A postulated model for photoimmunopathogenesis of chronic actinic dermatitis around adaptive immunity, including Th17 cells, Tregs, TRMs, cytotoxic T cells, and/or common-γ chain receptor+ cells.

BACKGROUND/PURPOSE: The pathogenesis of chronic actinic dermatitis (CAD) is more complicated than other photodermatoses. However, the relationship between the clinical severity of CAD and the offending photocontact or contact allergens or both, and the correlations of CAD immunopathogenesis with the immunoregulatory molecules involved in adaptive immunity are yet to be investigated. METHODS: We performed phototesting with broad-spectrum ultraviolet (UV) B, UVA, and visible light to establish the presence of photosensitivity in 121 patients with CAD, together with photopatch and contact patch testing. Nine patients with CAD were selected according to their clinical severity score for CAD (CSS-CAD), and triple direct immunofluorescence analysis was performed with paraffin-embedded skin biopsy samples. RESULTS: As CSS-CAD was closely correlated with the multiplicity of photo(contact) allergens, particularly photoallergens, three or more photoallergens were detected in the severe CAD group (52.5%); less in the moderate group (32.8%); and only one in the mild group (14.8%; P = .025). In the groups showing greater severity of disease, the absolute numbers of IFN-γ+ , IL-17+ , CD4+, CD8+, common-γ chain receptor (common-γCR)+ , and CD69+ tissue-resident memory cells increased on average; there was also an increase in the CD4+/CD8+ cell ratio, with the more severely affected groups. However, the levels of TNF-α+ and FoxP3+ regulatory T (Treg) cells and the mean IL-17/IFN-γ cell ratio decreased in the more severely affected CSS-CAD subgroups. CONCLUSIONS: Based on the clinical analysis and immunopathogenic results, avoidance of excessive sun exposure, and topical and systemic blocking agents for photo(contact) allergens are recommended. Additionally, conventional immunomodulators and emerging agents including JAK-STAT inhibitors may be administered for CAD treatment in the future.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Suppression of Pax3-MITF-M Axis Protects from UVB-Induced Skin Pigmentation by Tetrahydroquinoline Carboxamide.

Paired box gene 3 (Pax3) and cAMP responsive element-binding protein (CREB) directly interact with the cis-acting elements on the promoter of microphthalmia-associated transcription factor isoform M (MITF-M) for transcriptional activation in the melanogenic process. Tyrosinase (Tyro) is a target gene of MITF-M, and functions as a key enzyme in melanin biosynthesis. Tetrahydroquinoline carboxamide (THQC) was previously screened as an antimelanogenic candidate. In the current study, we evaluated the antimelanogenic activity of THQC in vivo and elucidated a possible mechanism. Topical treatment with THQC mitigated ultraviolet B (UVB)-induced skin pigmentation in guinea pig with decreased messenger RNA (mRNA) and protein levels of melanogenic genes such as MITF-M and Tyro. Moreover, THQC inhibited cAMP-induced melanin production in α-melanocyte-stimulating hormone (α-MSH)- or histamine-activated B16-F0 cells, in which it suppressed the expression of the MITF-M gene at the promoter level. As a mechanism, THQC normalized the protein levels of Pax3, a transcriptional activator of the MITF-M gene, in UVB-exposed and pigmented skin, as well as in α-MSH-activated B16-F0 culture. However, THQC did not affect UVB- or α-MSH-induced phosphorylation (activation) of CREB. The results suggest that suppression of the Pax3-MITF-M axis might be a potential strategy in the treatment of skin pigmentary disorders that are at high risk under UVB radiation.

Health-related quality of life in adult males with lower urinary tract symptoms.

PURPOSE: To assess the status and impact of lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a community-based sample of Korean adult males. METHODS: We analyzed the data of 101,606 adult males aged ≥ 19 years of age obtained during the 2011 Korean Community Health Survey. Subject data were assessed for LUTS and HRQoL using international prostate symptom scores, and EuroQol-five-dimensions three-level version (EQ-5D-3L) and EuroQol-visual analogue scale (EQ-VAS) scores. RESULTS: Of the 101,606 subjects, 53,323 (52.5%) reported having at least one LUTS and 3116 (3.1%) had an IPSS of ≥ 20, indicating severe LUTS. In those aged 19-39 years, 28.7% (8343/29,072) reported they had mild to severe LUTS. The prevalence of LUTS was high among those aged 40-59 years (47.7%), 60-79 years (80.5%), and ≥ 80 years (91.2%). In addition, EQ-5D-3L and EQ-VAS scores decreased as LUTS severity and frequency increased. CONCLUSIONS: Adult men of all ages with mild to severe LUTS have poorer health statuses and quality of life. Even among young males, LUTS severity and was found to negatively affect HRQoL.

Application of acellular human dermis and skin grafts for lower extremity reconstruction.

OBJECTIVE: To use both acellular human dermis and skin grafting simultaneously for improved skin grafting without contracture. The study also aims to address the lack of research on the application of an acellular human dermis in diverse clinical cases. METHOD: The study examined patients who had received acellular human dermis (CGDerm, CGBio, Seoul, Korea) and split-thickness skin grafting (STSG) simultaneously for lower limb, full-thickness skin defects between September 2012 and June 2014. The researchers performed chart reviews retrospectively and examined the patients based on the following factors: gender, age, injury mechanism, size, exposed structure, pre-coverage dressing method, coverage method, post-operational engraftment and total healing period, contracture development, elasticity, and infection development. RESULTS: A sample of 27 patients with a total of 30 wounds took part in the study. Of these wounds, 29 showed successful engraftment without infection or contracture. In one case, continued seroma was observed and, following new coverage of both the acellular human dermis and STSG, engraftment was successful. CONCLUSION: Human dermis can play an important role in securing the availability of surrounding tissue and in contracture prevention, both of which are key to lower limb reconstruction. Of the types available, acellular human dermis showed lower infection rates than other human dermis types, and its engraftment rate was higher than in STSG-only cases. These findings suggest that acellular human dermis use in STSG is effective and safe in lower limb reconstruction.

Increased incidence of chronic actinic dermatitis in relation to climate changes and air pollution during the past 15 years in Korea.

BACKGROUND: Chronic actinic dermatitis (CAD) develops in seasons where there is high sun exposure, such as summer, and can persistent throughout the year in severely affected cases. The authors noted that CAD prevalence increased in relation to climate changes and air pollutants. METHODS: We retrospectively analyzed 294 patients with newly diagnosed CAD between December 2000 and November 2016. We investigated the annual trend of sun hours, humidity, and ground-level ozone and respirable particles (PM10) in Pusan, Korea; correlations between climate change and/or air pollution and the incidence of patient with CAD were analyzed. RESULTS: The incidence of patients with CAD apparently increased annually during the period of the study. The majority of patients presented in summer. Pearson's correlation analysis showed an increasing tendency of CAD occurrence to be correlated with sun hours (R = .706, P = .002), ground-level ozone (R = .542, P = .03), and mean air humidity (R = .608, P = .012). Inversely, PM10 showed a negative correlation with CAD occurrence (R = -.713, P = .002). The correlations identified by multiple regression analysis showed a strong positive association between the incidence of CAD and sun hours (P = .029) and a negative association between the incidence of CAD and PM10 (P = .027) (adjusted R2  = .778). CONCLUSION: The increased incidence of CAD may be related to sun hours and inversely related to PM10.

Sonographic Findings of Malignant Appendix Tumors in Seven Cases.

We report the sonographic features of confirmed malignant appendiceal tumors in seven cases. The histologic diagnoses of these tumors were mucinous cystadenocarcinoma (n = 2), colonic type adenocarcinoma (n = 4), and signet-ring cell carcinoma (n = 1). The 2 mucinous cystadenocarcinomas showed mucocele type, which had markedly enlarged inner luminal diameters (mean, 23 mm; range, 15-31 mm) and thick, irregular walls (mean wall thickness, 5.5 mm; range, 5-6 mm). In contrast, the 5 nonmucinous carcinomas (4 adenocarcinomas and 1 signet-ring cell carcinoma) showed nonmucocele type, which had relatively small inner luminal diameters (mean ± standard deviation [SD], 6.6 ± 4.5 mm; range, 2-15 mm) and prominent wall thickening (mean wall thickness ± SD, 6.2 ± 2.3 mm; range, 3-10 mm). Of the 5 nonmucinous tumors, only one had a discernible mass, three had thick irregular walls, two had loss of the wall layer pattern, and four had submucosal hypoechogenicity. Regardless of the histologic type, five of the seven malignant appendiceal tumors showed a severe periappendiceal fat infiltration or periappendiceal abscess, suggestive of perforation. Although the sonographic findings of the malignant appendiceal tumors were nonspecific, some of the sonographic features seen in these seven cases may help radiologists consider the possibility of underlying malignant appendiceal tumors.

Toe resurfacing with a thin thoracodorsal artery perforator flap.

BACKGROUND: In toe reconstruction, amputation procedures are much more common than salvage procedures. However, toe resurfacing, rather than amputation, provides superior functional and aesthetic results. In this study, we report the clinical outcomes of toe resurfacing using a thin thoracodorsal artery perforator flap. PATIENTS AND METHODS: Between January 2004 and June 2013, a total of 15 patients underwent toe resurfacing using thoracodorsal artery perforator flaps. Thin flaps were harvested by discarding the deep adipose layer. Twelve cases involved a great toe defect, three, a second toe defect, three, a third toe defect, and one, a fourth toe defect. Patient ages ranged from 19 to 82 years (mean, 42.9 years). The mechanism of injury varied, including crushing injury, degloving injury, and diabetic foot infection. RESULTS: The size of thoracodorsal artery perforator flap ranged from 4 × 3 to 20 × 8 cm2 and the thickness of the flap ranged from 4 to 9 mm (mean, 6.5 mm). All flap survived completely without complications. The mean follow-up period was 18.8 months (range, 12-60 months). Only one patient with rheumatoid arthritis had mild gait disturbance. All patients were satisfied with the aesthetic and functional results. CONCLUSION: Toe resurfacing with thin thoracodorsal artery perforator flaps appears to be a safer and more reliable option than amputation for preserving their function. © 2015 Wiley Periodicals, Inc. Microsurgery 37:312-318, 2017.

The clinical severity score of chronic actinic dermatitis correlates with in vivo photoallergic reactions and the immunologic parameters related to a shift towards Th2 immunity from the Th2/Th1 balanced status in patients with chronic actinic dermatitis.

BACKGROUND: Chronic actinic dermatitis (CAD) has a more complicated pathogenetic basis than others. The clinical grading system and its correlations with the clinical and immunological parameters still remained to be investigated to define the nature of CAD in a more detailed manner. OBJECTIVES: We investigated correlations of the clinical severity score of CAD (CSS-CAD) with the clinical and immunological parameters. METHODS: We evaluated 72 patients with CAD and classified them into three groups according to the CSS-CAD. We analysed total IgE level, peripheral blood (PB) eosinophil count, the ratio of Th2cell (CCR4 + CD4 +) percentage over Th1 cell (CXCR3 + CD4 +) percentage (Th2/Th1) and/or the sum of suppressor/cytotoxic T cells. RESULTS: The total IgE levels and the percentage of PB eosinophils were higher in the severer group than other groups. A shift towards Th2 from Th2/Th1 balanced status may be affected by total counts of suppressor T cells, and the patient with higher Th2/Th1 ratio than balanced status had the more proportion in the severer CSS-CAD group than other groups. CONCLUSION: The CSS-CAD correlates with total IgE level, PB eosinophil count and a shift towards Th2 immunity from Th2/Th1. So we suggest the Th1/Th2 dysbalance may be affected by the CSS-CAD.

Correlation between obesity and clinicopathological factors in patients with papillary thyroid cancer.

PURPOSE: Epidemiological studies have shown that obesity is associated with an increased risk of thyroid cancer. However, the exact nature of the relationship, especially with respect to the behavior of the cancer, remains uncertain. The objective of this study was to evaluate the correlation between the body mass index (BMI) and clinicopathological features of thyroid cancer patients. METHODS: From January 2009 to April 2010, 716 consecutive patients (602 females and 114 males; mean age 47.02 ± 11.73 years) with papillary thyroid cancer (PTC) were analyzed retrospectively. Patients were divided into two subgroups according to age (<45 years, ≥45 years). The BMI groupings were based on standardized categories set by the World Health Organization. The relationships between the BMI and these parameters were assessed. RESULTS: A non-overweight BMI was associated with a younger age and female gender. Tumor multiplicity was related to a higher BMI. In an age-related subgroup analysis, a higher BMI was correlated with more lymph node involvement (p = 0.004), lymphatic invasion (p = 0.003) and tumor multiplicity (p = 0.008) in patients ≥45 years of age. The absence of an association between the BMI and T stage, nodal status, vascular invasion, lymphatic invasion, and extrathyroidal extension was noted in a statistical analysis. In the subgroup of patients <45 years of age, no positive associations were observed between the BMI and any parameters other than age and sex. CONCLUSIONS: In PTC patients ≥45 years of age, a higher BMI was associated with more aggressive tumor features, such as lymph node metastasis, lymphatic invasion, and tumor multiplicity.

Portulaca oleracea extracts protect human keratinocytes and fibroblasts from UV-induced apoptosis.

Portulaca oleracea extracts, known as Ma Chi Hyun in the traditional Korean medicine, show a variety of biomedical efficacies including those in anti-inflammation and anti-allergy. In this study, we investigate the protective activity of the P. oleracea extracts against UVB-induced damage in human epithelial keratinocytes and fibroblasts by several apoptosis-related tests. The results suggest that P. oleracea extracts have protective effects from UVB-induced apoptosis.

Efficacy of fluorescence diagnosis-guided Mohs micrographic surgery for pigmented vs non-pigmented basal cell carcinoma.

Pigmented basal cell carcinoma (PBCC) occurs more frequently in Asian population. The efficacy of fluorescence diagnosis (FD) for PBCCs treated with Mohs micrographic surgery has not yet been determined. This study enrolled 255 patients with 258 biopsy-proven BCC lesions: 199 PBCCs (77.1%) and 59 non-PBCCs (22.9%). We compared the clinicopathological and surgical features of the PBCCs and non-PBCCs. Each group was divided into 2 sub-groups, those assessed and not assessed by FD, to retrospectively analyse surgical features. Aggressive histological subtypes were less prevalent in PBCCs than in non-PBCCs. PBCCs required significantly fewer stages of Mohs excision, with significantly smaller surgical margins and surgical depth, than non-PBCCs. FD did not confer any benefits on PBCCs during Mohs micrographic surgery. However, non-PBCCs assessed by FD required significantly fewer Mohs stages, with significantly smaller surgical margins, than lesions not assessed by FD. These findings suggest that FD should be performed before Mohs micrographic surgery to delineate the margins of non-PBCCs in Asians.

Added value of ultrasound re-evaluation for patients with equivocal CT findings of acute appendicitis: a preliminary study.

PURPOSE: To prospectively estimate the additional diagnostic value of ultrasound (US) re-evaluation for patients with equivocal computed tomography (CT) findings of acute appendicitis. METHODS: Between April 2011 and October 2011, 869 consecutive patients with suspected appendicitis who were referred for CT were included. The likelihood of appendicitis was prospectively categorized into five categories. US re-evaluation was recommended for patients in the 'equivocal appendix' and 'probably not appendicitis' groups. The overall negative appendectomy rate during the study period was compared with the rate of the previous year, and negative appendectomy rates of the US and non-US evaluation groups were also compared. RESULTS: Among 869 patients, 71 (8.2 %) had equivocal appendicitis findings and 63 (7.2 %) were diagnosed as probably not appendicitis. The sensitivity and specificity of CT combined with US re-evaluation group (100 % and 98.1 %, respectively) exceeded those of the CT alone group (93 % and 99 %; equivocal group considered as negative appendicitis, 100 % and 89.9 %; as positive, respectively, P < 0.0001). After adding US re-evaluation, the overall negative appendectomy rate in our institution decreased from 3.4 to 2.3 %. CONCLUSION: For patients with equivocal CT findings of acute appendicitis, US re-evaluation can improve diagnostic accuracy and decrease the rate of negative appendectomies. KEY POINTS: • Misdiagnosis of appendicitis still occurs, especially in patients with equivocal radiological findings. • The sensitivity and specificity of CT followed by US exceeded those of CT alone. • After US re-evaluation, the negative appendectomy rate decreased from 3.4 to 2.3 %. • US re-evaluation in equivocal cases helps diagnostic confidence and further management.

Efficacy of photodynamic diagnosis-guided Mohs micrographic surgery in primary squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) usually has ill-defined margins because of its irregular invasive patterns. OBJECTIVE: To evaluate the surgical efficacy of photodynamic diagnosis (PDD) in primary cSCC treated using Mohs micrographic surgery (MMS). METHODS & MATERIALS: We examined 67 cases of biopsy-proven primary facial cSCC treated with MMS. The 67 SCC were divided into the two groups depending on PDD application: PDD group (n = 38, 56.7%) and non-PDD group (n = 29, 43.3%). We analyzed the differences in surgical features between the PDD and non-PDD groups. RESULTS: The PDD group required fewer Mohs stages (1.37 vs 1.83, p = .02) and smaller surgical margins (8.03 vs 11.24 mm, p = .03). PDD showed additional benefits in terms of surgical margin and Mohs stage, especially in low-risk SCC, including thin (≤4 mm), small (≤20 mm), well-differentiated, and nonulcerative tumors (p < .05) but did not show beneficial effects in high-risk SCC (p > .05) during MMS. CONCLUSION: PDD can increase surgical efficacy of primary cSCC during MMS. These benefits are more pronounced in low-risk SCC. We recommend PDD as a simple and useful technique for delineating the margins of low-risk SCC before MMS.

Tinea incognito in Korea and its risk factors: nine-year multicenter survey.

Tinea incognito (TI) is a dermatophytic infection which has lost its typical clinical appearance because of improper use of steroids or calcineurin inhibitors. The incidence of TI is increasing nowadays. We conducted retrospective review on 283 patients with TI from 25 dermatology training hospitals in Korea from 2002-2010 to investigate the demographical, clinical, and mycological characteristics of TI, and to determine the associated risk factors. More than half (59.3%) patients were previously treated by non-dermatologists or self-treated. The mean duration of TI was 15.0 ± 25.3 months. The most common clinical manifestations were eczema-like lesion, psoriasis-like, and lupus erythematosus-like lesion. The trunk and face were frequently involved, and 91 patients (32.2%) also had coexisting fungal infections. Among 67 isolated strains, Trichophyton rubrum was the most frequently detected (73.1%). This is the largest study of TI reported to date and the first investigational report concerning TI in Korea. We suggest that doctors should consider TI when a patient has intractable eczema-like lesions accompanied by tinea pedis/unguium. Furthermore, there should be a policy change, which would make over-the-counter high-potency topical steroids less accessible in some countries, including Korea.

Refractory Bullous Pemphigoid Successfully Treated with Reslizumab: A Possible Novel Therapeutic Modality.

Bullous pemphigoid (BP) is a chronic, autoimmune blistering disease that has concerning morbidity and mortality rates. Recently, several studies have focused on eosinophils due to their significant role in the pathogenesis of BP, considering that they are ubiquitous in the serum, tissue, and blister fluids of patients with BP. With this context, precision therapy that targets mediators of eosinophil activity could be a possible novel therapeutic strategy. Interleukin (IL)-5 is crucial for B-cell maturation, which consequently results in immunoglobulin production, and promotes eosinophil differentiation, proliferation, and activation. To our best knowledge, reslizumab has not yet been reported to treat BP. Herein, we report a case of steroid- and omalizumab-resistant BP treated successfully using reslizumab. Our data suggest that IL-5 could be a novel specific biologic target within the entire immunopathogenesis of BP, and reslizumab would be a novel therapeutic modality.

Missense Variant c.3301C>T (p.R1101W) in von Willebrand Factor A Sequence in a Patient with Recessive Dystrophic Epidermolysis Bullosa Pruriginosa with Compound Heterozygous COL7A1 Variants.

Dystrophic epidermolysis bullosa (DEB) pruriginosa is a rare subtype of DEB characterized by multiple, violaceous, and severe pruritic lichenified nodules along with blisters. Here, we report the case of a Korean male who, since the age of 3 years, had multiple pruritic nodules with blisters on both lower extremities. Genetic testing is required to diagnose DEB pruriginosa because its clinical and histologic features are inconclusive. We identified compound heterozygous COL7A1 variants of c.5797C>T (p.R1933*) and c.3301C>T (p.R1101W) in the patient, leading to a diagnosis of recessive DEB pruriginosa. Among the variants identified, c.3301C>T is a novel missense variant that has not been reported previously. This variant is in exon 26, which encodes von Willebrand factor A (vWFA) in collagen type VII. vWFA is known to preserve normal dermal structures by interacting with dermal collagens and basement membranes. Considering that this variant contradicts the general concept that autosomal dominant inheritance is more common and that variants typically occur in the triple helical collagenous domain of COL7A1 in DEB pruriginosa, we focus on the rarity of this case and the possible pathogenic role of the c.3301C>T (p.R1101W) variant.

Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models.

BACKGROUND: Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4-O-methylhonokiol, a constituent of Magnolia officinalis, on memory deficiency caused by LPS, along with the underlying mechanisms. METHODS: We investigated whether 4-O-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 µg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-O-methylhonkiol (0.5, 1 and 2 µM). RESULTS: Oral administration of 4-O-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-O-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In in vitro study, we also found that 4-O-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-1ß in the LPS-stimulated cultured astrocytes. 4-O-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4-O-methylhonokiol inhibited LPS-induced Aß1-42 generation, ß- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells. CONCLUSION: These results suggest that 4-O-methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4-O-methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.

Comparison of surgical outcomes between endoscopic and robotic thyroidectomy.

OBJECTIVES: Gasless transaxillary endoscopic thyroidectomy offers a distinct advantage over the conventional open operation because it leaves no visible neck scar. Indications have expanded with the development of new surgical techniques and instruments. However, because of the two-dimensional view and the nonflexible instruments, this procedure is not easily amenable for total thyroidectomy. So, robotic surgery has been introduced and offers improved visualization and dexterity. But, it remains unclear whether robotic thyroidectomy offers any potential benefits over endoscopic thyroidectomy. The aim of this present study was to determine whether robotic surgery is superior to endoscopic surgery through a comparison of surgical outcomes. METHODS: Between May 2009 and February 2011, 165 patients underwent endoscopic thyroidectomy (endoscopy group) and 46 patients underwent robotic thyroidectomy (robot group). A gasless transaxillary approach was used in both groups. The two groups were compared in terms of patient characteristics, perioperative clinical results, pathologic findings, and postoperative complication. RESULTS: Both patient groups were similar in terms of patient characteristics, mean number of retrieved central lymph nodes, pathological features, length of hospital stays, postoperative complication rate, and serum Tg level. However, the mean total operation time for thyroidectomy was 126.2 ± 37.84 min in the endoscopy group and 179.6 ± 44.34 min in the robot group (P < 0.001). Postoperative total drainage for lobectomy was 153.3 ± 45.64 for the endoscopy group and 179.9 ± 49.15 for the robot group (P = 0.031). Cost effectiveness is also an important consideration when evidence for predominance of two surgical techniques is lacking. The mean cost of robotic thyroidectomy was $6,655, compared with $829 for endoscopic thyroidectomy (P < 0.001). There was no significant difference in postoperative complications as hypocalcemia, recurrent laryngeal nerve injury, chyle leakage and tracheal injury in the two groups (P = 0.332). CONCLUSION: Robotic thyroidectomy was lengthier in duration than endoscopic thyroidectomy, more costly, and associated with increased postoperative drainage with no improvement in oncologic outcomes or complication rates. Therefore our data do not support any advantage of robotic surgery over endoscopic surgery.