early displacement, which should be treated before malunion occurs, especially in older children with less potential for remodelling. Cite this article: Bone Joint J 2013;95-B:689–93

The aim of limb-salvage surgery in malignant bone tumours in children is to restore function and eradicate local disease with as little morbidity as possible. Allografts are associated with a high rate of complications, particularly malunion at the allograft-host junction. We describe a simple technique which enhances union of allograft to host bone taking advantage of the discrepancy in size between the adult allograft and the child’s bone. This involves lifting a flap of periosteum before resection from the host bone, which is then telescoped into the allograft medullary canal, which may require internal burring or splitting, for a distance of 1.5 to 2 cm and covering the bone junction with the periosteal flap. This is more stable than conventional end-to-end opposition. For each centimetre of telescoping the surface area available for bony union is increased more than three times. The periosteal flap also augments union. Additional surface fixation with a plate and screws is not necessary. We have used this technique in nine children, in eight of whom there was complete union at a mean of 16 weeks. Delayed union, associated with generalised limb osteoporosis, occurred in one. Early mobilisation, with weight-bearing by three weeks, was possible. There was only one fracture of the allograft

Purpose of study. The aim of this study is to evaluate the role of low intensity pulsed ultrasound, Exogen in the treatment of delayed and non unions. Methodology: We conducted a retrospective study of 292 patients who has had Exogen treatment for delayed and non union from 2005 to 2009. Patient's age, sex, associated co morbidities, smoking history, medications, type of fractures (open/closed), infection and site of fractures were sought for. 271 patients' data (228 delayed and 43 non unions) were available during the study with mean age of 53.5 yrs. Exogen therapy was initiated at 3–4 months for delayed unions and 6–12 months for non unions in 61 tibia (15 open); 31 femur (2 open); 20 scaphoid; 38 5th metatarsal; 31 ankle (2 open); 17 ulna (1 open); 15 radius (3 open); 29 humerus (2 open); 16 clavicles; 6 olecranon; 4 pilon (2 open) and 2 metacarpal fractures. Discussion. Union was achieved in 196 patients (72.3%) of which 11 (5.6%) were smokers. In 73 (26.9 %) patients union was not achieved of which 53 (72 %) were smokers. The mean healing timing after application of Exogen was 16 weeks for delayed union and 26.6 weeks for non union. 5 (31.2%) pt out of 16 in the DM group went into non union. Conclusion. In our study we found an accelerated union rate with Exogen therapy in delayed union, however smoking is a negative predictor for bone healing, which appears to be unaltered despite Exogen therapy(p=0.0032). Prescribing Exogen therapy early may be potentially beneficial to prevent an established non union

We prospectively evaluated the percutaneous injection of autogenous bone marrow for the treatment of active simple bone cysts in ten consecutive children with cysts in the proximal humerus, proximal femur or tibia. The treatment included percutaneous biopsy, aspiration of fluid and the injection of autogenous bone marrow aspirated from the iliac crest. All the patients became painfree after a mean of two weeks and resumed full activities within six weeks. All ten cysts consolidated radiologically and showed remarkable remodelling within four months. Review at 12 to 48 months showed satisfactory healing without complications. Percutaneous injection of autologous bone marrow appears to be an effective treatment for active simple bone cysts

Background. Unicameral bone cysts (UBCs) are difficult to treat and have a high recurrence rate. Their pathogenesis is unknown making targeted therapies difficult. Attributed causes include venous and interstitial fluid obstruction, oxygen free radicals, lysosomal enzymes, prostaglandins and genetic factors. Skeletal stem cells (SSCs) are osteoblast precursors critical to bone formation and cyst fluid may influence their growth, however the association between SSCs and cyst fluid has never been investigated. Aim. To investigate the effect of UBC fluid on SSC growth. Methods. Fluid was aspirated from a UBC in the proximal femur of a nine year old boy and centrifuged to isolate the acellular supernatant. SSCs were harvested from bone marrow of a haematologically normal adult and cultured with graded concentrations of cyst fluid in culture media (0,10,25,50%). Cell growth was assessed by alkaline phosphatase staining, and cytokine levels in the fluid were measured. Results. High levels of cytokines known to be chemo-attractive for cells of the of macrophage-monocyte lineage were found, including Macrophage Chemotactic Protein-1 (1853pg/ml), Monokine Induced by γ-interferon (656pg/ml), Macrophage Inflammatory Protein (MIP)-1α (401pg/ml) and MIP-1β (34pg/ml) suggesting a role of osteoclasts in UBC pathogenesis. Furthermore, SSC growth in vitro was reduced in cyst fluid in a concentration dependent manner. Conclusion. This is the first time altered SSC and osteoprogenitor function has been associated with the fluid of a UBC. A negative effect on osteogenesis was demonstrated, the precise mechanisms of which are under investigation, and macrophage-monocyte chemokines suggest high osteoclast activity. This study has indicated a role of the cyst fluid in limiting osteogenesis and bone turnover, which may explain the high failure rate for current interventions. More patients are needed to validate these findings

Purpose. Analyze the results of reconstruction of post osteomyelitic bone defect using non-vascularised fibula graft in children and correlation of results with magnitude of defect. Methods. 11 boys and 15 girls (mean age 6.8±2.33 years) were prospectively enrolled in the study. All had primary acute hematogeneous osteomyelitis with diaphyseal sequestration and active discharging sinuses. 7 femur, 12 tibia, 3 humerus, 3 radius and 1 ulna were the bone involved. As first step a radical debridement and sequestrectomy was performed. Second step was considered after a ‘dry’ period judged clinically and by normalized CRP. A subperiosteal resection of fibula was done and used as graft to fill in the diaphyseal defect. Graft was stabilized using intramedullary ‘K’ wires and supported by post-operative casts. Weight-bearing was started on radiological evidence of union. Results. mean follow up was 3.02±0.74 years with mean union time of 38.76±12.02 weeks. Delayed union (n=4) was seen at sites with large discrepancy between diameter of native bone and graft (like proximal tibial metaphysis). These cases united with plate fixation and bone grafting. There was weak positive correlation between union time and preoperative bone defect (+0.699). Subgroup analysis showed that there no significant difference between union times of patients with defect <4cms (mean of 31.7±11.5 weeks) and defect >4<6cms (mean 36.6±9 weeks), however the union time of patients with defect >6cms was significantly more (51±6.7 weeks). Conclusion. Non-vascularised fibula graft gives predictable results in children with post-osteomyelitic bone defects. Delayed unions are expected if the size of bone defect is >6cms or there is large discrepancy between the diameters of native and grafted bone

The management of chronic osteomyelitis requires the excision of necrotic and infected material followed by the prolonged administration of antibiotics. Sequestrectomy may be required before an involucrum has formed, resulting in a longitudinal bone defect. This can be difficult to fill. Vascularised grafts are complicated by a high rate of recurrent infection and thrombosis. We have managed defects of long bones in children after sequestrectomy by the use of non-vascularised fibular grafts harvested subperiosteally and held by an intramedullary Kirschner wire. Eight children underwent this procedure. In six the tibia was involved and in one each the humerus and radius. One patient was lost to follow-up. Six grafts united at both ends within 12 weeks. The seventh developed an infected nonunion distally which united after further debridement. One patient required a further sequestrectomy which did not compromise union. We have found this to be a straightforward technique with reliable results and were able to salvage the limb in all the seven patients who were reviewed

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of congenital pseudarthrosis of the tibia has been investigated in only one previous study, with promising results. The aim of this study was to determine whether rhBMP-2 might improve the outcome of this disorder. We reviewed the medical records of five patients with a mean age of 7.4 years (2.3 to 21) with congenital pseudarthrosis of the tibia who had been treated with rhBMP-2 and intramedullary rodding. Ilizarov external fixation was also used in four of these patients. Radiological union of the pseudarthrosis was evident in all of them at a mean of 3.5 months (3.2 to 4) post-operatively. The Ilizarov device was removed after a mean of 4.2 months (3.0 to 5.3). These results indicate that treatment of congenital pseudarthrosis of the tibia using rhBMP-2 in combination with intramedullary stabilisation and Ilizarov external fixation may improve the initial rate of union and reduce the time to union. Further studies with more patients and longer follow-up are necessary to determine whether this surgial procedure may significantly enhance the outcome of congenital pseudarthrosis of the tibia, considering the refracture rate (two of five patients) in this small case series

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1. +/−. ) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1. +/−. mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1

Aim

Fractures are the second commonest presentation of non-accidental injury (NAI) in children. Approximately one third of abused children will present to Acute Trauma Services (ATS) with fractures. Any cases of suspected child maltreatment should be referred to Safeguarding Services for follow-up, as outlined by Trust Guidelines. Our aim was to examine the referral of children with suspicious fractures to safeguarding and assess if cases with high risk of abuse are being missed by ATS.

Aims. The aim of this study was to describe the incidence of refractures among children, following fractures of all long bones, and to identify when the risk of refracture decreases. Methods. All patients aged under 16 years with a fracture that had occurred in a bone with ongoing growth (open physis) from 1 May 2015 to 31 December 2020 were retrieved from the Swedish Fracture Register. A new fracture in the same segment within one year of the primary fracture was regarded as a refracture. Fracture localization, sex, lateral distribution, and time from primary fracture to refracture were analyzed for all long bones. Results. Of 40,090 primary fractures, 348 children (0.88%) sustained a refracture in the same long bone segment. The diaphyseal forearm was the long bone segment most commonly affected by refractures (n = 140; 3.4%). The median time to refracture was 147 days (interquartile range 82 to 253) in all segments of the long bones combined. The majority of the refractures occurred in boys (n = 236; 67%), and the left side was the most common side to refracture (n = 220; 62%). The data in this study suggest that the risk of refracture decreases after 180 days in the diaphyseal forearm, after 90 days in the distal forearm, and after 135 days in the diaphyseal tibia. Conclusion. Refractures in children are rare. However, different fractured segments run a different threat of refracture, with the highest risk associated with diaphyseal forearm fractures. The data in this study imply that children who have sustained a distal forearm fracture should avoid hazardous activities for three months, while children with a diaphyseal forearm fracture should avoid these activities for six months, and for four and a half months if they have sustained a diaphyseal tibia fracture. Cite this article: Bone Joint J 2023;105-B(8):928–934

Aims. Given the possible radiation damage and inaccuracy of radiological investigations, particularly in children, ultrasound and superb microvascular imaging (SMI) may offer alternative methods of evaluating new bone formation when limb lengthening is undertaken in paediatric patients. The aim of this study was to assess the use of ultrasound combined with SMI in monitoring new bone formation during limb lengthening in children. Methods. In this retrospective cohort study, ultrasound and radiograph examinations were performed every two weeks in 30 paediatric patients undergoing limb lengthening. Ultrasound was used to monitor new bone formation. The number of vertical vessels and the blood flow resistance index were compared with those from plain radiographs. Results. We categorized the new bone formation into three stages: stage I (early lengthening), in which there was no obvious callus formation on radiographs and ultrasound; stage II (lengthening), in which radiographs showed low-density callus formation with uneven distribution and three sub-stages could be identified on ultrasound: in Ia punctate callus was visible; in IIb there was linear callus formation which was not yet connected and in IIc there was continuous linear callus. In stage III (healing), the bone ends had united, the periosteum was intact, and the callus had disappeared, as confirmed on radiographs, indicating healed bone. A progressive increase in the number of vertical vessels was noted in the early stages, peaking during stages IIb and IIc, followed by a gradual decline (p < 0.001). Delayed healing involved patients with a prolonged stage IIa or those who regressed to stage IIa from stages IIb or IIc during lengthening. Conclusion. We found that the formation of new bone in paediatric patients undergoing limb lengthening could be reliably evaluated using ultrasound when combined with the radiological findings. This combination enabled an improved assessment of the prognosis, and adjustments to the lengthening protocol. While SMI offered additional insights into angiogenesis within the new bone, its role primarily contributed to the understanding of the microvascular environment rather than directly informing adjustments of treatment. Cite this article: Bone Joint J 2024;106-B(7):751–758

Purpose

To assess the initial rise in inflammatory markers in paediatric patients presenting with long bone osteomyelitis and whether this is comparable with that in septic arthritis, and diagnostic.

Aims. Temporary hemiepiphysiodesis (HED) is applied to children and adolescents to correct angular deformities (ADs) in long bones through guided growth. Traditional Blount staples or two-hole plates are mainly used for this indication. Despite precise surgical techniques and attentive postoperative follow-up, implant-associated complications are frequently described. To address these pitfalls, a flexible staple was developed to combine the advantages of the established implants. This study provides the first results of guided growth using the new implant and compares these with the established two-hole plates and Blount staples. Methods. Between January 2013 and December 2016, 138 patients (22 children, 116 adolescents) with genu valgum or genu varum were treated with 285 flexible staples. The minimum follow-up was 24 months. These results were compared with 98 patients treated with 205 two-hole plates and 92 patients treated with 535 Blount staples. In long-standing anteroposterior radiographs, mechanical axis deviations (MADs) were measured before and during treatment to analyze treatment efficiency. The evaluation of the new flexible staple was performed according to the idea, development, evaluation, assessment, long-term (IDEAL) study framework (Stage 2a). Results. Overall, 79% (109/138) of patients treated with flexible staples achieved sufficient deformity correction. The median treatment duration was 16 months (interquartile range (IQR) 8 to 21). The flexible staples achieved a median MAD correction of 1.2 mm/month/HED site (IQR 0.6 to 2.0) in valgus deformities and 0.6 mm/month/HED site (IQR 0.2 to 1.5) in varus deformities. Wound infections occurred in 1%, haematomas and joint effusions in 4%, and implant-associated complications in 1% of patients treated with flexible staples. Valgus AD were corrected faster using flexible staples than two-hole plates and Blount staples. Furthermore, the median MAD after treatment was lower in varus and valgus AD, fewer implant-associated complications were detected, and reduced implantation times were recorded using flexible staples. Conclusion. The flexible staple seems to be a viable option for guided growth, showing comparable or possibly better results regarding correction speed and reducing implant-associated complications. Further comparative studies are required to substantiate these findings. Cite this article: Bone Joint J 2023;105-B(3):331–340

Aims. The aim of this study was to explore parents’ experience of their child’s recovery, and their thoughts about their decision to enrol their child in a randomized controlled trial (RCT) of surgery versus non-surgical casting for a displaced distal radius fracture. Methods. A total of 20 parents of children from 13 hospitals participating in the RCT took part in an interview five to 11 months after injury. Interviews were informed by phenomenology and analyzed using thematic analysis. Results. Analysis of the findings identified the theme “being recovered”, which conveyed: 1) parents’ acceptance and belief that their child received the best treatment for them; 2) their memory of the psychological impact of the injury for their child; and 3) their pride in how their child coped with their cast and returned to activities. The process of recovery was underpinned by three elements of experience: accepting the treatment, supporting their child through challenges during recovery, and appreciating their child’s resilience. These findings extend our framework that highlights parents’ desire to protect their child during early recovery from injury, by making the right decision, worrying about recovery, and comforting their child. Conclusion. By one year after injury, parents in both treatment groups considered their child “recovered”. They had overcome early concerns about healing, the appearance of the wrist, and coping after cast removal. Greater educational support for families during recovery would enable parents and their child to cope with the uncertainty of recovery, particularly addressing the loss of confidence, worry about reinjury, and the appearance of their wrist. Cite this article: Bone Jt Open 2024;5(5):426–434