Purpose
To assess the impact of an
18
FFDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with ...indeterminate cytology.
Methods
In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent
18
FFDG-PET/CT and were randomised to an
18
FFDG-PET/CT-driven or diagnostic surgery group. In the
18
FFDG-PET/CT-driven group, management was based on the
18
FFDG-PET/CT result: when the index nodule was visually
18
FFDG-positive, diagnostic surgery was advised; when
18
FFDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules.
Results
Patient management was unbeneficial in 42% (38/91 95% confidence interval CI, 32–53%) of patients in the
18
FFDG-PET/CT-driven group, as compared to 83% (34/41 95% CI, 68–93%) in the diagnostic surgery group (
p
< 0.001).
18
FFDG-PET/CT-driven management avoided 40% (25/63 95% CI, 28–53%) diagnostic surgeries for benign nodules: 48% (23/48 95% CI, 33–63%) in non-Hürthle cell and 13% (2/15 95% CI, 2–40%) in Hürthle cell nodules (
p
= 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of
18
FFDG-PET/CT were 94.1% (80.3–99.3%), 39.8% (30.0–50.2%), 95.1% (83.5–99.4%), 35.2% (25.4–45.9%), and 31.1% (23.3–39.7%), respectively.
Conclusion
An
18
FFDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules.
Trial registration number
This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014),
https://clinicaltrials.gov/ct2/show/NCT02208544
.
Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Myocardial Triglyceride Content and Improves Myocardial Function Sebastiaan Hammer, Marieke Snel, Hildo J. ...Lamb, Ingrid M. Jazet, Rutger W. van der Meer, Hanno Pijl, Edo A. Meinders, Johannes A. Romijn, Albert de Roos, Johannes W. A. Smit In type 2 diabetes mellitus (T2DM), myocardial triglyceride (TG) stores are increased. We studied the effects of prolonged caloric restriction on myocardial TG content, myocardial function, and glucoregulation in obese patients with T2DM. Caloric restriction decreased body weight associated with improved glucoregulation, a decrease in myocardial TG content, and improvements in diastolic function. We conclude that myocardial TG stores in obese patients with T2DM are flexible and amendable to therapeutic intervention by caloric restriction. Therefore, the data emphasize the potential relevance of measuring myocardial TG content as a surrogate marker to assess the effects of metabolic interventions on the heart.
Introduction
Psoriasis is a chronic, inflammatory disease, which ranges in severity from mild to severe. Although topical therapies are frequently used to treat mild disease, they are not routinely ...used to treat patients with moderate-to-severe disease who have a larger proportion of their body surface area (BSA) affected (≥ 5% BSA). Based on well-controlled trials in adults with mild-to-severe disease, fixed-dose combination calcipotriol 50 μg/g + betamethasone dipropionate 0.5 mg/g (Cal/BD) cutaneous foam has been approved (Enstilar®, LEO Pharma) in the USA and EU for the treatment of psoriasis vulgaris for up to 4 weeks in adults. In this post-hoc subgroup analysis, we used pooled data from phase II/III trials to investigate the efficacy and safety of Cal/BD cutaneous foam in patients with moderate-to-severe psoriasis.
Methods
Patients included in this analysis had psoriasis affecting 5–15% BSA and a physician’s global assessment (PGA) ≥ 3. Endpoints included: treatment success by PGA (rating: clear/almost clear), patient’s global assessment (PaGA) at week 4 (rating: clear/very mild) and safety.
Results
A total of 340 patients in the three randomized trials met the BSA/PGA inclusion criteria, of whom 254 were treated with Cal/BD foam and 86 with vehicle foam. Treatment success by PGA and PaGA at week 4 was achieved in 143 (58.1%) and 138 (56.1%) patients receiving Cal/BD foam, respectively, versus three (3.6%) and 14 (16.7%) patients receiving vehicle foam. Sixty-six adverse events (AEs) occurred in 47 (18.5%) patients receiving Cal/BD foam and 11 AEs occurred in 11 (12.8%) patients receiving vehicle foam. Three severe AEs and 15 non-serious treatment-related AEs occurred in patients receiving Cal/BD foam.
Conclusion
The results from three clinical trials analyzed together show that topical Cal/BD foam is well tolerated and efficacious for treating patients with moderate-to-severe disease. Data support Cal/BD foam as a potential topical therapy for moderate-to-severe psoriasis.
Trial registrations
ClinicalTrials.gov registration numbers: NCT01866163, NCT02132936, NCT01536886.
Pericardial fat accumulation has been associated with an increased cardiovascular risk. A very low calorie diet (VLCD) improves the cardiovascular risk profile in patients with type 2 diabetes ...mellitus (T2DM), by improving the metabolic profile, heart function, and triglyceride (TG) stores in (non)adipose tissues. However, long‐term effects of a VLCD on pericardial fat volume and tissue‐specific TG accumulation have not been documented. The aim of this study was therefore to assess the effects of a 16‐week VLCD and of subsequent 14 months follow‐up on a regular diet on pericardial fat in relation to other TG stores in obese T2DM patients. We included 14 obese patients with insulin‐treated T2DM (mean ± s.e.m.: age 53 ± 2 years; BMI 35 ± 1 kg/m2). Pericardial fat and other (non)adipose TG stores were measured using magnetic resonance (MR) imaging and proton spectroscopy before and after a 16‐week VLCD and after a 14‐month follow‐up without dietary interventions. A 16‐week VLCD reduced body weight, pericardial fat, hepatic TG content, visceral and subcutaneous abdominal fat volumes to 78, 83, 16, 40, and 53% of baseline values respectively, (all P < 0.05). After an additional 14 months of follow‐up on a regular diet, the reduction in pericardial fat volume sustained, despite a substantial regain in body weight, visceral abdominal fat, and hepatic TG content (respectively 90, 83 and 73% of baseline values). In conclusion, VLCD‐induced weight loss in obese T2DM patients is accompanied by a substantial decrease in pericardial fat volume, which is sustained even after subsequent weight regain.
Objective This study assessed the health-related quality of life (HRQoL) in patients undergoing 2-18Ffluoro-2-deoxy-D-glucose (FDG)-PET/CT for an indeterminate (Bethesda III/IV) thyroid nodule. ...FDG-PET/CT accurately rules out malignancy and prevents 40% of futile diagnostic surgeries in these nodules. Design Secondary analyses of HRQoL data from a randomised controlled multicentre trial (NCT02208544) in 126 patients from 15 hospitals in the Netherlands were done. Methods Longitudinal HRQoL assessment was performed using the EuroQol 5-dimension 5-level (EQ-5D-5L), the RAND 36-item Health Survey v2.0 (RAND-36), and the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire on baseline, 3, 6, and 12 months, relative to the date of the FDG-PET/CT scan. Results Patients who were randomised to active surveillance following an FDG-negative nodule instead of diagnostic surgery reported stable HRQoL scores throughout the year. Univariate analysis indicated better HRQoL for patients undergoing surveillance than surgical patients with benign histopathology on multiple physical and psychosocial domains. Univariate within-group analysis suggested both temporary and continued HRQoL deteriorations in patients with benign histopathology over time. Multivariate within-group analysis demonstrated no significant longitudinal HRQoL changes in patients undergoing active surveillance. In contrast, in patients with benign histopathology, worse HRQoL was observed with regard to ThyPRO cognitive impairment (P = 0.01) and cosmetic complaints (P = 0.02), whereas goitre symptoms (P < 0.001) and anxiety (P = 0.04) improved over time. In patients with malignant histopathology, anxiety also decreased (P = 0.05). Conclusions The reassurance of a negative FDG-PET/CT resulted in sustained HRQoL throughout the first year of active surveillance. Diagnostic surgery for a nodule with benign histopathology resulted in more cognitive impairment and physical problems including cosmetic complaints, but improved goitre symptoms and anxiety. Anxiety was also reduced in patients with malignant histopathology.
Very low calorie diets (VLCD) with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not ...been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼ 450 kcal/day). Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS) and targeted multiple reaction monitoring (MRM) and a large scale isobaric tags for relative and absolute quantitation (iTRAQ) approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin), obesity-associated (complement C3), and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV). To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers.
Controlled-Trials.com ISRCTN76920690.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To evaluate our institutional experience with molecular diagnostics (MD) on thyroid cytology smears, evaluate the costs and describe MD guided clinical management of indeterminate Bethesda ...III/V thyroid nodules.
Methods
We performed a retrospective review of 164 Bethesda III or V thyroid cytopathology reports subjected to MD from 2013 to 2020, that altered Bethesda classification or management. MD consisted of mutation and gene fusion analysis by next‐generation sequencing (NGS) of morphologically analysed and selected cytological slides. Findings were modelled to nationwide data on Bethesda incidences from ‘the Dutch Pathology Registry’ PALGA, and costs were estimated.
Results
82 of 164 cases received an upgrade in Bethesda class. Twenty cases changed from Bethesda III to IV/V, 62 from Bethesda III or V to VI, and 72 remained unaltered. We estimate net savings with implementing MD, by preventing 454 repeat cytology and 326 (diagnostic) hemithyroidectomies, to be at least 2 million Euro annually in the Netherlands. Per Bethesda III and V patient, net savings would be about 100 Euro and 4100 Euro, respectively.
Conclusion
NGS‐based MD on nucleic acids extracted directly from cytology slides is a feasible and cost saving tool for personalized management in indeterminate Bethesda III/V thyroid cytology. Based on the interpretation of our retrospective data, we assume that this approach results in less disease burden for the patient, reduced surgical interventions and complication risks, reduced sick leave, among others. Further evaluation of structural implementation of the presented approach in routine thyroid Bethesda III/V cytology in a prospective setting is warranted.
We evaluated our institutional experience with molecular diagnostics (MD) on thyroid cytology smears, evaluated the costs and described MD guided clinical management of indeterminate Bethesda III/V thyroid nodules. NGS‐based MD on nucleic acids extracted directly from cytology slides is a feasible and cost saving tool for personalized management in indeterminate Bethesda III/V thyroid cytology.
Changing insights regarding radioiodine (I-131) administration in differentiated thyroid carcinoma (DTC) stir up discussions on the utility of pre-ablation diagnostic scintigraphy (DxWBS). Our ...retrospective study qualitatively and semi-quantitatively assessed posttherapy I-131 whole-body scintigraphy (TxWBS) data for thyroid remnant size and metastasis. Findings were associated with initial treatment success after nine months, as well as clinical, histopathological, and surgical parameters. Possible management changes were addressed. A thyroid remnant was reported in 89 of 97 (92%) patients, suspicion of lymph node metastasis in 26 (27%) and distant metastasis in 6 (6%). Surgery with oncological intent and surgery by two dedicated thyroid surgeons were independently associated with a smaller remnant. Surgery at a community hospital, aggressive tumor histopathology, histopathological lymph node metastasis (pN1) and suspicion of new lymph node metastasis on TxWBS were independently associated with an unsuccessful treatment. Thyroid remnant size was unrelated to treatment success. All 13 pN1 patients with suspected in situ lymph node metastases on TxWBS had an unsuccessful treatment, opposite 19/31 (61%) pN1 patients without (
= 0.009). Pre-ablative knowledge of these TxWBS findings had likely influenced management in 48 (50%) patients. Additional pre-ablative diagnostics could optimize patient-tailored I-131 administration. DxWBS should be considered, especially in patients with pN1 stage or suspected in situ lymph node metastasis. Dependent on local surgical expertise, DxWBS is not recommended to evaluate thyroid remnant size.
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