Kingella Research Articles

KINGELLA KINGAE SEQUENCE TYPE 25 MENINGITIS IN AN IMMUNOCOMPETENT TODDLER: CLINICAL AND MOLECULAR APPROACH.

Kingella kingae is a cause of bacteremia, endocarditis, and the leading cause of osteoarticular infections between 6 and 48 months of life. We report on a rare case of K. kingae meningitis in the absence of endocarditis and immune deficiency in a 26-month-old boy emphasizing the distinct genomic determinants of the strain which may be of importance to the pathogenesis of the disease.

Shoulder Septic Arthritis in the Pediatric Age - an Epidemiologic Study

Shouder septic arhtirtis in children may be a challenge due to its limited studies and absence of an algorithm. Elevated C-reactive protein (CRP) and pseudoparalysis of the shoulder may be the most preditive indicators. This paper aims to conduct a retrospective epidemiologic analysis of the pediatric shoulder arthritis cases of the last 5 years in our central pediatric hospital. It includes shoulder septic arthritis diagnosed in the last five years in our central pediatric hospital, in a total of twelve patients, treated surgically with aspiration and articular washout, or arthrtomy among other procedures, with patients between 13 days and 6 year-old. The most isolated pathogens where Kingella Kingae and Streptococcus pyogenes.

Clinical Utility of a Multiplex PCR Panel (BioFire Joint Infection®) in the Adjustment of Empiric Antimicrobial Therapy: Experience in Pediatric Osteoarticular Infections.

This study aims to evaluate the impact of the PCR multiplex panel (BioFire JI®) on the diagnosis and management of pediatric osteoarticular infections. This retrospective study analyzed data from pediatric patients diagnosed with osteoarticular infections between January 2023 and April 2024. The effectiveness of the PCR multiplex panel in identifying pathogens was compared with traditional culture methods. In total, 50 patients were identified (66.6% male, 74% under 3 years of age). They were diagnosed as follows: septic arthritis in 46%, osteomyelitis in 26%, and septic osteoarthritis in 22%. An identifiable agent was isolated by conventional culture in 22 cases (44%). Kingella kingae was the predominant pathogen identified, accounting for 50% of cases (11/22), followed by Staphylococcus aureus (9/22). The BioFire JI® Panel PCR demonstrated a sensitivity of 93%, with a specificity of 63% when evaluated against synovial fluid culture as the reference standard. The panel identified seven additional pathogens not detected by conventional culture methods: 2/9 MSSA (22%), 1/1 S. pyogenes (100%), and 4/11 K. kingae (37%), increasing the yield by 14%. The rapid identification of pathogens facilitated timely and targeted therapeutic interventions. The PCR multiplex panel (BioFire JI®) improved the diagnosis of pediatric osteoarticular infections.

The Seasonality of Childhood Bone and Joint Infection with Focus on Kingella kingae

Background: Seasonal trends in hospitalization for childhood bone and joint infection (BJI) are reported inconsistently. True seasonal variation would suggest an element of disease risk from environmental factors. This review evaluates all reported seasonal variations in childhood BJI, with additional analysis of seasonal trends for diseases secondary to Kingella kingae. Methods: A systematic review of the literature was undertaken from January 1, 1980, to August 1, 2024. Data were extracted on the hospitalization rate by season and/or month. Pathogen-specific studies for BJI secondary to K. kingae were examined separately. Results: Twenty studies met inclusion criteria encompassing 35,279 cases of childhood BJI. Most studies reported seasonal variation (n = 15, 75%). Eight studies specifically considered disease secondary to K. kingae, and all reported more frequent hospitalization in autumn and/or winter. This is in keeping with the role of respiratory pathogens and seasonal viruses in disease etiology for K. kingae BJI. Findings from other studies on the seasonality of childhood BJI were inconsistent. There were reported seasonal peaks in autumn/winter (4 studies), summer/spring (5 studies), or no variation (5 studies). Where microbiologic data were available, Staphylococcus aureus was the primary pathogen. The quality assessment demonstrated confounding and heterogeneous inclusion criteria affecting the seasonal analysis. Conclusion: For childhood BJI caused by K. kingae, there appears to be a higher risk of hospitalization in autumn and/or winter months. This may relate to the seasonal circulation of respiratory viruses. There is currently insufficient evidence to support other forms of seasonal variation. Reported findings are likely affected by regional disease and pathogen characteristics. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Epidemiology of childhood bone and joint disease during the COVID-19 pandemic in New Zealand.

It is unknown whether social distancing impacts frequency of presentation and severity of childhood bone and joint infection (BJI). In New Zealand, the COVID-19 disease elimination strategy involved strict social isolation policies spanning March 2020-September 2022. Examination of this period may provide insight around risk factors for BJI. A retrospective review of all patients < 16 years with presumed acute haematogenous osteomyelitis (AHO) or septic arthritis (SA) treated in the Auckland region was performed between 2018 and 2023. Frequency and severity of presentations has been examined before, during, and after periods of social restriction. Severe cases included those with intensive care admission, recurrent infection, or multiple surgeries. Pre-hospital experience, length of stay, and disease outcomes have also been assessed. A total of 563 cases met inclusion criteria. Compared to the pre-pandemic period, monthly case averages reduced between April 2020 to September 2022 (10.1 vs. 7.9 cases/month, p = 0.008). Separating cases by causative microbiology shows a statistically significant drop in culture negative and Kingella kingae mediated BJI cases (4.2 vs. 2.9 cases/month, p = 0.006) but not for cases secondary to Staphylococcus aureus and Streptococcus pyogenes (4.2 vs. 3.9 cases/month, p = 0.6). The frequency of severe disease reduced during this period (5.6 vs. 4.1 cases/month, p = 0.01) together with lower rates of recurrent infection (9% vs. 4%, p = 0.03). The COVID-19 management strategy in New Zealand utilised strict social isolation, mask wearing, and hand hygiene measures to control disease spread between 2020 and 2022. These measures coincided with reduction in frequency and severity of presentations for childhood BJI.

Type 1 secretion necessitates a tight interplay between all domains of the ABC transporter

Type I secretion systems (T1SS) facilitate the secretion of substrates in one step across both membranes of Gram-negative bacteria. A prime example is the hemolysin T1SS which secretes the toxin HlyA. Secretion is energized by the ABC transporter HlyB, which forms a complex together with the membrane fusion protein HlyD and the outer membrane protein TolC. HlyB features three domains: an N-terminal C39 peptidase-like domain (CLD), a transmembrane domain (TMD) and a C-terminal nucleotide binding domain (NBD). Here, we created chimeric transporters by swapping one or more domains of HlyB with the respective domain(s) of RtxB, a HlyB homolog from Kingella kingae. We tested all chimeric transporters for their ability to secrete pro-HlyA when co-expressed with HlyD. The CLD proved to be most critical, as a substitution abolished secretion. Swapping only the TMD or NBD reduced the secretion efficiency, while a simultaneous exchange abolished secretion. These results indicate that the CLD is the most critical secretion determinant, while TMD and NBD might possess additional recognition or interaction sites. This mode of recognition represents a hierarchical and extreme unusual case of substrate recognition for ABC transporters and optimal secretion requires a tight interplay between all domains.

Bacterial osteomyelitis in pediatric patients: a comprehensive review.

Bacterial osteomyelitis, an inflammatory response in the bone caused by microorganisms, typically affects the metaphysis in the skeletally immature. Bacterial osteomyelitis possesses a significant diagnostic challenge in pediatric patients due to its nonspecific clinical presentation. Because the metaphysis is the primary focus of infection in skeletally immature patients, understanding the normal physiologic, maturation process of bones throughout childhood allows to understand the pathophysiology of osteomyelitis.Timely and accurate diagnosis is crucial to initiate appropriate treatment, and prevent long-term sequelae and efforts must be made to isolate the causative organism. The potential causative organism changes according to the age of the patient and underlying medical conditions. Staphylococcus Aureus is the most common isolated bacteria in pediatric pyogenic osteomyelitis whereas Kingella Kingae is the most common causative agent in children aged 6months to 4years. Imaging plays a pivotal role in the diagnosis, characterization, evaluation of complications, and follow up of bacterial osteomyelitis. Imaging also plays a pivotal role in the evaluation of potential neoplastic and non-neoplastic mimickers of osteomyelitis. In children, MRI is currently the gold standard imaging modality when suspecting bacterial osteomyelitis, whereas surgical intervention may be required in order to isolate the microorganism, treat complications, and exclude mimickers.

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study.

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

Infective Endocarditis Due to Kingella kingae.

Infective endocarditis due to Kingella kingae is a rare but serious invasive infection that occurs mostly in children. Recent advances in nucleic acid amplification testing as well as in cardiac imaging have enabled more accurate diagnosis. A good understanding of the epidemiology and virulence factors remains crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, pathophysiological insights, complications, and therapy regarding Kingella kingae endocarditis in children and adults. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.

Expression of Concern for El Houmami et al., "Molecular Tests That Target the RTX Locus Do Not Distinguish between Kingella kingae and the Recently Described Kingella negevensis Species".

Expression of Concern for El Houmami et al., "Molecular Tests That Target the RTX Locus Do Not Distinguish between Kingella kingae and the Recently Described Kingella negevensis Species".

Chimeric vaccine design against the conserved TonB-dependent receptor-like β-barrel domain from the outer membrane tbpA and hpuB proteins of Kingella kingae ATCC 23330.

Kingella kingae is a Gram-negative bacterium that primarily causes pediatric infections such as septicemia, endocarditis, and osteoarticular infections. Its virulence is attributed to the outer membrane proteins having implications in bacterial adhesion, invasion, nutrition, and host tissue damage. TonB-dependent receptors (TBDRs) play an important role in nutrition and were previously implicated as vaccine targets in other bacteria. Therefore, we targeted the conserved β-barrel TBDR domain of these proteins for designing a vaccine construct that could elicit humoral and cellular immune responses. We used bioinformatic tools to mine TBDR-containing proteins from K. kingae ATCC 23330 and then predict B- and T-cell epitopes from their conserved β-barrel TDR domain. A chimeric vaccine construct was designed using three antigenic epitopes, covering >98% of the world population and capable of inciting humoral and adaptive immune responses. The final construct elicited a robust immune response. Docking and dynamics simulation showed good binding affinity of the vaccine construct to various receptors of the immune system. Additionally, the vaccine was predicted to be safe and non-allergenic, making it a promising candidate for further development. In conclusion, our study demonstrates the potential of immunoinformatics approaches in designing chimeric vaccines against K. kingae infections. The chimeric vaccine we designed can serve as a blueprint for future experimental studies to develop an effective vaccine against this pathogen, which can serve as a potential strategy to prevent K. kingae infections.

Challenges and Insights in Aggregatibacter aphrophilus endocarditis: a review of literature.

Infective endocarditis is a serious disease associated with high mortality despite recent advances in diagnosis and treatment. Aggregatibacter aphrophilus is a fastidious Gram-negative member of the HACEK organisms (Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). A. aphrophilus is associated with dental infections but has also been implicated in cases of infective endocarditis. We highlight the importance of a high index of suspicion in symptomatic patients with an initial negative blood culture, particularly in high-risk groups such as patients with congenital valve disease and prosthetic valve. The knowledge of this rare entity may lead to early diagnosis and appropriate management. We review the main characteristics of Aggregatibacter aphrophilus endocarditis reported in the medical literature.

Biological Predictors of Osteoarticular Infection Due to K. kingae-A Retrospective Cohort Study of 247 Cases.

Pediatric osteoarticular infections (OAIs) are serious conditions that can lead to severe septic complications, prolonged morbidity with long-term impaired function, and perturbed subsequent bone development. Kingella kingae (K. kingae) is currently accepted as the predominant pathogen in pediatric OAIs, especially among 6-48 month olds. The present study aimed to identify clinical and biological markers that would refine the detection of patients with an OAI due to K. kingae. We retrospectively studied every consecutive case of pediatric OAI admitted to our institution over 17 years. Medical records were examined for patient characteristics such as temperature at admission, affected segment, and biological parameters such as white blood cell (WBC) count, left shift, platelet count (PLT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The 247 patients included 52.2% males and 47.8% females and mean age was 18.5 ± 10 months old. Four patients were older than 48 months; none were younger than 6 months old. Mean temperature at admission was 37.4 ± 0.9 °C. Regarding biological parameters, mean WBC count was 12,700 ± 4180/mm3, left shift was only present in one patient, mean PLT was 419,000 ± 123,000/mm3, mean CRP was 26.6 ± 27.8 mg/L, and mean ESR was 35.0 ± 18.9 mm/h. Compared to the modified predictors of OAI defined by Kocher and Caird, 17.2% of our cases were above their cut-off values for temperature, 52.3% were above the WBC cut-off, 33.5% were above the ESR cut-off, and 46.4% were above the CRP cut-off. OAIs due to K. kingae frequently remain undetected using the classic biological parameters for investigating bacterial infections. As an addition to the predictors normally used (°C, WBC, CRP, and ESR), this study found that elevated platelet count was frequently present during OAIs caused by K. kingae. Although this biological characteristic was inconstant, its presence was highly significant and very suggestive of an invasive infection due to K. kingae.

Pediatric Osteoarticular Kingella kingae Infections of the Hand and Wrist: A Retrospective Study.

Our understanding of pediatric osteoarticular infections (OAIs) has improved significantly in recent decades. Kingella kingae is now recognized as the most common pathogen responsible for OAIs in pediatric populations younger than 4 years old. Research has provided a better understanding of the specific types, clinical characteristics, biological repercussions, and functional outcomes of these infections. Hands and wrists are rarely infected, with few reports available in the literature. The present study aimed to examine this specific condition in a large patient cohort, explore the implications for each anatomical area using magnetic resonance imaging (MRI), and critically evaluate the evolution of therapeutic management.

Kingella kingae RtxA toxin interacts with sialylated gangliosides

The membrane-damaging RTX family cytotoxin RtxA is a key virulence factor of the emerging pediatric pathogen Kingella kingae, but little is known about the mechanism of RtxA binding to host cells. While we have previously shown that RtxA binds cell surface glycoproteins, here we demonstrate that the toxin also binds different types of gangliosides. The recognition of gangliosides by RtxA depended on sialic acid side groups of ganglioside glycans. Moreover, binding of RtxA to epithelial cells was significantly decreased in the presence of free sialylated gangliosides, which inhibited cytotoxic activity of the toxin. These results suggest that RtxA utilizes sialylated gangliosides as ubiquitous cell membrane receptor molecules on host cells to exert its cytotoxic action and support K. kingae infection.

Common Diseases in Newborns Due to Abo Blood Group Mismatching in Parents

Hemolytic disease of the newborn, also called erythroblastosis fetalis refers to a blood disorder due to ABO incompatibility between mother and fetus. Manifestation of the disease ranges and depends on specific factors. In severe cases phototherapy is the therapy of choice. Potential consequences of HDN are jaundice, anemia and fetal hydrops. In order to prevent ABO-incompatibility’s occurrence, detection of mother’s blood type and monitoring during and post birth are necessary. Main text:- ABO blood group incompatibility between mother and newborn can lead to many serious and potentially life-threatening illnesses and complications. The ABO blood group consists of three allelic forms, A, B and O and child’s genotype and phenotype arises from parental genetic profile. The presence or absence of certain antigens on red blood cells determines blood type. The most common type of ABO incompatibility occurs when the mother's blood type is O and the newborn's blood type is A or B. This condition refers to the common hemolytic disease of the newborn (HDN). Hemolytic disease of the newborn (HDN) is a condition that occurs when the mother's antibodies attack the baby's red blood cells [1]. In ABO incompatibility, the mother's antibodies recognize the baby's red blood cells as foreign and attack them. HDN can range from mild to severe, with severe cases leading to jaundice, anemia, brain damage, and even death. The severity of HDN depends on the amount of antibodies in the mother's blood, the baby's blood type, and the baby's general health [2]. In most cases of ABO incompatibility, HDN is mild and resolves spontaneously without treatment. However, in severe cases, the baby may need phototherapy to treat jaundice or a blood transfusion to replace damaged red blood cells [3].

Whole-Genome Sequencing Reveals Differences among Kingella kingae Strains from Carriers and Patients with Invasive Infections.

As a result of the increasing use of sensitive nucleic acid amplification tests, Kingella kingae is being recognized as a common pathogen of early childhood, causing medical conditions ranging from asymptomatic oropharyngeal colonization to bacteremia, osteoarthritis, and life-threatening endocarditis. However, the genomic determinants associated with the different clinical outcomes are unknown. Employing whole-genome sequencing, we studied 125 international K. kingae isolates derived from 23 healthy carriers and 102 patients with invasive infections, including bacteremia (n = 23), osteoarthritis (n = 61), and endocarditis (n = 18). We compared their genomic structures and contents to identify genomic determinants associated with the different clinical conditions. The mean genome size of the strains was 2,024,228 bp, and the pangenome comprised 4,026 predicted genes, of which 1,460 (36.3%) were core genes shared by >99% of the isolates. No single gene discriminated between carried and invasive strains; however, 43 genes were significantly more frequent in invasive isolates, compared to asymptomatically carried organisms, and a few showed a significant differential distribution among isolates from skeletal system infections, bacteremia, and endocarditis. The gene encoding the iron-regulated protein FrpC was uniformly absent in all 18 endocarditis-associated strains but was present in one-third of other invasive isolates. Similar to other members of the Neisseriaceae family, the K. kingae differences in invasiveness and tropism for specific body tissues appear to depend on combinations of multiple virulence-associated determinants that are widely distributed throughout the genome. The potential role of the absence of the FrpC protein in the pathogenesis of endocardial invasion deserves further investigation. IMPORTANCE The wide range of clinical severities exhibited by invasive Kingella kingae infections strongly suggests that isolates differ in their genomic contents, and strains associated with life-threatening endocarditis may harbor distinct genomic determinants that result in cardiac tropism and severe tissue damage. The results of the present study show that no single gene discriminated between asymptomatically carried isolates and invasive strains. However, 43 putative genes were significantly more frequent among invasive isolates than among pharyngeal colonizers. In addition, several genes displayed a significant differential distribution among isolates from bacteremia, skeletal system infections, and endocarditis, suggesting that the virulence and tissue tropism of K. kingae are multifactorial and polygenic, depending on changes in the allele content and genomic organization. Further analysis of these putative genes may identify genomic determinants of the invasiveness of K. kingae and its affinity for specific body tissues and potential targets for a future protective vaccine.

Pan-genome mediated therapeutic target mining in Kingella kingae and inhibition assessment using traditional Chinese medicinal compounds: an informatics approach

Kingella kingae causes bacteremia, endocarditis, osteomyelitis, septic arthritis, meningitis, spondylodiscitis, and lower respiratory tract infections in pediatric patients. Usually it demonstrates disease after inflammation of mouth, lips or infections of the upper respiratory tract. To date, therapeutic targets in this bacterium remain unexplored. We have utilized a battery of bioinformatics tools to mine these targets in this study. Core genes were initially inferred from 55 genomes of K. kingae and 39 therapeutic targets were mined using an in-house pipeline. We selected aroG product (KDPG aldolase) involved in chorismate pathway, for inhibition analysis of this bacterium using lead-like metabolites from traditional Chinese medicinal plants. Pharmacophore generation was done using control ZINC36444158 (1,16-bis[(dihydroxyphosphinyl)oxy]hexadecane), followed by molecular docking of top hits from a library of 36,000 compounds. Top prioritized compounds were ZINC95914016, ZINC33833283 and ZINC95914219. ADME profiling and simulation of compound dosing (100 mg tablet) was done to infer compartmental pharmacokinetics in a population of 300 individuals in fasting state. PkCSM based toxicity analysis revealed the compounds ZINC95914016 and ZINC95914219 as safe and with almost similar bioavailability. However, ZINC95914016 takes less time to reach maximum concentration in the plasma and shows several optimal parameters compared to other leads. In light of obtained data, we recommend this compound for further testing and induction in experimental drug design pipeline. Communicated by Ramaswamy H. Sarma

Transphyseal Hematogenous Osteomyelitis: An Epidemiological, Bacteriological, and Radiological Retrospective Cohort Analysis.

Transphyseal hematogenous osteomyelitis (THO) is a serious condition that can affect the growing physis, yet it is insufficiently recognized in children. The aim of this study was to explore the prevalence and epidemiology of pediatric THO, and to discuss the underlying pathophysiology. All consecutive cases of acute and subacute osteomyelitis admitted to our institution over 17 years were retrospectively studied. Medical records were examined for patient characteristics, bacteriological etiology, and medical and surgical management. Magnetic resonance imaging was reviewed for all patients to identify those with transphyseal spread of infection. For positive cases, the surface area of the transphyseal lesion was estimated relative to the total physeal cross-sectional area. Fifty-four (25.7%) of the 210 patients admitted for acute or subacute osteomyelitis were diagnosed with THO. The study population's ages ranged from 1 month to 14 years old (median age 5.8 years, interquartile range 1-167 months). Fourteen (25.9%) patients were younger than 18 months old; the remaining 40 (74.1%) had a mean age of 8.5 years old. The most common sites of THO were the distal tibia (29.1%), the proximal tibia (16.4%), and the distal fibula (14.5%). Transphyseal lesions were due to acute infection in 41 cases and to subacute osteomyelitis in 14 cases. The two most frequently identified pathogens were Staphylococcus aureus (49.1%) and Kingella kingae (20.0%). An average transphyseal lesion represented 8.9% of the total physeal surface, and lesions comprised more than 7% of the physeal cross-sectional area in 51% of cases. Our study revealed that pediatric THO was more frequent than commonly thought. Transphyseal lesions were frequently above this 7% cut-off, which is of paramount importance since subsequent growth is more likely to be disturbed when more than 7% of the physeal cross-sectional area is injured. THO also affected children older than 18 months, an age at which transphyseal arterial blood supply to the epiphysis is believed to have disconnected. This finding suggests another pathophysiological reason for the transphyseal diffusion of infection, a topic deserving further studies and greater understanding.