Musculoskeletal pain in Parkinson's disease: Association with dopaminergic deficiency in the caudate nucleus.

BACKGROUND: Musculoskeletal (MSK) pain affects over 80% of People with Parkinson's (PD, PwP) and may, in part, be dopaminergic in origin, as dopaminergic medication often leads to its relief. METHODS: PwP who underwent striatal dopamine transporter visualization with a radiopharmaceutical DaTscan™ (123 I-Ioflupane Injection) using a single-photon emission computed tomography (SPECT) as a part of their clinical-diagnostic work up were enrolled in the "Non-motor International Longitudinal Study" (NILS; UK National Institute for Health Research Clinical Research Network Number 10084) and included in this cross-sectional analysis. The association between specific DaTscan binding ratios for each striatum, the caudate nucleus and putamen and clinical ratings for MSK pain (assessed using the King's Parkinson's Disease Pain Scale (KPPS)) were analysed. RESULTS: 53 PwP (30.2% female; age: 63.79 ± 11.31 years; disease duration (DD): 3.32 (0.31-14.41) years; Hoehn & Yahr stage (H&Y): 2 (1-4); Levodopa Equivalent Daily Dose (LEDD): 543.08 ± 308.94 mg) were assessed and included in this analysis. MSK pain was highly prevalent (71.7% of all participants, mean KPPS Item 1 score 5.34 ± 4.76) and did not correlate with the motor symptoms burden (SCOPA-Motor total score; p = 0.783) but showed a significant correlation with quality of life (PDQ-8, rs = 0.290, p = 0.035). z-scores for the caudate nucleus (Exp (B) = 0.367, 95% CI for Exp (B) 0.148-0.910, p = 0.031) and striatum (Exp (B) = 0.338, 95% CI for Exp (B) 0.123-0.931, p = 0.036), adjusted for DD, H&Y and LEDD, were significant determinants of MSK pain. CONCLUSIONS: Our findings suggest an association between MSK pain in PwP and the severity of dopaminergic deficiency in the caudate nucleus. SIGNIFICANCE: In People with Parkinson's, musculoskeletal pain does not arise simply as a direct sequel to motor symptoms-instead, it is linked to the severity of dopaminergic depletion in the caudate nucleus.

Chimeric Antigen Receptor T-Cell Therapy and Imaging Applications for Large B-Cell Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of large B-cell lymphoma (LBCL) and other hematologic malignancies. Its mechanism of action relies on recent biotechnological advances that allow clinicians to harness and enhance a patient's immune system to fight cancerous cells. The indications for CAR T-cell therapy continue to expand, with ongoing trials evaluating their use in other hematologic and solid organ malignancies. This review explores the vital role of diagnostic imaging in patient selection and treatment response in CAR T-cell therapy for LBCL and the management of specific therapy-related adverse events. For a patient-centered and cost-effective use of CAR T-cell therapy, it is crucial to select patients who are likely to derive long-term benefit and optimize their care during a lengthy treatment pathway. Metabolic tumor volume and kinetics assessed at PET/CT have emerged as powerful tools to predict outcome after CAR T-cell therapy in LBCL, allowing for the early identification of lesions refractory to treatment and identification of the severity of CAR T-cell therapy toxicity. Radiologists should be aware that the success of CAR T-cell therapy is mitigated by adverse events, most importantly neurotoxicity, which remains poorly understood and challenging to treat. Neuroimaging, with experienced clinical evaluation, is critical in the diagnosis and management of neurotoxicity and the exclusion of other central nervous system complications that can occur in this clinically vulnerable patient group. This review discusses current applications of imaging in the standard CAR T-cell therapy pathway for the treatment of LBCL, which serves as a model disease in the integration of diagnostic imaging and radiomic risk markers.

Diagnostic value of 18F-FDG PET/CT in infective endocarditis.

INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) is not routinely recommended for the diagnosis of infective endocarditis (IE) due to the lack of clinical impact. MATERIALS AND METHODS: Between January 2016 and January 2020, clinical data from patients with a possible diagnosis of IE were reviewed retrospectively to evaluate the value of 18F-FDG-PET/CT in the diagnosis of IE. 18F-FDG PET/CT scan was performed as an additional diagnostic tool in possible IE when echocardiography was inconclusive or in patients with definite IE to identify extracardiac complications. Cases were classified according to modified Duke criteria as rejected, definite or possible. RESULTS: 313 patients with suspected IE were included. 72 (23%) patients underwent 18F-FDG PET/CT. 18F-FDG PET/CT resulted in a reclassification of Duke criteria in 29/72 (40%) patients, from "possible" to "definite" (n, 10) and to "rejected" (n, 19). Patients who benefited from a Duke criteria reclassification following 18F-FDG PET/CT were more frequently classified as possible IE at inclusion or had a non-conclusive baseline echocardiography (100% vs 58%; p 0.001) and had more likely a prosthetic metallic valve replacement (59% vs 21%; p 0.001). Abnormal perivalvular uptake was identified in 46 patients (71% prosthetic vs 50% native; p 0.118). 18F-FDG PET/CT identified extracardiac uptake consistent with septic emboli in 14/72 (19%) patients. In addition, extracardiac uptake indicative of an alternative diagnosis was identified in 5 patients (2% prosthetic vs 17% native; p 0.039). CONCLUSION: The use of 18F-FDG-PET/CT has shown to be useful in the diagnosis of IE, particularly in prosthetic IE and may provide additional value in the detection of septic emboli and/or the identification of an alternative diagnosis different from IE.

Nodal metastases in small rectal neuroendocrine tumours.

AIM: Rectal neuroendocrine tumours (NETs) are the most common type of gastrointestinal NET. European Neuroendocrine Tumour Society guidelines suggest that rectal NETs measuring ≤10 mm are indolent with low risk of spread. In practice, many patients with lesions ≤1 cm do not undergo complete tumour staging. However, the size of the lesion may not be the only risk factor for nodal involvement/metastases. The aim of this study was to determine if MRI ± nuclear medicine imaging alters tumour stage in patients with rectal NETs ≤10 mm. METHODS: Patients referred to a tertiary NET centre between 2005 and 2020 who met the inclusion criteria of a rectal NET ≤10 mm, full cross-sectional imaging, primarily an MRI scan and, if abnormal findings were identified, a subsequent 68 Ga-DOTATATE positron emission tomography scan were included. All patients were followed up at our institution. RESULTS: In all, 32 patients with rectal NETs 10 mm or less were included in the study: 16 women; median age 58 years (range 33-71); 47% (n = 15) were referred from bowel cancer screening procedures. The median size of the lesions was 5 mm (range 2-10 mm). 81% (n = 26) were World Health Organization Grade 1 tumours with Ki67 <3%. Radiological staging confirmed nodal involvement in 25% (8/32); two cases had distant metastatic disease. Lymphovascular invasion was present in 3% (1/32) of patients but none demonstrated peri-neural invasion. CONCLUSION: This study demonstrates that small rectal NETs can develop nodal metastases; therefore it is important to stage these tumours accurately with MRI at baseline and, if there are concerns regarding potential lymph node metastases, to consider 68 Ga-DOTATATE positron emission tomography imaging.

COVID-19-related thyroiditis: A novel disease entity?

The literature on COVID-19-related thyroid complications has accumulated over the past year or so as the pandemic has accelerated throughout the world. In particular, several recent case reports have been published describing a possible correlation between COVID-19 disease and subacute thyroiditis (SAT). In this review, we briefly present one of our own patients and review the current published literature in this area up to January 2021, including analyses of major series of thyroid function tests in patients with significant COVID-19 infection. We conclude that while the great majority of patients with severe COVID-19 infection may show manifestations of the sick euthyroid syndrome, clinicians should be aware of the possibility of SAT, especially in the early weeks and months following even mild COVID-19 infection.

Clinical Non-Motor Phenotyping of Black and Asian Minority Ethnic Compared to White Individuals with Parkinson's Disease Living in the United Kingdom.

BACKGROUND: Ethnic phenotypic differences in Parkinson's disease (PD) are important to understand the heterogeneity of PD and develop biomarkers and clinical trials. OBJECTIVE: To investigate (i) whether there are non-motor symptoms (NMS)- and comorbidity-based phenotypic differences between Black, Asian and Minority Ethnic (BAME) and White PD patients and (ii) whether clinically available biomarkers may help differentiate and explain the differences between the groups. METHODS: This is a multicentre (four sites, London), real-life, cross-sectional study including PD patients of BAME or White ethnicity. The primary outcome was a detailed NMS assessment; additional measurements included disease and motor stage, comorbidity, sociodemographic parameters and brain MRI imaging. RESULTS: 271 PD patients (54 Asian, 71 Black, and 146 White) were included balanced for age, gender, and disease severity (HY). Black patients had a shorter disease duration compared to White and Asian populations. The SCOPA-Motor activities of daily living scores as well as the NMSS scores were significantly higher in both Black (total score and domain "miscellaneous") and Asian (total score and domains "sleep/fatigue", "mood/apathy" and "perception/hallucinations") than White individuals. Both BAME populations had higher prevalence of arterial hypertension, and the Black population had a higher prevalence of diabetes mellitus. Brain MRI revealed a greater severity of white matter changes in Black compared to the White and Asian cohorts. CONCLUSION: These findings suggest differences in phenotype of PD in BAME populations with greater burden of NMS and motor disability and a higher rate of cardiovascular comorbidities.

The Role of Bone Scintigraphy with SPECT/CT in the Characterization and Early Diagnosis of Stage 0 Charcot Neuroarthropathy.

We describe the use of Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the investigation and diagnosis of Charcot neuroarthropathy (CN) in patients with a hot swollen foot but normal radiographs and clinical suspicion of CN, usually termed Stage 0. This was a retrospective cohort review of 46 diabetes patients who underwent 3 phase bone scintigraphy with "High Resolution" SPECT/CT. The imaging demonstrated that Stage 0 Charcot foot has a distinct bone pathology, which can be classified into three groups: (1) fractures on Computed Tomography (CT) with accompanying focal uptake of tracer on SPECT, (2) bony abnormalities apart from fracture on CT with focal uptake of tracer on SPECT, and (3) normal CT but focal bony uptake of tracer on SPECT. The CT component of SPECT/CT detected bony fractures in 59% of patients. Early treatment with below knee cast and follow-up for 24 months showed only 4 patients who developed Stage 1 Eichenholtz Charcot foot. Our findings support the use of 3 phase bone scintigraphy with SPECT/CT in the characterization and early diagnosis of CN. Stage 0 Charcot foot has a distinct bone pathology which requires urgent treatment to prevent progression to Stage 1 Eichenholtz Charcot foot. If SPECT/CT is unavailable, CT alone will detect bone fracture in 59% patients.

Timing of peptide receptor radiotargeted therapy in relation to cardiac valve surgery for carcinoid heart disease in patients with neuroendocrine metastases and cardiac syndrome. A single-centre study from a centre of excellence.

INTRODUCTION: Perioperative mortality of patients who undergo heart valve surgery for carcinoid heart valve disease has been observed to be high (5%-10%). We investigated whether peptide receptor radiotherapy with lutetium-177 dotatate can be used safely in patients with neuroendocrine neoplasm carcinoid heart valve disease and if there is associated survival advantage by reducing overall exposure of the valves to high doses of vasoactive peptides. METHOD: Retrospective case notes review was performed on 18 neuroendocrine neoplasm patients (mean 60 years), who underwent heart valve surgery between 2003 and 2017 for carcinoid heart valve disease, 9 of whom received peptide receptor radiotherapy in addition to surgery. RESULTS: All patients were treated with somatostatin receptor antagonists and underwent cardiac valvular surgery (mean two valves replaced) and three benefitted from additional coronary bypass grafting. Nine patients underwent surgery alone: in this group, the time from surgery to progression was 14 months (mean; SD 13.5 months). Nine were treated with peptide receptor radiotherapy in addition to surgery. Six underwent surgery with peptide receptor radiotherapy on progression. Time to progression from surgery to first peptide receptor radiotherapy was mean 25.1 months (SD 23.6 months). No patients developed peritreatment cardiac complications. There were no deaths within the 30-day postoperative period. Average time from surgery to last follow-up/death was 41 months (6-79) in the surgery + lutetium group and in the surgery only group 17 months (1-24). Nine patients died, five in the surgery + lutetium group and four in the surgery only group, all at greater than 1-year postsurgery. DISCUSSION: Peptide receptor radiotherapy is safe in the setting of Carcinoid valvular heart disease in patients with controlled heart failure, PPRT can be use in the pre- and post-valve surgery period. There appears to be a survival benefit of having peptide receptor radiotherapy. Further evidence for peptide receptor radiotherapy in the neoadjuvant setting prior to cardiothoracic surgery is required.

A retrospective review of the role of B-mode and color Doppler ultrasonography in the investigation of primary hyperparathyroidism: Features that differentiate benign from malignant lesions.

PURPOSE: To identify the variant features encountered in parathyroid abnormalities and document those suggesting malignant change. MATERIALS AND METHODS: Data were collected from a cohort of patients who underwent investigation for primary hyperparathyroidism over a 10-year period. Ultrasonographic features: shape, presence of calcification, cystic changes, heterogeneous echogenicity, vascularity, capsular thickening, local invasion, and vascularity were reviewed retrospectively and were used to correlate with final histological findings. RESULTS: One hundred forty-seven patients with histology and concurrent ultrasonographic scans were reviewed, and divided into benign parathyroid lesions (nodular hyperplasia (n = 44), adenoma (n = 93)) and parathyroid carcinoma (n = 10). Parathyroid carcinomas were significantly larger than benign parathyroid lesions (P = 0.030). Benign parathyroid lesions showed variant sonographic features: irregular shape (16.8%), heterogenous echogenicity (24.1%), calcification (1.5%), capsular thickening (1.5%), and cystic change (19.7%). A significantly higher proportion of parathyroid carcinomas demonstrated heterogenous echogenicity (P = 0.022), capsular thickening (P = 0.023), and infiltrative margin (P < 0.0001) than benign parathyroid lesions. Of the 137 benign parathyroid lesions, 38 (27.7%), 76 (55.5%), 23 (16.8%) were avascular, vascular, and hypervascular, respectively. Of the 10 parathyroid carcinomas, 4 (40%), 3 (30%), and 3 (30%) of lesions were avascular, vascular, and hypervascular, respectively. The vascularity of the lesions did not differ significantly between the parathyroid carcinoma and benign parathyroid lesions (P = 0.281). CONCLUSION: Ultrasonographic features such as irregular shape, heterogeneous echogenicity, cystic change, and vascularity are nondiscriminatory features between benign or malignant lesions. Large lesion size together with the presence of calcification, capsular thickening, or infiltrative margin strongly raises the suspicion of a malignant parathyroid lesion, and management should be altered.

Guidelines for the use of imaging in the management of patients with myeloma.

The role of imaging in myeloma has gained increasing importance over the past few years. The recently revised definition of myeloma from the International Myeloma Working Group (IMWG) includes cross sectional imaging as a method to define bone disease and also incorporates its use in the disease definition for patients with suspected smouldering myeloma. The National Institute for Health and Care Excellence myeloma guidelines also recommend cross sectional imaging for patients with suspected myeloma. There is also increasing use of imaging in disease assessments and the International Myeloma Working Group has recently incorporated imaging in defining new response categories of minimal residual disease negativity, with or without imaging-based evidence of disease. Plain X-rays have previously been the standard imaging modality included in a myeloma work up at presentation but evidence is mounting for use of cross-sectional modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and 18 fluoro-deoxyglucose (18 F-FDG) positron emission tomography (PET)/CT. Funding and therefore availability of newer imaging techniques remains a barrier. Here, we propose an evidence-based approach to the use and technical application of the latest imaging modalities at diagnosis and in the follow-up of patients with myeloma and plasmacytoma.

Time to redefine Myeloma.

In November 2014 the International Myeloma Working Group (IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple myeloma without any of the traditional 'CRAB' (hypercalcaemia, renal impairment, anaemia, bone disease) end organ damage criteria but with one of three new criteria would be recommended to start treatment. Previously, the standard of care for such patients was expectant management. These three new criteria are: greater than 60% clonal plasma cells on bone marrow biopsy, a serum free light chain (sFLC) ratio of >100 (the involved sFLC must be >100 mg/l) and greater than one unequivocal focal lesion on advanced imaging (low dose whole body computerized tomography, magnetic resonance imaging, (18) F fluorodeoxyglucose positron emission tomography). Although this would appear to affect a small number of patients, the impact of these changes are broad, leading to an increased use of advanced imaging, a debate around the management of patients previously diagnosed with smouldering myeloma, changed terminology and clinical trial design and an extension of the use of biomarkers. For the first time the philosophy of treatment in myeloma will change from treatment initiation only being triggered by overt end organ damage to an era where sub clinical risk factors will also be taken into account.

Long-term outcomes of (131)Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders.

BACKGROUND: (131)Iodine (I131)-metaiodobenzylguanidine (mIBG) is a radionuclide-based treatment option for metastatic gastrointestinal-pancreatic neuroendocrine tumours (GEP NET). This study aimed at identifying prognostic indicators of long-term outcome based on initial evaluation following a first mIBG treatment (7400 MBq) in a patient cohort with such tumours, with a secondary aim of evaluating progression-free survival (PFS) and overall survival (OS) following mIBG therapy. METHODS: Retrospective review of the hospital records was performed to identify a cohort of 38 adult patients who underwent (131)Iodine-mIBG therapy over a 9-year period for metastatic GEP NETs and neuroendocrine tumours with an unknown primary. Treatment response was evaluated based on radiological criteria (RECIST1.1), biochemical markers [serum Chromogranin A (CgA)/urinary 5HIAA] and symptomatic response at clinical follow-up, all evaluated at 3-6 months from first mIBG treatment. Progression-free survival (PFS) and overall survival (OS) from the first mIBG treatment were recorded. RESULTS: At 3-6 months following a single mIBG therapy, 75%, 67%, and 63% of patients showed either a partial response (PR) or stable disease (SD) on radiological, biochemical, and symptomatic criteria, respectively. Complete response (CR) was not seen in any patient. OS from the date of diagnosis and from the first therapy was 8 years +/-1.1 (95% CI 5.7 to 10.2 years) and 4 years+/-0.69 (95% CI 2.6-5.3 years), respectively. Twenty-nine percent of patients were alive at 10 years. Significant survival advantage was seen in patients with SD/PR as compared to those who had progressive disease (PD) for each of these three criteria. CONCLUSION: Biochemical, radiological (RECIST 1.1) and symptomatic assessment of disease status at 3 to 6 months after first I131-mIBG therapy stratifies patients with a poor prognosis. This can be used to identify patients who may benefit from alternative strategies of treatment.

177Lu-Dotatate therapy for the treatment of metastatic neuroendocrine tumours in a patient on haemodialysis-dosimetric considerations.

We report on a case of a 68-year-old female, currently a dialysis-dependant patient with disseminated metastatic neuroendocrine tumour, treated with 177Lu-Dotatate. As 177Lu-Dotatate is cleared predominantly by the kidneys, there are concerns regarding the treatment plan strategy to avoid increased radiation exposure compared with patients with normal renal function. For this purpose, personalized dosimetry was used to calculate the safe administered activity using whole-body scans. Employing this strategy allowed us to adjust the administered activity for the third fraction. The whole-body doses calculated were not significantly different from those received by patients with normal renal function. The radiological follow-up showed a stable disease, suggesting effective treatment. We found negligible radiation protection problems involved with this procedure.

Transformation of the multidisciplinary diabetic foot clinic into a multidisciplinary diabetic foot day unit: results from a service evaluation.

The natural history of the diabetic foot is aggressive and complex. To counteract this, we describe the transformation of a Multidisciplinary Diabetic Foot Clinic into a Multidisciplinary Diabetic Foot Day Unit, which delivers an emergency open access system for patients, with a "one-stop," same day service in which investigations are performed, results reviewed and treatment implemented. It also provides joint clinics with vascular, orthopaedic, and plastic surgeons and specialized clinics for casting of complex neuropathic feet and for the administration of intravenous or intramuscular antibiotics on the same day. The aim was to document these increasingly wide-ranging facilities by undertaking a retrospective evaluation over a 6-week period, with analysis of notes, investigations, and an anonymous patient satisfaction survey. The clinic was visited by 597 patients who attended in 1076 appointments, of which 112 (10.4%) were emergency visits; these patients attended the clinic without a booked appointment but via an open access policy, 93 of whom were known to the clinic, but 19 were new self-referred patients to the service. Furthermore, 197 (18%) were seen in a Joint Vascular Diabetic Foot Clinic and 98 (9%) were seen in a Joint Orthopaedic Plastic Diabetic Foot Clinic, 570 (53%) were seen in an Active Ulcer Clinic and 97 (9%) in a Total Contact Casting Clinic. Forty-five percent of patients were prescribed antibiotics, including 188 (76%) as oral and 45(18%) as intravenous antibiotics and 15(6%) as intramuscular injections. Of the 1076 appointments, 150 (14%) patients were in the foot clinic for more than 4 hours. Sixty (10%) patients were reviewed 4 or more times over the 6-week period. Only 22 (2%) were admitted to hospital. Of the 125 survey responders, 98% were satisfied with this service, which has evolved from a Diabetic Foot Clinic into a Multidisciplinary Diabetic Foot Day Unit.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

OBJECTIVE: Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2ß-carbomethoxy-3ß-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. METHODS: The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. RESULTS: Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. CONCLUSIONS: Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Ultrasound features of malignancy in the preoperative diagnosis of parathyroid cancer: a retrospective analysis of parathyroid tumours larger than 15 mm.

OBJECTIVE: Nearly all reported parathyroid cancers are >15 mm at presentation. The objective was to identify ultrasound criteria of malignancy in parathyroid lesions of >15 mm in size. MATERIALS AND METHODS: This study was approved by a local ethics committee. A retrospective review of patients identified from a database from 2004-2009 was performed. All patients underwent ultrasound imaging according to the protocol. Two trained observers categorized findings using the pre-determined features: shape, calcification, pattern of vascularity, local infiltration and internal lesion gray scale appearances. RESULTS: Sixty-nine patients (mean age 54.3 years, range 19-79 years; male = 16, female = 53) fulfilled the criteria of a parathyroid lesion >15 mm; 8/69 (11.6%) with parathyroid cancer and 61/69 (88.4%) with benign solitary parathyroid adenoma. A high positive predictive value (PPV) for cancer was identified for infiltration (PPV 100%) and calcification (PPV 100%), whilst a high negative predictive value (NPV) was found for the absence of suspicious vascularity (NPV 97.6%), a thick capsule (NPV 96.7) and inhomogeneity (NPV 100%). CONCLUSION: In lesions >15 mm systematic ultrasound assessment of specific features provides a valuable tool to identify parathyroid cancers before surgery.