Preparing infection detection technology for hospital at home after lower limb external fixation.

Background: Patients with severe bone fractures and complex bone deformities are treated by orthopedic surgeons with external fixation for several months. During this long treatment period, there is a high risk of inflammation and infection at the superficial skin area (pin site). This can develop into a devastating, sometimes fatal, and always costly condition of deep bone infection. Objective: For pin site infection surveillance, thermography technology could be the solution to build an objective and continuous home-based remote monitoring tool to avoid frequent nursing care and hospital visits. However, future studies of infection monitoring require a preliminary step to automate the process of locating and detecting the pin sites in thermal images reliably for temperature measurement, and this step is the aim of this study. Methods: This study presents an automatic approach for identifying and annotating pin sites on visible images using bounding boxes and transferring them to the corresponding thermal images for temperature measurement. The pin site is detected by applying deep learning-based object detection architecture YOLOv5 with a novel loss evaluation and regression method, control distance intersection over union. Furthermore, we address detecting pin sites in a practical environment (home setting) accurately through transfer learning. Results and conclusion: The proposed model offers the pin site detection in 1.8 ms with a high precision of 0.98 and enables temperature information extraction. Our work for automatic pin site annotation on thermography paves the way for future research on infection assessment on thermography.

Do Surgeons Agree on Severity and Origin of Complications in Bone-lengthening Nails? An Inter- and Intra-rater Reliability Study.

Background: Bone-lengthening nails result in various complications with different severity and origin. However, no universal reporting system for complications has been agreed upon, making it difficult to compare different nail designs and patient populations. This study aimed to assess the inter- and intra-rater agreement of a classification system of complications according to severity and origin. Materials and methods: Four orthopaedic surgeons assessed 48 complications retrieved from patient charts in a single-centre cohort and 49 literature complications cases. Complications were classified according to severity grading (I, II, IIIA and IIIB) from Black et al. and origin with eight main types and 33 subtypes. A blinded independent assessment was performed twice at least six weeks apart. Cohen/Congers kappa estimated for the inter- and intra-rater agreement was interpreted after Svanholm et al. Results: The surgeons had a good inter-rater agreement for complication severity with a kappa value of 0.68 [95% confidence interval (CI): 0.56-0.79] and complication origin with a kappa value of 0.63 (CI: 0.53-0.73), respectively, on the cohort cases. In literature cases, a good agreement on complication severity and origin grading was shown by kappa values of 0.64 (CI: 0.53-0.75) and 0.74 (CI: 0.65-0.83). The intra-rater assessment of complication severity and origin grading had good to excellent agreement with kappa values ranging from 0.51 to 0.97. Conclusion and clinical significance: The study presents the first structured complication classification on severity and origin in intramedullary bone-lengthening nails. A good reproducibility agreement in both severity and origin was found between four orthopaedic surgeons for both cohort and literature complication cases. For clinical and research purposes, a shared language for communicating complications is essential. We encourage future studies to use a structured and validated complication classification. How to cite this article: Frost MW, Rahbek O, Fridberg M, et al. Do Surgeons Agree on Severity and Origin of Complications in Bone-lengthening Nails? An Inter- and Intra-rater Reliability Study. Strategies Trauma Limb Reconstr 2022;17(3):153-158.

Intrarater Reliability of Digital Thermography in Detecting Pin Site Infection: A Proof of Concept Study.

AIM AND OBJECTIVE: The purpose of this study was to explore the capability and Intrarater reliability of thermography in detecting pin site infection. MATERIALS AND METHODS: This is an explorative proof of concept study. Clinical assessment of pin sites was performed by one examiner with the Modified Gordon Pin Infection Classification from grade 0 to 6. Thermography of the pin sites was performed with a FLIR C3 camera. The analysis of the thermographic images was done in the software FLIR Tools. The maximum skin temperature around the pin site and the maximum temperature for the whole thermographic picture were measured. An Intrarater agreement was established and test-retests were performed with different camera angles. RESULTS: Thirteen (four females, nine males) patients (age 9-72 years) were included. Indications for frames: Fracture (n=4), two deformity correction, one lengthening and six bone transport. Days from surgery to thermography ranged from 27 to 385 days. Overall, 231 pin sites were included. Eleven pin sites were diagnosed with early signs of infection: five grade 1, five grade 2 and one grade 3. Mean pin site temperature for each patient was calculated, varied between patients from 29.0°C to 35.4°C (mean 33.9°C). With 34°C as cut-off value for infection, sensitivity was 73%; specificity, 67%; positive predictive value, 10%; and negative predictive value, 98%. Intrarater agreement for thermography was ICC 0.85 (0.77-0.92). The temperature measured was influenced by the camera positioning in relation to the pin site with a variance of 0.2. CONCLUSIONS: Measurements of pin site temperature using the hand-held FLIR C3 infrared camera was a reliable method and the temperature was related to infection grading. CLINICAL SIGNIFICANCE: This study demonstrated that digital thermography with a hand-held camera might be used for monitoring the pin sites after operations to detect early infection. HOW TO CITE THIS ARTICLE: Rahbek O, Husum HC, Fridberg M, et al. Intrarater Reliability of Digital Thermography in Detecting Pin Site Infection: A Proof of Concept Study. Strategies Trauma Limb Reconstr 2021;16(1):1-7.

Noticeable Variations in the Educational Exposure During Residency in Danish Orthopedic Departments.

OBJECTIVE: The objective of the study was to examine the educational exposure during residency in Danish orthopedic departments. DESIGN: Questionnaire-based cross-sectional study. SETTING: Data were gathered from January 1, 2014 to April 30, 2014 through a nationwide web-based questionnaire containing 15 questions within the areas of workload, surgical procedures, outpatient clinic, and research activities. The residents targeted worked at small-to-large hospitals and in tertiary care centers. PARTICIPANTS: Every resident in Denmark (n = 163) with at least 3 active months at a department was included. Questionnaires with less than 80% completion were excluded. In total, 152 entries were registered. Among those, 27 did not meet the inclusion criteria and 29 were excluded, leaving 96 participants, representing 22 of 26 departments, for further analysis. RESULTS: The average number of operative procedures as primary surgeon was 16 (range: 8-35) per month. In all, 18 of 22 (81%) departments offered the possibility to participate in research facilitated by the department and 38 of 96 (40%) worked for free (an average of 10h a month [range: 3-60]) to increase the amount of surgical procedures. CONCLUSIONS: A large variation in the educational exposure was found among the Danish orthopedic departments. Numbers indicate that Danish residents, compared with their US counterparts, operate considerably less during residency. Most residents work overtime and many of them work for free to participate in more surgical procedures.

Delineating transcriptional networks of prognostic gene signatures refines treatment recommendations for lymph node-negative breast cancer patients.

The majority of women diagnosed with lymph node-negative breast cancer are unnecessarily treated with damaging chemotherapeutics after surgical resection. This highlights the importance of understanding and more accurately predicting patient prognosis. In the present study, we define the transcriptional networks regulating well-established prognostic gene expression signatures. We find that the same set of transcriptional regulators consistently lie upstream of both 'prognosis' and 'proliferation' gene signatures, suggesting that a central transcriptional network underpins a shared phenotype within these signatures. Strikingly, the master transcriptional regulators within this network predict recurrence risk for lymph node-negative breast cancer better than currently used multigene prognostic assays, particularly in estrogen receptor-positive patients. Simultaneous examination of p16(INK4A) expression, which predicts tumours that have bypassed cellular senescence, revealed that intermediate levels of p16(INK4A) correlate with an intact pRB pathway and improved survival. A combination of these master transcriptional regulators and p16(INK4A), termed the OncoMasTR score, stratifies tumours based on their proliferative and senescence capacity, facilitating a clearer delineation of lymph node-negative breast cancer patients at high risk of recurrence, and thus requiring chemotherapy. Furthermore, OncoMasTR accurately classifies over 60% of patients as 'low risk', an improvement on existing prognostic assays, which has the potential to reduce overtreatment in early-stage patients. Taken together, the present study provides new insights into the transcriptional regulation of cellular proliferation in breast cancer and provides an opportunity to enhance and streamline methods of predicting breast cancer prognosis.

Locking plate osteosynthesis of clavicle fractures: complication and reoperation rates in one hundred and five consecutive cases.

PURPOSE: Locking plate osteosynthesis has become the preferred method for operative treatment of clavicle fractures. The method offers stable fixation, and would theoretically be associated with a low rate of fracture-related complications and reoperations. However, this remains to be explored in a large cohort, and our purpose was to assess the overall rates of complications and reoperations following locking plate osteosynthesis of mid-shaft clavicle fractures. METHODS: We identified all locking plate osteosynthesis of mid-shaft clavicle fractures operated upon in our department from January 2008 to November 2010 (n = 114). Nine patients did not attend the follow-up at our institution. The study group of 105 fractures (104 patients, 86 males) had a median age of 36 years (14-75 years). Follow-up ranged from 0.5 to 3.5 years. No patients were allowed to load the upper extremity for six weeks. By studying patient files and radiographic material, we assessed complications and reoperations. RESULTS: Overall, there were 31 cases (30 %) of plate removals for discomfort. There were five cases (5 %) of failure of osteosynthesis: two occurred early after approximately six weeks and three late after ten to 13 months postoperatively. CONCLUSION: The overall rate of failure of osteosynthesis is low (5 %). The burden of plate removals in approximately one third of patients should be included in the preoperative information.

High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma.

BACKGROUND: Malignant melanoma is the most lethal form of skin cancer with a variable clinical course even in patients with thin melanomas and localized disease. Despite increasing insights into melanoma biology, no prognostic biomarkers have yet been incorporated into clinical protocols. Reduced expression of the RNA binding motif protein 3 (RBM3) has been shown to correlate with tumour progression and poor prognosis in melanoma and several other cancer forms. In ovarian cancer, an inverse association was found between expression of RBM3 and the minichromosome maintenance 3 (MCM3) gene and protein. In melanoma, gene expression analysis and immunohistochemical validation has uncovered MCM3 as a putative prognostic biomarker. The aim of the present study was to examine the associations of MCM3 expression with clinical outcome and RBM3 expression in a prospective, population-based cohort of melanoma. METHODS: Immunohistochemical MCM3 expression was examined in 224 incident cases of primary melanoma from the Malmö Diet and Cancer Study, previously analysed for RBM3 expression. Spearman's Rho and Chi-Square tests were used to explore correlations between MCM3 expression, clinicopathological factors, and expression of RBM3 and Ki67. Kaplan Meier analysis, the log rank test, and univariable and multivariable Cox proportional hazards modelling were used to assess the impact of MCM3 expression on disease-free survival (DFS) and melanoma-specific survival (MSS). RESULTS: High MCM3 expression was significantly associated with unfavourable clinicopathological features and high Ki67 expression. A significant inverse correlation was seen between expression of MCM3 and RBM3 (p = 0.025). High MCM3 expression was associated with a reduced DFS (HR = 5.62) and MSS (HR = 6.03), and these associations remained significant in multivariable analysis, adjusted for all other factors (HR = 5.01 for DFS and HR = 4.96 for MSS). RBM3 expression remained an independent prognostic factor for MSS but not DFS in the multivariable model. CONCLUSIONS: These findings provide validation of the utility of MCM3 expression as an independent biomarker for prognostication of patients with primary melanoma. Moreover, the inverse association and prognostic impact of MCM3 and RBM3 expression indicate a possible interaction of these proteins in melanoma progression, the functional basis for which merits further study. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1814908129755401.

Modifying effect of gender on the prognostic value of clinicopathological factors and Ki67 expression in melanoma: a population-based cohort study.

BACKGROUND: Malignant melanoma is the most deadly form of skin cancer. Female sex is known to have a protective effect on incidence, tumour characteristics, and mortality from melanoma. However, the potentially modifying effect of sex on the prognostic significance of clinicopathological and investigative factors is generally not taken into consideration in biomarker studies. In this study, we compared the sex-specific distribution and prognostic value of established tumour characteristics and Ki67 expression in 255 cases of incident primary melanoma in a prospective, population-based cohort study. METHODS: The study included 255 incident cases of melanoma, 132 females and 123 males, in the Malmö Diet and Cancer Study. Tumours from 226 (88.6%) cases had been assembled in tissue microarrays. Clinicopathological factors and immunohistochemical Ki67 expression were assessed and correlated with disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier analysis, log rank test and univariable and multivariable Cox regression analyses, stratified for gender. Effect of gender on melanoma-specific survival (MSS) after first recurrence was also analysed. RESULTS: Women were significantly younger at diagnosis than men (p = 0.012). The most common tumour sites were the legs in women (37.5%) and the dorsal trunk in men (37.8%). Kaplan-Meier analysis revealed that tumour location had no prognostic impact in women, but in men, location to the frontal trunk was significantly associated with a reduced DFS compared with all other locations combined and location to the dorsal trunk was significantly associated with a prolonged OS. High Ki67 expression was significantly associated with a reduced DFS and OS in men but not in women, also when adjusted for other factors. In men, but not in women, ulceration was an independent prognostic factor for both DFS and OS. MSS after first local, regional or distant recurrence was significantly shorter for men than for women. CONCLUSIONS: The results from this study demonstrate that the prognostic value of tumour location, Ki67 expression and ulceration in melanoma differs according to gender. These findings need to be validated in future studies, as they may help improve prognostication in patients with melanoma. Moreover, our findings demonstrate that sex-stratified analyses add valuable information to biomarker studies.

Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer.

BACKGROUND: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. METHOD: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). RESULTS: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS.No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. CONCLUSIONS: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.

Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer.

BACKGROUND: The Dachshund homolog 2 (DACH2) gene has been implicated in development of the female genital tract in mouse models and premature ovarian failure syndrome, but to date, its expression in human normal and cancerous tissue remains unexplored. Using the Human Protein Atlas as a tool for cancer biomarker discovery, DACH2 protein was found to be differentially expressed in epithelial ovarian cancer (EOC). Here, the expression and prognostic significance of DACH2 was further evaluated in ovarian cancer cell lines and human EOC samples. METHODS: Immunohistochemical expression of DACH2 was examined in tissue microarrays with 143 incident EOC cases from two prospective, population-based cohorts, including a subset of benign-appearing fallopian tubes (n = 32). A nuclear score (NS), i.e. multiplier of staining fraction and intensity, was calculated. For survival analyses, cases were dichotomized into low (NS < = 3) and high (NS > 3) using classification and regression tree analysis. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the impact of DACH2 expression on survival. DACH2 expression was analysed in the cisplatin sensitive ovarian cancer cell line A2780 and its cisplatin resistant derivative A2780-Cp70. The specificity of the DACH2 antibody was tested using siRNA-mediated silencing of DACH2 in A2780-Cp70 cells. RESULTS: DACH2 expression was considerably higher in the cisplatin resistant A2780-Cp70 cells compared to the cisplatin-sensitive A2780 cells. While present in all sampled fallopian tubes, DACH2 expression ranged from negative to strong in EOC. In EOC, DACH2 expression correlated with several proteins involved in DNA integrity and repair, and proliferation. DACH2 expression was significantly higher in carcinoma of the serous subtype compared to non-serous carcinoma. In the full cohort, high DACH2 expression was significantly associated with poor prognosis in univariable analysis, and in carcinoma of the serous subtype, DACH2 remained an independent factor of poor prognosis. CONCLUSIONS: This study provides a first demonstration of DACH2 protein being expressed in human fallopian tubes and EOC, with the highest expression in serous carcinoma where DACH2 was found to be an independent biomarker of poor prognosis. Future research should expand on the role of DACH2 in ovarian carcinogenesis and chemotherapy resistance.

Immunohistochemical analyses of phosphatases in childhood B-cell lymphoma: lower expression of PTEN and HePTP and higher number of positive cells for nuclear SHP2 in B-cell lymphoma cases compared to controls.

Although many pediatric B-cell lymphoma patients are being cured today, much is still unknown about the pathogenesis of this disease. Protein tyrosine phosphatases are involved in the control of survival, growth, and differentiation of cells. The authors have analyzed 26 pediatric B-cell lymphoma cases for the expression of a panel of phosphatases and report a statistically significant lower expression intensity of PTEN and HePTP and higher nuclear SHP2 expression in B-cell lymphoma cases compared to lymphoid tissue. Knowledge about the expression of key regulatory proteins in pediatric B-cell lymphomas is necessary for revealing the complex molecular background of this disease.

Protein expression and cellular localization in two prognostic subgroups of diffuse large B-cell lymphoma: higher expression of ZAP70 and PKC-beta II in the non-germinal center group and poor survival in patients deficient in nuclear PTEN.

Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) show varying responses to conventional therapy, and this might be contributed to the differentiation stage of the tumor B-cells. The aim of the current study was to evaluate a panel of kinases (ZAP70, PKC-beta I and II and phosphorylated PKB/Akt) and phosphatases (PTEN, SHP1 and SHP2) known to be frequently deregulated in lymphoid malignancies. De novo DLBCL cases were divided into two subgroups, the germinal center (GC) group (14/28) and the non-germinal center (non-GC) or activated B-cell (ABC) group (14/28). ZAP70 and PKC-beta II were expressed in a significantly higher percentage of tumor cells in the clinically more aggressive non-GC group compared with the prognostically favourable GC group. Also, the subcellular localization of PKC-beta I and II differed in DLBCL cells, with the PKC-beta I isoform being expressed in both the cytoplasm and nucleus, while PKC-beta II was found exclusively in the cytoplasm. Loss of nuclear PTEN correlated with poor survival in cases from both subgroups. In addition, five cell lines of DLBCL origin were analyzed for protein expression and for mRNA levels of PTEN and SHP1. For the first time, we show that ZAP70 is expressed in a higher percentage of tumor cells in the aggressive non-GC subgroup of DLBCL and that PKC-beta I and II are differently distributed in the two prognostic subgroups of de novo DLBCL.

Abdominal strength after breast reconstruction using a free abdominal flap.

BACKGROUND: Today, breast reconstruction with autologous tissue is most commonly done either as a free muscle sparring TRAM flap or as a DIEP flap. Studies of donor site morbidity have shown an advantage in using the DIEP flap. However, this procedure might also be associated with an increased risk of flow related complications and it is also thought to be more demanding and time consuming. A few studies have evaluated the abdominal wall strength after dissection of a TRAM flap or a DIEP flap. However, these studies do not distinguish between the various types of free TRAM flaps and they also compare TRAM procedures preformed in an early period to DIEP procedures done in a later period. METHODS: We used an isokinetic dynamometer to measure concentric, eccentric and isometric abdominal muscle strength in 32 patients who had had a unilateral breast reconstruction with a free MS-2 (15) or a DIEP (17) flap in the year 2003. RESULTS: No significant reduction in muscle strength was observed for concentric or isometric muscle strength. However, significant lower eccentric muscle strength was found in the TRAM compared to the DIEP group (p=0.05). There was no significant difference in abdominal strength between the two flap groups at low to moderate work intensity (isometric/concentric). At the greatest work intensity (eccentric muscle strength) the patients reconstructed with a DIEP flap had a clinical small, but significant advantage over the patients reconstructed with a MS-2 TRAM flap.