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Abstract Small extracellular vesicles (sEVs) provide major promise for advances in cancer diagnostics, prognostics, and therapeutics, ascribed to their distinctive cargo reflective of pathophysiological status, active involvement in intercellular communication, as well as their ubiquity and stability in bodily fluids. As a result, the field of sEV research has expanded exponentially. Nevertheless, there is a lack of standardisation in methods for sEV isolation from cells grown in serum‐containing media. The majority of researchers use serum‐containing media for sEV harvest and employ ultracentrifugation as the primary isolation method. Ultracentrifugation is inefficient as it is devoid of the capacity to isolate high sEV yields without contamination of non‐sEV materials or disruption of sEV integrity. We comprehensively evaluated a protocol using tangential flow filtration and size exclusion chromatography to isolate sEVs from a variety of human and murine cancer cell lines, including HeLa, MDA‐MB‐231, EO771 and B16F10. We directly compared the performance of traditional ultracentrifugation and tangential flow filtration methods, that had undergone further purification by size exclusion chromatography, in their capacity to separate sEVs, and rigorously characterised sEV properties using multiple quantification devices, protein analyses and both image and nano‐flow cytometry. Ultracentrifugation and tangential flow filtration both enrich consistent sEV populations, with similar size distributions of particles ranging up to 200 nm. However, tangential flow filtration exceeds ultracentrifugation in isolating significantly higher yields of sEVs, making it more suitable for large‐scale research applications. Our results demonstrate that tangential flow filtration is a reliable and robust sEV isolation approach that surpasses ultracentrifugation in yield, reproducibility, time, costs and scalability. These advantages allow for implementation in comprehensive research applications and downstream investigations.

Background Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. Methods In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. Results Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P  = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P  < .01) and a longer OS (not reached vs. 5.5 months, P  = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P  < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P  = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P  = .97) compared to group B. Conclusions The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues. Methods: We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance. Results: A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914–4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score. Conclusions: The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEVs) provide major promise for advances in cancer diagnostics, prognostics, and therapeutics, ascribed to their distinctive cargo reflective of pathophysiological status, active involvement in intercellular communication, as well as their ubiquity and stability in bodily fluids. As a result, the field of sEV research has expanded exponentially. Nevertheless, there is a lack of standardisation in methods for sEV isolation from cells grown in serum‐containing media. The majority of researchers use serum‐containing media for sEV harvest and employ ultracentrifugation as the primary isolation method. Ultracentrifugation is inefficient as it is devoid of the capacity to isolate high sEV yields without contamination of non‐sEV materials or disruption of sEV integrity. We comprehensively evaluated a protocol using tangential flow filtration and size exclusion chromatography to isolate sEVs from a variety of human and murine cancer cell lines, including HeLa, MDA‐MB‐231, EO771 and B16F10. We directly compared the performance of traditional ultracentrifugation and tangential flow filtration methods, that had undergone further purification by size exclusion chromatography, in their capacity to separate sEVs, and rigorously characterised sEV properties using multiple quantification devices, protein analyses and both image and nano‐flow cytometry. Ultracentrifugation and tangential flow filtration both enrich consistent sEV populations, with similar size distributions of particles ranging up to 200 nm. However, tangential flow filtration exceeds ultracentrifugation in isolating significantly higher yields of sEVs, making it more suitable for large‐scale research applications. Our results demonstrate that tangential flow filtration is a reliable and robust sEV isolation approach that surpasses ultracentrifugation in yield, reproducibility, time, costs and scalability. These advantages allow for implementation in comprehensive research applications and downstream investigations. [ABSTRACT FROM AUTHOR]

Sorafenib has been used to treat advanced hepatocellular carcinoma (aHCC). However, there is no evidence for a response of different target lesions to sorafenib administration. Therefore, we aimed to evaluate the effect of sorafenib on various aHCC target lesions. The outcomes of sorafenib treatment on aHCC, i.e., treatment response for all Child A status patients receiving the drug, were analyzed. Of 377 aHCC patients, 73 (19.3%) had complete/partial response to sorafenib, while 134 (35.4%) and 171 (45.2) had a stable or progressive disease, respectively, in the first six months. Of the evaluated metastatic lesions, 149 (39.4%), 48 (12.7%), 123 (32.5%), 98 (25.9%), 83 (22.0%), and 45 (11.9%) were present in liver, bone, lung, portal/hepatic vein thrombus, lymph nodes, and peritoneum, respectively. The overall survival and duration of treatment were 16.9 ± 18.3 and 8.1 ± 10.5 months (with median times of 11.4 and 4.6, respectively). Our analysis showed poor outcomes in macroscopic venous thrombus and bone, higher AFP, and multiple target lesions. ALBI grade A had a better outcome. Sorafenib administration showed good treatment outcomes in selected situations. PD patients with thrombus or multiple metastases should be considered for sorafenib second-line treatment. The ALBI liver function test should be selected as a treatment criterion. [ABSTRACT FROM AUTHOR]

Background and Aims: The Albumin-Bilirubin (ALBI) grade is a good index for liver function evaluation and is also associated with the outcomes of hepatocellular carcinoma patients receiving TACE. However, the correlation between the dynamic change to the ALBI score and clinical outcome is seldom discussed. Therefore, this study aimed to investigate the application of ALBI grade and dynamic change of ALBI grade (delta ALBI grade) after first TACE for prognosis prediction in HCC patients with chronic hepatitis C infection. Method: From January 2005 to December 2015, newly diagnosed naive chronic hepatitis C-hepatocellular carcinoma (CHC-HCC) patients who were treated with TACE as the initial treatment at the Chang Gung Memorial Hospital, Linkou Medical Center, were retrospectively recruited. The pre-treatment host factors, tumor status and noninvasive markers were collected. The Cox regression model was used to identify independent predictors of overall survival and tumor recurrence. Results: Among 613 treatment-naive CHC-HCC patients, 430 patients died after repeated TACE during a median follow-up of 26.9 months. Complete remission after repeated TACE occurred in 46.2% patients, and 208 patients (33.9%) had tumor recurrence, with a median recurrence-free interval of 8.5 months. In Cox regression analysis, ALBI grade II/III (aHR: 1.088, p = 0.035) and increased delta ALBI grade (aHR: 1.456, p = 0.029) were independent predictive factors for tumor recurrence. Furthermore, ALBI grade II/III (aHR: 1.451, p = 0.005) and increased delta ALBI grade during treatment (aHR: 1.436, p = 0.006) were predictive factors for mortality, while achieving complete response after repeated TACE (aHR: 0.373, p < 0.001) and anti-viral therapy (aHR: 0.580, p = 0.002) were protective factors for mortality. Conclusion: Both ALBI and delta ALBI grade are independent parameters to predict survival and tumor recurrence of CHC-HCC patients receiving TACE treatment. [ABSTRACT FROM AUTHOR]

Probiotics comprise a large group of microorganisms, which have different properties and thus confer different benefits. The use of probiotics has shown promising results in the management of diarrheal diseases. While the availability of probiotic products has flourished in the marketplace, there is limited guidance on the selection of probiotics for clinical use. This position paper is aimed at informing clinicians about the proper selection criteria of probiotics based on current evidence on strain‐specific efficacy and safety for the management of diarrheal diseases. Members of the working group discussed issues on probiotic use in clinical practice, which were then drafted into statements. Literature to support or refute the statements were gathered through a search of medical literature from 2011 to 2020. Recommendations were formulated based on the drafted statements and evidence gathered, revised as necessary, and finalized upon agreement of all members. Twelve statements and recommendations were developed covering the areas of quality control in the manufacturing of probiotics, criteria for selection of probiotics, and established evidence for use of probiotics in diarrheal diseases in adults and children. Recommendations for the use of specific probiotic strains in clinical practice were categorized as proven and probable efficacy based on strength of evidence. Robust evidence is available to support the use of probiotics for diarrheal diseases in clinical practice. Based on the results obtained, we strongly advocate the careful evaluation of products, including manufacturing practices, strain‐specific evidence, and contraindications for at‐risk populations when choosing probiotics for use in clinical practice. [ABSTRACT FROM AUTHOR]

The distribution, free concentration and metabolism of drugs can be significantly altered as a result of binding to albumin. At the same time, the conformational of serum albumin was also changed by interaction with low molecular weight drugs. In present work, we first equilibrated HSA in aqueous solution to obtain the solvated-HSA model. Further solvated-HSA was performed molecular docking with paclitaxel to find the binding sites. The two docking HSA-paclitaxel complexes were obtained and further equilibrated by a 12 ns MD simulation. Then, MMPBSA method was used to investigate the binding free energy of them. Finally, we correlated the fluctuations of residues with corresponding changes in the secondary structure by dssp method. Two binding sites of paclitaxel were found on HSA having considered the solvation effect. More hydrogen bonds were formed at site I respected to site II. A larger binding energy for primary binding also indicated that paclitaxel showed higher binding affinity mainly due to the stronger hydrogen bonding interactions. There was a significant difference between the two complexes on structure according to the dssp results. Moreover, structure of the binding sites exhibited more fluctuations after binding paclitaxel compared with other regions. Paclitaxel binding also induced distinct conformational changes in drug binding site even when it was empty and have contributed to a reduced binding capacity of HSA towards adriamycin. [ABSTRACT FROM PUBLISHER]

A new polygon positron emission mammography imaging system (PEMi) was developed in 2009 by the Institute of High Energy Physics, Chinese Academy of Sciences. PEMi is constructed in a polygon structure with lutetium yttrium orthosilicate crystal arrays mounted on a position-sensitive photomultiplier. The system consists of 64 blocks and each block is arranged in 16 \times 16 crystal arrays with a pixel size of 1.9~\times 1.9~ \times 15 mm. The diameter of the detector ring is 166 mm, and the axial length is 128 mm. The transaxial field of view of PEMi is 110 mm. The goal of the initial study was to test PEMi’s performance and the clinical imaging ability with a small group of selected subjects. The detectors have a measured intrinsic spatial resolution averaging 1.67 mm. The axial and tangential resolution remained under 2.5-mm full width at half maximum within the central 5-cm diameter of the field of view. The hot rods with a diameter of 1.7 mm can be clearly identified, and the structure of the region containing 1.35-mm diameter rods can also be observed. Using a 6-ns coincidence timing window and a \ 360 \sim \ 660-keV energy window, the peak sensitivity of the tomograph is 6.88%. The noise-equivalent count rate peak is 110\thinspace766 cps for a breast-like cylindrical phantom of 100 mm in diameter at an activity concentration of 0.03~\MBq/cc. The recovery coefficients ranged from 0.21 to 0.85 for rods between 1 mm and 5 mm in the image-quality phantom. The reconstructed image resolution achieved an improvement compared with whole-body positron emission tomography (PET), which might reduce the lower threshold on detectable lesion size. Example patient images demonstrate that PEMi is clinically feasible. And more detailed structure information was obtained with PEMi than with the whole-body PET imaging. [ABSTRACT FROM AUTHOR]

Abstract: Differences in gender immune response have resulted in differences in immune protection and susceptibility to inflammatory diseases. Cultured peripheral blood mononuclear cells (PBMC) are widely used in immunomodulation studies, yet the influence of gender is usually not considered. We examined the effect of in vitro culture and phytohaemagglutinin (PHA) stimulation on PBMC lymphocyte subsets using flowcytometry. Full blood counts of whole blood showed higher levels of lymphocyte in male subjects. Lymphocyte subsets enumeration revealed higher NK cell counts in males and higher B cells in females. Cultured PBMC resulted in significant increases in B and total T cell percentages among females and NK cells among males. PHA stimulated significantly increased percentages of NK and total T cells in males and total activated T cells (CD69+) in females. Our results showed significant gender differences in lymphocyte subsets in cultured conditions. This may affect experimental outcome. [Copyright &y& Elsevier]

Background Purpose Methods Results Conclusions Long‐axis positron emission tomography (PET) has emerged as one of the recent research directions in PET due to its ability to significantly enhance sensitivity and counting performance for low‐dose imaging, rapid imaging, and whole‐body dynamic imaging.The PET system presented in this study is a long‐axis animal PET based on lutetium–yttrium orthosilicate and silicon photomultiplier, designed for whole‐body imaging in rats. It features a diameter of 143 mm and an axial length of 213.3 mm. This study evaluated the performance of this PET system in accordance with the National Electrical Manufacturers Association (NEMA) NU 4‐2008 standards.The performance evaluation was conducted according to the NEMA NU 4‐2008 standards in terms of spatial resolution, sensitivity, counting rate performance, scatter fraction (SF) and image quality. In addition, a rat imaging study was conducted to assess the imaging capability of this PET system.The average energy resolution of the PET system was 12.87%, the average coincidence timing resolution was 751 ps. The FWHM of spatial resolution reconstructed by filtered back projection and 3D‐OSEM‐PSF algorithm at 5 mm radial offset from the axial center were 1.65 and 0.88 mm. The peak absolute sensitivity measured by a point source at the center of the field of view was evaluated as 6.71% (361–661 keV) and 10.31% (250–750 keV). For the mouse‐like phantom, the SF was 11.0% and the peak noise equivalent counting rate (NECR) was 1193 kcps at 94.2 MBq (2.54 mCi). For the rat‐like phantom, the SF was 26.8% and the NECR was 682.5 kcps at 78.6 MBq (2.12 mCi).The performance measurement results demonstrate that this PET system exhibits high sensitivity and count rate performance, making it potential for high‐quality whole‐body dynamic imaging of rats. [ABSTRACT FROM AUTHOR]

Background: Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats. Results: SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p < 0.05). We observed that 3 months of exposure to PM2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure. Conclusions: Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension. [ABSTRACT FROM AUTHOR]

The Eplus-260 primate PET is an animal PET imaging system developed by the Institute of High Energy Physics, Chinese Academy of Sciences, which is designed to image non-human primates, especially the brain of large non-human primates. The system consists of 48 block detectors arranged in two 24-sided rings with a ring diameter of 263 mm and an axial extent of 64 mm. Each block detector is composed of a 16  ×  16 cerium-doped lutetium–yttrium orthosilicate crystal array with a pixel size of 1.9  ×  1.9  ×  10 mm3. This article presents a performance evaluation of the PET scanner according to the National Electrical Manufacturers Association NU-4 2008 standards. All measurements were made for an energy window of 360–660 keV and a coincidence timing window of 2 ns. In terms of the FWHM, the FBP reconstructed spatial resolution results in all three directions at the radial position of 5 mm were better than or approached to 2 mm, and remained below 3.0 mm within the central 5 cm diameter of the FOV. The peak absolute sensitivity of the scanner was measured 1.80%. For a monkey-sized phantom, the scatter fraction was 34.2% and the peak noise equivalent count rate (NECR) was 26.5 kcps at 64.3 kBq/cc. The overall imaging capabilities of the scanner were also assessed using in vivo imaging study of a rhesus macaque. The performance measurements demonstrate that the Eplus-260 primate PET scanner has the potential ability to obtain good quality and high-contrast images for non-human primates, especially the brain of large non-human primates and could be considered as one technologically advanced dedicated non-human primate PET scanner available today. [ABSTRACT FROM AUTHOR]

A point spread function (PSF) for the blurring component in positron emission tomography (PET) is studied. The PSF matrix is derived from the single photon incidence response function. A statistical iterative reconstruction (IR) method based on the system matrix containing the PSF is developed. More specifically, the gamma photon incidence upon a crystal array is simulated by Monte Carlo (MC) simulation, and then the single photon incidence response functions are calculated. Subsequently, the single photon incidence response functions are used to compute the coincidence blurring factor according to the physical process of PET coincidence detection. Through weighting the ordinary system matrix response by the coincidence blurring factors, the IR system matrix containing the PSF is finally established. By using this system matrix, the image is reconstructed by an ordered subset expectation maximization (OSEM) algorithm. The experimental results show that the proposed system matrix can substantially improve the image radial resolution, contrast, and noise property. Furthermore, the simulated single gamma-ray incidence response function depends only on the crystal configuration, so the method could be extended to any PET scanner with the same detector crystal configuration. [ABSTRACT FROM AUTHOR]

Abstract: Structural brain abnormalities have been widely reported in major depressive disorder (MDD). However, many previous results cannot exclude the interferences of medication or multiple recurrent episodes. In this study, we examined structural brain abnormalities by comparing 68 drug-naïve first-episode adult-onset MDD and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) methods were used. The mean values of grey matter volume/white matter volume (GMV/WMV) were calculated, then the differences between MDD and HCs were analyzed, and the associations of the differences with clinical characteristics of depression were discussed. The whole brain GMV/WMV did not differ between MDD patients and HCs; however, the regional GMV of the right pre-supplementary motor area (pre-SMA) was smaller in MDD patients. The GMV of both hippocampi was positively correlated with symptom severity and lower in patients with long durations. These results indicate the GMV reduction of the pre-SMA at an early stage of depression, whereas the GMV of the hippocampus is associated with depressive characteristics. Moreover, the whole brain GMV/WMV was negatively related to the duration of depression, supporting that volume loss could become progressive during the development of disease. These results may suggest the importance of identifying and intervening depression at an early stage, especially the first year after onset, to prevent volume loss in the brain. [Copyright &y& Elsevier]

X-ray Computed Tomography (CT) method is an integral part of hydraulic-fracture imaging, but its application to micro-fractures in cores is limited. This paper documents the visualization of fractured cores via an accessorial PET-CT approach to improve both spatial resolution and image contrast. PET-CT approach combines X-ray Computed Tomography (CT) and positron emission tomography (PET) method. CT technique provides information of core structure and accurate location of fractures based on density variations. PET is a nuclear imaging technique through inducing radionuclide into fractures, offering the potential to overcome CT limitations by providing information of micro-fractures. Combined PET-CT approach has been demonstrated as a technical advancement for imaging fractured cores better than simply CT or PET method. Comprehensive information of core structure, micro-fractures and connected fractures could be provided by PET-CT method. The applicability of each visualization technique was evaluated, the favorable implementation of combined PET-CT for laboratory core analysis was discussed. • Combined PET-CT technique was introduced to imaging hydraulic fractures in shale cores. • Improved image fusion method was proposed to fuse PET images and CT images. • Images with high resolution and contrast were obtained. • Combined PET-CT method shows superior to CT and PET method alone in providing comprehensive information of fractured cores. [ABSTRACT FROM AUTHOR]

Abstract: A PET module that comprises a pair of compact, high-resolution and large-area detectors based on silicon photomultipliers (SiPM) was developed and evaluated. The detector''s effective area was 24mm×24mm. LYSO crystals measuring 1.9mm×1.9mm×10mm and charge division circuit were employed to obtain high spatial resolution with relatively concise Front-end electronics (FEE). Initial results showed the detector to be compatible with 1.5T magnetic fields. The system''s intrinsic FWHM spatial resolution is 1.50mm. The average energy resolution is 18.5% and the coincidence timing resolution is 2.6ns. [Copyright &y& Elsevier]

Background: The combination of anti-angiogenic therapy and immune checkpoint inhibitors has revolutionized the management of unresectable hepatocellular carcinoma (uHCC). While an early-phase study demonstrated promising outcomes for lenvatinib plus pembrolizumab (L+P) in treating uHCC, the LEAP-002 trial did not meet its primary endpoint. However, the comparative efficacy between L+P and atezolizumab plus bevacizumab (A+B) as first-line treatment remains a topic of uncertainty. This study aimed to assess the effectiveness and safety of L+P in contrast to A+B among patients diagnosed with uHCC., Methods: We conducted a retrospective analysis of enrolled patients with uHCC who received L+P or A+B as initial systemic treatment at Chang Gung Memorial Hospital from June 2019 to December 2022. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by modified RECIST were compared., Results: 121 patients were recruited, with 37 receiving L+P and 84 receiving A+B. Among them, 95 (78.5%) patients were BCLC stage C, and 99 (81.8%) patients had viral etiology for HCC, predominantly chronic HBV (68.6%). Both the L+P and the A+B groups demonstrated comparable OS (18.2 months versus 14.6 months, p = 0.35) and PFS (7.3 months versus 8.9 months, p = 0.75). The ORR and DCR were similar. After propensity score matching, the results remained consistent between the matched patients. Treatment-related adverse events of any grade occurred in 30 (81.1%) in the L+P group and 62 (73.8%) in the A+B group., Conclusions: Our findings suggest that L+P and A+B exhibit comparable efficacy and safety profiles in real-world settings.

For advanced hepatocellular carcinoma (HCC), the best second-line treatment after first-line treatment with sorafenib is unclear. This study aimed to compared the efficacy of second-line regorafenib (a tyrosine kinase inhibitor) and immune checkpoint inhibitors (ICIs) in patients with advanced HCC after sorafenib therapy. This retrospective study included 89 patients with HCC treated with sorafenib, and then regorafenib (n = 58) or an ICI (n = 31). Treatment response, overall survival (OS) and progression-free survival (PFS) of the 2 groups were compared, and factors associated with post-treatment mortality or disease progression were evaluated. During follow-up period, compared to regorafenib, treatment with an ICI results in a slight increase in a 20% decrease of AFP (35.7% vs. 31.8%), complete response rate (6.5% vs. 0%), objective response rate (16.1% vs. 6.9%), median overall survival (13.3 vs. 5 months), and median PFS (3.0 vs. 2.6 months). Combined locoregional treatment (LRT) (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.15-0.99) during second-line treatment was associated with a decreased risk of post-treatment mortality. After propensity scoring matching, combined LRT during second-line treatment had longer post-treatment OS than patients without combined LRT. A 20% decrease of AFP (HR = 0.54, 95% CI: 0.31-0.94) was associated with a decreased risk of post-treatment disease progression. In conclusions, second-line treatment with regorafenib or ICI prolongs OS in patients with advanced HCC treated with sorafenib. Combined LRT during second-line treatment is associated with decreased post-treatment mortality. A 20% decrease of AFP level may be predictive of a lower rate of disease progression., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment., Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed., Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients., Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome., Competing Interests: All authors have no conflict of interest to disclosure., (© 2023 Chan et al.)

Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients., Competing Interests: None., (AJCR Copyright © 2022.)

Probiotics comprise a large group of microorganisms, which have different properties and thus confer different benefits. The use of probiotics has shown promising results in the management of diarrheal diseases. While the availability of probiotic products has flourished in the marketplace, there is limited guidance on the selection of probiotics for clinical use. This position paper is aimed at informing clinicians about the proper selection criteria of probiotics based on current evidence on strain-specific efficacy and safety for the management of diarrheal diseases. Members of the working group discussed issues on probiotic use in clinical practice, which were then drafted into statements. Literature to support or refute the statements were gathered through a search of medical literature from 2011 to 2020. Recommendations were formulated based on the drafted statements and evidence gathered, revised as necessary, and finalized upon agreement of all members. Twelve statements and recommendations were developed covering the areas of quality control in the manufacturing of probiotics, criteria for selection of probiotics, and established evidence for use of probiotics in diarrheal diseases in adults and children. Recommendations for the use of specific probiotic strains in clinical practice were categorized as proven and probable efficacy based on strength of evidence. Robust evidence is available to support the use of probiotics for diarrheal diseases in clinical practice. Based on the results obtained, we strongly advocate the careful evaluation of products, including manufacturing practices, strain-specific evidence, and contraindications for at-risk populations when choosing probiotics for use in clinical practice., (© 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)