Role of the Locus Coeruleus Arousal Promoting Neurons in Maintaining Brain Criticality across the Sleep-Wake Cycle.

Sleep control depends on a delicate interplay among brain regions. This generates a complex temporal architecture with numerous sleep-stage transitions and intermittent fluctuations to micro-states and brief arousals. These temporal dynamics exhibit hallmarks of criticality, suggesting that tuning to criticality is essential for spontaneous sleep-stage and arousal transitions. However, how the brain maintains criticality remains not understood. Here, we investigate θ- and δ-burst dynamics during the sleep-wake cycle of rats (Sprague-Dawley, adult male) with lesion in the wake-promoting locus coeruleus (LC). We show that, in control rats, θ- and δ-bursts exhibit power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, as well as power-law long-range temporal correlations (LRTCs)-typical of non-equilibrium systems self-organizing at criticality. Furthermore, consecutive θ- and δ-bursts durations are characterized by anti-correlated coupling, indicating a new class of self-organized criticality that emerges from underlying feedback between neuronal populations and brain areas involved in generating arousals and sleep states. In contrast, we uncover that LC lesion leads to alteration of θ- and δ-burst critical features, with change in duration distributions and correlation properties, and increase in θ-δ coupling. Notably, these LC-lesion effects are opposite to those observed for lesions in the sleep-promoting ventrolateral preoptic (VLPO) nucleus. Our findings indicate that critical dynamics of θ- and δ-bursts arise from a balanced interplay of LC and VLPO, which maintains brain tuning to criticality across the sleep-wake cycle-a non-equilibrium behavior in sleep micro-architecture at short timescales that coexists with large-scale sleep-wake homeostasis.

Beyond pulsed inhibition: Alpha oscillations modulate attenuation and amplification of neural activity in the awake resting state.

Alpha oscillations are a distinctive feature of the awake resting state of the human brain. However, their functional role in resting-state neuronal dynamics remains poorly understood. Here we show that, during resting wakefulness, alpha oscillations drive an alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last for a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over a few alpha cycles to amplify neural activity. Furthermore, we show that long-term alpha amplitude fluctuations-the "waxing and waning" phenomenon-are an attenuation-amplification mechanism described by a power-law decay of the activity rate in the "waning" phase. Importantly, we do not observe such dynamics during non-rapid eye movement (NREM) sleep with marginal alpha oscillations. The results suggest that alpha oscillations modulate neural activity not only through pulses of inhibition (pulsed inhibition hypothesis) but also by timely enhancement of excitation (or disinhibition).

Criticality of neuronal avalanches in human sleep and their relationship with sleep macro- and micro-architecture.

Sleep plays a key role in preserving brain function, keeping brain networks in a state that ensures optimal computation. Empirical evidence indicates that this state is consistent with criticality, where scale-free neuronal avalanches emerge. However, the connection between sleep architecture and brain tuning to criticality remains poorly understood. Here, we characterize the critical behavior of avalanches and study their relationship with sleep macro- and micro-architectures, in particular, the cyclic alternating pattern (CAP). We show that avalanches exhibit robust scaling behaviors, with exponents obeying scaling relations consistent with the mean-field directed percolation universality class. We demonstrate that avalanche dynamics is modulated by the NREM-REM cycles and that, within NREM sleep, avalanche occurrence correlates with CAP activation phases-indicating a potential link between CAP and brain tuning to criticality. The results open new perspectives on the collective dynamics underlying CAP function, and on the relationship between sleep architecture, avalanches, and self-organization to criticality.

Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain.

Neurons in the brain are wired into adaptive networks that exhibit collective dynamics as diverse as scale-specific oscillations and scale-free neuronal avalanches. Although existing models account for oscillations and avalanches separately, they typically do not explain both phenomena, are too complex to analyze analytically or intractable to infer from data rigorously. Here we propose a feedback-driven Ising-like class of neural networks that captures avalanches and oscillations simultaneously and quantitatively. In the simplest yet fully microscopic model version, we can analytically compute the phase diagram and make direct contact with human brain resting-state activity recordings via tractable inference of the model's two essential parameters. The inferred model quantitatively captures the dynamics over a broad range of scales, from single sensor oscillations to collective behaviors of extreme events and neuronal avalanches. Importantly, the inferred parameters indicate that the co-existence of scale-specific (oscillations) and scale-free (avalanches) dynamics occurs close to a non-equilibrium critical point at the onset of self-sustained oscillations.

A Survey of Stochastic Computing Neural Networks for Machine Learning Applications.

Neural networks (NNs) are effective machine learning models that require significant hardware and energy consumption in their computing process. To implement NNs, stochastic computing (SC) has been proposed to achieve a tradeoff between hardware efficiency and computing performance. In an SC NN, hardware requirements and power consumption are significantly reduced by moderately sacrificing the inference accuracy and computation speed. With recent developments in SC techniques, however, the performance of SC NNs has substantially been improved, making it comparable with conventional binary designs yet by utilizing less hardware. In this article, we begin with the design of a basic SC neuron and then survey different types of SC NNs, including multilayer perceptrons, deep belief networks, convolutional NNs, and recurrent NNs. Recent progress in SC designs that further improve the hardware efficiency and performance of NNs is subsequently discussed. The generality and versatility of SC NNs are illustrated for both the training and inference processes. Finally, the advantages and challenges of SC NNs are discussed with respect to binary counterparts.

Network Physiology of Cortico-Muscular Interactions.

Skeletal muscle activity is continuously modulated across physiologic states to provide coordination, flexibility and responsiveness to body tasks and external inputs. Despite the central role the muscular system plays in facilitating vital body functions, the network of brain-muscle interactions required to control hundreds of muscles and synchronize their activation in relation to distinct physiologic states has not been investigated. Recent approaches have focused on general associations between individual brain rhythms and muscle activation during movement tasks. However, the specific forms of coupling, the functional network of cortico-muscular coordination, and how network structure and dynamics are modulated by autonomic regulation across physiologic states remains unknown. To identify and quantify the cortico-muscular interaction network and uncover basic features of neuro-autonomic control of muscle function, we investigate the coupling between synchronous bursts in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing the concept of time delay stability and a novel network physiology approach, we find that the brain-muscle network exhibits complex dynamic patterns of communication involving multiple brain rhythms across cortical locations and different electromyographic frequency bands. Moreover, our results show that during each physiologic state the cortico-muscular network is characterized by a specific profile of network links strength, where particular brain rhythms play role of main mediators of interaction and control. Further, we discover a hierarchical reorganization in network structure across physiologic states, with high connectivity and network link strength during wake, intermediate during REM and light sleep, and low during deep sleep, a sleep-stage stratification that demonstrates a unique association between physiologic states and cortico-muscular network structure. The reported empirical observations are consistent across individual subjects, indicating universal behavior in network structure and dynamics, and high sensitivity of cortico-muscular control to changes in autonomic regulation, even at low levels of physical activity and muscle tone during sleep. Our findings demonstrate previously unrecognized basic principles of brain-muscle network communication and control, and provide new perspectives on the regulatory mechanisms of brain dynamics and locomotor activation, with potential clinical implications for neurodegenerative, movement and sleep disorders, and for developing efficient treatment strategies.

Computed tomography-derived myocardial extracellular volume: an early biomarker of cardiotoxicity in esophageal cancer patients undergoing radiation therapy.

OBJECTIVES: We aimed to assess extracellular volume (ECV) through non-gated, contrast-enhanced computed tomography (CT) before and after radiation therapy (RT) in patients with esophageal cancer (EC). MATERIALS AND METHODS: EC patients who had undergone CT before and after RT were retrospectively assessed. Patients with preexisting cardiovascular disease or with heavily artifacted CT were excluded. ECV was calculated using density values for the myocardial septum and blood pool. Data were reported as mean and standard deviation or median and interquartile range according to their distribution; t test or Wilcoxon and Pearson r or Spearman ρ were subsequently used. RESULTS: Twenty-one patients with stage ≥ IB EC, aged 64 ± 18 years, were included. Mean and maximum RT doses were 21.2 Gy (16.9-24.1) and 42.5 Gy (41.8-49.2), respectively. At baseline (n = 21), hematocrit was 39% ± 4%, ECV 27.9% ± 3.5%; 35 days (30-38) after RT (n = 20), hematocrit was 36% ± 4%, lower than at baseline (p = 0.002), ECV 30.3% ± 8.3%, higher than at baseline (p = 0.081); at follow-up 420 days (244-624) after RT (n = 13), hematocrit was 36% ± 5%, lower than at baseline (p = 0.030), ECV 31.4% ± 4.5%, higher than at baseline (p = 0.011). No patients showed signs of overt cardiotoxicity. ECV early after RT was moderately positively correlated with maximum RT dose (ρ = 0.50, p = 0.036). CONCLUSIONS: In EC patients, CT-derived myocardial ECV was increased after RT and may thus appear as a potential early biomarker of cardiotoxicity.

Back to (new) normality-A CODRAL/AIRO-L survey on cancer radiotherapy in Lombardy during Italian COVID-19 phase 2.

BACKGROUND: Italy experienced one of the world's severest COVID-19 outbreak, with Lombardy being the most afflicted region. However, the imposed safety measures allowed to flatten the epidemic curve and hence to ease the restrictions and inaugurate, on the 4th of May 2020, the Italian phase (P) 2 of the pandemic. The present survey study, endorsed by CODRAL and AIRO-L, aimed to assess how radiotherapy (RT) departments in Lombardy have dealt with the recovery. MATERIALS AND METHODS: A questionnaire dealing with the management of pandemic was developed online and sent to all CODRAL Directors on the 10th of June 2020. Answers were collected in full anonymity one week after. RESULTS: All the 33 contacted RT facilities (100%) responded to the survey. Despite the scale of the pandemic, during P1 14 (42.4%) centres managed to safely continue the activity (≤ 10% reduction). During P2, 10 (30.3%) centres fully recovered and 14 (42.4%) reported an increase. Nonetheless, 6 (18.2%) declared no changes and, interestingly, 3 (9.1%) reduced activities. Overall, 21 centres (63.6%) reported suspected or positive cases within healthcare workforce since the beginning of the pandemic. Staff units were quarantined in 19 (57.6%) and 6 (18.2%) centres throughout P1 and P2, respectively. In the two phases, about two thirds centres registered positive or suspected cases amongst patients. CONCLUSION: The study revealed a particular attention to anti-contagion measures and a return to normal or even higher clinical workload in most RT centres in Lombardy, necessary to carry out current and previously deferred treatments.

Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality.

Physical and biological systems often exhibit intermittent dynamics with bursts or avalanches (active states) characterized by power-law size and duration distributions. These emergent features are typical of systems at the critical point of continuous phase transitions, and have led to the hypothesis that such systems may self-organize at criticality, i.e. without any fine tuning of parameters. Since the introduction of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality (SOC) has been very fruitful for the analysis of emergent collective behaviors in a number of systems, including the brain. Although considerable effort has been devoted in identifying and modeling scaling features of burst and avalanche statistics, dynamical aspects related to the temporal organization of bursts remain often poorly understood or controversial. Of crucial importance to understand the mechanisms responsible for emergent behaviors is the relationship between active and quiet periods, and the nature of the correlations. Here we investigate the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity during the sleep-wake cycle. We show the duality of power-law (θ, active phase) and exponential-like (δ, quiescent phase) duration distributions, typical of SOC, jointly emerge with power-law temporal correlations and anti-correlated coupling between active and quiet states. Importantly, we demonstrate that such temporal organization shares important similarities with earthquake dynamics, and propose that specific power-law correlations and coupling between active and quiet states are distinctive characteristics of a class of systems with self-organization at criticality.

Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.

Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ-δ coupling. Our empirical findings and model simulations demonstrate that θ-δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep-wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.SIGNIFICANCE STATEMENT We show that the complex micro-architecture of sleep-stage/arousal transitions arises from intrinsic non-equilibrium critical dynamics, connecting the temporal organization of dominant cortical rhythms with empirical observations across scales. We link such behavior to sleep-promoting neuronal population, and demonstrate that VLPO lesion (model of insomnia) alters dynamical features of θ and δ rhythms, and leads to significant reduction in θ-δ coupling. This indicates that VLPO neurons may have dual role for both sleep and arousal/brief wake control. The reported empirical findings and modeling simulations constitute first evidences of a neurophysiological fingerprint of self-organization and criticality in sleep- and wake-related cortical rhythms; a mechanism essential for spontaneous sleep-stage and arousal transitions that lays the bases for a novel, non-homeostatic paradigm of sleep regulation.

Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture.

Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.

Equipment, staffing, and provision of radiotherapy in Lombardy, Italy: Results of three surveys performed between 2012 and 2016.

INTRODUCTION:: Several efforts are being implemented at the European level to measure provision of up-to-date radiation treatments across the continent. METHODS:: A snapshot survey involving all radiation oncology centers within Lombardy, Italy, was performed in 2012 and repeated in 2014 and 2016, in cooperation with regional governmental officers. Centers were asked to provide detailed information concerning all individual patients being treated on the index day, and to report data on available local resources. RESULTS:: We observed an increase in the number of centers and of megavoltage units (MVU) (from 76 to 87, i.e., 8.7 MVU per million inhabitants in 2016). Mean number of MVU per center was 2.5. Average age of MVU increased from 5.3 to 7.5 years and patients on the waiting list also increased. Conformal 3D radiotherapy (RT) treatments decreased from 56% to 42% and were progressively replaced by intensity-modulated RT treatments (from 39% to 49%). Waiting times were overall satisfactory. Radiation oncologists treated on average 152 and radiation therapists 100 RT courses per year. Average reimbursement per course was €4,879 (range €2,476-€8,014). CONCLUSIONS:: The methodology of snapshot survey proved feasible and provided valuable information about radiation oncology provision and accessibility in Lombardy.

On the temporal organization of neuronal avalanches.

Spontaneous activity of cortex in vitro and in vivo has been shown to organize as neuronal avalanches. Avalanches are cascades of neuronal activity that exhibit a power law in their size and duration distribution, typical features of balanced systems in a critical state. Recently it has been shown that the distribution of quiet times between consecutive avalanches in rat cortex slice cultures displays a non-monotonic behavior with a power law decay at short time scales. This behavior has been attributed to the slow alternation between up and down-states. Here we further characterize the avalanche process and investigate how the functional behavior of the quiet time distribution depends on the fine structure of avalanche sequences. By systematically removing smaller avalanches from the experimental time series we show that size and quiet times are correlated and highlight that avalanche occurrence exhibits the characteristic periodicity of θ and ß/γ oscillations, which jointly emerge in most of the analyzed samples. Furthermore, our analysis indicates that smaller avalanches tend to be associated with faster ß/γ oscillations, whereas larger ones are associated with slower θ and 1-2 Hz oscillations. In particular, large avalanches corresponding to θ cycles trigger cascades of smaller ones, which occur at ß/γ frequency. This temporal structure follows closely the one of nested θ - ß/γ oscillations. Finally we demonstrate that, because of the multiple time scales characterizing avalanche dynamics, the distributions of quiet times between avalanches larger than a certain size do not collapse onto a unique function when rescaled by the average occurrence rate. However, when considered separately in the up-state and in the down-state, these distributions are solely controlled by the respective average rate and two different unique function can be identified.

Effects of Poisson noise in a IF model with STDP and spontaneous replay of periodic spatiotemporal patterns, in absence of cue stimulation.

We consider a network of leaky integrate and fire neurons, whose learning mechanism is based on the Spike-Timing-Dependent Plasticity. The spontaneous temporal dynamic of the system is studied, including its storage and replay properties, when a Poissonian noise is added to the post-synaptic potential of the units. The temporal patterns stored in the network are periodic spatiotemporal patterns of spikes. We observe that, even in absence of a cue stimulation, the spontaneous dynamics induced by the noise is a sort of intermittent replay of the patterns stored in the connectivity and a phase transition between a replay and non-replay regime exists at a critical value of the spiking threshold. We characterize this transition by measuring the order parameter and its fluctuations.

Iodine fortification of vegetables improves human iodine nutrition: in vivo evidence for a new model of iodine prophylaxis.

BACKGROUND: Iodine deficiency is the result of insufficient intake of dietary iodine and as a consequence causes multiple adverse effects. About 2 billion individuals in the world are affected by iodine deficiency. It has been found that the most effective way to control iodine deficiency is through the universal salt iodization. However, salt iodization alone may not be sufficient to assure adequate iodine nutrition. In most industrialized countries, excess consumption of salt has become recognized as a health risk. Therefore, biofortification of vegetables with iodine offers an excellent opportunity to increase iodine intake. AIM AND METHODS: The aim of this study was to test the efficiency of a new model of iodine prophylaxis in a group of 50 healthy volunteers through the intake of vegetables (potatoes, cherry tomatoes, carrots, and green salad) fortified with iodine. Each serving of vegetables consisted of 100 g of potatoes, carrots, tomatoes, or salad containing 45 mg of iodine (30% of the Recommended Daily Allowance), and the volunteers consumed a single serving of vegetables, as preferred, each day for 2 weeks. Urinary iodine (UI) excretion was measured before and after intake of vegetables. RESULTS: The UI concentration measured in volunteers before the intake of vegetables was 98.3 mg/L (basal value), increasing to 117.5 mg/L during the intake of vegetables. Seven days after the discontinuation of vegetable intake, UI was 85 mg/L. UI concentration increment was 19.6% compared with the basal value; therefore, the difference was statistically significant (P = .035). CONCLUSIONS: Biofortification of vegetables with iodine provides a mild but significative increase in UI concentration and, together with the habitual use of iodized salt, may contribute to improve the iodine nutritional status of the population without risks of iodine excess.

Incidental versus clinically evident thyroid cancer: a 5-year follow-up study.

BACKGROUND: The incidence of differentiated thyroid cancer in patients undergoing surgery for presumed benign thyroid disease (incidental thyroid cancer) is not negligible. The purpose of this study was to verify if incidental thyroid cancers have a different clinical course than the clinically evident thyroid cancer. METHODS: A group of patients with incidental thyroid cancer (n = 95) has been compared to a control group with clinically evident thyroid cancer (n = 93). Both the histology and the outcome after a 5-year follow-up have been compared. RESULTS: At the univariate analysis, the groups demonstrated significant differences in many pathologic features, remnant ablation (p < .001), and persistent disease (p = .006). Nevertheless, the multivariate analysis revealed that the outcome was not influenced by the preoperative or the incidental diagnosis. CONCLUSION: Incidental thyroid cancers show a different pathological pattern when compared to clinically evident thyroid cancers. Nonetheless, the final outcome is not influenced by preoperative or postoperative diagnosis. Hence, patients with incidental thyroid cancer should follow the same postoperative protocols of patients with clinically evident thyroid cancer.

Modeling gross damage in tile-based nanomanufacturing by DNA self-assembly.

This paper proposes a novel model for gross damage as occurring in tile-based nanomanufacturing by DNA self-assembly. Gross damage occurs due to exogenous agents (such as radiation and tip-sample interactions) and is modeled as a hole (with a large number of empty tile sites) in the aggregate of the self-assembly. A stochastic analysis based on Markov chains for the tile binding process is pursued for regrowth of the tiles. This analysis establishes resilience as the probability to regrow the target pattern in the area affected by the gross damage. The conditions by which regrowth of a hole is favorable (i.e., at high resilience) compared with normal growth are established by considering temperature of aggregation and bond energy. As examples, two patterns for nano interconnects are analyzed based on the proposed model.

New echocardiographic techniques in the evaluation of left ventricular mechanics in subclinical thyroid dysfunction.

The new echocardiographic techniques for the study of physiopathological intramyocardial phenomena include video densitometry (VD), integrated backscatter (IBS), and color Doppler myocardial imaging (CDMI). Being more independent from cardiac load and from rotational and translational heart motion, these new sensible, noninvasive techniques such as CDMI and IBS show a real incremental value in comparison with conventional echocardiography and allow to detect subtle functional and textural abnormalities of intramural myocardium, partially undetectable by conventional two-dimensional Doppler echocardiography. Subclinical thyroid dysfunction (STD), both in its hypo- and hyperthyroidism form, has a relatively high prevalence in general population (9-15% with a lower percentage of adult males), hence it could be very useful to study more deeply heart involvement in these physiopathological conditions and understand the complex relationship between thyroid and heart. The use of these new ultrasonic techniques in subclinical hypothyroidism helps to detect the early simultaneous involvement of both cardiac cycle phases, which causes a decrease of intramyocardial contractility and an impairment of both active and passive phases of diastole. In subclinical hyperthyroidism, these new ultrasonic techniques permitted to discover more complex and different early cardiac abnormalities of both systolic and diastolic phases.

Proportion of type 1 and type 2 amiodarone-induced thyrotoxicosis has changed over a 27-year period in Italy.

CONTEXT: Two main forms of amiodarone-induced thyrotoxicosis (AIT) exist. Type 1 AIT is a form of iodine-induced hyperthyroidism. Its management is complex and includes thionamides, potassium perchlorate and, occasionally, thyroidectomy. Type 2 AIT is a destructive thyroiditis, responds to glucocorticoids, and usually does not require further thyroid treatment once euthyroidism has been restored. OBJECTIVE: To assess retrospectively the prevalence and relative proportion of type 1 and type 2 AIT over a 27-year period at a tertiary referral centre in Italy. PATIENTS: Consecutive AIT patients (n = 215) seen at the department of endocrinology of the University of Pisa between 1980 and 2006. RESULTS: Type 1 AIT constituted the most frequent AIT form (60%) during the first years covered by this study. The annual mean number of type 1 AIT patients was 3.6 at the beginning of the study period, and 2.5 during the later years. In contrast, the mean annual number of new cases of type 2 AIT progressively increased from 2.4 to 12.5. Likewise, the proportion of type 2 AIT increased in a significant linear manner (P < 0.0001), currently accounting for 89% of AIT cases. Type 2 AIT patients showed a male preponderance, higher serum FT4/FT3 ratio (P < 0.002), lower 3-h and 24-h thyroidal radioactive iodine uptake values (P < 0.0001), and received a higher cumulative dose of amiodarone (P < 0.0001) than type 1 AIT patients. CONCLUSIONS: Over a 27-year period, the epidemiology of AIT changed, as the prevalence of type 2 AIT progressively increased and that of type 1 remained constant. Thus, under most circumstances, endocrinologists nowadays deal with type 2 AIT, which is a destructive thyroiditis, generally treated successfully with glucocorticoids. Although no additional treatment is usually required after the destructive process subsides, periodic assessment of thyroid function is warranted, because of the occurrence of hypothyroidism (up to 17%) during long-term follow-up of these patients.

Glucocorticoid response in amiodarone-induced thyrotoxicosis resulting from destructive thyroiditis is predicted by thyroid volume and serum free thyroid hormone concentrations.

CONTEXT: Amiodarone-induced thyrotoxicosis (AIT) resulting from destructive thyroiditis (type 2) is commonly treated with glucocorticoids, but time needed to restore euthyroidism may be unacceptable for patients with underlying cardiac disorders. OBJECTIVE: The objective of this prospective study was to identify factors affecting the response to glucocorticoids in a large cohort of patients with type 2 AIT followed prospectively. SETTING: This study was conducted at university centers. PATIENTS: Sixty-six untreated patients with type 2 AIT were enrolled in the study. INTERVENTION: All patients were treated with prednisone (initial dose, 0.5 mg/kg.d) as long as needed to restore euthyroidism, defined as cure of AIT. MAIN OUTCOME MEASURE: The main outcome measure was cure time. RESULTS: The median cure time was 30 d (95% confidence interval, 23-37 d). Serum free T4 concentration (picograms per milliliter) and thyroid volume (milliliters per square meter) (and, to a lesser extent, serum free T3 concentration) at diagnosis were the main determinants of response to glucocorticoids, with a cure hazard ratio of 0.97 (95% confidence interval, 0.95-0.99; P = 0.005) and 0.84 (95% confidence interval, 0.77-0.91; P = 0.000) for unit of increment, respectively. AIT was cured in all patients with a complete follow-up; euthyroidism was reached in 30 d or less in 60% of patients but in more than 90 d in 16%. A prompt control of thyrotoxicosis (