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Τετάρτη 21 Νοεμβρίου 2018

Opioidergic Regulation of Emotional Arousal: A Combined PET–fMRI Study

Abstract
Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify μ-opioid receptor and type 2 dopamine receptor (MOR and D2R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D2R availability—here reliably quantified only in striatum—was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.

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Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations

Abstract
Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.

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Guselkumab: A Review in Moderate to Severe Plaque Psoriasis

Abstract

Guselkumab (Tremfya®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response), with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab, administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.



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Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective

Abstract

Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.



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Thyroid® High-Impact Articles

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FREE ACCESS through December 5, 2018.
Latest Impact Factor: 7.557
The Official Journal of: American Thyroid Association®

Read now:

Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration
Petter Strømme, Stefan Groeneweg, Elaine C. Lima de Souza, Chantal Zevenbergen, Anette Torgersbråten, Asbjørn Holmgren, Ebrar Gurcan, Marcel E. Meima, Robin P. Peeters, W. Edward Visser, Linda Høneren Johansson, Almira Babovic, Henrik Zetterberg, Heike Heuer, Eirik Frengen, Doriana Misceo, and Theo J. Visser

Metal Coordinated Poly-Zinc-Liothyronine Provides Stable Circulating Triiodothyronine Levels in Hypothyroid Rats
Rodrigo R. Da Conceição, Gustavo W. Fernandes, Tatiana L. Fonseca, Barbara M.L.C. Bocco, and Antonio C. Bianco 

Response to Lenvatinib in Children with Papillary Thyroid Carcinoma
Priya Mahajan, Jonathan Dawrant, Albert Kheradpour, Norma M. Quintanilla, Monica E. Lopez, Robert C. Orth, Ioanna Athanassaki, and Rajkumar Venkatramani 

Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular Variant of Papillary Thyroid Carcinoma
Young Shin Song, Jae-Kyung Won, Seong-Keun Yoo, Kyeong Cheon Jung, Min Joo Kim, Su-Jin Kim, Sun Wook Cho, Kyu Eun Lee, Ka Hee Yi, Jeong-Sun Seo, and Young Joo Park 

Diagnostic Performance of Ultrasound-Based Risk-Stratification Systems for Thyroid Nodules: Comparison of the 2015 American Thyroid Association Guidelines with the 2016 Korean Thyroid Association/Korean Society of Thyroid Radiology and 2017 American Congress of Radiology Guidelines
Eun Ju Ha, Dong Gyu Na, Won-Jin Moon, Young Hen Lee, and Nami Choi 

The post <i>Thyroid<sup>®</sup></i> High-Impact Articles appeared first on American Thyroid Association.



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Combined Karapandzic-Abbé/Estlander/Stein Flap For Subtotal and Total Lower Lip Reconstruction

Background: Lower lip reconstruction remains a challenging task due to multi-functional and high aesthetic requirements that have to be achieved for successful outcome. This is particularly true to near-total lower lip defects, encompassing over 70% of lower lip loss due to cancer, trauma or burns. Despite the fact that numerous flaps and their modifications have been described over the past century, only a few valuable techniques and concepts withstood the test of time for sub-total lower lip defects, each having their own drawbacks.

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“Radiological Morphometric Analysis of the Zygomatic Arch: Application of Osteosynthesis on the Upper Arch Border for Rigid Fixation”

This study was designed to introduce a novel method of applying osteosynthetic materials to the upper zygomatic arch border for fracture fixation through a temporal incision, and analyze the radiologic morphometric dimensions of the arch to verify its validity.

https://ift.tt/2Kpwy3s

Temporal Trends in Immediate Post-Mastectomy Breast Reconstruction

Breast reconstruction after mastectomy offers significant improvements in quality of life for breast cancer (BC) patients. To improve access to post-mastectomy breast reconstruction (PMBR) for BC patients in the U.S., the Women's Health and Cancer Rights Act (WHCRA) was implemented in 1999, mandating coverage of PMBR by all insurers. Prior to WHCRA, post mastectomy breast reconstruction (PMBR) was variably covered by insurers as it was primarily viewed as a cosmetic procedure. The objectives of this study were to explore whether the incidence of PMBR has changed over time and whether patient age, receipt of radiation therapy, or tumor grade has an effect on the incidence of reconstruction over time.

https://ift.tt/2BoYPUF

Cancer Stem Cells within Moderately Differentiated Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-angiotensin System

To investigate expression of components of the renin-angiotensin system (RAS): pro-renin receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) by the cancer stem cell (CSC) subpopulations in moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNCSCC).

https://ift.tt/2KoNZkA

Sub-muscular Plane for Augmentation Mammoplasty Patients Increases Silicone Gel Implant Rupture Rate

Breast augmentation is one of the most common aesthetic procedures performed worldwide. One of the worst associated complications is implant rupture, a topic that will be addressed in the present study. The risk of developing silicone gel breast implant rupture following breast augmentation is associated with multiple factors, including: older generation implant, increased implant age, implant type, specific manufacturer, severe capsular contracture (Baker grade III or IV), and the presence of local symptoms.

https://ift.tt/2BqMbVl

Functional outcomes of upper eyelid blepharoplasty: a systematic review.

Various functional outcomes after upper blepharoplasty are reported in the literature. We systematically reviewed the literature to assess the objective and subjective functional effects of upper blepharoplasty.

https://ift.tt/2Kt9jWc

Impact of Incidental Findings in Preoperative CTA imaging for Autologous Breast Reconstruction

CT angiography (CTA) can be performed pre-operatively for perforator mapping in autologous breast reconstruction. The full impact of incidental CTA findings on breast reconstruction remains unclear.

https://ift.tt/2BoX0az

A retrospective comparison of 3M™ Micropore™ with other common dressings in cosmetic breast surgery

Surgical site infection has considerable cost implications for healthcare providers. Evidence suggests that the use of Micropore™ tape as a dressing for surgical incisions may be associated with reduced/comparable rates of infection in surgical wounds. 3M™ Micropore™ tape is significantly cheaper than conventional wound dressings. The purpose of this study was to compare differences in the rate of wound healing problems including superficial incisional surgical site infection (SSI) and wound healing problems following cosmetic breast procedures between Micropore™ tape and other common wound dressings.

https://ift.tt/2Kp3Gbr

Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients

Abstract

Purpose

The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC).

Methods

The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of patients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox's proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance.

Results

Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC.

Conclusions

The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available.



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Association of serum ghrelin with weight gain during pregnancy in overweight and normal women

Abstract

Purpose

Despite the fact that the ghrelin hormone plays pivotal role in the process of weight gain, its correlation with weighing during pregnancy has not been elucidated. Hence, the present study was conducted to evaluate the correlation between plasma ghrelin levels and gestational weight gain in overweight and normal women.

Methods

This prospective cohort study was conducted in 27 overweight and 18 normal body mass index (BMI) pregnant women referring to Tehran health care centers. Weight gain during all trimesters of pregnancy was measured and the blood samples were collected at 8–12 (first trimester) and 16–20 weeks (second trimester) of pregnancy. The plasma total ghrelin concentration was measured by ELISA method.

Results

The overweight pregnant women exhibited significantly lower weight gain at the second (p = 0.002), third trimesters (p = 0.005) as well as total weighing during pregnancy (p = 0.001) compared to the normal BMI pregnant women. There was no significant difference in plasma ghrelin levels between the groups from the first to the second trimesters of pregnancy (p > 0.05). Moreover, no correlation was found between ghrelin levels and gestational weight gain in the overweight and normal groups.

Conclusions

Our results indicate that the increased level of serum ghrelin could not be considered as a key mediator for weight gain difference during pregnancy of overweight women.



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Outcomes in Patients Treated With Carfilzomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

This 5-year follow-up of a phase 2 clinical trial assesses long-term durability of minimal residual disease–negative remission and time to disease progression among patients with newly diagnosed multiple myeloma who received triplet-based induction therapy with lenalidomide maintenance therapy.

https://ift.tt/2DNEefr

Circulating Tumor Cells and Radiotherapy Benefit in Early Breast Cancer

To the Editor Goodman et al recently described a consistent benefit from radiotherapy (RT) in terms of survival and distant disease control after breast-conserving surgery (BCS), but not mastectomy, in 2 cohorts of patients with breast cancer (BC) harboring any circulating tumor cells (CTCs). Speers and Rugo emphasize that the lack of benefit from RT in patients with CTC-negative status is probably owing to the study being underpowered to detect small benefits, and the findings should not be regarded as contradictory to abundant randomized evidence of the benefit of RT. We agree and value the identification of a predictive biomarker of RT benefit.

https://ift.tt/2S74hRL

Second Solid Cancers After Hematopoietic Stem Cell Transplantation in European Patients

This cohort study examines patient data in the European Society for Blood and Marrow Transplantation Registry for causes of death, risk factors, and overall survival rates among patients who received a second cancer diagnosis after being treated with stem cell transplant.

https://ift.tt/2DNEdbn

Body Composition and Overall Survival in Patients With Nonmetastatic Breast Cancer

To the Editor Cann et al conducted an interesting study to evaluate the associations of 3 body composition measures with overall survival (OS) in patients with nonmetastatic breast cancer. Comparing patients with and without sarcopenia, the authors report a hazard ratio (HR) of 1.41 (95% CI, 1.18-1.69). Although a statistically significant association between sarcopenia and OS was established, a 40% increase in the HR for sarcopenia is difficult to interpret clinically. The hazard cannot be interpreted as a risk (ie, the chance or likelihood of an event occurring). Moreover, without the background hazard function as a benchmark in patients without sarcopenia, a 40% increase might not amount to a clinically meaningful difference. Furthermore, when the HR is not constant over time, it is unclear how to interpret the observed HR.

https://ift.tt/2S0IJGq

Body Composition and Overall Survival in Patients With Nonmetastatic Breast Cancer—Reply

In Reply McCaw et al propose using restricted mean survival time (RMST) as an alternative to the Cox proportional hazards models we used to examine the influence of body composition on survival in patients with breast cancer. While we agree that RMST presents an alternative method of interpreting data with less restrictions about model fit, there are several reasons why we chose the approach used. First, our article is an epidemiological study examining body composition risk factors for survival, not a randomized clinical trial. Thus, it is unlikely that a clinician would ever inform a patient with low muscle or excess adiposity that she had 6 fewer months to live compared with a patient with normal weight or normal muscle, especially because it is unknown if losing adiposity or gaining muscle will change a patient's survival. Mean differences generated from RMST may be more appropriate for patients who need to make informed decisions about treatment. Our study is meant to generate new hypotheses for potential future clinical trials and to help clinicians understand the underlying mechanisms regarding the role of body composition to survival. Thus, presenting relative risks for this purpose is informative. Additionally, other studies on this topic have used statistical approaches similar to the approach we used so that results can easily be compared.

https://ift.tt/2DNEbAh

Circulating Tumor Cells and Radiotherapy Benefit in Early Breast Cancer—Reply

In Reply We thank Drs Tsoutsou and Vozenin for their insightful comments regarding our recent article detailing the potential for using circulating tumor cell (CTC) status as a predictive biomarker for benefit of radiotherapy among patients with early-stage breast cancer.

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Rechallenge for Patients With RAS and BRAF Wild-Type mCRC With Resistance to Cetuximab and Irinotecan

This multicenter, phase 2, single-arm trial assesses the activity of cetuximab plus irinotecan as third-line treatment for patients with RAS and BRAF wild-type metastatic colorectal cancer who were initially sensitive to and then resistant to first-line irinotecan- and cetuximab-based therapy.

https://ift.tt/2DNE8V7

Combination Immunotherapy in the First-line Treatment of Advanced Renal Cell Carcinoma

This narrative review discusses the rationale and results of clinical trials in immunotherapy-based combination therapy for patients with advanced renal cell carcinoma.

https://ift.tt/2S41VmA

Scholar : These new articles for The American Journal of Family Therapy are available online

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Articles

An Integration of Feminism into Experiential Psychotherapy
Justin Huft & Naveen Jonathan
Pages: 1-19 | DOI: 10.1080/01926187.2018.1502640


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Molecular mechanism of the ichthyosis pathology of Chanarin–Dorfman syndrome: stimulation of PNPLA1-catalyzed ω-O-acylceramide production by ABHD5

Publication date: Available online 20 November 2018

Source: Journal of Dermatological Science

Author(s): Yusuke Ohno, Atsuki Nara, Shota Nakamichi, Akio Kihara

Abstract
Background

ABHD5 mutations cause Chanarin–Dorfman syndrome accompanied by ichthyosis. ω-O-Acylceramide (acylceramide) is essential for skin permeability barrier formation. Acylceramide production is impaired in Abhd5 knockout mice. The transacylase PNPLA1 catalyzes the final step of acylceramide production: transfer of linoleic acid in triglyceride to ω-hydroxyceramide.

Objective

We aimed to elucidate the role of ABHD5 in acylceramide production and the molecular mechanism of the ichthyosis symptoms of Chanarin–Dorfman syndrome.

Methods

We investigated how ABHD5 influences acylceramide production using an acylceramide-producing cell system. The effects of ABHD5 and PNPLA1 expression on the morphology of lipid droplets were examined by indirect immunofluorescent microscopy and immunoelectron microscopy.

Results

When ABHD5 was expressed in the acylceramide-producing cell system, acylceramide synthesis by PNPLA1 was enhanced. Dispersed localization of PNPLA1 was observed by immunofluorescent microscopy in HeLa cells under lipid droplet-forming conditions. Co-expression with ABHD5 caused PNPLA1 to localize on the lipid droplet membranes or their periphery. This staining pattern was observed in cells where PNPLA1 and ABHD5 were expressed at low levels. In contrast, lipid droplets disappeared in cells where PNPLA1 and ABHD5 were highly expressed. Immunoelectron microscopic analyses suggested that lipid droplets underwent morphological changes, transforming into vesicles or becoming incorporated into the endoplasmic reticulum. ABHD5 mutations found in Chanarin–Dorfman syndrome patients reduced ABHD5's ability to promote PNPLA1-dependent acylceramide production.

Conclusion

ABHD5 enhances PNPLA1-catalyzed acylceramide production. We speculate that ABHD5 retains triglycerides in the endoplasmic reticulum, and presents them to PNPLA1 to promote substrate recognition.



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Type 2 diabetes treatment and progression of chronic kidney disease in Italian family practice

Abstract

Aims

Progressive chronic kidney disease represents a dreadful complication of type 2 diabetes mellitus (T2DM). We tested the pattern of use and the renal effects of old glucose-lowering drugs in T2DM patients cared for by Italian general practitioners (GPs).

Methods

Data of 2606 T2DM patients were extracted from the databases of GPs, who do not have access to the most recent glucose-lowering drugs in Italy. The rate of kidney function decline was calculated by CKD-EPIcr, based on two consecutive creatinine values.

Results

Metformin was used in 55% of cases, either alone or with sulfonylureas/repaglinide, across the whole spectrum of CKD (from 66% in stage G1 to only 8% in G4). Sulfonylurea use peaked at 21–22% in stage G2–G3a, whereas repaglinide use significantly increased from 8% in G1 to 22% in G4. The median rate of CKD decline was − 1.64 mL/min/1.73 m2 per year; it was higher in G1 (− 3.22 per year) and progressively lower with CKD severity. 826 cases (31.7%) were classified as fast progressors (eGFR decline more negative than − 5 mL/min/1.73 m2 per year). The risk of fast progressing CKD was associated with increasing BMI, albuminuria, and sulfonylurea use, alone (OR, 1.47; 95% confidence interval, 1.16–1.85), or in association with metformin (OR, 1.40; 95% CI 1.04–1.88). No associations were demonstrated for metformin, cardiovascular and lipid lowering drug use.

Conclusion

In the setting of Italian family practice, sulfonylurea use is associated with progressive CKD in patients with T2DM. Metformin, at doses progressively reduced according to CKD stages, as recommended by guidelines, is not associated with fast progression.



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Issue Information



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The Number Interval Position Effect (NIPE) in the mental bisection of numerical intervals might reflect the influence of the decimal-number system on the Gaussian representations of numerosities: a combined developmental and computational-modelling study

Publication date: Available online 20 November 2018

Source: Cortex

Author(s): Francesca Rotondaro, Michela Ponticorvo, Onofrio Gigliotta, Mario Pinto, Michele Pellegrino, Simone Gazzellini, Pasquale Dolce, Orazio Miglino, Fabrizio Doricchi

Abstract

Healthy adults show typical error biases when they mentally bisect number intervals without exact calculations. For a given number interval length, the bisection bias is in fact modulated by the position that the interval occupies within a ten. For intervals positioned at the beginning of tens the error bias is directed toward values that are higher than those of the true interval midpoint whereas for intervals at the end of tens the direction of the error bias is reversed toward values that are lower than that of the true midpoint (Doricchi et al., 2009; Rotondaro et al., 2015). This effect has been defined Number Interval Position Effect (NIPE). The NIPE recurs over consecutive tens and it is not found when intervals are bisected through exact calculations. For this reasons we have hypothesised that the NIPE reflects the influence that the habit of counting in tens has on the neural representations of numerosities that humans share with other species. Here, in a developmental study we demonstrate that children from preschool to fifth-grade display a NIPE that is comparable to that of healthy adults. Then, through a computational-modelling study we investigated whether the NIPE might reflect specific patterns in the Gaussian representations of numerosities that are found in the parietal and pre-frontal neuronal populations of macaque monkeys and that underlie approximate numerosity estimations also in humans. The findings of computational simulations suggest that the NIPE might reflect the influence that the learning and use of the decimal numerical system has on the phylogenetically and ontogenetically older representation of numerosities that humans share with other species. These changes in the representation of numerosities have an influence on approximate numerical estimations even when these, like in the case of the mental bisection of number intervals, are elicited by numerical symbols or words.



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Evaluation of body composition using dual-energy X-ray absorptiometry in patients with non-functioning adrenal incidentalomas and an intermediate phenotype: Is there an association with metabolic syndrome?

Abstract

Purpose

Metabolic syndrome (MS) and sarcopenia are associated with increased cardiovascular risk. No studies using dual-energy x-ray absorptiometry (DXA) have evaluated association between body composition (BC) changes and MS in adrenal incidentaloma (AI). Our aim was to analyse BC in non-functioning AI (NFAI) and intermediate phenotype (IP) relative to controls and to correlate with cortisol levels.

Methods

Cross-sectional study with 44 NFAI (serum cortisol ≤ 50 nmol/L after the overnight 1 mg dexamethasone suppression test), 27 IP (cortisol 51–138 nmol/L), and 41 controls (normal adrenal on imaging examination) using DXA. Autonomic cortisol secretion (cortisol > 138 nmol/L) was excluded from the study. BC data were compared using criteria for MS (World Health Organization, National Cholesterol Education Program-Adult Treatment Panel-III, American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation).

Results

There was no significant difference in clinical data and body mass index (BMI) among the three groups. Waist circumference (WC) was larger in AI vs. controls (p < 0.01). Waist-to-hip ratio was higher in NFAI vs. controls and waist-to-height ratio was higher in IP vs. controls (p = 0.03 and p = 0.02, respectively). The frequency of MS was higher in AI vs. controls. BC was not different among the groups. Patients with AI there was a significant association of MS with both an increase in total fat and body fat index (all criteria), and a significant difference between MS and smaller BMI-adjusted lean mass (AACE, p = 0.036). No correlation of cortisol after 1 mg dexamethasone test with BC or MS. AI and WC were independently associated with MS.

Conclusions

AI presented high frequency of MS and was independently associated with MS. Possible deleterious effects of cortisol secretion seem to initially affect the muscular system.



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Potassium Iodide for Cutaneous Inflammatory Disorders: A Monocentric, Retrospective Study

Objectives: Potassium iodide (KI) is a medication that has been used for decades in dermatology and it is mentioned as a treatment option in all major dermatology textbooks. Yet, there is little recent information on its efficacy. In our study, we wanted to retrospectively evaluate the therapy response to KI in our patients. Methods: The hospital information system was searched for patients treated with KI at the Department of Dermatology (University Hospital Zurich) in the last 20 years (January 1, 1998 to December 31, 2017). A total of 52 patients were found and, subsequently, 35 patients were included in our study. Results: KI was prescribed for the following skin conditions: erythema nodosum, disseminated granuloma anulare, necrobiosis lipoidica, nodular vasculitis, cutaneous sarcoidosis, and granulomatous perioral dermatitis/ rosacea. The median duration of KI intake was 5 ± 7.7 weeks (range 1–26). The global assessment of efficacy by the treating physician showed an improvement of disease in about a third of all patients. No response was seen in 14 patients and 9 even had a progression of disease. An adverse event was documented in 16 cases. Conclusions: Our findings show that an improvement was reached in only about a third of all cases. High response rates with only mild side effects (in 16 out of 35 patients) were observed.
Dermatology

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Scholar : New articles have been published for Journal of Natural History, Volume 52, Issue 37-38

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The following articles have been newly published in the issue Journal of Natural History, Volume 52, Issue 37-38 on Taylor & Francis Online:

Articles
Description of a new species of Haminoea (Gastropoda: Cephalaspidea) from India, with an account of the diversity of the genus in the Indo-West Pacific
Monisha Bharate, Trond R. Oskars, Sumantha Narayana, Raveendhiran Ravinesh, Appukuttannair Biju Kumar, Manuel António E. Malaquias
Pages: 2437-2456 | DOI: 10.1080/00222933.2018.1533598

The issue is in progress. To view all articles already published in this issue, please visit:
https://www.tandfonline.com/toc/tnah20/52/37-38

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Highlights from 2017: impactful topics published in the Annals of Nuclear Medicine

Abstract

The aim of the review is to highlight articles published in 2017 in the Annals of Nuclear Medicine, an official peer-reviewed journal of the Japanese Society of Nuclear Medicine. Among all published manuscripts during the past year, we conducted a subjective selection of the most relevant topics. Fourteen fascinating articles are included in this review, ranging in topic from preclinical to clinical arenas.



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C.R. Goldfarb, M. Chamarthy, F. Ongseng, S.R. Parmett, D.L. Bushnell, R. Mirtcheva-Trocheva, U. Sen, L.S. Zuckier. Nuclear Medicine Board Review: Questions and answers for self-assessment, 4th Edition



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18 F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study

Abstract

Purpose

To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese population, as well as the characteristics of PET/CT in different category of etiological disease.

Methods

A total of 376 consecutive patients with FUO/IUO who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale respectively. A questionnaire survey to the clinicians was used to evaluate the significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the etiological distribution in the study population, image characteristics in different category of diseases, and clinical significance of PET/CT.

Results

In 376 studied patients, the infectious diseases accounted for 33.0% of patients, rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among hospitals was varied. In addition, the etiological disease composition ratio has changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients had a positive finding. Within them, local high uptake lesion was found in 219 cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake in malignant diseases was significantly higher than in other category diseases both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value < 0.001). Based on a clinical questionnaire survey, PET/CT provided additional diagnostic information for 77.4% of patients, and 89.6% of patients benefited from PET/CT examination.

Conclusions

FDG PET/CT is a valuable tool for clinical diagnosis of FUO/IUO, and it is of great significance in further investigating the usefulness of PET/CT in non-neoplastic diseases.



https://ift.tt/2KnOICl

FDG PET/CT imaging in detecting and guiding management of invasive fungal infections: a retrospective comparison to conventional CT imaging

Abstract

Purpose

Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy.

Methods

FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment.

Results

Between 2007 and 2017, 45 patients had 48 proven/probable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT.

Conclusion

FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.



https://ift.tt/2KoDFsL

FDG PET in response evaluation of bulky masses in paediatric Hodgkin’s lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial

Abstract

Purpose

We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial.

Methods

We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors.

Results

Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01).

Conclusion

After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.



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Challenges are opportunities



https://ift.tt/2BnqPYK

Correction to: Highlights from 2017: impactful topics published in the Annals of Nuclear Medicine

The author names in the original version of this article were inversed. Correct author names were reflected here.



https://ift.tt/2Kq7Sb6

Value proposition of PSMA-targeted α–particle radioligand therapy in metastatic prostate cancer



https://ift.tt/2BnvYjO

Outcome of patients with early-stage follicular lymphoma staged with 18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and treated with radiotherapy alone

Abstract

Purpose/objective(s)

To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone.

Materials/methods

Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan–Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks.

Results

Median age was 57 years (range 24–83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123–607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30–36Gy in 15–24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25–6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15–18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79–100) for the whole cohort.

Conclusion

FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.



https://ift.tt/2BnCwir

FDG-PET imaging to detect and characterize underlying causes of fever of unknown origin: an unavoidable path for the foreseeable future



https://ift.tt/2KlSEni

Salvage extended field or involved field nodal irradiation in 18 F-fluorocholine PET/CT oligorecurrent nodal failures from prostate cancer

Abstract

Purpose

The concept of metastasis-directed therapy for nodal oligorecurrences with stereotactic body radiotherapy is increasingly accepted. Hence, the comparison between salvage extended field radiotherapy (s-EFRT) and salvage involved field radiotherapy (s-IFRT) in patients with 18F-fluorocholine (FCH) PET/CT+ nodal oligorecurrences from prostate cancer is worthy of investigation.

Methods

Patients with oligorecurrent nodes on FCH PET/CT treated with salvage radiotherapy between 2009 and 2017 in a single tertiary cancer centre were selected for this study. Patients treated with s-IFRT were compared with those treated with s-EFRT. Toxicities and times to failure (TTF) were compared between the two groups.

Results

The study included 62 patients with positive lymph nodes only who underwent FCH PET/CT for a rising PSA level after radical prostatectomy or radiotherapy. Of these patients, 35 had s-IFRT and 27 had s-EFRT. After a median follow-up of 41.8 months (range 5.9–108.1 months), no differences were observed in acute or late gastrointestinal and genitourinary toxicities of grade 2 or more between the two groups. The 3-year failure rates were 55.3% (95% CI 37.0–70.3%) in the s-IFRT group and 88.3% (95% CI 66.9–96.1%) in the s-EFRT group (p = 0.0094). In multivariate analysis of TTF, an interval of >5 years was significantly correlated with better outcomes (HR = 0.33, 95% CI 0.13–0.86, p = 0.023). There was a strong trend toward better outcomes with s-EFRT even after adjusting for concomitant androgen-deprivation therapy (HR = 0.38, 95% CI 0.12–1.27, p = 0.116).

Conclusion

FCH PET-positive node-targeted s-EFRT is feasible with low rates of toxicity and longer TTF, suggesting that oligorecurrent nodal disease diagnosed on FCH PET is unlikely.



https://ift.tt/2Kq7t8A

68 Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy

Abstract

Objectives

The primary objective was the evaluation of Gallium 68 (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PET/CT) detection rate, for identifying the site of prostate cancer (PCa) relapse (local vs systemic), stratifying the population according to different clinical stages of biochemical recurrence (BCR). Secondary aims were: 1) to evaluate the association of clinical/pathologic features and 68Ga-PSMA-11 PET/CT detection rate, 2) to compare 68Ga-PSMA-11 PET/CT with other imaging procedures, and 3) to evaluate the positive predictive value (PPV) in a per-patient analysis.

Material and methods

This population was enrolled through a prospective, open label, single-center trial performed at the Nuclear Medicine of the University Hospital of Bologna (Eudract: 2015-004589-27 OsSC). The inclusion criteria were: (1) proven PCa, (2) surgery or radiotherapy as definitive therapy, (3) proven BCR, (4) prostate-specific antigen (PSA) 0.2–2 ng/ml, (5) age ≥ 35 years, and 6() willing to sign an informed consent. Three-hundred and thirty-two (332) patients were enrolled between March 2016 and June 2017; mean/median PSA was 0.84/0.61 ng/ml, 97.9% (325/332) of patients received radical prostatectomy and 2.1% (7/332) radiotherapy. Different patterns of BCR were identified by referent physicians as follows: (a) persisting detectable PSA after radical prostatectomy in 13.5% (45/332) of patients (subgroup 1), (b) first-time PSA failure after radical therapy in 44.9% (149/332) (subgroup 2), and (c) PSA increase after salvage or hormonal therapy in 41.6% (138/332) (subgroup 3).

Results

Primary objective: 68Ga-PSMA-11 PET/CT detection rate was 53.6% (CI 95% 48.1%–59.1%). In a patient-based analysis, disease confined to pelvis (prostate bed and/or lymph-nodes) was detected in 24.7% of cases (82/332). The presence of at least one distant lesion was observed in 28.9% of cases (96/332). The detection rate in different subgroups was: subgroup 1 = 64.5%, subgroup 2 = 45.6%, and subgroup-3  = 58.7%. Secondary objectives: 1) PSA (p = 0.041) and PSAdt (p = 0.001) showed association with 68Ga-PSMA-11 PET/CT detection rate, and 2) correlative imaging was available in 73.2% of patients (243/332). When 68Ga-PSMA-11 PET/CT was positive, correlative imaging resulted negative in 83% of cases (108/130). 3) The calculated PPV was 96.2%.

Conclusion

Our data confirmed the efficacy of 68Ga-PSMA-11 PET/CT for detecting local vs systemic disease in PCa patients presenting PSA failure after radical therapy. Furthermore, 68Ga-PSMA-11 PET/CT detection rate is different depending on the clinical stage of BCR, and this information should be taken into consideration by referring physicians.



https://ift.tt/2BnpLUK

18 F-FDG PET/CT is useful for determining survival outcomes of patients with multiple myeloma classified as stage II and III with the Revised International Staging System

Abstract

Purpose

This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS).

Method

We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to induction therapy in patients with newly diagnosed MM.

Results

In the total cohort, the presence of more than three hypermetabolic focal lesions (FLs) or extramedullary disease (EMD) on baseline PET/CT was associated with significantly inferior progression-free survival (PFS) and overall survival (OS) than other patients. Because most patients (91%) with EMD had more than three FLs, PET/CT positivity was defined as the presence of more than three FLs or the presence of EMD. In multivariate analyses, PET/CT positivity was an independent predictor of PFS and OS in all patients. Fifty-five patients (46.1%) with R-ISS II were PET/CT-positive at baseline and had significantly shorter PFS and OS. PET/CT positivity was also correlated with poor PFS and OS in patients with R-ISS III.

Conclusion

18F-FDG PET/CT was an independent predictor of survival outcomes in patients with newly diagnosed MM. In addition, performing 18F- FDG PET/CT at diagnosis may be useful for determining the survival outcomes of MM patients with R-ISS II and III.



https://ift.tt/2BorNUI

Initial clinical experience performing sialendoscopy for salivary gland protection in patients undergoing 225 Ac-PSMA-617 RLT

Abstract

Purpose

The main side effect of prostate-specific membrane antigen targeting alpha therapy (PSMA TAT) is dry mouth syndrome. Inflammation of the salivary glands and consequent reduced salivary function have been reported in patients after radioiodine therapy. The beneficial effects of sialendoscopy on radiation-induced inflammation in tissue are well known. Thus sialendoscopy with dilatation, saline irrigation and steroid injections (prednisolone) was performed before and after 225Ac-PSMA-617 TAT to reduce inflammatory effects in the salivary glands and to improve or prevent xerostomia.

Methods

Eleven men with metastatic castration-resistant prostate cancer (mean age 68.5 years, range 58–80 years) underwent sialendoscopy, dilatation, saline irrigation and steroid injection of both submandibular and both parotid glands before or after every cycle of 225Ac-PSMA-617 TAT. Sialendoscopy and steroid injection were performed by a senior ENT physician. Quality of life was evaluated using two health-related quality of life (HRQOL) questionnaires, the Xerostomia Questionnaire (XQ) and the Xerostomia Inventory (XI) before and 3 months after the intervention.

Results

In all 11 patients both parotid and both submandibular glands were affected by radiation sialadenitis and sialendoscopy was performed. The patients experienced no complications after sialendoscopy, and showed a significant improvement in HRQOL as measured using the XQ and XI. After sialendoscopy the XQ score decreased significantly from 77.7 ± 13.6 to 42.7 ± 14.8 (p = 0.003) and the XI score decreased from 44.5 ± 6.9 to 25.8 ± 12.8 (p = 0.003). Due to the limited number of patients we only report tendencies.

Conclusion

Sialendoscopy with dilatation, saline irrigation and steroid injection had beneficial effects on salivary gland function and HRQOL in patients undergoing 225Ac-PSMA-617 RLT. However, even with sialadenoscopic support after multiple cycles of TAT, salivary gland function was reduced and xerostomia was present. Therefore, not only inflammation but also the direct effect of radiation is a putative cause of dry mouth. Further research is necessary to determine the main side effects of PSMA TAT.



https://ift.tt/2Klb3k0

68 Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy

Abstract

Purpose

The primary aim of this retrospective, single-centre analysis was to assess the performance of 68Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68Ga-PSMA-11 PET/CT on treatment strategy.

Methods

68Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2–0.5 ng/ml at the time of the 68Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68Ga-PSMA-11 PET/CT images.

Results

We enrolled 119 PCa patients (mean age 66 years, range 44–78 years) with a mean PSA level at the time of 68Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20–0.50 ng/ml). 68Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68Ga-PSMA-11 PET/CT result.

Conclusion

In our patient series with PSA levels <0.5 ng/ml, 68Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.



https://ift.tt/2BnCA1F

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