Educational Review: Intraoperative Parathyroid Fluorescence Detection Technology in Thyroid and Parathyroid Surgery.

BACKGROUND: Accurate parathyroid gland (PG) identification is a critical yet challenging component of cervical endocrine procedures. PGs possess strong near-infrared autofluorescence (NIRAF) compared with other tissues in the neck. This property has been harnessed by image- and probe-based near-infrared fluorescence detection systems, which have gained increasing popularity in clinical use for their ability to accurately aid in PG identification in a rapid, noninvasive, and cost-effective manner. All NIRAF technologies, however, cannot differentiate viable from devascularized PGs without the use of contrast enhancement. Here, we aim to provide an overview of the rapid evolution of these technologies and update the surgery community on the most recent advancements in the field. METHODS: A PubMed literature review was performed using the key terms "parathyroid," "near-infrared," and "fluorescence." Recommendations regarding the use of these technologies in clinical practice were developed on the basis of the reviewed literature and in conjunction with expert surgeons' opinions. RESULTS: The use of near-infrared fluorescence detection can be broadly categorized as (1) using parathyroid NIRAF to identify both healthy and diseased PGs, and (2) using contrast-enhanced (i.e., indocyanine green) near-infrared fluorescence to evaluate PG perfusion and viability. Each of these approaches possess unique advantages and disadvantages, and clinical trials are ongoing to better define their utility. CONCLUSIONS: Near-infrared fluorescence detection offers the opportunity to improve our collective ability to identify and preserve PGs intraoperatively. While additional work is needed to propel this technology further, we hope this review will be valuable to the practicing surgeon.

Langerhans cell histiocytosis of the suprasellar region: diagnosis based on thyroid cytology.

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D), and weight gain. Transcranial biopsy is necessary to define diagnosis and guide treatment decisions, but it is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was made by thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose (FDG) avidity on PET/CT and volume increase during follow-up.

Differences in surgical outcomes between cervical goiter and retrosternal goiter: an international, multicentric evaluation.

Introduction: Goiter is a common problem in clinical practice, representing a large part of clinical evaluations for thyroid disease. It tends to grow slowly and progressively over several years, eventually occupying the thoracic inlet with its lower portion, defining the situation known as retrosternal goiter. Total thyroidectomy is a standardized procedure that represents the treatment of choice for all retrosternal goiters, but when is performed for such disease, a higher risk of postoperative morbidity is variously reported in the literature. The aims of our study were to compare the perioperative and postoperative outcomes in patients with cervical goiters and retrosternal goiters undergoing total thyroidectomy. Methods: In our retrospective, multicentric evaluation we included 4,467 patients, divided into two groups based on the presence of retrosternal goiter (group A) or the presence of a classical cervical goiter (group B). Results: We found statistically significant differences in terms of transient hypoparathyroidism (19.9% in group A vs. 9.4% in group B, p < 0.001) and permanent hypoparathyroidism (3.3% in group A vs. 1.6% in group B, p = 0.035). We found no differences in terms of transient RNLI between group A and group B, while the occurrence of permanent RLNI was higher in group A compared to group B (1.4% in group A vs. 0.4% in group B, p = 0.037). Moreover, no differences in terms of unilateral RLNI were found, while bilateral RLNI rate was higher in group A compared to group B (1.1% in group A vs. 0.1% in group B, p = 0.015). Discussion: Wound infection rate was higher in group A compared to group B (1.4% in group A vs. 0.2% in group B, p = 0.006). Based on our data, thyroid surgery for retrosternal goiter represents a challenging procedure even for highly experienced surgeons, with an increased rate of some classical thyroid surgery complications. Referral of these patients to a high-volume center is mandatory. Also, intraoperative nerve monitoring (IONM) usage in these patients is advisable.

Robotic and Laparoscopic Adrenalectomy for Pheochromocytoma: An International Multicenter Study.

BACKGROUND AND OBJECTIVE: Robotic adrenalectomy (RA) has attracted interest as an alternative to laparoscopic adrenalectomy (LA) for patients with pheochromocytoma, although its beneficial effects are uncertain. Our aim was to compare RA and LA outcomes for these patients. METHODS: Data for patients who underwent RA or LA for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed. We analyzed baseline characteristics and postoperative complications at discharge, 90 d, and 1 yr. We conducted propensity score matching (PSM; 1:1 ratio) and multivariable analyses to evaluate outcomes and risk factors for the occurrence of complications and higher Comprehensive Complication Index (CCI). KEY FINDINGS AND LIMITATIONS: Of 1755 patients, 1613 (91.9%) underwent LA and 142 (8.1%) underwent RA. Estimated blood loss, conversion rate, complication rate, and CCI at discharge, 90 d, and 1 yr were similar between the groups. However, RA was associated with a longer operative time in comparison to LA (100 vs 123 min; p < 0.001), but not after PSM (p = 0.120). Multivariable analysis revealed that Charlson comorbidity index (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.07-1.29; p = 0.001), and tumor size per 1-cm increment (OR 1.13, 95% CI 1.07-1.21; p < 0.001) were independently associated with the incidence of complications, but there was no significant difference in complication rates between the LA and RA groups (OR 1.09, 95% CI 0.63-1.87; p = 0.767). After PSM, RA was associated with a lower rate of severe (grade ≥3a) complications in comparison to LA (p = 0.023). CONCLUSIONS AND CLINICAL IMPLICATIONS: RA is a safe alternative to LA and yields similar outcomes for patients with pheochromocytoma. RA may be associated with a lower likelihood of severe complications. Further studies are warranted to determine the role of robotic surgery in pheochromocytoma. PATIENT SUMMARY: Pheochromocytoma is a rare tumor in the adrenal gland and the gold-standard treatment is surgical removal. We assessed patient outcomes after robot-assisted surgery compared with laparoscopic surgery and found that outcomes are similar, but the rate of severe complications may be lower if a surgical robot is used.

Central node dissection in papillary thyroid carcinoma in the era of near-infrared fluorescence.

The most common site of lymph node metastases in papillary thyroid carcinoma is the central compartment of the neck (level VI). In many patients, nodal metastases in this area are not clinically apparent, neither on preoperative imaging nor during surgery. Prophylactic surgical clearance of the level VI in the absence of clinically suspicious lymph nodes (cN0) is still under debate. It has been suggested to reduce local recurrence and improve disease-specific survival. Moreover, it helps to accurately diagnose the lymph node involvement and provides important staging information useful for tailoring of the radioactive iodine regimen and estimating the risk of recurrence. Yet, many studies have shown no benefit to the long-term outcome. Arguments against the prophylactic central lymph node dissection (CLND) cite minimal oncologic benefit and concomitant higher operative morbidity, with hypoparathyroidism being the most common complication. Recently, near-infrared fluorescence imaging has emerged as a novel tool to identify and preserve parathyroid glands during thyroid surgery. We provide an overview of the current scientific landscape of fluorescence imaging in thyroid surgery, of the controversies around the prophylactic CLND, and of fluorescence imaging applications in CLND. To date, only three studies evaluated fluorescence imaging in patients undergoing thyroidectomy and prophylactic or therapeutic CLND for thyroid cancer. The results suggest that fluorescence imaging has the potential to minimise the risk of hypoparathyroidism associated with CLND, while allowing to exploit all its potential benefits. With further development, fluorescence imaging techniques might shift the paradigm to recommend more frequently prophylactic CLND.

Safety of continuous intraoperative vagus nerve neuromonitoring during thyroid surgery.

BACKGROUND: Continuous intraoperative neuromonitoring has successfully demonstrated to predict impending damage to the recurrent laryngeal nerve, by detecting changes in electromyographic recordings. Despite the apparent benefits associated with continuous intraoperative neuromonitoring, its safety is still a debate. The aim of this study was to investigate the electrophysiological impact of continuous intraoperative neuromonitoring on the vagus nerve. METHODS: In this prospective study, the amplitude of the electromyographic wave of the vagus nerve-recurrent laryngeal nerve axis was measured both proximally and distally to the stimulation electrode placed upon the vagus nerve. Electromyographic signal amplitudes were collected at three distinct events during the operation: during the dissection of the vagus nerve, before application of the continuous stimulation electrode onto the vagus nerve and after its removal. RESULTS: In total, 169 vagus nerves were analysed, among 108 included patients undergoing continuous intraoperative neuromonitoring-enhanced endocrine neck surgeries. Electrode application resulted in a significant overall decrease in measured proximo-distal amplitudes of -10.94 µV (95 per cent c.i. -17.06 to -4.82 µV) (P < 0.005), corresponding to a mean(s.d.) decrease of -1.4(5.4) per cent. Before the removal of the electrode, the measured proximo-distal difference in amplitudes was -18.58 µV (95 per cent c.i. -28.31 to -8.86 µV) (P < 0.005), corresponding to a mean(s.d.) decrease of -2.50(9.59) per cent. Seven nerves suffered a loss of amplitude greater than 20 per cent of the baseline measurement. CONCLUSION: In addition to supporting claims that continuous intraoperative neuromonitoring exposes the vagus nerve to injury, this study shows a mild electrophysiological impact of continuous intraoperative neuromonitoring electrode placement on the vagus nerve-recurrent laryngeal nerve axis. However, the small observed differences are negligible and were not associated with a clinically relevant outcome, making continuous intraoperative neuromonitoring a safe adjunct in selected thyroid surgeries.

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

Risk factors for postoperative cervical haematoma in patients undergoing thyroidectomy: a retrospective, multicenter, international analysis (REDHOT study).

Background: Postoperative cervical haematoma represents an infrequent but potentially life-threatening complication of thyroidectomy. Since this complication is uncommon, the assessment of risk factors associated with its development is challenging. The main aim of this study was to identify the risk factors for its occurrence. Methods: Patients undergoing thyroidectomy in seven high-volume thyroid surgery centers in Europe, between January 2020 and December 2022, were retrospectively analysed. Based on the onset of cervical haematoma, two groups were identified: Cervical Haematoma (CH) Group and No Cervical Haematoma (NoCH) Group. Univariate analysis was performed to compare these two groups. Moreover, employing multivariate analysis, all potential independent risk factors for the development of this complication were assessed. Results: Eight thousand eight hundred and thirty-nine patients were enrolled: 8,561 were included in NoCH Group and 278 in CH Group. Surgical revision of haemostasis was performed in 70 (25.18%) patients. The overall incidence of postoperative cervical haematoma was 3.15% (0.79% for cervical haematomas requiring surgical revision of haemostasis, and 2.35% for those managed conservatively). The timing of onset of cervical haematomas requiring surgical revision of haemostasis was within six hours after the end of the operation in 52 (74.28%) patients. Readmission was necessary in 3 (1.08%) cases. At multivariate analysis, male sex (P < 0.001), older age (P < 0.001), higher BMI (P = 0.021), unilateral lateral neck dissection (P < 0.001), drain placement (P = 0.007), and shorter operative times (P < 0.001) were found to be independent risk factors for cervical haematoma. Conclusions: Based on our findings, we believe that patients with the identified risk factors should be closely monitored in the postoperative period, particularly during the first six hours after the operation, and excluded from outpatient surgery.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Near-infrared fluorescent imaging techniques for the detection and preservation of parathyroid glands during endocrine surgery.

Objectives: In over 30% of all thyroid surgeries, complications arise from transient and definitive hypoparathyroidism, underscoring the need for real-time identification and preservation of parathyroid glands (PGs). Here, we evaluate the promising intraoperative optical technologies available for the identification, preservation, and functional assessment of PGs to enhance endocrine surgery. Methods: We performed a review of the literature to identify published studies on fluorescence imaging in thyroid and parathyroid surgery. Results: Fluorescence imaging is a well-demonstrated approach for both in vivo and in vitro localization of specific cells or tissues, and is gaining popularity as a technique to detect PGs during endocrine surgery. Autofluorescence (AF) imaging and indocyanine green (ICG) angiography are two emerging optical techniques to improve outcomes in thyroid and parathyroid surgeries. Near-infrared-guided technology has significantly contributed to the localization of PGs, through the detection of glandular AF. Perfusion through the PGs can be visualized with ICG, which can also reveal the blood supply after dissection. Conclusions: Near infrared AF and ICG angiography, providing a valuable spatial and anatomical information, can decrease the incidence of complications in thyroid surgery.

Is the indocyanine green score an accurate predictor of postoperative parathyroid hormone level?

BACKGROUND: Hypoparathyroidism is common after total thyroidectomy, primarily due to inadvertent disruption of the parathyroid gland blood supply during thyroid dissection. Indocyanine green helps determine the degree of vascularization and correlates with parathyroid gland vitality. It is difficult to determine how the indocyanine green score affects postoperative parathyroid hormone levels because all 4 parathyroid glands must be evaluated during surgery. We determined whether there is a correlation between intraoperative indocyanine green score and postoperative serum parathyroid hormone levels. METHODS: We retrospectively studied patients who underwent total thyroidectomy where we could identify all 4 parathyroid glands and establish a global indocyanine green score. Each parathyroid gland was scored from 0 to 2 depending on indocyanine green uptake. The global indocyanine green score was the sum of the individual scores for each gland. The scores were then correlated to parathyroid hormone and calcium levels on days 1 and 10 after surgery. RESULTS: We included 83 patients, 11 of whom presented with postoperative transient hypoparathyroidism; all but one had an indocyanine green score lower than 4 of 8. There was a significant correlation between the global indocyanine green score and postoperative parathyroid hormone level. A global indocyanine green score >3.75 can exclude postoperative hypoparathyroidism with a true negative value of 98%. Indocyanine green angiography is a better diagnostic test to predict a postoperative transient hypoparathyroidism compared with visual perfusion scoring. CONCLUSION: These findings suggest that the indocyanine green score based on intraoperative indocyanine green angiography predicts parathyroid gland function. It is a valuable instrument to predict hypoparathyroidism after total thyroidectomy.

Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: Results of an intercontinental, multidisciplinary Delphi survey.

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.

Fluorescence Image-Guided Surgery for Thyroid Cancer: Utility for Preventing Hypoparathyroidism.

Background: Hypoparathyroidism is one of the most frequent complications of thyroid surgery, especially when associated with lymph node dissection in cases of thyroid cancer. Fluorescence-guided surgery is an emerging tool that appears to help reduce the rate of this complication. The present review aims to highlight the utility of fluorescence imaging in preserving parathyroid glands during thyroid cancer surgery. Methods: We performed a systematic review of the literature according to PRISMA guidelines to identify published studies on fluorescence-guided thyroid surgery with a particular focus on thyroid cancer. Articles were selected and analyzed per indication and type of surgery, autofluorescence or exogenous dye usage, and outcomes. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess the methodological quality of the included articles. Results: Twenty-five studies met the inclusion criteria, with three studies exclusively assessing patients with thyroid cancer. The remaining studies assessed mixed cohorts with thyroid cancer and other thyroid or parathyroid diseases. The majority of the papers support the potential benefit of fluorescence imaging in preserving parathyroid glands in thyroid surgery. Conclusions: Fluorescence-guided surgery is useful in the prevention of post-thyroidectomy hypoparathyroidism via enhanced early identification, visualization, and preservation of the parathyroid glands. These aspects are notably beneficial in cases of associated lymphadenectomy for thyroid cancer.

Hypoparathyroidism: Consequences, economic impact, and perspectives. A case series and systematic review.

BACKGROUND: Postoperative hypoparathyroidism (PH) is the most common complication after total thyroidectomy. Incidence varies from 2% to 83%, depending on the definition. OBJECTIVE: We performed a systematic review of the literature to determine the medico-economic effects of PH and update understanding of long-term consequences, morbidity, and quality of life related to hypoparathyroidism. METHODS: We considered relevant articles published between 2000 and 2020 concerning long-term consequences of PH and quality of life. All studies concerning the medico-economic assessment of PH were included. We compared data from 2018 to results in the literature. RESULTS: A proportion of 64/403 (16.8%) patients presented with transient PH during 2018, and 7/403 (1.7%) had permanent PH. Seven patients needed supplementation with alfacalcidol at 6-month follow-up. Factors predicting the need for alfacalcidol were age <45, thyroidectomy for goiter, and lymph node dissection. Additional therapy costs related to PH were €9781.10, and additional hospital costs were €230,400. We qualitatively synthesized 41 studies. Most were retrospective studies and only a few reported costs. No series assessed direct or indirect costs of postoperative PH. CONCLUSION: To our knowledge, no previous studies reported the medico-economic impact of PH. Decreasing PH associated with fluorescence usage should be considered, particularly concerning cost-effectiveness.

Intraoperative Autofluorescence and Indocyanine Green Angiography for the Detection and Preservation of Parathyroid Glands.

Fluorescence imaging is a well-known method for both the in vivo and in vitro identification of specific cells or tissues. This imaging tool is gaining importance in the intraoperative detection and preservation of parathyroid glands during endocrine surgery owing to the intrinsic properties of parathyroid tissue. The aim of this paper is to provide an overview of the basics of the technology, its history, and the recent surgical intraoperative applications of near-infrared imaging methods. Moreover, a literature review of the utilization of fluorescence devices in thyroid surgery suggests that the use of near-infrared imaging seems to be beneficial in reducing postoperative hypoparathyroidism, which is one of the most frequent complications of thyroid surgery.

Electrocardiographic changes and false-positive troponin I in a patient with acute cholecystitis.

Cardiac troponins are the most sensitive and specific serum markers of myocardial cell injury, but they can also arise without apparent cardiac injury. Besides, acute cholecystitis may be associated with nonspecific ST-T wave changes in electrocardiography (ECG). The signs and symptoms of gallbladder and heart disease may overlap, which can make diagnosis difficult. We describe the case of a 75-year-old woman with clinical features suggestive of acute cholecystitis associated with transient ST segment elevation and elevated troponin I that, after extensive workup, did not seem to be attributable to myocardial ischemia or any other acute cardiac problem, but were exclusively related to cholecystitis. We show that cholecystitis with gallbladder distension can be the sole cause of pathological ECG changes and an increased troponin I level; this should be considered when evaluating patients with similar presentations.