Value of PET imaging for radiation therapy.

This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.

An optimized imaging protocol for [99mTc]Tc-DPD scintigraphy and SPECT/CT quantification in cardiac transthyretin (ATTR) amyloidosis.

BACKGROUND: In [99mTc]Tc-DPD scintigraphy for myocardial ATTR amyloidosis, planar images 3 hour p.i. and SPECT/CT acquisition in L-mode are recommended. This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°). METHODS: In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i. RESULTS: In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence. CONCLUSIONS: Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.

Posterior laxity increases over time after PCL reconstruction.

PURPOSE: Restoration of posterior tibial translation (PTT) after reconstruction of the posterior cruciate ligament (PCL) is deemed necessary to restore physiological knee kinematics. However, current surgical techniques have failed to show a complete reduction of posterior laxity. It was hypothesized that early postoperative PTT increases over time. METHODS: The study comprised of 46 patients (10 female, 36 male; 30 ± 9 years), who underwent PCL reconstruction in a single-surgeon series. Patients were evaluated by bilateral stress radiographs in a prospective manner preoperatively; at 3, 6, 12 and 24 months; and at a final follow-up (FFU) of at least 5 years. Covariants included age, gender, BMI, tibial slope (TS) and the number of operated ligaments. Two blinded observers reviewed all radiographs, evaluating the TS and the posterior tibial translation. RESULTS: All patients were evaluated at a mean final follow-up of 102 (range 65-187) months. Mean side-to-side difference of the PTT significantly improved from preoperative to 3-month postoperative values (10.9 ± 3.1 vs. 3.6 ± 3.8 mm; P < 0.0001). The PTT increased to 4.6 ± 3.7 mm at 6 months, to 4.8 ± 3.3 mm at 12 months, to 4.8 ± 3.2 mm at 24 months, to 5.4 ± 3.4 mm at FFU. Consequently, there was a significant increase of PTT between 3-month and final follow-up (3.6 ± 3.8 vs. 5.4 ± 3.4 mm; P = 0.02). Flattening of the TS resulted in a significantly higher PTT compared to subjects with a high TS at 24 months and FFU. There was no significant influence by BMI, age, gender and the number of operated ligaments. CONCLUSIONS: Early results after PCL reconstruction seem promising as posterior tibial translation is significantly improved. However, there is a significant increase in PTT from early postoperative values to the final follow-up of at least 5 years. This is particularly notable in patients with flattening of the TS. As a consequence, surgeons and patients need to be aware that initial posterior stability should not be equated with the final outcome. LEVEL OF EVIDENCE: Cohort study, Level III.

Assessment of the tibial slope is highly dependent on the type and accuracy of the preceding acquisition.

BACKGROUND: Precise measurement of the tibial slope (TS) is crucial for realignment surgery, ligament reconstruction, and arthroplasty. However, there is little consensus on the ideal assessment. It was hypothesized that the tibial slope changes according to the acquisition technique and both tibial length as well as femoral rotation serve as potential confounders. METHODS: 104 patients (37 women, 67 men; range 12-66 years) were retrospectively selected, of which all patients underwent a 1.5-Tesla MRI and either additional standard lateral radiographs (SLR, n = 52) or posterior stress radiographs (PSR, n = 52) of the index knee. Two blinded observers evaluated the medial tibial slope as the medial TS is primarily used in clinical practice. Additionally, the length of the diaphyseal axis and the extent of radiographic malrotation were measured. RESULTS: Mean TS on MRI was significantly lower compared to radiographs (4.2° ± 2.9° vs. 9.1° ± 3.6°; p < 0.0001). There was a significant correlation between MRI and PSR (p < 0.0001 with r = 0.7), but not with SLR (p = 0.93 with r = 0.24). Tibial length was a significant predictor for the difference between MRI and SLR (regression coefficient ß = - 0.03; p = 0.035), yet not between MRI and PSR (ß = - 0.003; p = 0.9). Femoral rotation proved to be a significant predictor for the agreement between both observers (PSR: ß = 0.14; p = 0.001 and SLR: ß = 0.08; p = 0.04). ICC indicated a high interrater agreement for the radiographic assessment (ICC ≥ 0.72). CONCLUSIONS: There is a substantial variance between MRI and radiographic measurement of the tibial slope. However, as MRI assessment is time-consuming and requires specialized software, instrumented radiographs might be an alternative. Due care has to be taken to ensure that radiographs contain a sufficient tibial length, and femoral rotation is avoided. STUDY DESIGN: Case series (diagnosis); Level of evidence, 4.

Pretherapeutic FDG-PET total metabolic tumor volume predicts response to induction therapy in pediatric Hodgkin's lymphoma.

BACKGROUND: Standardized treatment in pediatric patients with Hodgkin's lymphoma (HL) follows risk stratification by tumor stage, erythrocyte sedimentation rate and tumor bulk. We aimed to identify quantitative parameters from pretherapeutic FDG-PET to assist prediction of response to induction chemotherapy. METHODS: Retrospective analysis in 50 children with HL (f:18; m:32; median age, 14.8 [4-18] a) consecutively treated according to EuroNet-PHL-C1 (n = 42) or -C2 treatment protocol (n = 8). Total metabolic tumor volume (MTV) in pretherapeutic FDG-PET was defined using a semi-automated, background-adapted threshold. Metabolic (SUVmax, SUVmean, SUVpeak, total lesion glycolysis [MTV*SUVmean]) and heterogeneity parameters (asphericity [ASP], entropy, contrast, local homogeneity, energy, and cumulative SUV-volume histograms) were derived. Early response assessment (ERA) was performed after 2 cycles of induction chemotherapy according to treatment protocol and verified by reference rating. Prediction of inadequate response (IR) in ERA was based on ROC analysis separated by stage I/II (1 and 26 patients) and stage III/IV disease (7 and 16 patients) or treatment group/level (TG/TL) 1 to 3. RESULTS: IR was seen in 28/50 patients (TG/TL 1, 6/12 patients; TG/TL 2, 10/17; TG/TL 3, 12/21). Among all PET parameters, MTV best predicted IR; ASP was the best heterogeneity parameter. AUC of MTV was 0.84 (95%-confidence interval, 0.69-0.99) in stage I/II and 0.86 (0.7-1.0) in stage III/IV. In patients of TG/TL 1, AUC of MTV was 0.92 (0.74-1.0); in TG/TL 2 0.71 (0.44-0.99), and in TG/TL 3 0.85 (0.69-1.0). Patients with high vs. low MTV had IR in 86 vs. 0% in TG/TL 1, 80 vs. 29% in TG/TL 2, and 90 vs. 27% in TG/TL 3 (cut-off, > 80 ml, > 160 ml, > 410 ml). CONCLUSIONS: In this explorative study, high total MTV best predicted inadequate response to induction therapy in pediatric HL of all pretherapeutic FDG-PET parameters - in both low and high stages as well as the 3 different TG/TL. TRIAL REGISTRATION: Ethics committee number: EA2/151/16 (retrospectively registered).

High tibial slope correlates with increased posterior tibial translation in healthy knees.

PURPOSE: Notwithstanding the importance of the tibial slope (TS) for anterior tibial translation, little information is available regarding the implications on posterior laxity, particularly in healthy subjects. It was hypothesized that increased TS is associated with decreased posterior tibial translation (PTT) in healthy knees. METHODS: A total of 124 stress radiographs of healthy knees were enrolled in this study. Tibial slope and the posterior tibial translation were evaluated using a Telos device with a 150-N force at 90° of knee flexion. Two blinded observers reviewed independently on two different occasions. RESULTS: One hundred and twenty-four patients [35 females and 89 males; 41 (range 18-75) years] were enrolled in this study, with a mean PTT of 2.8 mm (±1.9 mm; range 0-8 mm) and a mean TS of 8.6° (±2.6°; range 1°-14°). Pearson correlation showed a significant correlation between the PTT and TS in the overall patient cohort (P < 0.0001) with r = 0.76 and R 2 = 0.58. There was no statistical difference between female and male patients regarding the PTT or the TS. Subgrouping of the patient cohort (four groups with n = 31) according to their TS (groups I < 7°; II = 7°-8.5°; III = 9°-10.5°; IV ≥ 11°) revealed significant differences between each subgroup, respectively. Furthermore, there was a weak but significant correlation between age and PTT (P = 0.004, r = 0.26). CONCLUSION: In addition to the substantial variance in tibial slope and posterior laxity among healthy knees, high tibial slope significantly correlates with increased posterior tibial translation. Increasing age is further associated with a greater magnitude of posterior tibial translation. Consequently, knowledge of the tibial slope facilitates simple estimation of posterior knee laxity, which is mandatory for PCL reconstruction and knee arthroplasty.

Individualized risk assessment in neuroblastoma: does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?

PURPOSE: Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic 123I-MIBG SPECT for individualized image-based prediction of outcome. METHODS: This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic 123I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell's C and likelihood ratio χ 2. RESULTS: Median follow-up was 36 months (range 7-107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS. CONCLUSIONS: In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy.

A randomized, double-blind, crossover comparison of novel continuous bed motion versus traditional bed position whole-body PET/CT imaging.

PURPOSE: Continuous bed motion has recently been introduced for whole-body PET/CT, and represents a paradigm shift towards individualized and flexible acquisition without the limitations of bed position-based planning. Increased patient comfort due to lack of abrupt table position changes may be another albeit still unproven advantage. For robust clinical implementation, image quality and quantitative accuracy should at least be equal to the prior standard of bed position-based step-and-shoot imaging. METHODS: The study included 68 consecutive patients referred for whole-body PET/CT for various malignancies. The patients underwent traditional step-and-shoot and novel continuous bed motion acquisition in the same session in a randomized crossover design. The patients and two independent observers were blinded to the sequence of scan techniques. Patient comfort/satisfaction was examined using a standardized questionnaire. SUVs were compared for reference tissue (liver, muscle) and tumour lesions. PET image quality and misalignment with CT images were evaluated on a scale of 1 - 4. RESULTS: Patients preferred continuous bed motion over step-and-shoot (P = 0.0001). It was considered to be more relaxing (38 % vs. 8 %), quieter (34 % vs. 8 %), and more fluid (64 % vs. 8 %). Image quality, SUV and CT misalignment did not differ between the techniques. Continuous bed motion resulted in better end-plane image quality (P < 0.0001). Regardless of the technique, second examinations had significantly higher tumour lesion SUVmax values (P = 0.0002), and a higher CT misalignment score (P = 0.0017). CONCLUSION: Oncological PET/CT with continuous bed motion enhances patient comfort and is associated with image quality at least comparable to that with traditional bed position-based step-and-shoot acquisition.qq.

Keeping Up With ChatGPT: Evaluating Its Recognition and Interpretation of Nuclear Medicine Images.

PURPOSE: The latest iteration of GPT4 (generative pretrained transformer) is a large multimodal model that can integrate both text and image input, but its performance with medical images has not been systematically evaluated. We studied whether ChatGPT with GPT-4V(ision) can recognize images from common nuclear medicine examinations and interpret them. PATIENTS AND METHODS: Fifteen representative images (scintigraphy, 11; PET, 4) were submitted to ChatGPT with GPT-4V(ision), both in its Default and "Advanced Data Analysis (beta)" version. ChatGPT was asked to name the type of examination and tracer, explain the findings and whether there are abnormalities. ChatGPT should also mark anatomical structures or pathological findings. The appropriateness of the responses was rated by 3 nuclear medicine physicians. RESULTS: The Default version identified the examination and the tracer correctly in the majority of the 15 cases (60% or 53%) and gave an "appropriate" description of the findings or abnormalities in 47% or 33% of cases, respectively. The Default version cannot manipulate images. "Advanced Data Analysis (beta)" failed in all tasks in >90% of cases. A "major" or "incompatible" inconsistency between 3 trials of the same prompt was observed in 73% (Default version) or 87% of cases ("Advanced Data Analysis (beta)" version). CONCLUSIONS: Although GPT-4V(ision) demonstrates preliminary capabilities in analyzing nuclear medicine images, it exhibits significant limitations, particularly in its reliability (ie, correctness, predictability, and consistency).

Tibial Slope on Conventional Lateral Radiographs in Anterior Cruciate Ligament-Injured and Intact Knees: Mean Value and Outliers.

BACKGROUND: An increased tibial slope (TS) has been identified as a risk factor for anterior cruciate ligament (ACL) injury and graft failure after ACL reconstruction. However, different imaging modalities are used to determine the TS, resulting in divergent values. Consequently, no reference values and no consensus on thresholds can be reached, which in turn is mandatory for indicating correction osteotomies when facing outlier TS. PURPOSE: To determine the mean values of the TS and the incidence of their outliers in large cohorts of patients with ACL-injured and noninjured knees and to determine the feasibility of measuring TS on conventional lateral radiographs (CLRs). STUDY DESIGN: Cross-sectional study; Level of evidence 3. METHODS: TS of ACL-injured knees (n = 1000, group A) and ACL-intact knees (n = 1000, group B) was measured by 3 experienced examiners. Medial TS was measured on CLRs using the technique of Dejour and Bonnin. Patients with radiographs with poor image quality, osteoarthritis, previous osteotomies, or nondigital radiographs were excluded. The intra- and interrater reliability was calculated using the intraclass correlation coefficient. RESULTS: The mean TS was significantly higher in group A than in group B (10.04°± 3° [range, 2°-22°] vs 9.02°± 2.9° [range, 1°-18°], respectively; P < .001). Significantly more participants in group A had TS larger than 12° (≥12°, 32.2% vs 19.8%, P < .001; ≥13°, 20.9% vs 11.1%, P < .001; ≥14°, 13.5% vs 5.7%, P < .001; ≥15°, 8% vs 2.7%, P < .001; ≥16°, 3.7% vs 1.4%, P = .0005), respectively. In contrast, significantly more participatns in group B had TS 8° or less (≤8°, 32.1% vs 42.7%, P < .001; ≤7°, 20% vs 30.9%, P < .001; ≤6°, 12.4% vs 19.8%, P < .001; ≤5°, 6.6% vs 12%, P = .0003; ≤4°, 2.8% vs 5.3%, P = .0045). The intraclass correlation coefficient revealed a good to excellent reliability throughout measurements. CONCLUSION: Median values for the TS were 9° for uninjured and 10° for ACL-injured knees on CLRs. Notwithstanding its statistical significance, this finding might be negligible in clinical practice. However, a significantly larger number of outliers were found in the ACL-injured group exceeding a TS of 12° and demonstrating an incremental proportion with increasing TS, serving as a potential threshold for correction osteotomy. Furthermore, CLRs in the largest cohort to date exhibited high reproducibility, proving the feasibility of CLRs as a routine measurement for TS.

ChatGPT: Can You Prepare My Patients for [18F]FDG PET/CT and Explain My Reports?

We evaluated whether the artificial intelligence chatbot ChatGPT can adequately answer patient questions related to [18F]FDG PET/CT in common clinical indications before and after scanning. Methods: Thirteen questions regarding [18F]FDG PET/CT were submitted to ChatGPT. ChatGPT was also asked to explain 6 PET/CT reports (lung cancer, Hodgkin lymphoma) and answer 6 follow-up questions (e.g., on tumor stage or recommended treatment). To be rated "useful" or "appropriate," a response had to be adequate by the standards of the nuclear medicine staff. Inconsistency was assessed by regenerating responses. Results: Responses were rated "appropriate" for 92% of 25 tasks and "useful" for 96%. Considerable inconsistencies were found between regenerated responses for 16% of tasks. Responses to 83% of sensitive questions (e.g., staging/treatment options) were rated "empathetic." Conclusion: ChatGPT might adequately substitute for advice given to patients by nuclear medicine staff in the investigated settings. Improving the consistency of ChatGPT would further increase reliability.

Same same but different: dopamine transporter SPECT on scanners with CZT vs. NaI detectors.

BACKGROUND: The aims of this study were to establish a normal database (NDB) for semiquantification of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with [123I]FP-CIT on a cadmium zinc telluride (CZT) camera, test the preexisting NaI-derived NDB for use in CZT scans, and compare the diagnostic findings in subjects imaged with a CZT scanner with either the preexisting NaI-based NDB or our newly defined CZT NDB. METHODS: The sample comprised 73 subjects with clinically uncertain parkinsonian syndrome (PS) who prospectively underwent [123I]FP-CIT SPECT on a CZT camera according to standard guidelines with identical acquisition and reconstruction protocols (DaTQUANT). Two experienced readers visually assessed the images and binarized the subjects into "non-neurodegenerative PS" and "neurodegenerative PS". Twenty-five subjects from the "non-neurodegenerative PS" subgroup were randomly selected to establish a CZT NDB. The remaining 48 subjects were defined as "test group". DaTQUANT was used to determine the specific binding ratio (SBR). For the test group, SBR values were transformed to z-scores for the putamen utilizing both the CZT NDB and the manufacturer-provided NaI-based NDB (GE NDB). A predefined fixed cut-off of -2 was used for dichotomization of z-scores to classify neurodegenerative and non-neurodegenerative PS. Performance of semiquantification using the two NDB to identify subjects with neurodegenerative PS was assessed in comparison with the visual rating. Furthermore, a randomized head-to-head comparison of both detector systems was performed semiquantitatively in a subset of 32 out of all 73 subjects. RESULTS: Compared to the visual rating as reference, semiquantification based on the dedicated CZT NDB led to fewer discordant ratings than the GE NDB in CZT scans (3 vs. 8 out of 48 subjects). This can be attributed to the putaminal z-scores being consistently higher with the GE NDB on a CZT camera (median absolute difference of 1.68), suggesting an optimal cut-off of -0.5 for the GE NDB instead of -2.0. Average binding ratios and z-scores were significantly lower in CZT compared to NaI data. CONCLUSIONS: Use of a dedicated, CZT-derived NDB is recommended in [123I]FP-CIT SPECT with a CZT camera since it improves agreement between semiquantification and visual assessment.

Plasma Markers for Therapy Response Monitoring in Patients with Neuroendocrine Tumors Undergoing Peptide Receptor Radionuclide Therapy.

BACKGROUND: Pretherapeutic chromogranin A, alkaline phosphatase (ALP), or De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) are prognostic factors in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). However, their value for intratherapeutic monitoring remains unclear. We evaluated if changes in plasma markers during PRRT can help identify patients with unfavorable outcomes. METHODS: A monocentric retrospective analysis of 141 patients with NET undergoing PRRT with [177Lu]Lu-DOTATOC was conducted. Changes in laboratory parameters were calculated by dividing the values determined immediately before each cycle of PRRT by the pretherapeutic value. Patients with low vs. high PFS were compared with the Wilcoxon rank-sum test. RESULTS: Progression, relapse, or death after PRRT was observed in 103/141 patients. Patients with low PFS showed a significant relative ALP increase before the third (p = 0.014) and fourth (p = 0.039) cycles of PRRT. Kaplan-Meier analysis revealed a median PFS of 24.3 months (95% CI, 20.7-27.8 months) in patients with decreasing ALP values (Δ > 10%) during treatment, 12.5 months (95% CI, 9.2-15.8 months) in patients with increasing ALP values (Δ > 10%), and 17.7 months (95% CI, 13.6-21.8 months) with stable ALP values (Δ ± 10%). CONCLUSIONS: Based on these exploratory data, a rise in plasma ALP might indicate disease progression and should be interpreted cautiously during therapy.

Hsp70-A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers.

Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal tumor biomarker. Since viable, mHsp70-positive tumor cells actively release Hsp70 in lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal tumor biomarker and its potential as an early predictive marker of therapeutic failure. We have also evaluated mHsp70 as a target for the isolation and enumeration of circulating tumor cells (CTCs) in patients with different tumor entities. Circulating vesicular Hsp70 levels were measured in the peripheral blood of tumor patients with the compHsp70 ELISA. CTCs were isolated using cmHsp70.1 and EpCAM monoclonal antibody (mAb)-based bead approaches and characterized by immunohistochemistry using cytokeratin and CD45-specific antibodies. In two out of 35 patients exhibiting therapeutic failure two years after initial diagnosis of non-metastatic breast cancer, progressively increasing levels of circulating Hsp70 had already been observed during therapy, whereas levels in patients without subsequent recurrence remained unaltered. With regards to CTC isolation from patients with different tumors, an Hsp70 mAb-based selection system appears superior to an EpCAM mAb-based approach. Extracellular and mHsp70 can therefore serve as a predictive biomarker for therapeutic failure in early-stage tumors and as a target for the isolation of CTCs in various tumor diseases.

Reconstruction of the posterior oblique ligament and the posterior cruciate ligament in knees with posteromedial instability.

PURPOSE: Posterior cruciate ligament (PCL) injuries are often associated with injuries of the posteromedial structures of the knee. The motivation for this study was the attempt to test different reconstruction techniques for the structures of the posteromedial corner in a biomechanical experiment. METHODS: Kinematic studies were carried out on 10 cadaveric knees exposed to a 134-N posterior tibial load, 10-Nm valgus torque, and 5-Nm internal torque at 0°, 30°, 60°, and 90° of flexion. The resulting posterior tibial translation (PTT) was determined using a robotic/universal force-moment sensor testing system for (1) intact knees, (2) PCL-deficient knees, (3) knees with deficiency of the PCL and the posteromedial structures, (4) knees with only the PCL reconstructed, (5) knees with the PCL and posterior oblique ligament (POL) reconstructed, and (6) knees with the PCL, medial collateral ligament (MCL), and POL reconstructed. Kinematic data were analyzed by a 2-factor repeated analysis of variance. RESULTS: When both the PCL and the posteromedial structures were cut, PTT increased significantly at all flexion grades under a posterior tibial load (P < .05). Reconstruction of only the PCL could not restore PTT at 0°, 30°, 60°, and 90° of flexion under loading conditions in a knee with combined injury of the PCL and the posteromedial structures (P > .05). Additional reconstruction of the POL improved PTT at all flexion angles in comparison with only the PCL-reconstructed knee. Reconstruction of the MCL had no significant effect on PTT. CONCLUSIONS: This study shows that reconstruction of the POL contributes significantly to the normalization of coupled PTT in knees with combined injury of the PCL and the posteromedial structures under valgus or internal rotational moment. The supplementary reconstruction of the MCL did not provide significant improvement in knee kinematics. CLINICAL RELEVANCE: The POL should be addressed in the patient with combined injuries of the PCL and the posteromedial structures.

Same same, but different? The neurological presentation of wildtype transthyretin (ATTRwt) amyloidosis.

BACKGROUND: Both hereditary transthyretin (ATTRv) amyloidosis and wildtype transthyretin (ATTRwt) amyloidosis can be associated with neurological diseases such as carpal tunnel syndrome and polyneuropathy. While ATTRv amyloidosis has been extensively studied, to date little is known about neurological complications of ATTRwt amyloidosis. In particular, the prevalence, pattern and extent of polyneuropathy and autonomic dysfunction has not been adequately investigated in the context of ATTRwt amyloidosis. To tackle this issue, we aimed to characterise the neurological presentation of ATTRwt amyloidosis and to compare between the presentations of ATTRv and ATTRwt amyloidoses. PATIENTS AND METHODS: Between November 2019 and September 2020, we included 50 patients with ATTRwt amyloidosis in this cohort study. All patients presented to the amyloidosis centre in Berlin, Germany and underwent neurological, cardiological and radiological work-up including neurological examination, laboratory testing, nerve conduction studies (NCS), echocardiography and scintigraphy. Patients were screened for symptoms of autonomic dysregulation and a subgroup of patients underwent tilt-table testing for orthostatic dysregulation. RESULTS: The cohort included 46 men and 4 women; the mean age of the study participants was 80.6 (standard deviation [SD] ± 5.0) years. All patients showed signs of cardiomyopathy on echocardiography. Neurological examination revealed peripheral, symmetric and length-depended predominately sensory polyneuropathy in 74% (n = 37) of patients. Neuropathy impairment scores (NIS) ranged from 0 to 50 with an average score of 8.4 (SD ± 10.1) indicating mild to moderate impairment. 90% and 92% of patients were classified as FAP stage I and PND stage I, respectively. Unilateral or bilateral carpal tunnel syndrome (CTS) was present in 70% (n = 35) and spinal stenosis was seen in 11% (n = 5) of patients. We detected a low rate of autonomic symptoms with a median COMPASS-31 total score of 18.4 points (IQR 32.4 points). Additional tilt-table testing of a subgroup of 8 patients yielded negative results for orthostatic intolerance. CONCLUSION: Distal-symmetric, predominantly sensory polyneuropathy is a common neurological complication in ATTRwt amyloidosis besides carpal tunnel syndrome and spinal stenosis, further substantiating the systemic character of the disease. Compared to ATTRv amyloidosis, the severity of polyneuropathy in ATTRwt amyloidosis is milder and without relevant motor involvement. Symptoms of autonomic dysfunction were not common in this cohort. Nevertheless, ATTRwt amyloidosis is a treatable disease and should be included in the differential diagnosis of sensory polyneuropathy in the elderly.

Transarterial Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma Patients: Outcome Assessment Applying a Prognostic Score.

Radioembolization (RE) is a viable therapy option in patients with intrahepatic cholangiocarcinoma (ICC). This study delineates a prognostic score regarding overall survival (OS) after RE using routine pre-therapeutic parameters. A retrospective analysis of 39 patients (median age, 61 [range, 32−82] years; 26 females, 13 males) with ICC and 42 RE procedures was conducted. Cox regression for OS included age, ECOG, hepatic and extrahepatic tumor burden, thrombosis of the portal vein, ascites, laboratory parameters and dose reduction due to hepatopulmonary shunt. Median OS after RE was 8.0 months. Using univariable Cox, ECOG ≥ 1 (hazard ratio [HR], 3.8), AST/ALT quotient (HR, 1.86), high GGT (HR, 1.002), high CA19-9 (HR, 1.00) and dose reduction of 40% (HR, 3.8) predicted shorter OS (each p < 0.05). High albumin predicted longer OS (HR, 0.927; p = 0.045). Multivariable Cox confirmed GGT ≥ 750 [U/L] (HR, 7.84; p < 0.001), ECOG > 1 (HR, 3.76; p = 0.021), albumin ≤ 41.1 [g/L] (HR, 3.02; p = 0.006) as a three-point pre-therapeutic prognostic score. More specifically, median OS decreased from 15.3 months (0 risk factors) to 7.6 months (1 factor) or 1.8 months (≥2 factors; p < 0.001). The proposed score may aid in improved pre-therapeutic patient identification with (un-)favorable OS after RE and facilitate the balance between potential life prolongation and overaggressive patient selection.

Analysis of cartilage injury patterns and risk factors for knee joint damage in patients with primary lateral patella dislocations.

BACKGROUND: Lateral patellar dislocation (LPD) frequently causes damage to the knee. Injury patterns and risk factors contributing to such injuries have not yet been examined in detail. METHODS: We retrospectively analyzed 50 consecutive patients with primary LPD. Two reviewers evaluated the MRI images regarding risk factors for LPD (Dejours classification; Caton-Deschamps Index, CDI; distance from the tibial tuberosity to trochlear groove, TT-TG; trochlear depth, TD) as well as joint damages according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS). RESULTS: 33 male and 17 female patients with a mean age of 23.2 (±9.6) years were included in this study. 52% were classified Dejours ≥ B, 34% had a CDI ≥ 1.3, 22% a TT-TG ≥ 20mm and 52% a TD < 3mm. 49 out of 50 patients (98%) showed abnormalities according to WORMS. The most frequently observed abnormalities were synovitis/effusion (49/50, 98%), bone marrow oedema (44/50, 88%) and cartilage damage (42/50, 84%). Most frequently affected subregions were medial (41/50, 82%) and lateral (31/50, 62%) patella as well as the anterior (43/50, 86%), central (42/50, 84%) and posterior (11/50, 22%) portion of the lateral femoral condyle. There was no significant correlation between any of the examined risk factors and joint damages according to WORMS. Male patients had higher scores regarding total cartilage damage (5.11 vs. 2.56, p = 0.029), total score for the lateral femorotibial joint (3.15 vs. 1.65, p = 0.026) and overall total WORMS score (12.15 vs. 8.29, p = 0.038). CONCLUSION: Risk factors for LPD do not influence the risk of damages to the knee joint after primary LPD. Although LPD is generally known to affect more female than male patients, male patients suffered more severe injuries after primary LPD, particularly of the lateral femorotibial joint. Overall, our results underline the importance of MRI imaging after primary LPD.