Improved recurrence-free survival in patients with HCC with post-transplant plasma exchange.

Total plasma exchange (TPE) can play a role in cancer treatment by eliminating immune checkpoint inhibitors. This study investigated whether TPE improved oncological outcomes in patients with HCC who underwent ABO-incompatible living donor liver transplantation (LT). The study included 152 patients who underwent ABO-incompatible living donor LT for HCC between 2010 and 2021 at Samsung Medical Center. Overall survival was analyzed using the Kaplan-Meier curve, whereas HCC-specific recurrence-free survival (RFS) was analyzed using the cumulative incidence curve after propensity score matching. Cox regression and competing risks subdistribution hazard models were used to identify the risk factors associated with overall survival and HCC-specific RFS, respectively. The propensity score matching resulted in 54 matched pairs, grouped according to whether they underwent postoperative TPE [post-transplant TPE(+)] or not [post-transplant TPE(-)]. The 5-year HCC-specific RFS cumulative incidence was superior in the post-transplant TPE (+) group [12.5% (95% CI: 3.1%-21.9%)] compared with the post-transplant TPE(-) group [38.1% (95% CI: 24.4%-51.8%), p = 0.005]. In subgroup analysis for patients with microvascular invasion and those beyond the Milan criteria, the post-transplant TPE(+) group showed significantly superior HCC-specific survival. The multivariable analysis also showed that postoperative TPE had a protective effect on HCC-specific RFS (HR = 0.26, 95% CI: 0.10-0.64, p = 0.004) and that the more post-transplant TPE was performed, the better RFS was observed (HR = 0.71, 95% CI: 0.55-0.93, p = 0.012). Post-transplant TPE was found to improve RFS after ABO-incompatible living donor LT for HCC, particularly in advanced cases with microvascular invasion and beyond Milan criteria. These findings suggest that TPE may have a potential role in improving oncological outcomes in patients with HCC undergoing LT.

Development of an in vitro coculture device for the investigation of host-microbe interactions via integrative multiomics approaches.

The commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host-Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco-2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell-cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells.

New quantified measurement of fatty infiltration of the rotator cuff muscles using magnetic resonance imaging.

BACKGROUND: The degree of fatty infiltration of the rotator cuff muscle is typically evaluated using the Goutallier-Fuchs grading system, but its consistency remains controversial. This study aimed to evaluate a new quantified measurement of fatty infiltration based on three-dimensionally reconstructed volumetric data obtained from magnetic resonance images of non-pathologic shoulders using open-source software. METHODS: Fourteen shoulder 3-T magnetic resonance images (8 men, 6 women) without lesions obtained between 2010 and 2017 were analysed. Slicer version 4.6.2 was used to semi-automatically reconstruct the three-dimensional volumetric data from T2 sagittal oblique images and to differentiate fat tissue from rotator cuff muscle using the difference in signal intensity. RESULTS: The cutoff value for dividing muscle and fat was 508.9. The inter-class and intra-class correlations of each rotator cuff muscle and fat tissue were >0.9 (all P < 0.001). The mean muscle volume of the supraspinatus, infraspinatus, teres minor, and subscapularis were 15.2, 20.9, 13.3, and 29.7 mL, respectively. The muscle volume of the men was greater than that of the women (all P < 0.001), and the fat infiltration ratio was positively correlated with body mass index (all P < 0.05). CONCLUSIONS: The semi-automated quantified measurement of fatty infiltration of the rotator cuff muscles using magnetic resonance imaging and Slicer software presented excellent consistency. This technique could be an alternative measurement to complement the weak consistency of the Goutallier-Fuchs grading system. However, to reduce the error of measurement, this study evaluated non-pathologic shoulders. Therefore, further study using magnetic resonance imaging of pathologic shoulders is necessary for actual clinical application. LEVEL OF EVIDENCE: Level IV, case series, diagnostic study.

A novel series of enoyl reductase inhibitors targeting the ESKAPE pathogens, Staphylococcus aureus and Acinetobacter baumannii.

S. aureus and A. baumannii are among the ESKAPE pathogens that are increasingly difficult to treat due to the rise in the number of drug resistant strains. Novel therapeutics targeting these pathogens are much needed. The bacterial enoyl reductase (FabI) is as potentially significant drug target for developing pathogen-specific antibiotics due to the presence of alternate FabI isoforms in many other bacterial species. We report the identification and development of a novel N-carboxy pyrrolidine scaffold targeting FabI in S. aureus and A. baumannii, two pathogens for which FabI essentiality has been established. This scaffold is unrelated to other known antibiotic families, and FabI is not targeted by any currently approved antibiotic. Our data shows that this scaffold displays promising enzyme inhibitory activity against FabI from both S. aureus and A. baumannii, as well as encouraging antibacterial activity in S. aureus. Compounds also display excellent synergy when combined with colistin and tested against A. baumannii. In this combination the MIC of colistin is reduced by 10-fold. Our first generation compound displays promising enzyme inhibition, targets FabI in S. aureus with a favorable selectivity index (ratio of cytotoxicity to MIC), and has excellent synergy with colistin against A. baumannii, including a multidrug resistant strain.

Automated detection and classification of the proximal humerus fracture by using deep learning algorithm.

Background and purpose - We aimed to evaluate the ability of artificial intelligence (a deep learning algorithm) to detect and classify proximal humerus fractures using plain anteroposterior shoulder radiographs. Patients and methods - 1,891 images (1 image per person) of normal shoulders (n = 515) and 4 proximal humerus fracture types (greater tuberosity, 346; surgical neck, 514; 3-part, 269; 4-part, 247) classified by 3 specialists were evaluated. We trained a deep convolutional neural network (CNN) after augmentation of a training dataset. The ability of the CNN, as measured by top-1 accuracy, area under receiver operating characteristics curve (AUC), sensitivity/specificity, and Youden index, in comparison with humans (28 general physicians, 11 general orthopedists, and 19 orthopedists specialized in the shoulder) to detect and classify proximal humerus fractures was evaluated. Results - The CNN showed a high performance of 96% top-1 accuracy, 1.00 AUC, 0.99/0.97 sensitivity/specificity, and 0.97 Youden index for distinguishing normal shoulders from proximal humerus fractures. In addition, the CNN showed promising results with 65-86% top-1 accuracy, 0.90-0.98 AUC, 0.88/0.83-0.97/0.94 sensitivity/specificity, and 0.71-0.90 Youden index for classifying fracture type. When compared with the human groups, the CNN showed superior performance to that of general physicians and orthopedists, similar performance to orthopedists specialized in the shoulder, and the superior performance of the CNN was more marked in complex 3- and 4-part fractures. Interpretation - The use of artificial intelligence can accurately detect and classify proximal humerus fractures on plain shoulder AP radiographs. Further studies are necessary to determine the feasibility of applying artificial intelligence in the clinic and whether its use could improve care and outcomes compared with current orthopedic assessments.

Urinary benzophenone concentrations and their association with demographic factors in a South Korean population.

Benzophenone (BP) and its derivatives are widely used in various cosmetics, personal care products, and food packaging ink. The use of BP has raised concerns about the potential health risks associated with its endocrine-disrupting effects. This study evaluated urinary concentrations of BP derivatives in a national sample of the South Koreans population aged 6-89 years. From July to September in each 2010 and 2011, 1576 urine samples were collected. Urinary concentrations of benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), benzophenone-8 (BP-8), and 4-hydroxybenzophenone (4-OH-BP) were analyzed using liquid chromatography-mass spectrometry. The detection rate for BP-1 and 4-OH-BP were 56% [limit of detection (LOD) 0.59ng/mL] and 88% (LOD 0.04ng/mL), respectively, whereas those for BP-2, BP-3, BP-4, and BP-8 were all below 25%. The geometric means of urinary BP-1 and 4-OH-BP concentrations were 1.24ng/mL and 0.45ng/mL, respectively. Multiple linear regression analysis indicated that concentrations of BP-1 in and of 4-OH-BP in adults were associated with sex and age. The BP-1 and 4-OH-BP concentration of children and adolescents was associated with sex, age, income, and current area of residence. The correlation was observed between urinary concentrations of BP derivatives, which is an important indication of exposure biomarkers and the metabolic pathways from BP-3. This is the first national study to evaluate the presence of BP derivatives in urine samples from the South Korean population, stratified by demographic factors.

Urinary concentrations of parabens and their association with demographic factors: A population-based cross-sectional study.

Parabens are broad-spectrum antimicrobial agents used in a range of consumer products, including personal care products, cosmetics, and food. Recently, the widespread use of parabens has raised concerns about the potential health risks associated with their endocrine-disrupting effect. In the present study, 2541 urine samples were collected and analyzed by liquid chromatography-mass spectrometry for the determination of the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP). The detection rate and geometric mean concentrations of parabens in the general population followed the order MeP (97.7%; 116ng/mL)>EtP (97.2%; 24.7ng/mL)>PrP (96.7%; 11.0ng/mL)>BuP (83.5%; 1.13ng/mL). The composition profiles showed that MeP and EtP accounted for >90% of the urinary paraben concentration. We performed statistical analysis in order to evaluate differences between demographic variables and urinary concentrations. Our results showed that adjusted proportional change of MeP, PrP, and BuP in adults were 2.67-6.13 times higher in females than in males. The urinary concentrations of PrP in adults increased significantly with age. The adjusted proportional changes of MeP and PrP in adults were associated with increased body mass index (BMI). The adjusted proportional changes of BuP and PrP in children and adolescents were 1.44 and 1.69 times higher in females than in males. However, there was no clear association between paraben concentrations and demographic variables in the children and adolescents groups. The estimated daily intake (EDIurine) of MeP and EtP in adults were 301µg/kg bw/day, which is lower than the acceptable daily intake (ADI; 10mg/kg bw/day). In summary, our results revealed that the general population in Korea was exposed to parabens during 2009-2010, and most Koreans are exposed to parabens. The urinary levels of parabens varied by age group with demographic factors in the Korean population. The results of study may be used to establish a nationally representative baseline of exposure to parabens in risk assessment.

The Association Between Urinary Benzophenone Concentrations and Personal Care Product Use in Korean Adults.

Benzophenone (BP) derivatives are widely used in personal care products (PCPs) for protection from ultraviolet radiation. Because of their broad applications, BP derivatives have been found in various human bodily fluids. In the present study, we investigated the relationship between urinary concentrations of BP derivatives and PCP use in Korean adults. A urinary BP biomonitoring survey was conducted in Korea by the Ministry of Food and Drug Safety in 2014. BP derivatives (BP-1, BP-3, and 4-OH-BP) were measured in urine samples from 168 Korean adults (mean age, 43.2 ± 15.4 years) by high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Information about the use of PCPs in the past 7 days was obtained by direct interviews. The mean levels of BP-1, BP-3, and 4-OH-BP were 0.87, 5.87, and 0.13 ng/g creatinine, respectively. The geometric mean levels of BP-1, BP-3, and 4-OH-BP were significantly higher in female than those in male. The medians of the urinary concentration of BP derivatives were significantly higher among users of the following PCPs than those in non-users; the PCPs included sunscreen, skin care products, functional cosmetics, makeup base, makeup, lip cosmetics, eye cosmetics, color cosmetics, perfume products, and nail products. A regression analysis revealed a significant linear association between urinary BP-3 concentrations and the number of additional cosmetic products used. These findings provide evidence of a positive association between exposure to PCPs and urinary BP derivative concentrations in Korean adults.

Use of fractional CO2 laser decreases the risk of skin cancer development during ultraviolet exposure in hairless mice.

BACKGROUND: Nonmelanoma skin cancers are caused mainly by prolonged ultraviolet (UV) exposure. There is a growing interest in the prevention of skin cancer and antiaging treatment because of aging of the population. Currently, ablative fractional photothermolysis (FP) laser treatment is actively being performed for facial rejuvenation. OBJECTIVE: The objective of this study was to prove the suppressive effect of CO2 fractional laser (FL) on skin cancer development. MATERIALS AND METHODS: Two groups of hairless mice were treated with either CO2 FL or nothing at 3-week intervals during the 20 weeks of UV exposure period. The number of tumors was subsequently counted every 2 weeks over the 30-week period to the termination of the experiment. At 30 weeks, representative tumors were evaluated for tumor type. The authors also determined the messenger RNA (mRNA) expression levels of the matrix metalloproteinase 13 (MMP-13) and Type 1 procollagen. RESULTS: At 30 weeks, the UV- and FL-treated group showed a significantly lower tumor occurrence rate and a more benign progression of tumors than the UV-only treated group. The UV- and FL-treated group presented a higher mRNA level of Type 1 procollagen and a lower level of MMP-13 than the UV-only treated group. CONCLUSION: The occurrence of UV-induced skin tumors can be decreased by multiple sessions of ablative FP with CO2 laser.

V advancement eversion flap for fingertip injury: Preventing ischemia and hook-nail deformity.

Introduction: Traumatic fingertip amputation is the most common type of upper extremity injuries. The V-Y advancement flap is a reliable method for reconstructing fingertip defects, but it is associated with complications such as hook-nail deformity and suture site ischemia. Here, we describe our modifications to V-Y advancement flap technique, termed as "V advancement eversion flap" and review the outcomes of this procedure in 21 patients with fingertip amputation. Methods: This was a retrospective review of 21 consecutive patients with fingertip injury who were treated surgically using the V advancement eversion flap technique at a single trauma center between 2006 and 2019. We analyzed the age, injury location and mechanism, Allen classification, injury geometry, and objective and subjective clinical outcomes. Results: Twenty-three fingertip amputations with defect sizes greater than 1.0 cm2 from the tip to lunula were included in this study. The mean age of the patients was 43.6 years (range, 24-65 years). The average follow-up period was 20 months (range, 12-37 months). The average wound healing time (apparent epithelization) was 29.4 days (range, 14-41 days). At the final follow-up, all flaps had healed uneventfully without noticeable hook-nail deformity. In the static two-point discrimination test, the mean value was 4.61 mm in the injured finger. Patient ratings of the outcomes were "excellent" in 18 and "good" in 5 cases. Conclusion: The V advancement eversion flap technique, when properly designed and executed in fingertip amputation cases, can minimize morbidity and result in successful wound healing without flap necrosis and hook-nail deformity.

Photophore-Anchored Molecular Switch for High-Performance Nonvolatile Organic Memory Transistor.

Over the past decade, molecular-switch-embedded memory devices, particularly field-effect transistors (FETs), have gained significant interest. Molecular switches are integrated to regulate the resistance or current levels in FETs. Despite substantial efforts, realizing large memory window with a long retention time, a critical factor in memory device functionality, remains a challenge. This is due to the inability of an isomeric state of a molecular switch to serve as a stable deep trap state within the semiconductor layer. Herein, the study addresses this limitation by introducing chemical bonding between molecular switch and conjugated polymeric semiconductor, facilitating closed isomer of diarylethene (DAE) to operate as a morphologically stable deep trap state. Azide- and diazirine-anchored DAEs are synthesized, which form chemical bonds to the polymer through photocrosslinking, thereby implementing permanent and controllable trapping states nearby conjugated backbone of polymer semiconductor. Consequently, when diazirine-anchored DAE is blended with F8T2 and subjected to photocrosslinking, the resulting organic FETs exhibit remarkable memory performance, including a memory window of 22 V with a retention time over 106 s, a high photoprogrammable on/off ratio over 103, and a high operational stability over 100 photocycles. Further, photophore-anchored DAEs can achieve precise patterning, which enables meticulous control over the semiconductor layer structure.

Development and validation of risk prediction model for post-donation renal function in living kidney donors.

This study aimed to create and validate a predictive model for renal function following live kidney donation, using pre-donation factors. Accurately predicting remaining renal function post live kidney donation is currently insufficient, necessitating an effective assessment tool. A multicenter retrospective study of 2318 live kidney donors from two independent centers (May 2007-December 2019) was conducted. The primary endpoint was the reduction in eGFR to below 60 mL/min/m2 6 months post-donation. The primary endpoint was achieved in 14.4% of the training cohort and 25.8% of the validation cohort. Sex, age, BMI, hypertension, preoperative eGFR, and remnant kidney proportion (RKP) measured by computerized tomography (CT) volumetry were found significant in the univariable analysis. These variables informed a scoring system based on multivariable analysis: sex (male: 1, female: 0), age at operation (< 30: 0, 30-39: 1, 40-59: 2, ≥ 60: 3), preoperative eGFR (≥ 100: 0, 90-99: 2, 80-89: 4, < 80: 5), and RKP (≥ 52%: 0, < 52%: 1). The total score ranged from 0 to 10. The model showed good discrimination for the primary endpoint in both cohorts. The prediction model provides a useful tool for estimating post-donation renal dysfunction risk, factoring in the side of the donated kidney. It offers potential enhancement to pre-donation evaluations.

Hydrophilic Photocrosslinkers as a Universal Solution to Endow Water Affinity to a Polymer Photocatalyst for an Enhanced Hydrogen Evolution Rate.

A universal approach for enhancing water affinity in polymer photocatalysts by covalently attaching hydrophilic photocrosslinkers to polymer chains is presented. A series of bisdiazirine photocrosslinkers, each comprising bisdiazirine photophores linked by various aliphatic (CL-R) or ethylene glycol-based bridge chains (CL-TEG), is designed to prevent crosslinked polymer photocatalysts from degradation through a safe and efficient photocrosslinking reaction at a wavelength of 365 nm. When employing the hydrophilic CL-TEG as a photocrosslinker with polymer photocatalysts (F8BT), the hydrogen evolution reaction (HER) rate is considerably enhanced by 2.5-fold compared to that obtained using non-crosslinked F8BT photocatalysts, whereas CL-R-based photocatalysts yield HER rates comparable to those of non-crosslinked counterparts. Photophysical analyses including time-resolved photoluminescence and transient absorption measurements reveal that adding CL-TEG accelerates exciton separation, forming long-lived charge carriers. Additionally, the in-depth study using molecular dynamics simulations elucidates the dual role of CL-TEG: it enhances water penetration into the polymer matrix and stabilizes charge carriers after exciton generation against undesirable recombination. Therefore, the strategy highlights endowing a high-permittivity environment within polymer photocatalyst in a controlled manner is crucial for enhancing photocatalytic redox reactivity. Furthermore, this study shows that this hydrophilic crosslinker approach has a broad applicability in general polymer semiconductors and their nanoparticulate photocatalysts.

Hepatic venous territory mapping in living donor liver transplantation using right liver graft: an objective parameter for venous reconstruction.

Purpose: This study evaluated the clinical implication of hepatic venous territory mapping in living donor liver transplantation. Methods: Living donor liver transplantations performed using right graft since 2017 were included. Hepatic venous volume mapping was started in 2019. Risk factors for graft failure and overall survival were analyzed. Analysis for factors related to occlusion of reconstructed vein was performed. Results: Among 445 patients included, 213 underwent hepatic venous mapping. Hepatic venous mapping itself was not a significant factor for graft (hazard ratio [HR], 0.958; 95% confidence interval [CI], 0.441-2.082; P = 0.913) and overall survival (HR, 0.627; 95% CI, 0.315-1.247; P = 0.183). Inferior hepatic vein occlusion was a significant risk factor for both graft survival (HR, 8.795; 95% CI, 1.628-47.523; P = 0.012) and overall survival (HR, 11.13; 95% CI, 2.460-50.300; P = 0.002). In a subgroup with middle hepatic vein reconstruction, occlusion was a significant risk factor for overall survival (HR, 3.289; 95% CI, 1.304-8.296; P = 0.012). In patients with middle hepatic vein reconstruction whose venous territory volumes were measured, right anterior volume of ≥300 cm3 was protective for vein occlusion (OR, 0.317; 95% CI, 0.152-0.662; P = 0.002). In patients with V5 reconstruction, V5 volume of ≥150 cm3 was protective for vein occlusion (OR, 0.253; 95% CI, 0.087-0.734; P = 0.011). Conclusion: Inferior and middle hepatic vein reconstruction has significant impact on clinical outcome. Hepatic venous territory mapping can provide an objective measure for successful reconstruction of venous branches.

Necessity of induction agent modification for old age kidney transplant recipients.

Background: Immunosenescence gradually deteriorates the function of the immune system, making elderly patients susceptible to infection, while reducing rejection of organ transplants. Therefore, age-adaptive immunosuppression is necessary in the elderly. We evaluated clinical outcomes such as rejection and infection rate when using basiliximab and rabbit anti-thymocyte globulin (r-ATG) as induction agents in elderly and young organ transplant recipients. Methods: We retrospectively reviewed patients who underwent kidney transplantation (KT) between June 2011 and April 2019. We enrolled 704 adult KT patients and classified the patients into groups according to patient age. We compared the outcomes of infection and biopsy-proven acute rejection (BPAR) according to the type of induction agent (basiliximab and r-ATG [4.5 mg/kg]). Results: The patient group included 520 recipients (74.6%) in the younger recipient group and 179 recipients (25.4%) in the older recipient group. When r-ATG was used as an induction agent, BPAR within 6 months occurred less (p = 0.03); however, infections within 6 months were higher in older recipients. Deaths due to infection were more common in older recipients (p = 0.003). Conclusion: It may be necessary to use less intensive induction therapy for older recipients, of which dose reduction of r-ATG is one option.

Multiomics analysis reveals the biological effects of live Roseburia intestinalis as a high-butyrate-producing bacterium in human intestinal epithelial cells.

Butyrate-producing bacteria play a key role in human health, and recent studies have triggered interest in their development as next-generation probiotics. However, there remains limited knowledge not only on the identification of high-butyrate-producing bacteria in the human gut but also in the metabolic capacities for prebiotic carbohydrates and their interaction with the host. Herein, it was discovered that Roseburia intestinalis produces higher levels of butyrate and digests a wider variety of prebiotic polysaccharide structures compared with other human major butyrate-producing bacteria (Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia hominis). Moreover, R. intestinalis extracts upregulated the mRNA expression of tight junction proteins (TJP1, OCLN, and CLDN3) in human intestinal epithelial cells more than other butyrate-producing bacteria. R. intestinalis was cultured with human intestinal epithelial cells in the mimetic intestinal host-microbe interaction coculture system to explore the health-promoting effects using multiomics approaches. Consequently, it was discovered that live R. intestinalis only enhances purine metabolism and the oxidative pathway, increasing adenosine triphosphate levels in human intestinal epithelial cells, but that heat-killed bacteria had no effect. Therefore, this study proposes that R. intestinalis has potentially high value as a next-generation probiotic to promote host intestinal health.

Graft-recipient-weight ratio and lowered immunosuppression is important for the success of adult liver retransplantation.

This study analyzed the risk of liver retransplantation and factors related to better outcome. Adult liver transplantations performed during 1996-2021 were included. Comparison between first transplantation and retransplantation were performed. Among retransplantation cases, comparison between whole liver and partial liver graft was performed. Multivariable Cox analyses for analyzing risk factors for primary graft and overall patient survival were performed for the entire cohort as well as the subgroup of patients with retransplantation. A total 2237 transplantations from 2135 adults were included and 103 cases were retransplantation. A total of 44 cases (42.7%) were related to acute graft dysfunction while 59 cases (57.3%) were related to subacute or chronic graft dysfunction. Retransplantation was related poor primary graft (HR 3.439, CI 2.230-5.304, P < 0.001) and overall patient survival. (HR 2.905, CI 2.089-4.040, P < 0.001) Among retransplantations, mean serum FK506 trough level ≥ 9 ng/mL was related to poor primary graft (HR 3.692, CI 1.288-10.587, P = 0.015) and overall patient survival. (HR 2.935, CI 1.195-7.211, P = 0.019) Graft-recipient-weight ratio under 1.0% was related to poor overall patient survival in retransplantations. (HR 3.668, CI 1.150-11.698, P = 0.028). Retransplantation can be complicated with poor graft and patient survival compared to first transplantation, especially when the graft size is relatively small. Lowering the FK506 trough level during the first month can be beneficial for outcome.

Upper thigh skeletal muscle index predicts outcomes in liver transplant recipients.

Purpose: The skeletal muscle index (SMI) at the L3 level is widely used to diagnose sarcopenia. The upper thigh (UT) also reflects changes in whole-body muscle mass, but no study has examined this using the UT to diagnose sarcopenia in liver transplantation (LT). This study aimed to determine an optimal cut-off value for UT-SMI and investigate how sarcopenia diagnosed by UT-SMI correlates with outcomes in LT recipients. Methods: In this retrospective study of 332 LT patients from 2018 to 2020, we investigated the association between sarcopenia diagnosed by UT-SMI and patient outcomes after LT. Results: The cut-off values for UT-SMI were 38.3 cm2/m2 for females (area under the curve [AUC], 0.927; P < 0.001) and 46.7 cm2/m2 for males (AUC, 0.898; P < 0.001). The prevalence of sarcopenia diagnosed by UT-SMI was 33.4% in our cohort. Patient and graft survival rates in the UT-SMI sarcopenia group were significantly poorer than those in the UT-SMI non-sarcopenia group (P < 0.001 and P < 0.001). UT-SMI was an independent prognostic factor for patient survival (hazard ratio [HR], 2.182; 95% confidence interval [CI], 1.183-4.025; P = 0.012) and graft survival (HR, 2.227; 95% CI, 1.054-4704; P = 0.036) in our multivariable Cox analysis. Conclusion: We confirmed that sarcopenia diagnosed by UT-SMI is associated with outcomes in LT recipients. In addition, UT-SMI was identified as an independent prognostic factor for patient survival and graft survival. Therefore, UT-SMI could be a good option for CT-based evaluations of sarcopenia in LT recipients.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.