Objectives
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry into the host cells depends on the expression of angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine ...2 (TMPRSS2). We investigated the distribution of ACE2‐ and TMPRSS2‐expressing cells in various oral tissues to identify the underlying mechanism of oral manifestations in patients with coronavirus disease 2019.
Subjects
We analyzed the expression patterns of ACE2 and TMPRSS2 in the oral mucosa (tongue, palate, and buccal mucosa), trigeminal ganglion, vessels, and salivary glands of 9 Sprague‐Dawley rats using immunohistochemistry and immunofluorescence.
Results
ACE2 and TMPRSS2 were strongly expressed in the intermediate layer of the squamous epithelia of tongue papillae and buccal mucosa. ACE2‐ and TMPRSS2‐positive cells were observed in the taste buds of the tongue. Additionally, ACE2 and TMPRSS2 were co‐expressed in the ductal epithelium and acinar cells of salivary glands. Furthermore, both ACE2 and TMPRSS2 were stained in the neuronal cell body of trigeminal ganglia, but not in Schwann cells. Moreover, ACE2 and TMPRSS2 were expressed in capillaries, but not in venules/arterioles.
Conclusions
SARS‐CoV‐2 can spread the suprabasal area of squamous epithelia of the oral mucosa, invades taste bud, trigeminal nerve, parotid gland, and microvessel, resulting in oral manifestations.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Various treatment modalities are used for head and neck cancer (HNC). This study analyzed the incidence and risks of myocardial infarction (MI) and stroke by cancer site and treatment modality in ...22,737 patients newly diagnosed with HNC registered in the Korean National Health Insurance Service database in 2007-2013. An additional 68,211 patients without HNC, stroke, or MI were identified as the control group. The risks for MI (hazard ratio HR = 1.38, 95% confidence interval CI 1.24-1.53), stroke (HR = 1.48, 95% CI 1.37-1.60), and mortality (HR = 5.30, 95% CI 5.14-5.47) were significantly higher in the HNC group. Analysis by cancer site showed the risk of MI and mortality was highest in hypopharynx cancer, while the risk of stroke was highest in nasopharynx and paranasal sinus cancer. Analysis by treatment modality showed the highest risks for MI (HR = 1.88, 95% CI 1.31-2.69) and mortality (HR = 2.95, 95% CI 2.75-3.17) in HNC patients receiving chemotherapy (CT) alone, while HNC patients receiving CT with surgery had the highest risk for stroke (HR = 1.81, 95% CI 1.14-2.88). Careful attention to MI and stroke risks in HNC patients is suggested, especially those who received both CT and radiotherapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Recurrent laryngeal nerve (RLN) palsy is a serious complication of thyroid surgery. During intraoperative neuromonitoring (IONM) of the RLN in thyroid surgery, repeated shifting between ...surgical instruments and the nerve stimulator is cumbersome and time-consuming. Therefore, we developed a simple detachable magnetic nerve stimulator that may be connected to all metallic surgical instruments. This study aimed to investigate the feasibility and efficacy of this detachable magnetic nerve stimulator for IONM in a porcine model and humans.
Methods
Eight RLNs in four pigs and thirteen in nine patients that underwent thyroidectomy were examined. We developed a detachable nerve stimulator that combined surgical instruments with the nerve-stimulating probe. We evaluated the electromyography (EMG) amplitudes of the RLNs in pigs and patients using conventional nerve probes and surgical instruments with the novel detachable magnetic nerve stimulator attached.
Results
The EMG amplitudes of the eight RLNs in pigs and thirteen in patients were analyzed. The detachable magnetic nerve stimulator was feasible and safe. There was no significant difference in the EMG amplitude between instruments (
P
= 0.423 in animals,
P
= 0.446 in humans).
Conclusions
The application of stimulating dissection using a detachable magnetic nerve stimulator during thyroidectomy with IONM is simple, convenient, and effective. It provides surgeons with real-time feedback of the EMG response during intermittent IONM. We propose that this novel device could be an essential guide for most surgeons, especially for less experienced head and neck surgeons.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
The role of sex hormones for voice changes in men and women is presently unknown. To determine the effect of sex hormone on the vocal fold, changes of the extracellular matrix (ECM) in ...vocal fold lamina propria were assessed in orchiectomized (ORX) and ovariectomized (OVX) rats.
Methods
Male and female Sprague‐Dawley rats were divided into sham‐operated control male (CON‐ORX), ORX, sham‐operated female (CON‐OVX), and OVX rats. Histological changes and expression of ECM‐related genes in lamina propria of the vocal fold were evaluated at 4 and 12 weeks after surgery.
Results
Testosterone and estradiol levels decreased in the ORX and OVX groups, respectively. ORX groups did not have significant changes compared with CON‐ORX groups. However, the expression of hyaluronic acid (HA) was decreased in the OVX group compared with the CON‐OVX group. The expression of collagen I in OVX was lower than in the CON‐OVX group. Collagen III levels were elevated at 4 weeks in the OVX group, but collagen III levels were diminished at 12 weeks in the OVX group. Expression of elastin in the ECM was less dense in the OVX group compared with controls. The expression MMP‐1 and MMP‐9 showed significantly increase in the OVX group compared to the CON‐OVX group.
Conclusion
No changes of the ECM‐related genes in the vocal fold lamina propria were observed in ORX groups with reduced testosterone. However, changes of several ECM‐related genes were observed in OVX groups with decreased estrogen. These results indicate that the vocal fold is an estrogen‐sensitive target organ and that decreased estrogen, not testosterone, can affect the expression of several ECM‐related molecules of vocal fold.
Level of Evidence
NA
Laryngoscope, 130:732–740, 2020
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Self-expanding metallic stents (SEMSs) are used as a bridge to surgery in patients with obstructive colorectal cancer. However, the role of laparoscopic resection after successful stent ...deployment is not well established. We aimed to compare the oncologic outcomes of laparoscopic vs open surgery after successful colonic stent deployment in patients with obstructive left-sided colorectal cancer.
Methods
In this multicenter study, 179 (97 laparoscopy, 82 open surgery) patients with obstructive left-sided colorectal cancer who underwent radical resection with curative intent after successful stent deployment were retrospectively reviewed. To minimize bias, we used inverse probability treatment-weighted propensity score analysis. The short- and long-term outcomes between the groups were compared.
Results
Both groups had similar demographic and tumor characteristics. The operation time was longer, but the degree of blood loss was lower in the laparoscopy than in the open surgery group. There were nine (9.3%) open conversions. After adjustment, the groups showed similar patient and tumor characteristics. The 5-year disease-free survival (DFS) (laparoscopic vs open: 68.7% vs 48.5%,
p
= 0.230) and overall survival (OS) (laparoscopic vs open: 79.1% vs 69.0%,
p
= 0.200) estimates did not differ significantly across a median follow-up duration of 50.5 months. Advanced stage disease (DFS: hazard ratio HR 1.825, 95% confidence interval CI: 1.072–3.107; OS: HR 2.441, 95% CI 1.216–4.903) and post-operative chemotherapy omission (DFS: HR 2.529, 95% CI 1.481–4.319; OS: HR 2.666, 95% CI 1.370–5.191) were associated with relatively worse long-term outcomes.
Conclusion
Stent insertion followed by laparoscopy with curative intent is safe and feasible; the addition of post-operative chemotherapy should be considered after successful treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Mesenchymal stromal cells (MSCs) are considered as a promising therapeutic tool for liver fibrosis, a main feature of chronic liver disease. Because small extracellular vesicles (sEVs) harboring a ...variety of proteins and RNAs are known to have similar functions with their derived cells, MSC-derived sEVs carry out the regenerative capacities of MSCs. Human tonsil-derived MSCs (T-MSCs) are reported as a novel source of MSCs, but their effects on liver fibrosis remain unclear. In the present study, we investigated the effects of T-MSC-derived sEVs on liver fibrosis. The expression of profibrotic genes decreased in human primary hepatic stellate cells (pHSCs) co-cultured with T-MSCs. Treatment of T-MSC-sEVs inactivated human and mouse pHSCs. Administration of T-MSC-sEVs ameliorated hepatic injuries and fibrosis in chronically damaged liver induced by carbon tetrachloride (CCl4). miR-486-5p highly enriched in T-MSC-sEVs targeting the hedgehog receptor, smoothened (Smo), was upregulated, whereas Smo and Gli2, the hedgehog target gene, were downregulated in pHSCs and liver tissues treated with T-MSC-sEVs or miR-486-5p mimic, indicating that sEV-miR-486 inactivates HSCs by suppressing hedgehog signaling. Our results showed that T-MSCs attenuate HSC activation and liver fibrosis by delivering sEVs, and miR-486 in the sEVs inactivates hedgehog signaling, suggesting that T-MSCs and their sEVs are novel anti-fibrotic therapeutics for treating chronic liver disease.
Display omitted
Kim and colleagues demonstrated the therapeutic potential of human tonsil-derived mesenchymal stromal cells (T-MSCs) and T-MSC-derived small extracellular vesicles (sEVs) in chronic liver disease. T-MSCs release sEVs containing miR-486-5p, which inactivates HSCs and alleviates liver fibrosis by suppressing the Hh-activated gene smoothened, suggesting T-MSC-derived sEVs as a novel therapeutic for treating liver fibrosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and ...transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.
Background
This study aimed to investigate the relationships between serum vascular endothelial growth factor (VEGF)‐A or VEGF‐C levels and lymph node metastasis (LNM) status in patients with ...papillary thyroid carcinoma (PTC).
Methods
The study enrolled 150 patients with pathologically proven PTC who underwent surgery: PTC without LNM, PTC with central neck metastasis, and PTC with lateral neck metastasis.
Results
Preoperative serum VEGF‐A levels were 300.12 ± 80.80 pg/mL overall and were not correlated with the presence of LNM. Preoperative serum VEGF‐C levels were 132.41 ± 48.48 pg/mL overall and were significantly correlated with the presence of LNM. Serum VEGF‐C levels were further increased in patients with lateral neck metastasis and positively correlated with the number of metastatic LNs (rho = 0.252, P = 0.002). Serum VEGF‐C, but not VEGF‐A, was identified as a significant predictor of lateral neck metastasis.
Conclusion
Serum VEGF‐C might be a clinically relevant biomarker of lateral neck metastasis in patients with PTC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions ...in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor β expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c (
), acetyl-CoA carboxylase (
), fatty acid synthase (
), cluster of differentiation 36 (
), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor β (
and
) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin (
and
) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.
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