Clinical manifestations of human Mpox infection: A systematic review and meta-analysis.

Little is known about the ongoing monkeypox (mpox) outbreak, and the clinical features of mpox in patients worldwide have not been rigorously analysed. Thus, we aimed to investigate the clinical features associated with mpox infection and understand the pathophysiology and characteristics of the disease. For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and the Cochrane Database of Systematic Reviews for articles published till 16 September 2022. We used a random effects model to calculate the pooled prevalence and 95% confidence interval (CI). We used the I2 statistic to assess heterogeneity, Egger's test to assess publication bias, 95% prediction interval to determine the level of uncertainty, and the Newcastle-Ottawa Scale and Joanna Briggs Institute quality assessment tool to assess the risk of bias. Twenty-six relevant articles from 19 countries across 5 continents were included, and data on 5472 mpox patients with 18 unique features were analysed. The pooled prevalence of clinical features of mpox were rash (85.7%, 95% CI: 68.3-94.3; k = 21), chills (77.8%, 95% CI: 70.5-83.7; k = 3), and fever (62.3%, 95% CI: 51.3-71.6; k = 25), lymphadenopathy (58.6%, 95% CI: 47.2-69.2; k = 21), lethargy or exhaustion (46.8%, 95% CI: 30.7-63.5; k = 14), pruritus (40.6%, 95% CI: 28.5-54.0; k = 5), myalgia (36.0%, 95% CI: 24.3-49.7; k = 16), headache (34.6%, 95% CI: 23.4-47.8; k = 17), skin ulcer (31.1%, 95% CI: 18.6-47.1; k = 7), abdomen symptom (24.2%, 95% CI: 17.9-31.9; k = 11), pharyngitis (23.0%, 95% CI: 12.7-37.9; k = 14), respiratory symptom (19.5%, 95% CI: 6.8-44.6; k = 6), nausea or vomiting (13.0%, 95% CI: 4.6-31.9; k = 3), scrotal or penile oedema (10.7%, 95% CI: 6.3-17.7; k = 4), conjunctivitis (7.1%, 95% CI: 2.4-18.9; k = 6), and death (0.9%, 95% CI: 0.4-2.0; k = 26). This is the first international and comprehensive study to examine all clinical presentations of human mpox infection. Our systematic review proposes a comprehensive understanding of the current mpox outbreak and may serve as key data for future studies on the pathological mechanisms and epidemiology of mpox infections.

Quantifying Risk Factors for Slipped Capital Femoral Epiphysis and Postslip Osteonecrosis.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a disorder of the proximal femoral physis occurring in late childhood and adolescence. Previously postulated risk factors include obesity and endocrinopathies. The purpose of this investigation was to identify risk factors for developing SCFE, as well as postslip osteonecrosis (ON), among the United States pediatric population. METHODS: A national database investigation was performed using PearlDiver Technologies, Inc., queried for SCFE and ON using International Classification of Disease codes (2010 to 2020). Regression analyses to determine the risk of developing a SCFE, and ON after a patient has already been diagnosed with a SCFE ("postslip"). Propensity matching between SCFE and control groups generated a pseudo-randomization model to compare the relative risk. RESULTS: There were 11,465 patients with SCFE available in the database, matched with 134,680 controls. After matching, vitamin D deficiency, obesity, hypothyroidism, and growth hormone use were risk factors for developing SCFE [relative risk ranges from 1.42 (95% CI: 1.21-1.39, vitamin D deficiency) to 3.45 (95% CI: 3.33-3.57, obesity)]. ON risk factors were vitamin D deficiency [1.65 (1.26-2.14)] and hypothyroidism [1.49 (1.10-2.07)]. CONCLUSIONS: This United States national database study quantified risk factors of developing an SCFE and postslip ON. Obesity is the most significant risk factor for the development of a slip, but not ON. Growth hormone use, hypothyroidism, and vitamin D deficiency are also risk factors for SCFE development, whereas only the latter two were associated with ON. These findings demonstrate the public health implications of obesity and comorbid conditions in pediatric hip pathology. LEVEL OF EVIDENCE: Level III.

Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976-2022: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Owing to 2018 expanded diagnostic criteria for eosinophilic esophagitis (EoE) and thus a possible increase in diagnosis, previous studies on the global incidence and prevalence of EoE may need to be updated. We aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2022 and analyze their associations with geographic, demographic, and social factors through a systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from their inception dates to December 20, 2022, for studies that reported the incidence or prevalence of EoE in the general population. We calculated the global incidence and prevalence of EoE using pooled estimates with 95% confidence intervals (CIs) and performed subgroup analysis based on age, sex, race, geographical area, World Bank income group, and diagnostic criteria of EoE. RESULTS: Forty studies met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents. The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years (95% CI, 3.98-6.63; number of studies, 27; sample population, 42,191,506) and 40.04 cases per 100,000 inhabitant-years (95% CI, 31.10-48.98; number of studies, 20; sample population, 30,467,177), respectively. The pooled incidence of EoE was higher in high-income countries (vs low- or middle-income countries), males, and North America (vs Europe and Asia). The global prevalence of EoE followed a similar pattern. The pooled prevalence of EoE gradually increased from 1976 to 2022 (1976-2001; 8.18; 95% CI, 3.67-12.69 vs 2017-2022; 74.42; 95% CI, 39.66-109.19 cases per 100,000 inhabitant-years). CONCLUSIONS: The incidence and prevalence of EoE have increased substantially and vary widely across the world. Further research is needed to evaluate the incidence and prevalence of EoE in Asia, South America, and Africa.

National trends in physical activity among adolescents in South Korea before and during the COVID-19 pandemic, 2009-2021.

With the ongoing COVID-19 pandemic, several previous studies from different countries showed that physical activity (PA) decreased during the COVID-19 outbreak. However, few studies have examined the recent tendency of PA in the adolescent population. Thus, we aimed to investigate the long-term trend of PA in Korean youth and the prevalence changes between before and during the COVID-19 pandemic. Data from Korea Youth Risk Behavior Web-Based Survey (KYRBS) was collected for consecutive years between 2009 and 2021. The period was separated into prepandemic (2009-2019), early-pandemic (2020), and mid-pandemic (2021). Self-reported amount of PA was categorized into four groups (insufficient, aerobic, muscle strengthening, and both physical activities) according to World Health Organization (WHO) PA guidelines. A total of 840 488 adolescents aged 12-18 who fully responded to the survey were selected (response rate: 95.2%). The 13-year trends in the proportion of adolescents who reported aerobic and muscle-strengthening activities met or exceeded 2020 WHO exercise guidelines for adolescents plateaued (11.9% from 2009 to 2011, 14.2% from 2018 to 2019, 14.4% from 2020, and 14.0% from 2021); however, the slope decreased during the pandemic (ßdiff , -0.076; 95% confidence interval [CI], -0.123 to -0.029). Proportion of sufficient aerobic exercise among adolescents sharply decreased midst the pandemic (28.0% from 2009 to 2011, 29.4% from 2018 to 2019, and 23.8% from 2020; ßdiff , -0.266; 95% CI, -0.306 to -0.226) but increased again in 2021 (26.0% from mid-COVID 19; 95% CI, 25.4-26.7). Similar patterns were observed in Metabolic Equivalent Task (MET) score (MET-min/week; 804.1 from 2018 to 2019, 720.9 from 2020, and 779.6 from 2021). The mean difference in MET score between pre-COVID and post-COVID was -55.4 MET-min/week (95% CI, -70.5 to -40.3). Through a nationwide representative study, there was no significant difference with regard to the number of Korean adolescents who achieved the PA guidelines (pre and postpandemic); however, the prevalence of recommended levels of PA needs to increase more based on the trend before the COVID-19 outbreak. The findings of this study suggest reinforcement of the importance of public health policies for Korean youths to be more physically active, especially during and after the pandemic.

How Do Standing Neutral, Supine Lateral, Standing Flexion, and Standing Extension Radiographs Compare in Detecting the Presence and Magnitude of Stable and Dynamic Spondylolisthesis?

BACKGROUND: Clinical guidelines recommend standing radiographs as the most appropriate imaging for detecting degenerative spondylolisthesis, although reliable evidence about the standing position is absent. To our knowledge, no studies have compared different radiographic views and pairings to detect the presence and magnitude of stable and dynamic spondylolisthesis. QUESTIONS/PURPOSES: (1) What is the percentage of new patients presenting with back or leg pain with stable (3 mm or greater listhesis on standing radiographs) and dynamic (3 mm or greater listhesis difference on standing-supine radiographs) spondylolisthesis? (2) What is the difference in the magnitude of spondylolisthesis between standing and supine radiographs? (3) What is the difference in the magnitude of dynamic translation among flexion-extension, standing-supine, and flexion-supine radiographic pairs? METHODS: This cross-sectional, diagnostic study was performed at an urban, academic institution between September 2010 and July 2016; 579 patients 40 years or older received a standard radiographic three-view series (standing AP, standing lateral, and supine lateral radiographs) at a new patient visit. Of those individuals, 89% (518 of 579) did not have any of the following: history of spinal surgery, evidence of vertebral fracture, scoliosis greater than 30°, or poor image quality. In the absence of a reliable diagnosis of dynamic spondylolisthesis using this three-view series, patients may have had flexion and extension radiographs, and approximately 6% (31 of 518) had flexion and extension radiographs. A total of 53% (272 of 518) of patients were female, and the patients had a mean age of 60 ± 11 years. Listhesis distance (in mm) was measured by two raters as displacement of the posterior surface of the superior vertebral body in relation to the posterior surface of the inferior vertebral body from L1 to S1; interrater and intrarater reliability, assessed with intraclass correlation coefficients, was 0.91 and 0.86 to 0.95, respectively. The percentage of patients with and the magnitude of stable spondylolisthesis was estimated on and compared between standing neutral and supine lateral radiographs. The ability of common pairs of radiographs (flexion-extension, standing-supine, and flexion-supine) to detect dynamic spondylolisthesis was assessed. No single radiographic view or pair was considered the gold standard because stable or dynamic listhesis on any radiographic view is often considered positive in clinical practice. RESULTS: Among 518 patients, the percentage of patients with spondylolisthesis was 40% (95% CI 36% to 44%) on standing radiographs alone, and the percentage of patients with dynamic spondylolisthesis was 11% (95% CI 8% to 13%) on the standing-supine pair. Standing radiographs detected greater listhesis than supine radiographs did (6.5 ± 3.9 mm versus 4.9 ± 3.8 mm, difference 1.7 mm [95% CI 1.2 to 2.1 mm]; p < 0.001). Among 31 patients, no single radiographic pairing identified all patients with dynamic spondylolisthesis. The listhesis difference detected between flexion-extension was no different from the listhesis difference detected between standing-supine (1.8 ± 1.7 mm versus 2.0 ± 2.2 mm, difference 0.2 mm [95% CI -0.5 to 1.0 mm]; p = 0.53) and flexion-supine (1.8 ± 1.7 mm versus 2.5 ± 2.2 mm, difference 0.7 mm [95% CI 0.0 to 1.5]; p = 0.06). CONCLUSION: This study supports current clinical guidelines that lateral radiographs should be obtained with patients in the standing position, because all cases of stable spondylolisthesis of 3 mm or greater were detected on standing radiographs alone. Each radiographic pair did not detect different magnitudes of listhesis, and no single pair detected all cases of dynamic spondylolisthesis. Clinical concern for dynamic spondylolisthesis may justify standing neutral, supine lateral, standing flexion, and standing extension views. Future studies could identify and evaluate a set of radiographic views that provides the greatest capacity to diagnose stable and dynamic spondylolisthesis. LEVEL OF EVIDENCE: Level III, diagnostic study.

The Potential of Campanula takesimana Callus Extract to Enhance Skin Barrier Function.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by epidermal barrier dysfunction and Th2-skewed inflammation. Campanula takesimana (C. takesimana), a Korean endemic plant grown on Ulleng Island, has long been associated with a traditional alternative medicine for asthma, tonsillitis, and sore throat. In this study, we reported the effect of C. takesimana callus extract on upregulating epidermal barrier-related proteins dysregulated by Th2 cytokines. C. takesimana callus extract induced the expression of skin barrier proteins, such as filaggrin, claudin-1, and zonula occludens-1, in both human primary keratinocytes and Th2-induced AD-like skin-equivalent models. Additionally, RNA sequencing analysis demonstrated that C. takesimana callus extract partially restored Th2 cytokine-induced dysregulation of the epidermal development and lipid metabolic pathways. Considering the advantages of callus as a sustainable eco-friendly source of bioactive substances, and its effect on skin barrier proteins and lipid metabolic pathways, C. takesimana callus extracts can possibly be utilized to improve the integrity of the skin barrier.

Severe atopic dermatitis and concurrent severe hidradenitis suppurativa successfully treated with dupilumab.

We report a clinical experience of treating concomitant atopic dermatitis and hidradenitis suppurativa (HS) with dupilumab. This report is particularly noticeable in terms of disease severity and treatment duration compared to previous reported cases, suggesting long-term dupilumab therapy can contribute to disease control even in patients with severe HS.

Utility of upright radiographs in traumatic thoracolumbar fracture management.

BACKGROUND: It is common practice to use a combination approach of computed tomography (CT) scan followed by upright radiographs when assessing traumatic thoracolumbar (TL) vertebral fractures. The purpose of this study was to determine the clinical utility of upright spine radiographs in the setting of traumatic TL fracture management. Our null hypothesis is that upright TL radiographs rarely change management of acute vertebral fractures. METHODS: A retrospective study was performed on patients with an initial plan of non-operative management for a TL fracture between January 2014 and June 2020 at a single Level 1 trauma center. Patients were followed from time of initial consult to either conversion to surgery (operative) or last available outpatient follow up imaging (non-operative). Lateral kyphotic angle of the fractured vertebra and anterior vertebral body height% loss on initial CT, first upright radiograph, and endpoint upright radiograph imaging were measured. Measurements were compared between and within operative and non-operative groups using t-tests and Mann-Whitney U tests when appropriate. P-values ≤ 0.05 were considered statistically significant. RESULTS: The study included 70 patients with an average age of 54 years and 37 (52.9%) were women. Six (8.6%) of 70 patients had a change from non-operative to operative management based on upright radiographs. The mean (standard deviation) change in degrees of kyphosis from CT scan to first X-ray was 4.6 (7.0) in the non-operative group and 11.5 (8.1) in the operative group (P = 0.03). Delta degrees of kyphosis from CT scan to endpoint X-ray was 6.4 (9.0) and 16.2 (6.2) in the non-operative and operative groups, respectively (P = 0.01). In the operative group, mean degrees of kyphosis increased from 1.6 (7.6) in initial CT to 13.1 (8.9) in first X-ray (P = 0.02). First X-ray mean anterior body height% loss was 37.5 (17.6) and 53.2 (16.1) in the non-operative and operative groups, respectively (P = 0.04). CONCLUSIONS: Upright radiographs are useful in guiding traumatic vertebral fracture management decisions. Larger studies are needed to determine the degree of change in kyphosis between CT and first standing radiograph that is suggestive of operative management. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Not applicable.

CRISPR/Cas9-based targeted genome editing for correction of recessive dystrophic epidermolysis bullosa using iPS cells.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin disorder caused by mutations in the COL7A1 gene encoding type VII collagen (C7). The spectrum of severity depends on the type of mutation in the COL7A1 gene. C7 is the major constituent of anchoring fibrils (AFs) at the basement membrane zone (BMZ). Patients with RDEB lack functional C7 and have severely impaired dermal-epidermal stability, resulting in extensive blistering and open wounds on the skin that greatly affect the patient's quality of life. There are currently no therapies approved for the treatment of RDEB. Here, we demonstrated the correction of mutations in exon 19 (c.2470insG) and exon 32 (c.3948insT) in the COL7A1 gene through homology-directed repair (HDR). We used the clustered regulatory interspaced short palindromic repeats (CRISPR) Cas9-gRNAs system to modify induced pluripotent stem cells (iPSCs) derived from patients with RDEB in both the heterozygous and homozygous states. Three-dimensional human skin equivalents (HSEs) were generated from gene-corrected iPSCs, differentiated into keratinocytes (KCs) and fibroblasts (FBs), and grafted onto immunodeficient mice, which showed normal expression of C7 at the BMZ as well as restored AFs 2 mo postgrafting. Safety assessment for potential off-target Cas9 cleavage activity did not reveal any unintended nuclease activity. Our findings represent a crucial advance for clinical applications of innovative autologous stem cell-based therapies for RDEB.

A Michael Acceptor Analogue, SKSI-0412, Down-Regulates Inflammation and Proliferation Factors through Suppressing Signal Transducer and Activator of Transcription 3 Signaling in IL-17A-Induced Human Keratinocyte.

The activation of signal transducer and activator of transcription 3 (STAT3), as well as up-regulation of cytokines and growth factors to promote STAT3 activation, have been found in the epidermis of psoriatic lesions. Recently, a series of synthetic compounds possessing the Michael acceptor have been reported as STAT3 inhibitors by covalently binding to cysteine of STAT3. We synthesized a Michael acceptor analog, SKSI-0412, and confirmed the binding affinity between STAT3 and SKSI-0412. We hypothesized that the SKSI-0412 can inhibit interleukin (IL)-17A-induced inflammation in keratinocytes. The introduction of IL-17A increased the phosphorylation of STAT3 in keratinocytes, whereas the inactivation of STAT3 by SKSI-0412 reduced IL-17A-induced STAT3 phosphorylation and IκBζ expression. In addition, human ß defensin-2 and S100A7, which are regulated by IκBζ, were significantly decreased with SKSI-0412 administration. We also confirmed that SKSI-0412 regulates cell proliferation, which is the major phenotype of psoriasis. Based on these results, we suggest targeting STAT3 with SKSI-0412 as a novel therapeutic strategy to regulate IL-17A-induced psoriatic inflammation in keratinocytes.

Administration of encapsulated L-tryptophan improves duodenal starch digestion and increases gastrointestinal hormones secretions in beef cattle.

OBJECTIVE: This study investigated the effects of oral administration of rumen-protected L-tryptophan (RPL-T) on duodenal starch digestion and gastrointestinal hormones (GIH) secretions using Hanwoo beef steers as the animal models. METHODS: Four steers (423±24 kg) fitted with ruminal and duodenal cannulas were employed in a crossover design replicated twice. Treatments were control (basal diet) and RPL-T (basal diet+191.1 mg/kg body weight [BW]) group. Blood and duodenal samples were collected to measure serum GIH levels and pancreatic α-amylase activity at day 0, 1, 3, and 5 (-30, 30, 90, 150, and 210 min) of the study. Samples from each segment of the gastrointestinal tract were collected via ruminal and duodenal cannulas and were used to determine soluble protein and the starch digestion rate at days 6 (-30, 180, 360, and 540 min) and 8 (-30, 90, 270, and 450 min) of the experiment. RESULTS: No significant difference in ruminal pH, NH3-N, and total volatile fatty acid including the levels of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, and the acetate-to-propionate ratio was observed between groups (p>0.05). Crude protein uptake was higher and feces starch content was lower in RPL-T group than the control group (p<0.05). The D-glucose contents of feces in RPL-T group decreased at day 5 compared to those in the control group (p<0.05), however, no change was found at day 0, 1, or 3 compared to the control group (p>0.05). Serum cholecystokinin (CCK), melatonin, duodenal pancreatic α-amylase activity, and starch digestion were significantly higher in RPL-T group than the control group (p<0.05). CONCLUSION: Taken together, oral administration of RPL-T at the rate of 191.1 mg/kg BW consistently increased CCK concentration, pancreatic α-amylase activity in duodenal fluids, and starch digestion rate in the small intestine and thus found to be beneficial.

Lower Urinary Tract Symptoms and Urinary Bother Are Common in Patients Undergoing Elective Cervical Spine Surgery.

BACKGROUND: Lower urinary tract symptoms (LUTS) and urinary bother have been reported in adults undergoing surgery and have been associated with urinary tract infections, longer hospital stays, increased surgical costs, and decreased patient satisfaction. Previous reports indicate that up to one in two patients with lumbar spine pathology have moderate-to-severe LUTS, but little is known about LUTS in patients with cervical spine conditions. QUESTIONS/PURPOSES: (1) What is the prevalence of moderate-to-severe LUTS and clinically relevant urinary bother among patients undergoing elective cervical spine surgery? (2) Does the presence of myelopathy affect frequency of moderate-to-severe LUTS or clinically relevant urinary bother among patients undergoing elective cervical spine surgery? (3) Do MRI findings of spinal cord injury or compression correlate with presence and severity of LUTS? METHODS: We performed a cross-sectional study using clinical data collected from adult patients undergoing elective cervical spine surgery. Over an approximately 30-month period, we approached all patients who were evaluated in the preoperative clinic before undergoing elective cervical spine surgery. Of the 257 approached, 242 participated (94%). Study participants ranged in age from 34 to 83 years with a mean age of 58 years (SD 12). There were 108 males (45%) and 134 females (55%). A validated questionnaire, the International Prostate Symptom Score (IPSS), was used to identify LUTS. The IPSS score ranges from 0 to 35 points with LUTS presence defined as a score of ≥ 8 and LUTS severity categorized as mild (IPSS 0-7), moderate (IPSS 8-19), or severe (IPSS 20-35). Quality of life resulting from urinary bother is scored 0 to 6 with scores ≥ 4 considered clinically relevant urinary bother. Patients were grouped into a myelopathy group and a nonmyelopathy group based on diagnosis as assigned by the operating surgeon. MRIs were analyzed by one spine surgeon to identify the presence of cord signal, number of levels with cord compression (mm), and a calculated compression ratio score with cord compression and with compression ratio among patients with myelopathy. RESULTS: The prevalence of moderate LUTS in our patient sample was 40% (97 of 242; 95% confidence interval [CI], 34%-47%). The prevalence of severe LUTS in our patient sample was 8% (19 of 242; 95% CI, 5%-12%). Clinically relevant urinary bother was reported in 18% of patients (41 of 228; 95% CI, 13%-24%). After adjustment for age and sex, the odds of moderate-to-severe LUTS among patients with myelopathy was greater than that observed in patients without myelopathy (adjusted odds ratio, 2.0; p = 0.015). The prevalence of clinically relevant urinary bother was higher in patients with myelopathy (30% [26 of 88]) compared with those with no myelopathy (11% [15 of 140]; p < 0.001). With the numbers available, among patients with myelopathy, there was no difference in distribution of LUTS symptom severity or IPSS score according to cord signal presence (50% [23 of 46]) and absence (65% [31 of 48]; p = 0.153), number of levels with compression (70% [seven of 10 with four levels]; 59% [13 of 22 with three levels]; 51% [19 of 37] with two levels; and 60% [15 of 25] with one level; p = 0.730), millimeters of cord compression (r = 0.02; p = 0.854), or compression ratio (r = 0.09; p = 0.413). CONCLUSIONS: Nearly half of all patients undergoing elective cervical spine surgery had moderate-to-severe LUTS. This is more than double the prevalence that has been reported in a community-dwelling adult population. These symptoms can impair quality of life, lead to surgical complications (urinary retention or incontinence), and may be mistaken for cauda equina, prompting potentially unnecessary imaging and studies. Given that urinary bother is reported less frequently than LUTS, patients may be less likely to seek care for urinary symptoms before undergoing surgery. Therefore, it is important to increase provider awareness of the high prevalence of LUTS. LEVEL OF EVIDENCE: Level III, prognostic study.

Comparative Effects of Topical 0.2% Sirolimus for Angiofibromas in Adults and Pediatric Patients with Tuberous Sclerosis Complex.

BACKGROUND: Recent reports have suggested that the topical formulation of sirolimus is effective in treating facial angiofibromas in tuberous sclerosis complex (TSC). Here, we determined the safety and efficacy of 0.2% topical sirolimus for the treatment of facial angiofibroma and compared its effects based on age. METHOD: This was a retrospective study which involved 36 TSC patients with facial angiofibromas who were treated with 0.2% sirolimus ointment. Its effect was evaluated using the Facial Angiofibroma Severity Index (FASI). In order to observe its comparative effect based on patient age, a subgroup analysis was performed, between the adult group (> 18 years old) and the pediatric group (≤18 years old). RESULTS: The total FASI as well as its subcategories (erythema, size, and extent) showed statistically significant improvements after the topical treatment with 0.2% sirolimus ointment (FASI before treatment: 7.2 ± 1.1, FASI after treatment: 4.4± 1.4, p < 0.001). Among the subcategories of FASI, the erythema was most significantly reduced with the fastest response to the treatment. In a subgroup analysis, the pediatric group showed significantly greater improvements in FASI (improvement of FASI in the pediatric group = 49.7 ± 12.2%, adult group = 27.9 ± 15.6%, p < 0.001). The serial improvement analysis also showed that the pediatric group achieved a consistently greater improvement in FASI at all visits. Its 1-year application in 3 patients demonstrated a continuous maintenance effect. No significant adverse effects were observed. CONCLUSION: 0.2% sirolimus ointment is safe and effective for facial angiofibromas. Considering its higher efficacy in younger patients, an early initiation of the treatment is recommended.

Effects of dietary phytoncides extracted from Korean pine (Pinus koraiensis) cone on performance, egg quality, gut microflora, and immune response in laying hens.

This study was conducted to evaluate the effects of dietary phytoncides extracted from discarded Korean pine cones (Pinus koraiensis) on the performance, egg quality, immune response and gut microflora in laying hens. A total of 400 Hy-Line brown laying hens (50-week old) were allotted into four dietary treatments including a control diet or a diet supplemented with phytoncides at 0.002%, 0.004% and 0.008%. During the 6 weeks of experimental feeding, 0.008% of dietary phytoncides improved egg production, feed conversion ratio (p < 0.05), but not feed intake, egg weight or feed efficiency. Although dietary phytoncides had no effect on egg quality, decreases in Haugh units depending on storage periods were improved by 0.008% of dietary phytoncides (p < 0.05). To investigate the roles of dietary phytoncides on the alteration of the immune response during inflammation, lipopolysaccharide (LPS) or saline was intraperitoneally injected into 10 hens per diet group on the end date of the experimental feeding period. Serum immunoglobulins and splenic cytokine expression at mRNA levels were then measured at 4 hr postinjection. Although the levels of IgA were decreased by LPS injection in all dietary groups, dietary phytoncides at 0.008% showed a higher level of IgA by LPS (p < 0.05). Interestingly, although LPS injection resulted in an enhanced expression of proinflammatory cytokines such as IL-1ß and IL-6, dietary phytoncides at 0.008% showed less increased levels of them (p < 0.05). Gut microflora was examined from 10 hens per diet group at the end of the experimental period. While the number of Lactobacillus spp. was increased (p < 0.05), Escherichia coli counts in the cecal contents were decreased by 0.008% of dietary phytoncides. Taken together, these results demonstrate that dietary supplementation of 0.008% phytoncides improved the egg production, immune responses during inflammation and gut microflora in laying hens.