Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

PURPOSE: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. METHODS: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. RESULTS: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. CONCLUSION: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

Relationship between intraoperative requirement for anesthetics and postoperative analgesic consumption in laparoscopic colectomy: a randomized controlled double-blinded study.

BACKGROUND: This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. METHODS: The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. RESULTS: Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). CONCLUSIONS: The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

CRISPR-based editing strategies to rectify EYA1 complex genomic rearrangement linked to haploinsufficiency.

Pathogenic structure variations (SVs) are associated with various types of cancer and rare genetic diseases. Recent studies have used Cas9 nuclease with paired guide RNAs (gRNAs) to generate targeted chromosomal rearrangements, focusing on producing fusion proteins that cause cancer, whereas research on precision genome editing for rectifying SVs is limited. In this study, we identified a novel complex genomic rearrangement (CGR), specifically an EYA1 inversion with a deletion, implicated in branchio-oto-renal/branchio-oto syndrome. To address this, two CRISPR-based approaches were tested. First, we used Cas9 nuclease and paired gRNAs tailored to the patient's genome. The dual CRISPR-Cas9 system induced efficient correction of paracentric inversion in patient-derived fibroblast, and effectively restored the expression of EYA1 mRNA and protein, along with its transcriptional activity required to regulate the target gene expression. Additionally, we used CRISPR activation (CRISPRa), which leads to the upregulation of EYA1 mRNA expression in patient-derived fibroblasts. Moreover, CRISPRa significantly improved EYA1 protein expression and transcriptional activity essential for target gene expression. This suggests that CRISPRa-based gene therapies could offer substantial translational potential for approximately 70% of disease-causing EYA1 variants responsible for haploinsufficiency. Our findings demonstrate the potential of CRISPR-guided genome editing for correcting SVs, including those with EYA1 CGR linked to haploinsufficiency.

Emergence and genomic chion of Proteus mirabilis harboring blaNDM-1 in Korean companion dogs.

Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-ß-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a "one health approach".

Comparing quality of recovery and satisfaction between spinal anesthesia and nerve block in orthopedic below-knee surgery: A prospective controlled trial.

BACKGROUND: Postoperative quality of recovery (QoR) and patient satisfaction have gained increasing significance in medical services. This study aimed to compare these 2 parameters between 2 types of regional anesthetics (spinal anesthesia and combined sciatic-femoral nerve block) in orthopedic lower knee surgery. METHODS: A total of 101 patients were classified into 2 groups (combined sciatic-femoral nerve block, group N; spinal anesthesia, group S) according to patient preference. In group N, sciatic and femoral nerve blocks were performed on the popliteal and groin regions, respectively, under ultrasound guidance. Spinal anesthesia was performed in group S. The primary outcomes were QoR and patient satisfaction. QoR was measured using the Korean translation of the QoR-15K. Patient satisfaction was assessed using an 11-point Likert scale (0-10) and a dichotomous question addressing anesthesia preferences for future surgeries. RESULTS: The physical independence of the postoperative QoR-15K was significantly higher in group N than in group S (14.2 vs 12.0, P = .04). On the 11-point Likert scale, group N scored 8.8, and group S scored 7.8 (P = .001). In the dichotomous question, 93.8% of the group N and 52.8% of the group S answered that they would like to choose the same anesthesia method for the next surgery (P < .001). In addition, fewer participants in group N complained of backache than those in group S, and the time to first urination after anesthesia was shorter in group N than in group S (P = .004, <.001, respectively). CONCLUSION: Combined sciatic-femoral nerve block may provide better physical independence and satisfaction than spinal anesthesia in orthopedic below-knee surgeries.

Identification of maximal tumor size associated with negligible lymph node metastasis for endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND AND AIMS: When treating undifferentiated-type early gastric cancer (UD-EGC) that is limited to the mucosa (clinically T1a), endoscopic submucosal dissection (ESD) can be considered if the tumor is 2 cm or less and is not ulcerated. However, there is insufficient evidence to determine the relationships between tumor size and oncological safety of ESD in UD-EGC. METHODS: The pathology reports of Korean patients who were diagnosed with UD-EGC (n = 5286) were retrospectively reviewed. The cumulative incidence of lymph node metastasis (LNM) according to tumor size was evaluated in subgroups. The tumor-size cut-off was identified as the upper limit of the 95% confidence interval (CI) of cumulative LNM incidence that did not exceed 1.0%. RESULTS: We identified 1516 patients with non-ulcerated T1a tumors ≤2 cm in size. Among patients without lymphatic invasion, 1.5% (95% CI 0.91-2.16%) had LNM. In patients with poorly differentiated tubular adenocarcinoma (PD), LNM increased from 0 to 0.74% based on a tumor size of 1.0 cm. Regardless of tumor size, smaller percentages of undifferentiated-type (UD) and poorly cohesive carcinoma (PCC) patients experienced LNM than did those with PD. In non-ulcerated mucosal cancer without lymphatic invasion and tumor size ≤0.9 cm, no LNM was observed in patients with UD (95% CI 0-0.53%), PCC (95% CI 0-0.59%), or PD (95% CI 0-0.86%) histologic type. CONCLUSION: In patients diagnosed with non-ulcerated T1a UD-EGC, ESD can be performed if the tumor size is 0.9 cm or less, regardless of histologic type.

Predictors for Dexmedetomidine Requirement for Sedation under Regional Anesthesia.

(1) Background: This prospective observational study aimed to investigate the predictors affecting DMT requirements for sedation during regional anesthesia. (2) Method: A total of 108 patients who received regional anesthesia with intravenous DMT administration for orthopedic upper- or lower-extremity surgery were enrolled. Following successful regional anesthesia, DMT was administered at a rate of 4 µg/kg/h until reaching loss of consciousness (LOC). The administered dose of DMT per body weight until LOC (DMTLOC; µg/kg) was evaluated. The infusion was maintained at a rate of 0.2-0.7 µg/kg/h during the surgery. At the end of surgery, the elapsed time to a BIS value of 90 (TBIS90; s) was recorded. Linear regression models were used to identify potential predictors of DMTLOC and TBIS90. (3) Results: One hundred patients were analyzed. There were negative relationships between DMTLOC and age (r = -0.297, p = 0.003) and DMTLOC and body mass index (BMI) (r = -0.425, p < 0.001), respectively. Multiple linear regression models revealed that both increasing age and BMI were significantly related to DMTLOC (r2 = 0.259, p < 0.001), but those variables showed no association with TBIS90. (4) Conclusions: The results of this study suggest that initial loading of DMT should be carefully titrated to minimize risk in elderly and obese surgical populations.

Strategies for Overcoming Immune Evasion in Bladder Cancer.

Tumors intricately shape a highly immunosuppressive microenvironment, hampering effective antitumor immune responses through diverse mechanisms. Consequently, achieving optimal efficacy in cancer immunotherapy necessitates the reorganization of the tumor microenvironment and restoration of immune responses. Bladder cancer, ranking as the second most prevalent malignant tumor of the urinary tract, presents a formidable challenge. Immunotherapeutic interventions including intravesical BCG and immune checkpoint inhibitors such as atezolizumab, avelumab, and pembrolizumab have been implemented. However, a substantial unmet need persists as a majority of bladder cancer patients across all stages do not respond adequately to immunotherapy. Bladder cancer establishes a microenvironment that can actively hinder an efficient anti-tumor immune response. A deeper understanding of immune evasion mechanisms in bladder cancer will aid in suppressing recurrence and identifying viable therapeutic targets. This review seeks to elucidate mechanisms of immune evasion specific to bladder cancer and explore novel pathways and molecular targets that might circumvent resistance to immunotherapy.

Insufficient nutrient intake in individuals with disabling hearing loss and the restoration of nutritional sufficiency in hearing aid users.

Hearing loss affects some nutrient intake. Disabling hearing loss may exacerbate these issues. We aimed to evaluate nutrient intake and assess deficiencies based on functional hearing status. The study included 6907 participants with information on demographic factors, nutrient intake, weight, height, disease status, and hearing level in the eighth Korea National Health and Nutrition Examination Survey, conducted from 2019 to 2021. We categorized the participants into 3 groups based on their functional hearing status: bilateral hearing, unilateral hearing, and disabling hearing loss. The disabling hearing loss group showed lower intake of most major nutrients (P < 0.05), dietary fiber (P < 0.001), and most minerals and vitamins (P < 0.05), with some insufficiencies. The unilateral hearing group showed lower intake only for potassium (P = 0.036) compared to the bilateral hearing group and significantly higher intake of hydration (P = 0.039), dietary fiber (P = 0.039), and calcium (P = 0.009) than the disabling hearing loss group. Nutrient insufficiency in the disabling hearing loss group was more prominent in women, and was partially resolved by using hearing aids. Clinicians and nutritionists should consider undernourishment in these patients, and appropriate interventions for nutrition and hearing aids should be recommended.

Association of Range of Motion Deficit and Recurrence of Pain After Treatment of Adhesive Capsulitis.

INTRODUCTION: We evaluated the factors influencing the duration of significant pain reduction after conservative management for adhesive capsulitis (AC). METHODS: Follow-up for 6-8 months was performed with 141 patients with AC who experienced significant pain reduction after treatment. Clinical and demographic factors, numeric rating scale (NRS) scores, and shoulder range of motion (ROM) were collected and assessed pretreatment (T0), at 5 weeks post-treatment (T1), and at 6-8 months post-treatment (T2). Patients were divided into successful (n = 96) and unsuccessful (n = 45) NRS groups according to the degree of pain reduction at T2. We assessed post-treatment NRS and ROM improvement scores within each group and compared these parameters between the two groups. RESULTS: Significant NRS and ROM improvements were achieved in all patients who participated in our study. The unsuccessful NRS group demonstrated a lack of significant improvement in abduction at T1 and T2. All T1 and shoulder ROM measurements among the unsuccessful NRS group were significantly smaller than those among the successful NRS group. CONCLUSIONS: Failure to achieve a significant improvement in abduction angle after conservative management of AC was significantly associated with pain recurrence.

Relationship between Serum Total Testosterone Concentration and Metabolic Syndrome in Premenopausal Obese Women.

Background: Men with low testosterone levels are at an increased risk of developing metabolic syndrome, irrespective of age or obesity. However, the relationship between metabolic syndrome and testosterone levels in women remains unclear. We compared the total testosterone concentrations between premenopausal obese women with and without metabolic syndrome and identified the factors affecting these concentrations. Methods: A single-center retrospective analysis was conducted using the medical records of 580 premenopausal women with obesity. The diagnostic criteria for metabolic syndrome were established using the National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: The mean±standard deviation age, weight, and body mass index were 38.8±8.4 years, 78.0±11.8 kg, and 30.0±4.1 kg/m2, respectively. The mean total testosterone concentration was lower in the metabolic syndrome group than in the non-metabolic syndrome group (n=385 vs. n=195; 0.22±0.10 ng/mL vs. 0.24±0.11 ng/mL; P<0.001). In a model adjusted for age, body mass index, skeletal muscle mass, body fat mass, and body fat percentage, the odds ratio for metabolic syndrome with respect to the total testosterone level was 0.128 (P=0.028). Testosterone concentration was negatively correlated with age (r=-0.334), systolic blood pressure (r=-0.084), and triglyceride concentration (r=-0.093) but positively correlated with weight (r=0.144), body mass index (r=0.140), waist circumference (r=0.133), body fat mass (r=0.167), and body fat percentage (r=0.167). Stepwise regression analysis revealed that age (ß=-0.004, P<0.001), body mass index (ß=0.003, P=0.004), and high-density lipoprotein cholesterol concentration (ß=0.001, P=0.019) were independently associated with total testosterone concentration (adjusted R2=12.6%). Conclusion: Metabolic syndrome and obesity may be independently associated with testosterone levels in premenopausal women with obesity.

Surgical Correction of Left Ventricular Assist Device Outflow Graft Obstruction Caused by a Wrapped Expanded Polytetrafluoroethylene Graft: A Case Report.

A 70-year-old man with dilated cardiomyopathy underwent left ventricular assist device (LVAD) implantation, using a HeartWare ventricular assist device, as a bridge to candidacy. After 26 months, computed tomography (CT) angiography indicated stenosis in the LVAD outflow graft; however, the patient was asymptomatic, prompting a decision to manage his condition with close monitoring. Ten months later, the patient presented with dizziness and low-flow alerts. Subsequent CT angiography revealed a critical obstruction involving the entire LVAD outflow graft. The patient underwent emergency surgery, during which an organized seroma causing the graft obstruction was found between a wrapped expanded polytetrafluoroethylene (ePTFE) graft and a Dacron outflow graft. The covering of the outflow graft was removed, along with the organized seroma. Following removal of the ePTFE wrap and decompression of the outflow graft, normal LVAD flow was reestablished. The practice of wrapping the outflow graft with synthetic material, commonly done to facilitate later redo sternotomy, may pose a risk for outflow graft obstruction.

Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson's Disease: A Promising Therapeutic Approach.

As the global population ages, the prevalence of Parkinson's disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer's disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment.

Adipose tissue-derived exosomes alleviate particulate matter-induced inflammatory response and skin barrier damage in atopic dermatitis-like triple-cell model.

Recently, particulate matter (PM) has been shown to exacerbate atopic dermatitis (AD) by inducing an inflammatory response. Meanwhile, several studies revealed that exosomes derived from adipose tissue-derived mesenchymal stem cells promote wound healing and alleviate inflammation via their regenerative and immunomodulatory capacities. Our study aimed to investigate the effects of human adipose tissue-derived mesenchymal stem cell-derived (ASC)-exosomes in PM-induced AD. An AD-like triple-cell model was established by treating human keratinocytes, dermal fibroblasts, and mast cells with polyinosinic:polycytidylic acid (Poly I:C) and interleukin 1 alpha (IL-1α). The effects of PM and ASC-exosomes on the expression of pro-inflammatory cytokines and skin barrier proteins were examined using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. PM increased pro-inflammatory cytokines (IL-6, IL-1ß, and IL-1α) and decreased the anti-inflammatory cytokine IL-10, while the mRNA expression of skin barrier proteins (loricrin and filaggrin) decreased. However, when the cells were treated with ASC-exosomes, the PM-induced effects on pro-inflammatory cytokines and skin barrier proteins were reversed. Our results confirmed that PM-induced inflammation and skin barrier damage were alleviated by ASC-exosomes in our AD-like triple-cell model. These data suggest that ASC-exosomes can serve as a therapeutic agent for PM-exacerbated AD.

Complete microbial synthesis of crocetin and crocins from glycerol in Escherichia coli.

BACKGROUND: Crocin, a glycosylated apocarotenoid pigment predominantly found in saffron, has garnered significant interest in the field of biotechnology for its bioactive properties. Traditional production of crocins and their aglycone, crocetin, typically involves extraction from crocin-producing plants. This study aimed to develop an alternative biosynthetic method for these compounds by engineering the metabolic pathways of zeaxanthin, crocetin, and crocin in Escherichia coli strains. RESULTS: Employing a series of genetic modifications and the strategic overexpression of key enzymes, we successfully established a complete microbial pathway for synthesizing crocetin and four glycosylated derivatives of crocetin, utilizing glycerol as the primary carbon source. The overexpression of zeaxanthin cleavage dioxygenase and a novel variant of crocetin dialdehyde dehydrogenase resulted in a notable yield of crocetin (34.77 ± 1.03 mg/L). Further optimization involved the overexpression of new types of crocetin and crocin-2 glycosyltransferases, facilitating the production of crocin-1 (6.29 ± 0.19 mg/L), crocin-2 (5.29 ± 0.24 mg/L), crocin-3 (1.48 ± 0.10 mg/L), and crocin-4 (2.72 ± 0.13 mg/L). CONCLUSIONS: This investigation introduces a pioneering and integrated microbial synthesis method for generating crocin and its derivatives, employing glycerol as a sustainable carbon feedstock. The substantial yields achieved highlight the commercial potential of microbial-derived crocins as an eco-friendly alternative to plant extraction methods. The development of these microbial processes not only broadens the scope for crocin production but also suggests significant implications for the exploitation of bioengineered compounds in pharmaceutical and food industries.