Musculoskeletal Infections In Children Research Articles

Maternal Profile In Infants With Musculoskeletal Infections- Evaluation In A Tertiary Care Centre

BACKGROUND: Musculoskeletal infections in pediatric age group account for 23% of the total infections. The most common musculoskeletal infections in children are Osteomyelitis and Septic Arthritis. Maternal health primarily impacts infants as they get immunity from mothers. In this context, this study was done to evaluate maternal parameters which include serum proteins, hemoglobin levels,maternal history, mode of delivery, type of feed to infant. MATERIAL AND METHODS: 21 infants were admitted in GMC Jammu with musculoskeletal infections over a period of 9 months who underwent treatment. Their mothers were evaluated thoroughly and various investigations were done. RESULTS: 32% of the mothers suffered from Gestational Diabetes Mellitus, 24% from anemia, 10% from PIH and 3 % from eclampsia. 70% of infants took birth by vaginal delivery while 30% were by caesarean section.80% of the infants were breastfed whereas 20% of them were fed artificially. Serum Globulin was low in majority of mothers. Serum Albumin was raised in all the mothers. CONCLUSIONS: Mother’s health had a positive correlation with the infant’s nutritional status & susceptibility to infections.

Magnetic resonance imaging in the evaluation of suspected hip sepsis in children.

Background:Rapid and accurate diagnosis of musculoskeletal infection in children is critical to enable appropriate, targeted surgical interventions. Distinguishing between septic arthritis, myositis, and osteomyelitis around the hip can be difficult using clinical criteria and ultrasound scan alone.Materials and methods:We performed a retrospective 5-year observational review of selective magnetic resonance imaging scanning for hip sepsis in a pediatric tertiary referral center. Included were children with atraumatic hip pain with symptom duration <2 weeks, minimum of two positive modified Kocher’s criteria, and a hip effusion on ultrasound. All cases were followed up to discharge. We evaluated hip ultrasound and magnetic resonance imaging findings, operative procedures, microbiology results, duration of treatment, outcomes, and complications.Results:Fifty-one patients, 55% male, with a mean age 6.4 (0–16) years were included. Thirty-nine underwent magnetic resonance imaging scan for suspected septic arthritis of the hip; 24 prior to surgical washout (pre-emptive), and 15 afterwards (postoperative). In the pre-emptive group, 1/24 had septic arthritis, 7/24 had osteomyelitis, 6/24 had myositis, 5/24 had osteomyelitis and myositis, and 5/24 had no evidence of infective pathology. In the postoperative group, 3/15 had myositis, 3/15 had osteomyelitis, 3/15 had re-accumulation of the hip effusion requiring repeat washout, 3/15 had myositis and osteomyelitis, and 1/15 had septic arthritis of a contiguous joint.Conclusion:Pre-emptive magnetic resonance imaging scanning avoided unnecessary hip washout in 23 cases and enabled targeted drainage of an alternative focus in four of those. Magnetic resonance imaging scanning after hip washout indicated that four cases required further surgery to drain a different focus of infection.

Transient synovitis of the hip: Current practice and risk of misdiagnosis

IntroductionTransient synovitis (TS) is a common and benign cause of hip pain in children, but must be distinguished from more serious entities such as septic arthritis, osteomyelitis, and pyomyositis. Our objectives were to determine the risk of missed bacterial musculoskeletal infection and rates of diagnostic testing in children diagnosed with TS. MethodsWe performed a cohort study using the Pediatric Heath Information System of children 1–10 years diagnosed with TS in the ED. We determined rates of missed bacterial musculoskeletal infection (defined as a new diagnosis of septic arthritis, osteomyelitis, or pyomyositis within 14 days of initial ED visit). We described the initial diagnostic evaluation and ED management of children diagnosed with TS and variability between sites. ResultsWe analyzed 6419 encounters from 37 hospitals. 62 (1.0%, 95%CI: 0.7–1.2%) children were diagnosed with a missed bacterial musculoskeletal infection. Children with missed infection were younger than those without (median age 2.6 vs. 4.6 years, p < 0.01). Serum laboratory testing was performed in 76% of encounters with minimal variation across sites. There was significant variation in the rates of hip ultrasound by site (2 to 92%), which has increased in use over time (from 42% in 2016 to 62% in 2021). ConclusionIn this large observational study, missed bacterial musculoskeletal infection in children diagnosed with TS was rare but more common in younger children. The optimal combination of bloodwork and radiographic testing, especially ultrasound, to distinguish TS from more serious disease remains unclear.

Magnetic resonance imaging protocols for pediatric acute hematogenous osteomyelitis.

Pediatric musculoskeletal infection can be a challenging clinical diagnosis. MRI protocols should be tailored appropriately to diagnose and localize sites of infection, to determine alternative pathologies that could explain the child's presentation, and to identify complications that could alter treatment or lead to devastating consequences in growing bones. In this review, we discuss MRI protocols tailored for suspected acute appendicular musculoskeletal infection in children. These protocols are based on patient age in order to generally reflect the developmental stage of the child, the corresponding relevant anatomy and physiology, and the skeletal maturity-dependent physiopathology of musculoskeletal infections.

A Clinical Prediction Rule for Bacterial Musculoskeletal Infections in Children with Monoarthritis in Lyme Endemic Regions

Children with a bacterial musculoskeletal infection (MSKI) require prompt identification and treatment. In Lyme disease endemic areas, children with an MSKI can present similarly to those with Lyme arthritis. Our goal was to derive a clinical prediction rule to accurately identify children at a low risk for an MSKI. We enrolled children with monoarthritis presenting to 1 of 6 Pedi Lyme Net centers and performed a procalcitonin (PCT) and a first-tier Lyme C6 enzyme immunoassay (EIA) test. Our primary outcome was an MSKI (septic arthritis, osteomyelitis, or pyomyositis). Using recursive partitioning with k-fold cross validation, we derived a clinical prediction rule to identify children at a low risk of an MSKI. We calculated the accuracy of our novel rule in a derivation cohort. Of the 735 children in the derivation cohort with an available research biosample, 39 (5%) had an MSKI (18 had septic arthritis, 20 had osteomyelitis, and 1 had pyomyositis), 260 (37%) had Lyme arthritis, and 436 (53%) had other inflammatory arthritis. Children with a PCT level of more than or equal to 0.50 ng/mL and those with a C-reactive protein (CRP) level of more than or equal to 0.6 mg/dL with a negative Lyme C6 EIA were classified as not low risk for an MSKI. Of the 451 (61%) children categorized as low risk, none had an MSKI (sensitivity 100%, 95% confidence interval 91.0% to 100%; specificity 74.2%, 95% confidence interval 70.5% to 77.6%). A novel clinical decision rule that includes PCT, CRP, and a first-tier Lyme EIA was highly sensitive for MSKIs. Although broader external validation is required, the application of this rule may safely reduce invasive testing, procedures, and treatment for low risk children.

Acute musculoskeletal infection in children: diagnostic difficulties and when to operate

Paediatric septic arthritis, osteomyelitis and pyomyositis are infrequent diagnoses in general orthopaedic practice. However, when they present they require early diagnosis and expeditious treatment to prevent sepsis and long-term morbidity. This is challenging as the early stages of each disease can closely mimic more common and often less significant pathologies. Here we aim to address the diagnostic challenges encountered in paediatric acute musculoskeletal infection and identify when urgent surgical intervention is required. In particular we cover which key symptoms and signs should be identified in the initial clinical assessment and how blood tests and imaging can help guide diagnosis, including the use of clinical predictive algorithms. We also discuss theories regarding disease pathogenesis and how different causative organisms can lead to a wide variety of clinical presentations. Finally we present up-to-date clinical evidence regarding treatment, whether this be via surgery or antibiotics alone.

Systematic Review of Kingella kingae Musculoskeletal Infection in Children: Epidemiology, Impact and Management Strategies.

Kingella kingae, a pathogen often responsible for musculoskeletal infections in children is the most common cause of septic arthritis and osteomyelitis in children 6 to 36 months of age. The aim of this study was to perform a systematic review of previous studies to determine the proportion of K. kingae in bacteriologically proven musculoskeletal infections among the pediatric population. A secondary objective was to describe the diagnostic strategies and outcome of patients with musculoskeletal infections caused by K. kingae. A systematic review was conducted to identify publications that report on musculoskeletal infections caused by K. kingae in the pediatric population (patients 0 to <18 years old with microbiologic culture and/or polymerase chain reaction (PCR) confirmation of K. kingae and a description of the musculoskeletal infection involved). Of 144 studies included in this review, we sought to determine the proportion of K. kingae pediatric musculoskeletal infections. A total of 711 (30.8%) out of 2308 pediatric cases with culture and/or PCR proven musculoskeletal infections had K. kingae successfully identified from twenty-nine studies. Of the 1070 patients who were aged less than 48 months, K. kingae was the organism identified in 47.6% of infections. We found the average age from the collated studies to be 17.73 months. Of 520 pediatric musculoskeletal patients in which K. kingae infections were identified and where the studies reported the sites of infection, a large proportion of cases (65%) were joint infections. This was followed by 18.4% osteoarticular infection (concomitant bone and joint involvement), with isolated bone and spine at 11.9% and 3.5%, respectively. Twenty-one papers reported clinical and laboratory findings in children with confirmed K. kingae infection. The median temperature reported at admission was 37.9°C and mean was 38.2°C. Fourteen studies reported on impact and treatment, with the majority of children experiencing good clinical outcome and function following antibiotic treatment with no serious orthopaedic sequelae.

Sonography of musculoskeletal infection in children.

Musculoskeletal infection, especially in young children, often presents with non-specific clinical signs and symptoms necessitating early imaging to identify the source of infection. While MRI is the investigation of choice to demonstrate bone infection, it is expensive and often requires a general anaesthetic in the young child. Ultrasound can be a useful tool in the initial assessment due to its easy availability and portable equipment. It does not involve ionising radiation and is used to guide aspiration and drainage procedures. This review explains sonographic features of septic arthritis, osteomyelitis, pyomyositis and soft tissue infection in children and highlights advantages and limitations of sonography when assessing the child with suspected musculoskeletal infection.

Comparison of Musculoskeletal Infections due to Nontyphoidal Salmonella Species and Staphylococcus aureus in Immunocompetent Children.

Nontyphoidal Salmonella species (NTS) rarely cause musculoskeletal infections in healthy children. Data on NTS musculoskeletal infections in healthy children are limited. No previous studies have directly compared children with NTS musculoskeletal infections with those with Staphylococcus aureus. This was a case-control study of children 30 days-18 years old seen at Texas Children's Hospital between 2010 and 2017 with NTS musculoskeletal infections. Controls were children with S. aureus musculoskeletal infections matched on date of infection. Patients with known predisposing conditions were excluded. Demographic and clinical risk factors between the 2 groups were compared. From 2010 to 2017, 27 cases of NTS musculoskeletal infections were identified, 12 (46.0%) of which occurred in healthy children. The control group had 53 patients. Predictors of NTS musculoskeletal infections included exposure to reptiles [odds ratio (OR) 8.50, 95% confidence interval (CI): 11.24-58.23] and preceding gastrointestinal symptoms (OR 5.63, 95% CI: 1.45-21.89). Children with NTS musculoskeletal infections had greater odds of pelvic and/or spinal involvement than S. aureus controls (OR 5.32, 95% CI: 1.42-20.13). Complications occurred in 16.7% of NTS cases versus 32% of S. aureus controls. Healthy children with NTS musculoskeletal infections more frequently report reptile exposure and preceding gastrointestinal symptoms and have pelvic and spinal involvement compared with children with musculoskeletal infections due to S. aureus. NTS should be considered as a potential cause of musculoskeletal infections in children with these risk factors. In contrast to previous case reports and case series, children with NTS musculoskeletal infections had a low rate of complications.

Managing of musculoskeletal infections in children.

Epidemiological features of musculoskeletal infections are in continuous evolution. The incidence of emerging causative pathogen is arising. Nevertheless, up to 50% of osteoarticular infections shows negative cultures. Septic arthritis, with or without concurrent osteomyelitis, are most common in newborn while osteomyelitis frequently affects older patients. We retrospectively analyzed all the children affected by musculoskeletal infections treated at the Children's Hospital Bambino Gesù in ten years, focusing on the results of an early diagnostic and therapeutic management. The study population consists of 150 children with acute septic arthritis, osteomyelitis and discitis, treated from 2006 to 2016, excluding patients with less than 12 months of follow-up and previous treatment sustained in others hospitals. A wide spectrum of data has been extracted from clinical charts, laboratory studies and imaging. Patients were categorized into 3 groups on the base of their age. The diagnostic and therapeutic protocol consisted of intravenous empirical treatment while diagnosis was ongoing then switched to oral treatment, according to the pathogen and the systemic symptoms. Only 31% of pathogens were identified. The most common was Staphylococcus aureus methicillin-sensible (MSSA) but an increase of cases caused by Kingella Kingae and Staphylococcus aureus methicillin-resistant (MRSA) was observed. The mean antibiotic treatment was 6.8 weeks. It's important to underline a significant correlation between age and C-reactive protein serum levels. Among others frequent pathogens, MRSA shows a high rate of physis involvement. Musculoskeletal infections represent a challenge in skeletally immature patients because of their potential severe complications. Timing of diagnosis and consequent targeted treatment is fundamental to avoid complications and functional sequelae.

Evaluation of suspected musculoskeletal infection in children over 2years of age using only fluid-sensitive sequences at MRI.

This study was conducted in order to evaluate whether an MRI protocol with only fluid-sensitive sequences can be used to evaluate for musculoskeletal (MSK) infection of the pelvis and limbs in children. This retrospective study analyzed 90 contrast-enhanced (CE) MRI studies from 88 consecutive patients (52 boys and 36 girls; mean age 9 ± 4.3years; range 2-17) that were performed for the clinical suspicion of MSK infection. Two radiologists reviewed each study twice. The initial study review included only the fluid-sensitive sequences (fluid-sensitive study); the second review, performed at least 1month later, included all sequences of the contrast-enhanced study (CE study). At each review, anatomic sites of abnormal signal and overall suspicion for infection were recorded. Cohen's kappa and percent agreement were performed to compare agreement between readers, types of studies, and clinical diagnoses. Interreader agreement for both types of studies had kappa values between 0.86 and 1. For the assessment of MSK infection, the fluid-sensitive study had 100% sensitivity and 61.3% specificity, with 84.8% interreader agreement; and the CE study had 100% sensitivity and 71.0% specificity, with 88.6% interreader agreement. All cases of septic arthritis (13 cases) and osteomyelitis (25 cases) were identified as possible infection or infection until proven otherwise (negative predictive value 100%) with 100% interreader agreement on fluid-sensitive sequences. An abbreviated MRI study using only fluid-sensitive sequences has the same high degree of sensitivity as a CE study to identify MSK infection in children and could be used to exclude septic arthritis and osteomyelitis. • MRI with only fluid-sensitive sequences can be used to evaluate for musculoskeletal infection in children.

Sequential Parenteral to Oral Clindamycin Dosing in Pediatric Musculoskeletal Infection: A Retrospective Review of 30 mg/kg/d Versus 40 mg/kg/d.

Children with musculoskeletal infection in methicillin-resistant Staphylococcus aureus (MRSA) prevalent communities are often treated with oral clindamycin. Current guidelines recommend approximately 40 mg/kg/d for MRSA infections. This study investigates the clinical practice of using 30 mg/kg/d of clindamycin as an alternative for outpatient dosing. Children with musculoskeletal infection treated with outpatient clindamycin from 2009 to 2014 were studied by retrospective review. The amount of clindamycin administered was determined from dose, interval and duration of outpatient treatment. Hospital readmission, surgeries and sequelae were assessed. Severity of illness was determined for children with osteomyelitis. The readmission rate of 25 children treated with 40 mg/kg/d was compared with that of 190 children treated with 30 mg/kg/d. The reason for readmission was evaluated to consider whether antibiotic dosing strategy was a potential factor. Among 215 children studied, the average outpatient duration of treatment was 32.8 days. There was no significant difference in the rate of readmission between dosing cohorts. Severity of illness scores (0-10 scale) was significantly higher among readmitted children with osteomyelitis (mean 9.8 ± 0.4) than among those with osteomyelitis who were not readmitted (mean 2.9 ± 3.2), P = 0.001. Sequelae were more common in the high-dose group and were noted in 3 children (12%) in that cohort compared with 6 children (3.2%) in the low-dose cohort (P > 0.05). Oral dosing of 30 mg/kg/d was effective for musculoskeletal infection in children in an MRSA prevalent community. Illness severity appeared to have greater impact on readmission and sequelae than did antibiotic dosing.

Septic Arthritis in Children: Frequency of Coexisting Unsuspected Osteomyelitis and Implications on Imaging Work-Up and Management

Osteomyelitis and septic arthritis clinically present at any age with overlapping signs and symptoms. The purposes of this study were to evaluate the demographic distribution of septic arthritis and osteomyelitis in children and to explore optimal imaging guidelines for these patients. We performed a retrospective study of children up to 18 years old who were treated for osteomyelitis or septic arthritis between January 2011 and September 2013. All patients underwent MRI without previous intervention. Studies were reviewed to determine the incidence of septic arthritis or superimposed osteomyelitis. The reference diagnosis was based on the combined review by the orthopedic surgeon and infectious disease notes, discharge summary, operative report, and MRI examination. One hundred sixty-two children who underwent 177 MRI examinations were diagnosed with acute musculoskeletal infection. One hundred three patients were included in the septic arthritis category, of whom 70 (68%) had septic arthritis with osteomyelitis. Seventy-four (42.1%) patients had isolated osteomyelitis without septic arthritis. Children under 2 years old were more likely to have septic arthritis (either isolated or with osteomyelitis) than isolated osteomyelitis compared with older children (p = 0.0003). In children who underwent MRI for suspected musculoskeletal infection, septic arthritis was more prevalent in children under the age of 2 years than in older children. However, both septic arthritis and osteomyelitis were found frequently in older children. Musculoskeletal infection imaging workup guidelines for children of all ages should address the frequent association of osteomyelitis and septic arthritis. We recommend that MRI should be used in the evaluation of suspected musculoskeletal infections in children, and the nearest joint should always be included to evaluate the extent of articular disease.

Managing musculoskeletal infections in children in the era of increasing bacterial resistance.

The continually changing spectrum of bacterial resistance in children with musculoskeletal infections underscores the importance of prompt diagnosis coupled with timely and appropriate treatment. This article focuses on two serious childhood musculoskeletal infections commonly encountered by primary care providers: acute hematogenous osteomyelitis and septic arthritis.

Diagnosis and Initial Management of Musculoskeletal Coccidioidomycosis in Children

Coccidioidomycosis is an invasive fungal infection caused by the inhalation of aerosolized spores of Coccidioides spp., which reside in the arid soil of the southwestern United States and northern Mexico. Approximately two thirds of cases are asymptomatic, and the remainder usually present with mild flu-like symptoms. Dissemination of coccidioidomycosis is rare, and can lead to extrapulmonic diseases including meningitis, osteomyelitis, and skin and soft-tissue involvement. The purpose of this study is to report our experience with musculoskeletal coccidioidomycosis in children. This was a retrospective chart review of patients with musculoskeletal infection with Coccidioides spp. at a tertiary care pediatric hospital from 1997 to 2010, identified by a search of ICD-9 codes and hospital diagnoses. Demographic and clinical data were collected from medical records, including the age of the patient, sex, white blood cell count, immunocompetence, length of stay, location of involvement, and initial treatment. In total, 20 children were identified with musculoskeletal coccidioidomycosis. The mean age was 12.3 years (range, 2 to 17 y) at time of diagnosis. Diagnostic criteria included positive imaging tests (plain film+MRI), serologic positive titers, and/or biopsy with positive cultures. The most common presenting symptom was bone pain (100%); only 3 (15%) patients had accompanying signs/symptoms of pulmonary infection. Only 2 (5%) patients had a white blood cell count >15×10/L (5%). Locations of infection included the foot (28%), knee (14%), spine (12%), forearm (10%), lower leg (6%), and other sites (30%). Fluconazole was the most common antifungal agent used (75%). Surgical intervention was required in 10 (50%) patients. This is the first series that has described musculoskeletal coccidioidomycosis exclusively in children. This study suggests that the initial presentation of this disease can be nonspecific and difficult to recognize in children. Clinicians should consider this diagnosis when faced with a musculoskeletal infection in children from the southwestern United States and northern Mexico. IV (case series).

Independent Analysis of a Clinical Predictive Algorithm to Identify Methicillin-resistant Staphylococcus aureus Osteomyelitis in Children

The number of serious, life-threatening musculoskeletal infections in children due to methicillin-resistant Staphylococcus aureus (MRSA) infections is increasing. The early identification of the bacteria causing osteomyelitis is critical to determine the appropriate antibiotic treatment. A recent study proposed a clinical algorithm to predict which infections were caused by MRSA by stratifying basic clinical values at the time of admission for children with osteomyelitis. The purpose of this study is to apply that predictive algorithm on an independent patient population to determine its wider applicability. This was a retrospective chart review at a tertiary care children's hospital. All children who were treated for a culture-positive osteomyelitis were identified over a 3-year period. The previously reported predictors, determined by multivariate regression analysis, of MRSA infection (temperature >38°C, hematocrit <34%, white blood cell count >12,000/µL, and C-reactive protein >13 mg/L) were determined for each patient. The number of positive predictors was then correlated with the percentage of cases that were MRSA positive. A total of 58 patients with culture-positive osteomyelitis were identified from 2008 to 2010. Sixteen of the infections were caused by MRSA (overall 26%). The percentage of patients with MRSA osteomyelitis according to the number of risk factors were as follows: all 4 risk factors, 50% (1 out of 2 patients); 3 risk factors, 42% (5 out of 12 patients); 2 risk factors, 21% (4 out of 19 patients); 1 risk factor, 50% (6 out of 12 patients); and 0 risk factor, 0% (0 out of 13 patients). The previously reported clinical predictive algorithm had a relatively poor diagnostic performance in this independent patient population. Specifically, the percentages of MRSA were the same for 1 risk factor compared with 4 (50%). Differences in bacteria strain, host responses, and a variety of other confounding variables could be responsible for these differences. Specific genetic markers may be the best early test to identify MRSA infections in the future. Level III-case-control series.

Imaging Pediatric Musculoskeletal Infection

Imaging of musculoskeletal infections in children often differs from that of adults because of several factors, including inability to localize disease, potential need for sedation, and transphyseal spread of infection in infants. In addition, the rise of community-associated methicillin-resistant Staphylococcus aureus has increased the use of advanced imaging techniques because of its association with increased complication rates. We present the different types of imaging modalities with their respective advantages and disadvantages and also the imaging findings unique to pediatric patients.

Clinical impact of gadolinium in the MRI diagnosis of musculoskeletal infection in children

Clinical impact of gadolinium in the MRI diagnosis of musculoskeletal infection in children

Serious musculoskeletal infections in children receiving anti-tumor necrosis factor-α therapy: a case series

Anti-tumor necrosis factor-alpha (anti-TNF-alpha) agents are widely used to treat children with juvenile idiopathic arthritis (JIA) whose disease is resistant to conventional therapy. Although generally well tolerated, use of these agents has been associated with an increased risk of infection. In particular, in patients treated with anti-TNF-alpha agents, there is an increased susceptibility to infection by intracellular organisms such as tuberculosis, and common infections may present atypically or be more severe. We report four cases of serious musculoskeletal infections among 31 children with JIA being treated with anti-TNF-alpha agents, two of which were secondary to group A beta-hemolytic Streptococcus.

Clinical impact of gadolinium in the MRI diagnosis of musculoskeletal infection in children

The incremental value of gadolinium in the diagnosis of musculoskeletal infection by MRI is controversial. To compare diagnostic utility of noncontrast with contrast MRI in the evaluation of pediatric musculoskeletal infections. We reviewed 90 gadolinium-enhanced MRIs in children with suspected musculoskeletal infection. Noncontrast and contrast MRI scans were evaluated to determine sensitivity and specificity in the diagnosis of musculoskeletal infection and identification of abscesses. Pre- and post-contrast diagnosis of osteomyelitis sensitivity was 89% and 91% (P = 1.00) and specificity was 96% and 96% (P = 1.00), respectively; septic arthritis sensitivity was 50% and 67% (P = 1.00) and specificity was 98% and 98% (P = 1.00), respectively; cellulitis/myositis sensitivity was 100% and 100% (P = 1.00) and specificity was 84% and 88% (P = 0.59), respectively; abscess for the total group was 22 (24.4%) and 42 (46.6%), respectively (P < 0.0001). Abscesses identified only on contrast sequences led to intervention in eight additional children. No child with a final diagnosis of infection had a normal pre-contrast study. Intravenous gadolinium should not be routinely administered in the imaging work-up of nonspinal musculoskeletal infections, particularly when pre-contrast images are normal. However, gadolinium contrast significantly increases the detection of abscesses, particularly small ones that might not require surgical intervention.