Clinical Efficacy and Safety of an Automatic Closed-Suction System in Mechanically Ventilated Patients with Pneumonia: A Multicenter, Prospective, Randomized, Non-Inferiority, Investigator-Initiated Trial.

Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (-0.13 ± 1.58 in the intervention group, -0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.

Safety of deer antler extract in children: A 12-week randomized controlled clinical trial.

BACKGROUND: Deer antlers have been used as strong tonifying medicine in Asian countries, especially for the growth and development of children in pediatrics of Korean medicine. The safety of deer antler in adults cannot be applied directly to children because of their physiological characteristics. To accumulate reliable data on the safety of deer antler in pediatric populations, well-designed clinical studies are required. METHODS: This research is a 12-week, randomized, double-blind, placebo-controlled clinical trial evaluating the safety of deer antler extract (DAE) in children. The DAE group received an intervention containing 1586 mg of DAE, whereas the control group received a placebo for 12 weeks. The safety was assessed by monitoring adverse drug reactions (ADRs) and laboratory test results. RESULTS: One hundred participants were included in the safety analysis. Three and 2 participants in the DAE and control groups, respectively, reported ADRs. There was no significant difference in incidence between the 2 groups. ADRs are categorized into gastrointestinal and skin-related symptoms. No serious ADR was observed throughout the study. The laboratory test results were within or outside the normal range at clinically insignificant levels. CONCLUSION: The research discovered that the DAE is safe in terms of ADRs and laboratory parameters under the conditions studied. Further studies are required to accumulate safety data about DAE dosage adjustment and potential interactions with other medicines.

Dose-toxicity surface histogram-based prediction of radiation dermatitis severity and shape.

Objective.This study aimed to develop a new approach to predict radiation dermatitis (RD) by using the skin dose distribution in the actual area of RD occurrence to determine the predictive dose by grade.Approach.Twenty-three patients with head and neck cancer treated with volumetric modulated arc therapy were prospectively and retrospectively enrolled. A framework was developed to segment the RD occurrence area in skin photography by matching the skin surface image obtained using a 3D camera with the skin dose distribution. RD predictive doses were generated using the dose-toxicity surface histogram (DTH) calculated from the skin dose distribution within the segmented RD regions classified by severity. We then evaluated whether the developed DTH-based framework could visually predict RD grades and their occurrence areas and shapes according to severity.Main results.The developed framework successfully generated the DTH for three different RD severities: faint erythema (grade 1), dry desquamation (grade 2), and moist desquamation (grade 3); 48 DTHs were obtained from 23 patients: 23, 22, and 3 DTHs for grades 1, 2, and 3, respectively. The RD predictive doses determined using DTHs were 28.9 Gy, 38.1 Gy, and 54.3 Gy for grades 1, 2, and 3, respectively. The estimated RD occurrence area visualized by the DTH-based RD predictive dose showed acceptable agreement for all grades compared with the actual RD region in the patient. The predicted RD grade was accurate, except in two patients.Significance. The developed DTH-based framework can classify and determine RD predictive doses according to severity and visually predict the occurrence area and shape of different RD severities. The proposed approach can be used to predict the severity and shape of potential RD in patients and thus aid physicians in decision making.

Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

PURPOSE: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. METHODS: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. RESULTS: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). CONCLUSIONS: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

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.

Entosis implicates a new role for P53 in microcephaly pathogenesis, beyond apoptosis.

Entosis, a form of cell cannibalism, is a newly discovered pathogenic mechanism leading to the development of small brains, termed microcephaly, in which P53 activation was found to play a major role. Microcephaly with entosis, found in Pals1 mutant mice, displays P53 activation that promotes entosis and apoptotic cell death. This previously unappreciated pathogenic mechanism represents a novel cellular dynamic in dividing cortical progenitors which is responsible for cell loss. To date, various recent models of microcephaly have bolstered the importance of P53 activation in cell death leading to microcephaly. P53 activation caused by mitotic delay or DNA damage manifests apoptotic cell death which can be suppressed by P53 removal in these animal models. Such genetic studies attest P53 activation as quality control meant to eliminate genomically unfit cells with minimal involvement in the actual function of microcephaly associated genes. In this review, we summarize the known role of P53 activation in a variety of microcephaly models and introduce a novel mechanism wherein entotic cell cannibalism in neural progenitors is triggered by P53 activation.

A 12-Week, Single-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial for the Evaluation of the Efficacy and Safety of Lactiplantibacillus plantarum SKO-001 in Reducing Body Fat.

There is growing evidence linking gut microbiota to overall health, including obesity risk and associated diseases. Lactiplantibacillus plantarum SKO-001, a probiotic strain isolated from Angelica gigas, has been reported to reduce obesity by controlling the gut microbiome. In this double-blind, randomised clinical trial, we aimed to evaluate the efficacy and safety of SKO-001 in reducing body fat. We included 100 participants randomised into SKO-001 or placebo groups (1:1) for 12 weeks. Dual-energy X-ray absorptiometry was used to objectively evaluate body fat reduction. Body fat percentage (p = 0.016), body fat mass (p = 0.02), low-density lipoprotein-cholesterol levels (p = 0.025), and adiponectin levels (p = 0.023) were lower in the SKO-001 group than in the placebo group after 12 weeks of SKO-001 consumption. In the SKO-001 group, the subcutaneous fat area (p = 0.003), total cholesterol levels (p = 0.003), and leptin levels (p = 0.014) significantly decreased after 12 weeks of SKO-001 consumption compared with baseline values. Additionally, SKO-001 did not cause any severe adverse reactions. In conclusion, SKO-001 is safe and effective for reducing body fat and has the potential for further clinical testing in humans.

Effects of dexmedetomidine on renal function after cardiac surgery for infective endocarditis: An interim analysis of a randomized controlled trial.

BACKGROUND: Patients undergoing cardiac surgery for infective endocarditis (IE) are at a high risk of postoperative acute kidney injury (AKI) owing to heightened systemic inflammation. Therefore, we aimed to investigate the effect of dexmedetomidine on postoperative AKI in patients who underwent cardiac surgery for IE. METHODS: A total of 63 patients who underwent cardiac surgery for IE were randomly assigned to receive either intravenous dexmedetomidine infusion of 0.4 µg kg-1 h-1 (DEX group) or normal saline infusion (control group) for 24 h after induction of anesthesia. The occurrence of AKI within seven days postoperation, epinephrine, norepinephrine, and interleukin-6 levels, as well as postoperative morbidities, were assessed. An intertrim analysis was conducted using Pocock's alpha spending function at α = 0.05 and ß = 0.2. RESULTS: This trial was early terminated according to the results of interim analysis performed when 60 % of the pre-set number of patients have been collected. The incidence of AKI was significantly lower in the DEX group than in the control group (32.3 % vs. 9.4 %, p = 0.025). Patients in the DEX group had significantly lower epinephrine levels than those in the control group, whereas norepinephrine and interleukin-6 levels were similar. Perioperative mean arterial pressure or heart rate did not differ between the groups. CONCLUSIONS: Dexmedetomidine administration for 24 h starting from induction of anesthesia significantly reduced the incidence of postoperative AKI after cardiac surgery for IE (by 29 % vs. control) without hemodynamic side effects. This was accompanied by a significant attenuation of postoperative increase in serum epinephrine levels.

Bisphenol Analogs Downregulate the Self-Renewal Potential of Spermatogonial Stem Cells.

PURPOSE: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. MATERIALS AND METHODS: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. RESULTS: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. CONCLUSIONS: Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

The effect of Bruton's tyrosine kinase (BTK) inhibitor in the eosinophilic asthma model of mouse.

Bruton's Tyrosine kinase (BTK) plays a pivotal role as the key mediator in B cell signaling. Recent research has revealed that it is also expressed in cells critical to asthma development, such as T cells, and eosinophils. This study aims to investigate the potential of BTK inhibitor in eosinophilic asthma mouse model. BALB/c mice were sensitized with ovalbumin (OVA) via intraperitoneal injections and followed by OVA nebulizations. The mice were treated with 250 µg/ml or 500 µg/ml of ibrutinib before the second intraperitoneal injection and the first nebulization. Two days after the last OVA challenge, airway hyperresponsiveness (AHR) was assessed with methacholine, and differential cell count in bronchoalveolar lavage fluid (BALF) was performed. The cytokines were measured in BALF, and serum OVA-specific IgE and IgG antibody levels were evaluated by ELISA. The inhibitory effect of ibrutinib was also evaluated in splenic mononuclear cells, mast cells, eosinophils, and T cells in vitro. Treatment with ibrutinib significantly attenuated AHR and airway inflammation, compared to the OVA-induced positive control. The treatment also reduced IL-4, IL-5, IL-13 and IFN-γ cytokine levels and suppressed OVA-specific IgE and IgG production compared to the OVA-induced positive control. Additionally, ibrutinib decreased beta-hexosaminidase release from mast cells, type 2 cytokine productions from mononuclear cells and T cells, and eosinophilic activation markers in vitro. The results of this study suggest that ibrutinib treatment could exert anti-allergic effects by inactivating B cells and other BTK-expressing cells. Further studies are needed to investigate the potential therapeutic effect of ibrutinib on allergic diseases.

Impartial feature selection using multi-agent reinforcement learning for adverse glycemic event prediction.

We developed an attention model to predict future adverse glycemic events 30 min in advance based on the observation of past glycemic values over a 35 min period. The proposed model effectively encodes insulin administration and meal intake time using Time2Vec (T2V) for glucose prediction. The proposed impartial feature selection algorithm is designed to distribute rewards proportionally according to agent contributions. Agent contributions are calculated by a step-by-step negation of updated agents. Thus, the proposed feature selection algorithm optimizes features from electronic medical records to improve performance. For evaluation, we collected continuous glucose monitoring data from 102 patients with type 2 diabetes admitted to Cheonan Hospital, Soonchunhyang University. Using our proposed model, we achieved F1-scores of 89.0%, 60.6%, and 89.8% for normoglycemia, hypoglycemia, and hyperglycemia, respectively.

Changes in frequency of benign convulsions with mild gastroenteritis and their viral causes before and during the COVID-19 pandemic: a single-center study.

BACKGROUND: Benign convulsions with mild gastroenteritis (CwG) are prevalent in young children during the winter. Early in the coronavirus disease 2019 (COVID-19) pandemic, viral gastroenteritis occurrence decreased and seasonal variation was lost, which can change CwG. PURPOSE: Here we investigated changes in frequency, seasonal variation, and causative viruses of CwG during the COVID-19 pandemic. METHODS: We screened 1134 patients (3-36 months) with "other and unspecified convulsions" treated at Chonnam National University Hospital between March 2017 and February 2023; of them, we enrolled 41 (3.6%) with CwG. We compared their medical records from period I (March 2017 to February 2020) to those from period II (March 2020 to February 2023). Publicly available viral gastroenteritis surveillance data from the Korea Disease Control and Prevention Agency (KDCA) were reviewed as reference. RESULTS: Of the 41 patients with CwG, 18 (2.9% of 613) were affected in period I versus 23 (4.4% of 512) in period II (P=0.184). In period I, CwG mainly occurred in winter and spring (55.6% and 22.2%, respectively). In period II, there were fewer CwG cases (39.1%) in winter and more cases in summer and autumn (26.1% and 17.4%, respectively): the cases of norovirus genogroup II (GII)-associated CwG increased significantly in the summer (38.5% vs. 0%, P= 0.046). Norovirus GII was the most common virus (56.1% of isolates). Enteric adenovirus was the second most common (19.5%), with one case in period I and 7 cases in period II (P=0.059). The clinical characteristics of enteric adenovirus-associated CwG were similar to those of norovirus. Seasonal changes in and viral causes of CwG were consistent with those observed in the KDCA stool surveillance data. CONCLUSION: During the COVID-19 pandemic, CwG frequency did not change, seasonal variation was unapparent, and enteric adenovirus-associated CwG frequency increased.

Effect of high-dose vitamin C on renal ischemia-reperfusion injury.

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation.

Experience of Implementing Deep Learning-Based Automatic Contouring in Breast Radiation Therapy Planning: Insights From Over 2000 Cases.

PURPOSE: This study evaluated the impact and clinical utility of an auto-contouring system for radiation therapy treatments. METHODS AND MATERIALS: The auto-contouring system was implemented in 2019. We evaluated data from 2428 patients who underwent adjuvant breast radiation therapy before and after the system's introduction. We collected the treatment's finalized contours, which were reviewed and revised by a multidisciplinary team. After implementation, the treatment contours underwent a finalization process that involved manual review and adjustment of the initial auto-contours. For the preimplementation group (n = 369), auto-contours were generated retrospectively. We compared the auto-contours and final contours using the Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD95). RESULTS: We analyzed 22,215 structures from final and corresponding auto-contours. The final contours were generally larger, encompassing more slices in the superior or inferior directions. Among organs at risk (OAR), the heart, esophagus, spinal cord, and contralateral breast demonstrated significantly increased DSC and decreased HD95 postimplementation (all P < .05), except for the lungs, which presented inaccurate segmentation. Among target volumes, CTVn_L2, L3, L4, and the internal mammary node showed increased DSC and decreased HD95 postimplementation (all P < .05), although the increase was less pronounced than the OAR outcomes. The analysis also covered factors contributing to significant differences, pattern identification, and outlier detection. CONCLUSIONS: In our study, the adoption of an auto-contouring system was associated with an increased reliance on automated settings, underscoring its utility and the potential risk of automation bias. Given these findings, we underscore the importance of considering the integration of stringent risk assessments and quality management strategies as a precautionary measure for the optimal use of such systems.

Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract.

Background: For maintenance therapy in type 2 diabetes, glucagon-like peptide-1 agonist (GLP-1A), which exhibits low cardiovascular risk and high efficacy, is a promising peptide therapeutic. However, developing an oral GLP-1A presents challenges due to the analog's poor cellular permeability and gastrointestinal (GI) stability. Methods: To mitigate such limitations, an oral nanoformulation of liraglutide (LG) was designed and achieved by combining LG with bile acid derivatives using the nanoprecipitation method. This strategy allowed the bile acid moieties to localize at the nanoparticle surface, enhancing the binding affinity for apical sodium-dependent bile acid transporter (ASBT) and improving GI stability. The in vitro characteristics, cellular permeability, and absorption mechanisms of the LG nanoformulation (LG/TD-NF) were thoroughly investigated. Furthermore, the in vivo oral absorption in rats and the glucose-lowering effects in a diabetic (db/db) mouse model were evaluated. Results: The LG/TD-NF produced neutral nanoparticles with a diameter of 58.7 ± 4.3 nm and a zeta potential of 4.9 ± 0.4 mV. Notably, when exposed to simulated gastric fluid, 65.7 ± 3.6% of the LG/TD-NF remained stable over 120 min, while free LG was fully degraded. Relative to unformulated LG, the Caco-2 cellular permeability of the nanoformulation improved, measuring 10.9 ± 2.1 (× 10-6 cm/s). The absorption mechanism prominently featured endocytosis simultaneously mediated by both ASBT and epidermal growth factor receptor (EGFR). The oral bioavailability of the LG/TD-NF was determined to be 3.62% at a dosage of 10 mg/kg, which is 45.3 times greater than that of free LG. In a diabetes model, LG/TD-NF at 10 mg/kg/day exhibited commendable glucose sensitivity and reduced HbA1c levels by 4.13% within 28 days, similar to that of subcutaneously administered LG at a dosage of 0.1 mg/kg/day. Conclusion: The oral LG/TD-NF promotes ASBT/EGFR-mediated transcytosis and assures cellular permeability within the GI tract. This method holds promise for the development of oral GLP-1A peptides as an alternative to injections, potentially enhancing patient adherence to maintenance therapy.

Enhanced Postsurgical Cancer Treatment Using Methacrylated Glycol Chitosan Hydrogel for Sustained DNA/Doxorubicin Delivery and Immunotherapy.

Background: Cancer recurrence and metastasis are major contributors to treatment failure following tumor resection surgery. We developed a novel implantable drug delivery system utilizing glycol chitosan to address these issues. Glycol chitosan is a natural adjuvant, inducing dendritic cell activation to promote T helper 1 cell immune responses, macrophage activation, and cytokine production. Effective antigen production by dendritic cells initiates T-cell-mediated immune responses, aiding tumor growth control. Methods: In this study, we fabricated multifunctional methacrylated glycol chitosan (MGC) hydrogels with extended release of DNA/doxorubicin (DOX) complex for cancer immunotherapy. We constructed the resection model of breast cancer to verify the anticancer effects of MGC hydrogel with DNA/DOX complex. Results: This study demonstrated the potential of MGC hydrogel with extended release of DNA/DOX complex for local and efficient cancer therapy. The MGC hydrogel was implanted directly into the surgical site after tumor resection, activating tumor-related immune cells both locally and over a prolonged period of time through immune-reactive molecules. Conclusions: The MGC hydrogel effectively suppressed tumor recurrence and metastasis while enhancing immunotherapeutic efficacy and minimizing side effects. This biomaterial-based drug delivery system, combined with cancer immunotherapy, can substantial improve treatment outcomes and patient prognosis.

Facile and cost-effective fabrication of wearable alpha-naphtholphthalein-based halochromic sensor for wound pH monitoring.

The sensor, designed to be worn directly on the skin, is suitable for real-time monitoring of the recovery level of not only general wounds, but also difficult-to-heal wounds, such as those with chronic inflammation. Notably, healthy skin has a pH range of 4-6. When a wound occurs, the pH is known to be approximately 7.4. In this study, alpha-naphtholphthalein (Naph) was immersed in a cotton-blended textile to produce a wearable halochromic sensor that clearly changed color depending on the pH of the skin in the range 6-9, including pH 7.4, which is the skin infection state. The coating was performed without using an organic solvent by dissolving it in micelle form using cetyltrimethylammonium bromide, a surfactant, in water. Naph-based halochromic sensor shows light yellow, which is the dye's own color, at pH 6, which is a healthy skin condition, and gradually showed a clear color change to light green-green-blue as pH increased. Even after washing and drying by rubbing with regular tap water, the color change due to pH was maintained more than 10 times. Naph-based halochromic sensors use a simple solution production and coating method and are not only reusable sensors that can be washed with water but also use environmentally friendly water, making them very suitable for developing commercial products for wound pH monitoring. In addition, it can be easily applied to medical supplies, such as medical gauze, patient clothes, and compression bandages, as well as everyday wear, such as clothing, gloves, and socks. Therefore, it is expected to be widely used as a wound pH sensor, allowing real-time monitoring of the skin condition of individuals with chronic skin inflammation, including patients requiring wound recovery.

Assessing the accuracy and reliability of application-based audiometry for hearing evaluation.

Pure-tone audiometry (PTA) is the gold standard for assessing hearing loss. However, traditional PTA tests require specialized equipment, trained personnel, and a soundproof environment. Recently, smartphone-based PTA tests have been developed as an alternative method for hearing assessment. The aim of this study was to validate the accuracy and reliability of a smartphone application-based audiometry test. This study was conducted to assess the performance of application-based audiometry from November 2021 to January 2022. Pure-tone thresholds were measured using a smartphone application-based PTA test and compared with results obtained using a traditional audiometer in a sound-treated booth. The smartphone application used in this study was the "Care4Ear (Care4ear, version 1.0.6, MIJ Co., Ltd.)". Hearing thresholds less than 35 dB HL were classified as group A, 35-64 dB HL as group B, and 65 dB HL or greater as group C for the classification of hearing levels. We evaluated the accuracy of smartphone audiometry for each group and compared the results of frequency-specific hearing tests. Additionally, we examined the results of smartphone audiometry in individuals (n = 27) with asymmetric hearing loss. Seventy subjects completed both conventional audiometry and smartphone application-based hearing tests. Among the ears assessed, 55.7% were classified as group A, while 25.7% and 18.6% were classified as group B and group C, respectively. The average hearing threshold obtained from conventional pure-tone audiometry was 37.7 ± 25.2 dB HL, whereas the application-based hearing test yielded thresholds of 21.0 ± 23.0 dB HL. A significant correlation (r = 0.69, p < 0.01) was found between the average hearing thresholds obtained from the application-based and conventional pure-tone audiometry tests. The application-based test achieved a 97.4% hit rate for classifying hearing thresholds as class A, but lower rates of 22.2% for class B and 38.5% for class C. Notably, a discrepancy was observed between the hearing threshold measured by the application and the conventional audiometry for the worse ear with asymmetric hearing. The smartphone-based audiometry is a feasible method for hearing evaluation especially in persons with normal hearing. In cases of hearing loss or asymmetric hearing loss, the results of the application-based audiometry may be inaccurate, limiting its diagnostic utility.

Efficacy of stereotactic ablative radiotherapy in patients with oligometastatic hepatocellular carcinoma: A phase II study.

BACKGROUND & AIMS: Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC. METHODS: We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR. RESULTS: Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p = 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p = 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores. CONCLUSIONS: SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL. IMPACT AND IMPLICATIONS: Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes. CLINICAL TRIAL NUMBER: NCT05173610.

Clinical, qualitative imaging biomarkers, and tumor oxygenation imaging biomarkers for differentiation of midline-located IDH wild-type glioblastomas and H3 K27-altered diffuse midline gliomas in adults.

PURPOSE: To compare the clinical, qualitative and quantitative imaging phenotypes, including tumor oxygenation characteristics of midline-located IDH-wildtype glioblastomas (GBMs) and H3 K27-altered diffuse midline gliomas (DMGs) in adults. METHODS: Preoperative MRI data of 55 adult patients with midline-located IDH-wildtype GBM or H3 K27-altered DMG (32 IDH-wildtype GBM and 23 H3 K27-altered DMG patients) were included. Qualitative imaging assessment was performed. Quantitative imaging assessment including the tumor volume, normalized cerebral blood volume, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), relative cerebral metabolic rate of oxygen values, and mean ADC value were performed from the tumor mask via automatic segmentation. Univariable and multivariable logistic analyses were performed. RESULTS: On multivariable analysis, age (odds ratio [OR] = 0.92, P = 0.015), thalamus or medulla location (OR = 10.48, P = 0.013), presence of necrosis (OR = 0.15, P = 0.038), and OEF (OR = 0.01, P = 0.042) were independent predictors to differentiate H3 K27-altered DMG from midline-located IDH-wildtype GBM. The area under the curve, accuracy, sensitivity, and specificity of the multivariable model were 0.88 (95 % confidence interval: 0.77-0.95), 81.8 %, 82.6 %, and 81.3 %, respectively. CONCLUSIONS: Along with younger age, tumor location, less frequent necrosis, and lower OEF may be useful imaging biomarkers to differentiate H3 K27-altered DMG from midline-located IDH-wildtype GBM. Tumor oxygenation imaging biomarkers may reflect the less hypoxic nature of H3 K27-altered DMG than IDH-wildtype GBM and may contribute to differentiation.