BACKGROUND

Despite the presence of SARS-CoV-2 antivirals, namely, remdesivir, nirmatrelvir and toremifene, these drugs entail adverse effects and limited effectiveness. Thus, development of a safer alternative is imperative, and likely candidates include the cell-free supernatant (CFS) and protein fractions from Lactiplantibacillus plantarum strains. These postbiotics have known antiviral properties primarily mediated by plantaricins and enhanced by organic acids.

The study determined the in silico mechanism of plantaricins against the receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), as well as compared the in vitro activities of the L. plantarum BS25 CFS, semi-purified and crude protein fractions, against the SARS-CoV-2 pseudotyped viruses (nCoV-S-EGFP) expressing the spike of wild-type (wt) Wuhan strain, Omicron BA.1 and BA.4/5 variants. Further, this study determined the metabolome of the strain BS25 CFS.

A quasi-experimental approach was utilized in the study. Plantaricins were screened for safety in silico, followed by molecular docking with RBD and ACE2. Using a cell culture model, two-fold dilutions of the CFS and fractions were tested for cytotoxicity and microneutralization against the pseudoviruses. Mass spectrometry was utilized for the metabolomics.

Plantaricins interact stably with RBD than ACE2 which were mediated by hydrogen, hydrophobic and covalent bonds. The activities of the CFS and fractions were substantially higher against the nCoV-SEGFP BA.4/5 variant. The 1:8 dilution of CFS entailed no cytotoxicity and displayed higher activities than toremifene. Metabolomics has identified a relatively abundant putative peptide, followed by organic acids and cyclic peptides.

Plantaricins can prevent SARS-CoV-2 entry by interacting with key RBD mutations or with intrinsically disordered RBD residues. The cationic and hydrophobic RBD mutations in the BA.4/5 variant may facilitate interactions with the putative peptide from the CFS and fractions, hence the observed potent activities. These findings can be used as basis for the development of an alternative antiviral targeting the RBD of live or pseudotyped SARS-CoV-2 variants.

Background: The Act on Decisions on Life-Sustaining Treatment (LST) has been implemented in Korea since 2018, yet data on its application in neurocritical care units remain scarce. This study aimed to evaluate the clinical characteristics and outcomes of LST withdrawal or withholding in the neurocritical care unit. Methods: This study was a retrospective analysis conducted at a tertiary university hospital in Busan, South Korea. Among patients admitted to the neurocritical care unit between February 2018 and August 2023, those with documented decisions for LST withdrawal or withholding were enrolled. Demographic and clinical characteristics, underlying and combined conditions, reasons for LST decisions, measures taken, and time from LST withdrawal to death were extracted from medical records. Results: A total of 69 patients were included, with a median age of 67 years, and 38 (55%) were male. Cerebrovascular disease (62%) and traumatic brain injury (22%) were the most common underlying diagnoses. The primary reason for LST decisions was irreversible neurological damage (71%), followed by systemic complications (19%). Mechanical ventilation cessation (91%) and extubation (86%) were most frequently used measures for LST withdrawal. The median time from LST withdrawal to death was 22 minutes. Conclusions Our study demonstrates that LST decisions in the neurocritical care unit predominantly occur among patients with cerebrovascular disease or traumatic brain injury, mostly triggered by neurological deterioration. Most patients died shortly after withdrawal. These findings provide important insight into current LST withdrawal practices in neurocritical care and may assist clinical and ethical decision making in similar settings.

Cerebrospinal fluid (CSF) dynamics are increasingly recognized as central to brain waste clearance. Beyond the classical view of unidirectional CSF circulation, recent studies have identified the glymphatic system and meningeal lymphatic vessels as major complementary pathways. Glymphatic transport is driven by arterial pulsation, respiration, vasomotion, and strongly enhanced during slow-wave sleep. Advances in neuroimaging, including DTI-ALPS, EPVS quantification, contrast-enhanced magnetic resonance imaging (MRI), and ultrafast functional MRI, have enabled in vivo assessment of these mechanisms. Impaired glymphatic function has been linked to neurodegenerative and cerebrovascular diseases, highlighting its clinical relevance. Potential interventions range from lifestyle measures such as sleep optimization, exercise, and vascular risk control, to pharmacological and experimental strategies aiming to modulate CSF flow. These insights open new opportunities to target the glymphatic-lymphatic axis for the prevention and treatment of neurological disorders.

Purpose: To investigate indicators of dry eye disease that influence punctal plug loss. Methods: A retrospective review was conducted on patients who received SuperFlex® punctal plugs. To analyze the relationship between punctal plug loss and markers for dry eye, patients were categorized into a loss group, defined as those who experienced unintended loss within 3 months of insertion, and a retention group. In total, 11 indicators were compared between the two groups, including meibomian gland expressibility, cloudiness of meibomian gland secretions, telangiectasis of the eyelid margin, tear osmolarity, Schirmer’s test value, the expression levels of matrix metalloproteinase-9 in tears, NEI/Industry grading system score, Sjögren’s International Collaborative Clinical Alliance ocular staining score, tear lipid layer thickness (LLT), and meiboscore. Results: In all, 47 eyes of 30 patients were included in the study. Of these, 16 eyes (34%) were assigned to the loss group. Meibomian gland expressibility grade was significantly higher in the loss group (1.60 ± 0.58) compared to the retention group (1.04 ± 0.37, p = 0.0247). Additionally, LLT was significantly lower in the loss group (58.7 ± 17.0 nm vs. 88.4 ± 17.6 nm, p = 0.0303). However, no significant correlations were found between punctal plug loss and other indicators of dry eye. Conclusions Worse meibomian gland expressibility and thinner LLT are associated with a higher rate of punctal plug loss.

Purpose: We investigated the ophthalmic manifestations of Korean patients with Williams syndrome registered at a single regional rare disease center over the past 30 years. Methods: We conducted a retrospective analysis of the medical records of 19 patients who underwent complete ophthalmic examinations among 56 patients diagnosed with Williams syndrome and enrolled between September 1994 and August 2024. Results: Nineteen patients with Williams syndrome (7 boys and 12 girls) underwent their first ophthalmic examination at a mean age of 2.6 ± 2.8 years and were followed for 5.5 ± 5.1 years. Of these, 16 patients (84%) had cardiovascular abnormalities, 2 (11%) had infantile hypercalcemia, and 17 (89%) exhibited developmental delay. All patients displayed characteristic facial features with puffy eyelids. Congenital nasolacrimal duct obstruction occurred in 3 patients (16%) and resolved spontaneously. A stellate iris pattern involving approximately half the iris width was observed in 10 patients (53%). Strabismus was present in 13 patients (68%), including 6 with exotropia (1 with Duane retraction syndrome type 2) and 7 with esotropia. At the final refractive assessment (mean age 8.1 ± 2.5 years), 4 patients had hyperopia, 4 had myopia (including 1 with high myopia), 4 had astigmatism, and 3 had anisometropia; 7 patients (37%) required spectacle correction. Of the 11 patients with measurable visual acuity, 5 (45%) had amblyopia. Retinal vascular tortuosity was observed in 11 patients (58%), and attenuated retinal vessels in 10 (53%). Optical coherence tomography performed in 5 patients with normal visual acuity revealed markedly reduced central macular thickness in all, and a wide foveal pit in 1 patient. Conclusions Williams syndrome is associated with diverse ophthalmic manifestations that warrant regular and comprehensive ophthalmic follow-up.

Purpose: We present a case of dupilumab-associated ocular surface disease presenting as atypical superior filamentary keratitis and describe our treatment approach.Case summary: A 20-year-old male receiving dupilumab for atopic dermatitis was referred for bilateral ocular discomfort 2 months after treatment initiation. Examination revealed follicular hyperplasia of the left superior palpebral conjunctiva, limbal elevation and hyperemia, corneal infiltration, and superficial neovascularization, consistent with severe atopic keratoconjunctivitis. Considering the inflammation was refractory to prior long-term therapy, the patient was treated with topical corticosteroids, antibiotics, and a sub-Tenon triamcinolone injection; however, the clinical course fluctuated with repeated improvement and deterioration. Despite subsequent tacrolimus therapy, characteristic filaments developed in the superior cornea of both eyes with significant exacerbation following dupilumab administration. Subjective symptoms improved after the patient voluntarily discontinued dupilumab. Subsequently, the condition stabilized after extending the dupilumab dosing interval and the patient remains under observation with ongoing medication adjustments. Conclusions Dupilumab treatment can induce corneal filament formation, particularly in the superior area. Patients with a history of ocular disease or those receiving ophthalmic medications should be monitored closely during therapy.

Objectives: Osteoporosis is a silent disease with low screening rates in many developing countries. This study aimed to evaluate the feasibility of using an artificial intelligence (AI)-based system to screen osteoporosis from pelvic and hip radiographs in Vietnam. Methods: We conducted a cross-sectional study at a tertiary medical center in Central Vietnam in 2023. A total of 2000 consecutive pelvic and hip radiographs from patients aged ≥ 40 years were collected. After excluding poorquality images, 1987 radiographs were analyzed using an AI-based software designed to estimate bone mineral density (BMD) from plain radiographs and derive T-scores. Osteoporosis was defined as a T-score ≤ − 2.5. Patient characteristics, radiographic findings, and risk factors for osteoporosis were analyzed. Results: Among 1987 patients (mean age 66.4 ± 15.1 years; 41.3% men), osteoporosis was identified in 872 patients (43.9%). The prevalence increased with age and was higher in women than in men (58.7% vs 22.8%, P < 0.001). Osteoporosis was associated with femoral neck (OR = 3.8, 95% CI: 2.7–5.2) and intertrochanteric fractures (OR = 7.0, 95% CI: 4.5–11.0). Patients with lower T-scores had a higher risk of hip fractures, especially those with T-scores ≤ − 3.0 (OR = 11.5, 95% CI: 5.5–24.5). Conclusions AI-based analysis of pelvic and hip radiographs is a feasible and effective tool for osteoporosis screening in Vietnam. The prevalence of osteoporosis in this hospital-based setting was high, particularly among elderly women.AI-assisted screening may offer an accessible strategy for early detection of osteoporosis in resource-limited settings.

A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

Dilated cardiomyopathy is the most common form of cardiomyopathy in children and often leads to irreversible myocardial dysfunction. To improve the prognosis, it is critical to identify rare but reversible causes. We report a 12-year-old girl referred to the emergency department for dyspnea on exertion and generalized edema that lasted for 1 month. She gained 20 kg over the past 3 years, which had gone uninvestigated. Transthoracic echocardiography demonstrated left ventricular dysfunction with pericardial effusion. Thyroid function tests revealed concentrations of free T4 and thyroid-stimulating hormone of 0.12 ng/dL (reference value, 0.93-1.7) and 86.9 µIU/mL (0.3-4.2), respectively, with anti-thyroid peroxidase and anti-thyroglobulin antibodies elevated, confirming the presence of autoimmune hypothyroidism. We initiated heart failure management alongside levothyroxine replacement therapy. After 5 months of treatment, a follow-up echocardiography showed improved left ventricular and thyroid function.