Effect of a Combination of Lactiplantibacillus plantarum KC3 and Leonurus japonicus Extracts in Respiratory Discomfort: A Randomized, Double-Blind, Placebo-Controlled Trial.

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.

Polyacrylamide/Gel-Based Self-Healing Artificial Tympanic Membrane for Drug Delivery of Otitis Treatment.

One of the bacterial infections caused by tympanic membrane perforation is otitis media (OM). Middle ear inflammation causes continuous pain and can be accompanied by aftereffects such as facial nerve paralysis if repeated chronically. Therefore, it is necessary to develop an artificial tympanic membrane (TM) that can effectively regenerate the eardrum due to the easy implantation and removal of OM inflammation. In this study, we synthesized hydrogel by mixing gelatin and polyacrylamide. Cefuroxime sodium salt was then incorporated into this hydrogel to both regenerate the TM and treat OM. Cytotoxicity experiments confirmed the biocompatibility of hydrogels equipped with antibiotics, and we conducted drug release and antibacterial experiments to examine continuous drug release. Through experiments, we have verified the excellent biocompatibility, drug release ability, and antibacterial effectiveness of hydrogel. It holds the potential to serve as an effective strategy for treating OM and regenerating TM as a drug delivery substance.

The Ray Method: Aesthetic and Simple Technique for Prosthesis Coverage in Prepectoral Breast Reconstruction.

In prepectoral breast reconstruction, the acellular dermal matrix (ADM) is commonly used to envelop breast implants. Various wrapping methods have been proposed. We present a simple but aesthetic method (ie, the ray method) for wrapping in prepectoral breast reconstruction. Without any complicated design, we folded the four corners of one large ADM and sewed them together to completely envelop the implant. Then, the 6 o'clock corner of the ADM envelope was folded up and sutured to make a pentagonal shape. The other corners of the ADM envelope were quilted to determine the position and movement of the internal implant. Additional sutures were placed on the ADM envelope to separate the implant from the host tissue. The folded 6 o'clock corner was cut to a convex contour and had a diagonal gap to prevent the collection of fluid in the ADM envelope. Finally, the wrapped implant was inserted in the postmastectomy space, and the ADM envelope was spread widely to support soft tissue effectively. This simple design is straightforward for inexperienced surgeons and reduces operation time. The position and movement of the breast implant in the ADM envelope can be easily controlled by using quilted sutures. Subclavian depression and step-off deformities can be minimized by this wide-stretched ADM. By total coverage with a large ADM, the breast implant is separated from the surrounding tissue, and foreign body reactions are reduced. This method is reliable for maximizing the aesthetic advantages of prepectoral direct-to-implant breast reconstruction.

Alveolar Microdynamics during Tidal Ventilation in Live Animals Imaged by SPring-8 Synchrotron.

It is self-evident that our chests expand and contract during breathing but, surprisingly, exactly how individual alveoli change shape over the respiratory cycle is still a matter of debate. Some argue that all the alveoli expand and contract rhythmically. Others claim that the lung volume change is due to groups of alveoli collapsing and reopening during ventilation. Although this question might seem to be an insignificant detail for healthy individuals, it might be a matter of life and death for patients with compromised lungs. Past analyses were based on static post-mortem preparations primarily due to technological limitations, and therefore, by definition, incapable of providing dynamic information. In contrast, this study provides the first comprehensive dynamic data on how the shape of the alveoli changes, and, further, provides valuable insights into the optimal lung volume for efficient gas exchange. It is concluded that alveolar micro-dynamics is nonlinear; and at medium lung volume, alveoli expand more than the ducts.

Glycaemic Status and Risk of Abdominal Aortic Aneurysm: A Nationwide Cohort Study of Four Million Adults using Korean National Health Screening Data.

OBJECTIVE: This retrospective cohort study aimed to confirm the previously reported inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) using large population based data. It also investigated the associations between AAA and impaired fasting glucose (IFG) and new onset DM (not yet treated). METHODS: A representative dataset was obtained from the Korean National Health Insurance Service. Participants who were aged ≥ 50 years and received a national health examination in 2009 were included and followed until 31 December 2019. Glycaemic status was defined based on fasting plasma glucose level and the relevant diagnostic codes. AAA was ascertained using medical facility use records with relevant diagnostic codes or aneurysm repair surgery. A Cox proportional hazards model was used to examine the association between glycaemic status and AAA, with adjustment for confounders. Additionally, the interactions between glycaemic status and subgroups based on baseline characteristics were examined. RESULTS: The study population comprised 4 162 640 participants. Participants with IFG or DM were significantly more likely to be male, older, and have comorbidities compared with normoglycaemic participants at baseline. The incidence of AAA was lower in participants with IFG or DM compared with normoglycaemic participants. The AAA risk was lower in patients with DM than in patients with IFG, and decreased linearly according to glycaemic status: the adjusted hazard ratio was 0.88 (95% confidence interval [CI] 0.85 - 0.91) for IFG, 0.72 (95% CI 0.67 - 0.78) for newly diagnosed DM, 0.65 (95% CI 0.61 - 0.69) for DM duration < 5 years, and 0.47 (95% CI 0.44 - 0.51) for DM duration ≥ 5 years compared with the normoglycaemia group. Both IFG and DM were related to reduced AAA risk in all subgroups, suggesting an independent association. CONCLUSION: Both IFG and DM, even when not treated with antihyperglycaemic medication, were associated with a lower incidence of AAA. The AAA risk decreased linearly according to DM duration.

Surgical outcome of mitral valve surgery in atrial functional mitral regurgitation compared with degenerative etiology.

OBJECTIVE: To analyze and compare the outcomes of mitral valve surgery for atrial functional mitral regurgitation (AFMR) and for degenerative mitral regurgitation (DMR). METHODS: Patients with AFMR or DMR who underwent mitral valve repair/replacement at 2 institutions between January 2012 and December 2022 were included. Patients <18 years of age and patients undergoing concomitant cardiac surgery (except for the maze procedure or tricuspid annuloplasty) were excluded. Propensity score analysis was used to adjust for baseline differences. RESULTS: A total of 642 patients were enrolled. After propensity score analysis, 164 patients were classified into the DMR group, and 82 patients were classified into the AFMR group. All matched patients in both groups had atrial fibrillation. In DMR and AFMR, the 5-year freedom from readmission for heart failure and cardiac death was 96.3% in the DMR group versus 88.6% in the AFMR group (P = .045) and freedom from readmission for cardiac death in the 2 groups was 100% and 90.0%, respectively (P = .002). The recurrence rate of significant mitral regurgitation (MR) after mitral valve repair was not significantly different between the 2 groups (P = .699, log-rank test), and the 5-year freedom from MR recurrence (moderate or greater) was 89.8% and 93.0%, respectively. After the maze procedure, significantly more patients in the AFMR group than the DMR group were in junctional rhythm (49.1% vs 3.3%; P < .001) and required permanent pacemaker insertion during the follow-up period (11.4% vs 1.5% after 5 years; P = .041, log-rank test). CONCLUSIONS: AFMR was associated with acceptable outcomes of mitral valve surgery, and mitral valve repair is a good treatment option. However, significantly more patients were in junctional rhythm after the maze procedure, needing more permanent pacemaker insertion.

Higher exposure to 1,3-butadiene is associated with more severe hearing loss.

While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-L-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, P < 0.001) showed associations with HL. Additionally, HFHL exhibited significant associations with BMA (P = 0.005), 3- and 4-methylhippuric acid (3, 4 MHA, P = 0.049), mandelic acid (MA, P = 0.015), SPMA (P < 0.001), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3-HPMA, P < 0.001), and DHBMA (P < 0.001). After controlling other factors, DHBMA were associated with HL (P = 0.021) and HFHL (P = 0.014) and exhibited a linear association with the mean hearing level (ß = 0.054, P = 0.024) and high-frequency hearing level (ß = 0.045, P = 0.037). Since 1,3-butadiene may act as an ototoxic material, early screening for workers exposed to 1,3-butadiene and reducing exposure to 1,3-butadiene in everyday life may be helpful to prevent further HL.

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.

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.

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.

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".

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.

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.

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.

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.

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.

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.