Trends in congenital clubfoot prevalence and co-occurring anomalies during 1994-2021 in Denmark: a nationwide register-based study.

BACKGROUND: Congenital talipes equinovarus (clubfoot) is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. Herein, we used publicly available data to ascertain liveborn infants with clubfoot delivered in Denmark during 1994-2021, and to classify co-occurring congenital anomalies, estimate annual prevalence, and compare clubfoot occurrence with maternal smoking rates, a commonly reported risk factor. Characterizing this nationwide, liveborn cohort provides a population-based resource for etiopathogenic investigations and life course surveillance. METHODS: This case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,315,282 liveborn infants delivered during 1994-2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources. RESULTS: Infants most often presented with nonsyndromic clubfoot (isolated = 88.6%; MCA = 11.4%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45-1.58) for isolated and 0.19 (CI 0.17-0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained relatively stable during the study period, despite marked decreases in population-based maternal smoking rates. CONCLUSIONS: From 1994 to 2021, prevalence of nonsyndromic clubfoot in Denmark was relatively stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates, providing some support for the suspected multifactorial etiopathogenesis of this anomaly. This nationwide, liveborn cohort, ascertained and clinically characterized using publicly available data from the Danish Biobank Register, provides a population-based clinical and biological resource for future etiopathogenic investigations and life course surveillance.

Plate-assisted bone-segment transport in the femur with 2 internal lengthening nails: a technical note and a case report.

A novel technique to resolve large bone defects, using 2 internal lengthening nails (ILNs), one antegrade and one retro-grade, aligned in a custom-made tube is presented. A 28-year-old, healthy, asymptomatic male presented with a slowly growing mass in the left femur.

Pretreatment Plasma IL-6 and YKL-40 and Overall Survival after Surgery for Metastatic Bone Disease of the Extremities.

BACKGROUND: Plasma IL-6 and YKL-40 are prognostic biomarkers for OS in patients with different types of solid tumors, but they have not been studied in patients before surgery of metastatic bone disease (MBD) of the extremities. The aim was to evaluate the prognostic value of plasma IL-6 and YKL-40 in patients undergoing surgery for MBD of the extremities. PATIENTS AND METHODS: A prospective study included all patients undergoing surgery for MBD in the extremities at a tertiary referral center during the period 2014-2018. Preoperative blood samples from index surgery were included. IL-6 and YKL-40 concentrations in plasma were determined by commercial ELISA. A total of 232 patients (median age 66 years, IQR 58-74; female 51%) were included. RESULTS: Cox regression analysis was performed to identify independent prognostic factors for OS. IL-6 correlated with YKL-40 (rho = 0.46, p < 0.01). In univariate analysis (log2 continuous variable) IL-6 (HR = 1.26, 95% CI 1.16-1.37), CRP (HR = 1.20, 95% CI 1.12-1.29) and YKL-40 (HR = 1.25, 95% CI 1.15-1.37) were associated with short OS. In multivariable analysis, adjusted for known risk factors for survival, only log2(IL-6) was independently associated with OS (HR = 1.24, 95% CI 1.08-1.43), whereas CRP and YKL-40 were not. CONCLUSION: High preoperative plasma IL-6 is an independent biomarker of short OS in patients undergoing surgery for MBD.

Use of endoprostheses for proximal femur metastases results in a rapid rehabilitation and low risk of implant failure. A prospective population-based study.

BACKGROUND AND OBJECTIVES: Endoprosthesis is considered a durable implant for treating metastatic bone disease of the proximal femur (MBDf). OBJECTIVES:   â€¢ What is the revision risk after surgery for MBDf using endoprosthesis versus internal fixation?• When do patients with MBDf treated with endoprosthesis restore quality of life (QoL) and how long time does it take to rehabilitate functional outcome? METHODS: A prospective, population-based, multicentre study of 110 patients. Patients were followed for a minimum of two years after surgery. No patients were lost to implant failure nor survival follow-up. RESULTS: Forty-four patients were treated with internal fixation and 66 patients received endoprostheses. Two-year implant failure risk for internal fixation was 7% (95CI: 0-14%) versus 2% (95CI: 0-5%) for endoprostheses (p = 0.058).Eq-5D improved to the same level as one month prior to surgery six-weeks after surgery, and the score improved further six months after surgery (median score from 0.603 to 0.694, p = 0.007). MSTS score increased from 12 points after surgery to 23 points six-months after surgery (p<0.001). CONCLUSIONS: Endoprosthesis for treatment of MBDf results in low implant failure rate. Patients are satisfied with the functional outcome. QoL is restored six-weeks after surgery. Authors advocate for caution using internal fixation for MBDf due to findings of a possible high early postoperative revision risk.

Multiple Fractures and Impaired Bone Fracture Healing in a Patient with Pycnodysostosis and Hypophosphatasia.

Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.

Incidence of surgical interventions for metastatic bone disease in the extremities: a population-based cohort study.

BACKGROUND: The incidence of surgery due to metastatic bone disease in the extremities (MBDex) and postoperative survival remain uninvestigated in the population. The aim of the current study was: to identify (1) incidence, demographics and survival of a population-based cohort of patients having surgery for MBDex (2) rate of referrals and referral pattern to a musculoskeletal tumour centre (MTC). MATERIAL AND METHOD: A prospective study of a consecutive population-based cohort of patients having surgery for MBDex from 2014 to 2016. Patient demographics, indication for surgery, oncological status, and postoperative survival was obtained from patient interviews, surveillance scans and patient records. RESULTS: We identified 164 patients treated for 175 bone lesions resulting in an incidence of MBDex surgery of 48.6 lesions/million inhabitants/year and a 10% risk of undergoing surgery for MBDex for every year liven with metastatic bone disease. The most common primary cancers were breast, lung, renal, prostate and myeloma. Twenty-nine lesions represented debut of cancer and 22 lesions debut of relapse of a previous cancer. Overall one-year survival was 41% (95% C.I.: 33%-48%). Fifty-nine percent of patients were referred for treatment at MTC. Patients referred had better prognostic baseline characteristic than patients treated at secondary surgical centres (SSC) (lower ASA score (p < .001), no visceral metastasis (p < .001), lower age (p < .001) and less aggressive primary cancer (p < .001)). The one-year probability of overall survival was higher for MTC patients compared to SSC patients (p < .001). CONCLUSIONS: Present study describes a prospective population-based cohort of patients having surgery for MBDex identifying incidence and postoperative survival. Referral of patient is biased by selection where 'long-term survivors' are referred for treatment at MTC. We can, however, not exclude that treatment centre influences chance of survival after surgery for MBDex although our study was not designed to identify any potential influence.

External Validation and Optimization of the SPRING Model for Prediction of Survival After Surgical Treatment of Bone Metastases of the Extremities.

BACKGROUND: Survival predictions before surgery for metastatic bone disease in the extremities (based on statistical models and data of previous patients) are important for choosing an implant that will function for the remainder of the patient's life. The 2008-SPRING model, presented in 2016, enables the clinician to predict expected survival before surgery for metastatic bone disease in the extremities. However, to maximize the model's accuracy, it is necessary to maintain and update the patient database to refit the prediction models achieving more accurate calibration. QUESTIONS/PURPOSES: The purposes of this study were (1) to refit the 2008-SPRING model for prediction of survival before surgery for metastatic bone disease in the extremities with a more modern cohort; and (2) to evaluate the performance of the refitted SPRING model in a population-based cohort of patients having surgery for metastatic bone disease in the extremities. METHODS: We produced the 2013-SPRING model by adding to the 2008-SPRING model (n = 130) a cohort of patients from a consecutive institutional database of patients who underwent surgery for bone metastases in the extremities with bone resection and reconstruction between 2009 and 2013 at a highly specialized surgical center in Denmark (n = 140). Currently the model is only available as the nomogram fully available in the current article, which is sufficient to use in daily clinical work, but we are working on making the tool available online. As such, the 2013-SPRING model was produced using a consecutive cohort of patients (n = 270) treated during an 11-year period (2003-2013) called the training cohort, all treated with bone resection and reconstruction. We externally validated the 2008-SPRING and the 2013-SPRING models in a prospective cohort (n = 164) of patients who underwent surgery for metastatic bone disease in the extremities from May 2014 to May 2016, called the validation cohort. The validation cohort was identified from a cross-section of the Danish population who were treated for metastatic lesions (using endoprostheses and internal fixation) in the extremities at five secondary surgical centers and one highly specialized surgical center. This cross-section is representative of the Danish population and no patients were treated outside the included centers as a result of public healthcare settings. The indications for surgery for training and the validation cohort were pathologic fracture, impending fracture, or intractable pain despite radiation. Exact date of death was known for all patients as a result of the Danish Civil Registration System and no loss to followup existed. In the training cohort, 150 patients (out of 270 [56%]) and in the validation cohort 97 patients (out of 164 [59%]) died of disease within 1 year postoperatively. The 2013 model did not differ from the 2008 model and included hemoglobin, complete fracture/impending fracture, visceral and multiple bone metastases, Karnofsky Performance Status, and the American Society of Anesthesiologists score and primary cancer. The models were evaluated by area under the receiver operating characteristic curve (AUC ROC) and Brier score (the lower the better). RESULTS: The 2013-SPRING model was successfully refitted with a cohort using more patients than the 2008-SPRING model. Comparison of performance in external validation between the 2008 and 2013-SPRING models showed the AUC ROC was increased by 3% (95% confidence interval [CI], 0%-5%; p = 0.027) and 2% (95% CI, 0%-4%; p = 0.013) at 3-month and 6-month survival predictions, respectively, but not at 12 months at 1% (95% CI, 0%-3%; p = 0.112). Brier score was improved by -0.018 (95% CI, -0.032 to -0.004; p = 0.011) for 3-month, -0.028 (95% CI, -0.043 to -0.0123; p < 0.001) for 6-month, and -0.014 (95% CI, -0.025 to -0.002; p = 0.017) for 12-month survival prediction. CONCLUSIONS: We improved the SPRING model's ability to predict survival after surgery for metastatic bone disease in the extremities. As such, the refitted 2013-SPRING model gives the surgeon a tool to assist in the decision-making of a surgical implant that will serve the patient for the remainder of their life. The 2013-SPRING model may provide increased quality of life for patients with bone metastasis because potential implant failures can be minimized by precise survival prediction preoperatively and the model is freely available and ready to use from the current article. LEVEL OF EVIDENCE: Level I, diagnostic study.

Prognostic value of biochemical variables for survival after surgery for metastatic bone disease of the extremities.

BACKGROUND AND OBJECTIVE: Prediction of survival in patients having surgery for metastatic bone disease in the extremities (MBDex) has been of interest in more than two decades. Hitherto no consensus on the value of biochemical variables has been achieved. Our purpose was (1) to investigate if standard biochemical variables have independent prognostic value for survival after surgery for MBDex and (2) to identify optimal prognostic cut off values for survival of biochemical variables. METHODS: In a consecutive cohort of 270 patients having surgery for MBDex, we measured preoperative biochemical variables: hemoglobin, alkaline phosphatase, C-reactive protein and absolute, neutrophil and lymphocyte count. ROC curve analyses were performed to identify optimal cut off levels. Independent prognostic factors for variables were addressed with multiple Cox regression analyses. RESULTS: Optimal cut off levels were identified as: hemoglobin 7.45 mmol/L, absolute lymphocyte count 8.5 × 109 /L, neutrophil 5.68 × 109 /L, lymphocyte 1.37 × 109 /L, C-reactive protein 22.5 mg/L, and alkaline phosphatase 129 U/L. Regression analyses found alkaline phosphatase (HR 2.49) and neutrophil count (HR 2.49) to be independent prognostic factors. CONCLUSIONS: We found neutrophil count and alkaline phosphatase to be independent prognostic variables in predicting survival in patients after surgery for MBDex.

Extent of Surgery Does Not Influence 30-Day Mortality in Surgery for Metastatic Bone Disease: An Observational Study of a Historical Cohort.

Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent of the surgery and thus the surgical trauma reduces survival in this patient group. We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton. We retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss), demographic (age, gender, American Society of Anesthesiologist score [ASA score], and Karnofsky score), and disease-specific (primary cancer) variables. An association with 30-day mortality was addressed using univariate and multivariable analyses and calculation of odds ratio (OR). All patients were included in the analysis. ASA score 3 + 4 (OR 4.16 [95% confidence interval, CI, 1.80-10.85], P = 0.002) and Karnofsky performance status below 70 (OR 7.34 [95% CI 3.16-19.20], P < 0.001) were associated with increased 30-day mortality in univariate analysis. This did not change in multivariable analysis. No parameters describing the extent of the surgical trauma were found to be associated with 30-day mortality. The 30-day mortality in patients undergoing surgery for MBD is highly dependent on the general health status of the patients as measured by the ASA score and the Karnofsky performance status. The extent of surgery, measured as duration of surgery, blood loss, and degree of bone resection were not associated with 30-day mortality.

[Organisation and reimbursement of surgical practice in Denmark 2004-2008]. / Udvikling og afregningsmønster for kirurgi i privat og offentligt sygehusregi i Danmark 2004-2008.

INTRODUCTION: The organisation and the reimbursement pattern for surgery in Denmark are relatively unknown. MATERIAL AND METHODS: The organisation and activity of hip and knee replacement, laparoscopic cholecystectomy and inguinal herniotomy, low-back surgery and obesity surgery were analysed together with the surgery reimbursement pattern in Denmark in the 5-year period 2004-2008 based on national register data. RESULTS: During the 4-year period 2004-2007 activity rose for all types of surgery, except laparoscopic cholecystectomy. A predominant part of the increased activity was seen within the private sector, especially in obesity and low-back surgery. A predominant part of the activity in the private sector was financed via public sector funding. CONCLUSION: The results show increased surgical activity in five common operations and call for intensified monitoring of activity and quality to secure research and further development on a nationwide basis.

[Bacterial pyomyositis in a 12-year-old girl without fever]. / Pyomyositis uden feber hos 12-årig pige.

Bacterial pyomyositis is generally found in tropical countries. This case report presents pyomyositis in a 12-year-old girl who was admitted without fever to the paediatric department. The only symptom was pain in the left hip. Staphylococcus aureus was cultured from the blood on day 4. Magnetic resonance imaging (MRI) revealed infection in the left m. ileopsoas. Previous ultrasound, computerised tomography, x-ray and bone-scintigraphy were normal. After 11 days of intravenous antibiotic therapy and clinical remission, secondary bone affection was detected by a new MRI. Long-term antibiotic treatment is required in such cases because of the risk of secondary bone affection. This patient was treated for 11 days with intravenous antibiotic therapy and for the subsequent three months with tablets.

[Primary synovial sarcoma in the groin]. / Primaert synovialt sarkom i ingvinalregionen.

This is a case report of a rare case of primary synovial sarcoma in the groin. A 19-year old male was admitted with a mass in his left inguinal region suspecting an inguinal hernia. He had been aware of the swelling for 10 years but only experienced pain during the previous few months when the mass had grown. Excision took place, but microscopy showed synovial sarcoma. PET/MR scan showed no signs of dissemination. Wide surgical excision was undertaken, followed by adjuvant radiation treatment. The case illustrates possible differential diagnoses before the treatment of an apparent inguinal hernia.