Ultramicronized Palmitoylethanolamide and Luteolin Supplement Combined with Olfactory Training to Treat Post-COVID-19 Olfactory Impairment: A Multi-Center Double-Blinded Randomized Placebo- Controlled Clinical Trial.

BACKGROUND: Olfactory training is the only evidence-based treatment for post-viral olfactory dysfunction. Smell disorders after SARS-CoV-2 infection have been attributed to neuroinflammatory events within the olfactory bulb and the central nervous system. Therefore, targeting neuroinflammation is one potential strategy for promoting recovery from post-COVID-19 chronic olfactory dysfunction. Palmitoylethanolamide and luteolin (PEA-LUT) are candidate antiinflammatory/ neuroprotective agents. OBJECTIVE: To investigate recovery of olfactory function in patients treated with PEA-LUT oral supplements plus olfactory training versus olfactory training plus placebo. METHODS: Multicenter double-blinded randomized placebo-controlled clinical trial was held. Eligible subjects had prior COVID-19 and persistent olfactory impairment >6 months after follow-up SARS-CoV-2 negative testing, without prior history of olfactory dysfunction or other sinonasal disorders. Participants were randomized to daily oral supplementation with ultramicronized PEA-LUT 770 mg plus olfactory training (intervention group) or olfactory training with placebo (control). Sniffin' Sticks assessments were used to test the patients at baseline and 90 days. RESULTS: A total of 185 patients, including intervention (130) and control (55) were enrolled. The intervention group showed significantly greater improvement in olfactory threshold, discrimination, and identification scores compared to controls (p=0.0001). Overall, 92% of patients in the intervention group improved versus 42% of controls. Magnitude of recovery was significantly greater in the intervention group versus control (12.8 + 8.2 versus mean 3.2 + 3), with >10-fold higher prevalence of anosmia in control versus intervention groups at the 90-day endpoint. CONCLUSION: Among individuals with olfactory dysfunction post-COVID-19, combining PEA-LUT with olfactory training resulted in greater recovery of smell than olfactory training alone.

3D 4K VITOM-assisted transoral removal of distal stone in the Wharton's duct.

BACKGROUND: The aim of this study was to describe the potential advantages of the transoral 3D 4K exoscope-assisted removal of calculus of the Wharton's duct. METHODS: A 24-year-old female with swelling in the left oral pelvis was diagnosed of sialolithiasis of distal Wharton's duct. A CT scan confirmed the lithiasic formation and a transoral removal in local anesthesia was planned through the 3D 4K exoscope (VITOM 3D, Karl Storz). RESULTS: A high-quality magnification of the oral pelvis was obtained, with an easy identification of the entrance of the left submandibular gland's duct and the calculus. After blunt dissection the Wharton's duct was incised and the calculus removed. An angiocatheter (20G) was carefully inserted in the duct and removed after 3 days. No postoperative complications occurred. At 7 days post-operative follow-up the patient had developed a neo-ostium 5 mm from the papilla. The exoscope provided a better involvement in the surgery and more interactions of all operating room personnel, residents and students, that had access to the same field of view of the first surgeon with the perception of the depth of the surgical field with 3D technology. CONCLUSIONS: The exoscope could represent a valid option for transoral removal of calculi, allowing for precise surgical dissection of the oral floor, thus reducing the risks for iatrogenic lesion of the lingual nerve. It showed also a high potential for training and educational purposes.

Cost-effectiveness in transient hypocalcemia post-thyroidectomy.

BACKGROUND: Three different strategies to manage transient hypocalcemia after total thyroidectomy were compared to evaluate cost-effectiveness. The reliability of total serum calcium (TSCa), ionized calcium (ICa), and intact parathyroid hormone (iPTH) were investigated to achieve this goal. METHODS: A multicenter, prospective randomized study was carried out with 169 patients. The strategies were "preventive" (oral calcium + vitamin D supplementation), "reactive" (therapy in hypocalcemia), and "predictive" (therapy if iPTH <10 pg/mL). RESULTS: TSCa had higher accuracy in identifying patients who developed hypocalcemia-related symptoms than ICa (84.6% vs 50.0%). TSCa 24 h after surgery showed 24.8% of patients with hypocalcemia, whereas TSCa 48 h after surgery identified a further 10.6% with hypocalcemia (only in the "reactive" and "predictive" groups). iPTH showed low sensitivity as a predictor of hypocalcemia. Between the 3 groups, there was no significant difference in hospitalization time or number of symptomatic hypocalcemic patients. Interestingly, the cost-per-patient was significantly different among the groups. CONCLUSIONS: None of the discussed strategies allowed for early discharge of patients without any risk of transient hypocalcemia. The "preventive" strategy was the most cost-effective, despite overtreatment.

LATERAL NECK DISSECTION FOR AGGRESSIVE VARIANTS OF WELL-DIFFERENTIATED THYROID CANCER.

Objective: Well-differentiated thyroid cancer (WDTC) is characterized by favorable disease course and excellent survival. However, some histologic subtypes, known as aggressive histologic variants (AHVs), present a more aggressive behavior than conventional WDTC. The aim of this study was to evaluate the pattern of nodal involvement and factors influencing prognosis in N1b patients with AHVs. Methods: A multicentric retrospective analysis of patients who underwent therapeutic lateral neck dissection (ND) for WDTC between 1994 and 2015 was accomplished. AHVs included the following subtypes: tall cell, Hürtle cell, diffuse sclerosing, and poorly differentiated papillary thyroid cancer. Results: The study included a total of 352 N1b patients, 40 (11.4%) of whom had AHVs. AHVs present a similar distribution of positive nodes if compared with conventional WDTC. In AHV patients, 5-year overall survival (OS), disease-specific survival (DSS), locoregional control, and metastasis-free survival were 82.2%, 93.6%, 80.3%, and 87.3%, respectively. Advanced age (>55 years) was the only significant factor affecting survival (OS, P<.001; DSS, P = .011) in this group. In the AHV group, there were 9 (22.5%) recurrences; patients with regional recurrence and without distant metastases were effectively treated by surgery. Conclusion: The distribution of positive lymph nodes in case of AHVs is similar to that of conventional WDTC, with only level V at a relatively greater risk of harboring metastases in the former group. Survival outcomes in N1b patients with AHVs remain optimal. Total thyroidectomy, ND, and adjuvant radioiodine administration have been demonstrated to be effective treatments in the setting of AHVs. Abbreviations: AHV = aggressive histologic variant; DOD = died of disease; DSS = disease-specific survival; DSV = diffuse sclerosing variant; ETE = extrathyroidal extension; HCC = Hürthle cell carcinoma; LRC = locoregional control; LVI = lymphovascular invasion; MFS = metastasis-free survival; ND = neck dissection; NED = no evidence of disease; OS = overall survival; PDA = poorly differentiated areas; PTC = papillary thyroid carcinoma; RAI = radioiodine therapy; TCV = tall cell variant; WDTC = well-differentiated thyroid cancer.

Vitamin E neuroprotection against cisplatin ototoxicity: Preliminary results from a randomized, placebo-controlled trial.

BACKGROUND: Few studies have investigated the effect of vitamin E in reducing the cisplatin (CDDP)-induced ototoxicity. This study evaluated vitamin E supplementation as a protecting agent against CDDP-induced ototoxicity. METHODS: Patients who started CDDP were randomly assigned to receive vitamin E supplementation at 400 mg per day (group 1) or placebo (group 2). Audiograms and evoked brainstem responses were obtained at baseline, and after 1, 2, and 3 months. RESULTS: Twenty-three patients affected by solid malignancies were enrolled (13 in group 1 and 10 in group 2). At 1 month, a significant hearing loss in group 2 at both 2000 HZ (right ear: p = .05; left ear: p = .04) and 8000 HZ (right ear: p = .04; left ear: p = .03) was detected when compared to baseline values. Audiograms did not show significant changes. At 1 month, evoked brainstem responses remained unchanged in both arms without significant differences between groups. CONCLUSION: These preliminary findings confirm the neuroprotective properties of vitamin E against the CDDP-induced ototoxicity. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2118-E2121, 2016.

Mixed squamous cell carcinoma and follicular carcinoma of the thyroid gland.

Primary squamous cell carcinoma of the thyroid gland (PSCCT) is rare and its aetiology is debated. A 67-year-old man presented with neck mass. Fine-needle-aspiration (FNA) cytology and through-cut biopsy were suggestive of poorly differentiated or anaplastic carcinoma. The patient was offered tracheostomy and palliative cure for unresectable tumor of the thyroid; he refused and decided for other opinion. Lobe-isthmusectomy was performed with diagnostic and debulking intent. Final pathology report was of mixed squamous cell and follicular carcinoma of the thyroid. The tumor was a PSCCT. The patient underwent adjuvant chemoradiotherapy. After 2 years, an iliac crest metastasis of follicular carcinoma was diagnosed. The patient is disease free, after surgery and radio-active-iodine treatment. The hypothesis of squamous cell carcinoma transformation from well differentiated thyroid cancer has to be considered in case of PSCCT. Primary squamous cell carcinoma of the thyroid gland (PSCCT) is rare [1-3]; different theories on its aetiology do exist [4-6]. Mixed squamous cell and follicular carcinoma is even more rare than pure squamous cell of the thyroid gland and only few cases are reported in literature [7]. Preoperative diagnosis can be very challenging and the differential diagnosis with secondary squamous cell carcinoma of the thyroid (SSCCT) is manadatory in order to plan a correct management of the disease. The presence of PSCCT with distant metastasis of follicular carcinoma supports the histogenesis of squamous cell carcinomas arising from follicular epithelial cells.