Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma.

We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab ("Pom-PAD-Dara"), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.

18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in Patients with Smoldering Multiple Myeloma: Imaging Pattern and Clinical Features.

This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUVmean) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUVmean of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBRmean) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBRmean in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBRmax of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.

The Link between Cytogenetics/Genomics and Imaging Patterns of Relapse and Progression in Patients with Relapsed/Refractory Multiple Myeloma: A Pilot Study Utilizing 18F-FDG PET/CT.

Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1-10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUVmax) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUVmax of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUVmax of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUVmax on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.

Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease.

Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40-80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5-6.5) and ten (95% CI, 7.5-12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.

Impairments of postural control, functional performance and strength in morbidly obese patients awaiting bariatric surgery in comparison to healthy individuals.

[Purpose] There is a lack of information evaluating specific markers of performance in patients awaiting bariatric surgery. We aimed to assess the postural control, functional performance, strength and endurance performance for morbidly obese patients awaiting bariatric surgery compared to lean controls. [Subjects and Methods] All parameters were assessed by modified Y-balance test, timed-up-and-go-test, maximum strength testing on resistance exercise equipment and cardio-pulmonary exercise testing on a cycle ergometer in 10 morbidly obese patients awaiting bariatric surgery and 10 age- and sex-matched lean controls. [Results] It was found that significant differences existed for overall modified Y-balance test in morbidly obese patients awaiting bariatric surgery versus lean controls (0.37 ± 0.03 vs. 0.47 ± 0.02 cm.cm-1), timed-up-and-go-test (9.33 ± 1.23 vs. 7.85 ± 1.73 sec) and several variables of cardio-pulmonary exercise testing. Overall absolute strength expressed in kilogram was similar, yet when relativized to body weight strength differences were notable (0.4 ± 0.17 vs. 0.83 ± 0.32 kg.kg-1). [Conclusion] The results of this study demonstrate the need for comprehensive functional assessment prior to surgery with an identified demand for subsequent tailored physical training prescription that should begin before surgery.

Reliability of Evaluating Achilles Tendon Vascularization Assessed With Doppler Ultrasound Advanced Dynamic Flow.

OBJECTIVES: The reliability of quantifying intratendinous vascularization by high-sensitivity Doppler ultrasound advanced dynamic flow has not been examined yet. Therefore, this study aimed to investigate the intraobserver and interobserver reliability of evaluating Achilles tendon vascularization by advanced dynamic flow using established scoring systems. METHODS: Three investigators evaluated vascularization in 67 recordings in a test-retest design, applying the Ohberg score, a modified Ohberg score, and a counting score. Intraobserver and interobserver agreement for the Ohberg score and modified Ohberg score was analyzed by the Cohen κ and Fleiss κ coefficients (absolute), Kendall τ b coefficient, and Kendall coefficient of concordance (W; relative). The reliability of the counting score was analyzed by intraclass correlation coefficients (ICC) 2.1 and 3.1, the standard error of measurement (SEM), and Bland-Altman analysis (bias and limits of agreement [LoA]). RESULTS: Intraobserver and interobserver agreement (absolute/relative) ranged from 0.61 to 0.87/0.87 to 0.95 and 0.11 to 0.66/0.76 to 0.89 for the Ohberg score and from 0.81 to 0.87/0.92 to 0.95 and 0.64 to 0.80/0.88 to 0.93 for the modified Ohberg score, respectively. The counting score revealed an intraobserver ICC of 0.94 to 0.97 (SEM, 1.0-1.5; bias, -1; and LoA, 3-4 vessels). The interobserver ICC for the counting score ranged from 0.91 to 0.98 (SEM, 1.0-1.9; bias, 0; and LoA, 3-5 vessels). CONCLUSIONS: The modified Ohberg score and counting score showed excellent reliability and seem convenient for research and clinical practice. The Ohberg score revealed decent intraobserver but unexpected low interobserver reliability and therefore cannot be recommended.

Accuracy of Continuous Glucose Monitoring (CGM) during Continuous and High-Intensity Interval Exercise in Patients with Type 1 Diabetes Mellitus.

Continuous exercise (CON) and high-intensity interval exercise (HIIE) can be safely performed with type 1 diabetes mellitus (T1DM). Additionally, continuous glucose monitoring (CGM) systems may serve as a tool to reduce the risk of exercise-induced hypoglycemia. It is unclear if CGM is accurate during CON and HIIE at different mean workloads. Seven T1DM patients performed CON and HIIE at 5% below (L) and above (M) the first lactate turn point (LTP1), and 5% below the second lactate turn point (LTP2) (H) on a cycle ergometer. Glucose was measured via CGM and in capillary blood (BG). Differences were found in comparison of CGM vs. BG in three out of the six tests (p < 0.05). In CON, bias and levels of agreement for L, M, and H were found at: 0.85 (-3.44, 5.15) mmol·L(-1), -0.45 (-3.95, 3.05) mmol·L(-1), -0.31 (-8.83, 8.20) mmol·L(-1) and at 1.17 (-2.06, 4.40) mmol·L(-1), 0.11 (-5.79, 6.01) mmol·L(-1), 1.48 (-2.60, 5.57) mmol·L(-1) in HIIE for the same intensities. Clinically-acceptable results (except for CON H) were found. CGM estimated BG to be clinically acceptable, except for CON H. Additionally, using CGM may increase avoidance of exercise-induced hypoglycemia, but usual BG control should be performed during intense exercise.

A detailed comparative study of high-resolution ultrasound and micro-computed tomography for detection of arthritic bone erosions.

OBJECTIVE: To test whether bony lesions appearing on ultrasound (US) imaging are cortical breaks detectable by micro-computed tomography (micro-CT). METHODS: Twenty-six subjects (14 with rheumatoid arthritis, 6 with psoriatic arthritis, and 6 healthy controls) were assessed for bone erosions at the radial, palmar, and dorsal regions of the second metacarpophalangeal (MCP) joint and the palmar and dorsal regions of the third and fourth MCP joints. All patients underwent US and, for validation of the results, micro-CT scanning. The prevalence and severity of bone erosions as determined by US and by micro-CT were recorded and compared. RESULTS: Overall there was a good correlation between the severity of erosions as assessed by US and by micro-CT (r = 0.463, P < 0.0001). False-negative results (US negative/micro-CT positive) were obtained in only 9.9% of the joint regions and were mostly due to small erosive lesions at the dorsal sides of the MCP joints. False-positive results (US positive/micro-CT negative) were more frequent (28.6%) and were primarily based on vascular bone channels at the palmar sides of the MCP joints as well pseudo-erosions created by osteophytes. CONCLUSION: These data show that the majority of bone lesions appearing on US are indeed bone erosions with a cortical break. The sensitivity of US for detecting bone erosions was high and there was a good correlation between the severity of bone erosions as assessed by US and as assessed by micro-CT. Specificity of US for bone erosions was substantially lower, suggesting that smaller lesions seen on US do not always represent breaks in the cortical bone surface.