Ultrasound Follow-Up of Benign Thyroid Nodules: A Scoping Review.

Background: For cytologically benign thyroid nodules with very low to intermediate suspicion ultrasound patterns, optimal ultrasound follow-up intervals and outcomes of discontinuing follow-up are unclear. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched through August 2022 for studies comparing different ultrasound follow-up intervals and discontinuation versus continuation of ultrasound follow-up. The population was patients with cytologically benign thyroid nodules and very low to intermediate suspicion ultrasound patterns, and the primary outcome was missed thyroid cancers. Utilizing a scoping approach, we also included studies that were not restricted to very low to intermediate suspicion ultrasound patterns or evaluated additional outcomes such as thyroid cancer-related mortality rate, nodule growth, and subsequent procedures. Quality assessment was performed, and evidence was synthesized qualitatively. Results: One retrospective cohort study (n = 1254; 1819 nodules) compared different first follow-up ultrasound intervals for cytologically benign thyroid nodules. There was no difference between >4- versus 1- to 2-year intervals to first follow-up ultrasound in the likelihood of malignancy (0.4% [1/223] vs. 0.3% [2/715]), and no cancer-related deaths occurred. Follow-up ultrasound at >4 years was associated with increased likelihood of ≥50% nodule growth (35.0% [78/223] vs. 15.1% [108/715]), repeat fine needle aspiration (19.3% [43/223] vs. 5.6% [40/715]), and thyroidectomy (4.0% [9/223] vs. 0.8% [6/715]). The study did not describe ultrasound patterns or control for confounders, and analyses were based on interval to first follow-up ultrasound only. Other methodological limitations were not controlling for variability in follow-up duration and unclear attrition. The certainty of evidence was very low. No study compared discontinuation of ultrasound follow-up versus continuation. Conclusions: This scoping review found that evidence comparing different ultrasound follow-up intervals in patients with benign thyroid nodules is limited to one observational study, but suggests that the subsequent development of thyroid malignancies is very uncommon regardless of follow-up interval. Longer follow-up may be associated with more repeat biopsies and thyroidectomies, which could be related to more interval nodule growth that meets thresholds for further evaluation. Research is needed to clarify optimal ultrasound follow-up intervals for low to intermediate suspicion cytologically benign thyroid nodules and outcomes of discontinuing ultrasound follow-up for very low suspicion nodules.

An Assessment of Diversity, Inclusion, and Health Equity Training in Endocrinology Fellowship Programs in the United States.

CONTEXT: The Accreditation Council for Graduate Medical Education has instituted common program requirements related to diversity, equity, and inclusion (DEI) for postgraduate trainees in the United States; however, the extent to which DEI training is being incorporated across endocrinology fellowship programs is unknown. OBJECTIVES: To describe the sociodemographic representation and DEI training experiences within endocrinology fellowship programs. DESIGN, SETTING, AND PARTICIPANTS: National cross-sectional survey study of fellows and fellowship program leaders in the United States whose fellowships were members of the Association of Program Directors in Endocrinology and Metabolism. MAIN OUTCOME MEASURES: (1) Demographics of fellows and program leaders and (2) programs' experience, confidence, and interest in formal DEI training. RESULTS: A total of 108 and 106 fellow and faculty responded to the survey, respectively. The majority of fellows and faculty are female. Less than 3% of fellows and 3.7% of faculty identify as Black. More than 90% of fellows/faculty are heterosexual and no respondents identified as transgender/nonbinary; however, 5% and 2% of all respondents preferred not to disclose their sexual orientation and gender identity, respectively. While 85% of faculty received institutional diversity and inclusion training, 67.6% of fellows did. Fellows are more likely to have received training in health equity than program leaders. Both fellows and program leaders express a high interest in health equity curriculum. CONCLUSIONS: Within the diversity of endocrinology training programs, Black physicians are underrepresented in medicine, which persists in endocrinology fellowships. Fellowship programs express enthusiasm for national diversity and health equity curricula, with the majority of programs reporting institutional DEI training.

Clinical Life in the Context of the Pandemic.

In this article, six analysts describe theory and practice in the time of COVID-19, examining the quality of après-coup in the way that the pandemic and its attendant crises trigger early memory and early experiences of helplessness. In the clinical events we see that the age of the patient, the circumstances and approach of the analyst, the novelty of the frame are all crucial determinants of clinical outcomes.

Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs. American College of Radiology Thyroid Image Reporting and Data System [TI-RADS] systems), radiation exposure, or family history of thyroid cancer can modify the probability of thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) predicted by MT. Methods: We studied 257 thyroid nodules in 232 patients from 10 study centers with indeterminate fine needle aspiration cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression was used for data analysis. Results: The presence of cancer/NIFTP was associated with positive TSv3 results (odds ratio 61.39, p < 0.0001). On univariate regression, patient sex, age, and Bethesda category were associated with cancer/NIFTP probability (p < 0.05 for each). Although ATA (p = 0.1211) and TI-RADS (p = 0.1359) US categories demonstrated positive trends, neither was significantly associated with cancer/NIFTP probability. A multivariate regression model incorporating the four most informative non-MT covariates (sex, age, Bethesda category, and ATA US pattern; Model No. 1) yielded a C index of 0.653; R2 = 0.108. When TSv3 was added to Model number 1, the C index increased to 0.888; R2 = 0.572. However, age (p = 0.341), Bethesda category (p = 0.272), and ATA US pattern (p = 0.264) were nonsignificant, and other than TSv3 (p < 0.0001), male sex was the only non-MT parameter that potentially contributed to cancer/NIFTP risk (p = 0.095). The simplest and most efficient clinical model (No. 3) incorporated TSv3 and sex (C index = 0.889; R2 = 0.588). Conclusions: In this multicenter study of thyroid nodules with indeterminate cytology and MT, neither the ATA nor TI-RADS US scoring systems further informed the risk of cancer/NIFTP beyond that predicted by TSv3. Although age and Bethesda category were associated with cancer/NIFTP probability on univariate analysis, in sequential nomograms they provided limited incremental value above the high predictive ability of TSv3. Patient sex may contribute to cancer/NIFTP risk in thyroid nodules with indeterminate cytology.

Tailoring the approach to radioactive iodine treatment in thyroid cancer.

The treatment of differentiated thyroid cancer continues to move away from a 'one size fits all' approach to a process of tailored therapeutic decision-making that incorporates disease-specific factors and individual patient preferences. Management options range from active surveillance to thyroid lobectomy to total thyroidectomy with or without the use of postoperative radioactive iodine (RAI). RAI may be administered for one or more reasons: Thyroid remnant ablation, adjuvant therapy, or therapy for persistent structural disease. It is important to be cognizant of the therapeutic intent of RAI and weigh the risks and benefits of treatment for each individual patient. Risk stratification should be used to identify those patients who are most likely to benefit from RAI and guide therapeutic choices. Available data suggest that RAI can be safely deferred for most patients considered at low risk for structural recurrence, while adjuvant RAI is associated with improved disease-free survival in patients with higher-risk disease. Although progress has been made, many areas of uncertainty related to the use of RAI remain. These include: (1) The appropriate selection of intermediate-risk patients to receive adjuvant RAI, (2) the superiority or inferiority of different RAI dosing activities, (3) the optimal approach to the use of RAI in special populations, including patients with end-stage renal disease and children, and (4) the management of patients with RAI-refractory disease.

Molecular Diagnostic Evaluation of Thyroid Nodules.

The historical management approach for many patients with indeterminate thyroid nodule fine needle aspiration cytology is a diagnostic lobectomy or thyroidectomy. However, the majority of patients undergo surgery unnecessarily, because most are proven to have benign disease on histology. Molecular testing is a diagnostic tool that can be used to help guide the clinical management of thyroid nodules with indeterminate cytology results. Testing has evolved substantially over the last decade with significant advances in testing methodology and improvements in our understanding of the genetic basis of thyroid cancer.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

Acceptance, Psychiatric Symptoms, and Migraine Disability: An Observational Study in a Headache Center.

OBJECTIVE: To evaluate relationships between psychiatric symptoms, acceptance, and migraine-related disability in a sample of people with migraine presenting at a tertiary care headache center. BACKGROUND: Migraine is a chronic disease that can be severely disabling. Despite a strong theoretical basis and evidence in other pain conditions, little is known about relationships between acceptance, psychiatric symptoms, and migraine-related disability. METHODS: Ninety patients with physician-diagnosed migraine completed surveys assessing demographics, headache symptoms, severe migraine-related disability (Migraine Disability Assessment Scale total score dichotomized at ≥ 21), depression (Patient Health Questionnaire-9) and anxiety symptoms (Generalized Anxiety Disorder-7), and acceptance (Chronic Pain Acceptance Questionnaire; subscales: Pain Willingness and Activity Engagement). RESULTS: Participants (77.8% white, non-Hispanic; 85.6% women; and 50.0% with a graduate level education) reported an average headache pain intensity of 6.7/10 (SD = 2.0). One-third (36.0%) reported chronic migraine, and half (51.5%) reported severe migraine-related disability. Lower acceptance was associated with severe migraine-related disability, t(54) = 4.13, P < .001. Higher activity engagement was associated with lower average headache pain intensity (r = -.30, P = .011). Higher acceptance was associated with lower levels of depression (r = -.48, P < .001) and anxiety symptoms (r = -.37, P = .003). Pain willingness and activity engagement serially mediated relationships between depression symptoms and severe migraine-related disability (indirect effect = 0.05, 95% CI = 0.01, 0.15), and between anxiety symptoms and severe migraine-related disability (indirect effect = 0.12, 95% CI = 0.02, 0.31). CONCLUSION: Results provided preliminary support for a theoretical pathway by which psychiatric symptoms may influence migraine-related disability, in part, through their relationships with pain willingness and activity engagement.

Oncocytic variant of medullary thyroid carcinoma; a rare tumor with numerous diagnostic mimics by fine needle aspiration.

Oncocytic variant of medullary thyroid carcinoma is rare form of thyroid carcinoma that is easily misdiagnosed on fine needle aspiration specimens due to it is low incidence and cytomorphologic overlap with other more common Hurtle cell lesions. A correct initial diagnosis by fine needle aspiration is imperative as the clinical treatment for medullary carcinoma differs significantly from the mimickers. We present a case of this rare variant tumor that on initial fine needle aspiration was described as a Hurthle cell lesion and was subsequently correctly classified on the resection specimen. In this brief review, we describe the cytomorphologic features of medullary carcinoma, oncocytic variant of medullary carcinoma and it is most common mimickers, and we discuss the ancillary studies required to confirm the diagnosis. This case highlights the importance of a complete clinical history and radiologic correlation, which in conjunction with a careful attention to the cytologic features of the fine needle aspiration sample, should in most cases ensure a correct initial diagnosis.

Psychological Factors Associated With Chronic Migraine and Severe Migraine-Related Disability: An Observational Study in a Tertiary Headache Center.

OBJECTIVE: To evaluate the relationships among modifiable psychological factors and chronic migraine and severe migraine-related disability in a clinic-based sample of persons with migraine. BACKGROUND: Evidence evaluating relationships between modifiable psychological factors and chronic migraine and severe migraine-related disability is lacking in people with migraine presenting for routine clinical care. METHODS: Adults with migraine completed surveys during routinely scheduled visits to a tertiary headache center. Participants completed surveys assessing chronic migraine (meeting criteria for migraine with ≥15 headache days in the past month), severe migraine disability (Migraine Disability Assessment Scale score ≥ 21), and modifiable psychological factors (depressive symptoms [Patient Health Questionnaire-9], anxious symptoms [Generalized Anxiety Disorder-7], Pain Catastrophizing Scale and Headache Specific Locus of Control). Logistic regression evaluated relationships between modifiable psychological factors and chronic migraine and severe migraine disability. RESULTS: Among 90 eligible participants the mean age was 45.0 (SD = 12.4); 84.8% were women. One-third (36.0%) met study criteria for chronic migraine; half of participants (51.5%) reported severe migraine-related disability. Higher depressive symptoms (OR = 1.99, 95% CI = 1.11, 3.55) and chance HSLC (OR = 1.85, 95% CI = 1.13, 1.43) were associated with chronic migraine. Higher depressive symptoms (OR = 3.54, 95%CI = 1.49, 8.41), anxiety symptoms (OR = 3.65, 95% CI = 1.65, 8.06), and pain catastrophizing (OR = 1.95, 95% CI = 1.14, 3.35), were associated with severe migraine-related disability. CONCLUSIONS: Psychiatric symptoms and pain catastrophizing were strongly associated with severe migraine-related disability. Depression and chance locus of control were associated with chronic migraine. This study supports the need for longitudinal observational studies to evaluate the relationships among naturalistic variation in psychological factors, migraine-related disability, and migraine chronification.

Prevalence of clinically silent corticotroph macroadenomas.

OBJECTIVE: The prevalence of clinically silent corticotroph macroadenomas is unknown. Our aim was to determine the prevalence of clinically silent corticotroph macroadenomas among all pituitary macroadenomas. DESIGN: Patients scheduled to have transsphenoidal surgery for any sellar mass were prospectively evaluated clinically and biochemically. PATIENTS: Adults who were scheduled for transsphenoidal surgery for a sellar mass at a single academic medical centre. MEASUREMENTS: Patients were assessed clinically prior to surgery and graded as having typical, mild or no Cushingoid features. They were assessed biochemically by plasma ACTH and 24-h urine free cortisol (UFC). Excised tissue was examined histologically, and pituitary macroadenomas, examined by immunohistochemistry. Patients with corticotroph macroadenomas were classified as clinically silent if they exhibited no Cushingoid features but had elevated plasma ACTH and/or 24-h UFC. They were classified as totally silent if they exhibited neither Cushingoid features nor elevated plasma ACTH or 24-h UFC. RESULTS: Of 124 patients who had pathologically confirmed pituitary macroadenomas, 20 (16%) had corticotroph macroadenomas. Eight (40%) of these were clinically silent, in that they had no Cushingoid features but could be identified biochemically by elevated plasma ACTH (seven) and/or 24-h UFC (three). Five (25%) were totally silent. CONCLUSIONS: A substantial minority (16%) of pituitary macroadenomas treated surgically are corticotroph adenomas. Of these, 40% are clinically silent but can be recognized by elevated plasma ACTH and/or 24-h UFC. Recognizing these adenomas may influence the surgical approach and provide a marker by which to follow the response to treatment.

Brain structural anomalies in borderline and avoidant personality disorder patients and their associations with disorder-specific symptoms.

BACKGROUND: Borderline personality disorder (BPD) and avoidant personality disorder (AvPD) are characterized by hyper-reactivity to negatively-perceived interpersonal cues, yet they differ in degree of affective instability. Recent work has begun to elucidate the neural (structural and functional) and cognitive-behavioral underpinnings of BPD, although some initial studies of brain structure have reached divergent conclusions. AvPD, however, has been almost unexamined in the cognitive neuroscience literature. METHODS: In the present study we investigated group differences among 29 BPD patients, 27 AvPD patients, and 29 healthy controls (HC) in structural brain volumes using voxel-based morphometry (VBM) in five anatomically-defined regions of interest: amygdala, hippocampus, medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC). We also examined the relationship between individual differences in brain structure and self-reported anxiety and affective instability in each group. RESULTS: We observed reductions in MPFC and ACC volume in BPD relative to HC, with no significant difference among patient groups. No group differences in amygdala volume were found. However, BPD and AvPD patients each showed a positive relationship between right amygdala volume and state-related anxiety. By contrast, in HC there was an inverse relationship between MPFC volume and state and trait-related anxiety as well as between bilateral DLPFC volume and affective instability. LIMITATIONS: Current sample sizes did not permit examination of gender effects upon structure-symptom correlations. CONCLUSIONS: These results shed light on potentially protective, or compensatory, aspects of brain structure in these populations-namely, relatively reduced amygdala volume or relatively enhanced MPFC and DLPFC volume.

Silent pituitary adenomas.

Pituitary adenomas are frequently silent. Among silent adenomas, some are clinically silent but can be detected on the basis of the excessive secretion of hormonal products, whereas others are totally silent and cannot be detected by hormonal measurements. Treatment of a silent pituitary adenoma depends on its size and extent. Silent adenomas that are associated with neurologic compromise should be treated by surgery. Postoperative radiation therapy may be used to prevent or treat recurrences. Only occasional silent pituitary adenomas respond to treatment with dopamine agonists or somatostatin analogs.

Elevated amygdala activity during reappraisal anticipation predicts anxiety in avoidant personality disorder.

BACKGROUND: Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplored question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli. METHODS: We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients. In addition to assessing individual differences in state and trait anxiety levels, self-reported affect as well as measures of neural activity were compared between 17 avoidant patients and 21 healthy control participants both in anticipation of and during performance of a reappraisal task. RESULTS: Avoidant patients showed greater state and trait-related anxiety relative to healthy participants. In addition, relative to healthy participants, avoidant patients showed pronounced amygdala hyper-reactivity during reappraisal anticipation, and this hyper-reactivity effect was positively associated with increasing self-reported anxiety levels. LIMITATIONS: Our finding of exaggerated amygdala activity during reappraisal anticipation could reflect anxiety about the impending need to reappraise, anxiety about the certainty of an upcoming negative image, or anxiety relating to anticipated scrutiny of task responses by the experimenters. While we believe that all of these possibilities are consistent with the phenomenology of avoidant personality disorder, future research may clarify this ambiguity. CONCLUSIONS: These results suggest that amygdala reactivity in anticipation of receiving negative social information may represent a key component of the neural mechanisms underlying the heightened anxiety present in avoidant patients.

The evolving use of radioiodine therapy in differentiated thyroid cancer.

The incidence of differentiated thyroid cancer has increased worldwide over the last three decades, but thyroid cancer-related mortality remains stable. Until recently, the standard treatment for most thyroid cancers has been near-total thyroidectomy followed by radioiodine remnant ablation. Observational data support lower recurrence rates and improved survival after radioiodine ablation in patients with high-risk cancers; however, a similar benefit has not been established for all patients with thyroid cancer. Risk stratification should be used to identify patients who are likely to benefit from radioiodine ablation and guide therapeutic decisions. For most patients who need radioiodine remnant ablation, preparation for therapy with recombinant human thyroid-stimulating hormone stimulation is as effective as thyroid hormone withdrawal. Lower therapeutic doses of radioiodine are recommended for the majority of thyroid remnant ablations. Higher doses are reserved for advanced disease at initial diagnosis, local recurrences that cannot be treated with surgery alone, and distant metastatic disease.

Silent (clinically nonfunctioning) pituitary adenomas.

Silent, or clinically nonfunctioning, pituitary adenomas can arise from any anterior pituitary cell type. Some are "clinically silent" in that they result in a supranormal serum concentration of the hormonal product of the cell type from which the adenoma arose but do not cause the clinical manifestations typical of excessive levels of that hormone. Others are "totally silent" in that they result in neither hormonal excess nor clinical manifestations. Gonadotroph and null cell adenomas are the most prevalent types and are typically silent. Somatotroph and corticotroph adenomas typically cause clinical syndromes but occasionally are clinically or totally silent. Those that are silent are usually larger and grow more aggressively than those that cause clinical syndromes. Silent adenomas are usually not discovered until they become very large and cause neurologic defects, such as visual impairment, but are also often discovered incidentally when neuroimaging is performed for another reason. Silent adenomas may become, rarely, clinically apparent over time. The diagnosis of a silent pituitary adenoma begins with the detection of a sellar mass by MRI. Biochemical testing can identify the adenoma cell type in those that are clinically silent. Silent adenomas that cause neurologic deficits require transsphenoidal surgery, but those that do not can be followed by MRI. Residual or recurrent disease is treated by radiation therapy, which is usually effective in preventing further growth but results in hormonal deficiencies in about half of patients. Dopamine agonists and somatostatin analogs are usually ineffective, but occasionally have been associated with reduced adenoma size.

The neural correlates of anomalous habituation to negative emotional pictures in borderline and avoidant personality disorder patients.

OBJECTIVE: Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder. METHOD: During fMRI scanning, borderline patients, healthy subjects, and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeated versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups. RESULTS: Unlike healthy subjects, neither borderline nor avoidant personality disorder patients exhibited increased activity in the dorsal anterior cingulate cortex when viewing repeated versus novel pictures. This lack of an increase in dorsal anterior cingulate activity was associated with greater affective instability in borderline patients. In addition, borderline and avoidant patients exhibited smaller increases in insula-amygdala functional connectivity than healthy subjects and, unlike healthy subjects, did not show habituation in ratings of the emotional intensity of the images. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate functional connectivity during habituation. CONCLUSIONS: Unlike healthy subjects, borderline patients fail to habituate to negative pictures, and they differ from both healthy subjects and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline patients.

Insula-amygdala functional connectivity is correlated with habituation to repeated negative images.

Behavioral habituation during repeated exposure to aversive stimuli is an adaptive process. However, the way in which changes in self-reported emotional experience are related to the neural mechanisms supporting habituation remains unclear. We probed these mechanisms by repeatedly presenting negative images to healthy adult participants and recording behavioral and neural responses using functional magnetic resonance imaging. We were particularly interested in investigating patterns of activity in insula, given its significant role in affective integration, and in amygdala, given its association with appraisal of aversive stimuli and its frequent coactivation with insula. We found significant habituation behaviorally along with decreases in amygdala, occipital cortex and ventral prefrontal cortex (PFC) activity with repeated presentation, whereas bilateral posterior insula, dorsolateral PFC and precuneus showed increased activation. Posterior insula activation during image presentation was correlated with greater negative affect ratings for novel presentations of negative images. Further, repeated negative image presentation was associated with increased functional connectivity between left posterior insula and amygdala, and increasing insula-amygdala functional connectivity was correlated with increasing behavioral habituation. These results suggest that habituation is subserved in part by insula-amygdala connectivity and involves a change in the activity of bottom-up affective networks.

Severe insulin resistance and hypertriglyceridemia after childhood total body irradiation.

OBJECTIVE: To characterize the metabolic phenotype of 2 cases of normal weight young women who developed type 2 diabetes (T2D), severe insulin resistance (insulin requirement >200 units/day), marked hypertriglyceridemia (>2000 mg/dL), and hepatic steatosis beginning 9 years after undergoing total body irradiation (TBI) and bone marrow transplantation for childhood cancer. METHODS: Fasting plasma glucose, insulin, free fatty acids (FFAs), leptin, adiponectin, resistin, TNFα, and IL-6 were measured in each case and in 8 healthy women; Case 1 was also assessed after initiating pioglitazone. Coding regions and splice junctions of PPARG, LMNA, and AKT2 were sequenced in Case 1 and of PPARG in Case 2 to evaluate for familial partial lipodystrophies. Genotyping of APOE was performed in Case 1 to rule out type III hyperlipoproteinemia. RESULTS: Both cases had elevated plasma levels of insulin, leptin, resistin, and IL-6, high-normal to elevated TNFα, and low to low-normal adiponectin in keeping with post-receptor insulin resistance and adipose tissue inflammation. Case 1 experienced a biochemical response to pioglitazone. No causative mutations for partial lipodystrophies or type III hyperlipoproteinemia were identified. CONCLUSION: Though metabolic derangements have previously been reported in association with TBI, few cases have described insulin resistance and hypertriglyceridemia as severe as that seen in our patients. We speculate that early childhood TBI may impede adipose tissue development leading to metabolic complications from an attenuated ability of adipose tissue to accommodate caloric excess, and propose that this extreme metabolic syndrome be evaluated for as a late complication of TBI.

The changing face of postoperative atrial fibrillation prevention: a review of current medical therapy.

Atrial fibrillation is the most common postoperative arrhythmia with significant consequences on patient health. Postoperative atrial fibrillation (POAF) complicates up to 8% of all noncardiac surgeries, between 3% and 30% of noncardiac thoracic surgeries, and between 16% and 46% of cardiac surgeries. POAF has been associated with increased morbidity, mortality, and longer, more costly hospital stays. The risk of POAF after cardiac and noncardiac surgery may be affected by several epidemiologic and intraoperative factors, as well as by the presence of preexisting cardiovascular and pulmonary disorders. POAF is typically a transient, reversible phenomenon that may develop in patients who possess an electrophysiologic substrate for the arrhythmia that is present before or as a result of surgery. Numerous studies support the efficacy of beta-blockers in POAF prevention; they are currently the most common medication used in POAF prophylaxis. Perioperative amiodarone, sotalol, nondihydropyridine calcium channel blockers, and magnesium sulfate have been associated with a reduction in the occurrence of POAF. Biatrial pacing is a nonpharmacologic method that has been associated with a reduced risk of POAF. Additionally, recent studies have demonstrated that hydroxymethylglutaryl-CoA reductase inhibitors may decrease the risk of POAF. Finally, based on recent evidence that angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce the risk of permanent atrial fibrillation, these medications may also hold promise in POAF prophylaxis. However, there is a need for further large-scale investigations that incorporate standard methodologies and diagnostic criteria, which have been lacking in past trials.