Different extramedullary disease shown in chemokine receptor 4 targeted PET/CT with [68Ga]Ga-pentixafor in patients with Waldenström macroglobulinemia and smoldering disease.

INTRODUCTION: It is important to distinguish Waldenström macroglobulinemia from smoldering Waldenström macroglobulinemia (sWM), because only patients with Waldenström macroglobulinemia require treatment, however the distinction can be clinically complex. The aim of this study is to investigate whether [68Ga]Ga-pentixafor PET/CT shows different characteristics in sWM and Waldenström macroglobulinemia patients and therefore can help to differentiate Waldenström macroglobulinemia and sWM. RESULTS: Thirty-seven patients with newly diagnosed Waldenström macroglobulinemia and 11 sWM patients were analyzed [35 men and 13 women; 64.3 ±â€…10.7 (range, 29-87) years old]. The SUVmax of bone marrow disease, lymph nodes, and other extramedullary diseases on [68Ga]Ga-pentixafor were significantly higher than those on 2-[18F]FDG PET/CT (P < 0.05). On [68Ga]Ga-pentixafor PET/CT, patients with Waldenström macroglobulinemia had more lymph node regions involved, significantly higher incidence of involvement in more than three lymph node regions, larger nodal disease, and higher incidence of other extramedullary disease when compared with sWM patients (P < 0.05). Waldenström macroglobulinemia patients showed significantly higher total lesions uptake, total lesion volume, and SUVmax of extramedullary disease than sWM patients did (P < 0.05). None of the visual or semiquantitative indexes in 2-[18F]FDG PET/CT showed significant difference between Waldenström macroglobulinemia and sWM patients. CONCLUSION: [68Ga]Ga-pentixafor PET/CT had better diagnostic performance than 2-[18F]FDG PET/CT in Waldenström macroglobulinemia. Patients with Waldenström macroglobulinemia presented with more extensive extramedullary disease shown in [68Ga]Ga-pentixafor PET/CT than sWM patients did.

Research on likelihood ratio evaluation method of fingerprint evidence based on parameter estimation method.

Fingerprints with similar morphological characteristics but from different individuals can lead to errors in individual identification, especially when dealing with large databases containing millions of fingerprints. To address this issue and enhance the accuracy of similar fingerprint identification, the use of the likelihood ratio (LR) model for quantitative evaluation of fingerprint evidence has emerged as an effective research method. In this study, the LR fingerprint evidence evaluation model was established by using mathematical statistical methods, such as parameter estimation and hypothesis testing. This involved various steps, including database construction, scoring, fitting, calculation, and visual evaluation. Under the same-source conditions, the optimal parameter methods selected by different number of minutiae are gamma and Weibull distribution, while normal, Weibull, and lognormal distributions were the fitting parameters selected for minutiae configurations. The fitting parameters selected by different number of minutiae under different-source conditions are lognormal distribution, and the parameter methods selected for different minutiae configurations include Weibull, gamma, and lognormal distributions. The results of the LR model showed increased accuracy as the number of minutiae increased, indicating strong discriminative and corrective power. However, the accuracy of the LR evaluation based on different configurations was comparatively lower. In addition, the LR models with different numbers of minutiae outperformed those with different minutiae configurations. Our study shows that the use of LR models based on parametric methods is favoured in reducing the risk of fingerprint evidence misidentification, improving the quantitative assessment methods of fingerprint evidence, and promoting fingerprint identification from experience to science. Key points: Likelihood ratio (LR) method based on parameter estimation was applied to scientific evaluation of fingerprint evidence with excellent discriminatory and calibration capabilities.Both the number of minutiae and configuration of minutiae have significant effects on the score-based LR method.Fingerprints from the same source contain many different patterns of deformation.Databases containing 10 million fingerprints from different sources have been used for building the LR model.

Similarity quantification of bare footprint based on linear measurement and shape context contour combined score-based likelihood ratio evaluation.

Bare footprints are a type of physical evidence that can be crucial for solving difficult cases. To assist with identification, we explored a similarity quantification method using 3062 bare footprints from 1391 volunteers. We used linear similarity to cover seven linear lengths and then calculated the contour similarity of the heel region, anterior margin, and toe region using the shape context. Discriminant analysis was applied to determine the weights of the linear and contour similarities. Linear similarity had a weight of 0.56 whereas contour similarity had a weight of 0.44. The similarity between the same source and non-matches bare footprints was significantly different, with a leave-one-out cross-validation accuracy of 98.8%. Using the constructed similarity model, we developed a score-based likelihood ratio model based on similarity scores. We applied this model to five representative test samples including different volunteers, six months apart bare footprints, dynamic walking and static bare footprints. This method eliminated the interference of motion states and allowed for accurate determination of the same source and non-matches test samples. Overall, we quantified the shape contour and established a similarity assessment system for bare footprints that can assist in evaluation and identification.

[68 Ga]Ga-FAPI-04 PET/CT may be a predictor for early treatment response in rheumatoid arthritis.

BACKGROUND: The identification of biomarkers predicting the treatment response of rheumatoid arthritis (RA) is important. [68 Ga]Ga-FAPI-04 showed markedly increased uptake in the joints of patients with RA. The purpose of this study is to investigate whether [68 Ga]Ga-FAPI-04 PET/CT can be a predictor of treatment response in RA. RESULTS: Nineteen patients diagnosed with RA in the prospective cohort study were finally enrolled. Both total synovitis uptake (TSU) and metabolic synovitis volume (MSV) in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT of the responders were significantly higher than those in non-responders according to Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) response criteria at 3-months' follow-up (P < 0.05). The PET joint count (PJC) detected in [68 Ga]Ga-FAPI-04 and [18F]FDG PET/CT were also significantly higher in CDAI responders than non-responders (P = 0.016 and 0.045, respectively). The clinical characteristics of disease activity at baseline did not show significant difference between the responders and non-responders, except CRP (P = 0.035 and 0.033 in CDAI and SDAI response criteria, respectively). The baseline PJCFAPI, TSUFAPI and MSVFAPI > cutoff values in [68 Ga]Ga-FAPI-04 PET/CT successfully discriminated CDAI and SDAI responders and non-responders at 3-months' follow-up. CONCLUSION: [68 Ga]Ga-FAPI-04 uptake at baseline were significantly higher in early responders than those in non-responders. Trial registration ClinicalTrials. NCT04514614. Registered 13 August 2020, https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000A4PN&selectaction=Edit&uid=U0001JRW&ts=2&cx=-x9t7cp.

The effectiveness of fracture liaison services in patients with hip fractures: A systematic review and meta-analysis of randomized controlled trials.

Background: In recent years, fracture liaison services (FLS) have been applied for hip fractures; however, their effectiveness remains uncertain. Objective: To evaluate the effectiveness of FLS in patients with hip fractures. Design: A systematic review and meta-analysis of randomized controlled trials. Data sources: Embase, PubMed, Cochrane Library, Ebsco, Ovid, Web of Science, Medline, CNKI, Wangfang, and Vip were searched from their date of inception to March 2023. Two researchers screened the literature based on the inclusion and exclusion criteria, evaluated the quality, extracted data, and conducted a meta-analysis using ReviewManager 5.4. Results: After screening, 12 randomised controlled trials (RCT) including 2136 patients were used in the meta-analysis. The primary outcomes were hip function rate of recurrent fracture, medication adherence, and degree of weakness. FLS improved hip function in patients with hip fractures [MD = 9.37, 95 % CI (7.69, 11.06), P < 0.0001], P < 0.0001], medication adherence [OR = 10.59, 95 % CI (1.64, 68.41), P＜0.0001], degree of weakness [MD = -1.45, 95%CI (-1.68，-1.23), P＜0.0001], and reduced the rate of recurrent fractures [OR = 0.60, 95 % CI (0.44, 0.82). Conclusion: Implementation of the FLS management model was beneficial for patients with hip fractures. It can positively impact the prognosis of patients with hip fractures by improving hip function, reducing the rate of recurrent fractures, and improving medication adherence and degree of weakness.

Langerhans Cell Histiocytosis Showed Intense Uptake of 68 Ga-FAPI.

ABSTRACT: A 23-year-old man was recently diagnosed with Langerhans cell histiocytosis (LCH). 68 Ga-FAPI PET/CT showed multiple lesions with intense FAPI uptake in the axial and appendicular skeleton with lytic or mixed bone destruction, consistent with osseous lesions of LCH. FAPI-avid foci around the right atrium and inferior vena cava, as well as micronodules and thin-walled cysts in the lungs, were also noted, possibly also involvement of LCH. This case suggested that 68 Ga-FAPI PET/CT may have the potential to be applied in evaluation of LCH.

Cardiac Metastasis of Malignant Melanoma Detected by 18F-FDG PET/CT.

A 63-year-old man with a history of right plantar malignant melanoma (T3bN0M0, IIb) developed multiple metastases in bilateral lungs 19 months after surgery. Subsequent 18F-FDG PET/CT revealed multiple pulmonary metastases with intense FDG uptake and detected a hypermetabolic lesion in the lateral wall of the left ventricle, which was considered to be a cardiac metastasis of malignant melanoma. This lesion was later confirmed in the dynamic myocardial perfusion MR. This case demonstrates the effectiveness of 18F-FDG PET/CT in detecting occult cardiac metastases of malignant melanoma.

Renal Involvement of Immunoglobulin G4-Related Disease Presenting as a Solitary Hypermetabolic Mass Mimicking Renal Tumor on 18 F-FDG PET/CT.

ABSTRACT: A 62-year-old woman with a 5-year history of diabetes insipidus was found with a solitary renal mass in contrast-enhanced CT. 18 F-FDG PET/CT showed a hypermetabolic mass in the right kidney. Besides, there was increased uptake in the pituitary stalk. The histopathological examination of renal biopsy confirmed the diagnosis of immunoglobulin G4-related disease. After treatment with prednisone and cyclophosphamide, there was obvious radiographic improvement of the renal lesion.

Bing-Neel Syndrome and Coexisting Pituitary Macroadenoma in a Patient with Waldenström Macroglobulinemia Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT.

A 63-year-old man presenting with peripheral neuropathies was diagnosed of Waldenström's macroglobulinemia, and Bing-Neel syndrome was subsequently confirmed via cerebrospinal fluid examinations. Besides involvement in bone marrow, lymph nodes, as well as the thoracic and sacral nerve root, 68Ga-Pentixafor PET/CT detected active tracer uptake in bilateral choroid plexus, which was negative in 18F-FDG PET/CT, possibly suggesting the involvement of Bing-Neel syndrome. The coexisting pituitary macroadenoma was FDG-avid but negative in 68Ga-Pentixafor PET/CT. After six cycles of chemotherapy, the follow-up PET/CT showed complete remission of the previous disease, including the high uptake of 68Ga-Pentixafor in choroid plexus. However, the hypermetabolic pituitary macroadenoma remained unchanged.

Prominent 68 Ga-FAPI Uptake in Renal Parenchyma Caused by Immunoglobulin G4-Related Nephropathy.

ABSTRACT: A 57-year-old man presented with a dry cough and renal insufficiency. Serum immunoglobulin G4 (IgG4) level was markedly elevated, and IgG4-related disease was clinically considered. 18 F-FDG PET/CT revealed mild uptake in salivary glands and also moderately increased activity in renal parenchyma and prostate. 68 Ga-FAPI PET/CT detected prominent and evenly distributed 68 Ga-FAPI uptake in the kidney, and the pancreas, salivary gland, and prostate also showed intense activity, consistent with IgG4-related disease involving the kidney, pancreas, salivary gland, and prostate.

68Ga-Pentixafor PET/CT May Fail to Detect Recurrent Multiple Myeloma with Extramedullary Disease.

Two patients with a history of multiple myeloma experienced a recurrence of the disease.18F-FDG PET/CT revealed prominent extramedullary disease as well as multi-foci in the bone marrow, both with increased FDG uptake. However, on 68Ga-Pentixafor PET/CT, all the myeloma lesions showed significantly lower tracer uptake in comparison with 18F-FDG PET. This false-negative result of recurrent multiple myeloma with extramedullary disease may be a potential limitation of 68Ga-Pentixafor in assessing multiple myeloma.

Characterizing Rosai-Dorfman disease with [18F]FDG PET/CT: a retrospective analysis of a single-center study.

OBJECTIVES: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferative disorder. We performed a retrospective study to characterize the clinical and [18F]FDG PET/CT features of RDD. METHODS: We retrospectively recruited 38 RDD patients with [18F]FDG PET/CT scan in our center. [18F]FDG PET/CT features were assessed, and clinical and follow-up data were recorded. RESULTS: In the recruited patients, 20/38 (52.6%) patients had single-system disease, while others (18/38, 47.4%) had disease affecting multiple system. RDD most commonly involved the upper respiratory tract (47.4%), followed by cutaneous/subcutaneous lesion (39.5%), lymph node (36.8%), bone (31.6%), central nervous system (28.9%), and cardiovascular system (13.2%) in the recruited patients. In PET/CT, the RDD lesions were FDG-avid, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels (r = 0.418, p = 0.014), and negatively correlated with hemoglobin levels (r = -0.359, p = 0.036). The overall response rate of the first-line treatment was 80.8% in newly diagnosed RDD patients, and for patients with relapsed/progressive RDD, the overall response rate was 72.7%. CONCLUSION: [18F]FDG PET/CT could be a useful tool for evaluating RDD. KEY POINTS: • About half of the patients with Rosai-Dorfman disease had single-system disease, while others had disease affecting multiple system. Rosai-Dorfman disease most commonly involved the upper respiratory tract, followed by cutaneous/subcutaneous lesion, lymph node, bone, central nervous system, and cardiovascular system. • In [18F]FDG PET/CT, Rosai-Dorfman disease was usually hypermetabolic, and the SUVmax of the hottest lesion in an individual patient was positively correlated with C-reactive protein levels. • Rosai-Dorfman disease usually has a high overall response rate after treatment.

68Ga-FAPI PET/CT for Rheumatoid Arthritis: A Prospective Study.

Background In rheumatoid arthritis (RA), fibroblast-like synoviocyte cells, which are involved in inflammation of the articular cartilage and bone, overexpress fibroblast activation protein (FAP). This is a feature that could be leveraged to improve imaging assessment of disease. Purpose To determine the performance of gallium 68 (68Ga)-labeled FAP inhibitor (FAPI) in assessing joint disease activity of RA and to compare with fluorine 18 (18F) fluorodeoxyglucose (FDG) imaging. Materials and Methods Twenty participants with RA (15 women; mean age, 55 years ± 10 [SD]) were prospectively enrolled from September 2020 to December 2021 and underwent clinical and laboratory assessment of disease activity and dual-tracer PET/CT (68Ga-FAPI and 18F-FDG) imaging. Imaging-derived variables of PET joint count (the number of joints positive for RA at PET) and PET articular index (a sum of the points of the joints using a three-point scale) were correlated to clinical and laboratory variables of disease activity. Results The combined output of both PET/CT techniques helped detect 244 affected joints, all of which showed positive results at 68Ga-FAPI PET/CT. However, fifteen of 244 (6.1%) FAPI-avid joints in six of 20 (30%) participants were not detected at 18F-FDG PET/CT. The maximum standardized uptake value of the most affected joint in each participant was higher in 68Ga-FAPI than in 18F-FDG PET/CT (9.54 ± 4.92 vs 5.85 ± 2.81, respectively; P = .001). The maximum standardized uptake values of the joints at both 68Ga-FAPI and 18F-FDG PET/CT were positively correlated with laboratory evaluation of C-reactive protein levels (r = 0.49 [P = .03] and 0.54 [P = .01], respectively). The PET joint count and PET articular index scores at 68Ga-FAPI PET/CT were also positively correlated with most clinical disease activity variables and radiographic progression of joint damage (P < .05). Conclusion In participants with rheumatoid arthritis who underwent gallium 68 fibroblast activation protein inhibitor PET/CT, the extent of joint involvement correlated with clinical and laboratory variables of disease activity and showed a greater amount and degree of affected joints than at fluorine 18 fluorodeoxyglucose PET/CT. Clinical trial registration no. NCT04514614 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Williams and Ahlman in this issue.

Research on the local regional similarity of automatic fingerprint identification system fingerprints based on close non-matches in a ten million people database-Taking the central region of whorl as an example.

The local regional similarity of fingerprints has always been a hot issue in the field of fingerprint research. With the increasing size of ten-print databases, the appearance of close non-matches (CNMs) in automatic fingerprint identification system (AFIS) candidate lists has attracted increasing attention from forensic science departments worldwide. In this study, three categories (high-, medium-, and low-level) of standards for CNMs were established and 60 whorl samples were marked with different numbers of minutiae to explore the occurrence and influencing factors of CNMs in AFIS candidate lists based on a ten million people database. The results showed that all prints could be found with their corresponding CNMs. The average occurrence rate of CNMs for every query was 52.7% in the top 100 lists, and the most similar CNM was exactly the same in the local area of 12 coincidence points. CNMs appeared more in the middle and lower parts of the central region of the whorl. Moreover, shorter C2C distances and the same finger number and hand led to more CNMs being inspected. CNMs with higher similarity required a more extensive regional area and smaller minutiae density. We concluded that CNMs have a high occurrence rate in large-scale databases and many factors are closely related to them. Fingerprint examiners and researchers need to strengthen their understanding of CNMs to avoid the occurrence of misidentification like the Madrid bombings.

New advances in Nrf2-mediated analgesic drugs.

BACKGROUND: Oxidative stress is an inevitable process that occurs during life activities, and it can participate in the development of inflammation. Although great progress has been made according to research examining analgesic drugs and therapies, there remains a need to develop new analgesic drugs to fill certain gaps in both the experimental and clinical space. PURPOSE: This review reports the research and preclinical progress of this class of analgesics by summarizing known nuclear factor E-2-related factor-2 (Nrf2) pathway-modulating substances. STUDY DESIGN: We searched and reported experiments that intervene in the Nrf2 pathway and its various upstream and downstream molecules for analgesic therapy. METHODS: The medical literature database (PubMed) was searched for experimental studies examining the reduction of pain in animals through the Nrf2 pathway, the research methods were analyzed, and the pathways were classified and reported according to the pathway of these experimental interventions. RESULTS: Humans have identified a variety of substances that can fight pain by regulating the expression of Nrf2 and its upstream and downstream pathways. CONCLUSION: The Nrf2 pathway exerts anti-inflammatory activity by regulating oxidative stress, thereby playing a role in the fight against pain.

A single-center experience on endoscopic ultrasonography-guided ethanol ablation of insulinomas.

BACKGROUND/OBJECTIVES: As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence. METHODS: A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed. RESULTS: The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment. CONCLUSIONS: For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.

Myocardial Uptake of 68Ga-Pentixafor in a Patient With Systemic Amyloidosis.

ABSTRACT: A 55-year-old man presented with chest tightness and lower-limb edema for 1 year. Laboratory and imaging examinations suggested cardiac amyloidosis. Both 18F-FDG and 68Ga-pentixafor PET/CT showed increased uptake in the myocardium of the left ventricle, whereas the bone marrow had diffusely mild uptake of 68Ga-pentixafor without bone destruction. 99mTc-MDP bone scintigraphy also detected extraosseous uptake in the heart, gut, kidneys, and soft tissue. The biopsy of the abdominal subcutaneous fat confirmed amyloid deposits, and the patient was finally diagnosed with primary systemic amyloidosis. This case demonstrated that cardiac amyloidosis might show increased 68Ga-pentixafor uptake in myocardium.

TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease.

OBJECTIVE: To figure out the functions of thymic stromal lymphopoietin (TSLP) in IgG4-related disease (IgG4-RD). METHODS: Plasma TSLP levels were tested by Elisa, and its receptors were detected by flow cytometry. Expressions of TSLP and TSLPR in involved tissues were stained by immunohistochemistry and immunofluorescence. Proliferation, apoptosis, and B subsets of TSLP stimulated-B cells were analyzed by flow cytometry. TSLP-stimulated B cells were co-cultured with CD4+ Naïve T cells. Signaling pathway was identified by RNA-sequencing and western blot. Anti-TSLP therapy was adapted in LatY136F knock-in mice (Lat, IgG4-RD mouse model). RESULTS: Plasma TSLP level was increased in IgG4-RD patients and was positively correlated with serum IgG4 level and responder index (RI). TSLPR was co-localized with CD19+ B cells in the submandibular glands (SMGs) of IgG4-RD. TSLP promoted B cell proliferation, and TSLP-activated B cells polarized CD4+ naive T cells into follicular helper T (Tfh) cells through OX40L. RNA-sequencing identified JAK-STAT signaling pathway in TSLP-activated B cells and it was verified by western blot. Anti-TSLP therapy alleviated the inflammation of lung in Lat mice. CONCLUSION: Elevated TSLP in IgG4-RD promoted B cells proliferation and polarized Tfh cells and might be served as a potential therapeutic target.