Association between preoperative frontal electroencephalogram alpha asymmetry and postoperative quality of recovery: an observational study.

BACKGROUND: Left-sided frontal alpha asymmetry on electroencephalograms, which indicates decreased relative left-hemispheric activity, has been associated with depression, anxiety, and stress responsivity. We aimed to evaluate the association between perioperative measures of frontal alpha asymmetry and quality of recovery (QoR) after surgery. METHODS: We enrolled 110 female patients undergoing thyroidectomy and recorded perioperative electroencephalograms. The power of the prefrontal alpha band (8-13 Hz) was measured in the Fp1 and Fp2 leads. Left-sided frontal alpha asymmetry was defined as a higher alpha band power in Fp1 than in Fp2 and vice versa. QoR was assessed using the QoR-15 score on the day before surgery and postoperative days 1 and 2. The primary study endpoint was a difference in postoperative global QoR-15 score between preoperative left-sided and right-sided alpha asymmetry groups. The predictability of frontal alpha asymmetry for poor QoR-15 score was also evaluated. RESULTS: The global QoR-15 score showed a significant group-by-time interaction, and post-hoc analysis revealed significantly lower scores on postoperative days 1 (P=0.006) and 2 (P<0.001) in the left-sided frontal alpha asymmetry group. In the multivariate logistic regression analysis, preoperative left-sided frontal alpha asymmetry was associated with a 3.3-fold increased risk of the lowest tertile for the postoperative day 1 QoR-15 score (95% CI: 1.31-8.24; P=0.011). CONCLUSIONS: Preoperative left-sided frontal alpha asymmetry was independently associated with a lower postoperative QoR-15 score in female patients undergoing thyroidectomy, highlighting the potential role of preoperative frontal electroencephalography in predicting patient-centred outcomes after surgery. CLINICAL TRIAL REGISTRATION: KCT0006586 (http://cris.nih.go.kr/).

Robotic parathyroidectomy is a feasible technique for primary hyperparathyroidism.

PURPOSE: Focused parathyroidectomy is the gold standard treatment modality for primary hyperparathyroidism, which allows accurate preoperative localization. Robotic parathyroidectomy has emerged as a feasible procedure for focused parathyroidectomy. This study aimed to report the experiences of gasless robotic transaxillary parathyroidectomy for primary hyperparathyroidism in a single center. METHODS: We assessed the data obtained from patients who underwent gasless robotic parathyroidectomy with the transaxillary approach between December 2013 and August 2022 and were diagnosed with primary hyperparathyroidism at our institute. The data included clinical, biochemical, and pathological features and operation time. RESULTS: Of the 12 patients, 11 were women and one was a man. The median age of the patients was 44.5 years (range: 15-65 years). The median preoperative maximum mass diameters on ultrasonography and neck computed tomography were 1.2 ± 0.5 and 1.1 ± 0.6 cm, respectively. The median size of the postoperative maximum mass diameter in gross pathology was 1.3 ± 0.4 cm. The location of the enlarged parathyroid was left superior in five patients, right inferior in four, left inferior in three, and no right superior in one. In the final pathological examination, all cases were parathyroid adenomas. Only one case experienced a postoperative bleeding complication. At six months from surgery, average of an axillary scar length was 5.85 cm, and an average width was 0.21 cm. The mean operative time was 113 ± 48 min. The mean robot docking and console times were 9 ± 5 and 47 ± 52 min, respectively. CONCLUSIONS: Robotic transaxillary parathyroidectomy is a feasible technique in select patients with primary hyperparathyroidism and preoperatively localized disease. The gasless robotic transaxillary approach provides procedural safety as well as superior cosmetic results without a neck scar.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone.

Mutations in lysosomal genes increase the risk of neurodegenerative diseases, as is the case for Parkinson's disease. Here, we found that pathogenic and protective mutations in arylsulfatase A (ARSA), a gene responsible for metachromatic leukodystrophy, a lysosomal storage disorder, are linked to Parkinson's disease. Plasma ARSA protein levels were changed in Parkinson's disease patients. ARSA deficiency caused increases in α-synuclein aggregation and secretion, and increases in α-synuclein propagation in cells and nematodes. Despite being a lysosomal protein, ARSA directly interacts with α-synuclein in the cytosol. The interaction was more extensive with protective ARSA variant and less with pathogenic ARSA variant than wild-type. ARSA inhibited the in vitro fibrillation of α-synuclein in a dose-dependent manner. Ectopic expression of ARSA reversed the α-synuclein phenotypes in both cell and fly models of synucleinopathy, the effects correlating with the extent of the physical interaction between these molecules. Collectively, these results suggest that ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein.

Intravitreal Injection of Liposomes Loaded with a Histone Deacetylase Inhibitor Promotes Retinal Ganglion Cell Survival in a Mouse Model of Optic Nerve Crush.

Various neuroprotective agents have been studied for the treatment of retinal ganglion cell (RGC) diseases, but issues concerning the side effects of systemically administered drugs and the short retention time of intravitreally injected drugs limit their clinical applications. The current study aimed to evaluate the neuroprotective effects of intravitreally injected trichostatin A (TSA)-loaded liposomes in a mouse model of optic nerve crush (ONC) and determine whether TSA-loaded liposomes have therapeutic potential in RGC diseases. The histone deacetylase inhibitor, TSA, was incorporated into polyethylene glycolylated liposomes. C57BL/6J mice were treated with an intravitreal injection of TSA-loaded liposomes and liposomes loaded with a lipophilic fluorescent dye for tracking, immediately after ONC injury. The expression of macroglial and microglial cell markers (glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1), RGC survival, and apoptosis were assessed. We found that the liposomes reached the inner retina. Their fluorescence was detected for up to 10 days after the intravitreal injection, with peak intensity at 3 days postinjection. Intravitreally administered TSA-loaded liposomes significantly decreased reactive gliosis and RGC apoptosis and increased RGC survival in a mouse model of ONC. Our results suggest that TSA-loaded liposomes may help in the treatment of various RGC diseases.

Serum cystatin C level: An excellent predictor of mortality in patients with cirrhotic ascites.

BACKGROUND AND AIM: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. METHODS: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS-1). RESULTS: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS-1. Serum creatinine level was not significantly associated with mortality and development of HRS-1 on multivariate analysis. CONCLUSION: Serum cystatin C level was an independent predictor of mortality and development of HRS-1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites.

Sirtuin inhibition leads to autophagy and apoptosis in porcine preimplantation blastocysts.

Sirtuins are nicotinamide adenine dinucleotide dependent class III histone deacetylase proteins that play a crucial role in several cellular processes, including DNA repair, apoptosis, and lifespan. Previous studies have shown that sirtuin inhibition leads to embryonic developmental arrest and oxidative stress in porcine and murine. However, sirtuin-mediated mechanisms have not been examined in porcine preimplantation blastocysts. We therefore investigated the relationship between sirtuins and autophagy. Embryos were cultured with 100 µM sirtinol (SIRT1/2 inhibitor) in NCSU-23 media after in vitro fertilization. Treatment with sirtinol significantly reduced the rates of morula (21.34 ± 1.84 vs. 11.89 ± 2.01), blastocyst development (17.18 ± 1.81 vs. 9.00 ± 2.02), and total cell number (50.80 ± 1.47 vs. 37.71 ± 1.79), compared to controls, with an associating decrease the levels of Sirt2 transcript. Sirtinol treatment induced autophagy through an increase in LC3 transcript and LC3 protein. BECLIN1 and ATG5 expression showed a slight increase in treated group. Finally, treatment with sirtinol dramatically increased TUNEL indices (6.55 ± 0.84 vs. 11.44 ± 0.81) and fragmentation indices (0.33 ± 0.05 vs. 1.40 ± 0.30). BCL2L1 expression was lower, while Caspase-3 expression was significantly elevated in the sirtinol-treated group. Therefore, these findings suggest that sirtuins may elicit their effects through modifying autophagy and apoptosis, leading to developmental arrest and reducing the quality of porcine preimplantation embryos.

The effect of poly(ADP-ribosyl)ation inhibition on the porcine cumulus-oocyte complex during in vitro maturation.

Poly(ADP-ribosyl)ation (PARylation) plays important roles in DNA repair, apoptosis, transcriptional regulation, and cell death, and occurs via the activity of poly(ADP-ribose) polymerases (PARPs). Previous studies have shown that PARylation affects mouse and porcine pre-implantation development and participates in mechanisms of autophagy. However, there have not yet been reported the role of PARylation during in vitro maturation (IVM) of porcine oocytes. Thus, we investigated the effect of PARylation inhibition on this process; cumulus-oocyte complexes (COCs) were cultured with 3-aminobenzamide (3-ABA, PARP inhibitor) during porcine IVM. Full cumulus expansion was significantly reduced (10.34 ± 1.23 [3-ABA] vs. 48.17 ± 2.03% [control]), but nuclear maturation rates were not changed in the 3-ABA treatment group. Especially, we observed that cumulus cells were little expanded after 22 h in 3-ABA treated COCs. The mRNA expression levels of oocyte maturation- and cumulus expansion-related genes were evaluated at 22 and 44 h. GDF9, BMP15, COX-2, and PTX3 expression were upregulated at 44 h, whereas the levels of HAS2 and TNFAIP6 were downregulated in the 3-ABA treated group. Furthermore, 3-ABA treatment significantly decreased the developmental rate (28.24 ± 1.06 vs. 40.24 ± 3.03%) and total cell number (41.12 ± 2.10 vs. 50.38 ± 2.27), but increased the total apoptotic index (6.44 ± 0.81 vs. 3.08 ± 0.51) in parthenogenetically activated embryos. In conclusion, these results showed that PARylation regulates cumulus expansion through the regulation of gene expression and affects developmental competence and quality in parthenogenetic embryos.

The regulation of autophagy in porcine blastocysts: Regulation of PARylation-mediated autophagy via mammalian target of rapamycin complex 1 (mTORC1) signaling.

Poly(ADP-ribosyl)ation (PARylation) acts as a modulator of selective autophagic degradation of ubiquitinated aggregates for cellular quality control, functioning in pro-survival role. It was reported previously that the inhibition of PARylation resulted in autophagy defects leading accumulation of ubiquitinated aggregates SQSTM1/p62 and apoptosis in porcine blastocysts. Thus, this study aims to investigate the mechanism between PARylation and autophagy in porcine blastocysts. In vitro produced (IVP) embryos were treated with 3-aminobenzamide (3ABA, poly (ADP-ribose) polymerase inhibitor) and/or rapamycin (RAPA, an mTORC1 inhibitor) during blastocyst formation. Then, these treated blastocysts were analyzed by real-time PCR, immunocytochemistry and TUNEL Assay. We found that the 3ABA treatment increased mTORC1 downstream target, phosphorylation of thr389 p70S6K (p-p70S6K-thr389), suggesting an increase in mTORC1 activity. Co-treatment with rapamycin (RAPA), mTORC1 inhibitor, restored the 3ABA-induced autophagy defects to those of the controls by normalizing mTORC1 activity. Moreover, autophagy induction, with only RAPA treatment, increased the rate of blastocyst development (70.05 ± 0.93 vs. 50.61 ± 3.49%), total cell number (58.48 ± 2.94 vs. 49.58 ± 2.43) and blastomere survival, but decreased the accumulation of SQSTM1/p62 aggregates. In summary, mTORC1 signaling is a key mechanism of PARylation-autophagy and its inhibition improved developmental ability and embryo quality by promoting selective autophagic degradation of ubiquitinated aggregates in porcine blastocysts. Therefore, these findings have significant implications for understanding the importance of autophagy regulation for successful in vitro production of porcine embryos.

No Change in Complications Following Thyroidectomy Despite Increase in Thyroid Cancer Surgeries: A Meta-Regression Analysis.

PURPOSE: The increase in thyroid cancer incidence has inevitably led to an increase in thyroid cancer surgeries. This meta-regression analysis aimed to determine if the rate of post-thyroidectomy complications changes by year. MATERIALS AND METHODS: PubMed and Embase databases were used to perform a systematic literature search of studies published from January 1, 2005, using the keywords "thyroidectomy" and "complication." A meta-regression was performed for post-thyroidectomy hypocalcemia and bleeding. RESULTS: This meta-analysis included 25 studies involving 927751 individuals. Through the years of publications in this study, there was no significant difference in the proportion of post-thyroidectomy hypocalcemia and bleeding (p=0.9978, 0.6393). CONCLUSION: Although the number of thyroid surgeries has recently increased, the incidence of post-thyroidectomy hypocalcemia and bleeding did not significantly increase.

Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Aggressive Subtypes of Papillary Thyroid Carcinoma Smaller Than 1 cm.

CONTEXT: Tumor size is important in determining the range of surgery in papillary thyroid carcinomas (PTCs), especially those smaller than 1 cm. OBJECTIVE: We aimed to analyze the features of small PTCs with aggressive subtypes based on histological characteristics. METHODS: In this retrospective study, we reviewed the medical records of 11 570 patients with PTCs smaller than or equal to 1 cm who underwent thyroidectomy between January 2009 and December 2016. Aggressive subtypes included diffuse sclerosing, solid, tall cell, columnar cell, and hobnail subtypes. RESULTS: Among the 11 570 patients with PTCs smaller than or equal to 1 cm, 177 aggressive PTC subtypes were identified. Propensity score matching revealed 110 tumors (62.1%) with extrathyroidal extension of aggressive PTC subtypes and 451 (51.1%) nonaggressive PTC subtypes (95% CI, 0.41-0.80; P < .001). Metastatic central and lateral neck lymph nodes constituted 3.06 ± 3.67 and 3.81 ± 5.39 of aggressive PTC subtypes and 1.22 ± 2.14 and 2.85 ± 3.79 of nonaggressive PTC subtypes, respectively (central neck nodes: 95% CI, 1.42-2.26; P < .001; lateral neck nodes: 95% CI, 2.9-5.90; P < .001). Seven patients with aggressive PTC subtypes (3.95%) and 12 with nonaggressive PTC subtypes (1.7%) exhibited recurrence. CONCLUSION: Aggressive subtypes of small PTC tumors smaller than or equal to 1 cm exhibited more extrathyroidal extension and neck node metastasis. This study suggests that surgeons should consider the aggressive subtypes as important factors when deciding the range of surgery in PTCs smaller than 1 cm.

Lateral neck dissection for the treatment of synchronous and metachronous lateral neck metastasis of N1b papillary thyroid cancer.

Introduction: Metachronous lateral neck recurrence after thyroidectomy for N1b papillary thyroid cancer is accompanied by high morbidity and increased difficulty of reoperation. From the perspective of recurrence, the objective of this study was to compare patients who underwent metachronous lateral neck dissection (mLND) despite initial thyroidectomy and patients who underwent synchronous lateral neck dissection (sLND) for papillary thyroid cancer and analyze the risk factors for recurrence after mLND. Method: This retrospective study involved 1,760 patients who underwent lateral neck dissection for papillary thyroid cancer at the Gangnam Severance Hospital, a tertiary medical center in Korea, from June 2005 to December 2016. The primary outcome was structural recurrence, and secondary outcome measures were risk factors of recurrence in the mLND group. Result: A total of 1,613 patients underwent thyroidectomy and sLND at diagnosis. In 147 patients, thyroidectomy alone was performed at the time of diagnosis, and mLND was performed when recurrence to the lateral neck lymph node was confirmed. During a median follow-up of 102.1 months, 110 (6.3%) patients experienced a recurrence. There was no significant difference in the recurrence between the sLND and mLND groups (6.1% vs 8.2%, P=.32). The period from lateral neck dissection to recurrence was longer in the mLND group than in the sLND group (113.6 ± 39.4 months vs 87.0 ± 33.8 months, respectively, P<.001). Age ≥50 years (adjusted HR=5.209, 95% CI=1.359-19.964; P=.02), tumor size >1.45 cm (adjusted HR=4.022, 95% CI=1.036-15.611; P=.04), and lymph node ratio in the lateral compartment (adjusted HR=4.043, 95% CI=1.079-15.148; P=.04) were independent variables predictive of recurrence after mLND. Conclusion: mLND is suitable for treating lateral neck recurrence in patients with N1b papillary thyroid cancer who previously underwent thyroidectomy. Lateral neck recurrence after treatment in patients who underwent mLND was predicted by age, tumor size, and lymph node ratio in the lateral compartment.

Comparison of delayed bleeding to immediate bleeding following thyroidectomy.

It is important to identify risk factors for post-thyroidectomy bleeding requiring airway intervention or reoperation. Therefore, we aimed to compare the characteristics of patients with postoperative bleeding after thyroid surgery according to the period until reoperation. We conducted a retrospective study analyzing data between April 2009 and July 2022 and included 126 patients who had postoperative bleeding. The patients were grouped according to the period between thyroidectomy and reoperation due to bleeding (0 day, 1-7 days, > 7 days). We performed among-group comparisons of patient characteristics and surgical aspects, including the extent of surgery. The ratios of male-female and lateral neck dissection were higher in the post-operative bleeding group than in the group without bleeding. In the analysis of patients with postoperative bleeding, grouped according to period between thyroidectomy and reoperation, there was a significant among-group difference in the male-female ratio. The male sex was positively correlated with the reoperation period. Further, the reoperation period was also positively correlated with total thyroidectomy and lateral neck dissection and the operation time showed a significant among-group difference. Our results indicate that the male sex and lateral neck dissection are risk factors for postoperative bleeding after thyroidectomy. Furthermore, male sex, total thyroidectomy, and lateral neck dissection are risk factors for delayed bleeding. Therefore, clinicians should consider these factors for interventions against immediate or delayed bleeding after thyroidectomy.

Prognosis of Anaplastic Thyroid Cancer with Distant Metastasis.

Anaplastic thyroid cancer (ATC) is derived from follicular thyroid cells and is associated with high mortality risk. Obtaining information to characterize ATC is difficult because ATC with distant metastasis is extremely rare. This study determined the clinical characteristics of ATC with distant metastasis. The medical records of 152 patients with ATC at Gangnam Severance Hospital were reviewed between January 2004 and March 2022. The primary endpoint was the overall survival of the total patient sample, patients with ATC and distant metastasis, and those with ATC and brain metastasis. Of the 152 patients with ATC, 88 had distant metastasis at diagnosis. The 5-year disease-specific survival was 24% for total ATC and 10% for ATC with distant metastasis. Survival for >1 year was 32% for total ATC and 15% for ATC with distant metastasis. The median survival rate differed significantly between the total ATC and ATC with distant metastasis groups (228.5 vs. 171 days). Among the ATC cases, 11% had brain metastasis; thus, brain MRI or CT is worth considering at diagnosis and follow-up, even if there were no statistical difference in overall survival between patients with ATC with and without brain metastasis.

Prophylactic antibiotics may not be necessary for transoral endoscopic thyroidectomy.

Background: With the recent advances in thyroid cancer surgery techniques and the increasing number of patients concerned about cosmetics, the use of transoral endoscopic thyroidectomy is increasing globally. The aim of this study was to determine whether transoral endoscopic thyroidectomy is truly a clean-contaminated surgery. Methods: From September 2016 to April 2018, 20 patients with thyroid cancer underwent transoral endoscopic thyroidectomy performed by a single surgeon at Gangnam Severance Hospital. Before and after surgery, the oral cavity was swabbed to obtain culture samples, and antibiotics were administered before and after surgery each once. Results: Of the total 20 patients, no bacteria were identified before or after surgery in eight (40%) patients. Bacteria were identified both before and after surgery in seven patients (35%). In four patients (20%), bacteria were not identified before surgery, but bacteria were identified after surgery. Bacteria were identified before surgery but not after surgery in one patient (5%). No surgical site infection was observed. All the bacteria identified were normal flora of the oral cavity and skin. Conclusions: There was no difference between the preoperative culture and postoperative culture of the oral cavity in patients undergoing TOET, and there were no postoperative surgical site infection with prophylactic pre & post-operative antibiotics use. Considering the patient's position and surgical extent in TOET, it appears to be difficult for non-indigenous bacteria to invade the surgical site in oral cavity.

TNF-α promotes α-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis.

Cell-to-cell propagation of α-synuclein is thought to be the underlying mechanism of Parkinson's disease progression. Recent evidence suggests that inflammation plays an important role in the propagation of protein aggregates. However, the mechanism by which inflammation regulates the propagation of aggregates remains unknown. Here, using in vitro cultures, we found that soluble factors secreted from activated microglia promote cell-to-cell propagation of α-synuclein and further showed that among these soluble factors, TNF-α had the most robust stimulatory activity. Treatment of neurons with TNF-α triggered cellular senescence, as shown by transcriptomic analyses demonstrating induction of senescence-associated genes and immunoanalysis of senescence phenotype marker proteins. Interestingly, secretion of α-synuclein was increased in senescent neurons, reflecting acquisition of a senescence-associated secretory phenotype (SASP). Using vacuolin-1, an inhibitor of lysosomal exocytosis, and RNAi against rab27a, we demonstrated that the SASP was mediated by lysosomal exocytosis. Correlative light and electron microscopy and immunoelectron microscopy confirmed that propagating α-synuclein aggregates were present in electron-dense lysosome-like compartments. TNF-α promoted the SASP through stimulation of lysosomal exocytosis, thereby increasing the secretion of α-synuclein. Collectively, these results suggest that TNF-α is the major inflammatory factor that drives cell-to-cell propagation of α-synuclein by promoting the SASP and subsequent secretion of α-synuclein.

Conformation-specific Antibodies Targeting Aggregated Forms of α-synuclein Block the Propagation of Synucleinopathy.

Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.

Inflammation promotes synucleinopathy propagation.

The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. The current understanding of the mechanism of proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. However, when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. Aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.