Radiofrequency ablation for symptomatic, non-functioning, thyroid nodules: a single-center learning curve.

Objective: Radiofrequency ablation (RFA) is increasingly considered the prime option for treating symptomatic, benign, non-functioning thyroid nodules (NFTN). However, little is known about the degree of operator experience required to achieve optimal results. This study describes the RFA learning curve of a single-center team. Methods: A retrospective cohort study of the first 103 patients receiving RFA treatment for a single, symptomatic, and benign NFTN, with a follow-up of at least 1 year. The primary outcome measure was technique efficacy, defined as the percentage of patients with a 6-month nodal volume reduction ratio (VRR) >50% after single-session RFA. Optimal treatment efficacy was defined as a 6-month VRR >50% achieved in at least 75% of patients. Secondary outcomes were complications of RFA and indications of secondary interventions. Results: Median nodal volume at baseline was 12.0 mL (range 2.0-58.0 mL). A 6-month VRR >50% was achieved in 45% of the first 20 patients, 75% of the next 20, and 79% of the following 63 patients. Complications included minor bleeding (N = 4), transient hyperthyroidism (N = 4), and transient loss of voice (N = 1). Poor volume reduction or nodular regrowth led to diagnostic lobectomy in 11 patients and a second RFA in 5. Lobectomy revealed a follicular carcinoma (T2N0M0) in 2 patients. In 1 patient, nodule regrowth was caused by an intranodular solitary B-cell lymphoma. Conclusion: About 40 procedures are required to achieve a 6-month VRR >50% in the majority of patients. Appropriate follow-up with re-evaluation is recommended for all patients with a VRR <50% and in those with regrowth to exclude underlying malignancy.

Optimal current frequency for the detection of changes in extracellular water in patients on hemodialysis by measurement of total body electrical resistance.

BACKGROUND & AIMS: Measurement of total body electrical resistance (TBER) to an alternating current is useful to monitor extracellular water (ECW) in patients on hemodialysis (HD). Which current frequency is preferable is subject of ongoing debate. The aim of this study was to quantify the implications of TBER measurements at current frequencies ranging from 0 to 1000 kHz for ECW monitoring in patients on HD. METHODS: Bioimpedance spectroscopy measurements were performed in 39 patients on HD using the Body Composition Monitor (BCM, Fresenius Medical Care). TBER data at 5, 50, 200, 500, and 1000 kHz were compared with the extrapolated TBER at 0 kHz (TBER0) assessed by Cole-Cole analysis. Sensitivity of each TBER configuration was evaluated at individual level, by assessment of the smallest ultrafiltration (UF) volume that induced a significant change in TBER, i.e. a change in TBER ≥ 2.7%. RESULTS: TBER precision was very high for all frequencies, with coefficients of variation of 0.25%-0.28%. Baseline TBER decreased with increasing current frequency. TBER was 2.9% lower at 5 kHz (P < 0.001), 11.6% lower at 50 kHz, and up to 22.0% lower at 1000 kHz. This pattern is attributed to a progressive increase in intracellular current conduction at higher frequencies. Sensitivity to volume changes induced by UF also decreased with increasing current frequency. At 0 and 5 kHz, an UF volume ≤ 0.5 L was sufficient to induce a significant increase in TBER in 87% of patients. This decreased to 69% at higher frequencies. CONCLUSION: ECW monitoring by TBER requires measurement at 5 kHz or less to ensure optimal performance.

Prediction of total body electrical resistance normal values based on limb muscle thickness assessed by ultrasound.

BACKGROUND: Recently, a new model has been proposed to assess hydration in patients by measurement of total body electrical resistance (TBER), with results expressed in ohm rather than in liter body water. According to this approach, hydration is considered to be normal if TBER is within the normal range. As TBER is inversely related to the size of the limb muscle compartment, this relationship can be used to calculate the patient-specific TBER normal value (TBERnorm). The present study investigates whether the prediction of TBERnorm can be improved by the use of ultrasound (US) instead of anthropometrically derived parameters of limb muscularity. METHODS: In total, 129 healthy subjects (60 men and 69 women) ranging in age from 18 to 75 yr, and in BMI from 17.4 to 52.0 kg/m2 were included in the study. Arm muscle cross-sectional area assessed by anthropometry (AMAcaliper) was compared with mean muscle thickness (MMT) of arm and leg assessed by B-mode US. RESULTS: MMT correlated stronger with TBER than AMA, and reduced the standard error of the estimate (SEE) by 15% in men and by 26% in women. Muscularity was overestimated by AMAcaliper due to a systematic error directly proportional to subcutaneous fat layer thickness. The gender independent relation between MMT and TBERnorm is described by the equation: TBERnorm = 705-75.4⋅MMT (R2 = 0.85, SEE = 22.3 Ω/m, P < 0.001). CONCLUSIONS: US-based measurement of limb muscularity provides a more precise prediction of TBERnorm, in particular in obese subjects, and is recommended as the method of choice.

Sensitivity of total body electrical resistance measurements in detecting extracellular volume expansion induced by infusion of NaCl 0.9.

BACKGROUND: Fluid balance management in hospitalized patients is hampered by the limited sensitivity of currently available tools. The aim of this study was to assess the sensitivity of total body electrical resistance (TBER) measurements for the detection of extracellular volume (ECV) expansion. METHODS: TBER and plasma resistivity (ρplasma) were measured during a 4-h infusion of NaCl 0.9% at a rate of 500 mL/h in 23 patients undergoing a diagnostic saline infusion test for primary hyperaldosteronism. Extracellular fluid gain (EFG) was defined as infusion volume minus urinary volume. RESULTS: Infusion of 2.0 L NaCl 0.9% was associated with a mean diuresis of 1.1 ± 0.5 L, an EFG of 0.9 ± 0.5 L, a decrease in ρplasma of 1.1 ± 0.7 Ω·cm or 1.7 ± 1.0% (P < 0.001), and a decline in TBER of 23.2 ± 10.9 Ω or 4.6 ± 2.2% (P < 0.001). At group level, infusion of 80 mL saline was sufficient to induce a statistically significant decline in mean TBER. At personal level, the decline in TBER was significant on 76% of occasions after an EFG of 0.5-0.75 L, and on all occasions after an EFG of 1.0 L or greater. CONCLUSION: Raw TBER data are very informative for the detection of ECV expansion induced by the infusion of NaCl 0.9%, with a sensitivity at a personal level that is relevant for clinical practice.

Hyperactive thyroid nodules treated by radiofrequency ablation: a Dutch single-centre experience.

BACKGROUND: Hyperactive thyroid nodules (HTN) are usually treated with radioactive iodine (RAI). However, as RAI is associated with a 30-60% long-term risk of permanent hypothyroidism, radiofrequency ablation (RFA) may be a good alternative. Primary aim of this study was to assess the percentage of patients achieving euthyroidism after RFA. PATIENTS AND METHODS: Patients with a symptomatic HTN were treated by ultrasound-guided RFA, using the trans-isthmic approach and moving-shot technique, in an outpatient setting under local anaesthesia. RESULTS: Twenty-one patients were included, ranging in age from 37-75 years. Follow-up was at least one year. All patients had a suppressed serum thyroid-stimulating hormone (TSH), with free thyroxine (FT4) and free triiodothyronine (FT3) concentrations mildly elevated in 33% and 43% of cases, respectively. RFA was not associated with clinically meaningful adverse effects. TSH normalisation was achieved in 11/21 patients (52%) after first RFA. A partial response, defined as a normalisation of FT4 and FT3, but incomplete improvement of TSH, was observed in 6/21 patients (29%). Three patients had no response (14%), and one patient developed mild, asymptomatic subclinical hypothyroidism. Five patients underwent a second RFA and this led to TSH normalisation in four, thereby raising the rate of complete remission to 71%. Recurrence of TSH suppression did not occur during the study period. CONCLUSION: These data suggest that RFA is a safe and promising treatment for symptomatic hyperactive thyroid nodules, with a low risk of permanent hypothyroidism. Long-term studies are needed to identify the recurrence risk of hyperthyroidism.

Towards personalized hydration assessment in patients, based on measurement of total body electrical resistance: Back to basics.

BACKGROUND & AIMS: Assessment of tissue hydration by conventional bioelectrical impedance analysis (BIA) has produced conflicting results because of flaws in the algorithms that are used to translate measurements of total body electrical resistance (TBER) into liters of body water. This type of error can be eliminated by a return to the TBER measurement itself, without attempting to convert Ohms into liters of body water. Aims of this study were to quantify tissue hydration based on TBER, to establish TBER normal values (TBERnorm), to improve the prediction of TBERnorm values in individual patients, and to evaluate this approach in patients on hemodialysis (HD). METHODS: TBERnorm values were obtained in 213 healthy controls and corrected for body height (H-TBERnorm). Inter-individual H-TBERnorm variability was reduced by correction for arm muscle cross-sectional area (AMA). Performance of this approach was evaluated in 94 patients on HD. RESULTS: H-TBERnorm was inversely related to AMA. Correction for AMA reduced the H-TBERnorm standard deviation by 31% in men and 23% in women. When applied to patients on HD, H-TBER changes within subjects were inversely related to ultrafiltration volumes, with a mean R2 of 0.95 ± 0.04 in men and 0.93 ± 0.07 in women. Clinically significant H-TBER increments occurred after volume reductions of 0.39 ± 0.25 L in men and 0.37 ± 0.18 L in women. CONCLUSIONS: TBER measurements, corrected for height and AMA, have the potential to become an objective and sensitive method to assess hydration in patients. Its clinical value remains to be shown in intervention studies.

Assessment of Plasma Resistivity as a Surrogate for Extracellular Fluid Resistivity: Analytical Performance and Impact of Fluid Composition.

Bio-electrical impedance analysis (BIA) is frequently used to assess body composition in man. Its accuracy in patients is limited, possibly because the employed algorithms are based on the assumption that total body electrical resistance (TBER) is exclusively related to body water volume, and that variation in fluid composition and its effect on fluid resistivity can be ignored. This may introduce substantial calculation errors. The aim of this study was to develop an objective method to assess plasma resistivity (ρplasma) based on measurements by a conductivity probe, as a surrogate for extracellular fluid resistivity (ρe). Sample measurements were standardized at body temperature. Analytical variation was 0.6% within runs and 0.9% between runs. The critical difference, i.e. the smallest difference needed to consider changes within individuals significant, was 1.8% for measurements within runs and 4.3% for measurements between runs. The normal range was defined by a mean ± SD of 66.9 ± 1.8 Ω cm. Multiple regression demonstrated that ρplasma was inversely related to plasma sodium and chloride concentrations, and positively related to total protein (overall R2 = 0.92, p < 0.001). In conclusion, ρplasma measurements were sufficiently robust to be useful as a tool to examine and improve the validity of BIA in clinical settings.

Success rate of thyroid remnant ablation for differentiated thyroid cancer based on 5550 MBq post-therapy scan.

BACKGROUND: Success rate of thyroid remnant ablation in patients with low-risk differentiated thyroid cancer (DTC) is commonly based on measurement of serum thyroglobulin levels and 185 MBq (5 mCi) diagnostic 131I scanning or neck ultrasound, performed 6-9 months after ablation. In the present study, we report the rates of successful 131I ablation based on a 5550 MBq (150 mCi) post-therapy scan performed 6-9 months after ablation. METHODS: Retrospective cohort study of 77 adult patients with DTC, stage T1-T3, N0 or N1, M0, demonstrating thyroid remnant uptake one week after a 2775 MBq (75 mCi) ablation dose. Six to nine months later, all patients received a 5550 MBq dose of 131I, followed by a post- therapy scan after one week. Complete thyroid ablation was defined as no thyroid remnant uptake and a thyroglobulin level < 0.2 µg/l after thyroid hormone withdrawal. RESULTS: Thyroid ablation was complete in 20 patients (26%). Forty-eight patients (62%) demonstrated persistent remnant uptake. This was associated with thyroglobulin levels > 0.2 µg/l in 24/48, and positive thyroglobulin antibodies in 4/48 patients. CONCLUSION: Thyroid remnant ablation success assessed by 5550 MBq post-therapy scanning was much lower than reported in studies evaluating ablation success based on 185 MBq diagnostic 131I scanning or neck ultrasound. The latter techniques may be too inaccurate to detect thyroid remnants and thus may not be sufficiently reliable to predict long-term disease outcome.

Chronic inhibition of the Na+/H+ - exchanger causes regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling.

BACKGROUND AND PURPOSE: Increased activity of the Na+/H+ -exchanger (NHE-1) in heart failure underlies raised [Na+]i causing disturbances of calcium handling. Inhibition of NHE-1, initiated at the onset of pressure/volume overload, prevents development of hypertrophy, heart failure and remodelling. We hypothesized that chronic inhibition of NHE-1, initiated at a later stage, would induce regression of hypertrophy, heart failure, and ionic and electrophysiological remodelling. EXPERIMENTAL APPROACH: Development of heart failure in rabbits was monitored electrocardiographically and echocardiographically, after one or three months. Cardiac myocytes were also isolated. One group of animals were treated with cariporide (inhibitor of NHE-1) in the diet after one month. Cytoplasmic calcium, sodium and action potentials were measured with fluorescent markers and sarcoplasmic reticulum calcium content by rapid cooling. Calcium after-transients were elicited after rapid pacing. Sodium channel current (INa) was measured using patch-clamp techniques. KEY RESULTS: Hypertrophy and heart failure developed after one month and progressed during the next two months. After one month, dietary treatment with cariporide was initiated. Two months of treatment reduced hypertrophy and heart failure, duration of action potential QT-interval and QRS, and restored sodium and calcium handling and the incidence of calcium after-transients. In cardiac myocytes, parameters of INa were not changed by cariporide. CONCLUSION AND IMPLICATIONS: In rabbit hearts with hypertrophy and signs of heart failure one month after induction of pressure/volume overload, two months of dietary treatment with the NHE-1 inhibitor cariporide caused regression of hypertrophy, heart failure and ionic and electrophysiological remodelling.

Increased Na+/H+-exchange activity is the cause of increased [Na+]i and underlies disturbed calcium handling in the rabbit pressure and volume overload heart failure model.

OBJECTIVE: Cytosolic sodium ([Na+]i) is increased in heart failure (HF). We hypothesize that up-regulation of Na+/H+-exchanger (NHE) in heart failure is causal to the increase of [Na+]i and underlies disturbance of cytosolic calcium ([Ca2+]i) handling. METHODS: Heart failure was induced in rabbits by combined volume and pressure overload. Age-matched animals served as control. [Na+]i, cytosolic calcium [Ca2+]i and cytosolic pH (pH(i)) were measured in isolated left ventricular midmural myocytes with SBFI, indo-1 and SNARF. SR calcium content was measured as the response of [Ca2+]i to rapid cooling (RC). Calcium after-transients were elicited by cessation of rapid stimulation (3 Hz) in the presence of 100 nmol/l noradrenalin. NHE and Na+/K+-ATPase activity were inhibited with 10 micromol/l cariporide and 100 micromol/l ouabain, respectively. RESULTS: At all stimulation rates (0-3 Hz) [Na+]i and diastolic [Ca2+]i were significantly higher in HF than in control. With increasing frequency [Na+]i and diastolic [Ca2+]i progressively increased in HF and control, and the calcium transient amplitude (measured as total calcium released from SR) decreased in HF and increased in control. In HF (at 2 Hz), SR calcium content was reduced by 40% and the calcium gradient across the SR membrane by 60%. Fractional systolic SR calcium release was 90% in HF and 60% in control. In HF the rate of pH(i) recovery following acid loading was much faster at all pH(i) and NHE dependent sodium influx was almost twice as high as in control. In HF cariporide (10 micromol/l, 5 min) reduced [Na+]i and end diastolic [Ca2+]i to almost control values, and reversed the relation between calcium transient amplitude and stimulation rate from negative to positive. It increased SR calcium content and SR membrane gradient and decreased fractional systolic SR depletion to 60%. Cariporide greatly reduced the susceptibility to develop calcium after-transients. In control animals, cariporide had only minor effects on all these parameters. Increase of [Na+]i with ouabain in control myocytes induced abnormal calcium handling as found in HF. CONCLUSIONS: In HF up-regulation of NHE activity is causal to increased [Na+]i and secondarily to disturbed diastolic, systolic and SR calcium handling. Specific inhibition of NHE partly normalized [Na+]i, end diastolic [Ca2+]i, and SR calcium handling and reduced the incidence of calcium after-transients. Chronic treatment with specific NHE inhibitors may provide a useful future therapeutic option in treatment of developing hypertrophy and heart failure.