Initial sarcopenia and body composition changes as prognostic factors in cervical cancer patients treated with concurrent chemoradiation: An artificial intelligence-based volumetric study.

OBJECTIVES: This study aimed to investigate the influence of baseline sarcopenia and changes in body composition on survival during cervical cancer treatment. METHODS: Patients diagnosed with stage IB1-IVB cervical cancer who underwent primary concurrent chemoradiation therapy (CCRT) between 2002 and 2022 were included. The exclusion criteria were prior radical hysterectomy, lack of pretreatment computed tomography (CT) imaging, or significant comorbidities. An artificial intelligence-based automatic segmentation program assessed body composition by analyzing CT images, defining L3 sarcopenia (L3 skeletal muscle index [SMI] <39cm2/m2) and volumetric sarcopenia (volumetric SMI <180.4 cm3/m3). Comparative and multivariate analyses identified the prognostic factors. The impact of body component changes during CCRT was explored. RESULTS: Among 347 patients, there were 125 recurrences and 59 deaths (median follow-up, 50.5 months). Seven patients were excluded from the volumetric sarcopenia analysis because of incomplete baseline CT data, and 175 patients were included in the analysis of body composition changes. Patients with L3 sarcopenia had a lower 5-year progression-free survival (PFS) rate (55.6% vs. 66.2%, p = 0.027), while those with volumetric sarcopenia showed a poorer 5-year overall survival rate (76.5% vs. 85.1%, p = 0.036). Patients with total fat loss during CCRT had a worse 5-year PFS rate than those with total fat gain (61.9% vs. 73.8%, p = 0.029). Multivariate analyses revealed that total fat loss (adjusted hazard ratio [aHR], 2.172; 95% confidence interval [CI], 1.066-4.424; p = 0.033) was a significant factor for recurrence, whereas L3 sarcopenia was not. Volumetric sarcopenia increased the risk of death by 1.75-fold (aHR, 1.750; 95% CI, 1.012-3.025; p = 0.045). CONCLUSIONS: Among patients with cervical cancer undergoing CCRT, initial volumetric sarcopenia and fat loss during treatment are survival risk factors. These findings suggest the potential importance of personalized supportive care, including tailored nutrition and exercise interventions.

A synergistic effect of herb and acupuncture on the methamphetamine.

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)'s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH. Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data. Results: Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05). Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

Successful desensitization to atezolizumab-induced near-fatal anaphylaxis in patients with hepatocellular carcinoma: A case report and literature review.

Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.

Near-infrared laser diode mitigates Aß1-42-induced neurodegeneration in cortical neurons.

Alzheimer's disease, a prevalent neurodegenerative condition primarily affecting older adults, remains incurable. Its principle pathological hallmark is the accelerated accumulation of amyloid ß (Aß) protein. This study investigates the potential of photobiomodulation using near infrared light to counteract Aß1-42-induced synaptic degeneration and neurotoxicity. We focused on the effect of 808 nm near-infrared laser diode (LD) on Aß1-42 cytotoxicity in primary cultured cortical neurons. We assessed cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, observing substantial benefits from LD irradiation with a power of 10 mW and a dose of 30 J. Cells exposed to Aß1-42 exhibited morphological changes indicative of synaptic damage and a significant decrease in the number of postsynaptic density protein-95 (PSD-95) contacts, which were significantly improved with near-infrared LD therapy. Furthermore, this therapy reduced Aß and phosphorylated tau (P-tau) protein accumulation. Additionally, near-infrared LD irradiation substantially lessened the Aß1-42-induced rise in glial fibrillary acid protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) in astrocytes and microglia. Remarkably, near-infrared LD irradiation effectively inhibited phosphorylation of key proteins involved in Aß1-42-induced necroptosis, namely Receptor-interacting protein kinase-3 (RIP3) and Mixed Lineage Kinase domain-Like protein (MLKL). Our findings suggest that near-infrared LD treatment significantly reduces neurodegeneration by reducing glial overactivation and neuronal necroptosis triggered by Aß1-42. Thus, near-infrared LD treatment emerges as a promising approach for slowing or treating Alzheimer's disease, offering new avenues in its management.

Long-term acclimation to organic carbon enhances the production of loliolide from Scenedesmus deserticola.

Production of functional biocompounds from microalgae has garnered interest from different industrial sectors; however, their overall productivity must be substantially improved for commercialization. Herein, long-term acclimation of Scenedesmus deserticola was conducted using glucose as an organic carbon source to enhance its heterotrophic capabilities and the production potential of loliolide. A year-long acclimation on agar plates led to the selection of S. deserticola HS4, which exhibited at least 2-fold increase in loliolide production potential; S. deserticola HS4 was subjected to further screening of its cultivation conditions and fed-batch cultivation was subsequently performed in liter-scale reactors. While S. deserticola HS4 exhibited shifts in cellular morphology and biochemical composition, the results suggested a substantial increase in its loliolide productivity regardless of trophic modes. Collectively, these results highlight the potential of long-term acclimation as an effective strategy for improving microalgal crops to align with industrial production practices.

Gilvirhabdus luticola gen. nov., sp. nov., a mesophilic and halophilic bacterium isolated from tidal flat sediment.

Two novel bacteria, MJ-SS3T and MJ-SS4, were isolated from tidal flat sediment sampled in Gochang, Republic of Korea. The isolates were Gram-stain-negative, aerobic, non-motile, rod-shaped, yellow-coloured, oxidase-positive, and catalase-positive. Strains MJ-SS3T and MJ-SS4 grew at 20-37 °C (optimum, 30 °C), at pH 6-8 (optimum, pH 7.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 2.0 % NaCl). Strains MJ-SS3T and MJ-SS4 showed 99.9 % 16S rRNA gene sequence similarity. Phylogenetic analysis based on genome and 16S rRNA gene sequences indicated that strains MJ-SS3T and MJ-SS4 were affiliated with the family Flavobacteriaceae and most closely related to Formosa maritima 1494T (95.3 %), Hanstruepera flava NBU2984T (95.2 %), Yeosuana marina JLT21T (95.2 %), Meridianimaribacter flavus NH57NT (95.1 %), and Geojedonia litorea YCS-16T (95.1 %). The major respiratory quinone was menaquinone-6. The major identified polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, and amino lipids. The major cellular fatty acids of strain MJ-SS3T were iso-C15 : 1 G (24.6 %), iso-C15 : 0 (21.6 %), and iso-C17 : 0 3-OH (15.8 %). The genome length of strain MJ-SS3T is 3.1 Mbp (DNA G+C content, 32.5 mol%) and it has 2822 coding and 59 tRNA genes. The average amino acid identity and average nucleotide identity values, as well as biochemical, phylogenetic, and physiological characteristics, strongly supported the genotypic and phenotypic differentiation of strains MJ-SS3T and MJ-SS4 from other members of the family Flavobacteriaceae. Hence, strains MJ-SS3T and MJ-SS4 are considered to represent a novel species of a new genus in the family Flavobacteriaceae, for which the Gilvirhabdus luticola gen. nov., sp. nov. is proposed. The type strain is MJ-SS3T (=KCTC 102114T=KEMB 20189T=JCM 36595T), with reference strain MJ-SS4 (=KCTC 102115=KEMB 20190).

Deep learning-based quantification of brain atrophy using 2D T1-weighted MRI for Alzheimer's disease classification.

Background: Determining brain atrophy is crucial for the diagnosis of neurodegenerative diseases. Despite detailed brain atrophy assessments using three-dimensional (3D) T1-weighted magnetic resonance imaging, their practical utility is limited by cost and time. This study introduces deep learning algorithms for quantifying brain atrophy using a more accessible two-dimensional (2D) T1, aiming to achieve cost-effective differentiation of dementia of the Alzheimer's type (DAT) from cognitively unimpaired (CU), while maintaining or exceeding the performance obtained with T1-3D individuals and to accurately predict AD-specific atrophy similarity and atrophic changes [W-scores and Brain Age Index (BAI)]. Methods: Involving 924 participants (478 CU and 446 DAT), our deep learning models were trained on cerebrospinal fluid (CSF) volumes from 2D T1 images and compared with 3D T1 images. The performance of the models in differentiating DAT from CU was assessed using receiver operating characteristic analysis. Pearson's correlation analyses were used to evaluate the relations between 3D T1 and 2D T1 measurements of cortical thickness and CSF volumes, AD-specific atrophy similarity, W-scores, and BAIs. Results: Our deep learning models demonstrated strong correlations between 2D and 3D T1-derived CSF volumes, with correlation coefficients r ranging from 0.805 to 0.971. The algorithms based on 2D T1 accurately distinguished DAT from CU with high accuracy (area under the curve values of 0.873), which were comparable to those of algorithms based on 3D T1. Algorithms based on 2D T1 image-derived CSF volumes showed high correlations in AD-specific atrophy similarity (r = 0.915), W-scores for brain atrophy (0.732 ≤ r ≤ 0.976), and BAIs (r = 0.821) compared with those based on 3D T1 images. Conclusion: Deep learning-based analysis of 2D T1 images is a feasible and accurate alternative for assessing brain atrophy, offering diagnostic precision comparable to that of 3D T1 imaging. This approach offers the advantage of the availability of T1-2D imaging, as well as reduced time and cost, while maintaining diagnostic precision comparable to T1-3D.

Different associations between body mass index and Alzheimer's markers depending on metabolic health.

BACKGROUND: Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status. METHODS: We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aß positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aß positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores. RESULTS: Being underweight increased the risk of Aß positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aß positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aß positivity (OR = 0.38, 95% CI 0.26-0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16-2.47). Decreased Aß positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (ß = 1.423, p = 0.037) compared to being normal weight, especially in the MH group. CONCLUSIONS: Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer's markers, which, in turn, lead to better clinical outcomes.

Post-calcination as an effective approach to enhance adsorption of arsenic and antimony anions by Mg/Al layered double hydroxide-decorated spent coffee ground biochars: Role of charge properties and active sites.

This study evaluated the effects of post-calcination on the charge properties and active sites of Mg/Al layered double hydroxide-decorated spent coffee ground biochars (LDHMgAl@SCGB) governing adsorption behaviors and mechanisms of arsenic (AsV) and antimony (SbV) anions from aqueous phases. Post-calcinated LDHMgAl@SCGB (PLDHMgAl@SCGB) exhibited higher adsorption capacities for AsV and SbV compared to spent coffee ground biochars (SCGB) and LDHMgAl@SCGB as post-calcination of LDHMgAl@SCGB enhanced the charge properties (surface zeta potential at pH 7.0: SCGB = -21.8 mV, LDHMgAl@SCGB = 28.5 mV, and PLDHMgAl@SCGB = 34.4 mV) and increased active sites by eliminating the anions (i.e., Cl- ions) and water molecules at its interlayers. The calculated kinetic, intra-particle diffusion, and isotherm parameters indicated that the chemisorption and intra-particle diffusion were mainly responsible for the adsorption of AsV and SbV by SCGB, LDHMgAl@SCGB, and PLDHMgAl@SCGB. Moreover, post-calcination of LDHMgAl@SCGB enhanced its selectivity toward AsV and SbV by reinforcing the electrostatic surface complexation via its improvement of charge properties. Since PLDHMgAl@SCGB exhibited the excellent reusability for the adsorption of AsV (reuse efficiency > 63.6%) and SbV (reuse efficiency > 52.1%), it can be concluded that post-calcination of LDHMgAl@SCGB is a promising method for improving the adsorption capacities for AsV and SbV in real water matrices.

Exposure to Radiofrequency Induces Synaptic Dysfunction in Cortical Neurons Causing Learning and Memory Alteration in Early Postnatal Mice.

The widespread use of wireless communication devices has necessitated unavoidable exposure to radiofrequency electromagnetic fields (RF-EMF). In particular, increasing RF-EMF exposure among children is primarily driven by mobile phone use. Therefore, this study investigated the effects of 1850 MHz RF-EMF exposure at a specific absorption rate of 4.0 W/kg on cortical neurons in mice at postnatal day 28. The results indicated a significant reduction in the number of mushroom-shaped dendritic spines in the prefrontal cortex after daily exposure for 4 weeks. Additionally, prolonged RF-EMF exposure over 9 days led to a gradual decrease in postsynaptic density 95 puncta and inhibited neurite outgrowth in developing cortical neurons. Moreover, the expression levels of genes associated with synapse formation, such as synaptic cell adhesion molecules and cyclin-dependent kinase 5, were reduced in the cerebral cortexes of RF-EMF-exposed mice. Behavioral assessments using the Morris water maze revealed altered spatial learning and memory after the 4-week exposure period. These findings underscore the potential of RF-EMF exposure during childhood to disrupt synaptic function in the cerebral cortex, thereby affecting the developmental stages of the nervous system and potentially influencing later cognitive function.

Comparison of survival and complications between minimally invasive and open staging surgeries in non-endometrioid endometrial cancer.

OBJECTIVE: This study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer. METHODS: Clinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004-2017). RESULTS: In total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521-6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455-10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660-15.378; P = .004). CONCLUSIONS: Surgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context.

Standardization of an antimicrobial resistance surveillance network through data management.

Introduction: The rapid spread of COVID-19 worldwide within 2 months demonstrated the vulnerability of the world's population to infectious diseases. In 2015, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) was launched to combat antimicrobial resistance (AMR). However, there has been no comprehensive assessment of the decade-long global battle against AMR based on GLASS data. Methods: South Korea established Kor-GLASS (Korean-GLASS) to proactively monitor data quality and enable international collaborations. A unique feature of Kor-GLASS is the quality control center (QCC), which uses network hubs and ensures standardized, high-quality data through interlaboratory proficiency testing (IPT) and external quality assessment (EQA). In addition, the QCC multifaceted endeavors for integrated data quality management. Results: Since 2020, high-quality AMR data have indicated fluctuating antibiotic resistance rates in South Korea. This trend does not align with the decrease in antibiotic usage seen in humans but coincides with non-human antibiotic sales, indicating a need for greater monitoring of non-human antibiotic resistance. Comprehensive and robust management taking account of the intricate interplay among humans, animals, and the environment is essential. Kor-GLASS has been expanded into a "One Health" multiagency collaborative initiative. Discussion: Although a standardized solution is not suitable for all countries, it must align with the local context and international standards. A centralized top-down management structure such as that of the QCC is essential to ensure continuous data quality coordination. Sustained efforts and surveillance systems are crucial for monitoring and managing AMR and safeguarding human health.

Licochalcone A attenuates NMDA-induced neurotoxicity.

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 µg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.

Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis.

Background: Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of transient elastography (TE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. Methods: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. Results: We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine TE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment TE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. TE >8.4-11 kPa and FIB-4 >3.25 measured after SVR, maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment TE. That of TE measured after the SVR was 11.2 kPa. Conclusion: TE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

Modeling of HIV-1 prophylactic efficacy and toxicity with islatravir shows non-superiority for oral dosing, but promise as a subcutaneous implant.

HIV prevention with pre-exposure prophylaxis (PrEP) constitutes a major pillar in fighting the ongoing epidemic. While daily oral PrEP adherence may be challenging, long-acting (LA-)PrEP in oral or implant formulations could overcome frequent dosing with convenient administration. The novel drug islatravir (ISL) may be suitable for LA-PrEP, but dose-dependent reductions in CD 4 + $$ \mathrm{CD}{4}^{+} $$ T cell and lymphocyte counts were observed at high doses. We developed a mathematical model to predict ISL pro-drug levels in plasma and active intracellular ISL-triphosphate concentrations after oral vs. subcutaneous implant dosing. Using phase II trial data, we simulated antiviral effects and estimated HIV risk reduction for multiple dosages and dosing frequencies. We then established exposure thresholds where no adverse effects on immune cells were observed. Our findings suggest that implants with 56-62 mg ISL offer effective HIV risk reduction without reducing lymphocyte counts. Oral 0.1 mg daily, 3-5 mg weekly, and 10 mg biweekly ISL provide comparable efficacy, but weekly and biweekly doses may affect lymphocyte counts, while daily dosing regimen offered no advantage over existing oral PrEP. Oral 0.5-1 mg on demand provided > 90 % $$ >90\% $$ protection, while not being suitable for post-exposure prophylaxis. These findings suggest ISL could be considered for further development as a promising and safe agent for implantable PrEP.

Optimal cut-offs of transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background/aims: Opinions differ regarding transient elastography and magnetic resonance elastography (TE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of TE and MRE for diagnosing AF. Methods: Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating TE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for TE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results: A total of 19,199 patients from 63 studies using TE showed diagnostic AUC of 0.83(95% confidence interval: 0.80-0.86), 0.83(0.80-0.86), 0.87(0.84-0.90), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89(0.86-0.92), 0.92(0.89-0.94), 0.89(0.86-0.92), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages respectively. The diagnostic AUC for AF using TE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. Conclusions: TE(7.1-7.9 kPa) and MRE(3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Assessment of the postoperative prognosis in patients with hepatocellular carcinoma using transient elastography: A systemic review and meta-analysis.

Background and Aims: This meta-analysis examined whether preoperative vibration-controlled transient elastography (VCTE) can predict postoperative complications and recurrence in patients undergoing hepatic resection for hepatocellular carcinoma (HCC). Methods: A systematic literature search was conducted using Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases. Out of 431 individual studies, thirteen published between 2008 and 2022 were included. Five studies focused on HCC recurrence, while eight examined postoperative complications. Results: The meta-analysis of five studies on HCC recurrence showed that the high-risk group with a high VCTE score had a significantly increased recurrence rate after hepatic resection (hazard ratio [HR], 2.14). The cutoff value of VCTE in the high-risk group of HCC recurrence was 7.4-13.4kPa, the sensitivity was 0.60 (95% CI 0.47-0.72), and the specificity was 0.60 (95% CI 0.46-0.72). The area under the receiver operating characteristic curve (AUC) of the liver stiffness measured by VCTE to predict the HCC recurrence was 0.63 (95% CI 0.59-0.67). The meta-analysis on the postoperative complications revealed a significantly increased risk of postoperative complications in the high-risk group (12-25.6kPa) with a high VCTE value (risk ratio [RR], 8.32). The AUC of the liver stiffness measured by VCTE to predict the postoperative complications was 0.87(95% CI 0.84-0.90), the sensitivity was 0.76 (95% CI 0.55-0.89) and the specificity was 0.85 (95% CI 0.73-0.92). Conclusions: This meta-analysis suggests that preoperative VCTE in patients undergoing hepatic resection for HCC is useful in identifying individuals at a high risk of postoperative complications and HCC recurrence.