Primary arthrodesis versus open reduction and internal fixation following intra-articular calcaneal fractures: a weight-bearing CT analysis.

PURPOSE: To compare primary arthrodesis (PA) versus open reduction and internal fixation (ORIF) in displaced intra-articular calcaneal fractures (DIACFs), based on clinical outcome and 2D and 3D geometrical analyses obtained from weight-bearing (WB) cone-beam CT images. MATERIALS AND METHODS: In this prospective study, 40 patients with surgically treated calcaneal fractures were included, consisting of 20 PA and 20 ORIF patients. Weight-bearing cone-beam CT-images of the left and right hindfoot and forefoot were acquired on a Planmed Verity cone-beam CT-scanner after a minimum of 1-year follow-up. Automated 2D and 3D geometric analyses, i.e., (minimal and average) talo-navicular joint space, calcaneal pitch (CP), and Meary's angle (MA), were obtained for injured and healthy feet. Clinical outcomes were measured using the EQ5D and FFI questionnaires. RESULTS: Overall, there were no differences in baseline patient characteristics apart from age (p < 0.005). The calcaneal pitch in 2D after treatment by ORIF (13.8° ± 5.6) was closer to the uninjured side (18.1° ± 5.5) compared to PA (10.9° ± 4.5) (p < 0.001). Meary's angle in 2D was closer to the uninjured side (8.7° ± 6.3) after surgery in the PA cohort (7.0° ± 5.8) compared to the ORIF cohort (15.5° ± 5.9) (p = 0.046). In 3D measurements, CP was significantly decreased for both cohorts after surgery (- 4.09° ± 6.2) (p = 0.001). MA was not significantly affected overall or between cohorts in 3D. Clinical outcomes were not significantly different between the ORIF and PA cohorts. None of the radiographic measurements in 2D or 3D correlated with any of the clinical outcomes studied. CONCLUSION: Three-dimensional WB CT imaging enables functional 2D and 3D analyses under natural load in patients with complex calcaneal fractures. Based on clinical outcome, both PA and ORIF appear viable treatment options. Clinical correlation with geometrical outcomes remains to be established.

Load-induced deformation of the tibia and its effect on implant loosening detection.

CT imaging under external valgus and varus loading conditions and consecutive image analysis can be used to detect tibial implant loosening after total knee arthroplasty. However, the applied load causes the tibia to deform, which could result in an overestimation of implant displacement. This research evaluates the extent of tibia deformation and its effect on measuring implant displacement. Ten cadaver specimen with TKA were CT-scanned under valgus/varus loading (20 Nm), first implanted without bone cement fixation (mimicking a loose implant) and subsequently with bone cement fixation (mimicking a fixed implant). By means of image analysis, three relative displacements were assessed: (1) between the proximal and distal tibia (measure of deformation), (2) between the implant and the whole tibia (including potential deformation effect) and (3) between the implant and the proximal tibia (reduced deformation effect). Relative displacements were quantified in terms of translations along, and rotations about the axes of a local coordinate system. As a measure of deformation, the proximal tibia moved relative to the distal tibia by, on average 1.27 mm (± 0.50 mm) and 0.64° (± 0.25°). Deformation caused an overestimation of implant displacement in the cemented implant. The implant displaced with respect to the whole tibia by 0.45 mm (± 0.22 mm) and 0.79° (± 0.38°). Relative to the proximal tibia, the implant moved by 0.23 mm (± 0.10 mm) and 0.62° (± 0.34°). The differentiation between loose and fixed implants improved when tibia deformation was compensated for by using the proximal tibia rather than the whole tibia.

The association between echogenicity and progression of Dupuytren's disease (DD): Birth of an imaging biomarker?

BACKGROUND: The shift of focus towards disease-controlling treatments to prevent DD progression at an early stage underlines the need for objective and reliable measurements that can monitor and predict the course of disease. Ultrasound has been studied as a potential tool for this purpose. This study examined to what extent echogenicity of early DD nodules predicts clinical progression. METHODS: Sonographic assessments of Dupuytren's nodules were performed by the same observer on 151 participants as part of an ongoing prospective cohort study on the course of DD. Echogenicity was assessed by determining the greyness of a nodule relative to the surrounding tissue, using ImageJ software. Progression of disease was defined as 1) an increase in total passive extension deficit (TPED) of ≥15 degrees and 2) surgical intervention of the examined ray, both occurring after the sonographic assessment. The associations between echogenicity and time to progression were estimated using Cox-regression models. RESULTS: The association between echogenicity and time to TPED progression showed that for every additional decrease of 1% in relative greyness (darker image) of a nodule, the risk of TPED progression during follow-up increases by 3.4% (hazard ratio [HR] = 0.966, 95% confidence interval [CI]: 0.935-0.966). Similarly, echogenicity was also associated with time to surgical intervention (HR = 0.967, 95% CI: 0.938-0.997), which indicates a higher risk for surgery during follow-up for darker nodules. CONCLUSIONS: These results suggest that echogenicity is predictive of the prognosis of the early stages of DD and might potentially be used as a prognostic imaging biomarker in the future.

Sub-calcaneal plantar fat pad assessment using dual-energy computed tomography: First experience in the diabetic foot.

BACKGROUND: This study assessed the use of dual-energy computed tomography (CT) to evaluate sub-calcaneal plantar fat pad changes in people with diabetic neuropathy. METHODS: Dual-energy CT scans of people with diabetic neuropathy and non-diabetic controls were retrospectively included. Average CT values (in Hounsfield Units) and thickness (in centimeters) of the sub-calcaneal plantar fat pad were measured in mono-energetic images at two energy levels (40 keV and 70 keV). The CT values measured in patients with diabetic neuropathy were correlated to barefoot plantar pressure measurements performed during walking in a clinical setting. FINDINGS: Forty-five dual-energy CT scans of people with diabetic neuropathy and eleven DECT scans of non-diabetic controls were included. Mean sub-calcaneal plantar fat pad thickness did not significantly differ between groups (diabetes group 1.20 ± 0.34 cm vs. control group 1.21 ± 0.28 cm, P = 0.585). CT values at both 40 keV (-34.7 ± 48.7 HU vs. -76.0 ± 42.8 HU, P = 0.013) and 70 keV (-11.2 ± 30.8 HU vs. -36.3 ± 27.2 HU, P = 0.017) were significantly higher in the diabetes group compared to controls, thus contained less fatty tissue. This elevation was most apparent in patients with Type 1 diabetes. CT values positively correlated with the mean peak plantar pressure. INTERPRETATION: Dual-energy CT was able to detect changes in the plantar fat pad of people with diabetic neuropathy.

The efficacy of flexor tenotomy to prevent recurrent diabetic foot ulcers (DIAFLEX trial): Study protocol for a randomized controlled trial.

Foot ulcers are a frequent and costly problem in people with diabetes mellitus and can lead to amputations. Prevention of these ulcers is therefore of paramount importance. Claw/hammer toe deformities are commonly seen in people with diabetes. These deformities increase the risk of ulcer development specifically at the (tip of) the toe. Percutaneous needle tenotomy of the tendon of the m. flexor digitorum longus (tendon tenotomy) can be used to reduce the severity of claw/hammer toe deformity with the goal to prevent ulcer recurrence. The main objective of this randomized controlled trial is to assess the efficacy of flexor tenotomy to prevent recurrence of toe ulcers in people with diabetes and a history of toe (pre-)ulcers. Additionally, we aim to assess interphalangeal joints (IPJ) and metatarsophalangeal joint (MTPJ) angles in a weight-bearing and non-weight-bearing position, barefoot plantar pressure during walking, cost-effectiveness and quality of life before and after the intervention and compare intervention and control study groups. Sixty-six subjects with diabetes and claw/hammer toe deformity and a recent history of (pre-)ulceration on the tip of the toe will be included and randomized between flexor tenotomy of claw/hammer toes (intervention) versus standard of care including orthosis and shoe offloading (controls) in a mono-center randomized controlled trial. Clinicaltrialsgov registration: NCT05228340.

Anti-high-mobility group box-1 treatment strategies improve trauma-induced coagulopathy in a mouse model of trauma and shock.

BACKGROUND: Trauma-induced coagulopathy is associated with platelet dysfunction and contributes to early mortality after traumatic injury. Plasma concentrations of the damage molecule high-mobility group box-1 (HMGB-1) increase after trauma, which may contribute to platelet dysfunction. We hypothesised that inhibition of HMGB-1 with a monoclonal antibody (mAb) or with recombinant thrombomodulin (rTM) improves trauma-induced coagulopathy in a murine model of trauma and shock. METHODS: Male 129S2/SvPasOrlRJ mice were anaesthetised, mechanically ventilated, and randomised into five groups: (i) ventilation control (VENT), (ii) trauma/shock (TS), (iii) TS+anti-HMGB-1 mAb (TS+AB), (iv) TS+rTM (TS+TM), and (v) TS+anti-HMGB-1 mAb+rTM (TS+COMBI). Primary outcome was rotational thromboelastometry EXTEM. Secondary outcomes included tail bleeding time, platelet count, plasma HMGB-1 concentration, and platelet activation. RESULTS: Trauma and shock resulted in a hypocoagulable thromboelastometry profile, increased plasma HMGB-1, and increased platelet activation markers. TS+AB was associated with improved clot firmness after 5 min compared with TS (34 [33-37] vs 32 [29-34] mm; P=0.043). TS+COMBI was associated with decreased clot formation time (98 [92-125] vs 122 [111-148] s; P=0.018) and increased alpha angle (77 [72-78] vs 69 [64-71] degrees; P=0.003) compared with TS. TS+COMBI also reduced tail bleeding time compared with TS (P=0.007). The TS+TM and TS+COMBI groups had higher platelet counts compared with TS (P=0.044 and P=0.041, respectively). CONCLUSIONS: Inhibition of HMGB-1 early after trauma in a mouse model improves clot formation and strength, preserves platelet count, and decreases bleeding time.

Preliminary evaluation of dual-energy CT to quantitatively assess bone marrow edema in patients with diabetic foot ulcers and suspected osteomyelitis.

OBJECTIVES: The purpose of this study is to evaluate the value of dual-energy CT (DECT) with virtual non-calcium (VNCa) in quantitatively assessing the presence of bone marrow edema (BME) in patients with diabetic foot ulcers and suspected osteomyelitis. METHODS: Patients with a diabetic foot ulcer and suspected osteomyelitis that underwent DECT (80 kVp/Sn150 kVp) with VNCa were retrospectively included. Two observers independently measured CT values of the bone adjacent to the ulcer and a reference bone not related to the ulcer. The patients were divided into two clinical groups, osteomyelitis or no-osteomyelitis, based on the final diagnosis by the treating physicians. RESULTS: A total of 56 foot ulcers were identified of which 23 were included in the osteomyelitis group. The mean CT value at the ulcer location was significantly higher in the osteomyelitis group (- 17.23 ± 34.96 HU) compared to the no-osteomyelitis group (- 69.34 ± 49.40 HU; p < 0.001). Within the osteomyelitis group, the difference between affected bone and reference bone was statistically significant (p < 0.001), which was not the case in the group without osteomyelitis (p = 0.052). The observer agreement was good for affected bone measurements (ICC = 0.858) and moderate for reference bone measurements (ICC = 0.675). With a cut-off value of - 40.1 HU, sensitivity was 87.0%, specificity was 72.7%, PPV was 69.0%, and NPV was 88.9%. CONCLUSION: DECT with VNCa has a potential value for quantitatively assessing the presence of BME in patients with diabetic foot ulcers and suspected osteomyelitis. KEY POINTS: • Dual-energy CT (DECT) with virtual non-calcium (VNCa) is promising for detecting bone marrow edema in the case of diabetic foot ulcers with suspected osteomyelitis. • DECT with VNCa has the potential to become a more practical alternative to MRI in assessing the presence of bone marrow edema in suspected osteomyelitis when radiographs are not sufficient to form a diagnosis.

Metatarsophalangeal and interphalangeal joint angle measurements on weight-bearing CT images.

BACKGROUND: The aim of this study was to present and evaluate methods of measuring toe joint angels using joint-surface based and inertial axes approaches. METHODS: Nine scans of one frozen human cadaveric foot were obtained using weight-bearing CT. Two observers independently segmented bones in the forefoot and measured metatarsalphalangeal joint (MTPJ) angles, proximal and distal interphalangeal joint (PIPJ and DIPJ) angles and interphalangeal angles of the hallux (IPJ) using 1) inertial axes, representing the long anatomical axes, of the bones and 2) axes determined using centroids of articular joint surfaces. RESULTS: The standard deviations (SD) of the IPJ/PIPJ and DIPJ angles were lower using joint-surface based axes (between 1.5˚ and 4.1˚) than when the inertial axes method was used (between 3.3˚ and 16.4˚), for MTPJ the SD's were similar for both methods (between 0.5˚ and 2.6˚). For the IPJ/PIPJ and DIPJ angles, the width of the 95% CI and the range were also lower using the joint-surface axes method (95% CI: 2.0˚-4.1˚ vs 3.2˚-16.3˚; range: 3.1˚-7.4˚ vs 3.8˚-35.8˚). Intra-class correlation coefficients (ICC) representing inter- and intra-rater reliability were good to excellent regarding the MTPJ and IPJ/PIPJ angles in both techniques (between 0.85 and 0.99). For DIPJ angles, ICC's were good for the inertial axes method (0.78 and 0.79) and moderate for the joint-surface axes method (0.60 and 0.70). CONCLUSION: The joint-surface axes method enables reliable and reproducible measurements of MTPJ, IPJ/PIPJ and DIPJ angles. For PIPJ and DIPJ angles this method is preferable over the use of inertial axes.

Assessment of foot deformities in individuals with cerebral palsy using weight-bearing CT.

OBJECTIVE: The aims of this study were to visualize and quantify relative bone positions in the feet of individuals with cerebral palsy (CP) with a foot deformity and compare bone positions with those of typically developed (TD) controls. MATERIALS AND METHODS: Weight-bearing CT images of 14 individuals with CP scheduled for tendon transfer and/or bony surgery and of 20 TD controls were acquired on a Planmed Verity WBCT scanner. Centroids of the navicular and calcaneus with respect to the talus were used to quantify foot deformities. All taluses were aligned and the size and dimensions of the individuals' talus were scaled to correct for differences in bone sizes. In order to visualize and quantify variations in relative bone positions, 95% CI ellipsoids and standard deviations in its principle X-, Y-, and Z-directions were determined. RESULTS: In individuals with CP (age 11-17), a large variation in centroid positions was observed compared to data of TD controls. Radiuses of the ellipsoids, representing the standard deviations of the 95% CI in the principle X-, Y-, and Z-directions, were larger in individuals with CP compared to TD controls for both the calcaneus (3.16 vs 1.86 mm, 4.26 vs 2.60 mm, 9.19 vs 3.60 mm) and navicular (4.63 vs 1.55 mm, 5.18 vs 2.10 mm, 16.07 vs 4.16 mm). CONCLUSION: By determining centroids of the calcaneus and navicular with respect to the talus on WBCT images, normal and abnormal relative bone positions can be visualized and quantified in individuals with CP with various foot deformities.

Percutaneous cryoablation: a novel treatment option in non-visceral metastases of the abdominal cavity after prior surgery.

PURPOSE: To assess the primary safety and oncological outcome of percutaneous cryoablation in patients with non-visceral metastases of the abdominal cavity after prior surgery. METHODS: All patients with non-visceral metastases after prior abdominal surgery, treated with percutaneous cryoablation, and at least one year of follow-up were retrospectively identified. Technical success was achieved if the ice-ball had a minimum margin of 10 mm in three dimensions on the per-procedural CT images. Complications were recorded using the Society of Interventional Radiology (SIR) classification system. Time until disease progression was monitored with follow-up CT and/or MRI. Local control was defined as absence of recurrence at the site of ablation. RESULTS: Eleven patients underwent cryoablation for 14 non-visceral metastases (mean diameter 20 ± 9 mm). Primary tumor origin was renal cell (n = 4), colorectal (n = 3), granulosa cell (n = 2), endometrium (n = 1) and appendix (n = 1) carcinoma. Treated metastases were localized retroperitoneal (n = 8), intraperitoneal (n = 2), or in the abdominal wall (n = 4). Technical success was achieved in all procedures. After a median follow-up of 27 months (12-38 months), all patients were alive. Local control was observed in 10/14 non-visceral metastases, and the earliest local progression was detected after ten months. No major adverse events occurred. One patient suffered a minor asymptomatic adverse event. CONCLUSION: This proof-of-concept study suggests that cryoablation can be a minimal invasive treatment option in a selected group of patients with non-visceral metastases in the abdominal cavity after prior surgery.

Favourable Tolerability and Drug Survival of Tioguanine Versus Methotrexate After Failure of Conventional Thiopurines in Crohn's Disease.

BACKGROUND AND AIMS: Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease. METHODS: We conducted a retrospective, multicentre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure [all causes] of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of [serious] adverse events, and ongoing monotherapy. RESULTS: In total, 219 patients starting either methotrexate [n = 105] or tioguanine [n = 114] were included. In all 65 [29.7%] patients (methotrexate 43.8% [46/105 people], tioguanine 16.7% [19/114 people], p <0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, p = 0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often [methotrexate 83%, tioguanine 46%, p <0.001]. Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine [p <0.001]. CONCLUSIONS: We observed a higher cumulative discontinuation incidence due to adverse events for methotrexate [44%] compared with tioguanine [17%] in Crohn's disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, whereas serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines.

Metal artifact reduction in computed tomography: Is it of benefit in evaluating sacroiliac joint fusion?

PURPOSE: The aim of this study was to compare image quality of computed tomography (CT) images with and without orthopedic metal artifact reduction (O-MAR) in the follow-up of patients after sacroiliac (SI) joint fusion. METHODS: Thirty-six consecutive patients (31 females and 5 males) undergoing CT within 24 h after SI joint fusion were included. CT images were reconstructed with and without O-MAR and scored by two radiologists with over 20 years of experience using a six-point ordinal scale. Images were scored on overall image quality and five criteria that are important to the clinician for the follow-up of patients after SI joint fusion. In addition, images were scored on how well four bony structures could be delineated. Wilcoxon signed-ranks tests with Holm-Bonferroni correction were used to test for differences between the radiologists' scores on CT images with and without O-MAR. RESULTS: Both radiologists scored overall image quality significantly higher (p < 0.05) on the images without O-MAR than on the images with O-MAR. In addition, two of the follow-up criteria, delineation of the sacrum and delineation of the implanted ilium were scored significantly higher (p < 0.05) on the images without O-MAR. Neither radiologist scored the images with O-MAR significantly higher than the images without O-MAR for any of the criteria. CONCLUSION: CT imaging without O-MAR provided higher image quality and better assessment of SI joint fusion follow-up criteria compared to CT imaging with O-MAR in the follow-up of patients after SI joint fusion.

The effect of shock duration on trauma-induced coagulopathy in a murine model.

BACKGROUND: Trauma-induced coagulopathy (TIC) is a life-threatening condition associated with high morbidity and mortality. TIC can present with different coagulation defects. In this study, the aim was to determine the effect of shock duration on TIC characteristics. We hypothesized that longer duration of shock leads to a more hypocoagulable rotational thromboelastometry (ROTEM) profile compared to a shorter duration of shock. METHODS: Male B57BL/6J(c) mice (n = 5-10 per group) were sedated and mechanically ventilated. Trauma was induced by bilateral lower limb fractures and crush injuries to the liver and small intestine. Shock was induced by blood withdrawals until a mean arterial pressure of 25-30 mmHg was achieved. Groups reflected trauma and shock for 30 min (TS30) and trauma and shock for 90 min (TS90). Control groups included ventilation only (V90) and trauma only (T90). RESULTS: Mice in the TS90 group had significantly increased base deficit compared to the V90 group. Mortality was 10% in the TS30 group and 30% in the TS90 group. ROTEM profile was more hypocoagulable, as shown by significantly lower maximum clot firmness (MCF) in the TS30 group (43.5 [37.5-46.8] mm) compared to the TS90 group (52.0 [47.0-53.0] mm, p = 0.04). ROTEM clotting time and parameters of clot build-up did not significantly differ between groups. CONCLUSIONS: TIC characteristics change with shock duration. Contrary to the hypothesis, a shorter duration of shock was associated with decreased maximum clotting amplitudes compared to a longer duration of shock. The effect of shock duration on TIC should be further assessed in trauma patients.

Defining disease status in gastroenteropancreatic neuroendocrine tumors: Choi-criteria or RECIST?

PURPOSE: Adequate monitoring of changes in tumor load is fundamental for the assessment of the course of disease and response to treatment. There is an ongoing debate on the utility of RECIST v1.1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: In this retrospective real-life cohort study, Choi-criteria were compared with RECIST v1.1. The agreement between both criteria and the association with survival endpoints were evaluated. RESULTS: Seventy-five patients were included with a median follow-up of 35 months (range 8-53). Median progression-free survival (mPFS) according to RECIST v1.1 was 15 months (range 2-50) compared to 14 months (range 2-50) in Choi. According to RECIST, 33 (44%) patients were classified as having stable disease (SD), 40 (53%) as progressive disease (PD) and two (3%) patients as partial response (PR), compared to 9 (12%) patients classified as SD, 50 (67%) as PD and 16 (21%) as PR according to Choi-criteria. Overall concordance between the criteria was moderate (Cohen's Kappa = 0.408, p < 0.001) and agreement varied between 57 and 69% at each consecutive scan (p < 0.001). Survival analysis showed significant differences in overall survival (OS) for RECIST v1.1 categories PD and non-PD (log-rank p = 0.02), however, in Choi no significant differences in OS were found (p = 0.27). CONCLUSION: RECIST v1.1 had a better clinical utility and prognostic value compared to Choi-criteria. Still, RECIST were also not sufficient to adequately predict OS. This outlines the need for new tools that provides accurate information on the disease course and treatment response to support precise prognostication in patients with GEP-NETs.

Osteoarthritic changes in the knees of recently retired male professional footballers: a pilot study.

Background: Knee osteoarthritis (OA) is common amongst retired male professional footballers. There is limited understanding with respect to the interplay between imaging findings, clinical presentation and patient-reported outcome measures (PROMs) in retired professional footballers with knee OA. Objectives: This pilot study aimed to evaluate the extent of radiological and clinical knee OA in a cohort of retired male professional footballers, and to explore the relationship between these findings and knee-related PROMs. Methods: Fifteen retired male professional footballers underwent knee radiographs and were surveyed on their history of clinical OA, severe knee injury and previous knee surgery. The Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) were used to assess health outcomes, such as level of function and pain. Results: Radiological knee OA was diagnosed in six out of 15 participants. Seven of the participants had a clinical diagnosis of knee OA. Evidence of clinical and radiological OA was present amongst four participants. Radiological knee OA and clinical OA was significantly associated with a history of severe knee injury and previous knee surgery. Low correlations (ρ<-0.40) were found between knee OA severity and knee-related PROMs. Moderate correlation (ρ=-0.65) was found between clinical knee OA and KOOS-SP. Conclusion: Clinical knee OA correlates with PROMs amongst retired professional footballers but radiological OA does not. Further studies are required to understand the relationship between imaging findings, clinical presentation and PROMs amongst retired professional footballers with knee OA.

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Plasma and rhADAMTS13 reduce trauma-induced organ failure by restoring the ADAMTS13-VWF axis.

Trauma-induced organ failure is characterized by endothelial dysfunction. The aim of this study was to investigate the role of von Willebrand factor (VWF) and its cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) in the occurrence of endothelial permeability and organ failure in trauma. In an observational study in a level-1 trauma center, 169 adult trauma patients with clinical signs of shock and/or severe injuries were included. Trauma was associated with low ADAMTS13 and high VWF antigen levels, thus generating an imbalance of ADAMTS13 to VWF. Patients who developed organ failure (23%) had greater ADAMTS13-to-VWF imbalances, persistently lower platelet counts, and elevated levels of high-molecular-weight VWF multimers compared with those without organ failure, suggesting microthrombi formation. To investigate the effect of replenishing low ADAMTS13 levels on endothelial permeability and organ failure using either recombinant human ADAMTS13 (rhADAMTS13) or plasma transfusion, a rat model of trauma-induced shock and transfusion was used. Rats in traumatic hemorrhagic shock were randomized to receive crystalloids, crystalloids supplemented with rhADAMTS13, or plasma transfusion. A 70-kDa fluorescein isothiocyanate-labeled dextran was injected to determine endothelial leakage. Additionally, organs were histologically assessed. Both plasma transfusion and rhADAMTS13 were associated with a reduction in pulmonary endothelial permeability and organ injury when compared with resuscitation with crystalloids, but only rhADAMTS13 resulted in significant improvement of a trauma-induced decline in ADAMTS13 levels. We conclude that rhADAMTS13 and plasma transfusion can reduce organ failure following trauma. These findings implicate the ADAMTS13-VWF axis in the pathogenesis of organ failure.

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.

Predicting local tumour progression after ablation for colorectal liver metastases: CT-based radiomics of the ablation zone.

PURPOSE: To assess whether CT-based radiomics of the ablation zone (AZ) can predict local tumour progression (LTP) after thermal ablation for colorectal liver metastases (CRLM). MATERIALS AND METHODS: Eighty-two patients with 127 CRLM were included. Radiomics features (with different filters) were extracted from the AZ and a 10 mm periablational rim (PAR)on portal-venous-phase CT up to 8 weeks after ablation. Multivariable stepwise Cox regression analyses were used to predict LTP based on clinical and radiomics features. Performance (concordance [c]-statistics) of the different models was compared and performance in an 'independent' dataset was approximated with bootstrapped leave-one-out-cross-validation (LOOCV). RESULTS: Thirty-three lesions (26 %) developed LTP. Median follow-up was 21 months (range 6-115). The combined model, a combination of clinical and radiomics features, included chemotherapy (HR 0.50, p = 0.024), cT-stage (HR 10.13, p = 0.016), lesion size (HR 1.11, p = <0.001), AZ_Skewness (HR 1.58, p = 0.016), AZ_Uniformity (HR 0.45, p = 0.002), PAR_Mean (HR 0.52, p = 0.008), PAR_Skewness (HR 1.67, p = 0.019) and PAR_Uniformity (HR 3.35, p < 0.001) as relevant predictors for LTP. The predictive performance of the combined model (after LOOCV) yielded a c-statistic of 0.78 (95 %CI 0.65-0.87), compared to the clinical or radiomics models only (c-statistic 0.74 (95 %CI 0.58-0.84) and 0.65 (95 %CI 0.52-0.83), respectively). CONCLUSION: Combining radiomics features with clinical features yielded a better performing prediction of LTP than radiomics only. CT-based radiomics of the AZ and PAR may have potential to aid in the prediction of LTP during follow-up in patients with CRLM.

Geometric 3D analyses of the foot and ankle using weight-bearing and non weight-bearing cone-beam CT images: The new standard?

OBJECTIVES: We hypothesize that three-dimensional (3D) geometric analyses in weight bearing CT-images of the foot and ankle are more reproducible compared to two-dimensional (2D) analyses. Therefore, we compared 2D and 3D analyses on bones of weight-bearing and non weight-bearing cone-beam CT images of healthy volunteers. METHODS: Twenty healthy volunteers (10 male, 10 female, mean age 37.5 years) underwent weight-bearing and non weight-bearing cone-beam CT imaging of both feet. Clinically relevant height and angle measurements were performed in 2D and 3D (for example: cuboid height, calcaneal pitch, talo-calcaneal angle, Meary's angle, intermetatarsal angle). Three-dimensional measurements were obtained using automated software. Intra-observer and inter-observer agreement were evaluated for all 2D measurements. RESULTS: Overall intraclass correlation coefficients (ICC's) were higher than 0.750 for most 2D measurements, ranging from 0.352 to 0.995. Calcaneal pitch, angle between the first metatarsal (MT1) and proximal phalange 1, between the fifth metatarsal (MT5) and the calcaneus and heights of the sesamoid bones, navicular, cuboid and talus decreased during weight-bearing in both 2D and 3D results (p < 0.01). Meary's angle was not statistically different in 2D (p = 0.627) and 3D (p = 0.765). Higher coefficients of variation in 2D geometric analysis parameters (0.27 versus 0.16) indicate that 3D analyses are more precise compared to 2D (p < 0.01). Results of left and right feet are comparable for 2D and 3D analyses. CONCLUSION: Although 2D and 3D geometrical analyses are fundamentally different, automated 3D analyses are more reproducible and precise compared to 2D analyses. In addition, 3D evaluation better demonstrates differences in bone configurations between weight-bearing and non weight-bearing conditions, which may be of value to demonstrate pathology.