Efficacy of denosumab monotherapy among adults with Langerhans cell histiocytosis: A prospective clinical trial.

This phase IIb clinical trial evaluated the efficacy of a bimonthly treatment schedule (Q8W) with 4 subcutaneous doses of denosumab 120 mg among adults with Langerhans cell histiocytosis needing first-line systemic therapy for either multifocal single-system disease or multisystem disease without risk organ involvement. Two months after the last treatment administration, seven patients showed disease regression, one stable disease, one non-active disease, and one disease progression. One year after treatment, progression was evident in two patients, while the remaining exhibited either a regression (three patients) or non-active disease (five patients). No permanent sequalae developed during the study and no adverse events were adjudicated in treatment. In conclusion, four doses of denosumab 120 mg Q8W subcutaneously are an effective treatment option in Langerhans cell histiocytosis patients without risk organ involvement exhibiting a response rate of 80%. Further studies are needed to confirm its role as a disease modifying agent.

A comparative study of heterogeneous antibiotic resistance of microbial populations in conventional periprosthetic tissue cultures and sonication fluid cultures of orthopaedics explanted prostheses.

BACKGROUND: "Heterogeneity" describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. We aim to investigate the frequency of heterogeneity among microbes isolated from infected prostheses, and its possible correlation with microbial resistance. METHODS: Between May 2014 and June 2019, we investigated 234 patients, at our institution, undergoing revision arthroplasty because of loosening of the prostheses or because of periprosthetic joint infection. All patients had periprosthetic tissue culture, sonication of prosthesis and direct inoculation of Sonication fluid into blood culture bottles. We assessed the presence of heterogeneity among all pathogens isolated from infected prostheses. RESULTS: Using standard non-microbiological criteria to determine periprosthetic joint infection, it was found that 143 patient (61.1%) had aseptic loosening while 91 patients (38.9%) had periprosthetic joint infection. Comparing the two methods, the results of our study showed that the method of sonication was significantly more sensitive than tissue culture [91% (83-96) vs. 43% (33-54); p < 0.005]. In this study, heterogeneity was reported in 15 cases, 16.5% of all infections and 6.4% in the total population. In our study, Staphylococcus epidermidis was the most commonly isolated strain followed by Staphylococcus aureus, at a rate of 35.2% and 19.8%, respectively. Antibiotics in which the microorganisms exhibited heterogeneous bacterial behavior most frequently were Gendamicin (5.3%), Vancomycin (4.9%). CONCLUSION: There is increasing evidence that heterogeneity can lead to therapeutic failure and that the detection of this phenotype is a prerequisite for a proper antibiotic choice to have a successful therapeutic effect.

Mycophenolate mofetil as an alternative treatment in sarcoidosis.

INTRODUCTION: In sarcoidosis although no better drug therapy than corticosteroids (CS) has emerged, alternative immunosuppressive agents are used when indicated. Mycophenolate mofetil (MMF) presents rapid action, a considerable safety profile and absence of lung toxicity. Few data exist so far on its use in patients with sarcoidosis. This is a retrospective study on the effectiveness and safety of MMF in patients with sarcoidosis. MATERIALS AND METHODS: All patients with biopsy proven sarcoidosis treated for at least 1 year with MMF from 2008 to 2017 in our department are evaluated. RESULTS: Eight patients with both pulmonary and extrapulmonary disease are included in the analysis. During follow-up, symptoms and chest radiological findings improved in all. A statistically significant improvement of FEV1 and FVC is reported (p = 0.010 and p = 0.021 respectively). Cardiac and renal disease resolved during treatment while dermal disease significantly improved. MMF permitted CS dose reduction from 15.0 (10.0, 35.0) to 2.5 (0.0, 5.0) mg prednisolone (or equivalent), p = 0.016. All patients but one, tolerated well MMF. CONCLUSION: MMF as an alternative drug in systemic sarcoidosis, proved safe and effective, permitting the reduction of the dose of oral CS and leading to clinical, functional and radiological improvement.

Experimental Candida albicans osteomyelitis: Microbiologic, antigenic, histologic, and 18FDG-PET-CT imaging characteristics in a newly established rabbit model.

Candida osteomyelitis is a debilitating disease that is difficult to diagnose and treat. As there are no animal models or prospective studies for this uncommon infection, little is known about the pathogenesis, diagnosis, or treatment. We therefore sought to establish an animal model for the study of the pathophysiology, diagnostic modalities, and therapeutic interventions of Candida osteomyelitis. We developed a modified version of the Norden rabbit model of tibial osteomyelitis, in which the right tibia was inoculated intraoperatively with different inocula of C. albicans or normal saline as control. On days 7, 14, and 21 after inoculation, the animals underwent bone radiography, 18-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET/CT) scan, and blood sampling for blood cultures, blood counts, erythrocyte sedimentation rate, and Candida mannan antigen serum levels. On day 21, animals were euthanized, and infected tibias harvested for culture and histology. Among eight evaluable animals inoculated with 1 × 106 to 1 × 107 cfu, histology and bone cultures established the presence of Candida osteomyelitis in seven, with a host response of neutrophils, mononuclear cells, multinucleate giant cells, fibrosis, and necrosis. Infected animals demonstrated radiological signs of osteomyelitis with significantly increased tracer uptake in 18FDG-PET/CT scans (P < .01) and elevated serum mannan levels (P < .01). All blood cultures were negative. Indices of inflammation were only slightly increased. In conclusion, we report successful establishment of a new animal model of Candida albicans osteomyelitis that may be applicable to advancing our understanding of the pathophysiology, diagnostic modalities, and treatment of this debilitating infection.

The effect of patient anxiety and depression on motion during myocardial perfusion SPECT imaging.

BACKGROUND: Patient motion during myocardial perfusion SPECT imaging (MPI) may be triggered by a patient's physical and/or psychological discomfort. The aim of this study was to investigate the impact of state anxiety (patient's reaction to exam-related stress), trait anxiety (patient's personality characteristic) and depression on patient motion during MPI. METHODS: All patients that underwent MPI in our department in a six-month period were prospectively enrolled. One hundred eighty-three patients (45 females; 138 males) filled in the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory (BDI), along with a short questionnaire regarding their age, height and weight, level of education in years, occupation, and marital status. Cardiovascular and other co-morbidity factors were also evaluated. Through inspection of raw data on cinematic display, the presence or absence of patient motion was registered and classified into mild, moderate and severe, for both phases involved in image acquisition. RESULTS: The correlation of patient motion in the stress and delay phases of MPI and each of the other variables was investigated and the corresponding Pearson's coefficients of association were calculated. The anxiety-motion (r = 0.43, P < 0.0001) and depression-motion (r = 0.32, P < 0.0001) correlation results were moderately strong and statistically significant for the female but not the male patients. All the other variables did not demonstrate any association with motion in MPI, except a weak correlation between age and motion in females (r = 0.23, P < 0.001). CONCLUSIONS: The relationship between anxiety-motion and depression-motion identified in female patients represents the first supporting evidence of psychological discomfort as predisposing factor for patient motion during MPI.

Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan contributes to the diagnosis and management of brucellar spondylodiskitis.

BACKGROUND: Limited data suggest that fluorine-18 fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography combined with computed tomography (PET/CT) scan may be useful for diagnosing infections of the spine. Brucellar spondylodiskitis might be devastating and current imaging techniques lack sensitivity and specificity. The aim of this prospective study was to determine the role of F-18 FDG PET/CT scan in the diagnosis of brucellar spondylodiskitis and in monitoring the efficacy of its treatment. METHODS: Ten consecutive patients with brucellar spondylitis were prospectively evaluated with PET/CT. Baseline evaluation included also magnetic resonance imaging (MRI) of the affected spine, indices of inflammation, the slide agglutination test (SAT), and the standard hematology and biochemistry. All cases were treated with suitable antibiotics until resolution or significant improvement of clinical and radiological (MRI) findings. Upon completion of treatment, they were re-evaluated with follow-up PET/CT scan. The maximum standardized uptake values (SUV) were measured and compared with SAT. RESULTS: In all patients there was an increased F-18 FDG activity in the infected spine region detected by the initial MRI. F-18 FDG PET/CT provided additional information, compared to MRI, in 4 (40%) patients. More specifically it revealed additional spine lesions (in 3 patients), lymphadenitis, arthritis, organomegaly, as well as new paravertebral soft tissue involvement and epidural masses. This additional information had an impact on the duration of treatment in these patients. At the end of treatment all patients had a complete clinical response; 5 patients had positive serology, 6 patients had residual MRI findings, while 9 had a positive PET/CT but with significantly decreased FDG uptake compared to baseline (median 2.6, range 1.4 - 4.4 vs. median 5.5, range 2.8 - 9.4, p = 0.005). During the follow up period (median 12.5 months) no relapses have been observed. No significant association was observed between the SUV and SAT. CONCLUSIONS: Our study suggests that in patients with brucellar spondylodiskitis F-18 FDG PET/CT scan can provide additional information on the spread of the infection, compared to MRI. Successful treatment is associated with a significant decrease in SUVmax values; thus, PET/CT scan may be a complementary method for determining the efficacy of treatment.

From Karl Wurm and Guy Scadding's staging to 18F-FDG PET/CT scan phenotyping and far beyond: perspective in the evading history of phenotyping in sarcoidosis.

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the 18F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current "omics." The hybrid molecular imaging of the 18F-FDG PET/CT scan, by unveiling the glucose metabolism of inflammatory cells, can identify high sensitivity inflammatory active granulomas, the hallmark of sarcoidosis-even in clinically and physiologically silent sites-and, as recently shown, is successful in identifying an unexpected ordered stratification into four phenotypes: (I) hilar-mediastinal nodal, (II) lungs and hilar-mediastinal nodal, (III) an extended nodal supraclavicular, thoracic, abdominal, inguinal, and (IV) all the above in addition to systemic organs and tissues, which is therefore the ideal phenotyping instrument. During the "omics era," studies could provide significant, distinct, and exclusive insights into sarcoidosis phenotypes linking clinical, laboratory, imaging, and histologic characteristics with molecular signatures. In this context, the personalization of treatment for sarcoidosis patients might have reached its goal.

Tumor Size Measurements for Predicting Hodgkin's and Non-Hodgkin's Lymphoma Response to Treatment.

The purpose of this study was to investigate the value of tumor size measurements as prognostic indicators of treatment outcome of Hodgkin's and Non-Hodgkin's lymphomas. 18F-FDG PET/CT exams before and after treatment were analyzed and metabolic and anatomic parameters-tumor maximum diameter, tumor maximum area, tumor volume, and maximum standardized uptake value (SUVmax)-were determined manually by an expert and automatically by a computer algorithm on PET and CT images. Results showed that the computer algorithm measurements did not correlate well with the expert's standard maximum tumor diameter measurements but yielded better three dimensional metrics that could have clinical value. SUVmax was the strongest prognostic indicator of the clinical outcome after treatment, followed by the automated metabolic tumor volume measurements and the expert's metabolic maximum diameter measurements. Anatomic tumor measurements had poor prognostic value. Metabolic volume measurements, although promising, did not significantly surpass current standard of practice, but automated measurements offered a significant advantage in terms of time and effort and minimized biases and variances in the PET measurements. Overall, considering the limited value of tumor size in predicting response to treatment, a paradigm shift seems necessary in order to identify robust prognostic markers in PET/CT; radiomics, namely combinations of anatomy, metabolism, and imaging, may be an option.

Clinical Perspectives for 18F-FDG PET Imaging in Pediatric Oncology: Μetabolic Tumor Volume and Radiomics.

Pediatric cancer, although rare, requires the most optimized treatment approach to obtain high survival rates and minimize serious long-term side effects in early adulthood. 18F-FDG PET/CT is most helpful and widely used in staging, recurrence detection, and response assessment in pediatric oncology. The well-known 18F-FDG PET metabolic indices of metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) have already revealed an independent significant prognostic value for survival in oncologic patients, although the corresponding cut-off values remain study-dependent and not validated for use in clinical practice. Advanced tumor "radiomic" analysis sheds new light into these indices. Numerous patterns of texture 18F-FDG uptake features can be extracted from segmented PET tumor images due to new powerful computational systems supporting complex "deep learning" algorithms. This high number of "quantitative" tumor imaging data, although not decrypted in their majority and once standardized for the different imaging systems and segmentation methods, could be used for the development of new "clinical" models for specific cancer types and, more interestingly, for specific age groups. In addition, data from novel techniques of tumor genome analysis could reveal new genes as biomarkers for prognosis and/or targeted therapies in childhood malignancies. Therefore, this ever-growing information of "radiogenomics", in which the underlying tumor "genetic profile" could be expressed in the tumor-imaging signature of "radiomics", possibly represents the next model for precision medicine in pediatric cancer management. This paper reviews 18F-FDG PET image segmentation methods as applied to pediatric sarcomas and lymphomas and summarizes reported findings on the values of metabolic and radiomic features in the assessment of these pediatric tumors.

A few-shot U-Net deep learning model for lung cancer lesion segmentation via PET/CT imaging.

Over the past few years, positron emission tomography/computed tomography (PET/CT) imaging for computer-aided diagnosis has received increasing attention. Supervised deep learning architectures are usually employed for the detection of abnormalities, with anatomical localization, especially in the case of CT scans. However, the main limitations of the supervised learning paradigm include (i) large amounts of data required for model training, and (ii) the assumption of fixed network weights upon training completion, implying that the performance of the model cannot be further improved after training. In order to overcome these limitations, we apply a few-shot learning (FSL) scheme. Contrary to traditional deep learning practices, in FSL the model is provided with less data during training. The model then utilizes end-user feedback after training to constantly improve its performance. We integrate FSL in a U-Net architecture for lung cancer lesion segmentation on PET/CT scans, allowing for dynamic model weight fine-tuning and resulting in an online supervised learning scheme. Constant online readjustments of the model weights according to the users' feedback, increase the detection and classification accuracy, especially in cases where low detection performance is encountered. Our proposed method is validated on the Lung-PET-CT-DX TCIA database. PET/CT scans from 87 patients were included in the dataset and were acquired 60 minutes after intravenous18F-FDG injection. Experimental results indicate the superiority of our approach compared to other state-of-the-art methods.

Radiomics/Radiogenomics in Lung Cancer: Basic Principles and Initial Clinical Results.

Lung cancer is the leading cause of cancer-related deaths worldwide, and elucidation of its complicated pathobiology has been traditionally targeted by studies incorporating genomic as well other high-throughput approaches. Recently, a collection of methods used for cancer imaging, supplemented by quantitative aspects leading towards imaging biomarker assessment termed "radiomics", has introduced a novel dimension in cancer research. Integration of genomics and radiomics approaches, where identifying the biological basis of imaging phenotypes is feasible due to the establishment of associations between molecular features at the genomic-transcriptomic-proteomic level and radiological features, has recently emerged termed radiogenomics. This review article aims to briefly describe the main aspects of radiogenomics, while discussing its basic limitations related to lung cancer clinical applications for clinicians, researchers and patients.

Balloon kyphoplasty: scintigraphy as the ultimate decision maker?

Balloon kyphoplasty is still controversial as a treatment for vertebral compression fractures (VCFs) due to osteoporosis. Nevertheless, the authors conducted a prospective study in 60 patients about the effectiveness of scintigraphy, after the conventional roentgenographic examination, as an ultimate decision maker for the identification of the levels to be treated. Seventy-one levels were radiographically and scintigraphically positive, were seen as active, and thus treated. Thirty-seven levels were radiographically negative but positive scintigraphically, were considered as imminent fractures, and thus treated. Ten levels were positive radiographically, but negative scintigraphically, and were not treated as they were considered as healed. The Oswestry Disability Score (100% = worst possible condition) improved from 38.8% +/- 39.5% at baseline, to 2.38% +/- 3.99% on the first postoperative day (p < 0.001), to 2.00% +/- 3.40% at 1 month (p < 0.001) and to 1.93% +/- 3.33% at 6 months (p < 0.001). This preliminary study gives a hint that scintigraphy might work as the ultimate decision maker, even when plain radiographs are negative. Further studies will be needed to compare patients with VCFs positive radiographically and scintigraphically, and other patients with VCFs negative radiographically, but positive scintigraphically.

High (18)F-FDG uptake by the remaining adrenal gland four months after surgery and initiation of mitotane treatment in two patients with adrenocortical carcinoma.

Two men, one 42 and the other 35 years old were both subjected to adrenalectomy for adrenocortical carcinoma (ACC). Adjuvant treatment with mitotane [o,p΄-dichloro-diphenyl-dichloroethane, (o,p΄-DDD)], was initiated following surgery. Mitotane is the only agent available at present for treatment in ACC because of a late-onset specific adrenocortical cell toxicity. Both patients underwent a (18)F-FDG-PET/CT scan, which revealed 4 months after starting treatment with mitotane significantly high (18)F-FDG uptake in the contralateral adrenal gland. Both patients underwent magnetic resonance imaging, while one had a laparotomy, because of an abcess at the site of previous adrenalectomy. No metastasis or size increase of the remaining adrenal glands were found suggesting that their hypermetabolic state could be attributed to mitotane treatment. Beside its cytotoxic delayed-effect, mitotane has an early -onset effect on steroid metabolism. In conclusion, an abnormal high (18)F-FDG uptake was observed in the contralateral adrenal gland in both our adrenalectomized ACC patients, 4 months after starting mitotane treatment, probably related to mitotane's effect on steroid metabolism, not yet fully understood.

Can pain influence the severity of findings of an (18)F-FDG PET/CT scan in loosening hip arthroplasty?

Pain is a common symptom after loosening and/or after infection of arthroplasty. The aim of the present case report is to indicate that fluorine-18-fluorodeoxy-glucose positron emission tomography/computerized tomography((18)F-FDG PET/CT) scan can be used for the evaluation of pain at the site of arthroplasty with a semi quantitative measurement. An 84 years old male patient, with a history of papillary thyroid cancer was referred to our Nuclear Medicine Department for an (18)F-FDG PET/CT scan for evaluation of his metastatic disease. He reported right hip prosthesis thirty years ago and now suffered from significant pain in the right hip joint which on a scale from 1 to 10 could be rated as grade 8. White blood cell count, sedimentation rate and C-reactive protein were within normal limits. Four years ago he also had severe pain on the right leg that could be rated as grade 8, and underwent an (18)F-FDG PET/CT scan that showed a maximum standardized uptake value (SUV(max)) of 9.8. A year later, at a follow up (18)F-FDG PET/CT scan and under a similar severe pain, SUV(max) was 10. The patient had a hip prosthesis in the left leg 3 years ago, for which he reported pain that could be rated as grade 3 and the SUV(max) was then 3.7. The degree of (18)F-FDG uptake is related to cellular metabolic rate and to the number of glucose transporters. In inflammation, the activated inflammatory cells demonstrate increased expression of glucose transporters and the affinity of glucose transporters for deoxyglucose is increased by various cytokines and growth factors. Furthermore, when the mononuclear cells and the granulocytes are activated by certain infectious humoral stimuli, they use large amounts of glucose by the hexose monophosphate shunt and the rate of oxygen uptake is intensely increased, during the so called "respiratory burst". In the present case, it was interesting to note that the degree of (18)F-FDG uptake at the sites of loosening hip arthroplasty was related to the severity of pain. Signs of infection or inflammation although not obvious in our case, could not be excluded because sensitivity, specificity and accuracy of PET for detecting infection associated with hip prostheses has been reported to be, 90%, 89.3% and 89.5%, respectively and sensitivity and specificity for detecting periprosthetic inflammation 100% and 45.5%,respectively. In another study using as a criterion for periprosthetic infection the increased (18)F-FDG activity at the bone-prosthesis interface of the femoral component, sensitivity, specificity, positive and negative predictive values for the (18)F-FDG PET study where 85%, 93%, 80% and 95%, respectively. Inflammation, often intense, may be present in aseptic loosening and characterized by increased periprosthetic (18)F-FDG uptake. In conclusion, in our case the degree of (18)F-FDG uptake in a loosening hip arthroplasty was related to the severity of pain although inflammation or infection could also play some role. Further studies are required to prove this suggestion.

Clinical Utility of 18F-FDG PET in Neuroendocrine Tumors Prior to Peptide Receptor Radionuclide Therapy: A Systematic Review and Meta-Analysis.

The role of 18F-FDG PET in patients with variable grades of neuroendocrine tumors (NETs) prior to peptide receptor radionuclide therapy (PRRT) has not been adequately elucidated. We aimed to evaluate the impact of 18F-FDG PET status on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in neuroendocrine tumor (NET) patients receiving PRRT. We searched the MEDLINE, Embase, Cochrane Library, and Web of Science databases up to July 2020 and used the Newcastle-Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5091 articles were screened. In 12 studies, 1492 unique patients with NETs of different origins were included. The DCR for patients with negative 18F-FDG PET status prior to PRRT initiation was 91.9%, compared to 74.2% in patients with positive 18F-FDG PET status (random effects odds ratio (OR): 4.85; 95% CI: 2.27-10.36). Adjusted analysis of pooled hazard ratios (HRs) confirmed longer PFS and OS in NET patients receiving PRRT with negative 18F-FDG PET (random effects HR:2.45; 95%CIs: 1.48-4.04 and HR:2.25; 95% CIs:1.55-3.28, respectively). In conclusion, 18F-FDG PET imaging prior to PRRT administration appears to be a useful tool in NET patients to predict tumor response and survival outcomes and a negative FDG uptake of the tumor is associated with prolonged PFS and OS.

Routine needle biopsy during vertebral augmentation procedures. Is it necessary?

Vertebral augmentation procedures are currently widely performed to treat vertebral compression fractures. The purpose of this study was to determine the frequency of underlying previously unrecognized etiology in a consecutive series of patients undergoing kyphoplasty to treat vertebral compression fractures. A prospective histological evaluation of vertebral body biopsy specimens from presumed osteoporotic vertebral compression fractures were performed in order to identify aforementioned causes. Over a 2-year period, vertebral body biopsies from 154 vertebral levels were performed in 75 patients undergoing kyphoplasty for vertebral compression fractures. All patients received a preoperative workup that included plain radiographs, MRI, whole body bone scan, and laboratory examinations. Bone specimens were obtained from affected vertebral bodies and submitted for histologic evaluation to identify the prevalence of an underlying cause. All specimens demonstrated fragmented bone with variable amounts of unmineralised bone, signs of bone-remodeling and/or fracture-healing. In 11 patients underlying pathology other than osteoporosis was identified (prostate cancer, 1; pancreatic cancer, 1; colon cancer, 1; breast cancer, 2; multiple myeloma, 3; leukemia, 1; and lung cancer, 2). In all but one patient the results of the biopsy confirmed the diagnosis suspected from the preoperative workup. For the last patient, namely the one with pancreatic cancer, the workup did not identify the origin of the primary tumor, although the patient was considered to have a compression fracture secondary to metastatic disease of unknown origin, the vertebral biopsy suggested the presence of adenocarcinoma which eventually was proven to be pancreatic cancer. In augmentation procedures for vertebral compression fractures, bone biopsy should be reserved for the patients where the preoperative evaluation raises the suspicion of a non-osteoporotic etiology.

18 F-FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic heart failure patients with impaired systolic function.

AIMS: Depression is an important issue in heart failure (HF). The study investigated whole-brain and regional brain glucose metabolism in HF patients and its association with depression comorbidity. METHODS AND RESULTS: Twenty-nine hospitalized patients with symptomatic systolic HF (left ventricular ejection fraction <40%), New York Heart Association (NYHA) class II-IV and mean age of 55.5 ± 12.0 years, had psychometric questionnaires before discharge and an 18 F-FDG PET/CT brain scan after discharge. Semi-automated image analysis was performed on all cases and 30 matched controls. The metabolic parameter mean standardized uptake value (SUVmean ) was calculated for the whole brain and three brain regions implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing regional brain SUVmean with whole-brain SUVmean . Cases had lower average whole-brain SUVmean (3.90 ± 1.49 vs. 5.10 ± 1.35, P = 0.001) and average regional brain SUVmean (4.57 ± 2.31 vs. 9.96 ± 3.58, P < 0.001) compared to controls. Whole-brain SUVmean had a significant correlation with patient age, NYHA class, diabetes, creatinine levels, depression, and cognitive impairment. Regional brain SUVmean was correlated with whole-brain SUVmean and depression. The standardized SUVmean , in particular, was found to be a robust index that could differentiate HF patients with 'epiphenomenal' (>0.93) or 'real' (≤0.93) depression. CONCLUSION: Heart failure patients with more severe disease showed whole-brain and regional brain hypometabolism in 18 F-FDG PET/CT. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between 'epiphenomenal' and 'real' depression. Namely, presence of whole-brain hypometabolism suggested 'epiphenomenal' depression, whereas absence suggested 'real' depression. Presence of significant relative regional brain hypometabolism enhanced the likelihood of 'real' depression diagnosis.

18F-FDG PET/CT in Pulmonary Sarcoidosis:Quantifying Inflammation by the TLG index.

Objectives: In sarcoidosis progressive pulmonary disease affects prognosis. Pulmonary disease activity estimated by classic means poorly predicts severity and progressiveness. 18F-fluoro-2-deoxyglucose-positron-emission-tomography computed-tomography (18F-FDG-PET/CT) estimates pulmonary activity by inflammatory-cells metabolism. We aimed to investigate pulmonary sarcoidosis by 18F-FDG-PET/CT and evaluate the role of total-lesion-glycolysis (TLG) value, as an index quantifying the whole burden of lung inflammation.Methods: This is a retrospective study of sequentially gathered data. From a Greek cohort of 195 sarcoidosis-patients, 87 were identified with lung increased 18F-FDG uptake and further studied.Results: Visualizing lung by 18F-FDG-PET/CT identified new imaging patterns and revealed activity in all Scadding stages. Ever-smokers presented significantly higher TLG and lower DLCO compared to never-smokers. However, TLG value did not correlate with functional indices and did not differ between symptomatic and non-symptomatic patients. Among treatment-naïve patients, TLG did not differ significantly in those requiring therapy compared to those remained off.Conclusion: 18F-FDG PET/CT improved imaging and detection of pulmonary involvement and through TLG value revealed the deleterious smoking effect. The fact that TLG neither detected patients with clinical symptoms and functional impairment nor identified those requiring treatment once again confirms that in pulmonary sarcoidosis the link between activity, severity and decision to treat still eludes us.

Emerging phenotypes of sarcoidosis based on 18F-FDG PET/CT: a hierarchical cluster analysis.

Objectives: In sarcoidosis, the definition of organ involvement with traditional means appears laborious and somewhat controversial, and phenotyping by the above overlapping. 18F-FDG PET/CT defines disease extent by activity more precisely, and may result in a better understanding of sarcoidosis disease behavior and phenotypes expression. We hypothesized that 18F-FDG PET/CT could add in the phenotyping of sarcoidosis patients by unveiling in detail sites of involvement even in clinically and physiologically silent disease.Methods: This study was designed to investigate the role of 18F-FDG PET/CT in phenotyping sarcoidosis using cluster analysis by adding this new means in the routine work-up of 195 sarcoidosis patients of a single academic center.Results: 18F-FDG PET/CT succeeded to identify despite the random distribution of the disease, an ordered stratification into 4 phenotypes: I) thoracic nodal hilar-mediastinal, II) thoracic nodal hilar-mediastinal and lungs, III) an extended thoracic and extra-thoracic only nodal phenotype including inguinal-abdominal-supraclavicular stations, and IV) all the above plus systemic organs and tissues such as muscles-bones-spleen and skin.Conclusion: Though further studies are necessary to confirm findings as patterns of disease behavior; the proposed phenotypes may prove useful in the design of future studies with homogeneous cohorts facilitating in sarcoidosis patients a personalized medicine approach.

Erdheim-Chester Disease and Acute Myeloid Leukemia with Mutated NPM1 in a Patient with Clonal Hematopoiesis: A Case Report.

BACKGROUND: Erdheim-Chester Disease (ECD) is a clonal non-Langerhans histiocytosis, classified as a macrophage-dendritic cell neoplasm in the 2016 WHO classification. The exact cell of origin of ECD is unknown, although some limited evidence suggests that it arises from myeloid progenitors. CASE PRESENTATION: A 43-year-old patient, diagnosed with BRAF V600E mutated ECD, developed NPM1+/FLT3+ acute myeloid leukemia (AML) with wild-type BRAF, 15 months after the initial ECD diagnosis. The patient received intensive chemotherapy plus midostaurin, followed by midostaurin maintenance. Six months into maintenance, the patient remains in complete remission with low-level measurable residual disease, whereas ECD shows a sustained partial metabolic response. Molecular karyotype at several distinct timepoints, namely ECD diagnosis, AML diagnosis, and following treatment of AML, highlighted a molecular signature, indicative of a persistent, underlying clonal hematopoiesis. CONCLUSION: This case report suggests that ECD and AML might represent an expansion of two distinct clones in a background of clonal hematopoiesis, indicating their shared origin. Moreover, molecular karyotype might serve as a strong, inexpensive tool for revealing clonal hematopoiesis in cases of negative targeted next-generation sequencing. Finally, the moderate response of ECD to midostaurin suggests that kinase inhibition might have a potential role in ECD treatment.