The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes.

Introduction: Although the contribution of enhanced glial activity in seizure induction is increasingly recognized, the role of glia-induced neuroinflammation in the physiopathology of epileptic encephalopathy (EE) has been scarcely investigated. Methods: To delineate the contribution of glial activity in EE, we measured levels of glia-derived mediators with previously described biomarker value, including glial fibrillary acidic protein (GFAP), high mobility group box 1 (HMGB1), chitinase-3-like protein 1 (CHI3L1), soluble CD163 (sCD163) and triggering receptor expressed on myeloid cells 2 (TREM2) by ELISA in sera of patients with idiopathic West syndrome (WS, n=18), idiopathic Lennox-Gastaut syndrome (LGS, n=13) and healthy controls (n=31). Results: Patients with EE showed significantly higher CHI3L1 levels compared to healthy controls. Levels of HMGB1, CHI3L1, sCD163 and TREM2 were higher in LGS patients than WS patients and/or healthy controls. One or more of the investigated mediators were associated with treatment responsiveness, disease severity and presence of pathological features on electroencephalography (EEG). Conclusions: To our knowledge, our findings provide the initial patient-based evidence that astrocyte- and microglia-mediated neuroinflammation might be involved in the pathogenesis of LGS and WS. Moreover, glial mediators may serve as prognostic biomarkers in patients with idiopathic EE.

Distribution of peripheral blood mononuclear cell subtypes in patients with West syndrome: Impact of synacthen treatment.

BACKGROUND: West Syndrome (WS) is an epileptic encephalopathy that typically occurs in infants and is characterized by hypsarrhythmia, infantile spasms, and neurodevelopmental impairment. Demonstration of autoantibodies and cytokines in some WS patients and favorable response to immunotherapy have implicated inflammation as a putative trigger of epileptiform activity in WS. Our aim was to provide additional support for altered inflammatory responses in WS through peripheral blood immunophenotype analysis. METHODS: Eight WS cases treated with synacthen and 11 age- and sex-matched healthy volunteers were included. Peripheral blood mononuclear cells (PBMC) were isolated and immunophenotyping was performed in pre-treatment baseline (8 patients) and 3 months post-treatment (6 patients) samples. The analysis included PBMC expressing NFκB transcription and NLRP3 inflammasome factors. RESULTS: In pre-treatment baseline samples, switched memory B cells (CD19+IgD-CD27+) were significantly reduced, whereas plasma cells (CD19+CD38+CD138+) and cytotoxic T cells (CD3+CD8+) were significantly increased. Regulatory T and B cell ratios were not significantly altered. Synacthen treatment only marginally reduced helper T cell ratios and did not significantly change other T, B, NK and NKT cell and monocyte ratios. CONCLUSIONS: Our findings lend further support for the involvement of inflammation-related mechanisms in WS. New-onset WS patients are inclined to display increased plasma cells in the peripheral blood. Synacthen treatment does not show a beneficial effect on most effector acquired and innate immunity subsets.

Recurrent Laryngeal Nerve Invasion by Thyroid Cancer: Laryngeal Function and Survival Outcomes.

BACKGROUND: Recurrent laryngeal nerve (RLN) invasion by thyroid carcinoma represents an advanced disease status with potentially significant co-morbidity. METHODS: In a retrospective single-center study, we included patients with invaded RLNs operated on while using nerve monitoring techniques. We studied pre-, intra-, and postoperative parameters associated with postoperative vocal cord paralysis (VCP); 5-year recurrence-free survival (RFS); and 5-year overall survival (OS) in addition to two subgroup analyses of postoperative VCP in patients without preoperative VCP and based on source of RLN invasion. RESULTS: Of 65 patients with 66 nerves-at-risk, 39.3% reported preoperative voice complaints. Preoperative VCP was documented in 43.5%. The RLN was invaded by primary tumor in 59.3% and nodal metastasis in 30.5%. Papillary thyroid carcinoma was the most common pathologic subtype (80%). After 6 months, 81.8% had VCP. Complete tumor resection of the RLN was not associated with 5-year RFS (p = 0.24) or 5-year OS (p = 0.9). Resecting the RLN did not offer statistically significant benefit on 5-year RFS (p = 0.5) or 5-year OS (p = 0.38). Radioactive Iodine (RAI) administration was associated with improvement in 5-year RFS (p = 0.006) and 5-year OS (p = 0.004). Patients without preoperative VCP had higher IONM amplitude compared with patients with VCP. After a mean follow-up of 65.8 months, 35.9% of patients had distant metastases, whereas 36.4% had recurrence. CONCLUSION: Preoperative VCP accompanies less than half of patients with RLN invasion. Invaded RLNs may have existent electrophysiologic stimulability. Complete tumor resection and RLN resection were not associated with better 5-year RFS or OS, but postoperative RAI was. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2285-2292, 2022.

Limitations of preoperative cytology for medullary thyroid cancer: Proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery.

BACKGROUND: Preoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine-needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases. DESIGN/METHOD: Histopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected. RESULTS: Out of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA. CONCLUSION: In a tertiary-care setting, one-third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients.

Endocrine Surgery during the COVID-19 Pandemic: Recommendations from the Turkish Association of Endocrine Surgery.

The 2019 novel coronavirus disease (COVID-19) was initially seen in Wuhan, China, in December 2019. World Health Organization classified COVID-19 as a pandemic after its rapid spread worldwide in a few months. With the pandemic, all elective surgeries and non-emergency procedures have been postponed in our country, as in others. Most of the endocrine operations can be postponed for a certain period. However, it must be kept in mind that these patients also need surgical treatment, and the delay time should not cause a negative effect on the surgical outcome or disease process. It has recently been suggested that elective surgical interventions can be described as medically necessary, time-sensitive (MeNTS) procedures. Some guidelines have been published on proper and safe surgery for both the healthcare providers and the patients after the immediate onset of the COVID-19 pandemic. We should know that these guidelines and recommendations are not meant to constitute a position statement, the standard of care, or evidence-based/best practice. However, these are mostly the opinions of a selected group of surgeons. Generally, only life-threatening emergency operations should be performed in the stage where the epidemic exceeds the capacity of the hospitals (first stage), cancer and transplantation surgery should be initiated when the outbreak begins to be controlled (second stage), and surgery for elective cases should be performed in a controlled manner with suppression of the outbreak (third stage). In this rapidly developing pandemic period, the plans and recommendations to be made on this subject are based on expert opinions by considering factors, such as the course and biology of the disease, rather than being evidence-based. In the recent reports of many endocrine surgery associations and in various reviews, it has been stated that most of the cases can be postponed to the third stage of the epidemic. We aimed to evaluate the risk reduction strategies and recommendations that can help plan the surgery, prepare for surgery, protect both patients and healthcare workers during the operation and care for the patients in the postoperative period in endocrine surgery.

The Presence of Hürthle Cells Does Not Increase the Risk of Malignancy in Most Bethesda Categories in Thyroid Fine-Needle Aspirates.

Background: Hürthle cell/oncocytic change is commonly reported on thyroid fine-needle aspiration (FNA) and may be considered an "atypical cell" by clinicians. This study aims to delineate the association between Hürthle cells in preoperative cytology and subsequent pathology of the indexed thyroid nodule and to report rates of malignancy. Methods: Retrospective review of records of 300 patients with Hürthle cell/oncocytic change on FNA and final surgical pathology at a tertiary referral center between 2000 and 2013 was performed and compared with a multi-institutional FNA cohort. The degree of Hürthle cell presence was correlated with histopathologic diagnoses. Results: In the Hürthle cell FNA group, Bethesda System for Reporting Thyroid Cytopathology (BSRTC) categories were as follows: I (nondiagnostic) 14 (4.7%); II (benign) 113 (37.7%); III (atypia of undetermined significance/follicular lesion of undetermined significance) 33 (11%); IV (follicular neoplasm/suspicious for a follicular neoplasm) 125 (41.6%); V (suspicious for malignancy) 12 (4%); and VI (malignant) 3 (1%). When categorized based on the degree of Hürthle cell change, 59 (29%) were classified as mild, 13 (6%) moderate, and 131 (65%) as predominant. When comparing the results with a multi-institutional FNA cohort (all with surgical confirmation), the presence of Hürthle cells was found to be associated with a lower risk of malignancy in all BSRTC categories, with a statistically significant difference in the BSRTC IV and V groups. The sole exception was when Hürthle cell presence was classified as predominant (defined as >75% of the cellular population); the rate of malignancy was significantly elevated in FNAs interpreted as benign/Bethesda II. Conclusions: Although Hürthle cells have been considered by clinicians as an "atypical cell," their presence does not increase the risk of malignancy within BSRTC categories overall. However, when predominant Hürthle cell change is present, the risk of malignancy is increased in the benign cytology/BSRTC category II.

Anterior laryngeal electrodes for recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: New expanded options for neural monitoring.

OBJECTIVES/HYPOTHESIS: Intraoperative neural monitoring is a useful adjunct for the laryngeal nerve function assessment during thyroid and parathyroid surgery. Typically, monitoring is performed by measurement of electromyographic responses recorded by endotracheal tube (ETT) surface electrodes. Tube position alterations during surgery can cause displacement of the electrodes relative to the vocal cords, leading to false positive loss of signal. Numerous reports have denoted monitoring equipment-related issues, especially endotracheal tube displacement, as the dominant source of false positive error. The false positive error may result in inappropriate decisions by the surgeon. This study tests the hypothesis that anterior laryngeal electrodes (ALEs) can help reduce this error. Placement of ALEs directly onto the thyroid cartilage represent an adjunctive and possible alternative method to standard ETT surface electrodes. STUDY DESIGN: Retrospective review. METHODS: Fifteen consecutive patients undergoing thyroid and parathyroid surgery with intraoperative neuromonitoring using both ETT electrodes and ALEs were studied. Data collected included site of neural stimulation, laterality, and electromyographic parameters. RESULTS: With vagal and recurrent laryngeal nerve stimulation, the ALEs recorded mean vocalis muscle waveform amplitude within 83% of that recorded with standard ETT electrodes. The latency measurements with the anterior laryngeal and endotracheal electrodes were similar, with both electrodes recording significantly longer latency for the left vagus nerve as compared to the right vagus nerve. With superior laryngeal nerve stimulation, the ALEs recorded a 800% greater mean amplitude than the ETT electrodes. The ALEs demonstrated similar sensitivity to stimulation at low current as ETT electrodes and provided stable intraoperative monitoring information. CONCLUSIONS: Compared to ETT surface electrodes, the ALEs provide similar and stable electromyographic responses with equal sensitivity for recording evoked responses during neural monitoring in thyroid and parathyroid surgery. The ALEs offer significantly more robust monitoring of the external branch of the superior laryngeal nerve. Furthermore, ALEs are contained within the operative field, are totally surgeon controlled, and are unaffected by the potential vicissitudes of ETT position during surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2910-2915, 2018.

Silk suture reaction in thyroid surgery.

Silk suture reaction (i.e., a benign granulomatous inflammatory foreign body reaction) is a rare complication of thyroid surgery. Here, two cases of post-thyroidectomy suture reaction are presented. Both of the patients were female, one is 48 and the other is 34 years old. The patients were presented with neck swelling and leakage of serous fluid from the Kocher's incision. Both patients had normal free T4, free T3, and TSH values. The 48-year-old female patient had a right subtotal and left near-total thyroidectomy 6 years ago and the other had bilateral total thyroidectomy 6 years ago. In the physical examination a mobile, painless, red, swelling was palpated in front of neck. In the ultrasound of both patients, a heterogeneous nodule with hypoechoic rim was seen, however, in scintigraphy no radiopharmaceutical involvement was observed in thyroid region. Due to suspicion of thyroid malignancy, a fine needle aspiration biopsy was performed and foreign body reaction was revealed cytologically. A suture reaction can vary from an erythematous swelling to chronic granulomatous reaction. The time interval between the operation and formation of suture reaction was 6 years in both of the cases thus these patients were considered as chronic patients. Foreign body reaction diagnosis was confirmed with fine needle aspiration biopsy. It is important to diagnose these chronic inflammation cases since these cases can mimic recurrence in thyroid malignancies. A post-thyroidectomy suture reaction is diagnosed cytologically with fine needle aspiration biopsy and by surgical removal of suture, this chronic inflammatory reaction can be cured.

Skin metastasis on the neck: an unusual presentation of recurrence of papillary thyroid carcinoma.

Skin metastasis of papillary thyroid carcinoma (PTC) is rare. Here, two cases of skin metastases of PTC are presented. Both of the patients were females, one is 83 and the other is 65 years old. The patients were admitted to the hospital with a movable skin lesion on anterior neck region. Free T3 and T4 levels were in normal levels and TSH levels were low in both patients. The 83-year-old patient underwent total thyroidectomy due to papillary thyroid cancer and received 131I ablation therapy and then thyroid suppression therapy. After the surgery, the patient lived without evidence of disease for 3 years and then skin metastasis occurred. The 65-year-old patient had a total thyroidectomy 5 years ago due to PTC then neck dissection due to metastasis 3 years later and then received 131I ablation therapy. Thyroid ultrasonography of both patients showed hypoechoic nodules with central vascularization. In the histological examination of both patients, cystic lesions filled with papillary structures were seen. Fine needle aspiration biopsy (FNAB) taken from both patients were papillary carcinoma with solid trabecular pattern. PTC tends to metastasize to regional lymph nodes but distant metastasis is rare. When distant metastasis develops, prognosis of the disease is poor. Therefore, skin metastasis of papillary thyroid cancer is a poor prognostic factor. If the patient does not have a thyroid malignancy history, diagnosis of PTC metastatic to the skin may be difficult since primary skin tumors such as apocrine tumors have similar histopathological features. However, in the presented cases since there was a PTC history, the diagnosis was easier with the help of histopathological examination. Skin metastasis of PTC should be kept in mind when differential diagnosis of atypical skin lesions are made especially in the patients with thyroid malignancy history.

Bupivacaine application reduces post thyroidectomy pain: Cerrahpasa experience.

BACKGROUND: We aimed to evaluate the impact of bupivacaine administration into the surgical field after total thyroidectomy on post-operative pain and analgesic requirement with a double-blind, prospective, clinical and randomized study. METHODS: The study was performed between 2010 and 2011. Pain assessment was performed with the visual analog score (VAS). Patients were pre-operatively, randomly divided into two groups to receive either bupivacaine or saline. One group received a 10-mL of bupivacaine solution while the other group was treated with the same volume of 0.9% NaCl through the drain after completion of total thyroidectomy procedure. All patients were anesthetized and operated with the same anesthesia and surgical team. RESULTS: Ninety-one patients (20 males) were included in the study. No patient dropped out of the study during the procedures. No mortality was seen. The VAS scores were significantly lower in the bupivacaine administered group at post-operative minute 30 (3.7±3.2 vs. 5±2.9; P=0.03), hour one (3.04±2.4 vs. 4.2±2.8; P=0.04), and hour eight (1.8±2.04 vs. 3.2±2.1; P=0.005). Thirteen patients required analgesia during their hospital stay in the bupivacaine group while this number was twenty-two in the saline group (P=0.005). CONCLUSIONS: Local bupivacaine administration into the surgical field after total thyroidectomy reduces pain and analgesic requirement during the hospital stay.

Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years.

Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids.