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Patients may experience long-term physical, psychological and cognitive impairment after intensive care unit (ICU) discharge, a condition commonly described as post-intensive care syndrome. The relative contribution of each of these components to long-term quality of life was never investigated.The aim of this study is to identify the type and severity of disability and QoL at the discharge from ICU and up to following 6 months.Material and Methods. All patients (n=218) discharged from a university hospital ICU between April 2016 and July 2017 were eligible. Exclusion criteria included: age

Abstract Arginine methylation has been recognized as a post-translational modification with pleiotropic effects that span from regulation of transcription to metabolic processes that contribute to aberrant cell proliferation and tumorigenesis. This has brought significant attention to the development of therapeutic strategies aimed at blocking the activity of protein arginine methyltransferases (PRMTs), which catalyze the formation of various methylated arginine products on a wide variety of cellular substrates. GSK3368715 is a small molecule inhibitor of type I PRMTs currently in clinical development. Here, we evaluate the effect of type I PRMT inhibition on arginine methylation in normal human peripheral blood mononuclear cells and utilize a broad proteomic approach to identify type I PRMT substrates. This work identified heterogenous nuclear ribonucleoprotein A1 (hnRNP-A1) as a pharmacodynamic biomarker of type I PRMT inhibition. Utilizing targeted mass spectrometry (MS), methods were developed to detect and quantitate changes in methylation of specific arginine residues on hnRNP-A1. This resulted in the development and validation of novel MS and immune assays useful for the assessment of GSK3368715 induced pharmacodynamic effects in blood and tumors that can be applied to GSK3368715 clinical trials.

Abstract Background Abnormal beta-amyloid (Aβ) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer’s disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1–4, 2017). Previously, we established the scopolamine challenge test (SCT) as a “cognitive stress test” screening measure to identify individuals at risk for AD (Alzheimer’s & Dementia 10(2):262–7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval. Methods Older adults (N = 63, aged 55–75 years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27 months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam. Results Significant differences in both cognitive performance and in Aβ neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period. Conclusions Cognitive response to the SCT (Alzheimer’s & Dementia 10(2):262–7, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27 months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years.

Background: Recent genome-wide association screening (GWAS) studies have linked Alzheimer's disease (AD) neuropathology to gene networks that regulate immune function. Kan et al. recently reported that Arg1 (an anti-inflammatory gene that codes for arginase-1) is expressed in parts of the brain associated with amyloidosis prior to the onset of neuronal loss, suggesting that chronic brain arginine deprivation promotes AD-related neuropathology. They blocked arginine catabolism in their mouse AD model by administration of eflornithine (DFMO) to juvenile animals, effectively blocking the expression of AD-related amyloid pathology as the mice aged. We report results from a single-case study in which DFMO was administered, for the first time, in an attempt to slow progression of AD in a single woman with multi-domain, amnestic MCI who was unable to tolerate an acetylcholinesterase inhibitor.Methods: Patient C.S. is a 74-year old female with a 5-year history of cognitive decline who was placed on DFMO (500 mg b.i.d.) for 12 months, with amyloid PET scans (baseline and 12-months), APOE genotyping and neuropsychological exams at baseline, 3, 9, and 12 months.Results: C.S. suffered continued cognitive decline over 12 months, including progressive worsening of orientation, social functions and ability to engage in IADL's. She also showed progressive decline on measures of episodic memory and executive function. Florbetapir PET imaging yielded elevated total neocortical SUVr scores at both baseline (SUVr = 1.55) and at 12 months (SUVr = 1.69).Conclusions: We report a first attempt at using DFMO to slow AD progression. This 12-month single-case trial did not halt continued amyloidosis nor cognitive decline. Although this trial was predicated on data reported by Kan et al. (2015) showing that DFMO administered to juvenile AD-prone mice led to diminished amyloid aggregation, this attempt to treat an older mild AD patient may not be a fair test of Kan et al.'s model and results. A future trial might seek to block amyloidosis in young adults who are autosomal gene carriers for early onset AD, or perhaps in adults who are very clearly in the pre-clinical disease stage.Trial Registration: This trial was registered as a Compassionate Use IND #128888 with the United States Food and Drug Administration (FDA).

Background: Thyroid nodules are common yet remain a diagnostic challenge. While ultrasound and Thyroid Imaging Reporting and Data Systems (TIRADS) are accepted as standard, the use of thyroid scintigraphy in euthyroid patients is debated. The European Association of Nuclear Medicine advocates it, whereas the American Thyroid Association and European Thyroid Association do not. However, it has not been evaluated whether scintigraphy adds value to TIRADS in a multimodal approach. Our study addresses this gap by assessing the impact of integrated pertechnetate scintigraphy on TIRADS accuracy. Methods: The diagnostic performance of ACR-TIRADS, EU-TIRADS, pertechnetate scintigraphy, and multimodal models were retrospectively analyzed for 322 nodules (231 benign, 91 malignant) in 208 euthyroid patients with histopathology as a reference. Generalized estimating equations were used for statistical analysis. Results: On scintigraphy, 210 nodules were hypofunctional, 99 isofunctional, and 13 hyperfunctional. The AUC for thyroid scintigraphy, ACR-TIRADS, and EU-TIRADS were 0.6 (95% CI: 0.55-0.66), 0.83 (95% CI: 0.78-0.88), and 0.78 (95% CI: 0.72-0.83). Integrating scintigraphy with ACR-TIRADS and EU-TIRADS slightly increased diagnostic accuracy (AUC 0.86 vs. 0.83, p = 0.039 and AUC 0.80 vs. 0.78, p = 0.008) and adjusted the malignancy probability for intermediate risk TIRADS categories, with iso- or hyperfunctioning nodules in ACR-TIRADS-TR4 or EU-TIRADS-4 showing comparable malignancy probabilities as hypofunctioning nodules in TR3 or EU-TIRADS-3, respectively. Conclusions: Integrating thyroid scintigraphy with ACR- or EU-TIRADS moderately improves diagnostic performance, potentially benefiting management, especially in complex cases like multinodular goiter or indeterminate FNA. Further research is warranted to validate these findings and explore their clinical implications.

Objectives: The aim of this proof-of-principle study combining data analysis and computer simulation was to evaluate the robustness of apparent diffusion coefficient (ADC) values for lymph node classification in prostate cancer under conditions comparable to clinical practice., Materials and Methods: To assess differences in ADC and inter-rater variability, ADC values of 359 lymph nodes in 101 patients undergoing simultaneous prostate-specific membrane antigen (PSMA)-PET/MRI were retrospectively measured by two blinded readers and compared in a node-by-node analysis with respect to lymph node status. In addition, a phantom and 13 patients with 86 lymph nodes were prospectively measured on two different MRI scanners to analyze inter-scanner agreement. To estimate the diagnostic quality of the ADC in real-world application, a computer simulation was used to emulate the blurring caused by scanner and reader variability. To account for intra-individual correlation, the statistical analyses and simulations were based on linear mixed models., Results: The mean ADC of lymph nodes showing PSMA signals in PET was markedly lower (0.77 × 10 -3 mm 2 /s) compared to inconspicuous nodes (1.46 × 10 -3 mm 2 /s, p < 0.001). High inter-reader agreement was observed for ADC measurements (ICC 0.93, 95%CI [0.92, 0.95]). Good inter-scanner agreement was observed in the phantom study and confirmed in vivo (ICC 0.89, 95%CI [0.84, 0.93]). With a median AUC of 0.95 (95%CI [0.92, 0.97]), the simulation study confirmed the diagnostic potential of ADC for lymph node classification in prostate cancer., Conclusion: Our model-based simulation approach implicates a high potential of ADC for lymph node classification in prostate cancer, even when inter-rater and inter-scanner variability are considered., Clinical Relevance Statement: The ADC value shows a high diagnostic potential for lymph node classification in prostate cancer. The robustness to scanner and reader variability implicates that this easy to measure and widely available method could be readily integrated into clinical routine., Key Points: • The diagnostic value of the apparent diffusion coefficient (ADC) for lymph node classification in prostate cancer is unclear in the light of inter-rater and inter-scanner variability. • Metastatic and inconspicuous lymph nodes differ significantly in ADC, resulting in a high diagnostic potential that is robust to inter-scanner and inter-rater variability. • ADC has a high potential for lymph node classification in prostate cancer that is maintained under conditions comparable to clinical practice., (© 2023. The Author(s).)

There is an increasing number of potential quantitative biomarkers that could allow for early assessment of treatment response or disease progression. However, measurements of such biomarkers are subject to random variability. Hence, differences of a biomarker in longitudinal measurements do not necessarily represent real change but might be caused by this random measurement variability. Before utilizing a quantitative biomarker in longitudinal studies, it is therefore essential to assess the measurement repeatability. Measurement repeatability obtained from test-retest studies can be quantified by the repeatability coefficient, which is then used in the subsequent longitudinal study to determine if a measured difference represents real change or is within the range of expected random measurement variability. The quality of the point estimate of the repeatability coefficient, therefore, directly governs the assessment quality of the longitudinal study. Repeatability coefficient estimation accuracy depends on the case number in the test-retest study, but despite its pivotal role, no comprehensive framework for sample size calculation of test-retest studies exists. To address this issue, we have established such a framework, which allows for flexible sample size calculation of test-retest studies, based upon newly introduced criteria concerning assessment quality in the longitudinal study. This also permits retrospective assessment of prior test-retest studies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The apparent diffusion coefficient (ADC) is a candidate marker of treatment response in osteoblastic metastases that are not evaluable by morphologic imaging. However, it is unclear whether the ADC meets the basic requirement for reliable treatment response evaluation, namely a low variance of repeated measurements in relation to the differences found between viable and nonviable metastases. The present study addresses this question by analyzing repeated in vivo ADC median measurements of 65 osteoblastic metastases in nine patients, as well as phantom measurements. PSMA-PET served as a surrogate for bone metastasis viability. Measures quantifying repeatability were calculated and differences in mean ADC values according to PSMA-PET status were examined. The relative repeatability coefficient %RC of ADC median measurements was 5.8% and 12.9% for phantom and in vivo measurements, respectively. ADC median values of bone metastases ranged from 595×10-6mm2/s to 2090×10-6mm2/s with an average of 63% higher values in nonviable metastases compared with viable metastases ( p < 0.001). ADC shows a small repeatability coefficient in relation to the difference in ADC values between viable and nonviable metastases. Therefore, ADC measurements fulfill the technical prerequisite for reliable treatment response evaluation in osteoblastic metastases.

Backgrounds: Elastic motion correction in PET has been shown to increase image quality and quantitative measurements of PET datasets affected by respiratory motion. However, little is known on the impact of respiratory motion correction on clinical image evaluation in oncologic PET. This study evaluated the impact of motion correction on expert readers' lymph node assessment of lung cancer patients., Methods: Forty-three patients undergoing F-18-FDG PET/CT for the staging of suspected lung cancer were included. Three different PET reconstructions were investigated: non-motion-corrected ("static"), belt gating-based motion-corrected ("BG-MC") and data-driven gating-based motion-corrected ("DDG-MC"). Assessment was conducted independently by two nuclear medicine specialists blinded to the reconstruction method on a six-point scale [Formula: see text] ranging from "certainly negative" (1) to "certainly positive" (6). Differences in [Formula: see text] between reconstruction methods, accounting for variation caused by readers, were assessed by nonparametric regression analysis of longitudinal data. From [Formula: see text], a dichotomous score for N1, N2, and N3 ("negative," "positive") and a subjective certainty score were derived. SUV and metabolic tumor volumes (MTV) were compared between reconstruction methods., Results: BG-MC resulted in higher scores for N1 compared to static (p = 0.001), whereas DDG-MC resulted in higher scores for N2 compared to static (p = 0.016). Motion correction resulted in the migration of N1 from tumor free to metastatic on the dichotomized score, consensually for both readers, in 3/43 cases and in 2 cases for N2. SUV was significantly higher for motion-corrected PET, while MTV was significantly lower (all p < 0.003). No significant differences in the certainty scores were noted., Conclusions: PET motion correction resulted in significantly higher lymph node assessment scores of expert readers. Significant effects on quantitative PET parameters were seen; however, subjective reader certainty was not improved., (© 2022. The Author(s).)

Background: Despite an excellent survival rate, impairments are recognized in the quality of life and emotional well-being of differentiated thyroid cancer (DTC) survivors. Predictors for anxiety and depression in DTC patients are not well characterized. Objective: To identify predictors for anxiety and depression in DTC survivors. Methods: In this cross-sectional study, all DTC survivors presenting for follow-up between 2014 and 2019 in a tertiary referral hospital were asked to complete the "Hospital Anxiety and Depression Scale" (HADS). Depression (HADS-D) and anxiety (HADS-A) subscores were dichotomized for analysis. Univariate and multivariable logistic regression analyses were performed to identify predictors of anxiety and depression. Inverse probability weighting was applied to correct for bias due to nonresponse. Results: Six hundred forty patients meeting study inclusion criteria completed the HADS questionnaire (73% female, mean age 50 years). Of these, 37.6% and 15.7% of patients demonstrated HADS-A and HADS-D scores ≥8. Female sex, elevated body mass index (BMI), permanent recurrent laryngeal nerve damage (RLND), permanent hypoparathyroidism (PH), comorbidities classified in chapter XIX of the International Classification of Diseases , 10th Revision (ICD-10; external causes of morbidity and mortality), and comorbidities in chapter XXI of ICD-10 (factors influencing health status and contact with health services) were independent predictors for elevated anxiety scores with adjusted odds ratios of 1.9 ([CI 1.2-3.2], p  < 0.01), 1.0 ([CI 1.0-1.1], p  = 0.02), 2.6 ([CI 1.0-6.3], p  = 0.04), 2.0 ([CI 1.1-3.5], p  = 0.02), 5.5 ([CI 1.0-29.6], p  < 0.05), and 1.7 ([CI 1.1-2.6], p  = 0.03). PH, elevated anti-Tg titer, comorbidities of the digestive system (chapter XI of ICD-10), and comorbidities of the genitourinary system (chapter XIV of ICD-10) were independent predictors for depression with adjusted odds ratios of 2.2 ([CI 1.2-4.2], p  = 0.01), 1.0 ([CI 1.0-1.0], p  = 0.04), 3.0 ([CI 1.5-6.1], p  < 0.01), and 2.4 ([CI 1.0-5.7], p  = 0.04). Conclusions: Female sex, elevated BMI, RLND, PH, and comorbidities classified in chapter XIX and chapter XXI of ICD-10 are predictors for anxiety in DTC patients. PH, elevated anti-Tg titer, comorbidities of the digestive system, and comorbidities of the genitourinary system are predictors for depression in DTC patients. Physicians involved in the follow-up of DTC patients should devote particular attention to the emotional well-being in DTC patients with PH or permanent RLND.

Background: Graft versus host disease (GvHD) is a frequent complication of allogeneic stem cell transplantation (alloSCT), significantly increasing mortality. Previous imaging studies focused on the assessment of intestinal GvHD with contrast-enhanced MRI/CT or 18 F-FDG-PET imaging alone. The objective of this retrospective study was to elucidate the diagnostic value of a combined 18 F-FDG-PET-MRI protocol in patients with acute intestinal GvHD., Methods: Between 2/2015 and 8/2019, 21 patients with acute intestinal GvHD underwent 18 F-FDG-PET-MRI. PET, MRI and PET-MRI datasets were independently reviewed. Readers assessed the number of affected segments of the lower gastrointestinal tract and the reliability of the diagnosis on a 5-point Likert scale and quantitative PET (SUVmax, SUVpeak, metabolic volume (MV)) and MRI parameter (wall thickness), were correlated to clinical staging of acute intestinal GvHD., Results: The detection rate for acute intestinal GvHD was 56.8% for PET, 61.4% for MRI and 100% for PET-MRI. PET-MRI (median Likert-scale value: 5; range: 4-5) offers a significantly higher reliability of the diagnosis compared to PET (median: 4; range: 2-5; p = 0.01) and MRI alone (median: 4; range: 3-5; p = 0.03). The number of affected segments in PET-MRI (r s  = 0.677; p <  0.001) and the MV (r s  = 0.703; p <  0.001) correlated significantly with the clinical stage. SUVmax (r s  = 0.345; p = 0.14), SUVpeak (r s  = 0.276; p = 0.24) and wall thickening (r s  = 0.174; p = 0.17) did not show a significant correlation to clinical stage., Conclusion: 18 F-FDG-PET-MRI allows for highly reliable assessment of acute intestinal GvHD and adds information indicating clinical severity., (© 2021. The Author(s).)

Graft-versus-host disease (GVHD) is a common complication that increases morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Fluorodeoxyglucose F 18 ( 18 F-FDG)-positron emission tomography (PET) imaging has been demonstrated to be highly informative for evaluating and mapping of intestinal GVHD. To corroborate and extend existing findings and to investigate whether glucose metabolism assessed by 18 F-FDG-PET might be an effective diagnostic tool to predict corticosteroid-refractory acute GVHD and overall survival. In this retrospective analysis, 101 patients with clinically suspected acute intestinal GVHD underwent 18 F-FDG-PET between June 2011 and February 2019. Seventy-four of these patients with clinically and/or histologically proven acute intestinal GVHD as well as positive 18 F-FDG-PET findings were analyzed in detail to assess the predictive value of 18 F-FDG-PET regarding the response to immunosuppressive therapy and survival. Quantitative PET parameters, particularly the maximum standard uptake value (SUVmax), of patients with a fast response (ie, clinical improvement and decreased GVHD activity by at least 1 stage after 1 week of GVHD treatment) or slow/no response (ie, persistent disease activity for more than 1 week or increasing GVHD activity following first-line immunosuppressive therapy) were evaluated. 18 F-FDG-PET detected intestinal GVHD with a sensitivity of 93% (95% confidence interval [CI], 85% to 97%) and specificity of 73% (95% CI, 45% to 91%). Patients with a fast response to immunosuppressive therapy had a mean SUVmax of 13.7 (95% CI, 11.0 to 16.5) compared with 7.6 (95% CI, 7.0 to 8.3; P = .005) observed in patients with prolonged or no response. The median overall survival (OS) was 573.0 days (95% CI, 539.5 to 606.5 days) for patients with fast response versus 255 days (95% CI, 161.0 to 349.0 days; P = .009) for patients with slow or no responses. A SUVmax threshold >8.95 applied to 18 F-FDG-PET performed within 100 days after transplantation identified patients with a median OS of 390 versus 117 days for patients with SUVmax ≤8.95 (P = .036). SUVmax threshold and donor type were independent factors for OS. Our results indicate that 18 F-FDG-PET is highly accurate in identifying patients with acute intestinal GVHD and may predict responses to immunosuppressive therapy as well as survival, particularly when applied within the first 100 days after transplantation. These results provide a strong rationale to integrate PET imaging in future prospective trials evaluating new therapies for acute GVHD., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Recently, a number of innovative anticancer agents such us the programmed death 1 (PD-1) immune checkpoint inhibitors have been developed. Nevertheless, this type of immunotherapy may be associated with immune-related adverse events whose pathophysiology is considered similar to those found in autoimmune diseases such as nephritis. We report the case of a 71-year-old female with metastatic renal carcinoma who underwent nephrectomy. After three lines of other chemotherapies (VEGF and mTOR inhibitors), the patient was treated by nivolumab (3 mg/kg) for 4 months and developed acute kidney injury 16 weeks after initiating this immunotherapy. Kidney biopsy displayed a diffuse extensive interstitial inflammation associated with moderate interstitial edema. The discontinuation of nivolumab and the administration of prednisone (at 1 mg/kg and tapered over 3 months) was an effective treatment of the interstitial edema and led to the recovery of the kidney function., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Nephrology.)

Aims: Minimal extrathyroid extension (mETE) is no longer considered in the new 8th edition of the AJCC/UICC staging system. Therefore, papillary thyroid microcarcinoma with mETE previously staged as pT3 will now be staged as pT1a and most likely not receive adjuvant radioiodine therapy. However, it remains unclear if mETE is associated with higher aggressiveness in papillary thyroid microcarcinoma. Therefore, the aim of this study was to investigate if mETE is associated with higher risk of lymph node or distant metastases. Methods: 721 patients with thyroid papillary microcarcinoma presenting at our department for postoperative counseling from 05/1983 to 8/2012 were included in this retrospective analysis (median follow-up time 9.30 years). The impact of mETE on the presence of lymph node metastases at thyroidectomy and relapse through lymph node and distant metastases was assessed by logistic regression and Fine-Gray model analyses. Results: 10.7% ( n = 77) of patients had mETE. mETE was an independent risk factor for lymph node metastases at thyroidectomy with an adjusted odds ratio of 4.33 (95%CI: 2.02-9.60, p<0.001) in multivariable analysis. Patients with mETE had significantly more relapses through lymph node (over 5 years: 13.1% vs. 1.25%; P < 0.001) and distant metastases (over 5 years: 7.8% vs. 1.1%; P < 0.001) compared to patients without mETE. mETE was an independent risk factor for relapse through lymph node and distant metastases in multivariable analysis (hazard ratio: 7.78, 95%CI: 2.87-21.16, p< 0.001 and 4.09, 95%CI: 1.25-13.36, P = 0.020). Conclusion: mETE is a statistically significant and independent risk factor for relapse through lymph node and distant metastases in papillary microcarcinoma. Therefore, future studies should evaluate, if patients with mETE and microcarcinoma might benefit from intensified surveillance and therapy., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: Given the large number of patients with thyroid nodules, improvement of the specificity of current ultrasound-based thyroid nodule classification systems (ATA, EU-TIRADS, and ACR-TIRADS) is warranted to reduce the number of diagnostic thyroidectomies. Thyroid scintigraphy has been shown to demonstrate hyperfunctional nodules, associated with a low malignancy risk, in euthyroid patients. However, it is not known if thyroid scintigraphy could improve specificity of current classification systems. The aim of this study, therefore, was to determine the frequency of hyperfunctional nodules among those nodules in need of fine needle aspiration cytology (FNA) according to current classification systems and to test if nodule functional status is associated with sonographic features., Methods: Five hundred sixty-six euthyroid patients (TSH 0.55-4.20 μU/ml) presenting for thyroid nodule workup including thyroid sonography and scintigraphy at our department between 09/2013 and 02/2018 were included in this retrospective study. All nodules > 10 mm were classified according to ATA, EU-TIRADS, and ACR-TIRADS and correlated to their functional status as assessed by 99m Tc-pertechnetate scintigraphy., Results: Ultrasound detected 1029 thyroid nodules ≥ 10 mm, including 545 nodules ≥ 15 mm. Prevalence of hyperfunctional nodules among those with recommendation for FNA according to ATA 2015, EU-TIRADS, and ACR-TIRADS was 6.4%, 6.9%, and 6.5% for nodules ≥ 10 mm and 7.2%, 7.6%, and 7.5% only considering nodules ≥ 15 mm. No sonographic feature was correlated to hyperfunctionality of nodules., Conclusion: In euthyroid patients, thyroid scintigraphy demonstrates hyperfunctionality, which cannot be predicted by ultrasound, in up to 6.9% of nodules in need of FNA according to ultrasound-based classifications. Given the known low risk of malignancy in hyperfunctional nodules, thyroid scintigraphy can lower the frequency of fine needle aspirations and-potentially-the frequency of diagnostic hemithyroidectomies in euthyroid patients.

Introduction: Autodialysis is the dialysis performed by the patient himself at a local center instead of a hemodialysis center. In Morocco, the practice of hemodialysis dates back to 1970; however, an autodialysis center does not yet exist. The objective was to assess the potential medical fitness and adherence of the patients to an autodialysis program., Methods: Descriptive and analytical multicenter study conducted in March 2015 involving patients from of eight hemodialysis centers in Casablanca (Morocco). The study was conducted in two steps: 1) a transversal assessment of the medical potential to achieve autodialysis that included 556 patients; 2) a survey of the autodialysis membership that included 383 out of 556 patients who were deemed eligible for autodialysis., Results: The average age was 54.63 ± 15.16 years; the average of hemodialysis duration was 85.9 ± 78.1 months. Diabetic nephropathy (22.7%) was the predominant cause of kidney disease. The assessment of medical potential to achieve autodialysis highlighted that almost all of the patients were in good condition (93%), independent (81%), and those without major comorbidities were less than 76 years old. Regarding the potential patients' adherence to autodialysis, among the 383 patients previously deemed suited for autodialysis, 293 (76.5%) responded favorably to the proposal of self-dialysis., Conclusion: The practice of hemodialysis should be implemented in a short time in Morocco because our patients' profile is perfectly suitable to this therapeutic method especially when they are young, in good general condition, autonomous, without major comorbidities, and willing to learn., Competing Interests: The authors declare no competing interests., (© Béfa Noto-Kadou-Kaza et al.)

Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression. This case demonstrates the possibility of PSMA-negative metastases of prostate cancer an important pitfall that should be known to physicians interpreting PSMA PET.

Background: Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression., Conclusions: The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Background: While 68 Ga-PSMA PET-MRI might be superior to PET-CT with regard to soft tissue assessment in prostate cancer evaluation, it is also known to potentially introduce additional PET image artefacts. Therefore, the impact of PET acquisition duration and attenuation data on artefact occurrence, lesion detectability, and quantification was investigated. To this end, whole-body PET list mode data from 12 patients with prostate cancer were acquired 1 h after injection of 2 MBq/kg [ 68 Ga]HBED-CC-PSMA on a hybrid PET-MRI system. List mode data were further transformed into data sets representing 300, 180, 90, and 30 s acquisition duration per bed position. Standard attenuation and scatter corrections were performed based on MRI-derived attenuation maps, complemented by emission-based attenuation data in areas not covered by MRI. A total of 288 image data sets were reconstructed with varying acquisition durations for emission and attenuation data with and without scatter and prompt gamma correction, and further analysed regarding image quality and diagnostic performance., Results: Decreased PET acquisition durations resulted in a significantly increased incidence of halo artefacts around kidneys and bladder, decreased lesion detectability and lower SUV as well as markedly lower arm attenuation values: Halo artefacts were present in 5 out of 12 cases at 300-s duration, in 6 at 180 s, in 10 at 90 s, and in 11 cases at 30 s. Using attenuation data of the 300 s scans restored artefact occurrence to the original 300-s level. Prompt gamma correction only led to small improvements in terms of artefact occurrence and size. Of the 141 detected lesions in the 300-s images one lesion was not detected at 180 s, 28 at 90 s, and 64 at 30 s. Using the 300-s attenuation map decreased non-detectability of lesions to zero at 180 s, 9 at 90 s, and 52 at 30 s. Attenuation maps at 90 and 30 s demonstrated markedly lower mean arm attenuation values (0.002 cm -1 ) than those at 300 s (0.084 cm -1 ), and 180 s (0.062 cm -1 )., Conclusions: Short acquisition durations of less than 3 minutes per bed position result in unacceptable image artefacts and decreased diagnostic performance in current whole-body 68 Ga-PSMA PET-MRI and should be avoided. Increased image noise and imperfections in generated attenuation maps were identified as a paramount cause for image degradation.

This study aims at assessing patients' quality of life during hemodialysis (HD) and determining influencing factors. This prospective study was conducted over a three-month period (December 1, 2012-February 28, 2013) at the Sylvanus Olympio University Hospital (CHU-SO) HD unit, the only center to provide such services in Togo. Respondents used the standard Medical Outcome Survey-Short Form 36 questionnaire. This study was conducted on 64 patients (44 males and 20 females = M/F ratio 2.2). Mean patient age was 45.51 ± 14.00 years old with the vast majority in the 16-44-year-old group (90.82%), and mean dialysis vintage was 2.84 ± 2.37 years (1 month to 9.5 years). The mean global quality of life score was 35.58 (standard deviation ± 15). Quality of life physical score and mental score were, respectively, 31.84 and 40.64. Physical limitation scores were 15.23, followed by general ill-health score 37.38 and poor physical function score 47.37. Mental limitation score was 30.20 and vitality score was 43.75. The quality of life was inversely proportional to patient age and the dialysis vintage, with female quality of life scores worse than male in all questionnaire parameters. Togolese dialysis patients suffer from poor quality of life. Factors underlying such poor quality of life include advanced age, female gender, long-standing history of dialysis, and patient profession.

A 70-year-old man with suspected prostate cancer was referred for Ga-PSMA-HBED-CC PET/CT (short PSMA PET/CT) for staging of tumor extent. Apart from vivid tracer uptake in the prostate gland and osseous metastasis, PSMA PET/CT revealed a large soft tissue mass with calcifications in the left upper abdomen showing intense tracer uptake. Histologic examination revealed the mass to be a gastrointestinal stromal tumor.

A 60-year-old woman was referred to contrast-enhanced CT for evaluation of jugular vein thrombosis incidentally detected by ultrasound. Contrast-enhanced CT showed an enhanced tumor of the right skull base highly suspicious of jugulotympanic paraganglioma. However, the jugular veins showed a nearly symmetric contrast enhancement without clear evidence of thrombosis. Consecutive Ga-DOTATATE PET/CT depicted high tumor uptake, which comprised the entire internal jugular vein. Endovascular growth of paraganglioma might be missed on contrast-enhanced CT because of high vascularization of the lesion. Ga-DOTATATE PET is suited for accurate determination of tumor extent.

Background: Attenuation correction is one of the most important steps in producing quantitative PET image data. In hybrid PET-MRI systems, this correction is far from trivial, as MRI data are not correlated to PET attenuation properties of the scanned object. Commercially available systems often employ correction schemes based on segmenting the body into different tissue classes (air, lung tissue, fat-, and water-like soft tissue), e.g. by using a dual time-point Dixon sequence. However, several pitfalls are known for this approach. Here a specific artefact of MR-based PET attenuation correction is reported, caused by misidentifying the liver as lung tissue due to iron overload., Case Presentation: A patient with a history of hematopoietic stem cell transplantation underwent a whole-body [ 18 F]FDG PET-MRI scan. Markedly low liver uptake values were noted in the PET images, seemingly caused by an erroneous assignment of lung tissue attenuation values to the liver. A closer investigation demonstrated markedly low MRI intensity values of the liver, indicative of secondary hemochromatosis (iron overload) most probably due to a history of multiple blood transfusions. Manual assignment of adequate liver attenuation values resulted in more realistic PET images., Conclusions: Iron overload of the liver was identified as a cause of a specific attenuation correction artefact. It remains to be seen how frequent this artefact will be encountered; however, this case highlights that attenuation maps should always be checked during PET image interpretation in hybrid PET-MRI., Competing Interests: This study was performed in accordance with the ethical standards of the local ethics committee and with the 1964 Helsinki declaration and its later amendments. Images were acquired with clinical indication, patient consent for this retrospective study is waived.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Depression is among the leading causes of disability and disease burden. Recent studies point to an involvement of altered serotonin 1A receptor (5-HT 1A R) -mediated adult neurogenesis in depression. However, the exact underlying mechanisms remain unclear, mainly due to the complexity of the serotonergic system with its various receptors and their locations. Mice with permanent overexpression of postsynaptic 5-HT 1A Rs (OE mice) represent a unique tool for investigating the involvement of postsynaptic 5-HT 1A Rs in this context. Correct 5-HT 1A R coupling and functioning has been demonstrated earlier, indicating that more postsynaptic 5-HT 1A Rs can be activated in these mice. Initially we examined morphometric parameters of the dentate gyrus (DG) and the prefrontal cortex as they are involved in adult hippocampal neurogenesis and/or depression. The volume of the DG in OE mice was increased in comparison to wildtype controls. We therefore investigated parameters of adult neurogenesis by the bromodeoxyuridine method. Proliferation and survival of newborn cells in the DG of OE mice were significantly increased. Significant increases in survived neurons were only detected in the female but not in the male subgroup. Additional staining for early precursor cells (Sox2) and progenitor cells of the neuronal lineage (doublecortin) showed an increase in type-1/2a as well as in type-2b/3 cells in OE mice. Our study suggests a leading role of the postsynaptic 5-HT 1A R in adult hippocampal neurogenesis and might open an important link to depression., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

A 65-year-old man with disseminated bone metastases of prostate cancer was referred for Ga-PSMA-HBED-CC-PET/CT (short PSMA-PET/CT) to exclude visceral metastases before treatment of bone metastases with Ra-dichloride. Apart from disseminated bone metastases, PSMA-PET/CT revealed a focal cerebral tracer uptake in the right frontal lobe highly suspicious for cerebral spread. According to patient history, a cerebral infarction occurred 14 days before PSMA imaging in corresponding localization confirmed by MRI scanning. This case demonstrates the possibility of false-positive finding of cerebral metastases in PSMA-PET early after stroke.

Purpose: The purpose of this study was to determine whether [(68)Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [(18)F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC)., Methods: The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [(18)F]FDG PET/CT and [(68)Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis. Histology, and prior and follow-up examinations served as the standard of reference., Results: Recurrent or metastatic tumour was confirmed in 11 of the 12 patients. [(68)Ga]DOTATATE PET(/MRI) correctly identified the tumour burden in all 11 patients, whereas in one patient local relapse was missed by [(18)F]FDG PET/CT. In the lesion-based analysis, overall lesion detection rates were 79/85 (93 %), 69/85 (81 %) and 27/82 (33 %) for [(18)F]FDG PET/CT, [(68)Ga]DOTATATE PET/MRI and DWI, respectively. [(18)F]FDG PET(/CT) was superior to [(68)Ga]DOTATATE PET(/MRI) in the overall evaluation and in the detection of pulmonary metastases. In the detection of extrapulmonary metastases, [(68)Ga]DOTATATE PET(/MRI) showed a higher sensitivity than [(18)F]FDG PET(/CT), at the cost of lower specificity. DWI achieved only poor sensitivity and was significantly inferior to [(18)F]FDG PET in the lesion-based evaluation in the detection of both extrapulmonary and pulmonary metastases., Conclusion: [(18)F]FDG PET/CT was more sensitive than [(68)Ga]DOTATATE PET/MRI in the evaluation of RAI-refractory DTC, mostly because of its excellent ability to detect lung metastases. In the evaluation of extrapulmonary lesions, [(68)Ga]DOTATATE PET(/MRI) was more sensitive and [(18)F]FDG PET(/CT) more specific. Furthermore, DWI did not provide additional information and cannot replace [(18)F]FDG PET for postoperative monitoring of patients with suspected RAI-refractory DTC.

Introduction: Pulmonary arterial hypertension (PAH), defined as a systolic pulmonary artery pressure above 35 mm Hg, is another vascular disease entity recently described in patients receiving hemodialysis. It is a major problem due to its high prevalence and morbidity and mortality. Its pathophysiological mechanism is just known and the strategies for its supported not yet defined., Aims: To determine the prevalence of PAH in our hemodialysis patients and its risk factors., Methodology: Single center descriptive and analytical cross-sectional study, including 111 hemodialysis patients who had benefit from a trans-thoracic cardiac Doppler ultrasound during 2014. A value greater than or equal to 35 mm Hg is considered PAH and classified as follows: mild PAH (35 50 mm Hg), moderate PAH (50 70 mm Hg), and severe pulmonary hypertension (> 70 mm Hg). Patients with a high probability of secondary PAH, especially those with the following history: chronic obstructive pulmonary disease, pulmonary embolism, were not included., Results: The mean age was 44.3 ± 14.2 years. Among the 111 patients, 18 had pulmonary arterial pressure above 35 mm Hg corresponding to 16.22% of PAH prevalence. The average pressure was 45 mm Hg. Of these 18 patients, 11.8% had mild PAH, 3.4% moderate PAH and 0.8% severe PAH. The average hemodialysis duration was significantly associated with PAH (p = 0.003); as well as valvular calcification (p = 0.000), mitral regurgitation (p = 0.001) and tricuspid regurgitation (p = 0.002)., Conclusion: Primary pulmonary hypertension is a major problem among our hemodialysis because of its high prevalence and its risk factors.