The Wikstroemia genus is highly regarded in traditional Asian medicine for its diverse therapeutic applications, including the treatment of inflammatory and infectious conditions. Among its members,Wikstroemia trichotoma (Thunb.) Makino remains a promising medicinal resource which is yet to be chemicallycharacterized. To ensure the chemical consistency of W. trichotoma, we developed and validated the first HPLC method for the simultaneous quantification of three major marker compounds: chlorogenic acid (1), miconioside B (2), and matteucinol 7-O-apiofuranosyl(1→6)-glucopyranoside (3). Chromatographic separation was achieved on a C18 column using a gradient elution system of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection was optimized using a photodiode array (PDA) detector at 280 and 325 nm, based on the absorption maxima of the markers. The method was validated in accordance with the International Council for Harmonisation (ICH) and the Ministry of Food and Drug Safety (MFDS) guidelines. The results demonstrated high linearity (r2 > 0.999), with limits of detection and quantitation ranging from 4.28–6.42 and 12.97–19.47 μg/ mL, respectively. Intra- and inter-day precision (% RSD ≤ 1.83%) and accuracy (recoveries of 92.5–101.7%) were within acceptable limits. Quantitative analysis revealed the contents of 1, 2, and 3 in the W. trichotoma extract to be 19.9, 139.8, and 264.9 mg/g, respectively. This study provides a reliable analytical framework for the standardization, quality control, and future pharmacological evaluation of W. trichotoma.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Background: Although many studies have been conducted on the association between the intercondylar notch size and the risk of anterior cruciate ligament (ACL) injury, few studies have examined its relationship with the condition after surgical treatment.Therefore, this study aimed to investigate the surgical outcomes of anatomical single-bundle ACL reconstruction according to intercondylar notch volumes. Methods: Medical records of patients who underwent anatomical single-bundle ACL reconstruction using a tibialis anterior allograft between 2015 and 2019 were retrospectively reviewed. For each sex, eligible patients were classified into two groups based on their percentile of intercondylar notch volumes, which were measured using postoperative three-dimensional computed tomography images (group S, ≤ 50th percentile of included patients; group L, > 50th percentile of included patients). Additional grouping was performed based on the group’s percentiles of normalized values of intercondylar notch volumes to body heights.Between-group comparative analyses were performed on the perioperative data and surgical outcomes in both objective and subjective aspects. Results: One hundred patients were included in the study. For male patients, there were no differences in the overall surgical outcomes between groups, whereas group L showed a significantly greater knee anteroposterior (AP) laxity than group S at the final follow-up (p = 0.042 for the side-to-side differences [SSD] at the maximum manual force). Similarly, there were no differences in the female patients in the overall surgical results between the groups, whereas group L showed a significantly greater knee AP laxity at the final follow-up (p = 0.020 for the SSD at 134 N; p = 0.011 for the SSD at the maximum manual force). Additional analyses based on the normalized values of the intercondylar notch volume showed consistent results for male patients, and additional grouping for female patients was identical to the existing grouping. Conclusions The surgical outcomes of anatomical single-bundle ACL reconstruction in patients with relatively small intercondylar notch volumes were comparable to those with large notch volumes, but rather showed favorable outcomes in postoperative knee AP laxity.

Numerous systemic diseases manifest with oral symptoms and signs. The molecular diagnosis of Alzheimer’s disease (AD), the most prevalent neurodegenerative disease worldwide, currently relies on invasive or expensive methods, emphasizing the imperative for easily accessible biomarkers.In this study, we explored the expression patterns of key proteins implicated in AD pathophysiology within the taste buds of mice. We detected the expression of amyloid precursor protein (APP) and tau protein in the taste buds of normal C57BL/6 mice. Phosphorylated tau was predominantly found in type II and III taste cells, while APP was located in type I taste cells. Remarkably, we observed significantly stronger immunoreactivity to phosphorylated tau in the taste buds of aged AD mouse models compared to age-matched controls. These findings underscore the oral expression of biomarkers associated with AD, highlighting the diagnostic potential of the oral cavity for neurodegenerative diseases.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrugresistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. Methods: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. Results: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days).Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13–2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20–2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23–2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15–2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. Conclusion A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

While the coronavirus disease 2019 pandemic is ongoing, monkeypox has been rapidly spreading in non-endemic countries since May 2022. Accurate and rapid laboratory tests are essential for identifying and controlling monkeypox. Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have proposed guidelines for diagnosing monkeypox in clinical laboratories in Korea. These guidelines cover the type of tests, selection of specimens, collection of specimens, diagnostic methods, interpretation of test results, and biosafety. Molecular tests are recommended as confirmatory tests. Skin lesion specimens are recommended for testing in the symptomatic stage, and the collection of both blood and oropharyngeal swabs is recommended in the presymptomatic or prodromal stage.

Purpose: To differentiate a non-cancer-related temporary increase in prostate-specific antigen (PSA) triggering unnecessary biopsy, we intentionally delayed biopsy with a serial follow-up, then investigated the efficacy of this strategy in identifying a significant prostate cancer (PCa). Materials and Methods: Retrospective data of patients who initially presented with a suspicious level of serum PSA (3–20 ng/mL), managed using the delayed strategy, and then eventually underwent biopsy were obtained from 4 tertiary centers between 2018–2020. Results: The collected 271 subjects had a median (interquartile range) PSA, age, and prostate volume of 5.03 ng/mL (4.46–7.79 ng/mL), 67 years (61–73 years), and 38 g (28–50 g), respectively. During the delay period of 8 weeks (4–19 weeks), most were managed with alpha-blockers (85.6%, n=232). Ninety-four (34.7%) experienced a PSA decrease of 20.53% (8.82–38.16). Eventual biopsy revealed 115 PCa cases (42.5%) including 82 significant ones and 46 high-risk diseases. Men with a PSA decrease had a lower probability of PCa (31.9% vs. 48%, p=0.014), a significant disease (21.3% vs. 35.0%, p=0.026), and high-risk PCa (7.4% vs. 22.0%, p=0.002) than the PSA-elevated counterparts. However, the degree of PSA decrease was not associated with the presence or the severity of PCa. In patients with PSA normalization (≤3 ng/mL), though 4 patients of them (66%) had PCa including a single significant disease, none had high-risk disease. Conclusions About one-third of individuals initially indicated for transrectal biopsy experienced a decrease in PSA, and their chance for significant PCa was diminished. This retrospective study suggests PSA normalization could be an acceptable notion, though requires further investigation.

Moyamoya syndrome (MMS) associated with hyperthyroidism, such as Graves’ disease, is a rare condition that causes ischemic stroke with thyrotoxicity. A 43-year-old woman with symptoms of right hemiparesis was admitted. Brain magnetic resonance imaging revealed a small cerebral infarction in the left frontal lobe. Cerebral angiography revealed multi-vessel intracranial occlusive disease. Several days later, neurologic deterioration and aggravation of cerebral infarction developed due to a thyroid storm. A thyroid function test revealed the following: thyroid-stimulating hormone (TSH) ＜0.01 μunits/mL (reference range, 0.55–4.78 μunits/mL); triiodo-thyronine ＞8.0 ng/mL (reference range, 0.77–1.81 ng/mL); free thyroxine (T4) of 9.47 pmol/L (reference range, 11.4–22.6 pmol/L); and TSH receptor antibody of 37.10 U/L (reference range, 0–10 U/L). For thyroid storm management, we initiated treatment with methimazole, Gemstein’s solution, and hydrocortisone. Finally, the thyroid disease was controlled, and neurologic deficits improved. We describe a case of acute cerebral infarction combined with a thyroid storm in a patient with Moyamoya syndrome and Graves’ disease. Hyperthyroidism such as Graves’ disease should be considered in the differential diagnosis for patho-etiologic mechanisms associated with MMS. A cerebrovascular disease with a thyroid storm can lead to severe mortality and morbidity. Prompt diagnosis and strict treatment are important.