Background The risk of developing decompression illness (DCI) in divers with a patent foramen ovale (PFO) has not been directly determined so far; neither has it been assessed in relation to the ...PFO's size. Methods In 230 scuba divers (age 39±8 years), contrast trans-oesophageal echocardiography (TEE) was performed for the detection and size grading (0–3) of PFO. Prior to TEE, the study individuals answered a detailed questionnaire about their health status and about their diving habits and accidents. For inclusion into the study, ⩾200 dives and strict adherence to decompression tables were required. Results Sixty-three divers (27%) had a PFO. Overall, the absolute risk of suffering a DCI event was 2.5 per 104 dives. There were 18 divers (29%) with, and 10 divers (6%) without, PFO who had experienced ⩾1 major DCI events \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((P=0.016)\) \end{document}. In the group with PFO, the incidence per 104 dives of a major DCI, a DCI lasting longer than 24 h and of being treated in a decompression chamber amounted to 5.1 (median 0, interquartile range IQR 0–10.0), 1.9 (median 0, IQR 0–4.0) and 3.6 (median 0, IQR 0–9.8), respectively and was 4.8–12.9-fold higher than in the group without PFO \batchmode \documentclassfleqn,10pt,legalpaper{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((P{<}0.001)\) \end{document}. The risk of suffering a major DCI, of a DCI lasting longer than 24 h and of being treated by recompression increased with rising PFO size. Conclusion The presence of a PFO is related to a low absolute risk of suffering five major DCI events per 104 dives, the odds of which is five times as high as in divers without PFO. The risk of suffering a major DCI parallels PFO size.
The addition of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) to endocrine therapy impressively improved the outcome of patients with hormone receptor-positive metastatic breast cancer. Despite ...their great efficacy, not all patients respond to treatment and many of them develop acquired resistance. The aim of this retrospective study was to assess the role of 18F-FDG PET/CT in predicting PFS and OS in breast cancer patients treated with CDK4/6i.
114 patients who performed an 18F-FDG PET/CT scan before (PET1) and 2-6 months (PET2) after starting treatment were retrospectively enrolled. Metabolic response was evaluated by EORTC, PERCIST and Deauville Score and correlated to PFS and OS.
In patients who did not progress at PET2 (n = 90), PFS rates were not significantly different between classes of response by EORTC and PERCIST. Conversely, patients showing a Deauville score ≤3 had a longer PFS (median PFS 42 vs 21.0 months; p = 0.008). A higher total metabolic tumor volume at PET1 (TMTV1) was also associated with a shorter PFS (median 18 vs 42 months; p = 0.0026). TMTV1 and Deauville score were the only independent prognostic factors for PFS at multivariate analysis and their combination stratified the population in four definite classes of relapse risk. Conversely, the above parameters did not affect OS which was only influenced by a progressive metabolic disease at PET2 (3-years survival rate 29.8 vs 84.9%; p<0.0001).
TMTV and metabolic response by Deauville score were significant prognostic factors for PFS in patients with breast cancer treated with CDK4/6i. Their determination could help physicians to select patients who may need a closer follow up.
The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate ...clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human-environment interactions during Humankind history.
Background .sup.223Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, ...based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of alpha-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize .sup.223Ra treatment. Methods Out of 20 mCRPC patients who underwent standard .sup.223Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each .sup.223Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar .sup.223Ra images were obtained at 2-4 and 18-24 h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET/CT, PSA value and ALP while haematological parameters were evaluated weekly after .sup.223Ra injection and 2 months after last cycle. Results 1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of .sup.223Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics. Conclusions This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate .sup.223Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during .sup.223Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose. Trial registration The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18-2111). Keywords: Dosimetry, Biological effects, .sup.223Ra
At a time of increasing evidence for dose-effect relationships in radioembolization (RE) with 90Y-microspheres, the general consensus is that there is an urgent need for accurate treatment planning ...and dose assessment in patients undergoing RE treatment. This work aimed at assessing the usefulness of 99mTc macroaggregated albumin (MAA) SPECT/CT imaging for personalized provisional RE dosimetry considering a 3D-printed patientlike phantom (AdboMan phantom). A homemade tool was developed in MATLAB for image analysis and absorbed dose calculation. Two dose calculaton methods were implemented and used to calculate dose volume histograms: (I) dose kernel method and (II) local energy deposition method. The accuracy of the two different dosimetric methods was evaluated by means of 3D γ-index (1%–1 mm and 2%–2 mm) implemented in the tool. Differences between the two dose calculation methods using the 3D γ-index are within 1%–1 mm and 2%–2 mm for all AbdoMan inserts, with a passing rate of 99.9% and 100%, respectively, proving a good agreement between the two calculation methods. The present study supports the use of 99mTc-MAA SPECT acquisition for provisional dosimetry along with the local energy deposition method to convert reconstructed SPECT data into absorbed dose maps. As long as 99mTc-MAA SPECT acquisitions are performed on liver lesions larger than 40 mm, the absorbed dose computed by means of the local energy deposition method can lead to results in line with those obtained by Monte Carlo calculations.
Background: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed ...local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). Methods: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP; subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater); a presumed local failure at mpMR; no distant metastases at 18F-fluorocholine PET/CT (CH/PET); no previous history of androgen deprivation therapy. Patients were offered both 64CuCl2 PET/CT (CU/PET) and 64Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. Results: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9–100%), DRs were 47.2% (95%CI: 36.1–58.6%) and 54.4% (95%CI: 42.7–65.7%) for CU/PET and PSMA/PET, respectively (p < 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. Conclusions: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy.
Background: Soft-tissue sarcomas (STS) represent a wide heterogeneous class of rare tumors. The exact role 18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) in the ...evaluation of STS is not well established. The aim of the present study was to evaluate how the use of 18F-FDG PET/CT in STS could influence patient therapy planning, looking for a possible added value over computed tomography and magnetic resonance imaging—the most used modalities in the study of STS. Differences in SUVmax according to histologic subtype and tumor grade were also considered. Methods: a total of 345 consecutive 18F-FDG PET/CT scans performed for initial staging (n = 171) or for suspected disease relapse (n = 174) in 282 patients with STS extracted from the local Information System database were retrospectively reviewed. Results: 18F-FDG PET/CT altered therapy planning in 80 cases (16.4% for staging and 29.9% in restaging), both for disease upstaging (58.8%) and downstaging (41.2%) Conclusions: 18F-FDG PET/CT could significantly influence management of patients with STS, particularly for restaging.
The ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-detected brown adipose tissue (BAT), is enhanced by cold stimulus and modulated by other factors that still have to be disentangled. We investigated the ...prevalence, mass, and glucose-uptake activity of ¹⁸F-FDG-detected BAT in a population of adults living in the temperate climatic zone of the Rome area.
We retrospectively analyzed 6454 patients who underwent ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) examinations. We found ¹⁸F-FDG BAT in 217 of the 6454 patients (3.36%). Some of them underwent more than one scan and the positive scans were 278 among 8004 (3.47%). The prevalence of patients with at least one positive scan was lower in men (1.77%; 56 of 3161) compared with women (4.88%; 161 of 3293). The BAT positive patients were most frequently younger, thinner and with lower plasma glucose levels compared with BAT negative patients. The amount of BAT in the defined region of interest, the activity of BAT and the number of positive sites of active BAT were similar in both sexes. The prevalence of patients with ¹⁸F-FDG positive PET/CT was highest in December-February, lower in March-May and September-November, and lowest in June-August and was positively correlated with night length and negatively correlated with ambient temperature. Changes in day length and variations of temperature, associated with the prevalence of positive BAT patients. Among the patients who had multiple scans, outdoor temperature was significantly lower and day length was shorter on the occasion when BAT was detected.
This study identifies day length, outdoor temperature, age, sex, BMI, and plasma glucose levels as major determinants of the prevalence, mass, and activity of ¹⁸F-FDG-detected BAT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Target therapy with BRAF/MEK inhibitors in metastatic melanoma is characterised by a high response rate; however, acquired resistance to treatment develops in many cases. We aimed to ...investigate if baseline total metabolic tumour volume (TMTV) and therapy-response assessment by
18
FFDG PET/CT have a prognostic role on progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma receiving BRAF ± MEK inhibitors.
Methods
Fifty-seven patients who performed an
18
FFDG PET/CT at baseline and on treatment were retrospectively evaluated. A Cox proportional-hazard model was used to examine associations between OS and PFS with baseline clinical/PET parameters as well as for PET response.
Results
According to EORTC criteria, 34 patients were classified as responders (partial/complete metabolic response PMR/CMR) and 23 as non-responders (progressive/stable metabolic disease PMD/SMD). Baseline characteristics associated with a shorter PFS were more than two metastatic organ sites and TMTV > 56 cm
3
; the latter was the only independent feature at multivariate analysis. Patients achieving a CMR were associated with a prolonged PFS compared with those with PMR (median PFS 42.9 vs 8.8 months;
p
= 0.009). Disease progression occurred in new-onset disease sites in 87.5% of CMR, 7.1% of PMR and 34.8% of PMD/SMD (
p
< 0.001). High baseline TMTV and lack of treatment response were independent prognostic factors for OS, stratifying patients in three different prognostic classes (median OS 6.7, 18.3 and 102.2 months, respectively).
Conclusions
Baseline TMTV and metabolic response may be useful prognostic indicators for PFS and OS in patients with advanced melanoma treated with BRAF/MEK inhibitors.
Key Points
• In a retrospective cohort of 57 metastatic melanoma patients treated with BRAF/MEK inhibitors, a TMTV > 56 cm
3
at baseline
18
FFDG PET/CT was significantly correlated with a shorter PFS and OS.
• The combined use of baseline TMTV along with PET response during treatment allowed for the identification of three groups of patients with very different median OS.
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